Pre-Transplant Therapy for Patients with Myelodysplastic Syndrome and Post-Transplant Outcome

Allogeneic hematopoietic cell transplantation (Allo-HSCT) has proven to have curative potential for myelodysplastic syndrome (MDS). However, relapse post HSCT continues to be a problem. Pre-HSCT cytoreduction with either intensive chemotherapy or hypomethylating agents has been used with limited data on pre- or post-HSCT outcomes. In this report, we evaluated the impact of pre-transplant therapy on post-HSCT outcomes including overall survival (OS) and Progression Free Survival (PFS).

Methods:

We retrospectively reviewed 31 patients who underwent allo-HSCT for MDS in our center between 1997 and 2012. Primary objective was to study the impact of therapy pre-HSCT on HSCT outcome. Demographics, disease-related and transplant-related variables were collected.  PFS was defined as the time from HSCT to the time of progression, death or last contact whichever occurred first. OS was defined as the time from HSCT to the time of death or last contact. The distributions of PFS and OS were estimated by the Kaplan-Meier method. The log-rank test was used to compare the survival distributions between the two groups. Regression analyses for survival data used Cox proportional hazards model.

Results:

Median age at HSCT was 58 years. Median time from diagnosis to HSCT was 145 days. Of the 31 patients, 38.8% had poor cytogenetic abnormalities. Conditioning regimen used was high-dose in 71% or a reduced-intensity in 29%. 18/31 patients (58.1%) received therapy before HSCT. Intensive therapy with cytarabine was used in 3 patients while non-intensive therapy, with hypomethylating agents, median of 4 cycles, were used in 11 patients, Thalidomide or Lenalidomide in 3 patients and hydroxyurea in 1. 13/31 (41.9%) did not get any therapy prior to HSCT.

On univariate analysis, the treatment prior to HSCT had adverse impact on PFS and OS (HR=2.8, p=0.0404 and HR=2.8, p=0.0387 respectively). In multivariate models, treatment prior to HSCT still emerged as a significant predictor of poor PFS and OS (HR=6.6, p =0.0070 and HR=8.1, p=0.0037 respectively) after adjusting for age, gender and WHO classification-based Prognostic Scoring System. There was no statistical significant difference in the change in percentage of blasts at diagnosis and just before transplant for those who received therapy compared to those who did not (p=0.5496).

Conclusion:

In this small cohort from a single center, the results are not in favor of MDS patients receiving therapy prior to HSCT. Prospective study with larger cohort should be conducted to address this issue and taking into consideration disease characteristics in patients who may and may not benefit from pre-transplant therapy. As recently published approximately 85% of bone marrow cells are clonal in MDS regardless of blast count (Walter et al. NEJM 2012) which may explain our result of no difference in blast percentage before or after therapy and should not be used as a surrogate marker.