Graft versus leukemia response without graft-versus-host disease elicited by adoptively transferred multivirus-specific T-cells

Jan J. Melenhorst; Paul Castillo; Patrick J. Hanley; Michael D. Keller; Robert A. Krance; Judith Margolin; Ann M. Leen; Helen E. Heslop; A. John Barrett; Cliona M. Rooney; Catherine M. Bollard

doi:10.1038/mt.2014.192

Graft versus leukemia response without graft-versus-host disease elicited by adoptively transferred multivirus-specific T-cells

Jan J. Melenhorst, Paul Castillo, Patrick J. Hanley, Michael D. Keller, Robert A. Krance, Judith Margolin, Ann M. Leen, Helen E. Heslop, A. John Barrett, Cliona M. Rooney, Catherine M. Bollard

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28 Scopus citations

Abstract

A 12-year-old boy with refractory acute lymphoblastic leukemia received a haploidentical transplant from his mother. As prophylaxis for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and adenovirus, he received ex vivo expanded virus-specific donor T cells 3.5 months after transplant. Four weeks later leukemic blasts bearing the E2A deletion, identified by fluorescent in situ hybridization (FISH), appeared transiently in the blood followed by a FISH-negative hematological remission, which was sustained until a testicular relapse 3.5 months later. Clearance of the circulating leukemic cells coincided with a marked increase in circulating virus-specific T cells. The virus-specific cytotoxic T-cell (CTL) line showed strong polyfunctional reactivity with the patient's leukemic cells but not phytohemagglutinin (PHA) blasts, suggesting that virus-specific CTL lines may have clinically significant antileukemia activity.

Original language	English (US)
Pages (from-to)	179-183
Number of pages	5
Journal	Molecular Therapy
Volume	23
Issue number	1
DOIs	https://doi.org/10.1038/mt.2014.192
State	Published - Jan 10 2015

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Pharmacology
Drug Discovery

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Melenhorst, J. J., Castillo, P., Hanley, P. J., Keller, M. D., Krance, R. A., Margolin, J., Leen, A. M., Heslop, H. E., Barrett, A. J., Rooney, C. M., & Bollard, C. M. (2015). Graft versus leukemia response without graft-versus-host disease elicited by adoptively transferred multivirus-specific T-cells. Molecular Therapy, 23(1), 179-183. https://doi.org/10.1038/mt.2014.192

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title = "Graft versus leukemia response without graft-versus-host disease elicited by adoptively transferred multivirus-specific T-cells",

abstract = "A 12-year-old boy with refractory acute lymphoblastic leukemia received a haploidentical transplant from his mother. As prophylaxis for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and adenovirus, he received ex vivo expanded virus-specific donor T cells 3.5 months after transplant. Four weeks later leukemic blasts bearing the E2A deletion, identified by fluorescent in situ hybridization (FISH), appeared transiently in the blood followed by a FISH-negative hematological remission, which was sustained until a testicular relapse 3.5 months later. Clearance of the circulating leukemic cells coincided with a marked increase in circulating virus-specific T cells. The virus-specific cytotoxic T-cell (CTL) line showed strong polyfunctional reactivity with the patient's leukemic cells but not phytohemagglutinin (PHA) blasts, suggesting that virus-specific CTL lines may have clinically significant antileukemia activity.",

author = "Melenhorst, {Jan J.} and Paul Castillo and Hanley, {Patrick J.} and Keller, {Michael D.} and Krance, {Robert A.} and Judith Margolin and Leen, {Ann M.} and Heslop, {Helen E.} and Barrett, {A. John} and Rooney, {Cliona M.} and Bollard, {Catherine M.}",

note = "Funding Information: The clinical trial was supported in part by the Production Assistance for Cellular Therapies program (NHLBI contract #HHSN268201000007C). We also appreciate the support of shared resources by Dan L Duncan Cancer Center support grant P30CA125123. Publisher Copyright: {\textcopyright} The American Society of Gene & Cell Therapy.",

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doi = "10.1038/mt.2014.192",

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AU - Krance, Robert A.

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AU - Leen, Ann M.

AU - Heslop, Helen E.

AU - Barrett, A. John

AU - Rooney, Cliona M.

AU - Bollard, Catherine M.

N1 - Funding Information: The clinical trial was supported in part by the Production Assistance for Cellular Therapies program (NHLBI contract #HHSN268201000007C). We also appreciate the support of shared resources by Dan L Duncan Cancer Center support grant P30CA125123. Publisher Copyright: © The American Society of Gene & Cell Therapy.

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N2 - A 12-year-old boy with refractory acute lymphoblastic leukemia received a haploidentical transplant from his mother. As prophylaxis for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and adenovirus, he received ex vivo expanded virus-specific donor T cells 3.5 months after transplant. Four weeks later leukemic blasts bearing the E2A deletion, identified by fluorescent in situ hybridization (FISH), appeared transiently in the blood followed by a FISH-negative hematological remission, which was sustained until a testicular relapse 3.5 months later. Clearance of the circulating leukemic cells coincided with a marked increase in circulating virus-specific T cells. The virus-specific cytotoxic T-cell (CTL) line showed strong polyfunctional reactivity with the patient's leukemic cells but not phytohemagglutinin (PHA) blasts, suggesting that virus-specific CTL lines may have clinically significant antileukemia activity.

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Graft versus leukemia response without graft-versus-host disease elicited by adoptively transferred multivirus-specific T-cells

Abstract

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