Risk Factors and Impact of Secondary Failure of Platelet Recovery After Allogeneic Stem Cell Transplantation

Abstract

Secondary failure of platelet recovery (SFPR), a late decrease in the platelet count after primary platelet recovery that is not due to relapse or graft rejection, occasionally occurs after allogeneic hematopoietic stem cell transplantation (HSCT). The risk factors and impact of SFPR on transplantation outcomes are not well known in the clinical setting. Therefore, we retrospectively evaluated 184 adult patients who underwent their first allogeneic HSCT and achieved primary platelet recovery. The cumulative incidence of SFPR, defined as a decrease in the platelet count to below 20,000/µL for more than 7 days, was 12.2% at 3 years, with a median onset of 81 days (range, 39 to 729) after HSCT. Among patients who developed SFPR (n = 23), 19 (82.6%) showed recovery to a sustained platelet count of more than 20,000/µL without transfusion support, and the median duration of SFPR was 23 days (range, 7 to 1048 days). A multivariate analysis showed that in vivo T cell depletion (hazard ratio [HR], 6.92; 95% confidence interval [CI], 2.31 to 20.7; P < .001), grades II to IV acute graft-versus-host disease (HR, 3.99; 95% CI, 1.52 to 10.5; P = .005), and the use of ganciclovir or valganciclovir (HR, 2.86; 95% CI, 1.05 to 7.77; P = .039) were associated with an increased risk for SFPR. The occurrence of SFPR as a time-dependent covariate was significantly associated with inferior overall survival (HR, 2.29; 95% CI, 1.18 to 4.46; P = .015) in a multivariate analysis. These findings may help to improve the management and treatment strategy for SFPR.

Recombinant Human Thrombopoietin Promotes Platelet Engraftment and Improves Prognosis of Patients with Myelodysplastic Syndromes and Aplastic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation

“…PPGF was associated with shorter survival time, which is consistent with the previous studies [4,8,11,12]. Numerous studies have reported risk factors that influence platelet engraftment, such as myelotoxic agent, conditioning regimen intensity, stem cell source, and number of infused CD34 + cells or MNC [5,6,11,28].…”

“…Thrombocytopenia is a common complication after allo-HSCT, and severe thrombocytopenia necessitates platelet transfusion and influences patient clinical outcome [8,11,12,26,27]. However, until now, there was no adequate therapy to promote platelet engraftment in patients after allo-HSCT.…”

“…Patients with PPGF have an increased risk of bleeding and acute graftversus-host disease (GVHD) [8][9][10]. These complications contribute to higher treatment-related mortality and poor prognosis [11,12].…”

Delayed platelet recovery after allogeneic hematopoietic stem cell transplantation: Association with chronic graft‐versus‐host disease and survival outcome

“…Particularly, persistent thrombocytopenia predicts a worse outcome than fluctuating thrombocytopenia . We previously evaluated secondary failure of platelet recovery, defined as a late decrease in the platelet count following primary platelet recovery that is not due to relapse or graft rejection and showed that the occurrence of secondary failure of platelet recovery was significantly associated with inferior overall survival (OS) . Although primary delayed platelet recovery (DPR) despite prompt neutrophil engraftment after HSCT is more common than secondary failure, only limited data are available with regard to DPR.…”

“…2 Previous studies have demonstrated that thrombocytopenia after HSCT has a uniformly dismal outcome. [3][4][5][6][7] Particularly, persistent thrombocytopenia predicts a worse outcome than fluctuating thrombocytopenia. 8 We previously evaluated secondary failure of platelet recovery, defined as a late decrease in the platelet count following primary platelet recovery that is not due to relapse or graft rejection and showed that the occurrence of secondary failure of platelet recovery was significantly associated with inferior overall survival (OS).…”