Clinical Edge Journal Scan

Key clinical point: In patients with chronic myeloid leukemia (CML), the transformation from chronic phase (CP) to blast crisis (BC) was associated with accumulation of somatic mutations with time in the absence of effective therapy, which may be suppressed by tyrosine kinase inhibitor (TKI) therapy, thereby preventing disease progression.

Major finding: The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. The number of mutations acquired during CP to BC progression was positively correlated with interval between progression (P = 9.4×10⁻¹²) and negatively correlated with TKI therapy after CP diagnosis (P = 9.3×10⁻³).

Study details: This study used exome and targeted sequencing to evaluate genetic alterations in 136 BC and 148 CP samples from 216 patients with CML.

Disclosures: This work was supported by the Grant-in-Aid for JSPS KAKENHI and Scientific Research on Innovative Areas and grants from AMED, MEXT, “Stem Cell Aging and Disease,” Takeda Science Foundation, Ministry of Science and Technology (Taiwan), and others. S Bradford reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ochi Y et al. Nat Commun. 2021 May 14. doi: 10.1038/s41467-021-23097-w.

Key clinical point: In patients with chronic myeloid leukemia (CML), the transformation from chronic phase (CP) to blast crisis (BC) was associated with accumulation of somatic mutations with time in the absence of effective therapy, which may be suppressed by tyrosine kinase inhibitor (TKI) therapy, thereby preventing disease progression.

Major finding: The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. The number of mutations acquired during CP to BC progression was positively correlated with interval between progression (P = 9.4×10⁻¹²) and negatively correlated with TKI therapy after CP diagnosis (P = 9.3×10⁻³).

Study details: This study used exome and targeted sequencing to evaluate genetic alterations in 136 BC and 148 CP samples from 216 patients with CML.

Disclosures: This work was supported by the Grant-in-Aid for JSPS KAKENHI and Scientific Research on Innovative Areas and grants from AMED, MEXT, “Stem Cell Aging and Disease,” Takeda Science Foundation, Ministry of Science and Technology (Taiwan), and others. S Bradford reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ochi Y et al. Nat Commun. 2021 May 14. doi: 10.1038/s41467-021-23097-w.

Key clinical point: In patients with chronic myeloid leukemia (CML), the transformation from chronic phase (CP) to blast crisis (BC) was associated with accumulation of somatic mutations with time in the absence of effective therapy, which may be suppressed by tyrosine kinase inhibitor (TKI) therapy, thereby preventing disease progression.

Major finding: The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. The number of mutations acquired during CP to BC progression was positively correlated with interval between progression (P = 9.4×10⁻¹²) and negatively correlated with TKI therapy after CP diagnosis (P = 9.3×10⁻³).

Study details: This study used exome and targeted sequencing to evaluate genetic alterations in 136 BC and 148 CP samples from 216 patients with CML.

Disclosures: This work was supported by the Grant-in-Aid for JSPS KAKENHI and Scientific Research on Innovative Areas and grants from AMED, MEXT, “Stem Cell Aging and Disease,” Takeda Science Foundation, Ministry of Science and Technology (Taiwan), and others. S Bradford reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ochi Y et al. Nat Commun. 2021 May 14. doi: 10.1038/s41467-021-23097-w.

In a comprehensive and detailed analysis, Ochi et al evaluated the genetic alterations in 136 blast crisis (BC) and 148 chronic phase (CP) samples from 216 patients with chronic myeloid leukemia (CML) by exome and targeted sequencing. The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients. As expected, the lineage of the BC and prior use of tyrosine kinase inhibitors (TKIs) correlate with distinct molecular profiles. TKIs markedly suppressed the number of genetic alterations increase during the transition from CP to BC. Notably, genetic alterations such AXL1 mutations complex CNAs, i(17q), and +21, rather than clinical variables, contribute to a better prediction of BC prognosis in early therapy with TKI in CP.

Switching to a second generation TKI with the goal of obtaining a deeper response and therefore a chance for treatment-free remission (TFR), is an option for certain patients and has been investigated in a few trials. ENEStop may be the most popular and Hughes et al had updated the 5 years follow up in a recent publication. The study includes patients with chronic-phase chronic myeloid leukemia (CML-CP)  who achieved sustained deep molecular response only after switching from imatinib to nilotinib and TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase. At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase including cardiovascular (CV) adverse events (AEs) as patients had a long duration of exposure for nilotinib.

After several publications and recommendations by NCCN and ELN, the optimal cut-off values of the duration of MR4 and deeper responses remain unresolved. Kim et al reported a large study of 131 patients enrolled into the Canadian TKI discontinuation study and evaluated the molecular relapse-free survival (mRFS) at 12 months after imatinib discontinuation. Based on this analysis they propose 6 years with imatinib treatment duration as the shortest imatinib duration- a superior success versus less than 6 years (61.8% vs. 36.0%; P = .01). Also a MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) was associated with a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Fatigue is a common complain of patients taking TKI and has been well reported as adverse effects in most of the CML trials. However, when evaluating fatigue, it is always difficult to understand if there are additional factors that can contribute to it. Hyland et al investigated if the use of cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) targeting fatigue perpetuating factors change over time. By delivering CBT via FaceTime or wait list control in CML patients with moderate or severe fatigue, they were able to see an improvement in TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer.

In a comprehensive and detailed analysis, Ochi et al evaluated the genetic alterations in 136 blast crisis (BC) and 148 chronic phase (CP) samples from 216 patients with chronic myeloid leukemia (CML) by exome and targeted sequencing. The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients. As expected, the lineage of the BC and prior use of tyrosine kinase inhibitors (TKIs) correlate with distinct molecular profiles. TKIs markedly suppressed the number of genetic alterations increase during the transition from CP to BC. Notably, genetic alterations such AXL1 mutations complex CNAs, i(17q), and +21, rather than clinical variables, contribute to a better prediction of BC prognosis in early therapy with TKI in CP.

Switching to a second generation TKI with the goal of obtaining a deeper response and therefore a chance for treatment-free remission (TFR), is an option for certain patients and has been investigated in a few trials. ENEStop may be the most popular and Hughes et al had updated the 5 years follow up in a recent publication. The study includes patients with chronic-phase chronic myeloid leukemia (CML-CP)  who achieved sustained deep molecular response only after switching from imatinib to nilotinib and TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase. At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase including cardiovascular (CV) adverse events (AEs) as patients had a long duration of exposure for nilotinib.

After several publications and recommendations by NCCN and ELN, the optimal cut-off values of the duration of MR4 and deeper responses remain unresolved. Kim et al reported a large study of 131 patients enrolled into the Canadian TKI discontinuation study and evaluated the molecular relapse-free survival (mRFS) at 12 months after imatinib discontinuation. Based on this analysis they propose 6 years with imatinib treatment duration as the shortest imatinib duration- a superior success versus less than 6 years (61.8% vs. 36.0%; P = .01). Also a MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) was associated with a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Fatigue is a common complain of patients taking TKI and has been well reported as adverse effects in most of the CML trials. However, when evaluating fatigue, it is always difficult to understand if there are additional factors that can contribute to it. Hyland et al investigated if the use of cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) targeting fatigue perpetuating factors change over time. By delivering CBT via FaceTime or wait list control in CML patients with moderate or severe fatigue, they were able to see an improvement in TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer.

In a comprehensive and detailed analysis, Ochi et al evaluated the genetic alterations in 136 blast crisis (BC) and 148 chronic phase (CP) samples from 216 patients with chronic myeloid leukemia (CML) by exome and targeted sequencing. The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients. As expected, the lineage of the BC and prior use of tyrosine kinase inhibitors (TKIs) correlate with distinct molecular profiles. TKIs markedly suppressed the number of genetic alterations increase during the transition from CP to BC. Notably, genetic alterations such AXL1 mutations complex CNAs, i(17q), and +21, rather than clinical variables, contribute to a better prediction of BC prognosis in early therapy with TKI in CP.

Switching to a second generation TKI with the goal of obtaining a deeper response and therefore a chance for treatment-free remission (TFR), is an option for certain patients and has been investigated in a few trials. ENEStop may be the most popular and Hughes et al had updated the 5 years follow up in a recent publication. The study includes patients with chronic-phase chronic myeloid leukemia (CML-CP)  who achieved sustained deep molecular response only after switching from imatinib to nilotinib and TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase. At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase including cardiovascular (CV) adverse events (AEs) as patients had a long duration of exposure for nilotinib.

After several publications and recommendations by NCCN and ELN, the optimal cut-off values of the duration of MR4 and deeper responses remain unresolved. Kim et al reported a large study of 131 patients enrolled into the Canadian TKI discontinuation study and evaluated the molecular relapse-free survival (mRFS) at 12 months after imatinib discontinuation. Based on this analysis they propose 6 years with imatinib treatment duration as the shortest imatinib duration- a superior success versus less than 6 years (61.8% vs. 36.0%; P = .01). Also a MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) was associated with a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Fatigue is a common complain of patients taking TKI and has been well reported as adverse effects in most of the CML trials. However, when evaluating fatigue, it is always difficult to understand if there are additional factors that can contribute to it. Hyland et al investigated if the use of cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) targeting fatigue perpetuating factors change over time. By delivering CBT via FaceTime or wait list control in CML patients with moderate or severe fatigue, they were able to see an improvement in TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer.

Key clinical point: Increased percentage of mature monocyte in bone marrow (PMMBM) may assist the Revised International Prognostic Scoring System (IPSS-R) to predict poor prognosis in patients with myelodysplastic syndromes (MDS).

Major finding: Elevated (>6%) vs. normal PMMBM was associated with shorter overall survival (24 months vs. 37 months; P = .026) along with higher risk distribution in terms of IPSS-R (P = .025) and higher frequency of IDH2 mutation (P = .007).

Study details: The data come from a retrospective analysis of 216 MDS patients, categorized into elevated and normal PMMBM groups.

Disclosures: The study was supported by the Zhejiang Provincial Natural Science Foundation of China, Medical and Health Science and Technology Projects of Zhejiang Province, National Science Foundation of Ningbo, and Chinese Medicine Science and Technology Plan Project of Zhejiang Province. The authors declared no conflicts of interest.

Source: Wu A et al. BMC Cancer. 2021 May 13. doi: 10.1186/s12885-021-08303-8.

Key clinical point: Increased percentage of mature monocyte in bone marrow (PMMBM) may assist the Revised International Prognostic Scoring System (IPSS-R) to predict poor prognosis in patients with myelodysplastic syndromes (MDS).

Major finding: Elevated (>6%) vs. normal PMMBM was associated with shorter overall survival (24 months vs. 37 months; P = .026) along with higher risk distribution in terms of IPSS-R (P = .025) and higher frequency of IDH2 mutation (P = .007).

Study details: The data come from a retrospective analysis of 216 MDS patients, categorized into elevated and normal PMMBM groups.

Disclosures: The study was supported by the Zhejiang Provincial Natural Science Foundation of China, Medical and Health Science and Technology Projects of Zhejiang Province, National Science Foundation of Ningbo, and Chinese Medicine Science and Technology Plan Project of Zhejiang Province. The authors declared no conflicts of interest.

Source: Wu A et al. BMC Cancer. 2021 May 13. doi: 10.1186/s12885-021-08303-8.

Key clinical point: Increased percentage of mature monocyte in bone marrow (PMMBM) may assist the Revised International Prognostic Scoring System (IPSS-R) to predict poor prognosis in patients with myelodysplastic syndromes (MDS).

Major finding: Elevated (>6%) vs. normal PMMBM was associated with shorter overall survival (24 months vs. 37 months; P = .026) along with higher risk distribution in terms of IPSS-R (P = .025) and higher frequency of IDH2 mutation (P = .007).

Study details: The data come from a retrospective analysis of 216 MDS patients, categorized into elevated and normal PMMBM groups.

Disclosures: The study was supported by the Zhejiang Provincial Natural Science Foundation of China, Medical and Health Science and Technology Projects of Zhejiang Province, National Science Foundation of Ningbo, and Chinese Medicine Science and Technology Plan Project of Zhejiang Province. The authors declared no conflicts of interest.

Source: Wu A et al. BMC Cancer. 2021 May 13. doi: 10.1186/s12885-021-08303-8.

Key clinical point: During remission induction chemotherapy in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), antibiotics can be safely stopped after 3 days of febrile neutropenia in the absence of infection.

Major finding: Serious medical complication (SMC) was seen in 12.5% of patients receiving the 3-day empirical broad-spectrum antibiotic therapy (EBAT) vs. 8.9% of patients receiving the prolonged regimen (P = .17). After adjustment for confounders, there was no significant difference between both strategies in the number of SMCs (hazard ratio, 1.357; P = .297).

Study details: AML or MDS patients who received chemotherapy were treated with either 3-day EBAT or a prolonged antibiotic regimen (until neutrophil recovery).

Disclosures: The study did not receive any specific funding. A Schauwvlieghe, J Maertens, and T Mercier reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Schauwvlieghe A et al. EClinicalMedicine. 2021 Apr 25. doi: 10.1016/j.eclinm.2021.100855.

Key clinical point: During remission induction chemotherapy in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), antibiotics can be safely stopped after 3 days of febrile neutropenia in the absence of infection.

Major finding: Serious medical complication (SMC) was seen in 12.5% of patients receiving the 3-day empirical broad-spectrum antibiotic therapy (EBAT) vs. 8.9% of patients receiving the prolonged regimen (P = .17). After adjustment for confounders, there was no significant difference between both strategies in the number of SMCs (hazard ratio, 1.357; P = .297).

Study details: AML or MDS patients who received chemotherapy were treated with either 3-day EBAT or a prolonged antibiotic regimen (until neutrophil recovery).

Disclosures: The study did not receive any specific funding. A Schauwvlieghe, J Maertens, and T Mercier reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Schauwvlieghe A et al. EClinicalMedicine. 2021 Apr 25. doi: 10.1016/j.eclinm.2021.100855.

Key clinical point: During remission induction chemotherapy in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), antibiotics can be safely stopped after 3 days of febrile neutropenia in the absence of infection.

Major finding: Serious medical complication (SMC) was seen in 12.5% of patients receiving the 3-day empirical broad-spectrum antibiotic therapy (EBAT) vs. 8.9% of patients receiving the prolonged regimen (P = .17). After adjustment for confounders, there was no significant difference between both strategies in the number of SMCs (hazard ratio, 1.357; P = .297).

Study details: AML or MDS patients who received chemotherapy were treated with either 3-day EBAT or a prolonged antibiotic regimen (until neutrophil recovery).

Disclosures: The study did not receive any specific funding. A Schauwvlieghe, J Maertens, and T Mercier reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Schauwvlieghe A et al. EClinicalMedicine. 2021 Apr 25. doi: 10.1016/j.eclinm.2021.100855.

Key clinical point: Higher pretransplant red blood cell (RBC) and platelet transfusion burden has an independent association with higher overall and relapse-related mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for de novo myelodysplastic syndrome (MDS).

Major finding: A higher pretransplant RBC transfusion burden was significantly associated with lower overall survival (OS; P less than .001) and higher relapse-related mortality (P less than .001). Similarly, a higher pretransplant platelet transfusion burden was associated with lower OS (P less than .001) and higher relapse-related mortality (P = .001).

Study details: A retrospective study examined the effects of pretransplant RBC and platelet transfusion burden on outcomes after allo-HSCT in 1,007 adults with de novo MDS.

Disclosures: This study was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development. The authors declared no conflicts of interest.

Source: Konuma T et al. Transplant Cell Ther. 2021 May 12. doi: 10.1016/j.jtct.2021.05.003.

Key clinical point: Higher pretransplant red blood cell (RBC) and platelet transfusion burden has an independent association with higher overall and relapse-related mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for de novo myelodysplastic syndrome (MDS).

Major finding: A higher pretransplant RBC transfusion burden was significantly associated with lower overall survival (OS; P less than .001) and higher relapse-related mortality (P less than .001). Similarly, a higher pretransplant platelet transfusion burden was associated with lower OS (P less than .001) and higher relapse-related mortality (P = .001).

Study details: A retrospective study examined the effects of pretransplant RBC and platelet transfusion burden on outcomes after allo-HSCT in 1,007 adults with de novo MDS.

Disclosures: This study was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development. The authors declared no conflicts of interest.

Source: Konuma T et al. Transplant Cell Ther. 2021 May 12. doi: 10.1016/j.jtct.2021.05.003.

Key clinical point: Higher pretransplant red blood cell (RBC) and platelet transfusion burden has an independent association with higher overall and relapse-related mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for de novo myelodysplastic syndrome (MDS).

Major finding: A higher pretransplant RBC transfusion burden was significantly associated with lower overall survival (OS; P less than .001) and higher relapse-related mortality (P less than .001). Similarly, a higher pretransplant platelet transfusion burden was associated with lower OS (P less than .001) and higher relapse-related mortality (P = .001).

Study details: A retrospective study examined the effects of pretransplant RBC and platelet transfusion burden on outcomes after allo-HSCT in 1,007 adults with de novo MDS.

Disclosures: This study was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development. The authors declared no conflicts of interest.

Source: Konuma T et al. Transplant Cell Ther. 2021 May 12. doi: 10.1016/j.jtct.2021.05.003.

Key clinical point: Less restrictive inclusion and exclusion criteria are warranted to improve the participation of patients with myelodysplastic syndrome (MDS) in clinical trials.

Major finding: Each trial was suitable for ~18% of patients in the cohort, whereas 34% of the patients were eligible for at least 1 of the 9 trials. Pharma-initiated trials excluded more than twice the fraction of patients vs. investigator-initiated trials (inclusion, 10% vs. 21%). Key reasons for exclusion included karyotype (average exclusion rate, 58%), comorbidities (40%), and previous therapies (55%)

Study details: A simulation exercise was performed to estimate the average proportion of MDS patients eligible for participation in a clinical trial. A total of 1,809 patients were included in the cohort.

Disclosures: This study did not receive any funding. K Nachtkamp, T Schroeder, E Schuler, J Kaivers, A Giagounidis, C Rautenberg, N Gattermann, and U Germing reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Nachtkamp K et al. Leuk Res. 2021 May 11. doi: 10.1016/j.leukres.2021.106611.

Key clinical point: Less restrictive inclusion and exclusion criteria are warranted to improve the participation of patients with myelodysplastic syndrome (MDS) in clinical trials.

Major finding: Each trial was suitable for ~18% of patients in the cohort, whereas 34% of the patients were eligible for at least 1 of the 9 trials. Pharma-initiated trials excluded more than twice the fraction of patients vs. investigator-initiated trials (inclusion, 10% vs. 21%). Key reasons for exclusion included karyotype (average exclusion rate, 58%), comorbidities (40%), and previous therapies (55%)

Study details: A simulation exercise was performed to estimate the average proportion of MDS patients eligible for participation in a clinical trial. A total of 1,809 patients were included in the cohort.

Disclosures: This study did not receive any funding. K Nachtkamp, T Schroeder, E Schuler, J Kaivers, A Giagounidis, C Rautenberg, N Gattermann, and U Germing reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Nachtkamp K et al. Leuk Res. 2021 May 11. doi: 10.1016/j.leukres.2021.106611.

Key clinical point: Less restrictive inclusion and exclusion criteria are warranted to improve the participation of patients with myelodysplastic syndrome (MDS) in clinical trials.

Major finding: Each trial was suitable for ~18% of patients in the cohort, whereas 34% of the patients were eligible for at least 1 of the 9 trials. Pharma-initiated trials excluded more than twice the fraction of patients vs. investigator-initiated trials (inclusion, 10% vs. 21%). Key reasons for exclusion included karyotype (average exclusion rate, 58%), comorbidities (40%), and previous therapies (55%)

Study details: A simulation exercise was performed to estimate the average proportion of MDS patients eligible for participation in a clinical trial. A total of 1,809 patients were included in the cohort.

Disclosures: This study did not receive any funding. K Nachtkamp, T Schroeder, E Schuler, J Kaivers, A Giagounidis, C Rautenberg, N Gattermann, and U Germing reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Nachtkamp K et al. Leuk Res. 2021 May 11. doi: 10.1016/j.leukres.2021.106611.

Key clinical point: Inhibition of T cells by programmed death-ligand 1 (PD-L1)-expressing hematopoietic stem cells could be an underlying mechanism in the development of myelodysplastic syndrome (MDS). The findings support the potential use of immune checkpoint inhibitors in the treatment of suitable MDS patients.

Major finding: Significantly increased proportions of PD-L1⁺CD34⁺ stem cells were seen in MDS patients compared with hematopoietic stem cell transplantation (HSCT) recipients in remission for both the CD38⁻ subset (P = .0127) and CD38⁺ subset (P = .0336).

Study details: The study included 7 MDS and 9 acute myeloid leukemia samples. Six HSCT recipients who remained in remission for more than 6 months were considered controls.

Disclosures: The study was supported by the Düsseldorf School of Oncology (funded by the Comprehensive Cancer Center Düsseldorf/Deutsche Krebshilfe and the Medical Faculty HHU Düsseldorf). The authors declared no conflicts of interest.

Source: Moskorz W et al. Br J Haematol. 2021 May 6. doi: 10.1111/bjh.17461.

Key clinical point: Inhibition of T cells by programmed death-ligand 1 (PD-L1)-expressing hematopoietic stem cells could be an underlying mechanism in the development of myelodysplastic syndrome (MDS). The findings support the potential use of immune checkpoint inhibitors in the treatment of suitable MDS patients.

Major finding: Significantly increased proportions of PD-L1⁺CD34⁺ stem cells were seen in MDS patients compared with hematopoietic stem cell transplantation (HSCT) recipients in remission for both the CD38⁻ subset (P = .0127) and CD38⁺ subset (P = .0336).

Study details: The study included 7 MDS and 9 acute myeloid leukemia samples. Six HSCT recipients who remained in remission for more than 6 months were considered controls.

Disclosures: The study was supported by the Düsseldorf School of Oncology (funded by the Comprehensive Cancer Center Düsseldorf/Deutsche Krebshilfe and the Medical Faculty HHU Düsseldorf). The authors declared no conflicts of interest.

Source: Moskorz W et al. Br J Haematol. 2021 May 6. doi: 10.1111/bjh.17461.

Key clinical point: Inhibition of T cells by programmed death-ligand 1 (PD-L1)-expressing hematopoietic stem cells could be an underlying mechanism in the development of myelodysplastic syndrome (MDS). The findings support the potential use of immune checkpoint inhibitors in the treatment of suitable MDS patients.

Major finding: Significantly increased proportions of PD-L1⁺CD34⁺ stem cells were seen in MDS patients compared with hematopoietic stem cell transplantation (HSCT) recipients in remission for both the CD38⁻ subset (P = .0127) and CD38⁺ subset (P = .0336).

Study details: The study included 7 MDS and 9 acute myeloid leukemia samples. Six HSCT recipients who remained in remission for more than 6 months were considered controls.

Disclosures: The study was supported by the Düsseldorf School of Oncology (funded by the Comprehensive Cancer Center Düsseldorf/Deutsche Krebshilfe and the Medical Faculty HHU Düsseldorf). The authors declared no conflicts of interest.

Source: Moskorz W et al. Br J Haematol. 2021 May 6. doi: 10.1111/bjh.17461.

Key clinical point: Increased cumulative exposure to the alkylating agent melphalan increases the subsequent risk for developing acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM).

Major finding: Cumulative exposure to melphalan was significantly higher (odds ratio, 2.8; P less than .001) among patients with MM and AML/MDS (median, 988 mg) than control participants (median, 578 mg). The median time to development of AML/MDS was 3.8 years.

Study details: The study included 26,627 patients diagnosed with MM between 1985 and 2011, of which 124 (0.5%) patients developed subsequent AML/MDS. Each patient with MM and AML/MDS diagnosis was matched with a control MM patient without AML/MDS.

Disclosures: The study was supported by grants from the Asrun Einarsdottir Foundation in Iceland, University of Iceland Research Fund, Icelandic Centre for Research, Landspitali University Hospital Research Fund, Thorman’s foundation, and Sylvester Comprehensive Cancer Center NCI Core Grant. O Landgren and M Björkholm reported ties with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Jonsdottir G et al. Eur J Haematol. 2021 May 9. doi: 10.1111/ejh.13650.

Key clinical point: Increased cumulative exposure to the alkylating agent melphalan increases the subsequent risk for developing acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM).

Major finding: Cumulative exposure to melphalan was significantly higher (odds ratio, 2.8; P less than .001) among patients with MM and AML/MDS (median, 988 mg) than control participants (median, 578 mg). The median time to development of AML/MDS was 3.8 years.

Study details: The study included 26,627 patients diagnosed with MM between 1985 and 2011, of which 124 (0.5%) patients developed subsequent AML/MDS. Each patient with MM and AML/MDS diagnosis was matched with a control MM patient without AML/MDS.

Disclosures: The study was supported by grants from the Asrun Einarsdottir Foundation in Iceland, University of Iceland Research Fund, Icelandic Centre for Research, Landspitali University Hospital Research Fund, Thorman’s foundation, and Sylvester Comprehensive Cancer Center NCI Core Grant. O Landgren and M Björkholm reported ties with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Jonsdottir G et al. Eur J Haematol. 2021 May 9. doi: 10.1111/ejh.13650.

Key clinical point: Increased cumulative exposure to the alkylating agent melphalan increases the subsequent risk for developing acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM).

Major finding: Cumulative exposure to melphalan was significantly higher (odds ratio, 2.8; P less than .001) among patients with MM and AML/MDS (median, 988 mg) than control participants (median, 578 mg). The median time to development of AML/MDS was 3.8 years.

Study details: The study included 26,627 patients diagnosed with MM between 1985 and 2011, of which 124 (0.5%) patients developed subsequent AML/MDS. Each patient with MM and AML/MDS diagnosis was matched with a control MM patient without AML/MDS.

Disclosures: The study was supported by grants from the Asrun Einarsdottir Foundation in Iceland, University of Iceland Research Fund, Icelandic Centre for Research, Landspitali University Hospital Research Fund, Thorman’s foundation, and Sylvester Comprehensive Cancer Center NCI Core Grant. O Landgren and M Björkholm reported ties with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Jonsdottir G et al. Eur J Haematol. 2021 May 9. doi: 10.1111/ejh.13650.

Key clinical point: Adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally exhibit better survival than their non-AYA counterparts.

Major finding: The 3-year overall survival (OS) in AYA patients was 71.2% (95% confidence interval, 67.4%-74.6%). Predictors of poor 3-year OS were active disease status (adjusted hazard ratio [aHR], 1.54; P = .016), poor cytogenetic risk (aHR, 1.62; P = .011), poor performance status (aHR, 2.01; P = .016), human leukocyte antigen (HLA)-matched unrelated donors (aHR, 2.23; P less than .001), HLA-mismatched unrelated donors (aHR, 2.16; P = .027), and cord blood transplantation (aHR, 2.44; P = 0.001).

Study details: The study included 645 AYA patients with MDS, aged 16-39 years, who received first allo-HSCT.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Shimomura Y et al. Bone Marrow Transplant. 2021 May 15. doi: 10.1038/s41409-021-01324-8.

Key clinical point: Adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally exhibit better survival than their non-AYA counterparts.

Major finding: The 3-year overall survival (OS) in AYA patients was 71.2% (95% confidence interval, 67.4%-74.6%). Predictors of poor 3-year OS were active disease status (adjusted hazard ratio [aHR], 1.54; P = .016), poor cytogenetic risk (aHR, 1.62; P = .011), poor performance status (aHR, 2.01; P = .016), human leukocyte antigen (HLA)-matched unrelated donors (aHR, 2.23; P less than .001), HLA-mismatched unrelated donors (aHR, 2.16; P = .027), and cord blood transplantation (aHR, 2.44; P = 0.001).

Study details: The study included 645 AYA patients with MDS, aged 16-39 years, who received first allo-HSCT.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Shimomura Y et al. Bone Marrow Transplant. 2021 May 15. doi: 10.1038/s41409-021-01324-8.

Key clinical point: Adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally exhibit better survival than their non-AYA counterparts.

Major finding: The 3-year overall survival (OS) in AYA patients was 71.2% (95% confidence interval, 67.4%-74.6%). Predictors of poor 3-year OS were active disease status (adjusted hazard ratio [aHR], 1.54; P = .016), poor cytogenetic risk (aHR, 1.62; P = .011), poor performance status (aHR, 2.01; P = .016), human leukocyte antigen (HLA)-matched unrelated donors (aHR, 2.23; P less than .001), HLA-mismatched unrelated donors (aHR, 2.16; P = .027), and cord blood transplantation (aHR, 2.44; P = 0.001).

Study details: The study included 645 AYA patients with MDS, aged 16-39 years, who received first allo-HSCT.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Shimomura Y et al. Bone Marrow Transplant. 2021 May 15. doi: 10.1038/s41409-021-01324-8.

Key clinical point: Lenalidomide had no relevant effect on DNA methylation status in patients with myelodysplastic syndrome with isolated deletion of chromosome 5q (MDS del5q).

Major finding: Lenalidomide treatment did not have a relevant impact on genome-wide DNA methylation in patients with MDS del5q. However, methylation analysis before treatment could identify a distinct subgroup of patients (27%) with a trend toward inferior overall survival but not inferior progression-free survival.

Study details: DNA methylation analysis was performed on 51 MDS del5q patients treated with lenalidomide. Direct effects of lenalidomide on DNA methylation were studied using 17 paired samples pre- and posttreatment.

Disclosures: Open access funding by Projekt DEAL. This study was supported by funds from the Deutsche Forschungsgemeinschaft, “Deutsche Krebshilfe,” Gutermuth Foundation, H.W. & J. Hector fund, Baden Wuerttemberg, and Dr Rolf M Schwiete Fund. Mannheim DN is an endowed Professor of the German José-Carreras-Stiftung. The study was partly funded by a research grant from Celgene Inc.

Source: Hecht A et al. Ann Hematol. 2021 April 27. doi: 10.1007/s00277-021-04492-1.

Key clinical point: Lenalidomide had no relevant effect on DNA methylation status in patients with myelodysplastic syndrome with isolated deletion of chromosome 5q (MDS del5q).

Major finding: Lenalidomide treatment did not have a relevant impact on genome-wide DNA methylation in patients with MDS del5q. However, methylation analysis before treatment could identify a distinct subgroup of patients (27%) with a trend toward inferior overall survival but not inferior progression-free survival.

Study details: DNA methylation analysis was performed on 51 MDS del5q patients treated with lenalidomide. Direct effects of lenalidomide on DNA methylation were studied using 17 paired samples pre- and posttreatment.

Disclosures: Open access funding by Projekt DEAL. This study was supported by funds from the Deutsche Forschungsgemeinschaft, “Deutsche Krebshilfe,” Gutermuth Foundation, H.W. & J. Hector fund, Baden Wuerttemberg, and Dr Rolf M Schwiete Fund. Mannheim DN is an endowed Professor of the German José-Carreras-Stiftung. The study was partly funded by a research grant from Celgene Inc.

Source: Hecht A et al. Ann Hematol. 2021 April 27. doi: 10.1007/s00277-021-04492-1.

Key clinical point: Lenalidomide had no relevant effect on DNA methylation status in patients with myelodysplastic syndrome with isolated deletion of chromosome 5q (MDS del5q).

Major finding: Lenalidomide treatment did not have a relevant impact on genome-wide DNA methylation in patients with MDS del5q. However, methylation analysis before treatment could identify a distinct subgroup of patients (27%) with a trend toward inferior overall survival but not inferior progression-free survival.

Study details: DNA methylation analysis was performed on 51 MDS del5q patients treated with lenalidomide. Direct effects of lenalidomide on DNA methylation were studied using 17 paired samples pre- and posttreatment.

Disclosures: Open access funding by Projekt DEAL. This study was supported by funds from the Deutsche Forschungsgemeinschaft, “Deutsche Krebshilfe,” Gutermuth Foundation, H.W. & J. Hector fund, Baden Wuerttemberg, and Dr Rolf M Schwiete Fund. Mannheim DN is an endowed Professor of the German José-Carreras-Stiftung. The study was partly funded by a research grant from Celgene Inc.

Source: Hecht A et al. Ann Hematol. 2021 April 27. doi: 10.1007/s00277-021-04492-1.