HLA-Matched Transplantation Improves OS in High-Risk MDS

HLA-matched allogeneic hematopoietic stem cell transplantation was associated with more than a doubling in 4-year overall survival rates for patients with intermediate-2 or high-risk myelodysplastic syndromes.

HLA-matched allogeneic hematopoietic stem cell transplantation (HSCT) was associated with more than a doubling in 4-year overall survival (OS) rates for patients with intermediate-2 or high-risk myelodysplastic syndromes (MDS), according to findings presented at the 2015 International MDS Symposium.1

In the prospective study, the probability of receiving a transplant from an HLA 10/10 donor was approximately 50%. In patients who did not receive HSCT, the 4-year OS rate was 15% compared with 37% in those who underwent the procedure (P = .02). Findings from the study suggest that all patients with high-risk MDS and an HLA identical donor should receive transplantation, according to the study's lead author Marie Robin, MD, PhD.

"The 2 survival curves were similar for the first 2 years. After the second year, the patients who had a donor had a better survival," Robin, a bone marrow transplantation specialist at Saint-Louis Hospital, Paris, France, said during her presentation. "This multivariate analysis confirmed that patients who received a transplant had a better prognosis after the second year of the transplant. This was very significant."

In the French study, 162 patients with higher-risk MDS who were candidates for transplantation were observed in a period between 2007 and 2013. Nearly all (92%) patients had IPSS intermediate-2 or high-risk MDS and 75% of patients had a blast marrow of >5%.

Patients were enrolled in the study at the time of eligibility for transplantation. While a donor was located, patients were treated with a demethylating agent (76%), intensive chemotherapy (28%), or no therapy (11%). Treatment prior to transplant was recommended for all patients with blast marrow of >10%.

An HLA-identical donor was found for 69% of patients enrolled, with 54 from siblings and 58 from unrelated donors. Fifty patients were unable to find a donor. Of those with a donor (n = 112), 70% went on to receive a transplant after a median of 8 months. Progressive disease (52%) was the primary cause for not receiving a transplant for those with an HLA-identical donor, followed by comorbidity (29%), early death (13%), and refusal (6%).

The response achieved with a demethylating agent or intensive chemotherapy impacted transplant eligibility. Those who developed acute myelogenous leukemia (AML) were unable to receive a transplant. Patients with a partial response were most likely to receive a transplant (HR = 6.84), followed by those who achieved a complete response (HR = 4.14) and those with progressive disease (HR = 2.46).

"The transplant achievement is influenced by various parameters, such as time-dependent parameters and disease status," Robin said. "Patients with persistent AML were unable to undergo the transplant. Patients with a partial remission to pretransplant treatment had a higher chance of undergoing a transplant."

Treatment response factors, along with age and cytogenetics, were utilized in a multivariate analysis for the impact of HSCT on survival. Patients who had a donor but did not receive a transplant represented an HR = 1.00.

At less than 1 year, the benefits of HSCT were unclear (HR = 1.07; P = .82). However, as time went on, a clear advantage could be seen with HSCT. At more than 2 years of follow-up posttransplant, the HR for survival was 0.024 (P = .0009).

"In the first 2 years, there were no differences in terms of a multivariate risk analysis," added Robin. "The only long-term survivors are transplanted patients."

Support for allogeneic HSCT in MDS has grown in recent years, as more data becomes available and prophylactic treatments for graft-versus-host disease are discovered. The NCCN guidelines recommend utilizing transplant in patients with MDS at high or very high IPSS risk.

In a clinical trial presented at the 2012 American Society of Hematology (ASH) annual meeting, a significant advantage in survival was seen with allogeneic HSCT at a 68-month median analysis.2 The median OS with transplantation in the IPSS high group was 42 months compared with 21 months without HSCT (P = .004). In the IPSS very high group, the median OS was 31 versus 12 months, with and without HSCT, respectively (P <.005).

In 2010, the Centers for Medicare & Medicaid Services (CMS) released documentation suggesting that it would not cover allogeneic HSCT for the treatment of MDS, unless administered in the context of an approved clinical study. To gain access to treatment, CMS encouraged enrollment in a protocol designed as a research database for HSCT and other cellular therapies. The study was established in 2002 and continues to enroll patients (NCT01166009).


  1. Robin M, Porcher R, Ades L, et al. HLA-matched allogeneic stem cell transplantation improves overall survival of higher risk myelodysplastic syndrome. Leukemia Research. 2015;39:1s (suppl; abstr 15).
  2. Mishra A, Ali NHA, Corrales-Yepez M, et al. Validation of the revised international prognostic scoring system (R-IPSS) for patients with myelodysplastic syndromes: therapeutic implications. Presented at: 2012 ASH annual meeting, December 8-11; Atlanta, GA. Abstract 2816.


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