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

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 (ײ=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.