Page 109 - Haematologica Vol. 109 - July 2024

ARTICLE - MUD versus haplo PT-CY stem cell transplantation in children with AML A. Ruggeri et al.
European Society for Blood and Marrow Transplantation. A matched pair analysis was performed to adjust for differences among groups. The final analysis was performed on 253 MUD and 95 haplo-HCT. In the matched cohort, median age at HCT was 11.2 and 10 years and median year of HCT was 2017 and 2018, in MUD and haplo-HCT recipients, respectively. The risk of grade III-IV acute graft-versus-host disease (aGVHD) was significantly higher in the haplo group (hazard ratio [HR]=2.33, 95% confidence interval [CI]: 1.18-4.58; P=0.01). No significant differences were found in 2 years overall survival (OS; 78.4% vs. 71.5%; HR=1.39, 95% CI: 0.84-2.31; P=0.19), leukemia-free survival (LFS; 72.7% vs. 69.5%; HR=1.22, 95% CI: 0.76-1.95; P=0.41), CI of relapse (RI; 19.3% vs. 19.5%; HR=1.14, 95% CI: 0.62-2.08; P=0.68) non-relapse-mortality (NRM; 8% vs. 11%; HR=1.39, 95% CI: 0.66-2.93; P=0.39) and graft-versus-host free relapse-free survival (GRFS; 60.7% vs. 54.5%, HR=1.38, 95% CI: 0.95-2.02; P=0.09) after MUD and haplo-HCT respectively. Our study suggests that haplo-HCT with PT-CY is a suitable option to trans- plant children with AML lacking a matched related donor.
Introduction
European Society for Blood and Marrow Transplantation (EBMT) registry.
Methods
Study design and definitions
This multicenter retrospective study was conducted on behalf of the Pediatric Diseases Working Party (PDWP) of EBMT after approval by the institutional review board of the PDWP. Data were collected according to EBMT rules. Patients or legal guardians provided written informed con- sent for data collection and analysis in accordance with the Declaration of Helsinki. Included were pediatric patients (age <18 years) diagnosed with AML, transplanted in first or second complete remission from 2011 to 2021, who un- derwent a first allo-HCT using either a 10/10 MUD with ATG or a haploidentical family donor (≥2 recipient-donor HLA mismatch number) in a haplo-HCT with PT-CY. Transplants were performed in 117 EBMT centers. All patients received a myeloablative conditioning (MAC) regimen, and the graft source was bone marrow (BM) or peripheral blood, accord- ing to the transplant center policy. In patients receiving ex vivo T-cell depletion, alemtuzumab or a combination of ATG and PT-CY was excluded.
Outcomes
The primary objective was to compare the leukemia-free survival (LFS) of AML patients receiving either a haplo-PT- CY or a MUD-ATG HCT. The secondary objectives were the comparison of overall survival (OS), non-relapse mortali- ty (NRM), relapse incidence (RI), incidence of both acute GVHD (aGVHD) and chronic GVHD (cGVHD), GVHD-free/ relapse-free survival (GRFS) in both groups. LFS was de- fined as time from HCT to first event of relapse or death. OS was defined as the time from HCT to death from any cause. RI was defined as the time from HCT to the first event of leukemia recurrence. Non-relapse mortality (NRM) was defined as death without evidence of relapse. RI and NRM were mutually competing events. GRFS was defined as the time from HCT to the first event among grade 3-4 aGVHD, extensive cGVHD, relapse, and death.20 Grade 2-4
Childhood acute myeloid leukemia (AML) is a rare and heterogeneous disease, with an incidence of seven cases per million children younger than 15 years.1 Improvements in genomic characterization, disease response monitoring,2 as well as the introduction of new drugs3 and advances in allogeneic hematopoietic cell transplantation (HCT) tech- niques4 have resulted in improved outcomes with survival rates reaching 70% in high-income countries. First line treatment approaches for pediatric AML include four or five cycles of myelosuppressive chemotherapy followed by HCT for high-risk patients,5 while HCT is offered in second clinical remission for other cases.5,6
In recent years, the development of HCT from alternative donors, preferably from matched unrelated donors (MUD), has provided the means to offer HCT, when no human leukocyte antigen (HLA)-matched family donor is available. However, in up to 40% of patients a MUD cannot be iden- tified in international donor registries.7 Recently, HCT from relatives sharing only one HLA-haplotype with the recipient (haplo-HCT) has emerged as a suitable alternative, with the great advantage that haplo-donors may be available for almost all patients, in due time, with a flexible schedule and additional cellular therapies being readily available. In haplo-HCT, different techniques to overcome the HLA barrier8-12 have been developed for improving immune re- constitution and graft-versus-leukemia with no excess of graft-versus-host disease (GVHD). In the last years, the use of T-cell replete haplo-HCT with post-transplant cyclophos- phamide (PT-CY),8 has rapidly increased across the world, showing identical clinical outcomes to matched donors (MD) in several retrospective studies in adults.8
Many studies demonstrated that PT-CY given after graft infusion can eliminate alloreactive T cells while preserving hematopoietic cells as well as memory and regulatory T cells.13,14 In pediatric patients affected by acute leukemia, promising clinical results have been reported,13,15-19 but spe- cific data on AML are lacking.
Here, we compared the results of a haplo-HCT with PT- CY to a MUD HCT using anti-thymocyte globulin (ATG) for the treatment of children affected by AML reported to the
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