Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission

for the Acute Leukemia Committee of the CIBMTR and the Dana Farber ALL Consortium

doi:10.1002/ajh.24285

Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission

for the Acute Leukemia Committee of the CIBMTR and the Dana Farber ALL Consortium

Research output: Contribution to journal › Article › peer-review

68 Citations (Scopus)

Abstract

For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT.

Original language	English
Pages (from-to)	322-329
Number of pages	8
Journal	American Journal of Hematology
Volume	91
Issue number	3
DOIs	https://doi.org/10.1002/ajh.24285
Publication status	Published - Mar 1 2016
Externally published	Yes

Bibliographical note

Funding Information:
Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children''s Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick''s Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. *Corporate Members

Publisher Copyright:
© 2016 Wiley Periodicals, Inc.

ASJC Scopus Subject Areas

Hematology

PubMed: MeSH publication types

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

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10.1002/ajh.24285

Cite this

@article{374acec312a7434b94044ee167d29549,

title = "Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission",

abstract = "For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT.",

author = "{for the Acute Leukemia Committee of the CIBMTR and the Dana Farber ALL Consortium} and Seftel, {Matthew D.} and Donna Neuberg and Zhang, {Mei Jie} and Wang, {Hai Lin} and Ballen, {Karen Kuhn} and Julie Bergeron and Stephen Couban and Freytes, {C{\'e}sar O.} and Mehdi Hamadani and Kharfan-Dabaja, {Mohamed A.} and Lazarus, {Hillard M.} and Taiga Nishihori and Kristjan Paulson and Wael Saber and Sallan, {Stephen E.} and Robert Soiffer and Tallman, {Martin S.} and Woolfrey, {Ann E.} and Deangelo, {Daniel J.} and Weisdorf, {Daniel J.} and Gorgun Akpek and Ulrike Bacher and Veronika Bachanova and Frederic Baron and Asad Bashey and Cahn, {Jean Yves} and Camitta, {Bruce M.} and Copelan, {Edward A.} and Lima, {Marcos De} and Abhinav Deol and Gale, {Robert Peter} and Usama Gergis and Hogan, {William J.} and Partow Kebriaei and Litzow, {Mark R.} and Loren, {Alison W.} and Miller, {Alan M.} and Maxim Norkin and Olsson, {Richard F.} and Ran Reshef and Mitchell Sabloff and Sandmaier, {Brenda M.} and Savani, {Bipin N.} and Schouten, {Harry C.} and Ravi Vij and Wiernik, {Peter H.} and Baldeep Wirk and Wood, {William Allen1}",

note = "Funding Information: Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children''s Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick''s Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. *Corporate Members Publisher Copyright: {\textcopyright} 2016 Wiley Periodicals, Inc.",

year = "2016",

month = mar,

day = "1",

doi = "10.1002/ajh.24285",

language = "English",

volume = "91",

pages = "322--329",

journal = "American Journal of Hematology",

issn = "0361-8609",

publisher = "Wiley-Liss Inc.",

number = "3",

}

TY - JOUR

T1 - Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission

AU - for the Acute Leukemia Committee of the CIBMTR and the Dana Farber ALL Consortium

AU - Seftel, Matthew D.

AU - Neuberg, Donna

AU - Zhang, Mei Jie

AU - Wang, Hai Lin

AU - Ballen, Karen Kuhn

AU - Bergeron, Julie

AU - Couban, Stephen

AU - Freytes, César O.

AU - Hamadani, Mehdi

AU - Kharfan-Dabaja, Mohamed A.

AU - Lazarus, Hillard M.

AU - Nishihori, Taiga

AU - Paulson, Kristjan

AU - Saber, Wael

AU - Sallan, Stephen E.

AU - Soiffer, Robert

AU - Tallman, Martin S.

AU - Woolfrey, Ann E.

AU - Deangelo, Daniel J.

AU - Weisdorf, Daniel J.

AU - Akpek, Gorgun

AU - Bacher, Ulrike

AU - Bachanova, Veronika

AU - Baron, Frederic

AU - Bashey, Asad

AU - Cahn, Jean Yves

AU - Camitta, Bruce M.

AU - Copelan, Edward A.

AU - Lima, Marcos De

AU - Deol, Abhinav

AU - Gale, Robert Peter

AU - Gergis, Usama

AU - Hogan, William J.

AU - Kebriaei, Partow

AU - Litzow, Mark R.

AU - Loren, Alison W.

AU - Miller, Alan M.

AU - Norkin, Maxim

AU - Olsson, Richard F.

AU - Reshef, Ran

AU - Sabloff, Mitchell

AU - Sandmaier, Brenda M.

AU - Savani, Bipin N.

AU - Schouten, Harry C.

AU - Vij, Ravi

AU - Wiernik, Peter H.

AU - Wirk, Baldeep

AU - Wood, William Allen1

N1 - Funding Information: Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children''s Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick''s Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. *Corporate Members Publisher Copyright: © 2016 Wiley Periodicals, Inc.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT.

AB - For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT.

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Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission

Abstract

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