Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for acute myeloid leukemia

• Published in: Blood advances 2021-03, Vol.5 (5), p.1199-1208
• Main Authors: Pierini, Antonio, Ruggeri, Loredana, Carotti, Alessandra, Falzetti, Franca, Saldi, Simonetta, Terenzi, Adelmo, Zucchetti, Claudio, Ingrosso, Gianluca, Zei, Tiziana, Iacucci Ostini, Roberta, Piccinelli, Sara, Bonato, Samanta, Tricarico, Sara, Mancusi, Antonella, Ciardelli, Sara, Limongello, Roberto, Merluzzi, Mara, Di Ianni, Mauro, Tognellini, Rita, Minelli, Olivia, Mecucci, Cristina, Martelli, Maria Paola, Falini, Brunangelo, Martelli, Massimo Fabrizio, Aristei, Cynthia, Velardi, Andrea
• Format: Article
• Language: English
• Subjects: Transplantation
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2020003739

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment in eradicating high-risk acute myeloid leukemia (AML). Here, we present data from a novel HLA-haploidentical HSCT protocol that addressed the 2 remaining major unmet medical needs: leukemia relapse and chronic graft-versus-host disease (cGVHD). Fifty AML patients were enrolled in the study. The conditioning regimen included total body irradiation for patients up to age 50 years and total marrow/lymphoid irradiation for patients age 51 to 65 years. Irradiation was followed by thiotepa, fludarabine, and cyclophosphamide. Patients received an infusion of 2 × 106/kg donor regulatory T cells on day −4 followed by 1 × 106/kg donor conventional T cells on day −1 and a mean of 10.7 × 106 ± 3.4 × 106/kgpurified CD34+ hematopoietic progenitor cells on day 0. No pharmacological GVHD prophylaxis was administered posttransplantation. Patients achieved full donor–type engraftment. Fifteen patients developed grade ≥2 acute GVHD (aGVHD). Twelve of the 15 patients with aGVHD were alive and no longer receiving immunosuppressive therapy. Moderate/severe cGVHD occurred in only 1 patient. Nonrelapse mortality occurred in 10 patients. Only 2 patients relapsed. Consequently, at a median follow-up of 29 months, the probability of moderate/severe cGVHD/relapse-free survival was 75% (95% confidence interval, 71%-78%). A novel HLA-haploidentical HSCT strategy that combines an age-adapted myeloablative conditioning regimen with regulatory and conventional T-cell adoptive immunotherapy resulted in an unprecedented cGVHD/relapse-free survival rate in 50 AML patients with a median age of 53 years. This trial was registered with the Umbria Region Institutional Review Board Public Registry as identification code 02/14 and public registry #2384/14 and at www.clinicaltrials.gov as #NCT03977103. •A novel irradiation-based conditioning regimen allows age-adapted myeloablative haploidentical transplantation for leukemia patients.•The combination of myeloablative conditioning with regulatory and conventional T-cell immunotherapy eradicates AML. [Display omitted]