PO-02. Haploidentical versus matched unrelated HSCT with post transplant cyclophosphamide based GvHD prophylaxis in children with acute leukemia

Summary

Use of post-transplantation cyclophosphamide (PTCy) with or without additional immunosuppression has been shown to be effective for GvHD prophylaxis following different types of HSCT in adults with hematological malignancies. Recent reports showed lower incidence of grade II-IV, III-IV aGvHD, cGvHD with PTCy in adults following HLA-matched allo-HSCT compared to haploidentical HSCT. However, there are no published data comparing results of MUD and haploidentical HSCT with PTCy in children. The aim of study was to compare the outcomes of allo-HSCT with PTCy between HLA-haploidentical and HLA-matched unrelated donors (MUD) in children with acute leukemia.

Patients and methods

We retrospectively analyzed outcomes of 140 first allogeneic HSCT from MUD (n=48) or haploidentical (n=92) donors performed in children <18y.o. in 1^st or 2^nd CR of acute leukemia. PTCy alone was used in 2 patients (4.2%) after MUD and 2 (2.2%) patients after haploidentical HSCT. Two patients (4.2%) after MUD and 8 patients (8.7%) after haplo-HSCT received PTCY with one additional immunosuppressive agent, triple combination of PTCY with CNI and mTOR inhibitors or MMF was used in 44 (91.7%) after MUD and 82 (89.1%) patients after haploidentical HSCT. Patients, donors and graft characteristics are seen from Table 1. The main characteristics of the patients (gender, diagnosis, disease status etc.) did not differ between treatment groups. Bone marrow was used in 91 (98.9%) and 27 (56.2%) of recipients of haploidentical and MUD HSCT respectively, 21 (43.8%) vs 1 (1.1%) received PBSC, p<0.001.

Results

Cumulative incidence of 42 day engraftment, time to neutrophils and platelet engraftment were similar between groups: 97.9% (95%CI 90.4-99.8%) vs 86.96% (95% CI 79.2%-92.9%) p=0,123; 19 (12-40) days vs 20 (9-29) days, p=0.808; 18.5 (8-114) days vs 18 (7-55) days, p=0.996, respectively. The cumulative incidence of grade II-IV, III-IV aGvHD at day 125, moderate/severe cGvHD were comparable among MUD and haplo groups: 14.7% (95%CI 6.5-26.2%) vs 12.2% (95% CI 6.5-19.8%), p=0.97; 4.1% (95%CI 0.8-12.6%) vs 5.6% (95% CI 2.1-11.7%), p=0.74; 16.3% (95%СI 7.2-28.9%) vs 24.5% (95%CI 15.8-34.3%), p=0.168, respectively. The 2-year GRFS was 54.5% (95%CI-38.8-67.8%) in MUD and 37.1% (95%CI 26.9-47.4%) after haploidentical HSCT, p=0.026. There was no difference in OS, 2-y LFS, 2-y NRM, 2-y relapse incidence between study cohorts: 71.7% (96%CI 56.0-82.6%) vs 65.6 (95%CI 52.2-76.2), p=0.46; 60.4% (95% CI 45.2-72.6%) vs 50,7% (95%CI 39.8-60.6%), p=0.228; 12.5% (95% CI 5.1-23.4%) vs 7.8% (95% CI 3.4-14.6%), p=0.38; 27.1% (95% CI 15.5-40.0%) vs 41.4% (95% CI 31.1-51.15%), p=0.08, respectively.

Conclusions

In our analysis, the transplant outcomes in children, including CI of engraftment, OS, LFS, NRM, CI of aGvHD II-IV, III-IV, cGvHD, and relapse rates did not differ significantly between the groups undergoing MUD or haploidentical transplans. However, MUD was associated with better 2-y GRFS compared to haploidentical HSCT (54.5% versus 37.1%, p<0.026). Of note, comparable incidence of acute and chronic GvHD between MUD and haplo-HSCT may be attributed to the use of PBSC in MUD group. Hence, both MUD with bone marrow/PBSC and haplo-HSCT with bone marrow are valid options for children with acute leukemia.

Keywords

Hematopoietic stem cell transplantation, haploidentical donors, matched unrelated donors, acute leukemia.