Current status of pretransplant intensive chemotherapy or hypomethylating agents for myelodysplastic syndrome?

2021 ◽  
pp. 101332
Author(s):  
Christian Niederwieser ◽  
Nicolaus Kröger
Keyword(s):  
Myelodysplastic Syndrome ◽  
Current Status ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents

Management of Patients After the Failure of Hypomethylating Treatment for Myelodysplastic Syndrome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4953-4953
Author(s):  
Je-Hwan Lee ◽  
Jung-Hee Lee ◽  
Yunsuk Choi ◽  
Dae-Young Kim ◽  
Kyoo-Hyung Lee ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Treatment Failure ◽  
Salvage Therapy ◽  
Disease Status ◽  
Chronic Myelomonocytic Leukemia ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents ◽  
Term Survival ◽  
Allogeneic Hct ◽  
Myelomonocytic Leukemia

Abstract Abstract 4953 Introduction: Although treatment with hypomethylating agents such as azacitidine or decitabine has been the standard of care for patient with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML), about half of the patients fail to respond to the agents and most responders progress within 2 years. Retrospective studies showed poor outcomes after failure of treatment with azacitidine or decitabine and there is no standard salvage therapy for patients who fail hypomethylating treatment (HMT). We retrospectively studied outcomes of patients who failed HMT and analyzed the effects of salvage therapy after HMT failure. Methods: Between September 2006 and October 2010, a total of 149 patients were treated with either azacitidine (n=75) or decitabine (n=74) for MDS defined by the WHO classification and chronic myelomonocytic leukemia (CMML) in 3 Korean institutes. Ninety-one of the 149 patients were included in this study and disease status at the end of HMT was categorized as stable disease (n=22), primary progression (n=17), progression after response (n=38), and intolerance (n=14). Six patients who were still receiving hypomethylating agents with a median of 19 courses (range, 15 to 48) and 52 patients who stopped hypomethylating agents for other reasons were excluded from the analysis. Results: Median age was 59 years (range, 23 to 80) at the time of HMT failure. Median follow-up duration of surviving patients was 47. 8 months (range, 5. 8 to 62. 9) and 69 patients died. Probability of overall survival (OS) at 3 years was 28. 1% and median OS was 12. 1 months (95% confidence interval [CI], 9. 8 to 14. 4). Multivariate analysis showed that disease status and evolution to acute myeloid leukemia (AML) at HMT failure were independent prognostic factors for OS. A total of 37 patients (40. 7%) received supportive care only after HMT failure and other patients were managed with one or more treatments including immunosuppressive therapy (n=7), low-dose cytarabine (n=9), androgen (n=8), alternate azanucleoside (n=2), intensive chemotherapy (n=24), and allogeneic hematopoietic cell transplantation (HCT) (n=23). Objective response to non-transplant treatment was observed in 11–17% of evaluable patients, while 17 (74%) of 23 patients who received allogeneic HCT attained complete response. Probability of OS at 2 years (from HCT) was 60. 9% in the transplanted patients; it was 78. 6% in patients who received HCT during MDS and 33. 3% in those who received HCT after AML evolution (P=0. 016). Conclusions: The clinical outcomes of patients after hypomethylating treatment failure are poor; especially, AML evolution at the time of hypomethylating treatment failure and primary progression after hypomethylating treatment indicated very poor prognosis. Responses to various low intensity therapies and intensive chemotherapy were infrequent. Long-term survival without disease evidence was observed in about half of the patients who received allogeneic HCT. In appropriately selected patients, allogeneic HCT should be performed in earlier period, especially before evolution to AML. Patients with MDS that has failed to respond to hypomethylating agents should be referred for clinical trials when available. Disclosures: No relevant conflicts of interest to declare.

Outcome Of Patients With Myelodysplastic Syndrome (MDS) With Bone Marrow Blasts Between 10-30% Treated With Hypomethylating Agents Versus Intensive Chemotherapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2788-2788 ◽  
Author(s):  
Aziz Nazha ◽  
Hagop M. Kantarjian ◽  
Elias Jabbour ◽  
Courtney D. DiNardo ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Regression Model ◽  
Conflicts Of Interest ◽  
World Health ◽  
Refractory Anemia ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents ◽  
Specific Protocol ◽  
Bone Marrow Blasts

Abstract Background In 2001, the World Health Organization modified the French-American-British (FAB) classification for myelodysplastic syndrome (MDS) by folding the refractory anemia with excess blasts in transformation (RAEB-t) category into acute myeloid leukemia (AML). Whether this group of patients (pts) should be treated with AML versus MDS therapy remains controversial. A subset analysis of the AZA-001 trial showed that azacitidine prolongs overall survival (OS) in elderly pts with low blasts AML (bone marrow blasts [BM] 20-30%). Aim To compare the clinical outcome and OS of patients with MDS or AML with BM blasts between 10-30%, treated with hypomethylating agents (HMA) vs intensive chemotherapy (IC). Patients and Methods We conducted a retrospective analysis of newly diagnosed pts with MDS (or AML by WHO) and BM blasts between 10-30% treated with either HMA (alone or in combination with investigational therapies) or IC on clinical trials. Eligibility was based on pt characteristics and specific protocol inclusion criteria. A univariate Cox proportional hazards regression model was used to evaluate the overall effects of treatments and outcome (remission duration (RD), and OS). Then a regression model with the interactions between treatments and baseline covariates were used for subgroup analysis. The final model was obtained by a stepwise selection using 0.05 as a cut off of significant values. Results 330 patients were included in the final analysis, with 93 (28%) HMA-treated pts and 237 (72%) pts treated with IC. Clinical characteristics at diagnosis are summarized in Table1. The overall response rate (ORR= CR+CR p) was 42% for the pts who treated with HMA and 60% for pts treated with IC (P = 0.01). The median RD was similar between the two groups (14.7 mos (m) vs. 14.7 mos, respectively, P = 0.74). Early induction mortality was also similar among the two groups (4-week mortality was 5% vs. 7%, respectively, and the 8-week mortality was 10% vs. 13 %, respectively). With median follow up of 37 mos (range, 1-94 mos), the median OS was 18.8 mos for pts who treated with HMA vs. 14.6 mos for pts treated with IC (P = 0.32). Moreover, the BM blasts percentage did not impact the overall outcome. In multivariate analysis, treatment with IC was associated with worse OS compared to HMA (HR 2.09, 95% CI 2.07-3.17, P = 0.003) but not for RD (HR 0.43, 95% CI 0.89-2.68, P = 0.13). Conclusion Although patients with MDS or AML with BM blasts between 10-30% initially achieve a higher ORR when treated with IC compared to HMA-based therapy, the OS was better for pts treated with HMA after accounting for all other covariates. Interestingly, BM blast percentages within this cohort did not impact overall outcome suggesting that pts with BM blasts 20-30% may achieve better outcome with MDS therapy. Disclosures: No relevant conflicts of interest to declare.

Intensive chemotherapy (IC) versus hypomethylating agents (HMA) for the treatment of younger patients with myelodysplastic syndrome (MDS) and elevated bone marrow blasts.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 7064-7064
Author(s):  
Paolo Strati ◽  
Guillermo Garcia-Manero ◽  
Tapan M. Kadia ◽  
Gautam Borthakur ◽  
Marina Konopleva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents ◽  
Younger Patients ◽  
Bone Marrow Blasts

scholarly journals Demethylation and upregulation of an oncogene post hypomethylating treatment

2020 ◽  
Author(s):  
Yao-Chung Liu ◽  
Emiliano Fabiani ◽  
Junsu Kwon ◽  
Chong Gao ◽  
Giulia Falconi ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Cell Lines ◽  
Prognostic Value ◽  
Leukemic Cell ◽  
Hypomethylating Agents ◽  
Poor Outcome ◽  
Leukemic Cell Lines ◽  
The Relationship

While hypomethylating agents (HMA) are currently used to treat myelodysplastic syndrome (MDS) patients, their effects on reactivation and/or upregulation of oncogenes have not been previously described. SALL4 is a known oncogene that plays an important role in MDS. In this study, we examined the relationship between SALL4 methylation and expression, and evaluated changes of SALL4 expression and their prognostic value in MDS patients undergoing HMA treatment. In no/low-SALL4 expressing leukemic cell lines, we identified that demethylation of a critical CpG region was associated with increased SALL4 expression, and HMA treatment led to demethylation of this region and upregulation of SALL4. In MDS patients, we observed SALL4 upregulation after four cycles of azacytidine (AZA) treatment in 40% of the cases. Significantly, patients in the responder group with SALL4 upregulation had the worst outcome. This is the first study focusing on demethylation and upregulation of an oncogene after HMA treatment. Our data indicate that MDS patients receiving HMA treatment should be monitored for upregulation of oncogenes such as SALL4 for poor outcome.

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