Anemia

A 46-year-old man who lives in Tacoma, Wash., is seen for fatigue. He has a no significant past medical history. He is not taking any medications. His physical exam is unremarkable. His hemoglobin is 12 gm/dL, hematocrit is 37 gm/dL, mean corpuscular volume (MCV) is 103 fL, and thyroid-stimulating hormone level is 1.2 mU/L.

What workup do you recommend?

A) B₁₂, folate testing

B) Alcohol history, B₁₂, folate testing

C) Alcohol history, B₁₂ testing

I would choose doing a careful alcohol history and vitamin B₁₂ testing.

Dr. Seppä and colleagues looked at all outpatients who had a blood count done over an 8-month period.¹ A total of 9,527 blood counts were ordered, and 287 (3%) had macrocytosis.¹ Further workup was done for 113 of the patients. The most common cause found for macrocytosis was alcohol abuse, in 74 (65%) of the patients (80% of the men and 36% of the women). In several studies, vitamin B₁₂ deficiency was the cause of macrocytosis in 5%-7% of patients.^2,3

In 1978, a study by Davidson and Hamilton looked at 200 consecutive patients with MCVs over 100, and were able to find a cause in 80%.⁴ Sixteen of these patients had a low B₁₂ level and 10 had a low folate level.

In recent years, folate has become an extremely unlikely cause of macrocytic anemias. In 1998, the Food and Drug Administration required folic acid fortification of enriched grain products in the United States to help decrease the risk of neural tube defects. Similar fortification efforts were undertaken in Canada. Since 1998, anemia due to folate deficiency has essentially disappeared in individuals who have access to fortified grain products.

Joelson and colleagues looked at data on folate testing from the year prior to fortification of the grain supply (1997) and after (2004).⁵ They found that, in 1997, 4.8% of tests had a folate level less than 160 ng/mL compared with only 0.6% of tests in 2004.

When a more stringent cutoff for deficiency was used (94 ng/mL) 0.98% of tests were below that level in 1997, and 0.09% in 2004. The mean RBC folate level in 1997 was 420 ng/mL and rose to 697 ng/mL in 2004. Of the patients who did have low folate levels, only a minority had elevated MCVs.

Shojania et al. looked at folate testing in Canada after widespread fortification had started.⁶ They found that 0.5% of 2,154 serum folate levels were low and 0.7% of 560 red blood cell folate levels were low. Folate deficiency was not the cause of anemia in any of the patients with low folate levels.

Theisen-Toupal and colleagues did a retrospective study looking at folate testing over an 11-year period after fortification.⁷ The researchers examined the results of 84,187 assessments of folate levels. Forty-seven (0.056%) of the tests found patients with folate deficiency, 166 (0.197%), found patients with low-normal folate levels, 57,411 (68.195%) of tests yielded normal results, and 26,563 (31.552%) of tests found high folate levels. The opinion of the authors was that folate testing should be severely reduced or eliminated. Furthermore, the American Society for Clinical Pathology, as part of the Choosing Wisely campaign, states: “Do not order red blood cell folate levels at all.”⁸

So what does this all mean? We have been taught to have a reflex response to the evaluation of macrocytosis to test for B₁₂ and folate. Neither of these are particularly common causes of macrocytosis, and in countries where there is grain fortification, folate deficiency is exceedingly uncommon, and should not be tested for early in any diagnostic process.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Seppä K et al. Evaluation of macrocytosis by general practitioners. J Stud Alcohol. 1996 Jan;57(1):97-100.

2. Seppä K et al. Blood count and hematologic morphology in nonanemic macrocytosis: Differences between alcohol abuse and pernicious anemia. Alcohol. 1993 Sep-Oct;10(5):343-7.

3. Wymer A, Becker DM. Recognition and evaluation of red blood cell macrocytosis in the primary care setting. J Gen Intern Med. 1990 May-Jun;5(3):192-7.

4. Davidson RJ, Hamilton PJ. High mean red cell volume: Its incidence and significance in routine haematology. J Clin Pathol. 1978 May;31[5]:493-8.

5. Joelson DW, Fiebig EW. Diminished need for folate measurements among indigent populations in the post folic acid supplementation era. Arch Pathol Lab Med. 2007 Mar;131(3):477-80.

6. Shojania AM, von Kuster K. Ordering folate assays is no longer justified for investigation of anemias, in folic acid fortified countries. BMC Res Notes. 2010 Jan 25;3:22. doi: 10.1186/1756-0500-3-22.

7. Theisen-Toupal et al. Low yield of outpatient serum folate testing. JAMA Intern Med. 2014 Oct. doi: 10.1001/jamainternmed.2014.3593.

8. Choosing Wisely: American Society for Clinical Pathology, Oct. 19, 2017. Recommendation.

A 46-year-old man who lives in Tacoma, Wash., is seen for fatigue. He has a no significant past medical history. He is not taking any medications. His physical exam is unremarkable. His hemoglobin is 12 gm/dL, hematocrit is 37 gm/dL, mean corpuscular volume (MCV) is 103 fL, and thyroid-stimulating hormone level is 1.2 mU/L.

What workup do you recommend?

A) B₁₂, folate testing

B) Alcohol history, B₁₂, folate testing

C) Alcohol history, B₁₂ testing

I would choose doing a careful alcohol history and vitamin B₁₂ testing.

Dr. Seppä and colleagues looked at all outpatients who had a blood count done over an 8-month period.¹ A total of 9,527 blood counts were ordered, and 287 (3%) had macrocytosis.¹ Further workup was done for 113 of the patients. The most common cause found for macrocytosis was alcohol abuse, in 74 (65%) of the patients (80% of the men and 36% of the women). In several studies, vitamin B₁₂ deficiency was the cause of macrocytosis in 5%-7% of patients.^2,3

In 1978, a study by Davidson and Hamilton looked at 200 consecutive patients with MCVs over 100, and were able to find a cause in 80%.⁴ Sixteen of these patients had a low B₁₂ level and 10 had a low folate level.

In recent years, folate has become an extremely unlikely cause of macrocytic anemias. In 1998, the Food and Drug Administration required folic acid fortification of enriched grain products in the United States to help decrease the risk of neural tube defects. Similar fortification efforts were undertaken in Canada. Since 1998, anemia due to folate deficiency has essentially disappeared in individuals who have access to fortified grain products.

Joelson and colleagues looked at data on folate testing from the year prior to fortification of the grain supply (1997) and after (2004).⁵ They found that, in 1997, 4.8% of tests had a folate level less than 160 ng/mL compared with only 0.6% of tests in 2004.

When a more stringent cutoff for deficiency was used (94 ng/mL) 0.98% of tests were below that level in 1997, and 0.09% in 2004. The mean RBC folate level in 1997 was 420 ng/mL and rose to 697 ng/mL in 2004. Of the patients who did have low folate levels, only a minority had elevated MCVs.

Shojania et al. looked at folate testing in Canada after widespread fortification had started.⁶ They found that 0.5% of 2,154 serum folate levels were low and 0.7% of 560 red blood cell folate levels were low. Folate deficiency was not the cause of anemia in any of the patients with low folate levels.

Theisen-Toupal and colleagues did a retrospective study looking at folate testing over an 11-year period after fortification.⁷ The researchers examined the results of 84,187 assessments of folate levels. Forty-seven (0.056%) of the tests found patients with folate deficiency, 166 (0.197%), found patients with low-normal folate levels, 57,411 (68.195%) of tests yielded normal results, and 26,563 (31.552%) of tests found high folate levels. The opinion of the authors was that folate testing should be severely reduced or eliminated. Furthermore, the American Society for Clinical Pathology, as part of the Choosing Wisely campaign, states: “Do not order red blood cell folate levels at all.”⁸

So what does this all mean? We have been taught to have a reflex response to the evaluation of macrocytosis to test for B₁₂ and folate. Neither of these are particularly common causes of macrocytosis, and in countries where there is grain fortification, folate deficiency is exceedingly uncommon, and should not be tested for early in any diagnostic process.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Seppä K et al. Evaluation of macrocytosis by general practitioners. J Stud Alcohol. 1996 Jan;57(1):97-100.

2. Seppä K et al. Blood count and hematologic morphology in nonanemic macrocytosis: Differences between alcohol abuse and pernicious anemia. Alcohol. 1993 Sep-Oct;10(5):343-7.

3. Wymer A, Becker DM. Recognition and evaluation of red blood cell macrocytosis in the primary care setting. J Gen Intern Med. 1990 May-Jun;5(3):192-7.

4. Davidson RJ, Hamilton PJ. High mean red cell volume: Its incidence and significance in routine haematology. J Clin Pathol. 1978 May;31[5]:493-8.

5. Joelson DW, Fiebig EW. Diminished need for folate measurements among indigent populations in the post folic acid supplementation era. Arch Pathol Lab Med. 2007 Mar;131(3):477-80.

6. Shojania AM, von Kuster K. Ordering folate assays is no longer justified for investigation of anemias, in folic acid fortified countries. BMC Res Notes. 2010 Jan 25;3:22. doi: 10.1186/1756-0500-3-22.

7. Theisen-Toupal et al. Low yield of outpatient serum folate testing. JAMA Intern Med. 2014 Oct. doi: 10.1001/jamainternmed.2014.3593.

8. Choosing Wisely: American Society for Clinical Pathology, Oct. 19, 2017. Recommendation.

A 46-year-old man who lives in Tacoma, Wash., is seen for fatigue. He has a no significant past medical history. He is not taking any medications. His physical exam is unremarkable. His hemoglobin is 12 gm/dL, hematocrit is 37 gm/dL, mean corpuscular volume (MCV) is 103 fL, and thyroid-stimulating hormone level is 1.2 mU/L.

What workup do you recommend?

A) B₁₂, folate testing

B) Alcohol history, B₁₂, folate testing

C) Alcohol history, B₁₂ testing

I would choose doing a careful alcohol history and vitamin B₁₂ testing.

Dr. Seppä and colleagues looked at all outpatients who had a blood count done over an 8-month period.¹ A total of 9,527 blood counts were ordered, and 287 (3%) had macrocytosis.¹ Further workup was done for 113 of the patients. The most common cause found for macrocytosis was alcohol abuse, in 74 (65%) of the patients (80% of the men and 36% of the women). In several studies, vitamin B₁₂ deficiency was the cause of macrocytosis in 5%-7% of patients.^2,3

In 1978, a study by Davidson and Hamilton looked at 200 consecutive patients with MCVs over 100, and were able to find a cause in 80%.⁴ Sixteen of these patients had a low B₁₂ level and 10 had a low folate level.

In recent years, folate has become an extremely unlikely cause of macrocytic anemias. In 1998, the Food and Drug Administration required folic acid fortification of enriched grain products in the United States to help decrease the risk of neural tube defects. Similar fortification efforts were undertaken in Canada. Since 1998, anemia due to folate deficiency has essentially disappeared in individuals who have access to fortified grain products.

Joelson and colleagues looked at data on folate testing from the year prior to fortification of the grain supply (1997) and after (2004).⁵ They found that, in 1997, 4.8% of tests had a folate level less than 160 ng/mL compared with only 0.6% of tests in 2004.

When a more stringent cutoff for deficiency was used (94 ng/mL) 0.98% of tests were below that level in 1997, and 0.09% in 2004. The mean RBC folate level in 1997 was 420 ng/mL and rose to 697 ng/mL in 2004. Of the patients who did have low folate levels, only a minority had elevated MCVs.

Shojania et al. looked at folate testing in Canada after widespread fortification had started.⁶ They found that 0.5% of 2,154 serum folate levels were low and 0.7% of 560 red blood cell folate levels were low. Folate deficiency was not the cause of anemia in any of the patients with low folate levels.

Theisen-Toupal and colleagues did a retrospective study looking at folate testing over an 11-year period after fortification.⁷ The researchers examined the results of 84,187 assessments of folate levels. Forty-seven (0.056%) of the tests found patients with folate deficiency, 166 (0.197%), found patients with low-normal folate levels, 57,411 (68.195%) of tests yielded normal results, and 26,563 (31.552%) of tests found high folate levels. The opinion of the authors was that folate testing should be severely reduced or eliminated. Furthermore, the American Society for Clinical Pathology, as part of the Choosing Wisely campaign, states: “Do not order red blood cell folate levels at all.”⁸

So what does this all mean? We have been taught to have a reflex response to the evaluation of macrocytosis to test for B₁₂ and folate. Neither of these are particularly common causes of macrocytosis, and in countries where there is grain fortification, folate deficiency is exceedingly uncommon, and should not be tested for early in any diagnostic process.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Seppä K et al. Evaluation of macrocytosis by general practitioners. J Stud Alcohol. 1996 Jan;57(1):97-100.

2. Seppä K et al. Blood count and hematologic morphology in nonanemic macrocytosis: Differences between alcohol abuse and pernicious anemia. Alcohol. 1993 Sep-Oct;10(5):343-7.

3. Wymer A, Becker DM. Recognition and evaluation of red blood cell macrocytosis in the primary care setting. J Gen Intern Med. 1990 May-Jun;5(3):192-7.

4. Davidson RJ, Hamilton PJ. High mean red cell volume: Its incidence and significance in routine haematology. J Clin Pathol. 1978 May;31[5]:493-8.

5. Joelson DW, Fiebig EW. Diminished need for folate measurements among indigent populations in the post folic acid supplementation era. Arch Pathol Lab Med. 2007 Mar;131(3):477-80.

6. Shojania AM, von Kuster K. Ordering folate assays is no longer justified for investigation of anemias, in folic acid fortified countries. BMC Res Notes. 2010 Jan 25;3:22. doi: 10.1186/1756-0500-3-22.

7. Theisen-Toupal et al. Low yield of outpatient serum folate testing. JAMA Intern Med. 2014 Oct. doi: 10.1001/jamainternmed.2014.3593.

8. Choosing Wisely: American Society for Clinical Pathology, Oct. 19, 2017. Recommendation.

Chiesi Global Rare Diseases announced that the Food and Drug Administration has approved a new formulation of deferiprone (Ferriprox) for the treatment of patients with transfusional iron overload caused by thalassemia syndromes when current chelation therapy is inadequate. The new formulation of twice-a-day Ferriprox 1,000 mg oral tablets eliminates the midday dose, according to a company press release.

“A treatment option that reduces serum ferritin, cardiac iron, and liver iron with an established safety profile and now twice-a-day tablet dosing can represent a significant advantage for patients,” stated Thomas Coates, MD, in the press release. Dr. Coates is the section head of hematology at Children’s Hospital Los Angeles.

Deferiprone was originally approved by the FDA in 2011 for the treatment of transfusional iron overload caused by thalassemia syndromes. Ferriprox contains a label warning that it can cause agranulocytosis that can lead to serious infections and death. As neutropenia may precede the development of agranulocytosis, the warning advises measurement of the absolute neutrophil count before starting Ferriprox and monitoring the ANC weekly on therapy. In addition, Ferriprox should be interrupted if infection develops, and the ANC should be monitored more frequently.

As Ferriprox can cause fetal harm, women of reproductive potential should be advised to use an effective method of contraception during treatment and for at least 6 months after the last dose, according to the company release.

[email protected]

Chiesi Global Rare Diseases announced that the Food and Drug Administration has approved a new formulation of deferiprone (Ferriprox) for the treatment of patients with transfusional iron overload caused by thalassemia syndromes when current chelation therapy is inadequate. The new formulation of twice-a-day Ferriprox 1,000 mg oral tablets eliminates the midday dose, according to a company press release.

“A treatment option that reduces serum ferritin, cardiac iron, and liver iron with an established safety profile and now twice-a-day tablet dosing can represent a significant advantage for patients,” stated Thomas Coates, MD, in the press release. Dr. Coates is the section head of hematology at Children’s Hospital Los Angeles.

Deferiprone was originally approved by the FDA in 2011 for the treatment of transfusional iron overload caused by thalassemia syndromes. Ferriprox contains a label warning that it can cause agranulocytosis that can lead to serious infections and death. As neutropenia may precede the development of agranulocytosis, the warning advises measurement of the absolute neutrophil count before starting Ferriprox and monitoring the ANC weekly on therapy. In addition, Ferriprox should be interrupted if infection develops, and the ANC should be monitored more frequently.

As Ferriprox can cause fetal harm, women of reproductive potential should be advised to use an effective method of contraception during treatment and for at least 6 months after the last dose, according to the company release.

[email protected]

Chiesi Global Rare Diseases announced that the Food and Drug Administration has approved a new formulation of deferiprone (Ferriprox) for the treatment of patients with transfusional iron overload caused by thalassemia syndromes when current chelation therapy is inadequate. The new formulation of twice-a-day Ferriprox 1,000 mg oral tablets eliminates the midday dose, according to a company press release.

“A treatment option that reduces serum ferritin, cardiac iron, and liver iron with an established safety profile and now twice-a-day tablet dosing can represent a significant advantage for patients,” stated Thomas Coates, MD, in the press release. Dr. Coates is the section head of hematology at Children’s Hospital Los Angeles.

Deferiprone was originally approved by the FDA in 2011 for the treatment of transfusional iron overload caused by thalassemia syndromes. Ferriprox contains a label warning that it can cause agranulocytosis that can lead to serious infections and death. As neutropenia may precede the development of agranulocytosis, the warning advises measurement of the absolute neutrophil count before starting Ferriprox and monitoring the ANC weekly on therapy. In addition, Ferriprox should be interrupted if infection develops, and the ANC should be monitored more frequently.

As Ferriprox can cause fetal harm, women of reproductive potential should be advised to use an effective method of contraception during treatment and for at least 6 months after the last dose, according to the company release.

[email protected]

Sickle cell disease is associated with worse long-term bone health than that of the general population, and SCD patients are more likely to experience vitamin D [25(OH)D] deficiency. Oral vitamin D3 supplementation can achieve protective levels in children with sickle cell disease, and a daily dose was able to achieved optimal blood levels, according to a report published online in Bone.

The researchers performed a prospective, longitudinal, single-center study of 80 children with SCD. They collected demographic, clinical, and management data, as well as 25(OH)D levels. Bone densitometries (DXA) were also collected.

Among the 80 patients were included in the analysis, there were significant differences between the means of 25(OH)D levels based on whether the patient started prophylactic treatment as an infant or not (35.7 vs. 27.9 ng/mL, respectively [P = .014]), according to the researchers.

They also found that, in multivariate analysis, an oral 800 IU daily dose of vitamin D3 was shown to be a protective factor (P = .044) in reaching optimal 25(OH)D blood levels (≥ 30 ng/mL).

Kaplan-Meier analysis showed that those patients younger than 10 years of age reached optimal levels significantly earlier than older patients when on supplementation (P = .002), as did those patients who were not being treated with hydroxyurea (P = .039), the researchers wrote.

Significant differences were seen between the mean bone mineral density in both DXAs performed when comparing suboptimal vs. optimal blood levels of 25(OH)D (0.54 g/cm² vs. 0.64 g/cm2, respectively, P = .001), for the initial DXA, and for the most recent DXA (0.59 g/cm² vs. 0.77 g/cm², respectively, P = .044). “VitD3 prophylaxis is a safe practice in SCD. It is important to start this prophylactic treatment when the child is an infant. The daily regimen with 800 IU could be more effective for reaching levels ≥ 30 ng/mL, and, especially in preadolescent and adolescent patients, we should raise awareness about the importance of good bone health,” the authors concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Garrido C et al. Bone. 2020;133: doi.org/10.1016/j.bone.2020.115228.

Sickle cell disease is associated with worse long-term bone health than that of the general population, and SCD patients are more likely to experience vitamin D [25(OH)D] deficiency. Oral vitamin D3 supplementation can achieve protective levels in children with sickle cell disease, and a daily dose was able to achieved optimal blood levels, according to a report published online in Bone.

The researchers performed a prospective, longitudinal, single-center study of 80 children with SCD. They collected demographic, clinical, and management data, as well as 25(OH)D levels. Bone densitometries (DXA) were also collected.

Among the 80 patients were included in the analysis, there were significant differences between the means of 25(OH)D levels based on whether the patient started prophylactic treatment as an infant or not (35.7 vs. 27.9 ng/mL, respectively [P = .014]), according to the researchers.

They also found that, in multivariate analysis, an oral 800 IU daily dose of vitamin D3 was shown to be a protective factor (P = .044) in reaching optimal 25(OH)D blood levels (≥ 30 ng/mL).

Kaplan-Meier analysis showed that those patients younger than 10 years of age reached optimal levels significantly earlier than older patients when on supplementation (P = .002), as did those patients who were not being treated with hydroxyurea (P = .039), the researchers wrote.

Significant differences were seen between the mean bone mineral density in both DXAs performed when comparing suboptimal vs. optimal blood levels of 25(OH)D (0.54 g/cm² vs. 0.64 g/cm2, respectively, P = .001), for the initial DXA, and for the most recent DXA (0.59 g/cm² vs. 0.77 g/cm², respectively, P = .044). “VitD3 prophylaxis is a safe practice in SCD. It is important to start this prophylactic treatment when the child is an infant. The daily regimen with 800 IU could be more effective for reaching levels ≥ 30 ng/mL, and, especially in preadolescent and adolescent patients, we should raise awareness about the importance of good bone health,” the authors concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Garrido C et al. Bone. 2020;133: doi.org/10.1016/j.bone.2020.115228.

Sickle cell disease is associated with worse long-term bone health than that of the general population, and SCD patients are more likely to experience vitamin D [25(OH)D] deficiency. Oral vitamin D3 supplementation can achieve protective levels in children with sickle cell disease, and a daily dose was able to achieved optimal blood levels, according to a report published online in Bone.

The researchers performed a prospective, longitudinal, single-center study of 80 children with SCD. They collected demographic, clinical, and management data, as well as 25(OH)D levels. Bone densitometries (DXA) were also collected.

Among the 80 patients were included in the analysis, there were significant differences between the means of 25(OH)D levels based on whether the patient started prophylactic treatment as an infant or not (35.7 vs. 27.9 ng/mL, respectively [P = .014]), according to the researchers.

They also found that, in multivariate analysis, an oral 800 IU daily dose of vitamin D3 was shown to be a protective factor (P = .044) in reaching optimal 25(OH)D blood levels (≥ 30 ng/mL).

Kaplan-Meier analysis showed that those patients younger than 10 years of age reached optimal levels significantly earlier than older patients when on supplementation (P = .002), as did those patients who were not being treated with hydroxyurea (P = .039), the researchers wrote.

Significant differences were seen between the mean bone mineral density in both DXAs performed when comparing suboptimal vs. optimal blood levels of 25(OH)D (0.54 g/cm² vs. 0.64 g/cm2, respectively, P = .001), for the initial DXA, and for the most recent DXA (0.59 g/cm² vs. 0.77 g/cm², respectively, P = .044). “VitD3 prophylaxis is a safe practice in SCD. It is important to start this prophylactic treatment when the child is an infant. The daily regimen with 800 IU could be more effective for reaching levels ≥ 30 ng/mL, and, especially in preadolescent and adolescent patients, we should raise awareness about the importance of good bone health,” the authors concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Garrido C et al. Bone. 2020;133: doi.org/10.1016/j.bone.2020.115228.

In a webinar designed to guide physicians in the care of hematology patients during the COVID-19 pandemic, three world experts on thalassemia and sickle cell disease (SCD) provided on-the-ground information from physicians who were dealing with the height of the crisis in their countries.

The webinar was organized by the European Hematology Association (EHA) and the Thalassemia International Federation (TIF).

Moderator Francesco Cerisoli, MD, head of research and mentoring at EHA, led the discussion with three guest speakers: Maria-Domenica Cappellini, MD, PhD, professor of hematology at the University of Milan; Androulla Eleftheriou, MD, executive director of TIF in Cyprus; and Raffaella Colombatti , MD, of the University of Padova in Italy, coordinator of the Red Cell Reserve Working Group of the Italian Association of Pediatric Hematology and Oncology.
 

Italian experience with thalassemia and COVID-19

Dr. Cappellini discussed the Italian experience with 11 thalassemia patients followed by a network survey who developed COVID-19 in the northern part of Italy, where the pandemic has been most widespread.

There are no published data focusing specifically on SARS-CoV-2 infection in patients with thalassemic syndromes, but patients with preexisting comorbidities are likely to be more severely affected by SARS-CoV-2, according to Dr. Cappellini.

Of particular concern is the fact that patients with thalassemia, especially older ones, are frequently splenectomized, which renders them more vulnerable to bacterial infections and can trigger life-threatening sepsis. However, splenectomy is not known to increase the risk of viral infection or severe viral illness. Of additional concern is the fact that many thalassemia patients need routine and frequent transfusions.

Overall, the 11 thalassemia patients who developed COVID-19 experienced only mild to moderate symptoms. This is despite the fact that 72% of the patients were splenectomized, which did not appear to affect the clinical course, and all of the patients had thalassemia-related comorbidities.

Around half of the patients were hospitalized, but none of them required transfer to the ICU. One patient who was treated with chemotherapy for diffuse large B-cell lymphoma in 2019 but is now in remission required more intense ventilation support with the use of continuous positive airway pressure.

Only three patients received specific treatment for COVID-19: one with hydroxychloroquine (HCQ) alone, one with HCQ plus anakinra, and one with HCQ plus ritonavir/darunavir.

Overall, “the number of infected thalassemia patients was lower than expected, likely due to earlier and more vigilant self-isolation compared to the general population,” Dr. Cappellini said. She pointed out that the first early response in February by thalassemia physicians was to warn their patients via email and phone calls about the need for self-isolation and precautions against the pandemic.

Physicians “rapidly reorganized activities, postponing nonessential ones” and managed to provide patients “a safe track at the hospital to receive their life-saving treatment in COVID-19–free areas with health care personnel wearing protective equipment” and assessment of all entering patients for COVID-19 infection, Dr. Cappellini said.
 

Results in additional thalassemia patients and SCD patients

Dr. Eleftheriou described 51 cases of thalassemia patients with SARS-CoV-2 infection reported to TIF as of April 16. Patients were from Cyprus, Italy, the United Kingdom, France, Turkey, Iran, Pakistan, and Indonesia.

Of the 51 patients, 46 presented with mild to moderate symptoms. Five patients had severe respiratory symptoms and required hospitalization, two were hospitalized and discharged, and three died between day 5 and day 15 post hospitalization.

Dr. Colombatti followed with a brief presentation of the intersection of COVID-19 with SCD patients. She presented anecdotal data involving 32 SCD patients who exhibited COVID-19 symptoms. Dr. Colombatti obtained the data via personal communication with Pablo Bartolucci, of Hôpitaux Universitaires Henri Mondor in Créteil, France.

All 32 SCD patients were screened and treated for COVID-19, and 17 of them continued treatment for 10 days. In all, 22 patients were hospitalized, 11 were transferred to the ICU, and 1 died.
 

Ensuring adequate blood supply

Dr. Eleftheriou also discussed the TIF response to the COVID-19 pandemic, which focused on the adequacy of blood supplies for these patients who so often need transfusions.

Dr. Eleftheriou stated that a shortage of blood was reported in 75% of the 62 member countries of the TIF, with 58% reporting severe shortages and 35% reporting moderate to severe shortages.

The shortages resulted in many countries returning to older family/friends donation practices, rare use of whole blood transfusions, and the use of older blood transfusions (older than 28 days).

In addition, physicians have modified their transfusion strategy. They have reduced the amount of blood given to thalassemia patients from two units to one unit during any transfusion, while making arrangements for more frequent transfusions; for example, one transfusion per week but with precautions made to “limit the time spent in the clinic and to control blood supplies while safeguarding that all [thalassemia] patients will be able to get their transfusion,” Dr. Eleftheriou said.

The information in the webinar was provided with the caveat that “no general evidence-based guidance can be derived from this discussion.” There were no other disclosures given.

[email protected]

In a webinar designed to guide physicians in the care of hematology patients during the COVID-19 pandemic, three world experts on thalassemia and sickle cell disease (SCD) provided on-the-ground information from physicians who were dealing with the height of the crisis in their countries.

The webinar was organized by the European Hematology Association (EHA) and the Thalassemia International Federation (TIF).

Moderator Francesco Cerisoli, MD, head of research and mentoring at EHA, led the discussion with three guest speakers: Maria-Domenica Cappellini, MD, PhD, professor of hematology at the University of Milan; Androulla Eleftheriou, MD, executive director of TIF in Cyprus; and Raffaella Colombatti , MD, of the University of Padova in Italy, coordinator of the Red Cell Reserve Working Group of the Italian Association of Pediatric Hematology and Oncology.
 

Italian experience with thalassemia and COVID-19

Dr. Cappellini discussed the Italian experience with 11 thalassemia patients followed by a network survey who developed COVID-19 in the northern part of Italy, where the pandemic has been most widespread.

There are no published data focusing specifically on SARS-CoV-2 infection in patients with thalassemic syndromes, but patients with preexisting comorbidities are likely to be more severely affected by SARS-CoV-2, according to Dr. Cappellini.

Of particular concern is the fact that patients with thalassemia, especially older ones, are frequently splenectomized, which renders them more vulnerable to bacterial infections and can trigger life-threatening sepsis. However, splenectomy is not known to increase the risk of viral infection or severe viral illness. Of additional concern is the fact that many thalassemia patients need routine and frequent transfusions.

Overall, the 11 thalassemia patients who developed COVID-19 experienced only mild to moderate symptoms. This is despite the fact that 72% of the patients were splenectomized, which did not appear to affect the clinical course, and all of the patients had thalassemia-related comorbidities.

Around half of the patients were hospitalized, but none of them required transfer to the ICU. One patient who was treated with chemotherapy for diffuse large B-cell lymphoma in 2019 but is now in remission required more intense ventilation support with the use of continuous positive airway pressure.

Only three patients received specific treatment for COVID-19: one with hydroxychloroquine (HCQ) alone, one with HCQ plus anakinra, and one with HCQ plus ritonavir/darunavir.

Overall, “the number of infected thalassemia patients was lower than expected, likely due to earlier and more vigilant self-isolation compared to the general population,” Dr. Cappellini said. She pointed out that the first early response in February by thalassemia physicians was to warn their patients via email and phone calls about the need for self-isolation and precautions against the pandemic.

Physicians “rapidly reorganized activities, postponing nonessential ones” and managed to provide patients “a safe track at the hospital to receive their life-saving treatment in COVID-19–free areas with health care personnel wearing protective equipment” and assessment of all entering patients for COVID-19 infection, Dr. Cappellini said.
 

Results in additional thalassemia patients and SCD patients

Dr. Eleftheriou described 51 cases of thalassemia patients with SARS-CoV-2 infection reported to TIF as of April 16. Patients were from Cyprus, Italy, the United Kingdom, France, Turkey, Iran, Pakistan, and Indonesia.

Of the 51 patients, 46 presented with mild to moderate symptoms. Five patients had severe respiratory symptoms and required hospitalization, two were hospitalized and discharged, and three died between day 5 and day 15 post hospitalization.

Dr. Colombatti followed with a brief presentation of the intersection of COVID-19 with SCD patients. She presented anecdotal data involving 32 SCD patients who exhibited COVID-19 symptoms. Dr. Colombatti obtained the data via personal communication with Pablo Bartolucci, of Hôpitaux Universitaires Henri Mondor in Créteil, France.

All 32 SCD patients were screened and treated for COVID-19, and 17 of them continued treatment for 10 days. In all, 22 patients were hospitalized, 11 were transferred to the ICU, and 1 died.
 

Ensuring adequate blood supply

Dr. Eleftheriou also discussed the TIF response to the COVID-19 pandemic, which focused on the adequacy of blood supplies for these patients who so often need transfusions.

Dr. Eleftheriou stated that a shortage of blood was reported in 75% of the 62 member countries of the TIF, with 58% reporting severe shortages and 35% reporting moderate to severe shortages.

The shortages resulted in many countries returning to older family/friends donation practices, rare use of whole blood transfusions, and the use of older blood transfusions (older than 28 days).

In addition, physicians have modified their transfusion strategy. They have reduced the amount of blood given to thalassemia patients from two units to one unit during any transfusion, while making arrangements for more frequent transfusions; for example, one transfusion per week but with precautions made to “limit the time spent in the clinic and to control blood supplies while safeguarding that all [thalassemia] patients will be able to get their transfusion,” Dr. Eleftheriou said.

The information in the webinar was provided with the caveat that “no general evidence-based guidance can be derived from this discussion.” There were no other disclosures given.

[email protected]

In a webinar designed to guide physicians in the care of hematology patients during the COVID-19 pandemic, three world experts on thalassemia and sickle cell disease (SCD) provided on-the-ground information from physicians who were dealing with the height of the crisis in their countries.

The webinar was organized by the European Hematology Association (EHA) and the Thalassemia International Federation (TIF).

Moderator Francesco Cerisoli, MD, head of research and mentoring at EHA, led the discussion with three guest speakers: Maria-Domenica Cappellini, MD, PhD, professor of hematology at the University of Milan; Androulla Eleftheriou, MD, executive director of TIF in Cyprus; and Raffaella Colombatti , MD, of the University of Padova in Italy, coordinator of the Red Cell Reserve Working Group of the Italian Association of Pediatric Hematology and Oncology.
 

Italian experience with thalassemia and COVID-19

Dr. Cappellini discussed the Italian experience with 11 thalassemia patients followed by a network survey who developed COVID-19 in the northern part of Italy, where the pandemic has been most widespread.

There are no published data focusing specifically on SARS-CoV-2 infection in patients with thalassemic syndromes, but patients with preexisting comorbidities are likely to be more severely affected by SARS-CoV-2, according to Dr. Cappellini.

Of particular concern is the fact that patients with thalassemia, especially older ones, are frequently splenectomized, which renders them more vulnerable to bacterial infections and can trigger life-threatening sepsis. However, splenectomy is not known to increase the risk of viral infection or severe viral illness. Of additional concern is the fact that many thalassemia patients need routine and frequent transfusions.

Overall, the 11 thalassemia patients who developed COVID-19 experienced only mild to moderate symptoms. This is despite the fact that 72% of the patients were splenectomized, which did not appear to affect the clinical course, and all of the patients had thalassemia-related comorbidities.

Around half of the patients were hospitalized, but none of them required transfer to the ICU. One patient who was treated with chemotherapy for diffuse large B-cell lymphoma in 2019 but is now in remission required more intense ventilation support with the use of continuous positive airway pressure.

Only three patients received specific treatment for COVID-19: one with hydroxychloroquine (HCQ) alone, one with HCQ plus anakinra, and one with HCQ plus ritonavir/darunavir.

Overall, “the number of infected thalassemia patients was lower than expected, likely due to earlier and more vigilant self-isolation compared to the general population,” Dr. Cappellini said. She pointed out that the first early response in February by thalassemia physicians was to warn their patients via email and phone calls about the need for self-isolation and precautions against the pandemic.

Physicians “rapidly reorganized activities, postponing nonessential ones” and managed to provide patients “a safe track at the hospital to receive their life-saving treatment in COVID-19–free areas with health care personnel wearing protective equipment” and assessment of all entering patients for COVID-19 infection, Dr. Cappellini said.
 

Results in additional thalassemia patients and SCD patients

Dr. Eleftheriou described 51 cases of thalassemia patients with SARS-CoV-2 infection reported to TIF as of April 16. Patients were from Cyprus, Italy, the United Kingdom, France, Turkey, Iran, Pakistan, and Indonesia.

Of the 51 patients, 46 presented with mild to moderate symptoms. Five patients had severe respiratory symptoms and required hospitalization, two were hospitalized and discharged, and three died between day 5 and day 15 post hospitalization.

Dr. Colombatti followed with a brief presentation of the intersection of COVID-19 with SCD patients. She presented anecdotal data involving 32 SCD patients who exhibited COVID-19 symptoms. Dr. Colombatti obtained the data via personal communication with Pablo Bartolucci, of Hôpitaux Universitaires Henri Mondor in Créteil, France.

All 32 SCD patients were screened and treated for COVID-19, and 17 of them continued treatment for 10 days. In all, 22 patients were hospitalized, 11 were transferred to the ICU, and 1 died.
 

Ensuring adequate blood supply

Dr. Eleftheriou also discussed the TIF response to the COVID-19 pandemic, which focused on the adequacy of blood supplies for these patients who so often need transfusions.

Dr. Eleftheriou stated that a shortage of blood was reported in 75% of the 62 member countries of the TIF, with 58% reporting severe shortages and 35% reporting moderate to severe shortages.

The shortages resulted in many countries returning to older family/friends donation practices, rare use of whole blood transfusions, and the use of older blood transfusions (older than 28 days).

In addition, physicians have modified their transfusion strategy. They have reduced the amount of blood given to thalassemia patients from two units to one unit during any transfusion, while making arrangements for more frequent transfusions; for example, one transfusion per week but with precautions made to “limit the time spent in the clinic and to control blood supplies while safeguarding that all [thalassemia] patients will be able to get their transfusion,” Dr. Eleftheriou said.

The information in the webinar was provided with the caveat that “no general evidence-based guidance can be derived from this discussion.” There were no other disclosures given.

[email protected]

The COVID-19 pandemic is putting a strain on the blood supply and could be putting people – including those who normally get transfusions, such as patients with sickle cell disease and cancer – at risk.

“Around the beginning of March, the hematology community got wind of what was going on because the blood banks were saying think about your patients and begin to restrict blood usage because we are expecting an increase in usage for COVID-positive ICU patients,” Ifeyinwa (Ify) Osunkwo, MD, a specialist in hematology and sickle cell disease at Levine Cancer Institute in Charlotte, N.C., said in an interview.

“I think that was the first call to arms around hematology ... you don’t want to shortchange somebody who is well and who is being sustained by life-giving transfusions and cut out their transfusion therapy because you are hoping to use the blood for people who are coming in with COVID-19,” she continued. “That is an ethical dilemma that no doctor wants to have to go through. But the reality is we have to do something to make it work for everybody.”

And the timing of the social restrictions due to the pandemic has added additional strain on the blood supply.

“Over the winter, traditionally, blood drives slow down because of the flu and different viruses,” she noted. “The spring and the summer are when we see the biggest recruitment and uptake of blood donation. COVID-19 hit [and] a lot of the blood drives that were traditionally scheduled to supply blood for the country have been canceled because of the new guidance for social distancing.”

Another big source of blood are health care professionals themselves and they may not be able to donate because of the extra hours being worked because of the pandemic.

In speaking about the needs for traditional patients such as those who are dealing with cancer or leukemia or sickle cell diseases as well as those who are being treated for COVID-19 in North Carolina, “we are not at the critical point, but I am a little bit nervous that we may get there because they are not going to up the usual blood drives anytime this summer. We project [sometime] in the fall, but maybe not even then. So there needs to be a significant call-out for people to make every effort to donate blood,” said Dr. Osunkwo. She added that in places such as New York City that are hot spots for the COVID-19 outbreak, the need is likely a lot greater.

She recalled a recent incident at a New York hospital that highlighted how those managing blood supplies are being restrictive and how this could be harming patients.

“A sickle cell patient came in with COVID-19 and the treatment recommendation was do a red blood cell exchange but the blood bank was nervous about getting enough blood to supply for that exchange transfusion,” she said, noting that the doctor still went to bat for that patient to get the needed treatment. “We gave her the supporting evidence that when you are on treatment for sickle cell disease, you tend to do better if you get COVID-19 or any other viral infection. The symptoms of COVID-19 in sickle cell disease is acute chest syndrome, for which the treatment is red blood cell exchange. Not doing that for [these patients] is really not giving them the optimal way of managing their disease, and managing their disease in the setting of COVID-19.”

To that end, Dr. Osunkwo stressed that doctors need to be doing all they can to get the word out that blood is needed and that the American Red Cross and other donation organizations are making it safe for people to donate. She has been using social media to highlight when her fellow doctors and others make donations as a way to motivate individuals.

“Everybody can do something during this pandemic,” she said. “Don’t feel like you are not working, that you are not a frontline worker, that you have nothing to contribute. You can donate blood. Your cousin can donate blood. You can tell your friends, your neighbors, your relatives, your enemies to go donate. We will take every kind of blood we can get because people are needing it more now. Even though we canceled elective surgeries, my patients when they get COVID-19, they need more blood ... than they usually do during their regular sickle cell admission. It is going to be the same for people who have other blood disorders like cancer and leukemia. We can’t stop life-saving treatments just because we have the COVID pandemic.”

Dr. Osunkwo also praised recent actions taken by the Food and Drug Administration to lessen some of the deferral periods for when an individual can donate.

The FDA on April 2 issued three sets of revised recommendations aimed at getting more people eligible to donate blood. All of the revised recommendations will remain in effect after the COVID-19 health emergency is declared over.

The first revised recommendation makes changes to December 2015 guidance.

For male blood donors who would have been deferred for having sex with another male partner, the deferral period has been reduced from 12 months to 3 months. That deferral period change also applies to female donors who had sex with a man who had sex with another man as well as for those with recent tattoos and piercings.

The second recommendation revises guidance from August 2013 and relates to the risk of transfusion-transmitted malaria.

Under the new recommendations, for those who traveled to malaria-endemic areas (and are residents of malaria non-endemic countries), the FDA is lowering the recommended deferral period from 12 months to 3 months, and also provides notices of an alternate procedure that permits donations without a deferral period provided the blood components are pathogen-reduced using an FDA-approved pathogen reduction device.

The third recommendation finalizes draft guidance from January that eliminates the referral period for donors who spent time in certain European countries or were on military bases in Europe and were previously considered to have been exposed to a potential risk of transmission of Creutzfeldt-Jakob Disease or Variant Creutzfeldt-Jakob Disease.

Dr. Osunkwo reports consultancy and being on the speakers bureau and participating in the advisory board for Novartis, and relationships with a variety of other pharmaceutical companies. She is the editor-in-chief for Hematology News.

[email protected]

The COVID-19 pandemic is putting a strain on the blood supply and could be putting people – including those who normally get transfusions, such as patients with sickle cell disease and cancer – at risk.

“Around the beginning of March, the hematology community got wind of what was going on because the blood banks were saying think about your patients and begin to restrict blood usage because we are expecting an increase in usage for COVID-positive ICU patients,” Ifeyinwa (Ify) Osunkwo, MD, a specialist in hematology and sickle cell disease at Levine Cancer Institute in Charlotte, N.C., said in an interview.

“I think that was the first call to arms around hematology ... you don’t want to shortchange somebody who is well and who is being sustained by life-giving transfusions and cut out their transfusion therapy because you are hoping to use the blood for people who are coming in with COVID-19,” she continued. “That is an ethical dilemma that no doctor wants to have to go through. But the reality is we have to do something to make it work for everybody.”

And the timing of the social restrictions due to the pandemic has added additional strain on the blood supply.

“Over the winter, traditionally, blood drives slow down because of the flu and different viruses,” she noted. “The spring and the summer are when we see the biggest recruitment and uptake of blood donation. COVID-19 hit [and] a lot of the blood drives that were traditionally scheduled to supply blood for the country have been canceled because of the new guidance for social distancing.”

Another big source of blood are health care professionals themselves and they may not be able to donate because of the extra hours being worked because of the pandemic.

In speaking about the needs for traditional patients such as those who are dealing with cancer or leukemia or sickle cell diseases as well as those who are being treated for COVID-19 in North Carolina, “we are not at the critical point, but I am a little bit nervous that we may get there because they are not going to up the usual blood drives anytime this summer. We project [sometime] in the fall, but maybe not even then. So there needs to be a significant call-out for people to make every effort to donate blood,” said Dr. Osunkwo. She added that in places such as New York City that are hot spots for the COVID-19 outbreak, the need is likely a lot greater.

She recalled a recent incident at a New York hospital that highlighted how those managing blood supplies are being restrictive and how this could be harming patients.

“A sickle cell patient came in with COVID-19 and the treatment recommendation was do a red blood cell exchange but the blood bank was nervous about getting enough blood to supply for that exchange transfusion,” she said, noting that the doctor still went to bat for that patient to get the needed treatment. “We gave her the supporting evidence that when you are on treatment for sickle cell disease, you tend to do better if you get COVID-19 or any other viral infection. The symptoms of COVID-19 in sickle cell disease is acute chest syndrome, for which the treatment is red blood cell exchange. Not doing that for [these patients] is really not giving them the optimal way of managing their disease, and managing their disease in the setting of COVID-19.”

To that end, Dr. Osunkwo stressed that doctors need to be doing all they can to get the word out that blood is needed and that the American Red Cross and other donation organizations are making it safe for people to donate. She has been using social media to highlight when her fellow doctors and others make donations as a way to motivate individuals.

“Everybody can do something during this pandemic,” she said. “Don’t feel like you are not working, that you are not a frontline worker, that you have nothing to contribute. You can donate blood. Your cousin can donate blood. You can tell your friends, your neighbors, your relatives, your enemies to go donate. We will take every kind of blood we can get because people are needing it more now. Even though we canceled elective surgeries, my patients when they get COVID-19, they need more blood ... than they usually do during their regular sickle cell admission. It is going to be the same for people who have other blood disorders like cancer and leukemia. We can’t stop life-saving treatments just because we have the COVID pandemic.”

Dr. Osunkwo also praised recent actions taken by the Food and Drug Administration to lessen some of the deferral periods for when an individual can donate.

The FDA on April 2 issued three sets of revised recommendations aimed at getting more people eligible to donate blood. All of the revised recommendations will remain in effect after the COVID-19 health emergency is declared over.

The first revised recommendation makes changes to December 2015 guidance.

For male blood donors who would have been deferred for having sex with another male partner, the deferral period has been reduced from 12 months to 3 months. That deferral period change also applies to female donors who had sex with a man who had sex with another man as well as for those with recent tattoos and piercings.

The second recommendation revises guidance from August 2013 and relates to the risk of transfusion-transmitted malaria.

Under the new recommendations, for those who traveled to malaria-endemic areas (and are residents of malaria non-endemic countries), the FDA is lowering the recommended deferral period from 12 months to 3 months, and also provides notices of an alternate procedure that permits donations without a deferral period provided the blood components are pathogen-reduced using an FDA-approved pathogen reduction device.

The third recommendation finalizes draft guidance from January that eliminates the referral period for donors who spent time in certain European countries or were on military bases in Europe and were previously considered to have been exposed to a potential risk of transmission of Creutzfeldt-Jakob Disease or Variant Creutzfeldt-Jakob Disease.

Dr. Osunkwo reports consultancy and being on the speakers bureau and participating in the advisory board for Novartis, and relationships with a variety of other pharmaceutical companies. She is the editor-in-chief for Hematology News.

[email protected]

The COVID-19 pandemic is putting a strain on the blood supply and could be putting people – including those who normally get transfusions, such as patients with sickle cell disease and cancer – at risk.

“Around the beginning of March, the hematology community got wind of what was going on because the blood banks were saying think about your patients and begin to restrict blood usage because we are expecting an increase in usage for COVID-positive ICU patients,” Ifeyinwa (Ify) Osunkwo, MD, a specialist in hematology and sickle cell disease at Levine Cancer Institute in Charlotte, N.C., said in an interview.

“I think that was the first call to arms around hematology ... you don’t want to shortchange somebody who is well and who is being sustained by life-giving transfusions and cut out their transfusion therapy because you are hoping to use the blood for people who are coming in with COVID-19,” she continued. “That is an ethical dilemma that no doctor wants to have to go through. But the reality is we have to do something to make it work for everybody.”

And the timing of the social restrictions due to the pandemic has added additional strain on the blood supply.

“Over the winter, traditionally, blood drives slow down because of the flu and different viruses,” she noted. “The spring and the summer are when we see the biggest recruitment and uptake of blood donation. COVID-19 hit [and] a lot of the blood drives that were traditionally scheduled to supply blood for the country have been canceled because of the new guidance for social distancing.”

Another big source of blood are health care professionals themselves and they may not be able to donate because of the extra hours being worked because of the pandemic.

In speaking about the needs for traditional patients such as those who are dealing with cancer or leukemia or sickle cell diseases as well as those who are being treated for COVID-19 in North Carolina, “we are not at the critical point, but I am a little bit nervous that we may get there because they are not going to up the usual blood drives anytime this summer. We project [sometime] in the fall, but maybe not even then. So there needs to be a significant call-out for people to make every effort to donate blood,” said Dr. Osunkwo. She added that in places such as New York City that are hot spots for the COVID-19 outbreak, the need is likely a lot greater.

She recalled a recent incident at a New York hospital that highlighted how those managing blood supplies are being restrictive and how this could be harming patients.

“A sickle cell patient came in with COVID-19 and the treatment recommendation was do a red blood cell exchange but the blood bank was nervous about getting enough blood to supply for that exchange transfusion,” she said, noting that the doctor still went to bat for that patient to get the needed treatment. “We gave her the supporting evidence that when you are on treatment for sickle cell disease, you tend to do better if you get COVID-19 or any other viral infection. The symptoms of COVID-19 in sickle cell disease is acute chest syndrome, for which the treatment is red blood cell exchange. Not doing that for [these patients] is really not giving them the optimal way of managing their disease, and managing their disease in the setting of COVID-19.”

To that end, Dr. Osunkwo stressed that doctors need to be doing all they can to get the word out that blood is needed and that the American Red Cross and other donation organizations are making it safe for people to donate. She has been using social media to highlight when her fellow doctors and others make donations as a way to motivate individuals.

“Everybody can do something during this pandemic,” she said. “Don’t feel like you are not working, that you are not a frontline worker, that you have nothing to contribute. You can donate blood. Your cousin can donate blood. You can tell your friends, your neighbors, your relatives, your enemies to go donate. We will take every kind of blood we can get because people are needing it more now. Even though we canceled elective surgeries, my patients when they get COVID-19, they need more blood ... than they usually do during their regular sickle cell admission. It is going to be the same for people who have other blood disorders like cancer and leukemia. We can’t stop life-saving treatments just because we have the COVID pandemic.”

Dr. Osunkwo also praised recent actions taken by the Food and Drug Administration to lessen some of the deferral periods for when an individual can donate.

The FDA on April 2 issued three sets of revised recommendations aimed at getting more people eligible to donate blood. All of the revised recommendations will remain in effect after the COVID-19 health emergency is declared over.

The first revised recommendation makes changes to December 2015 guidance.

For male blood donors who would have been deferred for having sex with another male partner, the deferral period has been reduced from 12 months to 3 months. That deferral period change also applies to female donors who had sex with a man who had sex with another man as well as for those with recent tattoos and piercings.

The second recommendation revises guidance from August 2013 and relates to the risk of transfusion-transmitted malaria.

Under the new recommendations, for those who traveled to malaria-endemic areas (and are residents of malaria non-endemic countries), the FDA is lowering the recommended deferral period from 12 months to 3 months, and also provides notices of an alternate procedure that permits donations without a deferral period provided the blood components are pathogen-reduced using an FDA-approved pathogen reduction device.

The third recommendation finalizes draft guidance from January that eliminates the referral period for donors who spent time in certain European countries or were on military bases in Europe and were previously considered to have been exposed to a potential risk of transmission of Creutzfeldt-Jakob Disease or Variant Creutzfeldt-Jakob Disease.

Dr. Osunkwo reports consultancy and being on the speakers bureau and participating in the advisory board for Novartis, and relationships with a variety of other pharmaceutical companies. She is the editor-in-chief for Hematology News.

[email protected]

A meta-analysis of four applicable studies found that the hemoglobin value was significantly lower in COVID-19 patients with severe disease, compared with those with milder forms, according to a letter to the editor of Hematology Transfusion and Cell Therapy by Giuseppe Lippi, MD, of the University of Verona (Italy) and colleague.

The four studies comprised 1,210 COVID-19 patients (224 with severe disease; 18.5%). The primary endpoint was defined as a composite of admission to the ICU, need of mechanical ventilation or death. The heterogeneity among the studies was high.

Overall, the hemoglobin value was found to be significantly lower in COVID-19 patients with severe disease than in those with milder forms, yielding a weighted mean difference of −7.1 g/L, with a 95% confidence interval of −8.3 g/L to −5.9 g/L.

“Initial assessment and longitudinal monitoring of hemoglobin values seems advisable in patients with the SARS-CoV-2 infection, whereby a progressive decrease in the hemoglobin concentration may reflect a worse clinical progression,” the authors stated. They also suggested that studies should be “urgently planned to assess whether transfusion support (e.g., with administration of blood or packed red blood cells) may be helpful in this clinical setting to prevent evolution into severe disease and death.”

The authors declared the had no conflicts of interest.

[email protected]

SOURCE: Lippi G et al. Hematol Transfus Cell Ther. 2020 Apr 11; doi:10.1016/j.htct.2020.03.001.

A meta-analysis of four applicable studies found that the hemoglobin value was significantly lower in COVID-19 patients with severe disease, compared with those with milder forms, according to a letter to the editor of Hematology Transfusion and Cell Therapy by Giuseppe Lippi, MD, of the University of Verona (Italy) and colleague.

The four studies comprised 1,210 COVID-19 patients (224 with severe disease; 18.5%). The primary endpoint was defined as a composite of admission to the ICU, need of mechanical ventilation or death. The heterogeneity among the studies was high.

Overall, the hemoglobin value was found to be significantly lower in COVID-19 patients with severe disease than in those with milder forms, yielding a weighted mean difference of −7.1 g/L, with a 95% confidence interval of −8.3 g/L to −5.9 g/L.

“Initial assessment and longitudinal monitoring of hemoglobin values seems advisable in patients with the SARS-CoV-2 infection, whereby a progressive decrease in the hemoglobin concentration may reflect a worse clinical progression,” the authors stated. They also suggested that studies should be “urgently planned to assess whether transfusion support (e.g., with administration of blood or packed red blood cells) may be helpful in this clinical setting to prevent evolution into severe disease and death.”

The authors declared the had no conflicts of interest.

[email protected]

SOURCE: Lippi G et al. Hematol Transfus Cell Ther. 2020 Apr 11; doi:10.1016/j.htct.2020.03.001.

A meta-analysis of four applicable studies found that the hemoglobin value was significantly lower in COVID-19 patients with severe disease, compared with those with milder forms, according to a letter to the editor of Hematology Transfusion and Cell Therapy by Giuseppe Lippi, MD, of the University of Verona (Italy) and colleague.

The four studies comprised 1,210 COVID-19 patients (224 with severe disease; 18.5%). The primary endpoint was defined as a composite of admission to the ICU, need of mechanical ventilation or death. The heterogeneity among the studies was high.

Overall, the hemoglobin value was found to be significantly lower in COVID-19 patients with severe disease than in those with milder forms, yielding a weighted mean difference of −7.1 g/L, with a 95% confidence interval of −8.3 g/L to −5.9 g/L.

“Initial assessment and longitudinal monitoring of hemoglobin values seems advisable in patients with the SARS-CoV-2 infection, whereby a progressive decrease in the hemoglobin concentration may reflect a worse clinical progression,” the authors stated. They also suggested that studies should be “urgently planned to assess whether transfusion support (e.g., with administration of blood or packed red blood cells) may be helpful in this clinical setting to prevent evolution into severe disease and death.”

The authors declared the had no conflicts of interest.

[email protected]

SOURCE: Lippi G et al. Hematol Transfus Cell Ther. 2020 Apr 11; doi:10.1016/j.htct.2020.03.001.

The American Society of Hematology has committed a portion of its website to providing continually updated information addressing specific hematologic disorders in relation to COVID-19.

“As the world grapples with the novel coronavirus, ASH believes that we can help each other be as knowledgeable and prepared as possible,” wrote the society’s president, Stephanie J. Lee, MD, MPH.

On its website, ASH provides relevant COVID-19 information in a series of FAQ divided into malignant and nonmalignant hematologic diseases and disorders. In the malignant category, the various lymphomas and leukemias are individually addressed, as well as other conditions such as myelodysplastic syndromes, myeloproliferative neoplasms, and multiple myeloma. In the nonmalignant category, ASH has provided FAQ on aplastic anemia, thalassemia, sickle cell disease, pulmonary embolism, venous thromboembolism/anticoagulation, coagulopathy, and immune as well as thrombotic thrombocytopenic purpura.

In addition to the continually updated series of relevant FAQ, as part of its response to the pandemic ASH is promoting two unique COVID-19 registries for physicians: the ASH Research Collaborative’s (ASH RC) Data Hub COVID-19 Registry and the Surveillance Epidemiology of Coronavirus (COVID-19) Under Research Exclusion Sickle Cell Disease (SECURE-SCD) Registry.

“The ASH Research Collaborative’s (ASH RC) Data Hub launched the COVID-19 Registry and is currently capturing data on people who test positive for COVID-19 and have been or are currently being treated for hematologic malignancy,” according to the website. The intention is to provide “near real-time observational data summaries,” which will hopefully provide useful information to clinicians treating hematologic malignancies in patients in the midst of the COVID-19 pandemic.

The registry allows clinicians to enter their own cases in a specified format to allow data analysis on clinical practice and patient outcomes that will be aggregated to provide rapid insights for clinicians to help them care for their patients, according to ASH.

The second registry specifically deals with COVID-19 cases in patients with sickle cell disease. It also allows clinicians to add cases with a similar intention of aggregating data to provide near real-time insights into patient care. “We are asking providers caring for these patients to report all of their cases of COVID-19 to this registry,” according to the registry website. The registry is for reporting COVID-19 cases in sickle cell disease patients “after sufficient time has passed to observe the disease course through resolution of acute illness and/or death.”

ASH also provides more generalized information for hematology practitioners dealing with COVID-19 on the topics of conducting their practice and using telemedicine, among others.

Correction, April 15, 2020: This story originally said incorrectly that ASH developed the 2 new registries. The registries are merely being promoted on the ASH website.

[email protected]

The American Society of Hematology has committed a portion of its website to providing continually updated information addressing specific hematologic disorders in relation to COVID-19.

“As the world grapples with the novel coronavirus, ASH believes that we can help each other be as knowledgeable and prepared as possible,” wrote the society’s president, Stephanie J. Lee, MD, MPH.

On its website, ASH provides relevant COVID-19 information in a series of FAQ divided into malignant and nonmalignant hematologic diseases and disorders. In the malignant category, the various lymphomas and leukemias are individually addressed, as well as other conditions such as myelodysplastic syndromes, myeloproliferative neoplasms, and multiple myeloma. In the nonmalignant category, ASH has provided FAQ on aplastic anemia, thalassemia, sickle cell disease, pulmonary embolism, venous thromboembolism/anticoagulation, coagulopathy, and immune as well as thrombotic thrombocytopenic purpura.

In addition to the continually updated series of relevant FAQ, as part of its response to the pandemic ASH is promoting two unique COVID-19 registries for physicians: the ASH Research Collaborative’s (ASH RC) Data Hub COVID-19 Registry and the Surveillance Epidemiology of Coronavirus (COVID-19) Under Research Exclusion Sickle Cell Disease (SECURE-SCD) Registry.

“The ASH Research Collaborative’s (ASH RC) Data Hub launched the COVID-19 Registry and is currently capturing data on people who test positive for COVID-19 and have been or are currently being treated for hematologic malignancy,” according to the website. The intention is to provide “near real-time observational data summaries,” which will hopefully provide useful information to clinicians treating hematologic malignancies in patients in the midst of the COVID-19 pandemic.

The registry allows clinicians to enter their own cases in a specified format to allow data analysis on clinical practice and patient outcomes that will be aggregated to provide rapid insights for clinicians to help them care for their patients, according to ASH.

The second registry specifically deals with COVID-19 cases in patients with sickle cell disease. It also allows clinicians to add cases with a similar intention of aggregating data to provide near real-time insights into patient care. “We are asking providers caring for these patients to report all of their cases of COVID-19 to this registry,” according to the registry website. The registry is for reporting COVID-19 cases in sickle cell disease patients “after sufficient time has passed to observe the disease course through resolution of acute illness and/or death.”

ASH also provides more generalized information for hematology practitioners dealing with COVID-19 on the topics of conducting their practice and using telemedicine, among others.

Correction, April 15, 2020: This story originally said incorrectly that ASH developed the 2 new registries. The registries are merely being promoted on the ASH website.

[email protected]

The American Society of Hematology has committed a portion of its website to providing continually updated information addressing specific hematologic disorders in relation to COVID-19.

“As the world grapples with the novel coronavirus, ASH believes that we can help each other be as knowledgeable and prepared as possible,” wrote the society’s president, Stephanie J. Lee, MD, MPH.

On its website, ASH provides relevant COVID-19 information in a series of FAQ divided into malignant and nonmalignant hematologic diseases and disorders. In the malignant category, the various lymphomas and leukemias are individually addressed, as well as other conditions such as myelodysplastic syndromes, myeloproliferative neoplasms, and multiple myeloma. In the nonmalignant category, ASH has provided FAQ on aplastic anemia, thalassemia, sickle cell disease, pulmonary embolism, venous thromboembolism/anticoagulation, coagulopathy, and immune as well as thrombotic thrombocytopenic purpura.

In addition to the continually updated series of relevant FAQ, as part of its response to the pandemic ASH is promoting two unique COVID-19 registries for physicians: the ASH Research Collaborative’s (ASH RC) Data Hub COVID-19 Registry and the Surveillance Epidemiology of Coronavirus (COVID-19) Under Research Exclusion Sickle Cell Disease (SECURE-SCD) Registry.

“The ASH Research Collaborative’s (ASH RC) Data Hub launched the COVID-19 Registry and is currently capturing data on people who test positive for COVID-19 and have been or are currently being treated for hematologic malignancy,” according to the website. The intention is to provide “near real-time observational data summaries,” which will hopefully provide useful information to clinicians treating hematologic malignancies in patients in the midst of the COVID-19 pandemic.

The registry allows clinicians to enter their own cases in a specified format to allow data analysis on clinical practice and patient outcomes that will be aggregated to provide rapid insights for clinicians to help them care for their patients, according to ASH.

The second registry specifically deals with COVID-19 cases in patients with sickle cell disease. It also allows clinicians to add cases with a similar intention of aggregating data to provide near real-time insights into patient care. “We are asking providers caring for these patients to report all of their cases of COVID-19 to this registry,” according to the registry website. The registry is for reporting COVID-19 cases in sickle cell disease patients “after sufficient time has passed to observe the disease course through resolution of acute illness and/or death.”

ASH also provides more generalized information for hematology practitioners dealing with COVID-19 on the topics of conducting their practice and using telemedicine, among others.

Correction, April 15, 2020: This story originally said incorrectly that ASH developed the 2 new registries. The registries are merely being promoted on the ASH website.

[email protected]

Although a low blood sodium level has been shown to be a prognostic factor for a number of disorders, it has not been reported on for sickle cell disease, according to French researchers Jean-Simon Rech, MD, and colleagues.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

They found that hyponatremia at hospital admission was predictive of complications in initially uncomplicated episodes of painful episodes of sickle cell disease (SCD), according to their study published online in the American Journal of Medicine. Dr. Rech is with the department of internal medicine, Sickle Cell Disease Reference Center, Tenon Hospital, Assistance Publique-Hôpitaux de Paris.

The study assessed 1,218 stays (406 patients) admitted to a single center and the analyses were adjusted for age, sex, hemoglobin genotype and concentration, LDH concentration, and white blood cell count.

The researchers found that hyponatremia (defined as plasma sodium ≤ 135 mmol/L) was significantly associated with the primary endpoint of a composite criterion including acute chest syndrome, intensive care unit transfer, red blood cell transfusion, or inpatient death (P = .001).

With regard to the components of the primary endpoint, hyponatremia was significantly associated with acute chest syndrome (P = .008), as well as with receiving a red blood cell transfusion (P < .001) However, hyponatremia at admission was not significantly associated with intensive care unit transfer (P = .074) and there were no patient deaths.

In addition, hyponatremia was significantly associated with longer stays: 1.1 days adjusted mean length of stay (P < .001).

“Hyponatremia may lead to direct clinical consequences in the management of sickle cell disease patients. Indeed, a plasma sodium concentration ≤ 135mmol/L at admission or a decreasing natremia over the first days of an acute painful episode could be regarded as early signs of incipient acute chest syndrome, prompting clinicians to closely monitor the clinical status of their patients,” the researchers concluded.

The authors declared that they had no conflicts and that there was no funding source.

[email protected]

SOURCE: Rech JS et al. Am J Med. 2020 Mar 18. doi.org/10.1016/j.amjmed.2020.02.017.

Although a low blood sodium level has been shown to be a prognostic factor for a number of disorders, it has not been reported on for sickle cell disease, according to French researchers Jean-Simon Rech, MD, and colleagues.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

They found that hyponatremia at hospital admission was predictive of complications in initially uncomplicated episodes of painful episodes of sickle cell disease (SCD), according to their study published online in the American Journal of Medicine. Dr. Rech is with the department of internal medicine, Sickle Cell Disease Reference Center, Tenon Hospital, Assistance Publique-Hôpitaux de Paris.

The study assessed 1,218 stays (406 patients) admitted to a single center and the analyses were adjusted for age, sex, hemoglobin genotype and concentration, LDH concentration, and white blood cell count.

The researchers found that hyponatremia (defined as plasma sodium ≤ 135 mmol/L) was significantly associated with the primary endpoint of a composite criterion including acute chest syndrome, intensive care unit transfer, red blood cell transfusion, or inpatient death (P = .001).

With regard to the components of the primary endpoint, hyponatremia was significantly associated with acute chest syndrome (P = .008), as well as with receiving a red blood cell transfusion (P < .001) However, hyponatremia at admission was not significantly associated with intensive care unit transfer (P = .074) and there were no patient deaths.

In addition, hyponatremia was significantly associated with longer stays: 1.1 days adjusted mean length of stay (P < .001).

“Hyponatremia may lead to direct clinical consequences in the management of sickle cell disease patients. Indeed, a plasma sodium concentration ≤ 135mmol/L at admission or a decreasing natremia over the first days of an acute painful episode could be regarded as early signs of incipient acute chest syndrome, prompting clinicians to closely monitor the clinical status of their patients,” the researchers concluded.

The authors declared that they had no conflicts and that there was no funding source.

[email protected]

SOURCE: Rech JS et al. Am J Med. 2020 Mar 18. doi.org/10.1016/j.amjmed.2020.02.017.

Although a low blood sodium level has been shown to be a prognostic factor for a number of disorders, it has not been reported on for sickle cell disease, according to French researchers Jean-Simon Rech, MD, and colleagues.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

They found that hyponatremia at hospital admission was predictive of complications in initially uncomplicated episodes of painful episodes of sickle cell disease (SCD), according to their study published online in the American Journal of Medicine. Dr. Rech is with the department of internal medicine, Sickle Cell Disease Reference Center, Tenon Hospital, Assistance Publique-Hôpitaux de Paris.

The study assessed 1,218 stays (406 patients) admitted to a single center and the analyses were adjusted for age, sex, hemoglobin genotype and concentration, LDH concentration, and white blood cell count.

The researchers found that hyponatremia (defined as plasma sodium ≤ 135 mmol/L) was significantly associated with the primary endpoint of a composite criterion including acute chest syndrome, intensive care unit transfer, red blood cell transfusion, or inpatient death (P = .001).

With regard to the components of the primary endpoint, hyponatremia was significantly associated with acute chest syndrome (P = .008), as well as with receiving a red blood cell transfusion (P < .001) However, hyponatremia at admission was not significantly associated with intensive care unit transfer (P = .074) and there were no patient deaths.

In addition, hyponatremia was significantly associated with longer stays: 1.1 days adjusted mean length of stay (P < .001).

“Hyponatremia may lead to direct clinical consequences in the management of sickle cell disease patients. Indeed, a plasma sodium concentration ≤ 135mmol/L at admission or a decreasing natremia over the first days of an acute painful episode could be regarded as early signs of incipient acute chest syndrome, prompting clinicians to closely monitor the clinical status of their patients,” the researchers concluded.

The authors declared that they had no conflicts and that there was no funding source.

[email protected]

SOURCE: Rech JS et al. Am J Med. 2020 Mar 18. doi.org/10.1016/j.amjmed.2020.02.017.

The US Food and Drug Administration has approved luspatercept (Reblozyl, Bristol-Myers Squibb/Acceleron) for the treatment of anemia in patients with myelodysplastic syndromes (MDS).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The green light represents the first treatment advancement in MDS in more than a decade, says an expert in the field.

Luspatercept is the first and so far only erythroid maturation agent (EMA), and was launched last year when it was approved for the treatment of anemia in adults with beta thalassemia, who require regular red blood cell transfusions.

The new approval is for the treatment of anemia in adult patients with very low- to intermediate-risk MDS with ring sideroblasts and patients with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, after they have progressed on treatment with an erythropoiesis-stimulating agent and who require two or more red blood cell (RBC) units over 8 weeks.

Luspatercept is not a substitute for RBC transfusions in patients who require immediate correction of anemia.

The FDA approval in MDS is based on results from the pivotal, placebo-controlled, phase 3 MEDALIST trial, conducted in 229 patients with very-low–, low- and intermediate-risk non-del(5q) MDS with ring sideroblasts. All patients were RBC transfusion-dependent and had disease that was refractory to, or unlikely to respond to, erythropoiesis-stimulating agents. Results were published in January in the New England Journal of Medicine. The study was funded by Acceleron Pharma and Celgene, which was later acquired by Bristol-Myers Squibb.

These results were first presented at the 2018 annual meeting of the American Society of Hematology (ASH), as reported by Medscape Medical News. At the time, ASH President Alexis Thompson, MD, said it appears that luspatercept can improve the production of endogenous RBCs by enhancing the maturation of these cells in the bone marrow. The drug significantly reduced the need for RBC transfusions, and “this is a very exciting advance for patients who would have few other treatment options,” she said.

“Anemia and the chronic need for transfusions is a very big issue for these patients,” commented lead study author Pierre Fenaux, MD, PhD, from Hôpital Saint-Louis in Paris, France. “With low hemoglobin levels, patients are tired all the time and have an increased risk of falls and cardiovascular events. When you can improve hemoglobin levels, you really see a difference in quality of life.”

The MEDALIST trial is an important milestone for patients with lower-risk, transfusion-dependent MDS, commented Elizabeth Griffiths, MD, associate professor of oncology and director of MDS, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

“No new agents have been approved for MDS in the last 10 years, highlighting this development as a substantial step forward for the MDS community,” she told Medscape Medical News. “Current therapies are time-intensive and only modestly beneficial.”

“The availability of a new, effective drug — particularly relevant to those harboring SF3B1 mutations — is an exciting development and is likely to offer meaningful improvements in quality of life,” Griffiths said. “Since these patients tend to live longer than others with MDS, there are many patients in my clinical practice who would have fit the enrollment criteria for this study. Such patients are eagerly awaiting the opportunity for a decrease in transfusion burden.”
 

Study Details

In the trial, luspatercept reduced the severity of anemia — 38% of the 153 patients who received luspatercept achieved transfusion independence for 8 weeks or longer compared with 13% of the 76 patients receiving placebo (P < .001).

In the study, patients received luspatercept at a starting dose of 1.0 mg/kg with titration up to 1.75 mg/kg, if needed, or placebo, subcutaneously every 3 weeks for at least 24 weeks.

During the 16 weeks before the initiation of treatment, study patients had received a median of 5 RBC units transfusions during an 8-week period (43.2% of patients had ≥ 6 RBC units, 27.9% had ≥ 4 to < 6 RBC units, and 28.8% had < 4 RBC units). At baseline, 138 (60.3%), 58 (25.3%), and 32 (14%) patients had serum erythropoietin levels less than 200 IU/L, 200-500 IU/L, and greater than 500 IU/L, respectively.

The most common luspatercept-associated adverse events (any grade) in the trial were fatigue, diarrhea, asthenia, nausea, and dizziness. Grade 3 or 4 treatment-emergent adverse events were reported in 42.5% of patients who received luspatercept and 44.7% of patients who received placebo. The incidence of adverse events decreased over time, according to the study authors.

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved luspatercept (Reblozyl, Bristol-Myers Squibb/Acceleron) for the treatment of anemia in patients with myelodysplastic syndromes (MDS).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The green light represents the first treatment advancement in MDS in more than a decade, says an expert in the field.

Luspatercept is the first and so far only erythroid maturation agent (EMA), and was launched last year when it was approved for the treatment of anemia in adults with beta thalassemia, who require regular red blood cell transfusions.

The new approval is for the treatment of anemia in adult patients with very low- to intermediate-risk MDS with ring sideroblasts and patients with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, after they have progressed on treatment with an erythropoiesis-stimulating agent and who require two or more red blood cell (RBC) units over 8 weeks.

Luspatercept is not a substitute for RBC transfusions in patients who require immediate correction of anemia.

The FDA approval in MDS is based on results from the pivotal, placebo-controlled, phase 3 MEDALIST trial, conducted in 229 patients with very-low–, low- and intermediate-risk non-del(5q) MDS with ring sideroblasts. All patients were RBC transfusion-dependent and had disease that was refractory to, or unlikely to respond to, erythropoiesis-stimulating agents. Results were published in January in the New England Journal of Medicine. The study was funded by Acceleron Pharma and Celgene, which was later acquired by Bristol-Myers Squibb.

These results were first presented at the 2018 annual meeting of the American Society of Hematology (ASH), as reported by Medscape Medical News. At the time, ASH President Alexis Thompson, MD, said it appears that luspatercept can improve the production of endogenous RBCs by enhancing the maturation of these cells in the bone marrow. The drug significantly reduced the need for RBC transfusions, and “this is a very exciting advance for patients who would have few other treatment options,” she said.

“Anemia and the chronic need for transfusions is a very big issue for these patients,” commented lead study author Pierre Fenaux, MD, PhD, from Hôpital Saint-Louis in Paris, France. “With low hemoglobin levels, patients are tired all the time and have an increased risk of falls and cardiovascular events. When you can improve hemoglobin levels, you really see a difference in quality of life.”

The MEDALIST trial is an important milestone for patients with lower-risk, transfusion-dependent MDS, commented Elizabeth Griffiths, MD, associate professor of oncology and director of MDS, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

“No new agents have been approved for MDS in the last 10 years, highlighting this development as a substantial step forward for the MDS community,” she told Medscape Medical News. “Current therapies are time-intensive and only modestly beneficial.”

“The availability of a new, effective drug — particularly relevant to those harboring SF3B1 mutations — is an exciting development and is likely to offer meaningful improvements in quality of life,” Griffiths said. “Since these patients tend to live longer than others with MDS, there are many patients in my clinical practice who would have fit the enrollment criteria for this study. Such patients are eagerly awaiting the opportunity for a decrease in transfusion burden.”
 

Study Details

In the trial, luspatercept reduced the severity of anemia — 38% of the 153 patients who received luspatercept achieved transfusion independence for 8 weeks or longer compared with 13% of the 76 patients receiving placebo (P < .001).

In the study, patients received luspatercept at a starting dose of 1.0 mg/kg with titration up to 1.75 mg/kg, if needed, or placebo, subcutaneously every 3 weeks for at least 24 weeks.

During the 16 weeks before the initiation of treatment, study patients had received a median of 5 RBC units transfusions during an 8-week period (43.2% of patients had ≥ 6 RBC units, 27.9% had ≥ 4 to < 6 RBC units, and 28.8% had < 4 RBC units). At baseline, 138 (60.3%), 58 (25.3%), and 32 (14%) patients had serum erythropoietin levels less than 200 IU/L, 200-500 IU/L, and greater than 500 IU/L, respectively.

The most common luspatercept-associated adverse events (any grade) in the trial were fatigue, diarrhea, asthenia, nausea, and dizziness. Grade 3 or 4 treatment-emergent adverse events were reported in 42.5% of patients who received luspatercept and 44.7% of patients who received placebo. The incidence of adverse events decreased over time, according to the study authors.

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved luspatercept (Reblozyl, Bristol-Myers Squibb/Acceleron) for the treatment of anemia in patients with myelodysplastic syndromes (MDS).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The green light represents the first treatment advancement in MDS in more than a decade, says an expert in the field.

Luspatercept is the first and so far only erythroid maturation agent (EMA), and was launched last year when it was approved for the treatment of anemia in adults with beta thalassemia, who require regular red blood cell transfusions.

The new approval is for the treatment of anemia in adult patients with very low- to intermediate-risk MDS with ring sideroblasts and patients with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, after they have progressed on treatment with an erythropoiesis-stimulating agent and who require two or more red blood cell (RBC) units over 8 weeks.

Luspatercept is not a substitute for RBC transfusions in patients who require immediate correction of anemia.

The FDA approval in MDS is based on results from the pivotal, placebo-controlled, phase 3 MEDALIST trial, conducted in 229 patients with very-low–, low- and intermediate-risk non-del(5q) MDS with ring sideroblasts. All patients were RBC transfusion-dependent and had disease that was refractory to, or unlikely to respond to, erythropoiesis-stimulating agents. Results were published in January in the New England Journal of Medicine. The study was funded by Acceleron Pharma and Celgene, which was later acquired by Bristol-Myers Squibb.

These results were first presented at the 2018 annual meeting of the American Society of Hematology (ASH), as reported by Medscape Medical News. At the time, ASH President Alexis Thompson, MD, said it appears that luspatercept can improve the production of endogenous RBCs by enhancing the maturation of these cells in the bone marrow. The drug significantly reduced the need for RBC transfusions, and “this is a very exciting advance for patients who would have few other treatment options,” she said.

“Anemia and the chronic need for transfusions is a very big issue for these patients,” commented lead study author Pierre Fenaux, MD, PhD, from Hôpital Saint-Louis in Paris, France. “With low hemoglobin levels, patients are tired all the time and have an increased risk of falls and cardiovascular events. When you can improve hemoglobin levels, you really see a difference in quality of life.”

The MEDALIST trial is an important milestone for patients with lower-risk, transfusion-dependent MDS, commented Elizabeth Griffiths, MD, associate professor of oncology and director of MDS, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

“No new agents have been approved for MDS in the last 10 years, highlighting this development as a substantial step forward for the MDS community,” she told Medscape Medical News. “Current therapies are time-intensive and only modestly beneficial.”

“The availability of a new, effective drug — particularly relevant to those harboring SF3B1 mutations — is an exciting development and is likely to offer meaningful improvements in quality of life,” Griffiths said. “Since these patients tend to live longer than others with MDS, there are many patients in my clinical practice who would have fit the enrollment criteria for this study. Such patients are eagerly awaiting the opportunity for a decrease in transfusion burden.”
 

Study Details

In the trial, luspatercept reduced the severity of anemia — 38% of the 153 patients who received luspatercept achieved transfusion independence for 8 weeks or longer compared with 13% of the 76 patients receiving placebo (P < .001).

In the study, patients received luspatercept at a starting dose of 1.0 mg/kg with titration up to 1.75 mg/kg, if needed, or placebo, subcutaneously every 3 weeks for at least 24 weeks.

During the 16 weeks before the initiation of treatment, study patients had received a median of 5 RBC units transfusions during an 8-week period (43.2% of patients had ≥ 6 RBC units, 27.9% had ≥ 4 to < 6 RBC units, and 28.8% had < 4 RBC units). At baseline, 138 (60.3%), 58 (25.3%), and 32 (14%) patients had serum erythropoietin levels less than 200 IU/L, 200-500 IU/L, and greater than 500 IU/L, respectively.

The most common luspatercept-associated adverse events (any grade) in the trial were fatigue, diarrhea, asthenia, nausea, and dizziness. Grade 3 or 4 treatment-emergent adverse events were reported in 42.5% of patients who received luspatercept and 44.7% of patients who received placebo. The incidence of adverse events decreased over time, according to the study authors.

This article first appeared on Medscape.com.

Hyponatremia, defined as a plasma sodium concentration ≤ 135 mmol/L at admission, was associated with complications during episodes of acute pain from sickle cell disease, according to a large retrospective analysis.

The French study assessed 1,218 stays of 406 patients admitted for treatment of an acute painful episode of sickle cell disease between 2010-2015. The primary composite endpoint comprised acute chest syndrome, intensive care unit transfer, red blood cell transfusion or inpatient death. The analyses were adjusted for age, sex, hemoglobin genotype and concentration, LDH concentration, and white blood cell count, according to the researchers.

Hyponatremia at admission in the center was associated with the primary endpoint (adjusted odds ratio (OR) 1.95, P = .001). This association was independent from baseline demographic characteristics (age, sex, hemoglobin genotype) and from other prognostic factors examined in the study (lower hemoglobin concentration, higher white blood cell count and LDH concentration).

With regard to individual components of the primary endpoint, hyponatremia was associated with acute chest syndrome (OR 1.95, P = .008) and red blood cell transfusion (OR 2.71, P <.001), but not significantly with intensive care unit transfer (OR 1.83, P  = .074). In addition, the adjusted mean length of stay was significantly longer by 1.1 days (P < .001) in patients with hyponatremia at admission.

The study received no funding and the researchers reported that they had no conflicts of interest.

SOURCE: Rech JS et al. Amer J Med. 2020. doi.org/10.1016/j.amjmed.2020.02.017.

Hyponatremia, defined as a plasma sodium concentration ≤ 135 mmol/L at admission, was associated with complications during episodes of acute pain from sickle cell disease, according to a large retrospective analysis.

The French study assessed 1,218 stays of 406 patients admitted for treatment of an acute painful episode of sickle cell disease between 2010-2015. The primary composite endpoint comprised acute chest syndrome, intensive care unit transfer, red blood cell transfusion or inpatient death. The analyses were adjusted for age, sex, hemoglobin genotype and concentration, LDH concentration, and white blood cell count, according to the researchers.

Hyponatremia at admission in the center was associated with the primary endpoint (adjusted odds ratio (OR) 1.95, P = .001). This association was independent from baseline demographic characteristics (age, sex, hemoglobin genotype) and from other prognostic factors examined in the study (lower hemoglobin concentration, higher white blood cell count and LDH concentration).

With regard to individual components of the primary endpoint, hyponatremia was associated with acute chest syndrome (OR 1.95, P = .008) and red blood cell transfusion (OR 2.71, P <.001), but not significantly with intensive care unit transfer (OR 1.83, P  = .074). In addition, the adjusted mean length of stay was significantly longer by 1.1 days (P < .001) in patients with hyponatremia at admission.

The study received no funding and the researchers reported that they had no conflicts of interest.

SOURCE: Rech JS et al. Amer J Med. 2020. doi.org/10.1016/j.amjmed.2020.02.017.

Hyponatremia, defined as a plasma sodium concentration ≤ 135 mmol/L at admission, was associated with complications during episodes of acute pain from sickle cell disease, according to a large retrospective analysis.

The French study assessed 1,218 stays of 406 patients admitted for treatment of an acute painful episode of sickle cell disease between 2010-2015. The primary composite endpoint comprised acute chest syndrome, intensive care unit transfer, red blood cell transfusion or inpatient death. The analyses were adjusted for age, sex, hemoglobin genotype and concentration, LDH concentration, and white blood cell count, according to the researchers.

Hyponatremia at admission in the center was associated with the primary endpoint (adjusted odds ratio (OR) 1.95, P = .001). This association was independent from baseline demographic characteristics (age, sex, hemoglobin genotype) and from other prognostic factors examined in the study (lower hemoglobin concentration, higher white blood cell count and LDH concentration).

With regard to individual components of the primary endpoint, hyponatremia was associated with acute chest syndrome (OR 1.95, P = .008) and red blood cell transfusion (OR 2.71, P <.001), but not significantly with intensive care unit transfer (OR 1.83, P  = .074). In addition, the adjusted mean length of stay was significantly longer by 1.1 days (P < .001) in patients with hyponatremia at admission.

The study received no funding and the researchers reported that they had no conflicts of interest.

SOURCE: Rech JS et al. Amer J Med. 2020. doi.org/10.1016/j.amjmed.2020.02.017.