Low toxicity and favorable overall survival in relapsed/refractory B-ALL following CAR T cells and CD34-selected T-cell depleted allogeneic hematopoietic cell transplant.

Autor: Fabrizio VA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA., Kernan NA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA.; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Boulad F; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA.; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Cancio M; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA., Allen J; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Higman M; Department of Pediatrics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Margossian SP; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA., Mauguen A; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Prockop S; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA., Scaradavou A; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA., Shah N; Department of Pediatric Hematology/Oncology, Yale Cancer Center, New Haven, CT, USA., Spitzer B; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA., Stieglitz E; Department of Pediatric Hematology/Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA., Yeager N; Department of Pediatric Hematology/Oncology, Nationwide Children's Hospital, Columbus, OH, USA., O'Reilly RJ; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA.; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Brentjens RJ; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Jan Boelens J; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Curran KJ; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. currank@mskcc.org.; Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA. currank@mskcc.org.; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA. currank@mskcc.org.
Jazyk: angličtina
Zdroj: Bone marrow transplantation [Bone Marrow Transplant] 2020 Nov; Vol. 55 (11), pp. 2160-2169. Date of Electronic Publication: 2020 May 10.
DOI: 10.1038/s41409-020-0926-1
Abstrakt: To define the tolerability and outcome of allogeneic hematopoietic stem cell transplant (allo-HSCT) following CAR T-cell therapy, we retrospectively reviewed pediatric/young adult patients with relapsed/refractory B-ALL who underwent this treatment. Fifteen patients (median age 13 years; range 1-20 years) with a median potential follow-up of 39 months demonstrated 24-month cumulative incidence of relapse, cumulative incidence of TRM, and OS of 16% (95% CI: 0-37%), 20% (95% CI: 0-40%), and 80% (95% CI: 60-100%), respectively. Severe toxicity following CAR T cells did not impact OS (p = 0.27), while greater time from CAR T cells to allo-HSCT (>80 days) was associated with a decrease in OS. In comparing CD34-selected T-cell depleted (TCD; n = 9) vs unmodified (n = 6) allo-HSCT, the cumulative incidence of relapse, TRM, and OS at 24 months was 22% (95% CI: 0-49%) vs 0% (p = 0.14), 0% vs 50% [95% CI: 10-90%] (p = 0.02) and 100% vs 50% [95% CI: 10-90%] (p = 0.02). In this small cohort of patients, CAR T cells followed by a CD34-selected TCD allo-HSCT appears to result in less TRM and favorable OS when compared with unmodified allo-HSCT. There was no evidence that disease control was impacted by the type of consolidative allo-HSCT, which demonstrates the feasibility of this approach.
Databáze: MEDLINE
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