Outcomes of Hematopoietic Stem Cell Transplantation from Non T– Cell Depleted Haploidentical Versus Matched Sibling Donor in Adult Patients with Acute Lymphoblastic Leukemia in Remission: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrowtransplantation

Background: Non T-cell depleted haploidentical hematopoietic stem cell transplantation (HaploSCT) is being increasingly used in acute lymphoblastic leukemia (ALL).We have recently reported that outcomes of adult patients (pts) with ALL in complete remission (CR) receiving HaploSCT are comparable to unrelated donor transplants (Shem-Tov N, Leukemia 2020; Al Malki MM Blood Adv. 2020 ). However, a direct comparison between HaploSCT and matched sibling donor transplants (MSD) in pts with ALL has not yet been undertaken.

Aim: To compare transplantation outcomes of HaploSCT and MSD in pts with ALL in CR.

Methods: We retrospectively analyzed adult pts (≥18 years) with ALL who underwent their first allogeneic stem cell transplantation (alloSCT) in first or second CR between 2012 to 2018, either from a Haplo or MSD donor, and whose data were reported to the acute leukemia working party (ALWP) of the European society for Blood and Marrow Transplantation (EBMT). Multivariate analysis (MVA) adjusting for differences between the groups was performed using the Cox proportional hazards regression model. Propensity score matching was also performed to reduce confounding effects.

Results: The analysis comprised 2304 pts: HaploSCT -413; MSD-1891. Median follow up was 25.0 (IQR: 12.3-45.3) months. Median age was 37 (range 18-75) and 37.7 (18-76) years, respectively. HaploSCT pts were transplanted more recently than those transplanted from MSD (2016 vs 2015, p<0.0001). A higher percentage of HaploSCT were in CR2 (33.4% vs 16.7%, p<0.0001), respectively, and fewer received myeloablative conditioning (68% vs 83.2%, p < 0.0001).Cytomegalovirus (CMV) seropositivity was lower in Haplo pts (22% vs 28%, p 0.01) and donors (27.1% vs 33%,p<0.02) and a higher percentage of the HaploSCTs were performed using a BM graft (46.2% vs 18.6%, p< 0.0001).The 2 groups did not differ with regard to gender, Karnofsky performance score (KPS), ALL phenotype, and pre alloSCT measurable residual disease (MRD). Graft versus host disease (GVHD) prophylaxis was mainly post-transplant cyclophosphamide (PTCy)-based (92.7%) in the HaploSCT setting while it was mostly pharmacologic in the setting of MSD (18.7% received ATG). Cumulative incidence of engraftment at day 60 was higher in MSD transplants compared to HaploSCT (98.7% vs 96.3%, p=0.001), respectively. Day 180 incidence of acute (a) GVHD II-IV and III-IV was higher in HaploSCT vs. MSD (36.3% vs 28.9%, p=0.002), and (15.2% vs 10.5%, p=0.005), respectively. Conversely, the 2- year chronic (c) GVHD and extensive cGVHD were 32% vs 38.8% (p=0.009), and 11.9% vs 19.5% (p=0.001) in HaploSCT vs MSD, respectively. Main causes of death were leukemia (31.8% vs 54.0%), infection (33.1% vs 19.7%), and GVHD (16.6% vs 19.7%) for HaploSCT and MSD, respectively. Two-year relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS), and GVHD free, relapse-free survival (GRFS) were 26% vs 31.6% (p=0.017); 22.9% vs 13% (p=0.001); 51% vs 55.4% p=0.07; 58.8% vs 67.4% (p=0.001), and 40.6% vs 39% (p=0.74) for HaploSCT and MSD, respectively. In MVA, RI was significantly lower in HaploSCT in comparison to MSD, hazard ratio (HR) =0.66 (95% CI 0.52-0.83, p=0.004) while NRM was significantly higher, HR=1.9 (95% CI 1.43-2.53, p<0.0001). aGVHD grade II-IV and grade III-IV were higher in HaploSCT than in MSD HR=1.53 (95% CI 1.23-1.9, p=0.0002), and HR=1.54 (95% CI 1.1-2.15, p=0.011), respectively. Extensive cGVHD was lower in HaploSCT compared with MSD, HR=0.61 (95% CI 0.43-0.88, p=0.007) while total cGVHD did not differ significantly, HR=0.94 (95% CI 0.74-1.18, p=0.58).LFS, OS and GRFS did not differ significantly between the 2 transplant groups, HR=0.96 (95% CI 0.81-1.14, p=0.66); HR=1.18 (95% CI 0.96-1.43, p=0.11), and HR=0.93 (95% CI 0.79-1.09, p=0.37), respectively. These results were confirmed in a matched-pair analysis (Figure).

Conclusions: Outcomes of adult patients with ALL in CR receiving alloSCT from haploidentical donors are not significantly different from those receiving transplants from MSD in terms of LFS, OS and GRFS.

Figure legend: Matched-pair analysis of transplantation outcome – Non-relapse mortality (NRM), relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) in allogeneic stem cell transplantation from haploidentical (Haplo) donors and matched sibling donors (MSD).