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

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

doi:10.1002/ajh.24285

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

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

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

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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 (US)
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
State	Published - Mar 1 2016

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© 2016 Wiley Periodicals, Inc.

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10.1002/ajh.24285

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Seftel, M. D., Neuberg, D., Zhang, M. J., Wang, H. L., Ballen, K. K., Bergeron, J., Couban, S., Freytes, C. O., Hamadani, M., Kharfan-Dabaja, M. A., Lazarus, H. M., Nishihori, T., Paulson, K., Saber, W., Sallan, S. E., Soiffer, R., Tallman, M. S., Woolfrey, A. E., Deangelo, D. J., ... Wood, W. A. (2016). Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission. American Journal of Hematology, 91(3), 322-329. https://doi.org/10.1002/ajh.24285

Seftel, MD, Neuberg, D, Zhang, MJ, Wang, HL, Ballen, KK, Bergeron, J, Couban, S, Freytes, CO, Hamadani, M, Kharfan-Dabaja, MA, Lazarus, HM, Nishihori, T, Paulson, K, Saber, W, Sallan, SE, Soiffer, R, Tallman, MS, Woolfrey, AE, Deangelo, DJ, Weisdorf, DJ, Akpek, G, Bacher, U, Bachanova, V, Baron, F, Bashey, A, Cahn, JY, Camitta, BM, Copelan, EA, Lima, MD, Deol, A, Gale, RP, Gergis, U, Hogan, WJ, Kebriaei, P, Litzow, MR, Loren, AW, Miller, AM, Norkin, M, Olsson, RF, Reshef, R, Sabloff, M, Sandmaier, BM, Savani, BN, Schouten, HC, Vij, R, Wiernik, PH, Wirk, B & Wood, WA 2016, 'Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission', American Journal of Hematology, vol. 91, no. 3, pp. 322-329. https://doi.org/10.1002/ajh.24285

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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 = "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}",

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

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

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

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