Primary Failure of Platelet Recovery Is the Foremost Prognostic Factor after Allogeneic Stem Cell Transplantation Following Myeloablative Conditioning for Myelodysplastic Syndrome: A Study from the SFGM-TC

BACKGROUND: Primary graft dysfunction (PGD) occurs in approximately 5 to 15% and is associated with very poor outcome after allogeneic stem cell transplantation (allo-SCT) (Dominietto et al, BJH, 2001). Despite the lack of consensual diagnostic criteria, PGD is commonly defined as the primary failure of hematologic recovery, often reflected by thrombocytopenia, along with full donor chimerism and hypocellular marrow. Few studies, however, have addressed the prognostic impact of platelet recovery on post-transplant outcome. Furthermore, all published cohorts varied in terms of disease types and transplantation modalities. The aim of this retrospective study was to evaluate the prognostic impact of primary platelet recovery in a homogeneous cohort of patients receiving allo-SCT following myeloablative conditioning (MAC) from an HLA-matched sibling or unrelated donor (10/10) for myelodysplastic syndrome (MDS).

METHODS: In this, multicenter study, we investigated the 5-year probabilities of overall survival (OS) and non-relapse mortality (NRM) of 155 MDS patients who underwent allo-SCT between January 1999 and December 2009. Variables were assessed at transplant and at d+100 post-transplant. Platelet recovery was defined as the first occurrence of a stable platelet count ≥ 20G/L before d+100, persisting for more than 7 days without transfusion. Twelve patients who relapsed before d+100 were excluded from the analysis.

RESULTS: According to WHO classification, 56 patients (36%) presented with refractory anemia, 43 (28%) with refractory anemia with excess blast type 1 (RAEB-1), 56 (36%) with RAEB-2 and RAEB-t/AML. IPSS was at the time of diagnosis low/intermediate-1, intermediate-2/high in 53 (34%) and 57 patients (37%), respectively (missing data for 45 patients). Progression to a more advanced disease before transplant was observed in 47 patients (30%). The IPSS cytogenetic risk was good/intermediate in 102 patients (66%), poor in 36 patients (23%). Cytogenetic data were missing in 17 cases. Stem cell source was bone marrow in 96 patients (62%) and peripheral blood stem cells in 59 patients (38%). Median age was 46 and marrow blasts was ≥ 10% in 49 patients (32%). Primary failure of platelet recovery was observed in 27 patients (17%) and grade III/IV acute GVHD in 39 patients (25%). In univariate analysis primary failure of platelet recovery (7% versus 50%, p < 0.001), grade III/IV acute GVHD (49% versus 25%, p < 0.001), previous progression (51% versus 28%, p = 0.02), marrow blasts ≥ 10% (50% versus 30%, p = 0.02) significantly impacted OS. After adjustment for significant covariates, absence of platelet recovery retained its adverse impact on outcome for both OS (HR = 6.72, CI = 3.70 - 12.2, p < 0.001) and NRM (HR = 6.57, HR = 3.10 - 13.90, p < 0.001). Importantly, grade III/IV acute GVHD was not an independent prognostic factor in multivariate analysis.

CONCLUSION: Primary failure of platelet recovery after allo-SCT following MAC was the only factor influencing both NRM and OS, offsetting the prognostic significance of grade III/IV acute GVHD. Our results emphasize the need to perform prospective trials to investigate therapeutic approaches to reverse graft dysfunction, such as mesenchymal stem cell infusion, and thrombopoietin agonists.