Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias Journal Article


Authors: Brentjens, R. J.; Riviere, I.; Park, J. H.; Davila, M. L.; Wang, X.; Stefanski, J.; Taylor, C.; Yeh, R.; Bartido, S.; Borquez-Ojeda, O.; Olszewska, M.; Bernal, Y.; Pegram, H.; Przybylowski, M.; Hollyman, D.; Usachenko, Y.; Pirraglia, D.; Hosey, J.; Santos, E.; Halton, E.; Maslak, P.; Scheinberg, D.; Jurcic, J.; Heaney, M.; Heller, G.; Frattini, M.; Sadelain, M.
Article Title: Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias
Abstract: We report the findings from the first 10 patients with chemotherapy- refractory chronic lymphocytic leukemia (CLL) or relapsed B-cell acute lymphoblastic leukemia (ALL) we have enrolled for treatment with autologous T cells modified to express 19-28z, a second-generation chimeric antigen (Ag) receptor specific to the B-cell lineage Ag CD19. Eight of the 9 treated patients tolerated 19-28z+ T-cell infusions well. Three of 4 evaluable patients with bulky CLL who received prior conditioning with cyclophosphamide exhibited either a significant reduction or a mixed response in lymphadenopathy without concomitant development of B-cell aplasia. In contrast, one patient with relapsed ALL who was treated in remission with a similar T-cell dose developed a predicted B-cell aplasia. The short-term persistence of infusedT cellswasenhanced by prior cyclophosphamide administration and inversely proportional to the peripheral blood tumor burden. Further analyses showed rapid trafficking of modified T cells to tumor and retained ex vivo cytotoxic potential of CD19-targeted T cells retrieved 8 days after infusion. We conclude that this adoptive T-cell approach is promising and more likely to show clinical benefit in the setting of prior conditioning chemotherapy and low tumor burden or minimal residual disease. These studies are registered at www.clinicaltrials.org as #NCT00466531 (CLL protocol) and #NCT01044069 (B-ALL protocol). © 2011 by The American Society of Hematology.
Keywords: adult; cancer chemotherapy; clinical article; controlled study; aged; t lymphocyte; tumor volume; cyclophosphamide; acute lymphoblastic leukemia; cancer relapse; chronic lymphatic leukemia; lymphadenopathy; cd19 antigen
Journal Title: Blood
Volume: 118
Issue: 18
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2011-11-03
Start Page: 4817
End Page: 4828
Language: English
DOI: 10.1182/blood-2011-04-348540
PROVIDER: scopus
PMCID: PMC3208293
PUBMED: 21849486
DOI/URL:
Notes: --- - "Cited By (since 1996): 4" - "Export Date: 9 December 2011" - "CODEN: BLOOA" - "Source: Scopus"
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