Long-Term Outcome of Children with Acute Leukemia (AL) Given Alphabeta T and B-Cell Depleted HLA-Haploidentical Hematopoietic Stem Cell Transplantation (TBdepl-haploHSCT)

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.799-799
• Main Authors: Merli, Pietro, Pagliara, Daria, Algeri, Mattia, Galaverna, Federica, Li Pira, Giuseppina, Bertaina, Valentina, Montanari, Mauro, Leone, Giovanna, Gaspari, Stefania, Massa, Michele, Cirillo, Valentina, Cefalo, Maria Giuseppina, Biagini, Simone, Becilli, Marco, Girolami, Elia, Carta, Roberto, Ruggeri, Annalisa, Locatelli, Franco
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-128416

Background: TBdepl-haploHSCT is a suitable option for children with AL in need of an allograft, lacking an HLA-compatible donor. We previously published promising results in a cohort of 80 children with AL, given this type of allograft (Locatelli et al., Blood 2017), demonstrating a low incidence of acute and chronic graft-versus-host disease (GvHD) and low non-relapse mortality (NRM), translating into a final outcome comparable to that of patients transplanted from an HLA-compatible donor. We present the long-term follow-up analysis of this study (NCT01810120), now including 134 patients, with a minimum observation time of 100 days after the allograft. Patients and methods: Between October 2010 and April 2019, 134 children with AL in morphological complete remission (CR) received TBdepl-haploHSCT from an HLA-partially matched relative (a parent in 97% of cases) at Ospedale Pediatrico Bambino Gesù in Rome, Italy. All patients were prepared to the allograft using a fully-myeloablative conditioning regimen including a combination of cytotoxic drugs and/or total body irradiation (TBI). Anti-T-lymphocyte globulin (ATLG) was used before transplantation (12 mg/kg total dose, from days -5 to day -3) to modulate bi-directional donor/recipient alloreactivity. Rituximab (200 mg/sqm) was administered on day -1 to prevent post-transplantation EBV-induced lymphoproliferative disorders (PTLD). No patient received any post-transplant GvHD prophylaxis. Results: Characteristics of patients enrolled in the study are shown in Table 1. Median follow-up of surviving patients is 60 months (range: 3 months - 8.7 years). Only 3 patients did not achieve engraftment (all affected by acute myeloid leukemia and who did not receive TBI during conditioning regimen); median time to neutrophil and platelet recovery was 13 (range 9-22) and 11 (range 8-23) days, respectively. Cumulative incidence of grade II-III acute GvHD was 16.5% (95% CI 9.9-22.6). One patient developed gut GvHD, while for all other patients skin was the sole organ involved; no case of grade IV GvHD was recorded. Eight out of the 123 patients at risk developed chronic GvHD, in all cases of limited severity, the cumulative incidence of this complication being 7.6% (95% CI 2.3-12.6). Six patients died for transplant-related complications (2 because of idiopathic pneumonitis and 1 each of disseminated adenovirus infection, cardiac insufficiency, combined CMV/rhinovirus pneumonia and sepsis from Pseudomonas aeruginosa), the