Meta-analysis of the benefit of hypomethylating agents before allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes

Abstract Hypomethylating agents (HMAs) are effective therapies in myelodysplastic syndromes (MDS), but allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only way to cure MDS. According to the current literature, it is difficult to confirm whether HMAs bridging therapy is beneficial for MDS patients receiving allo-HSCT. Therefore, we tried to evaluate the effect of HMAs on long-term survival of the MDS patients. Databases, including PubMed, Embase Ovid, and the Cochrane Library, were searched for studies published up to January 10, 2021. Patients who accepted HMAs bridging to allo-HSCT were defined as experimental group, while patients who received the best supportive care (BSC) before allo-HSCT were control group. Overall survival (OS) was the primary end point. Seven studies were included in the final analysis. The final results showed no OS differences between patients accepted HMAs before allo-HSCT and those received BSC (HR = 0.86, 95% CI: 0.64–1.15, p = 0.32), indicating that MDS patients' long-term survival did not benefit from HMAs bridging therapy before allo-HSCT. This conclusion needs to be further verified by a large number of prospective randomized controlled trials, which have guiding significance for the treatment of MDS patients.

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Multicenter study evaluating the impact of hypomethylating agents as bridging therapy to hematopoietic stem cell transplantation in myelodysplastic syndromes

International Journal of Hematology ◽

10.1007/s12185-014-1549-3 ◽

2014 ◽

Vol 99 (5) ◽

pp. 635-643 ◽

Cited By ~ 9

Author(s):

Yundeok Kim ◽

◽

In-Ho Kim ◽

Hyeong Joon Kim ◽

Silvia Park ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Multicenter Study ◽

Myelodysplastic Syndromes ◽

Hypomethylating Agents ◽

Bridging Therapy ◽

Hematopoietic Stem ◽

The Impact

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Multicenter Study Evaluating the Impact of Hypomethylating Agents As Bridging Therapy to Hematopoietic Stem Cell Transplantation in Myelodysplastic Syndromes

Blood ◽

10.1182/blood.v120.21.3806.3806 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3806-3806

Author(s):

Yundeok Kim ◽

Lee Je Hwang ◽

Inho Kim ◽

Jang Joon Ho ◽

Hyeoung Joon Kim ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Median Time ◽

Multicenter Study ◽

Myelodysplastic Syndromes ◽

Bridging Therapy ◽

Hematopoietic Stem ◽

Transplant Outcome

Abstract Abstract 3806 Introduction: Allogeneic hematopoietic stem cell transplantation (alloHCT) is the only curative modality for myelodysplastic syndromes (MDS). Recently, treatment paradigm has changed since the introduction of hypomethylating agent (HMA) to treatment of MDS. There is little known about effect of HMA to transplant outcome and appropriate dose and schedule when used as bridging therapy to alloHCT. Therefore this retrospective multicenter study aimed to assess the effect of pre-transplant HMA on transplant outcome and aimed to determinate the patient who would benefit from pre-transplant HMA therapy. Method: Medical record of 113 patients (male n=69; female n=44) were reviewed. Patients who received alloHCT from 2007 to 2010 were enrolled regardless of pre-transplant HMA therapy. Five institutions participated. Primary endpoint event-free survival (EFS) after alloHCT. Second endpoint was engraftment after alloHCT. Analysis was done by HMA versus non-HMA. Results: Eighty-five of the 113 patients were treated with HMA before HSCT (51 with Azacitidine (AZA), 30 with Decitabine (DCT) and 4 with both alternatively). Twenty-eight patients received alloHCT without HMA bridging. The median age 47 (range 20–69) for HMA group and 42 (range 17–64) for non-HMA group (P=0.035). Distribution of WHO classification group and IPSS score were similar criteria (P=0.230 and P=0.328), For HMA group, median number of HMA administration was 5 cycles (range 1∼20). Among HMA treated patients, 21 (18.5 %) achieved complete response (CR) or marrow CR (mCR) and 4 (3.5 %) achieved partial response (PR). For all patients, median EFS was 29 ± 2 months. IPSS score at diagnosis(Low/Intermediate (INT)-1 vs. INT-2/High) affected overall survival (OS) after alloHCT (32 ± 3 vs. 25 ± 4 months, respectively; P=0.020). Pre-transplant HMA didn't affect OS (P=0.771) and there was also no difference between AZA and DCT (P=0.60). However, for patient with high blast count (>5% of bone marrow at diagnosis) pre-transplant HMA therapy had a benefit of 1-yr EFS (16.7 % for non-HMA vs. 67.9 % for HMA, P=0.126) Median time to neutrophil engraftment was 28 (range, 2∼380 days) for HMA and 12 (range, 7∼18 days) for non-HMA (P=0.031). Median time for platelet engraftment was 35 for HMA group and 19 for non-HMA group (P=0.052). Effect of HMA to graft-versus-host disease or graft failure was uncertain. Conclusion: Benefit of bridging therapy of HMA before alloHCT was not definite by this retrospective study. However for a proportion of patients with high leukemic burden, HMA tended to have benefit for post-HCT EFS. There was considerable delay of engraftment among HMA treated patients. Therefore, pre-HCT bridging HMA therapy may not be appropriate for all MDS patients. Prospective trial is required to confirm the benefit and effect of HMA bridging therapy to alloHCT. Disclosures: No relevant conflicts of interest to declare.

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Prediction of Response and Survival Following Treatment with Azacitidine for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation

Cancers ◽

10.3390/cancers12082255 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2255 ◽

Cited By ~ 1

Author(s):

Christina Rautenberg ◽

Anika Bergmann ◽

Ulrich Germing ◽

Caroline Fischermanns ◽

Sabrina Pechtel ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Term Outcome ◽

Term Survival ◽

Hematopoietic Stem ◽

Long Term Outcome

To provide long-term outcome data and predictors for response and survival, we retrospectively analyzed all 151 patients with relapse of myeloid neoplasms after allogeneic hematopoietic stem cell transplantation (allo-HSCT) who were uniformly treated with first-line azacitidine (Aza) salvage therapy at our center. Patients were treated for molecular (39%) or hematologic relapse (61%), with a median of 5 cycles of Aza and at least one donor lymphocyte infusion in 70% of patients. Overall response was 46%, with 41% achieving complete (CR) and 5% achieving partial remission. CR was achieved after a median of 4 cycles and lasted for a median of 11 months (range 0.9 to 120 months). With a median follow-up of 22 months (range: 1 to 122 months), the 2-year survival rate was 38% ± 9%, including 17 patients with ongoing remission for >5 years. Based on results from multivariate analyses, molecular relapse and time to relapse were integrated into a score, clearly dividing patients into 3 subgroups with CR rates of 71%, 39%, and 29%; and 2-year survival rates of 64%, 38%, and 27%, respectively. In the subgroup of MDS and secondary AML, receiving upfront transplantation was associated with superior response and survival, and therefore pretransplant strategy was integrated together with relapse type into a MDS–sAML-specific score. Overall, Aza enables meaningful responses and long-term survival, which is a predictable with a simple-to-use scoring system.

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High Rate of Long-Term Survival for High-Risk Lymphoma Patients Treated With Hematopoietic Stem Cell Transplantation as Consolidation or Salvage Therapy

Transplantation Proceedings ◽

10.1016/j.transproceed.2008.08.092 ◽

2008 ◽

Vol 40 (9) ◽

pp. 3104-3105 ◽

Cited By ~ 4

Author(s):

I. Espigado ◽

E. Ríos ◽

A. Marín-Niebla ◽

M. Carmona ◽

R. Parody ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Salvage Therapy ◽

High Rate ◽

Term Survival ◽

Hematopoietic Stem

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Negative Impact of Pre-Transplant Anemia on Long-Term Outcome after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v104.11.1844.1844 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1844-1844

Author(s):

Chris Lazongas ◽

Cindy J. Wong ◽

David M. Sutton ◽

Jeffrey H. Lipton ◽

Anargyros Xenocostas ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Causes Of Death ◽

Term Survival ◽

Hematopoietic Stem

Abstract Background: Anemia is commonly present in patients with malignancies and is associated with reduced survival times. Recently, we described that low (<110 g/L) pre-transplant hemoglobin levels (PT-Hb) are associated with decreased early survival after allogeneic hematopoietic stem cell transplantation (alloHSCT)(Xenocostas et al. Transfusion2003;43:373–382). We are now presenting data on long-term survival and causes of death in BMT recipients with and without anemia prior to alloHSCT. Study Design and Methods: A retrospective analysis of 511 patients consecutively transplanted between January 1995 and March 2000 was performed to evaluate survival, cause of death, and PT-Hb. The end date for follow-up was June 2002. The median follow-up time was 993 days. Causes of death were categorized either as relapse, treatment-related mortality (TRM), or other. PT-Hb levels were determined within 2 weeks prior to transplantation, after commencing conditioning chemotherapy. Comparisons between groups were done using chi-squared tests. Results: The 180-day survival of patients with low PT-Hb levels (<110 g/L) was significantly worse than that of patients with PT-Hb levels ≥110 g/L (57.1% versus 83.1%, p<0.0001). The survival difference remained significant at 5 years (36.2% versus 59.4%, p<0.0001). The difference in 180-day survival was contributed to by an increase in TRM (36.1% versus 14.9%, p<0.0001) as well as a higher relapse rate (4.4% versus 0.3%, p=0.019 by Fisher’s exact test). For patients surviving more than 180 days, there was no difference in TRM (16.7% versus 16.7%, p=0.987) or relapse rate (12.0% versus 7.3%, p=0.150). No difference in the rate of other causes of death was found between the groups at either the 180-day or 5-year time points. Conclusions: Pre-transplant anemia is an independent risk factor for increased mortality following alloHSCT. Relapse and treatment-related deaths are both more likely to occur early in the post-transplant course of patients experiencing pre-transplant anemia. Differences in long-term survival are predominantly related to treatment-related deaths rather than relapse.

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