Adoptive immunotherapy with CB following chemotherapy for patients with refractory myeloid malignancy: Chimerism and response Journal Article
| Authors: | Chaekal, O. K.; Scaradavou, A.; Frenet, E. M.; Albano, M. S.; Cushing, M.; Desai, P.; Dobrila, L.; Gergis, U.; Guarneri, D.; Hsu, J. M.; Lee, S.; Mayer, S. A.; Phillips, A. A.; Orfali, N.; Ritchie, E. K.; Roboz, G. J.; Romeo, C.; Samuel, M. S.; Shore, T.; van Besien, K. |
| Article Title: | Adoptive immunotherapy with CB following chemotherapy for patients with refractory myeloid malignancy: Chimerism and response |
| 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. © 2020 by The American Society of Hematology |
| Keywords: | adult; cancer chemotherapy; clinical article; controlled study; treatment response; aged; fludarabine; salvage therapy; doxorubicin; advanced cancer; cancer growth; disease classification; drug efficacy; drug safety; treatment duration; cytarabine; drug megadose; follow up; prospective study; bone marrow; bone marrow suppression; etoposide; prediction; chimera; cord blood stem cell transplantation; disease severity; myelodysplastic syndrome; feasibility study; mitoxantrone; graft versus host reaction; sepsis; umbilical cord blood; therapy effect; bloodstream infection; hla a antigen; hla b antigen; leukemia relapse; lymphocyte; graft versus leukemia effect; adenovirus infection; adoptive immunotherapy; clofarabine; allotransplantation; cladribine; respiratory failure; blast cell crisis; filgrastim; antileukemic activity; posttransplant lymphoproliferative disease; cytokine release syndrome; acute myeloid leukemia; antigen function; bone marrow cancer; cancer prognosis; hla drb1 antigen; cell component; human; male; female; priority journal; article; fungal sinusitis; pulmonary veno-occlusive disease |
| Journal Title: | Blood Advances |
| Volume: | 4 |
| Issue: | 20 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2020-10-27 |
| Start Page: | 5146 |
| End Page: | 5156 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2020002805 |
| PUBMED: | 33091124 |
| PROVIDER: | scopus |
| PMCID: | PMC7594383 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 January 2021 -- Source: Scopus |
