AML

Key clinical point: No significant difference was seen in the 1-year relapse-free survival (RFS) relapse-free survival rate (RFS) and overall survival (OS) between intermediate-dose cytarabine (IDAC) and high-dose cytarabine (HiDAC) in patients with acute myeloid leukemia (AML).

Major finding: One-year RFS was 63.33% in the IDAC group vs. 46.87% in the HiDAC group (P = .137). One-year OS was 93.33% in the IDAC group vs. 84.37% in the HiDAC group (P = .691). IDAC group vs HiDAC group had significantly shorter duration of grade 3–4 thrombocytopenia (mean duration, 14.69 vs. 23.84 days; P = .045).

Study details: The data come from a retrospective study involvoing 62 patients with AML (30 patients in IDAC and 32 patients in HiDAC regimen).

Disclosures: The authors declared no conflicts of interest.

Source: Tangchitpianvit K et al. Hematology. 2021 Apr 14. doi: 10.1080/16078454.2021.1912949.

Key clinical point: No significant difference was seen in the 1-year relapse-free survival (RFS) relapse-free survival rate (RFS) and overall survival (OS) between intermediate-dose cytarabine (IDAC) and high-dose cytarabine (HiDAC) in patients with acute myeloid leukemia (AML).

Major finding: One-year RFS was 63.33% in the IDAC group vs. 46.87% in the HiDAC group (P = .137). One-year OS was 93.33% in the IDAC group vs. 84.37% in the HiDAC group (P = .691). IDAC group vs HiDAC group had significantly shorter duration of grade 3–4 thrombocytopenia (mean duration, 14.69 vs. 23.84 days; P = .045).

Study details: The data come from a retrospective study involvoing 62 patients with AML (30 patients in IDAC and 32 patients in HiDAC regimen).

Disclosures: The authors declared no conflicts of interest.

Source: Tangchitpianvit K et al. Hematology. 2021 Apr 14. doi: 10.1080/16078454.2021.1912949.

Key clinical point: No significant difference was seen in the 1-year relapse-free survival (RFS) relapse-free survival rate (RFS) and overall survival (OS) between intermediate-dose cytarabine (IDAC) and high-dose cytarabine (HiDAC) in patients with acute myeloid leukemia (AML).

Major finding: One-year RFS was 63.33% in the IDAC group vs. 46.87% in the HiDAC group (P = .137). One-year OS was 93.33% in the IDAC group vs. 84.37% in the HiDAC group (P = .691). IDAC group vs HiDAC group had significantly shorter duration of grade 3–4 thrombocytopenia (mean duration, 14.69 vs. 23.84 days; P = .045).

Study details: The data come from a retrospective study involvoing 62 patients with AML (30 patients in IDAC and 32 patients in HiDAC regimen).

Disclosures: The authors declared no conflicts of interest.

Source: Tangchitpianvit K et al. Hematology. 2021 Apr 14. doi: 10.1080/16078454.2021.1912949.

Key clinical point: Presence of acute kidney injury (AKI) may have an adverse impact on the clinical course of patients with acute myeloid leukemia (AML) treated with induction chemotherapy.

Major finding: 72 (18%) AML patients had AKI during induction chemotherapy. AML patients with AKI vs without AKI had more days with fever (7 vs. 5, P = .028) and require treatment intensive care unit more often (45.8% vs. 10.6%, P less than .001). AML patients with AKI also had a significantly lower complete remission rate following induction chemotherapy and shorter median overall survival.

Study details: Retrospective analysis of data from 401 patients with AML undergoing induction chemotherapy between 2007 and 2019.

Disclosures: Open access funding was enabled and organized by Projekt DEAL. The authors declared no conflicts of interest.

Source: Ballo O et al. Ann Hematol. 2021 March 11. doi: 10.1007/s00277-021-04482-3.

Key clinical point: Presence of acute kidney injury (AKI) may have an adverse impact on the clinical course of patients with acute myeloid leukemia (AML) treated with induction chemotherapy.

Major finding: 72 (18%) AML patients had AKI during induction chemotherapy. AML patients with AKI vs without AKI had more days with fever (7 vs. 5, P = .028) and require treatment intensive care unit more often (45.8% vs. 10.6%, P less than .001). AML patients with AKI also had a significantly lower complete remission rate following induction chemotherapy and shorter median overall survival.

Study details: Retrospective analysis of data from 401 patients with AML undergoing induction chemotherapy between 2007 and 2019.

Disclosures: Open access funding was enabled and organized by Projekt DEAL. The authors declared no conflicts of interest.

Source: Ballo O et al. Ann Hematol. 2021 March 11. doi: 10.1007/s00277-021-04482-3.

Key clinical point: Presence of acute kidney injury (AKI) may have an adverse impact on the clinical course of patients with acute myeloid leukemia (AML) treated with induction chemotherapy.

Major finding: 72 (18%) AML patients had AKI during induction chemotherapy. AML patients with AKI vs without AKI had more days with fever (7 vs. 5, P = .028) and require treatment intensive care unit more often (45.8% vs. 10.6%, P less than .001). AML patients with AKI also had a significantly lower complete remission rate following induction chemotherapy and shorter median overall survival.

Study details: Retrospective analysis of data from 401 patients with AML undergoing induction chemotherapy between 2007 and 2019.

Disclosures: Open access funding was enabled and organized by Projekt DEAL. The authors declared no conflicts of interest.

Source: Ballo O et al. Ann Hematol. 2021 March 11. doi: 10.1007/s00277-021-04482-3.

Key clinical point: Maintenance treatment with tyrosine kinase inhibitors (TKIs) following Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is safe and effective in patients with FLT3 mutated acute myeloid leukemia (AML).

Major finding: After a median follow-up of 10 months after allo-HSCT, 29 patients (71%) were alive and in complete remission (CR). In the subgroup of pretransplant TKI-treated patients, 25 patients (78%) were alive and in CR. 17 patients (41%) experienced side effects and 7 patients (17%) discontinued TKIs as a result of adverse events.

Study details: The data come from a retrospective observational study involving 41 patients treated with posttransplant TKIs (sorafenib, n = 23;  midostaurin, n = 18). 32  patients (79%) had also received TKIs before allo-HSCT.

Disclosures: The authors declared no conflicts of interest.

Source: Shimony S et al. Leuk Lymphoma. 2021 Apr 21. doi: 10.1080/10428194.2021.1913145.

Key clinical point: Maintenance treatment with tyrosine kinase inhibitors (TKIs) following Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is safe and effective in patients with FLT3 mutated acute myeloid leukemia (AML).

Major finding: After a median follow-up of 10 months after allo-HSCT, 29 patients (71%) were alive and in complete remission (CR). In the subgroup of pretransplant TKI-treated patients, 25 patients (78%) were alive and in CR. 17 patients (41%) experienced side effects and 7 patients (17%) discontinued TKIs as a result of adverse events.

Study details: The data come from a retrospective observational study involving 41 patients treated with posttransplant TKIs (sorafenib, n = 23;  midostaurin, n = 18). 32  patients (79%) had also received TKIs before allo-HSCT.

Disclosures: The authors declared no conflicts of interest.

Source: Shimony S et al. Leuk Lymphoma. 2021 Apr 21. doi: 10.1080/10428194.2021.1913145.

Key clinical point: Maintenance treatment with tyrosine kinase inhibitors (TKIs) following Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is safe and effective in patients with FLT3 mutated acute myeloid leukemia (AML).

Major finding: After a median follow-up of 10 months after allo-HSCT, 29 patients (71%) were alive and in complete remission (CR). In the subgroup of pretransplant TKI-treated patients, 25 patients (78%) were alive and in CR. 17 patients (41%) experienced side effects and 7 patients (17%) discontinued TKIs as a result of adverse events.

Study details: The data come from a retrospective observational study involving 41 patients treated with posttransplant TKIs (sorafenib, n = 23;  midostaurin, n = 18). 32  patients (79%) had also received TKIs before allo-HSCT.

Disclosures: The authors declared no conflicts of interest.

Source: Shimony S et al. Leuk Lymphoma. 2021 Apr 21. doi: 10.1080/10428194.2021.1913145.

Key clinical point: The addition of gemtuzumab ozogamycin (GO) to standard chemotherapy (SC) did not improve survival in younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk (IR) cytogenetics but was associated with significantly higher toxicities.

Major finding: During a median follow-up of 35 months, event-free survival (hazard ratio [HR], 1.35; P = .116) and overall survival (HR, 1.35; P = .146) were not different in patients receiving GO+SC vs. SC alone. Duration of neutropenia (P = .03) and thrombopenia (P less than .001) and grade 3/4 liver toxicities (P = .03) were significantly higher in patients receiving GO vs. SC alone.

Study details: Phase 3 AML 2006-IR trial included 238 younger patients (age, 18-60 years) with de novo AML and IR cytogenetics randomly assigned to receive cytarabine and daunorubicin with or without GO. GO arm was prematurely closed after 254 inclusions because of toxicity and early deaths.

Disclosures: This study was supported by the French government PHRC 2006 and PFIZER group. Some investigators reported being on advisory boards, receiving research and travel funding, honoraria, and personal fees from various pharmaceutical companies, including Pfizer.

Source: Bouvier A et al. Eur J Haematol. 2021 Mar 25. doi: 10.1111/ejh.13626.

Key clinical point: The addition of gemtuzumab ozogamycin (GO) to standard chemotherapy (SC) did not improve survival in younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk (IR) cytogenetics but was associated with significantly higher toxicities.

Major finding: During a median follow-up of 35 months, event-free survival (hazard ratio [HR], 1.35; P = .116) and overall survival (HR, 1.35; P = .146) were not different in patients receiving GO+SC vs. SC alone. Duration of neutropenia (P = .03) and thrombopenia (P less than .001) and grade 3/4 liver toxicities (P = .03) were significantly higher in patients receiving GO vs. SC alone.

Study details: Phase 3 AML 2006-IR trial included 238 younger patients (age, 18-60 years) with de novo AML and IR cytogenetics randomly assigned to receive cytarabine and daunorubicin with or without GO. GO arm was prematurely closed after 254 inclusions because of toxicity and early deaths.

Disclosures: This study was supported by the French government PHRC 2006 and PFIZER group. Some investigators reported being on advisory boards, receiving research and travel funding, honoraria, and personal fees from various pharmaceutical companies, including Pfizer.

Source: Bouvier A et al. Eur J Haematol. 2021 Mar 25. doi: 10.1111/ejh.13626.

Key clinical point: The addition of gemtuzumab ozogamycin (GO) to standard chemotherapy (SC) did not improve survival in younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk (IR) cytogenetics but was associated with significantly higher toxicities.

Major finding: During a median follow-up of 35 months, event-free survival (hazard ratio [HR], 1.35; P = .116) and overall survival (HR, 1.35; P = .146) were not different in patients receiving GO+SC vs. SC alone. Duration of neutropenia (P = .03) and thrombopenia (P less than .001) and grade 3/4 liver toxicities (P = .03) were significantly higher in patients receiving GO vs. SC alone.

Study details: Phase 3 AML 2006-IR trial included 238 younger patients (age, 18-60 years) with de novo AML and IR cytogenetics randomly assigned to receive cytarabine and daunorubicin with or without GO. GO arm was prematurely closed after 254 inclusions because of toxicity and early deaths.

Disclosures: This study was supported by the French government PHRC 2006 and PFIZER group. Some investigators reported being on advisory boards, receiving research and travel funding, honoraria, and personal fees from various pharmaceutical companies, including Pfizer.

Source: Bouvier A et al. Eur J Haematol. 2021 Mar 25. doi: 10.1111/ejh.13626.

Key clinical point: In patients with acute myeloid leukemia (AML), incomplete count recovery (CRi) or presence of measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (allo-HCT) was associated with inferior posttransplant outcomes vs. those in complete remission (CR) or without MRD.

Major finding: Patients in CRi vs. CR were at a higher risk for death (hazard ratio [HR], 1.27; P less than .001) and nonrelapse mortality (HR, 1.33; P = .002). Additionally, presence vs. absence of MRD was associated with shorter overall survival (HR, 1.52; P less than .001) and increased relapse (HR, 1.78; P less than .001).

Study details: This observational study included 2,492 adult patients with AML (CR, n=1,799; CRi, n=693) from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry, who underwent first allo-HCT between 2007 and 2015.

Disclosures: CIBMTR is primarily supported by the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research. The lead author had no disclosures. Some coinvestigators reported ties with various pharmaceutical companies.

Source: Percival ME et al. Bone Marrow Transplant. 2021 Apr 16. doi: 10.1038/s41409-021-01261-6.

Key clinical point: In patients with acute myeloid leukemia (AML), incomplete count recovery (CRi) or presence of measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (allo-HCT) was associated with inferior posttransplant outcomes vs. those in complete remission (CR) or without MRD.

Major finding: Patients in CRi vs. CR were at a higher risk for death (hazard ratio [HR], 1.27; P less than .001) and nonrelapse mortality (HR, 1.33; P = .002). Additionally, presence vs. absence of MRD was associated with shorter overall survival (HR, 1.52; P less than .001) and increased relapse (HR, 1.78; P less than .001).

Study details: This observational study included 2,492 adult patients with AML (CR, n=1,799; CRi, n=693) from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry, who underwent first allo-HCT between 2007 and 2015.

Disclosures: CIBMTR is primarily supported by the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research. The lead author had no disclosures. Some coinvestigators reported ties with various pharmaceutical companies.

Source: Percival ME et al. Bone Marrow Transplant. 2021 Apr 16. doi: 10.1038/s41409-021-01261-6.

Key clinical point: In patients with acute myeloid leukemia (AML), incomplete count recovery (CRi) or presence of measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (allo-HCT) was associated with inferior posttransplant outcomes vs. those in complete remission (CR) or without MRD.

Major finding: Patients in CRi vs. CR were at a higher risk for death (hazard ratio [HR], 1.27; P less than .001) and nonrelapse mortality (HR, 1.33; P = .002). Additionally, presence vs. absence of MRD was associated with shorter overall survival (HR, 1.52; P less than .001) and increased relapse (HR, 1.78; P less than .001).

Study details: This observational study included 2,492 adult patients with AML (CR, n=1,799; CRi, n=693) from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry, who underwent first allo-HCT between 2007 and 2015.

Disclosures: CIBMTR is primarily supported by the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research. The lead author had no disclosures. Some coinvestigators reported ties with various pharmaceutical companies.

Source: Percival ME et al. Bone Marrow Transplant. 2021 Apr 16. doi: 10.1038/s41409-021-01261-6.

Key clinical point: Prior treatment with gemtuzumab ozogamicin (GO) before allogeneic hematopoietic cell transplantation (allo-HCT) in pediatric patients with acute myeloid leukemia (AML) increased risk for veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) but did not affect survival.

Major finding: Compared with nonexposure, exposure to GO was associated with increased risk for VOD/SOS at 100 days (odds ratio, 2.26; P = .004). However, posttransplant overall survival (P = .43), disease-free survival (P = .20), relapse (P = .32), and nonrelapse mortality (P = .51) did not differ in patients with or without prior GO treatment.

Study details: Findings are from retrospective assessment of pediatric patients with AML who received myeloablative allo-HCT between 2008 and 2011 with (n=148) or without (n=348) prior GO treatment.

Disclosures: This study was funded by Pfizer. D Chirnomas, CJ Hoang, and FR Loberiza Jr declared being current/former employees of and/or had equity ownership in Pfizer. Other authors declared no conflicts of interest.

Source: Duncan C et al. Pediatr Blood Cancer. 2021 Apr 19. doi: 10.1002/pbc.29067.

Key clinical point: Prior treatment with gemtuzumab ozogamicin (GO) before allogeneic hematopoietic cell transplantation (allo-HCT) in pediatric patients with acute myeloid leukemia (AML) increased risk for veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) but did not affect survival.

Major finding: Compared with nonexposure, exposure to GO was associated with increased risk for VOD/SOS at 100 days (odds ratio, 2.26; P = .004). However, posttransplant overall survival (P = .43), disease-free survival (P = .20), relapse (P = .32), and nonrelapse mortality (P = .51) did not differ in patients with or without prior GO treatment.

Study details: Findings are from retrospective assessment of pediatric patients with AML who received myeloablative allo-HCT between 2008 and 2011 with (n=148) or without (n=348) prior GO treatment.

Disclosures: This study was funded by Pfizer. D Chirnomas, CJ Hoang, and FR Loberiza Jr declared being current/former employees of and/or had equity ownership in Pfizer. Other authors declared no conflicts of interest.

Source: Duncan C et al. Pediatr Blood Cancer. 2021 Apr 19. doi: 10.1002/pbc.29067.

Key clinical point: Prior treatment with gemtuzumab ozogamicin (GO) before allogeneic hematopoietic cell transplantation (allo-HCT) in pediatric patients with acute myeloid leukemia (AML) increased risk for veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) but did not affect survival.

Major finding: Compared with nonexposure, exposure to GO was associated with increased risk for VOD/SOS at 100 days (odds ratio, 2.26; P = .004). However, posttransplant overall survival (P = .43), disease-free survival (P = .20), relapse (P = .32), and nonrelapse mortality (P = .51) did not differ in patients with or without prior GO treatment.

Study details: Findings are from retrospective assessment of pediatric patients with AML who received myeloablative allo-HCT between 2008 and 2011 with (n=148) or without (n=348) prior GO treatment.

Disclosures: This study was funded by Pfizer. D Chirnomas, CJ Hoang, and FR Loberiza Jr declared being current/former employees of and/or had equity ownership in Pfizer. Other authors declared no conflicts of interest.

Source: Duncan C et al. Pediatr Blood Cancer. 2021 Apr 19. doi: 10.1002/pbc.29067.

Key clinical point: Survival outcomes have improved significantly in patients with de novo acute myeloid leukemia (AML) over a 4-decade period from 1980 to 2017; however, least improvement was observed in patients aged 70 years or older.

Major finding: Overall, 5-year survival increased from 9% during 1980-1989 to 15% in 1990-1999, 22% in 2000-2009, and 28% in 2010-2017 (all P less than .001). However, improvement in 5-year survival was poorest in patients aged 70 years or older with 1% in 1980-1989 to 5% in 2010-2017.

Study details: Findings are from a U.S. population-based study that evaluated 29,107 patients from the Surveillance, Epidemiology, and End Results registries, who were diagnosed with de novo AML between 1980 and 2017.

Disclosures: No funding source was identified. Some investigators including the lead author reported personal fees, research funding, honoraria, or other support from various pharmaceutical companies.

Source: Sasaki K et al. Cancer. 2021 Apr 5. doi: 10.1002/cncr.33458.

Key clinical point: Survival outcomes have improved significantly in patients with de novo acute myeloid leukemia (AML) over a 4-decade period from 1980 to 2017; however, least improvement was observed in patients aged 70 years or older.

Major finding: Overall, 5-year survival increased from 9% during 1980-1989 to 15% in 1990-1999, 22% in 2000-2009, and 28% in 2010-2017 (all P less than .001). However, improvement in 5-year survival was poorest in patients aged 70 years or older with 1% in 1980-1989 to 5% in 2010-2017.

Study details: Findings are from a U.S. population-based study that evaluated 29,107 patients from the Surveillance, Epidemiology, and End Results registries, who were diagnosed with de novo AML between 1980 and 2017.

Disclosures: No funding source was identified. Some investigators including the lead author reported personal fees, research funding, honoraria, or other support from various pharmaceutical companies.

Source: Sasaki K et al. Cancer. 2021 Apr 5. doi: 10.1002/cncr.33458.

Key clinical point: Survival outcomes have improved significantly in patients with de novo acute myeloid leukemia (AML) over a 4-decade period from 1980 to 2017; however, least improvement was observed in patients aged 70 years or older.

Major finding: Overall, 5-year survival increased from 9% during 1980-1989 to 15% in 1990-1999, 22% in 2000-2009, and 28% in 2010-2017 (all P less than .001). However, improvement in 5-year survival was poorest in patients aged 70 years or older with 1% in 1980-1989 to 5% in 2010-2017.

Study details: Findings are from a U.S. population-based study that evaluated 29,107 patients from the Surveillance, Epidemiology, and End Results registries, who were diagnosed with de novo AML between 1980 and 2017.

Disclosures: No funding source was identified. Some investigators including the lead author reported personal fees, research funding, honoraria, or other support from various pharmaceutical companies.

Source: Sasaki K et al. Cancer. 2021 Apr 5. doi: 10.1002/cncr.33458.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.

Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.

Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.

“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
 

Database review

Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).

They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).

They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).

They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.

In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).

Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).

Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.

Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.

Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
 

Opioids pre- and posttreatment?

“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.

Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.

The researchers plan to investigate this question in future studies, Dr. Ji replied.

They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.

Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.

Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.

Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.

“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
 

Database review

Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).

They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).

They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).

They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.

In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).

Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).

Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.

Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.

Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
 

Opioids pre- and posttreatment?

“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.

Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.

The researchers plan to investigate this question in future studies, Dr. Ji replied.

They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.

Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.

Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.

Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.

“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
 

Database review

Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).

They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).

They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).

They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.

In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).

Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).

Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.

Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.

Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
 

Opioids pre- and posttreatment?

“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.

Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.

The researchers plan to investigate this question in future studies, Dr. Ji replied.

They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.

Mitochondrial DNA (mtDNA) copy number alterations are known to occur in acute myeloid leukemia (AML), however their biological significance has not been well studied. Pediatric AML has a distinct biology, different from adults, and with heterogeneous clinical outcomes, the biological basis of which are not well understood, according to researchers Shilpi Chaudhary, PhD, of the All India Institute of Medical Sciences, New Delhi, and colleagues.

wir0man/GettyImages

Their analysis of 123 pediatric patients with AML found that mtDNA copy number was an independent predictor of aggressive disease, lower event-free survival, and overall survival, according to a report published in Mitochondrion.

In an attempt to find the biological factors involved in the increased mtDNA copy numbers and their effect on the development and aggressiveness of pediatric AML, the researchers studied the regulation and significance of mtDNA copy number in pediatric AML patients using quantitative real time–polymerase chain reaction, as well as in vitro studies. For patients, results were correlated with clinical outcomes.

Mitochondrial biogenesis genes (TFAM, POLG, POLRMT) and two regulator of mitochondrial biogenesis, MYC and PGC1A, were also assessed, according to Dr. Chaudhary and colleagues.
 

Predictive results

MtDNA copy number was significantly higher in patients, compared with controls (P < .001) and was found to be an independent predictor of aggressive disease (P = .006), lower event-free survival (P = .033), and overall survival (P = .007).

TFAM, POLG & POLRMT and ND3 were also found to be significantly up-regulated in patients, compared with controls as was the expression of the mitochondrial biogenesis regulator MYC (P < .001). However, correlation analysis showed that mtDNA copy number was not associated with the expression of these genes.

In contrast, PGC1A expression was not significantly different in patients, compared with controls overall, although there was a subset of patients whose PGC1A expression was extremely high, according to the researchers.

Importantly, however, in the subset of patients with high PGC1A expression (n = 28), mtDNA copy number had a positive correlation with PGC1A expression (P = .013). On the other hand, among patients with low MYC expression (n = 27), there was no correlation of mtDNA copy number with either PGC1A or MYC expression.

These results were corroborated in in vitro studies, where treatment with the inhibitor tigecycline led to a significant decrease in expression of MYC (P < .001), TFAM (P = .037) and ND3 (P = .010) but resulted in no significant change in mtDNA copy number (P = .23) or expression of PGC1A (P = .10).
 

Therapeutic candidate?

In contrast to the case of MYC, in vitro PGC1A inhibition significantly reduced mtDNA copy number in along with expression of TFAM and even expression of POLG and POLRMT at higher concentration.

“This observation is in line with our finding in patient samples as well that PGC1A expression positively correlated with mtDNA copy number, more so in patients with higher PGC1A expression,” the researchers stated.

“This makes it plausible to infer that PGC1A may have a possible role in enhancing mtDNA copy number in AML patients, likely independent of MYC,” they added. “Therefore, a strategy of designing therapeutics using already approved inhibitors targeting PGC1A may be an exciting area of therapeutic intervention.”

The authors reported that they have no competing financial conflicts of interests.

[email protected]

Mitochondrial DNA (mtDNA) copy number alterations are known to occur in acute myeloid leukemia (AML), however their biological significance has not been well studied. Pediatric AML has a distinct biology, different from adults, and with heterogeneous clinical outcomes, the biological basis of which are not well understood, according to researchers Shilpi Chaudhary, PhD, of the All India Institute of Medical Sciences, New Delhi, and colleagues.

wir0man/GettyImages

Their analysis of 123 pediatric patients with AML found that mtDNA copy number was an independent predictor of aggressive disease, lower event-free survival, and overall survival, according to a report published in Mitochondrion.

In an attempt to find the biological factors involved in the increased mtDNA copy numbers and their effect on the development and aggressiveness of pediatric AML, the researchers studied the regulation and significance of mtDNA copy number in pediatric AML patients using quantitative real time–polymerase chain reaction, as well as in vitro studies. For patients, results were correlated with clinical outcomes.

Mitochondrial biogenesis genes (TFAM, POLG, POLRMT) and two regulator of mitochondrial biogenesis, MYC and PGC1A, were also assessed, according to Dr. Chaudhary and colleagues.
 

Predictive results

MtDNA copy number was significantly higher in patients, compared with controls (P < .001) and was found to be an independent predictor of aggressive disease (P = .006), lower event-free survival (P = .033), and overall survival (P = .007).

TFAM, POLG & POLRMT and ND3 were also found to be significantly up-regulated in patients, compared with controls as was the expression of the mitochondrial biogenesis regulator MYC (P < .001). However, correlation analysis showed that mtDNA copy number was not associated with the expression of these genes.

In contrast, PGC1A expression was not significantly different in patients, compared with controls overall, although there was a subset of patients whose PGC1A expression was extremely high, according to the researchers.

Importantly, however, in the subset of patients with high PGC1A expression (n = 28), mtDNA copy number had a positive correlation with PGC1A expression (P = .013). On the other hand, among patients with low MYC expression (n = 27), there was no correlation of mtDNA copy number with either PGC1A or MYC expression.

These results were corroborated in in vitro studies, where treatment with the inhibitor tigecycline led to a significant decrease in expression of MYC (P < .001), TFAM (P = .037) and ND3 (P = .010) but resulted in no significant change in mtDNA copy number (P = .23) or expression of PGC1A (P = .10).
 

Therapeutic candidate?

In contrast to the case of MYC, in vitro PGC1A inhibition significantly reduced mtDNA copy number in along with expression of TFAM and even expression of POLG and POLRMT at higher concentration.

“This observation is in line with our finding in patient samples as well that PGC1A expression positively correlated with mtDNA copy number, more so in patients with higher PGC1A expression,” the researchers stated.

“This makes it plausible to infer that PGC1A may have a possible role in enhancing mtDNA copy number in AML patients, likely independent of MYC,” they added. “Therefore, a strategy of designing therapeutics using already approved inhibitors targeting PGC1A may be an exciting area of therapeutic intervention.”

The authors reported that they have no competing financial conflicts of interests.

[email protected]

Mitochondrial DNA (mtDNA) copy number alterations are known to occur in acute myeloid leukemia (AML), however their biological significance has not been well studied. Pediatric AML has a distinct biology, different from adults, and with heterogeneous clinical outcomes, the biological basis of which are not well understood, according to researchers Shilpi Chaudhary, PhD, of the All India Institute of Medical Sciences, New Delhi, and colleagues.

wir0man/GettyImages

Their analysis of 123 pediatric patients with AML found that mtDNA copy number was an independent predictor of aggressive disease, lower event-free survival, and overall survival, according to a report published in Mitochondrion.

In an attempt to find the biological factors involved in the increased mtDNA copy numbers and their effect on the development and aggressiveness of pediatric AML, the researchers studied the regulation and significance of mtDNA copy number in pediatric AML patients using quantitative real time–polymerase chain reaction, as well as in vitro studies. For patients, results were correlated with clinical outcomes.

Mitochondrial biogenesis genes (TFAM, POLG, POLRMT) and two regulator of mitochondrial biogenesis, MYC and PGC1A, were also assessed, according to Dr. Chaudhary and colleagues.
 

Predictive results

MtDNA copy number was significantly higher in patients, compared with controls (P < .001) and was found to be an independent predictor of aggressive disease (P = .006), lower event-free survival (P = .033), and overall survival (P = .007).

TFAM, POLG & POLRMT and ND3 were also found to be significantly up-regulated in patients, compared with controls as was the expression of the mitochondrial biogenesis regulator MYC (P < .001). However, correlation analysis showed that mtDNA copy number was not associated with the expression of these genes.

In contrast, PGC1A expression was not significantly different in patients, compared with controls overall, although there was a subset of patients whose PGC1A expression was extremely high, according to the researchers.

Importantly, however, in the subset of patients with high PGC1A expression (n = 28), mtDNA copy number had a positive correlation with PGC1A expression (P = .013). On the other hand, among patients with low MYC expression (n = 27), there was no correlation of mtDNA copy number with either PGC1A or MYC expression.

These results were corroborated in in vitro studies, where treatment with the inhibitor tigecycline led to a significant decrease in expression of MYC (P < .001), TFAM (P = .037) and ND3 (P = .010) but resulted in no significant change in mtDNA copy number (P = .23) or expression of PGC1A (P = .10).
 

Therapeutic candidate?

In contrast to the case of MYC, in vitro PGC1A inhibition significantly reduced mtDNA copy number in along with expression of TFAM and even expression of POLG and POLRMT at higher concentration.

“This observation is in line with our finding in patient samples as well that PGC1A expression positively correlated with mtDNA copy number, more so in patients with higher PGC1A expression,” the researchers stated.

“This makes it plausible to infer that PGC1A may have a possible role in enhancing mtDNA copy number in AML patients, likely independent of MYC,” they added. “Therefore, a strategy of designing therapeutics using already approved inhibitors targeting PGC1A may be an exciting area of therapeutic intervention.”

The authors reported that they have no competing financial conflicts of interests.

[email protected]