Impact of Donor Kinship on Non-T-Cell Depleted Haploidentical Stem Cell Transplantation (haploHCT) with Post Transplantation Cyclophosphamide (PTCy): From the ALWP of the EBMT

Background: Non-T-cell depleted haploidentical transplantation (haploHCT) is a unique transplantation setting in which several potential haploidentical family related donors are available for a given patient, allowing to optimize donor selection. The impact of donor kinship on outcome of haploHCT with post transplantation cyclophosphamide (PTCy) is not fully established.

Methods: To assess the impact of donor kinship on results of haploHCT in pts with acute leukemia (AL) we used the Acute Leukemia Working Party (ALWP) / European Society for Blood and Marrow Transplantation (EBMT) registry. Pts with de novo AL in all disease status who underwent haploHCT with PTCy from 2000 to 2016 were analyzed. ATG use and missing information on donor age, gender and kinship were exclusion criteria.

Results: 717 pts were analyzed: 577 (80%) with acute myeloid leukemia (AML) and 140 (20%) with acute lymphoblastic leukemia (ALL). Median follow up was 44.4 (95%CI, 41.9-48.1) months. Median age was 50.3 (IQR 35.4-61.5) years (y) and 40% of pts were female .Disease status was CR1 in 43.6%, CR2 in 23.4% and advanced in 32.9% of the pts. Conditioning was myeloablative in 54.8%. All pts received PTCy as graft-versus-host disease (GVHD) prophylaxis in combination with CSA+MMF (51%), or Tacro+MMF (34%). Grafts were PBSC in 57% and BM in 43%. HaploHCT donors comprised children (41.7%), siblings (36.5%), parents (15.8%) and extended family members (6%). Neutrophil engraftment was achieved in 92% of pts. Day100 CI of acute (a) GVHD II-IV and III-IV was 27.5% and 10.5%, respectively, and 3y CI of chronic (c) and extensive GVHD was 31.6% and 12.9%, respectively. 3y CI of relapse (RI), non-relapse mortality (NRM), leukemia free survival (LFS), overall survival (OS) and GVHD-free, relapse -free survival (GRFS) were 33.4%, 25.9%, 40.8%, 45.6% and 30.8%, respectively. As high correlation was observed between patient age and donor/recipient kinship (Figure 1A and 1B), outcomes analysis focused on sibling or parent as donors for pts <45y (n=260), and on child or sibling for those >45y (n= 412). In pts aged <45y, 140(54%) of the donors were siblings, 111(43%) were parents and 9(3%) were children. Disease and transplant characteristics did not differ between parent or sibling donor groups, except for the median age (33.6 vs 54.5y for sibling and parent, respectively, p<0.001). At 3y, OS was 53% vs 47% (p=0.43) and LFS was 43% vs 42% (p=0.76) for sibling vs parent, respectively. The 3y RI and NRM were 39% vs 40% (p=0.85) and 17% vs 17% (p=0.88) for sibling vs parent, respectively. Day100 CI of aGVHD was 27% vs 36% (p=0.14) and 3y CI of cGVHD was 31% vs 32% (p=0.99) for sibling vs parent, respectively. In multivariate analysis (MVA) for patients aged ≤45y (Table 1A) outcomes did not differ according to donor type. Other factors independently associated with poor risk of OS were diagnosis of AML (HR 0.63, p=0.012), advanced disease (HR 3.37, p<0.0001), later transplant year (HR 0.49, p=0.08) and PBSC (HR 1.48, p=0.038). In the 412 pts aged >45y, donors were siblings in 122 (30%) and children in 290 (70%). Sibling donors were older (median age 49.8 vs 30.7y, p<0.001). PBSC were used more often in haploHCT from sibling vs child donors (64.8% vs 51.4%, p=0.01). At 3y, OS was 44% vs 43.5% (p=0.98) and LFS was 40.4% vs 39.9% (p=0.97) for child vs sibling, respectively. At 3y RI was 26.6% vs 34.6% (p=0.15), NRM was 32.9 vs 25.5% (p=0.17). Day 100 aGVHD was 21.6% vs 37.3% (p<0.001) for child vs sibling, respectively, and 3y cGVHD was 30.7% in both types (p=0.99). In MVA of patients aged >45y (Table 1B) outcomes did not differ according to donor type. Other factors independently associated with a poor risk of OS were advanced disease status (HR 2.02, p<0.001) and later transplant year (HR 0.66, p=0.05).

Conclusion: In a large cohort of pts with AL undergoing haploHCT with PTCy we did not find a significant impact of donor kinship on transplantation outcome when analyzing by age group (≤45 y and >45 y) which may speak for the unique biological properties of PTCy. Donors selection hierarchy for haploHCT with PTCy in AL should be analyzed further considering other factors such as age, CMV serostatus, parity and gender mismatch.

Table: Multivariate analysis of factors predicting OS, LFS, RI, NRM, GVHD, acute and chronic GVHD for patients ≤ 45 years (1A); >45 year (1B).

Figure legend: 1A - Correlation between patient age and donor/recipient relationship:

1B - Correlation between donor and patient age