Hematologic Malignancies

A new class of cancer drugs, SMAC mimetics, induces apoptosis by mimicking a protein that regulates cancer cell survival. The drugs have shown promising results in studies on many fronts. In animal and cell-line studies, the drugs killed cancer cells and shrank tumors. Now National Cancer Institute (NCI) researchers are hoping to put them to the test in clinical trials with patients who have the ABC subtype of diffuse large B-cell lymphoma (DLBCL).

Of the 2 distinct molecular DLBCL subtypes, ABC DLBCL is the least curable, the researchers note. A hallmark of the ABC subtype is the continuous activation of the B-cell receptor (BCR) signaling pathway, which promotes cell growth and survival by overriding signals for apoptosis. When other research suggested that blocking a protein in the NF-ΚB protein complex in the BCR pathway was effective, the NCI researchers also began to look at other potentially targetable proteins.

In preliminary studies, the researchers showed that the proteins cIAP1 and cIAP2 control the activity of the BCR signaling pathway in ABC DLBCL. Birinapant, one of the SMAC mimetics in clinical development, reduced cIAP1 and cIAP2 levels in ABC cell lines. Further research showed that birinapant had the effect only in those cancer cells that depend on BCR signaling for survival.

According to NCI, SMAC mimetics are well tolerated and seem to be safe. In animal studies, birinapant “substantially shrank tumors while causing no evident toxicity.”

A new class of cancer drugs, SMAC mimetics, induces apoptosis by mimicking a protein that regulates cancer cell survival. The drugs have shown promising results in studies on many fronts. In animal and cell-line studies, the drugs killed cancer cells and shrank tumors. Now National Cancer Institute (NCI) researchers are hoping to put them to the test in clinical trials with patients who have the ABC subtype of diffuse large B-cell lymphoma (DLBCL).

Of the 2 distinct molecular DLBCL subtypes, ABC DLBCL is the least curable, the researchers note. A hallmark of the ABC subtype is the continuous activation of the B-cell receptor (BCR) signaling pathway, which promotes cell growth and survival by overriding signals for apoptosis. When other research suggested that blocking a protein in the NF-ΚB protein complex in the BCR pathway was effective, the NCI researchers also began to look at other potentially targetable proteins.

In preliminary studies, the researchers showed that the proteins cIAP1 and cIAP2 control the activity of the BCR signaling pathway in ABC DLBCL. Birinapant, one of the SMAC mimetics in clinical development, reduced cIAP1 and cIAP2 levels in ABC cell lines. Further research showed that birinapant had the effect only in those cancer cells that depend on BCR signaling for survival.

According to NCI, SMAC mimetics are well tolerated and seem to be safe. In animal studies, birinapant “substantially shrank tumors while causing no evident toxicity.”

A new class of cancer drugs, SMAC mimetics, induces apoptosis by mimicking a protein that regulates cancer cell survival. The drugs have shown promising results in studies on many fronts. In animal and cell-line studies, the drugs killed cancer cells and shrank tumors. Now National Cancer Institute (NCI) researchers are hoping to put them to the test in clinical trials with patients who have the ABC subtype of diffuse large B-cell lymphoma (DLBCL).

Of the 2 distinct molecular DLBCL subtypes, ABC DLBCL is the least curable, the researchers note. A hallmark of the ABC subtype is the continuous activation of the B-cell receptor (BCR) signaling pathway, which promotes cell growth and survival by overriding signals for apoptosis. When other research suggested that blocking a protein in the NF-ΚB protein complex in the BCR pathway was effective, the NCI researchers also began to look at other potentially targetable proteins.

In preliminary studies, the researchers showed that the proteins cIAP1 and cIAP2 control the activity of the BCR signaling pathway in ABC DLBCL. Birinapant, one of the SMAC mimetics in clinical development, reduced cIAP1 and cIAP2 levels in ABC cell lines. Further research showed that birinapant had the effect only in those cancer cells that depend on BCR signaling for survival.

According to NCI, SMAC mimetics are well tolerated and seem to be safe. In animal studies, birinapant “substantially shrank tumors while causing no evident toxicity.”

Background: Cat scratch disease is a benign, self-limiting but rare condition that causes significant lymphadenopathy. There is less than 1 case per 100,000 cases per year, mostly in children. Even rarer are cases presenting in association with malignancies, usually non-Hodgkin lymphoma. Our review of the literature revealed only 1 case of cat scratch disease as-sociated with Hodgkin lymphoma. We describe here a case of a 43-year-old white man who presented with a clinical picture of recurrent Hodgkin lymphoma but with negative serology for Bartonella antibodies, responding to a short course of antibiotic treatment.

Methods: This 43-year-old patient initially presented with stage IA Hodgkin lymphoma in January 2011. He had a me-diastinal mass, which was resected and followed by 4 cycles of ABVD (doxorubicin, bleomycin, vincristine, dexameth-asone) chemotherapy. In July 2011, he went into complete remission after 4 cycles of chemotherapy and remained so until October 2014, when he noted increasing left-sided in-guinal adenopathy accompanied by a constant stabbing pain. He had no other symptoms. On positron emission tomogra-phy/computed tomography (PET/CT) scanning he had sev-eral hypermetabolic splenic lesions and enlarged tonsillar, retroperitoneal, pelvic, axillary, and inguinal lymph nodes. His complete blood count and chemistries were normal. His sedimentation rate was also normal. Bilateral bone marrow biopsies were negative for Hodgkin disease recurrence. Bi-opsy of one of his inguinal nodes was positive for necrotiz-ing granulomas and stained positive for CD2, CD3, and CD5 with areas of high Ki-67 proliferation. Hodgkin disease, how-ever, was not confirmed. He mentioned a family history of cat scratch disease a decade ago when his 2 young children were diagnosed with cat scratch disease and treated with oral antibiotics, resulting in complete resolution of symptoms. Se-rologic testing for Bartonella antibodies was ordered for him but came back negative. An infectious disease consult was re-quested, and he was treated empirically with a 5-day course of azithromycin.

Results: After 2 months, he was seen in the clinic and found to have no palpable inguinal adenopathy. A repeat PET/CT scan at 3 months showed resolution of all areas of lymphadenop-athy with the exception of the left inguinal node basin. At 5 months, all areas of hypermetabolic adenopathy had resolved. A repeat serology for Bartonella antibodies remained negative.

Conclusions: Cat scratch disease is extremely rare but can occur in a patient with known hematologic malignancies. In this case, it was mistaken as a recurrent case of relapsed Hodgkin disease but fortunately resolved quickly. The pre-sentation can be acute; patients can have negative serologies for Bartonellosis, yet achievement of a complete clinical and radiographic response with a short course of oral antibiotics was successful.

Background: Cat scratch disease is a benign, self-limiting but rare condition that causes significant lymphadenopathy. There is less than 1 case per 100,000 cases per year, mostly in children. Even rarer are cases presenting in association with malignancies, usually non-Hodgkin lymphoma. Our review of the literature revealed only 1 case of cat scratch disease as-sociated with Hodgkin lymphoma. We describe here a case of a 43-year-old white man who presented with a clinical picture of recurrent Hodgkin lymphoma but with negative serology for Bartonella antibodies, responding to a short course of antibiotic treatment.

Methods: This 43-year-old patient initially presented with stage IA Hodgkin lymphoma in January 2011. He had a me-diastinal mass, which was resected and followed by 4 cycles of ABVD (doxorubicin, bleomycin, vincristine, dexameth-asone) chemotherapy. In July 2011, he went into complete remission after 4 cycles of chemotherapy and remained so until October 2014, when he noted increasing left-sided in-guinal adenopathy accompanied by a constant stabbing pain. He had no other symptoms. On positron emission tomogra-phy/computed tomography (PET/CT) scanning he had sev-eral hypermetabolic splenic lesions and enlarged tonsillar, retroperitoneal, pelvic, axillary, and inguinal lymph nodes. His complete blood count and chemistries were normal. His sedimentation rate was also normal. Bilateral bone marrow biopsies were negative for Hodgkin disease recurrence. Bi-opsy of one of his inguinal nodes was positive for necrotiz-ing granulomas and stained positive for CD2, CD3, and CD5 with areas of high Ki-67 proliferation. Hodgkin disease, how-ever, was not confirmed. He mentioned a family history of cat scratch disease a decade ago when his 2 young children were diagnosed with cat scratch disease and treated with oral antibiotics, resulting in complete resolution of symptoms. Se-rologic testing for Bartonella antibodies was ordered for him but came back negative. An infectious disease consult was re-quested, and he was treated empirically with a 5-day course of azithromycin.

Results: After 2 months, he was seen in the clinic and found to have no palpable inguinal adenopathy. A repeat PET/CT scan at 3 months showed resolution of all areas of lymphadenop-athy with the exception of the left inguinal node basin. At 5 months, all areas of hypermetabolic adenopathy had resolved. A repeat serology for Bartonella antibodies remained negative.

Conclusions: Cat scratch disease is extremely rare but can occur in a patient with known hematologic malignancies. In this case, it was mistaken as a recurrent case of relapsed Hodgkin disease but fortunately resolved quickly. The pre-sentation can be acute; patients can have negative serologies for Bartonellosis, yet achievement of a complete clinical and radiographic response with a short course of oral antibiotics was successful.

Background: Cat scratch disease is a benign, self-limiting but rare condition that causes significant lymphadenopathy. There is less than 1 case per 100,000 cases per year, mostly in children. Even rarer are cases presenting in association with malignancies, usually non-Hodgkin lymphoma. Our review of the literature revealed only 1 case of cat scratch disease as-sociated with Hodgkin lymphoma. We describe here a case of a 43-year-old white man who presented with a clinical picture of recurrent Hodgkin lymphoma but with negative serology for Bartonella antibodies, responding to a short course of antibiotic treatment.

Methods: This 43-year-old patient initially presented with stage IA Hodgkin lymphoma in January 2011. He had a me-diastinal mass, which was resected and followed by 4 cycles of ABVD (doxorubicin, bleomycin, vincristine, dexameth-asone) chemotherapy. In July 2011, he went into complete remission after 4 cycles of chemotherapy and remained so until October 2014, when he noted increasing left-sided in-guinal adenopathy accompanied by a constant stabbing pain. He had no other symptoms. On positron emission tomogra-phy/computed tomography (PET/CT) scanning he had sev-eral hypermetabolic splenic lesions and enlarged tonsillar, retroperitoneal, pelvic, axillary, and inguinal lymph nodes. His complete blood count and chemistries were normal. His sedimentation rate was also normal. Bilateral bone marrow biopsies were negative for Hodgkin disease recurrence. Bi-opsy of one of his inguinal nodes was positive for necrotiz-ing granulomas and stained positive for CD2, CD3, and CD5 with areas of high Ki-67 proliferation. Hodgkin disease, how-ever, was not confirmed. He mentioned a family history of cat scratch disease a decade ago when his 2 young children were diagnosed with cat scratch disease and treated with oral antibiotics, resulting in complete resolution of symptoms. Se-rologic testing for Bartonella antibodies was ordered for him but came back negative. An infectious disease consult was re-quested, and he was treated empirically with a 5-day course of azithromycin.

Results: After 2 months, he was seen in the clinic and found to have no palpable inguinal adenopathy. A repeat PET/CT scan at 3 months showed resolution of all areas of lymphadenop-athy with the exception of the left inguinal node basin. At 5 months, all areas of hypermetabolic adenopathy had resolved. A repeat serology for Bartonella antibodies remained negative.

Conclusions: Cat scratch disease is extremely rare but can occur in a patient with known hematologic malignancies. In this case, it was mistaken as a recurrent case of relapsed Hodgkin disease but fortunately resolved quickly. The pre-sentation can be acute; patients can have negative serologies for Bartonellosis, yet achievement of a complete clinical and radiographic response with a short course of oral antibiotics was successful.

Purpose: Today, patients with relapsed low-grade or follicular B-cell non-Hodgkin lymphoma have more treatment options available to them than ever. These therapies include infused chemotherapy regimens, radioimmunotherapy, and oral agents. There is limited information available about the impact of available treatment sequences on clinical outcomes and costs.

Methods: A budget impact model was developed to represent the current treatment pathways for relapsed low-grade or follicular B-cell non-Hodgkin lymphoma. First-line treatment regimens were selected based on the Category 1 recommendations from the National Comprehensive Cancer Network guidelines for follicular lymphoma. Those included were the most commonly used: BR, RCHOP, and RCVP. For purposes of this model, the second-line regimens included Y90 ibritumomab (Y90), rituximab monotherapy with 4 weekly doses, and idelalisib. Treatment outcomes were based on the published literature that summarized the overall response rate, median duration of response (DOR), and toxicity. Total costs per treatment regimen were based on medical care, drugs administered, and associated adverse effects. The 2015 Medicare fee schedule rates were used to estimate the medical care costs. Total DOR and costs were determined for each treatment regimen.

Results: The treatment sequence, BR followed by Y90 at the time of relapse, had the longest predicted DOR (7.2 years). The associated treatment sequence costs were $157,712 for BR followed by Y90, compared with $224,628 and $145,047 for BR followed by idelalisib and BR followed by rituximab monotherapy, respectively, with a predicted DOR of 6.7 years. The predicted DOR for treatment sequences starting with RCVP and RCHOP and followed by Y90 was about 3 years less than BR followed by Y90 at a cost increase of $11,102 and $37,866, respectively. The use of idelalisib after RCVP or RCHOP had a predicted DOR of 3.6 years, respectively, with associated costs that were greater than BR followed by Y90.

Conclusions: The use of Y90 ibritumomab after BR demonstrated the optimal patient outcomes at one of the lowest cost profiles.

Purpose: Today, patients with relapsed low-grade or follicular B-cell non-Hodgkin lymphoma have more treatment options available to them than ever. These therapies include infused chemotherapy regimens, radioimmunotherapy, and oral agents. There is limited information available about the impact of available treatment sequences on clinical outcomes and costs.

Methods: A budget impact model was developed to represent the current treatment pathways for relapsed low-grade or follicular B-cell non-Hodgkin lymphoma. First-line treatment regimens were selected based on the Category 1 recommendations from the National Comprehensive Cancer Network guidelines for follicular lymphoma. Those included were the most commonly used: BR, RCHOP, and RCVP. For purposes of this model, the second-line regimens included Y90 ibritumomab (Y90), rituximab monotherapy with 4 weekly doses, and idelalisib. Treatment outcomes were based on the published literature that summarized the overall response rate, median duration of response (DOR), and toxicity. Total costs per treatment regimen were based on medical care, drugs administered, and associated adverse effects. The 2015 Medicare fee schedule rates were used to estimate the medical care costs. Total DOR and costs were determined for each treatment regimen.

Results: The treatment sequence, BR followed by Y90 at the time of relapse, had the longest predicted DOR (7.2 years). The associated treatment sequence costs were $157,712 for BR followed by Y90, compared with $224,628 and $145,047 for BR followed by idelalisib and BR followed by rituximab monotherapy, respectively, with a predicted DOR of 6.7 years. The predicted DOR for treatment sequences starting with RCVP and RCHOP and followed by Y90 was about 3 years less than BR followed by Y90 at a cost increase of $11,102 and $37,866, respectively. The use of idelalisib after RCVP or RCHOP had a predicted DOR of 3.6 years, respectively, with associated costs that were greater than BR followed by Y90.

Conclusions: The use of Y90 ibritumomab after BR demonstrated the optimal patient outcomes at one of the lowest cost profiles.

Purpose: Today, patients with relapsed low-grade or follicular B-cell non-Hodgkin lymphoma have more treatment options available to them than ever. These therapies include infused chemotherapy regimens, radioimmunotherapy, and oral agents. There is limited information available about the impact of available treatment sequences on clinical outcomes and costs.

Methods: A budget impact model was developed to represent the current treatment pathways for relapsed low-grade or follicular B-cell non-Hodgkin lymphoma. First-line treatment regimens were selected based on the Category 1 recommendations from the National Comprehensive Cancer Network guidelines for follicular lymphoma. Those included were the most commonly used: BR, RCHOP, and RCVP. For purposes of this model, the second-line regimens included Y90 ibritumomab (Y90), rituximab monotherapy with 4 weekly doses, and idelalisib. Treatment outcomes were based on the published literature that summarized the overall response rate, median duration of response (DOR), and toxicity. Total costs per treatment regimen were based on medical care, drugs administered, and associated adverse effects. The 2015 Medicare fee schedule rates were used to estimate the medical care costs. Total DOR and costs were determined for each treatment regimen.

Results: The treatment sequence, BR followed by Y90 at the time of relapse, had the longest predicted DOR (7.2 years). The associated treatment sequence costs were $157,712 for BR followed by Y90, compared with $224,628 and $145,047 for BR followed by idelalisib and BR followed by rituximab monotherapy, respectively, with a predicted DOR of 6.7 years. The predicted DOR for treatment sequences starting with RCVP and RCHOP and followed by Y90 was about 3 years less than BR followed by Y90 at a cost increase of $11,102 and $37,866, respectively. The use of idelalisib after RCVP or RCHOP had a predicted DOR of 3.6 years, respectively, with associated costs that were greater than BR followed by Y90.

Conclusions: The use of Y90 ibritumomab after BR demonstrated the optimal patient outcomes at one of the lowest cost profiles.

Low-dose cytarabine in combination with valproic acid and all-transretinoic acid (ATRA) is used in stabilizing treatment for patients with acute myeloid leukemia (AML) who aren’t candidates for intensive therapy. In vivo studies have shown that the triple-drug treatment has immunomodulatory effects. But researchers from University of Bergen, Norway, say little was known about both the acute and long-term effects of such treatment on the T-cell system.

Related: Signaling Pathways and Novel Inhibitors in Chronic Lymphocytic Leukemia

To find out, they conducted an in vitro study to examine the effects of cytarabine, valproic acid, and ATRA on activated T cells, testing cytarabine at concentrations reached during in vivo treatment with high doses, conventional doses, and low doses. 

The researchers found that cytarabine—especially when combined with valproic acid and ATRA—can reduce T-cell viability and proliferation, alter the activation-induced expression of membrane molecules, and reduce the release of several cytokines. Cytarabine’s effects on T-cell activation were concentration dependent: Reduced viability was seen only at the higher concentrations. However, the researchers note that cytarabine had immunoregulatory effects even at lower levels. When cytarabine was combined with valproic acid and ATRA, the researchers observed no or minor effects on T-cell viability.

Related: Blast Phase Chronic Myelogenous Leukemia

Only cytarabine 44 μM had both antiproliferative and proapoptotic effects. The drug reduced AML cell viability only at 0.5 and 0.05 μM, not at the lowest concentration; but it inhibited AML cell proliferation even at 0.01 μM. By contrast, T-cell proliferation was inhibited only at concentrations  ≥ 0.35 μM.

Based on the proliferation studies, the researchers conclude that primary AML cells are more susceptible to cytarabine than are normal T cells, which suggests, they add, a therapeutic window for cytarabine treatment that “makes it possible to achieve antileukemic effects in vivo before severe T-cell toxicity occurs.”

Related:HIV-Negative Patients at Risk for Pneumocystosis

The triple-drug combination’s direct effects on the T cells may be offset by other effects on immunocompetent cells; the researchers say the possible risk of immunosuppression should be further investigated.

Source
Ersvaer E, Brenner AK, Vetås K, Reikvam H, Bruserud Ø. BMC Pharmacol Toxicol. 2015;16:12.
doi: 10.1186/s40360-015-0012-2.

Low-dose cytarabine in combination with valproic acid and all-transretinoic acid (ATRA) is used in stabilizing treatment for patients with acute myeloid leukemia (AML) who aren’t candidates for intensive therapy. In vivo studies have shown that the triple-drug treatment has immunomodulatory effects. But researchers from University of Bergen, Norway, say little was known about both the acute and long-term effects of such treatment on the T-cell system.

Related: Signaling Pathways and Novel Inhibitors in Chronic Lymphocytic Leukemia

To find out, they conducted an in vitro study to examine the effects of cytarabine, valproic acid, and ATRA on activated T cells, testing cytarabine at concentrations reached during in vivo treatment with high doses, conventional doses, and low doses. 

The researchers found that cytarabine—especially when combined with valproic acid and ATRA—can reduce T-cell viability and proliferation, alter the activation-induced expression of membrane molecules, and reduce the release of several cytokines. Cytarabine’s effects on T-cell activation were concentration dependent: Reduced viability was seen only at the higher concentrations. However, the researchers note that cytarabine had immunoregulatory effects even at lower levels. When cytarabine was combined with valproic acid and ATRA, the researchers observed no or minor effects on T-cell viability.

Related: Blast Phase Chronic Myelogenous Leukemia

Only cytarabine 44 μM had both antiproliferative and proapoptotic effects. The drug reduced AML cell viability only at 0.5 and 0.05 μM, not at the lowest concentration; but it inhibited AML cell proliferation even at 0.01 μM. By contrast, T-cell proliferation was inhibited only at concentrations  ≥ 0.35 μM.

Based on the proliferation studies, the researchers conclude that primary AML cells are more susceptible to cytarabine than are normal T cells, which suggests, they add, a therapeutic window for cytarabine treatment that “makes it possible to achieve antileukemic effects in vivo before severe T-cell toxicity occurs.”

Related:HIV-Negative Patients at Risk for Pneumocystosis

The triple-drug combination’s direct effects on the T cells may be offset by other effects on immunocompetent cells; the researchers say the possible risk of immunosuppression should be further investigated.

Source
Ersvaer E, Brenner AK, Vetås K, Reikvam H, Bruserud Ø. BMC Pharmacol Toxicol. 2015;16:12.
doi: 10.1186/s40360-015-0012-2.

Low-dose cytarabine in combination with valproic acid and all-transretinoic acid (ATRA) is used in stabilizing treatment for patients with acute myeloid leukemia (AML) who aren’t candidates for intensive therapy. In vivo studies have shown that the triple-drug treatment has immunomodulatory effects. But researchers from University of Bergen, Norway, say little was known about both the acute and long-term effects of such treatment on the T-cell system.

Related: Signaling Pathways and Novel Inhibitors in Chronic Lymphocytic Leukemia

To find out, they conducted an in vitro study to examine the effects of cytarabine, valproic acid, and ATRA on activated T cells, testing cytarabine at concentrations reached during in vivo treatment with high doses, conventional doses, and low doses. 

The researchers found that cytarabine—especially when combined with valproic acid and ATRA—can reduce T-cell viability and proliferation, alter the activation-induced expression of membrane molecules, and reduce the release of several cytokines. Cytarabine’s effects on T-cell activation were concentration dependent: Reduced viability was seen only at the higher concentrations. However, the researchers note that cytarabine had immunoregulatory effects even at lower levels. When cytarabine was combined with valproic acid and ATRA, the researchers observed no or minor effects on T-cell viability.

Related: Blast Phase Chronic Myelogenous Leukemia

Only cytarabine 44 μM had both antiproliferative and proapoptotic effects. The drug reduced AML cell viability only at 0.5 and 0.05 μM, not at the lowest concentration; but it inhibited AML cell proliferation even at 0.01 μM. By contrast, T-cell proliferation was inhibited only at concentrations  ≥ 0.35 μM.

Based on the proliferation studies, the researchers conclude that primary AML cells are more susceptible to cytarabine than are normal T cells, which suggests, they add, a therapeutic window for cytarabine treatment that “makes it possible to achieve antileukemic effects in vivo before severe T-cell toxicity occurs.”

Related:HIV-Negative Patients at Risk for Pneumocystosis

The triple-drug combination’s direct effects on the T cells may be offset by other effects on immunocompetent cells; the researchers say the possible risk of immunosuppression should be further investigated.

Source
Ersvaer E, Brenner AK, Vetås K, Reikvam H, Bruserud Ø. BMC Pharmacol Toxicol. 2015;16:12.
doi: 10.1186/s40360-015-0012-2.

Backround: Mastocytosis is a rare disease with a variable clinical course. Pure red cell aplasia has not been frequently reported in association with aggressive systemic mastocytosis. CD30 is often expressed on mast cells in systemic mastocytosis. The CD30-directed antibody-drug conjugate brentuximab vedotin has shown in vitro activity against CD30-positive neoplastic mast cells. We describe a case of systemic mastocytosis with the development of severe hemolytic anemia, pure red cell aplasia, and evidence of weak bone marrow CD30 positivity. Brentuximab vedotin was administered with some evidence of clinical benefit.

Patient: A 64-year-old man presented with fatigue and a 20 pound weight loss. He was found to have transfusion-dependent anemia, a low reticulocyte count, and splenomegaly. Evaluation for gastrointestinal blood loss was unremarkable. Bone marrow biopsy showed mast cell aggregates, spindle-shaped mast cells, CD-2 and CD25-positivity, increased myelopoiesis and dysmegakaryopoiesis, red cell aplasia, eosinophilia, and increased reticulin fibrosis. The D816V c-kit mutation was present, and serum tryptase level was elevated at 114 ng/mL. He later developed Coombs-positive hemolysis and direct hyperbilirubinemia, concerning for mast cell liver infiltration.

Intervention: The patient received high-dose steroids and red blood cell transfusions. Interferon alpha and cladribine were contraindicated, given severe liver dysfunction. He was started on hydroxyurea. He received a dose of brentuximab vedotin 1.8 mg/kg IV. Thirteen days after starting steroids and 10 days after brentuximab, haptoglobin became detectable, and total bilirubin decreased to 18.4 mg/dL from 40.5 mg/dL. Red blood cell transfusion requirements decreased. He then developed severe neutropenia, pneumonia with sepsis, and respiratory failure, requiring intubation, maximal pressor support, and broad-spectrum antibiotics. Despite these measures, he expired.

Discussion/Conclusion: This is a rare case of pure red cellaplasia in the setting of aggressive systemic mastocytosis. Therapeutic options were limited in the setting of liver dysfunction, and therapy with brentuximab vedotin resulted in initial clinical benefit. Brentuximab vedotin is being investigated in patients with advanced systemic mastocytosis or mast cell leukemia.

Backround: Mastocytosis is a rare disease with a variable clinical course. Pure red cell aplasia has not been frequently reported in association with aggressive systemic mastocytosis. CD30 is often expressed on mast cells in systemic mastocytosis. The CD30-directed antibody-drug conjugate brentuximab vedotin has shown in vitro activity against CD30-positive neoplastic mast cells. We describe a case of systemic mastocytosis with the development of severe hemolytic anemia, pure red cell aplasia, and evidence of weak bone marrow CD30 positivity. Brentuximab vedotin was administered with some evidence of clinical benefit.

Patient: A 64-year-old man presented with fatigue and a 20 pound weight loss. He was found to have transfusion-dependent anemia, a low reticulocyte count, and splenomegaly. Evaluation for gastrointestinal blood loss was unremarkable. Bone marrow biopsy showed mast cell aggregates, spindle-shaped mast cells, CD-2 and CD25-positivity, increased myelopoiesis and dysmegakaryopoiesis, red cell aplasia, eosinophilia, and increased reticulin fibrosis. The D816V c-kit mutation was present, and serum tryptase level was elevated at 114 ng/mL. He later developed Coombs-positive hemolysis and direct hyperbilirubinemia, concerning for mast cell liver infiltration.

Intervention: The patient received high-dose steroids and red blood cell transfusions. Interferon alpha and cladribine were contraindicated, given severe liver dysfunction. He was started on hydroxyurea. He received a dose of brentuximab vedotin 1.8 mg/kg IV. Thirteen days after starting steroids and 10 days after brentuximab, haptoglobin became detectable, and total bilirubin decreased to 18.4 mg/dL from 40.5 mg/dL. Red blood cell transfusion requirements decreased. He then developed severe neutropenia, pneumonia with sepsis, and respiratory failure, requiring intubation, maximal pressor support, and broad-spectrum antibiotics. Despite these measures, he expired.

Discussion/Conclusion: This is a rare case of pure red cellaplasia in the setting of aggressive systemic mastocytosis. Therapeutic options were limited in the setting of liver dysfunction, and therapy with brentuximab vedotin resulted in initial clinical benefit. Brentuximab vedotin is being investigated in patients with advanced systemic mastocytosis or mast cell leukemia.

Backround: Mastocytosis is a rare disease with a variable clinical course. Pure red cell aplasia has not been frequently reported in association with aggressive systemic mastocytosis. CD30 is often expressed on mast cells in systemic mastocytosis. The CD30-directed antibody-drug conjugate brentuximab vedotin has shown in vitro activity against CD30-positive neoplastic mast cells. We describe a case of systemic mastocytosis with the development of severe hemolytic anemia, pure red cell aplasia, and evidence of weak bone marrow CD30 positivity. Brentuximab vedotin was administered with some evidence of clinical benefit.

Patient: A 64-year-old man presented with fatigue and a 20 pound weight loss. He was found to have transfusion-dependent anemia, a low reticulocyte count, and splenomegaly. Evaluation for gastrointestinal blood loss was unremarkable. Bone marrow biopsy showed mast cell aggregates, spindle-shaped mast cells, CD-2 and CD25-positivity, increased myelopoiesis and dysmegakaryopoiesis, red cell aplasia, eosinophilia, and increased reticulin fibrosis. The D816V c-kit mutation was present, and serum tryptase level was elevated at 114 ng/mL. He later developed Coombs-positive hemolysis and direct hyperbilirubinemia, concerning for mast cell liver infiltration.

Intervention: The patient received high-dose steroids and red blood cell transfusions. Interferon alpha and cladribine were contraindicated, given severe liver dysfunction. He was started on hydroxyurea. He received a dose of brentuximab vedotin 1.8 mg/kg IV. Thirteen days after starting steroids and 10 days after brentuximab, haptoglobin became detectable, and total bilirubin decreased to 18.4 mg/dL from 40.5 mg/dL. Red blood cell transfusion requirements decreased. He then developed severe neutropenia, pneumonia with sepsis, and respiratory failure, requiring intubation, maximal pressor support, and broad-spectrum antibiotics. Despite these measures, he expired.

Discussion/Conclusion: This is a rare case of pure red cellaplasia in the setting of aggressive systemic mastocytosis. Therapeutic options were limited in the setting of liver dysfunction, and therapy with brentuximab vedotin resulted in initial clinical benefit. Brentuximab vedotin is being investigated in patients with advanced systemic mastocytosis or mast cell leukemia.

Background: Historically the Hematology Clinics at the Robley Rex VA Medical Center (RRVAMC) had a chronically elevated no-show rate (NSR). The major cause of these missed opportunities was patient adherence secondary to transportation, distance traveled, and patients’ lack of concern about their disease. Our hypothesis was that the no-show rates could be significantly reduced by providing virtual hematology services outside the main VA campus.

Methods: A comprehensive review of the hematology patient population was conducted to identify veterans with stable hematologic disorders (SHD), eg, stage 0 chronic lymphocytic leukemia, monoclonal gammopathy of undetermined significance, and chronic anemia. The NSR was determined for 2012. Patients with SHD were identified as potential subjects for the Telehematology Clinic. The clinic was started July 2013 and eventually expanded to a bimonthly clinic that visited 4 of the 6 community-based outpatient clinics. This review compares the RRVAMC Hematology and the Telehematology Clinics’ NSR from March31, 2014, to March 31, 2015.

Results: The Telehematology Clinic has a patient cohort of 57 patients, which will expand to at least 77 patients by May 2016. To date, there have been 157 Telehematology Clinic visits. Most patients have an annual Telehematology Clinic visit and either quarterly or semiannual laboratory studies. The Telehematology Clinic has had a NSR of 3% since 2013. The Hematology Clinic’s NSR decreased from 14% to 12% (P = .09). Comparing the NSR of traditional Hematology Clinics with NSR of Telehematology Clinics is statically significant, P < .0007.

Implications: Telehematology Clinics have proven sustainability with greater adherence and attendance than that of the traditional hematology clinics scheduled within the RRVAMC. The NSR did not decrease significantly and remains greater than our goal of < 10%. Future video supported clinics may increase access and improve NSRs within the veteran population. Our goal in the next year is to increase the frequency of Telehematology Clinics and to expand the clinic population in an effort to reduce our overall NSR.

Background: Historically the Hematology Clinics at the Robley Rex VA Medical Center (RRVAMC) had a chronically elevated no-show rate (NSR). The major cause of these missed opportunities was patient adherence secondary to transportation, distance traveled, and patients’ lack of concern about their disease. Our hypothesis was that the no-show rates could be significantly reduced by providing virtual hematology services outside the main VA campus.

Methods: A comprehensive review of the hematology patient population was conducted to identify veterans with stable hematologic disorders (SHD), eg, stage 0 chronic lymphocytic leukemia, monoclonal gammopathy of undetermined significance, and chronic anemia. The NSR was determined for 2012. Patients with SHD were identified as potential subjects for the Telehematology Clinic. The clinic was started July 2013 and eventually expanded to a bimonthly clinic that visited 4 of the 6 community-based outpatient clinics. This review compares the RRVAMC Hematology and the Telehematology Clinics’ NSR from March31, 2014, to March 31, 2015.

Results: The Telehematology Clinic has a patient cohort of 57 patients, which will expand to at least 77 patients by May 2016. To date, there have been 157 Telehematology Clinic visits. Most patients have an annual Telehematology Clinic visit and either quarterly or semiannual laboratory studies. The Telehematology Clinic has had a NSR of 3% since 2013. The Hematology Clinic’s NSR decreased from 14% to 12% (P = .09). Comparing the NSR of traditional Hematology Clinics with NSR of Telehematology Clinics is statically significant, P < .0007.

Implications: Telehematology Clinics have proven sustainability with greater adherence and attendance than that of the traditional hematology clinics scheduled within the RRVAMC. The NSR did not decrease significantly and remains greater than our goal of < 10%. Future video supported clinics may increase access and improve NSRs within the veteran population. Our goal in the next year is to increase the frequency of Telehematology Clinics and to expand the clinic population in an effort to reduce our overall NSR.

Background: Historically the Hematology Clinics at the Robley Rex VA Medical Center (RRVAMC) had a chronically elevated no-show rate (NSR). The major cause of these missed opportunities was patient adherence secondary to transportation, distance traveled, and patients’ lack of concern about their disease. Our hypothesis was that the no-show rates could be significantly reduced by providing virtual hematology services outside the main VA campus.

Methods: A comprehensive review of the hematology patient population was conducted to identify veterans with stable hematologic disorders (SHD), eg, stage 0 chronic lymphocytic leukemia, monoclonal gammopathy of undetermined significance, and chronic anemia. The NSR was determined for 2012. Patients with SHD were identified as potential subjects for the Telehematology Clinic. The clinic was started July 2013 and eventually expanded to a bimonthly clinic that visited 4 of the 6 community-based outpatient clinics. This review compares the RRVAMC Hematology and the Telehematology Clinics’ NSR from March31, 2014, to March 31, 2015.

Results: The Telehematology Clinic has a patient cohort of 57 patients, which will expand to at least 77 patients by May 2016. To date, there have been 157 Telehematology Clinic visits. Most patients have an annual Telehematology Clinic visit and either quarterly or semiannual laboratory studies. The Telehematology Clinic has had a NSR of 3% since 2013. The Hematology Clinic’s NSR decreased from 14% to 12% (P = .09). Comparing the NSR of traditional Hematology Clinics with NSR of Telehematology Clinics is statically significant, P < .0007.

Implications: Telehematology Clinics have proven sustainability with greater adherence and attendance than that of the traditional hematology clinics scheduled within the RRVAMC. The NSR did not decrease significantly and remains greater than our goal of < 10%. Future video supported clinics may increase access and improve NSRs within the veteran population. Our goal in the next year is to increase the frequency of Telehematology Clinics and to expand the clinic population in an effort to reduce our overall NSR.

Purpose: Review the clinical presentation and pathophysiology of hypercalcemia in diffuse large B-cell lymphoma.

Methods: Case study of a 59-year-old man with untreateddiffuse large B-cell lymphoma (DLBCL) who presented with anorexia, constipation, and weight loss in the setting of a fungating breast mass.

Results: The patient presented to an outside hospital 1.5 years prior for a left breast mass biopsy that was diagnosed as triple-hit DLBCL. However, he deferred treatment at that time. He subsequently experienced anorexia, nausea, vomiting, consti-pation, and a 20-pound unintentional weight loss. At hospital presentation, a physical examination revealed enlargement of the left breast mass measuring 8 x 14 cm with central ulceration and malodorous purulent discharge and a proximal 7 x 4 cm firm axillary mass. The patient reported no abdominal pain or fever. He was found to have acute kidney injury (creatinine 2.9 mg/dL); hyperuricemia (13.3 mg/dL); and corrected hypercalcemia (17.4 mg/dL). Empiric treatment for tumor lysis syndrome with rasburicase, allopurinol, and aggressive IV hydration was initiated. Further evaluation revealed normal lactate dehydrogenase and K+.The patient was found to have an elevated vitamin D 1,25-OH (244 pg/mL) but low parathyroid hormone (PTH) (6.4 pg/mL); normal PTH-rP; mild hyperphosphatemia (5.5 mg/dL); and negative serum protein electrophoresis/urine protein electrophoresis. Clinical presentation was suggestive of vitamin D-mediated hypercalcemia. The patient received pamidronate and aggressive IV hydration. Electrolyte abnormalities and renal function gradually improved. Computed tomography and positron emission tomography imaging revealed masses localized to the left chest wall with ipsilateral axillary lymphadenopathy. Surgical biopsy of the mass reconfirmed DLBCL ultimately staged as IIE. Following stabilization, the patient declined more aggressive chemotherapy and received R-CHOP with a complete response.

Conclusions: The patient presented with vitamin D-mediated hypercalcemia in the setting of aggressive triple-hit DLBCL. Vitamin D-mediated hypercalcemia occurs in < 1% of lymphomas, and < 0.5% of breast tumors are primary lymphomas. This case study presents a rare constellation of findings at diagnosis. The patient responded to IV hydration and pamidronate and subsequently received R-CHOP for stage IIE DLBCL. While hypercalcemia in the setting of malignancy is associated with poor prognosis, treatment of hypercalcemia does not improve survival.

Purpose: Review the clinical presentation and pathophysiology of hypercalcemia in diffuse large B-cell lymphoma.

Methods: Case study of a 59-year-old man with untreateddiffuse large B-cell lymphoma (DLBCL) who presented with anorexia, constipation, and weight loss in the setting of a fungating breast mass.

Results: The patient presented to an outside hospital 1.5 years prior for a left breast mass biopsy that was diagnosed as triple-hit DLBCL. However, he deferred treatment at that time. He subsequently experienced anorexia, nausea, vomiting, consti-pation, and a 20-pound unintentional weight loss. At hospital presentation, a physical examination revealed enlargement of the left breast mass measuring 8 x 14 cm with central ulceration and malodorous purulent discharge and a proximal 7 x 4 cm firm axillary mass. The patient reported no abdominal pain or fever. He was found to have acute kidney injury (creatinine 2.9 mg/dL); hyperuricemia (13.3 mg/dL); and corrected hypercalcemia (17.4 mg/dL). Empiric treatment for tumor lysis syndrome with rasburicase, allopurinol, and aggressive IV hydration was initiated. Further evaluation revealed normal lactate dehydrogenase and K+.The patient was found to have an elevated vitamin D 1,25-OH (244 pg/mL) but low parathyroid hormone (PTH) (6.4 pg/mL); normal PTH-rP; mild hyperphosphatemia (5.5 mg/dL); and negative serum protein electrophoresis/urine protein electrophoresis. Clinical presentation was suggestive of vitamin D-mediated hypercalcemia. The patient received pamidronate and aggressive IV hydration. Electrolyte abnormalities and renal function gradually improved. Computed tomography and positron emission tomography imaging revealed masses localized to the left chest wall with ipsilateral axillary lymphadenopathy. Surgical biopsy of the mass reconfirmed DLBCL ultimately staged as IIE. Following stabilization, the patient declined more aggressive chemotherapy and received R-CHOP with a complete response.

Conclusions: The patient presented with vitamin D-mediated hypercalcemia in the setting of aggressive triple-hit DLBCL. Vitamin D-mediated hypercalcemia occurs in < 1% of lymphomas, and < 0.5% of breast tumors are primary lymphomas. This case study presents a rare constellation of findings at diagnosis. The patient responded to IV hydration and pamidronate and subsequently received R-CHOP for stage IIE DLBCL. While hypercalcemia in the setting of malignancy is associated with poor prognosis, treatment of hypercalcemia does not improve survival.

Purpose: Review the clinical presentation and pathophysiology of hypercalcemia in diffuse large B-cell lymphoma.

Methods: Case study of a 59-year-old man with untreateddiffuse large B-cell lymphoma (DLBCL) who presented with anorexia, constipation, and weight loss in the setting of a fungating breast mass.

Results: The patient presented to an outside hospital 1.5 years prior for a left breast mass biopsy that was diagnosed as triple-hit DLBCL. However, he deferred treatment at that time. He subsequently experienced anorexia, nausea, vomiting, consti-pation, and a 20-pound unintentional weight loss. At hospital presentation, a physical examination revealed enlargement of the left breast mass measuring 8 x 14 cm with central ulceration and malodorous purulent discharge and a proximal 7 x 4 cm firm axillary mass. The patient reported no abdominal pain or fever. He was found to have acute kidney injury (creatinine 2.9 mg/dL); hyperuricemia (13.3 mg/dL); and corrected hypercalcemia (17.4 mg/dL). Empiric treatment for tumor lysis syndrome with rasburicase, allopurinol, and aggressive IV hydration was initiated. Further evaluation revealed normal lactate dehydrogenase and K+.The patient was found to have an elevated vitamin D 1,25-OH (244 pg/mL) but low parathyroid hormone (PTH) (6.4 pg/mL); normal PTH-rP; mild hyperphosphatemia (5.5 mg/dL); and negative serum protein electrophoresis/urine protein electrophoresis. Clinical presentation was suggestive of vitamin D-mediated hypercalcemia. The patient received pamidronate and aggressive IV hydration. Electrolyte abnormalities and renal function gradually improved. Computed tomography and positron emission tomography imaging revealed masses localized to the left chest wall with ipsilateral axillary lymphadenopathy. Surgical biopsy of the mass reconfirmed DLBCL ultimately staged as IIE. Following stabilization, the patient declined more aggressive chemotherapy and received R-CHOP with a complete response.

Conclusions: The patient presented with vitamin D-mediated hypercalcemia in the setting of aggressive triple-hit DLBCL. Vitamin D-mediated hypercalcemia occurs in < 1% of lymphomas, and < 0.5% of breast tumors are primary lymphomas. This case study presents a rare constellation of findings at diagnosis. The patient responded to IV hydration and pamidronate and subsequently received R-CHOP for stage IIE DLBCL. While hypercalcemia in the setting of malignancy is associated with poor prognosis, treatment of hypercalcemia does not improve survival.