Prognostic Impact of Delayed Platelet Engraftment after Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancy

Introduction: Delayed platelet engraftment (DPE) is one of important complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies suggested that DPE was risk factor for higher non-relapse mortality (NRM) and worse overall survival (OS). However, prognostic impact of DPE after allo-HSCT remains unclear. Therefore we conducted retrospective analysis to examine the clinical impact of DPE on transplant outcomes. Methods: Clinical data were collected from the clinical records of Kanagawa Cancer Center.Patients with hematological malignancies aged 16 years or older who underwent first allo-HCT between January 2002 and December 2014 were evaluated for analysis. Patients who died before day 60 after allo-HSCT were excluded. DPE was defined as non-achievement of platelet engraftment (continuous platelet counts 50×10⁹/L or higher without transfusion) before day 60. OS, relapse and NRM were compared between patients who achieved platelet engraftment before day 60 and DPE patients, using log-rank test and Gray's test respectively. In a multivariate analysis, the Cox proportional hazard model and Fine-Gray methods were used for OS and cumulative incidence of relapse and NRM respectively, using the following variables: age, gender, donor source, disease, disease status at allo-HSCT, donor-recipient gender mismatch, ABO mismatch, hematopoietic cell transplant comorbidity index (HCT-CI) and preemptive cytomegalovirus (CMV) therapy. Results: Of 291 patients with hematological malignancies who received first allo-HSCT (AML n = 175, ALL n = 75, others n = 41), 222 patients (76.3%) achieved platelet engraftment before day 60, 69 patients (23.7%) did not. Patients with ALL and disease low risk at allo-HSCT patients achieved early platelet engraftment. Cord blood transplantation (CBT), higher comorbidity and preemptive CMV therapy were significant risk factors for DPE. The 5-year OS and NRM for the patients who achieved platelet engraftment before day 60 were favorable, compared with the DPE group (OS; 60.3% vs. 23.2%; P < 0.001, NRM; 14.6% vs. 40.3%; P < 0.001). The 5-year relapse were comparable between both groups (30.3% vs. 37.3%; P = 0.19). Subgroup analysis stratified by donor source showed that similar results were observed both in the CBT group and in the non-CBT group. Multivariate analysis indicated that DPE was significantly associated with poorer OS (HR 3.51; 95%CI 2.40 - 5.15; P < 0.001) and higher NRM (HR 3.07; 95%CI 1.78 - 5.29; P < 0.001) after adjusting covariates. DPE had no significant impact on relapse (HR 0.95; 95%CI 0.58 - 1.56; P = 0.84). The incidence of fatal infectious disease in the DPE group was significantly higher than that in the non-DPE group (15.9% vs. 5.0%, P = 0.007), while there was no significant difference for fatal bleeding, GVHD and organ failure. Conclusions: DPE is a common complication after allo-HSCT for hematological malignancies. DPE is a useful prognostic factor for poorer OS and increased NRM. We may have to pay more attention to severe infectious disease in patients with DPE.