Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial

作者：Swati Naik, Ying Li, Aimee C. Talleur, Subodh Selukar, Emily Ashcraft, Cheng Cheng, Renee Madden, Ewelina Mamcarz, Amr Qudeimat, Akshay Sharma, Ashok Srinivasan, Ali Suliman, Rebecca Epperly, Esther A. Obeng, Mireya Paulina Velasquez, Deanna Langfitt, Sarah Schell, Jean‐Yves Métais, Paula Y. Arnold, Diego R. Hijano, Gabriela Marón, Thomas E. Merchant, Salem Akel, Wing Leung, Stephen Gottschalk, Brandon M. Triplett · 发表于：Journal of Hematology & Oncology · 年份：2024 · DOI：10.1186/s13045-024-01567-0 · 被引用次数：15 · 研究领域：Hematopoietic Stem Cell Transplantation、CAR-T cell therapy research、Immune Cell Function and Interaction

BACKGROUND: Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated with acute and long-term adverse effects. We used a CD45RA-depleted haploidentical graft for adoptive transfer of memory T cells combined with NK-cell addback and hypothesized that maximizing the graft-versus-leukemia (GVL) effect might allow for reduction in intensity of conditioning regimen. METHODS: In this phase II clinical trial (NCT01807611), 72 patients with hematological malignancies (complete remission (CR)1: 25, ≥ CR2: 28, refractory disease: 19) received haploidentical CD34 + enriched and CD45RA-depleted hematopoietic progenitor cell grafts followed by NK-cell infusion. Conditioning included fludarabine, thiotepa, melphalan, cyclophosphamide, total lymphoid irradiation, and graft-versus-host disease (GVHD) prophylaxis consisted of a short-course sirolimus or mycophenolate mofetil without serotherapy. RESULTS: The 3-year overall survival (OS) and event-free-survival (EFS) for patients in CR1 were 92% (95% CI:72-98) and 88% (95% CI: 67-96); ≥ CR2 were 81% (95% CI: 61-92) and 68% (95% CI: 47-82) and refractory disease were 32% (95% CI: 11-54) and 20% (95% CI: 6-40). The 3-year EFS for all patients in morphological CR was 77% (95% CI: 64-87) with no difference amongst recipients with or without minimal residual disease (P = 0.2992). Immune reconstitution was rapid, with mean CD3 and CD4 T-cel...