Early Lymphocyte Recovery Predicts Superior Survival after Unmanipulated HLA-Mismatched/Haploidentical Blood and Marrow Transplantation for Patients with Hematological Malignancies.

Abstract

Background: The crucial role of repopulating lymphocytes following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including the prevention of infections and erudiating residual tumor cells in the early post-transplant phase, has been demonstrated. Currently, unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation with T cell repletion has been an established treatment for patients without HLA-matched related or unrelated donors. However, the prognostic significance of early lymphocyte recovery in this transplant settings is not defined.Methods: We retrospectively analyzed the relationship between day 30 absolute lymphocyte count (ALC30) and transplant outcomes in 217 paients with hematological malignancies receiving T-cell-repleted transplantation from an HLA-mismatched/haploidentical related donors.Results: At the time of this analysis, 44 of the cohort patients had died. The choice of ALC ≥ 235 cells/μL as the cut-off value point was supported by the data because it yielded the greatest differential in survival, based on the chi-square (×2=23.448, P<0.0001) analysed at different cut-off points between the 25% and 75% quartiles (190–460 cells/μL) from the log-rank test. The median follow-up was 543 days (range: 150–1873 days). Patients with an ALC ≥ 235 cells/μL (n=136) experienced a superior median OS compared to patients with an ALC < 235 cells/μL (n=81) (median OS, 582 days vs 510 days, respectively, P<0.0001). Two groups were identified based on an ALC of ≥ 235 cells/μL and <235 cells/μL at days 30 post HSCT. There were no statistical differences in patient's characteristics between the two groups at days 30 taking into accout a P-value of 0.05. One patients (0.46%) failed to neutrophil engraft, 12 patients (5.53%) failed to platelet engraft. The median time to neutrophil and platelet recovery was 13 days (range, 9–49 days) and 16 days (range, 7–356 days), respectively. Eighty-two patients developed grade II to IV acute GVHD with a cumulative incidence of 49%±3.80%. 113 of 160 evaluable patients surviving more than 100 days developed chronic GVHD (limited 82 [51.25%]; extensive 31 [19.38%]) with a cumulative incidence of 63.8%±3.90%. Forty-four of 217 (20.28%) patients died from nonrelapse causes, with a cumulative incidence of TRM of 23.6%±3.40%. In multivariate analysis the ALC30 above the cutoff value 235 cells/μL was associated with improved overall survival (OS) (HR 0.331, 95% CI 0.189–0.578; P<0.0001), leukemia free survival (LFS) (HR 0.299, 95% CI 0.179–0.501; P<0.0001), less relapse (HR 0.345 (95% CI 0.147–0.808); P=0.014), and less transplant-related mortality (HR=0.284; 95%CI 0.148–0.544; P<0.0001). The beneficial effects of a higher ALC30 (≥235 cells/μL) influenced outcomes in patients with both standard and high-risk disease but did not affect relapse in these two groups. The higher ALC30 was also correlated with improved OS and LFS in patients with AML, ALL, and CML, respectively.Conclusion: Our results suggest that the day 30 ALC would appear to be a useful and simple measurement to predict those patients with superior survival after unmanipulated HLA-mismatched/haploidentical transplantation.