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

TitleAdoptive immunotherapy with CB following chemotherapy for patients with refractory myeloid malignancy: chimerism and response.
Publication TypeJournal Article
Year of Publication2020
AuthorsChaekal O-K, Scaradavou A, Frenet EMasson, Albano MS, Cushing M, Desai P, Dobrila L, Gergis U, Guarneri D, Hsu J-M, Lee S, Mayer SA, Phillips AA, Orfali N, Ritchie EK, Roboz GJ, Romeo C, Samuel MS, Shore T, Van Besien K
JournalBlood Adv
Volume4
Issue20
Pagination5146-5156
Date Published2020 10 27
ISSN2473-9537
KeywordsChimerism, Fetal Blood, Humans, Immunotherapy, Adoptive, Prospective Studies, Remission Induction, Transplantation, Homologous
Abstract

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.

DOI10.1182/bloodadvances.2020002805
Alternate JournalBlood Adv
PubMed ID33091124
PubMed Central IDPMC7594383
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
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