Prognostic Importance Of Thrombocytopenia On Day 60 After Allogeneic Stem Cell Transplantation For Acute Leukemia
Authors: Ogusa Eriko , Yamamoto Wataru , Matsumoto Kenji , Ishigatsubo Yoshiaki , Kanamori Heiwa 
Published: October 2019

Abstract

Background
Although thrombocytopenia is a common complication after allogeneic stem cell transplantation (SCT) and is a notable prognostic factor in patients with chronic graft-versus-host disease, the impact of thrombocytopenia in early period after SCT on the outcome is not clearly identified. In this study, we retrospectively assessed the association of thrombocytopenia after SCT with the result of transplantation in patients with acute leukemia.

Patients and Methods
This study included patients with acute leukemia who underwent SCT at our institute between 2000 and 2010. Patients who received repeat transplantation, relapsed, or died within 60 days after the first SCT were excluded. Thrombocytopenia was defined as the level of platelet count < 50 x 109/L on day 60 after SCT. Factors associated with thrombocytopenia were studied and the impact of thrombocytopenia on transplant outcomes was also analyzed in this study.

Results
There were 182 patients with acute leukemia (119 with acute myeloid leukemia and 63 with acute lymphoblastic leukemia), with median age was 43 years (range: 16-65 years). The disease risk at transplantation was standard risk in 89 patients and high risk in 93. Myeloablative conditioning (MAC) was employed for 139 patients and reduced-intensity conditioning (RIC) was done for 43. Bone marrow (BM) from related or unrelated donors was transplanted in 121 patients, as well as peripheral blood stem cell (PB) from related donors in 29 and cord blood (CB) in 32. Transplantation was done from HLA-matched related donors in 60 patients, HLA-mismatched related donors in 17, HLA-matched unrelated donors in 59, and HLA-mismatched unrelated donors in 46. Cumulative incidence of platelet recovery (≥50 x 109/L) on day 60 by grafts was 70% for BM, 69% for PB, and 50% for CB (p=0.11). Factors significantly associated with thrombocytopenia on day 60 after SCT were unrelated donor (vs related donor: 41% vs 25%, p=0.023), MAC (vs RIC: 38% vs 21 %, p=0.038), HLA-mismatch (vs HLA-match: 51% vs 25%, p<0.001), and cumulative incidence of grade II-IV acute GVHD (vs grade 0-I: 64% vs 42%, p=0.002). On multivariate analysis, older age, MAC, HLA-mismatch, and acute GVHD were significantly correlated with thrombocytopenia. After a median follow-up of 68.2 months (range: 4.7-144 months), 2-year overall survival (OS) was 58%. The cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 2 years was 31% and 15% respectively. The 2-year OS, CIR, and NRM at 2 years in patients with and without thrombocytopenia on day 60 were 40% and 68% (p<0.001), 34% and 30% (p=0.921), and 28% and 8% (p<0.001), respectively. Multivariate analysis showed that thrombocytopenia (relative to non-thrombocytopenia: HR 2.27 [95% CI 1.40-3.68], p<0.001) and high disease risk (relative to standard risk: HR 2.80 [95% CI 1.73-4.54], p<0.001) were significantly associated with worse 2-year OS. Furthermore, high disease risk (relative to standard risk: HR 3.41 [95% CI 1.87-6.22], p<0.001) for CIR, and thrombocytopenia (relative to non-thrombocytopenia: HR 2.71 [95% CI 1.23-6.00], p=0.013) and grade II-IV acute GVHD (relative to grade 0-I: HR 2.36 [95% CI 1.12-4.99], p=0.025) for NRM were also independent predictors on multivariate analysis.

Conclusions
Various factors might influence on thrombocytopenia following SCT, but our results suggest that thrombocytopenia on day 60 is a good predictor for complications and survival in patients receiving SCT for acute leukemia.

Disclosures:
No relevant conflicts of interest to declare.