Adoptive immunotherapy with CB following chemotherapy for patients with refractory myeloid malignancy: chimerism and response.

Autor:	Chaekal OK; Division of Hematology/Oncology and.; Division of Pathology, Department of Medicine, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY., Scaradavou A; National Cord Blood Program, New York Blood Center, New York, NY; and.; Stem Cell Transplantation and Cellular Therapies, MSK Kids, Memorial Sloan Kettering Cancer Center, New York, NY., Masson Frenet E; National Cord Blood Program, New York Blood Center, New York, NY; and., Albano MS; National Cord Blood Program, New York Blood Center, New York, NY; and., Cushing M; Division of Pathology, Department of Medicine, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY., Desai P; Division of Hematology/Oncology and., Dobrila L; National Cord Blood Program, New York Blood Center, New York, NY; and., Gergis U; Division of Hematology/Oncology and., Guarneri D; Division of Hematology/Oncology and., Hsu JM; Division of Hematology/Oncology and., Lee S; Division of Hematology/Oncology and., Mayer SA; Division of Hematology/Oncology and., Phillips AA; Division of Hematology/Oncology and., Orfali N; Division of Hematology/Oncology and., Ritchie EK; Division of Hematology/Oncology and., Roboz GJ; Division of Hematology/Oncology and., Romeo C; National Cord Blood Program, New York Blood Center, New York, NY; and., Samuel MS; Division of Hematology/Oncology and., Shore T; Division of Hematology/Oncology and., van Besien K; Division of Hematology/Oncology and.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2020 Oct 27; Vol. 4 (20), pp. 5146-5156.
DOI:	10.1182/bloodadvances.2020002805
Abstrakt:	We conducted a prospective evaluation of cord blood (CB)-derived adoptive cell therapy, after salvage chemotherapy, for patients with advanced myeloid malignancies and poor prognosis. Previously, we reported safety, feasibility, and preliminary efficacy of this approach. We present updated results in 31 patients who received intensive chemotherapy followed by CB infusion and identify predictors of response. To enhance the antileukemic effect, we selected CB units (CBU) with shared inherited paternal antigens and/or noninherited maternal antigens with the recipients. Twenty-eight patients with acute myeloid leukemia (AML), 2 with myelodysplastic syndrome, and 1 in chronic myeloid leukemia myeloid blast crisis were enrolled; 9 had relapsed after allogeneic transplant. Response was defined as <5% blasts in hypocellular bone marrow at 2 weeks after treatment. Thirteen patients (42%) responded; a rate higher than historical data with chemotherapy only. Twelve had CBU-derived chimerism detected; chimerism was a powerful predictor of response (P < .001). CBU lymphocyte content and a prior transplant were associated with chimerism (P < .01). Safety was acceptable: 3 patients developed mild cytokine release syndrome, 2 had grade 1 and 2 had grade 4 graft-versus-host disease. Seven responders and 6 nonresponders (after additional therapy) received subsequent transplant; 5 are alive (follow-up, 5-47 months). The most common cause of death for nonresponders was disease progression, whereas for responders it was infection. CB-derived adoptive cell therapy is feasible and efficacious for refractory AML. Banked CBU are readily available for treatment. Response depends on chimerism, highlighting the graft-versus-leukemia effect of CB cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT02508324. (© 2020 by The American Society of Hematology.)
Databáze:	MEDLINE
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