Clinical Characteristics and Survival Analysis of Patients with Chronic Myelomonocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, prognostic factors and efficacy of hypomethylating agent (HMA) in patients with chronic myelomonocytic leukemia (CMML).@*METHODS@#The clinical data of 37 newly diagnosed patients with CMML was analyzed retrospectively, and their clinical characteristics and the efficacy of HMA were summarized. Kaplan-Meier and Log-rank test were used for univariate survival analysis, and Cox proportional hazards regression model was used for multivariate analysis.@*RESULTS@#The median age at diagnosis was 67 years old. Their common manifestations included fatigue, bleeding, abnormal blood routine and fever. Most patients had splenomegaly. According to FAB classification, there were 6 cases of myelodysplastic CMML and 31 cases of myeloproliferative CMML, while according to WHO classification, 8 patients belonged to CMML-0, 9 patients to CMML-1 and 20 patients to CMML-2. At the time of diagnosis, the median white blood cell count was 32.84×109/L, median hemoglobin (Hb) was 101 g/L, median platelet count was 65×109/L, median absolute monocyte count was 9.53×109//L, median absolute neutrophil count (ANC) was 11.29×109//L and median lactate dehydrogenase (LDH) was 374 U/L. Cytogenetic abnormalities were found in 4 cases among the 31 patients who underwent karyotype analysis or fluorescence in situ hybridization detection. There were 12 patients who had analyzable results and gene mutations were identified in 11 cases, including ASXL1, NRAS, TET2, SRSF2 and RUNX1. Among the 6 patients who were treated with HMA and could be evaluated for efficacy, 2 patients achieved complete remission, 1 patient achieved partial remission and 2 patients achieved clinical benefit. Compared with the non-HMA treatment group, overall survival (OS) time was not significantly prolonged in the HMA treatment group. Univariate analysis showed that Hb<100 g/L, ANC≥12×109/L, LDH≥250 U/L and peripheral blood (PB) blasts ≥5% were significantly associated with poor OS, while WHO classification CMML-2, Hb<100 g/L, ANC≥12×109/L, LDH≥250 U/L and PB blasts≥5% were significantly associated with poor leukemia-free survival (LFS) (P<0.05). Multivariate analysis showed that ANC≥12×109/L and PB blasts≥5% were significantly associated with poor OS and LFS (P<0.05).@*CONCLUSION@#CMML has high heterogeneity in clinical characteristics, genetic changes, prognosis and treatment response. HMA can not significantly improve the survival of CMML patients. ANC≥12×109/L and PB blasts≥5% are independent prognostic factors of OS and LFS in patients with CMML.

No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome

BACKGROUND/AIMS: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. METHODS: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. RESULTS: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. CONCLUSIONS: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

Options for patients with myelodysplastic syndromes after the treatment failure of hypomethylating agent / 白血病·淋巴瘤

The treatment of patients with myelodysplastic syndromes (MDS) has included primarily supportive care (blood transfusions, colony stimulating agents, iron chelation, etc.) and new drugs, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For those who are no longer benefiting from these agents, there is nearly nothing to do with effective therapies. When those drugs are ineffective, what the doctors could do is optimizing the delivery of hypomethylating agents (HMT) by dosing appropriately, sequencing appropriately, and using thoughtful combinations; as well as improving drug formulations (oral formulations and/or novel formulations) and working toward better selection of patients for best upfront mutation-directed therapy. Hopefully, the drug targeting and patient selection for optimal HMT treatment of MDS will be improved. Furthermore, ongoing research is focused on identifying unique agents to rescue MDS patients who have progressed despite HMT. Agents such as rigosertib are now focused on its application in specific MDS populations who might most likely benefit from this therapeutic approach [primary refractory and high-risk international prognostic scoring system (IPSS) patients]. Doctors eagerly await results of single-agent programmed death 1 (PD-1) and its inhibitors, or combination with HMT to the upfront and relapsed MDS setting. For the minority of patients who have specific targetable mutations, the selective agents (IDH1/2) are highly promising. Bone marrow transplantation remains the only offer for cure, but is depressingly unrealistic given the majority of the elderly and frail patients at the time of MDS progression.

Options for patients with myelodysplastic syndromes after the treatment failure of hypomethylating agent / 白血病·淋巴瘤

The treatment of patients with myelodysplastic syndromes (MDS) has included primarily supportive care (blood transfusions, colony stimulating agents, iron chelation, etc.) and new drugs, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For those who are no longer benefiting from these agents, there is nearly nothing to do with effective therapies. When those drugs are ineffective, what the doctors could do is optimizing the delivery of hypomethylating agents (HMT) by dosing appropriately, sequencing appropriately, and using thoughtful combinations; as well as improving drug formulations (oral formulations and/or novel formulations) and working toward better selection of patients for best upfront mutation-directed therapy. Hopefully, the drug targeting and patient selection for optimal HMT treatment of MDS will be improved. Furthermore, ongoing research is focused on identifying unique agents to rescue MDS patients who have progressed despite HMT. Agents such as rigosertib are now focused on its application in specific MDS populations who might most likely benefit from this therapeutic approach [primary refractory and high-risk international prognostic scoring system (IPSS) patients]. Doctors eagerly await results of single-agent programmed death 1 (PD-1) and its inhibitors, or combination with HMT to the upfront and relapsed MDS setting. For the minority of patients who have specific targetable mutations, the selective agents (IDH1/2) are highly promising. Bone marrow transplantation remains the only offer for cure, but is depressingly unrealistic given the majority of the elderly and frail patients at the time of MDS progression.