Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia

Stella M. Davies, Norma K C Ramsay, John P. Klein, Daniel J. Weisdorf, Brian Bolwell, Jean Yves Cahn, Bruce M. Camitta, Robert Peter Gale, Sergio Giralt, Carsten Heilmann, P. Jean Henslee-Downey, Roger H. Herzig, Raymond Hutchinson, Armand Keating, Hillard M. Lazarus, Gustavo A. Milone, Steven Neudorf, Waleska S. Perez, Ray L. Powles, H. Grant Prentice & 6 others Gary Schiller, Gérard Socié, Marcus Vowels, Joseph Wiley, Andrew M Yeager, Mary M. Horowitz

Research output: Contribution to journalArticle

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Abstract

Purpose: Preparative regimens involving total-body irradiation (TBI) produce significant late toxicities in some children who receive bone marrow transplants, including impaired growth and intellectual development. Busulfan is often used as an alternative to TBI, but there are few data regarding its relative efficacy. Patients and Methods: We compared outcomes of HLA- identical sibling transplants for acute lymphoblastic leukemia (ALL) in children (< 20 years of age) who received cyclophosphamide plus TBI (CY/TBI) (n = 451)versus those who received busulfan plus cyclophosphamide (Bu/CY) (n = 176) for pretransplant conditioning. Patients received transplants between 1988 and 1995 and their results were reported to the International Bone Marrow Transplant Registry by 144 participating institutions. The CY/TBI and Bu/CY groups did not differ in gender, immune phenotype, leukocyte count at the time of diagnosis, chromosome abnormalities, remission status, or length of initial remission. T-cell depletion was used more frequently in the CY/TBI group; the Bu/CY group included a higher proportion of children who were less than 5 years of age. The median follow-up period was 37 months. Results: The 3-year probabilities of survival were 55% (95% confidence interval [CI], 50% to 60%) with TBI/CY and 40% (95% CI, 32% to 48%) with Bu/CY (univariate P = .003). The 3-year probabilities of leukemia-free survival were 50% (95% CI, 45% to 55%) and 35% (95% CI, 28% to 43%), respectively (univariate P = .005). In a multivariate analysis, the risks of relapse were similar in the two groups (relative risk [RR], 1.30 for Bu/CY v CY/TBI; P = .1). Treatment- related mortality was higher in the Bu/CY group (RR, 1.68; P = .012). Death and treatment failure (relapse or death, inverse of leukemia-free survival) were more frequent in the Bu/CY group (RR, 1.39; P = .017 for death; RR, 1.42; P = .006 for treatment failure). Conclusion: These data indicate superior survival with CY/TBI conditioning, compared with Bu/CY conditioning, for HLA-identical sibling bone marrow transplants in children with ALL.

Original languageEnglish (US)
Pages (from-to)340-347
Number of pages8
JournalJournal of Clinical Oncology
Volume18
Issue number2
StatePublished - Jan 2000
Externally publishedYes

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cyclophosphamide
Busulfan
Transplants
Whole-Body Irradiation
Confidence Intervals
Survival
Bone Marrow
Treatment Failure
Siblings
Leukemia
Recurrence
Leukocyte Count
Growth and Development
Chromosome Aberrations
Registries
Multivariate Analysis
T-Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Davies, S. M., Ramsay, N. K. C., Klein, J. P., Weisdorf, D. J., Bolwell, B., Cahn, J. Y., ... Horowitz, M. M. (2000). Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. Journal of Clinical Oncology, 18(2), 340-347.

Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. / Davies, Stella M.; Ramsay, Norma K C; Klein, John P.; Weisdorf, Daniel J.; Bolwell, Brian; Cahn, Jean Yves; Camitta, Bruce M.; Gale, Robert Peter; Giralt, Sergio; Heilmann, Carsten; Henslee-Downey, P. Jean; Herzig, Roger H.; Hutchinson, Raymond; Keating, Armand; Lazarus, Hillard M.; Milone, Gustavo A.; Neudorf, Steven; Perez, Waleska S.; Powles, Ray L.; Prentice, H. Grant; Schiller, Gary; Socié, Gérard; Vowels, Marcus; Wiley, Joseph; Yeager, Andrew M; Horowitz, Mary M.

In: Journal of Clinical Oncology, Vol. 18, No. 2, 01.2000, p. 340-347.

Research output: Contribution to journalArticle

Davies, SM, Ramsay, NKC, Klein, JP, Weisdorf, DJ, Bolwell, B, Cahn, JY, Camitta, BM, Gale, RP, Giralt, S, Heilmann, C, Henslee-Downey, PJ, Herzig, RH, Hutchinson, R, Keating, A, Lazarus, HM, Milone, GA, Neudorf, S, Perez, WS, Powles, RL, Prentice, HG, Schiller, G, Socié, G, Vowels, M, Wiley, J, Yeager, AM & Horowitz, MM 2000, 'Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia', Journal of Clinical Oncology, vol. 18, no. 2, pp. 340-347.
Davies SM, Ramsay NKC, Klein JP, Weisdorf DJ, Bolwell B, Cahn JY et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. Journal of Clinical Oncology. 2000 Jan;18(2):340-347.
Davies, Stella M. ; Ramsay, Norma K C ; Klein, John P. ; Weisdorf, Daniel J. ; Bolwell, Brian ; Cahn, Jean Yves ; Camitta, Bruce M. ; Gale, Robert Peter ; Giralt, Sergio ; Heilmann, Carsten ; Henslee-Downey, P. Jean ; Herzig, Roger H. ; Hutchinson, Raymond ; Keating, Armand ; Lazarus, Hillard M. ; Milone, Gustavo A. ; Neudorf, Steven ; Perez, Waleska S. ; Powles, Ray L. ; Prentice, H. Grant ; Schiller, Gary ; Socié, Gérard ; Vowels, Marcus ; Wiley, Joseph ; Yeager, Andrew M ; Horowitz, Mary M. / Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. In: Journal of Clinical Oncology. 2000 ; Vol. 18, No. 2. pp. 340-347.
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title = "Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia",
abstract = "Purpose: Preparative regimens involving total-body irradiation (TBI) produce significant late toxicities in some children who receive bone marrow transplants, including impaired growth and intellectual development. Busulfan is often used as an alternative to TBI, but there are few data regarding its relative efficacy. Patients and Methods: We compared outcomes of HLA- identical sibling transplants for acute lymphoblastic leukemia (ALL) in children (< 20 years of age) who received cyclophosphamide plus TBI (CY/TBI) (n = 451)versus those who received busulfan plus cyclophosphamide (Bu/CY) (n = 176) for pretransplant conditioning. Patients received transplants between 1988 and 1995 and their results were reported to the International Bone Marrow Transplant Registry by 144 participating institutions. The CY/TBI and Bu/CY groups did not differ in gender, immune phenotype, leukocyte count at the time of diagnosis, chromosome abnormalities, remission status, or length of initial remission. T-cell depletion was used more frequently in the CY/TBI group; the Bu/CY group included a higher proportion of children who were less than 5 years of age. The median follow-up period was 37 months. Results: The 3-year probabilities of survival were 55{\%} (95{\%} confidence interval [CI], 50{\%} to 60{\%}) with TBI/CY and 40{\%} (95{\%} CI, 32{\%} to 48{\%}) with Bu/CY (univariate P = .003). The 3-year probabilities of leukemia-free survival were 50{\%} (95{\%} CI, 45{\%} to 55{\%}) and 35{\%} (95{\%} CI, 28{\%} to 43{\%}), respectively (univariate P = .005). In a multivariate analysis, the risks of relapse were similar in the two groups (relative risk [RR], 1.30 for Bu/CY v CY/TBI; P = .1). Treatment- related mortality was higher in the Bu/CY group (RR, 1.68; P = .012). Death and treatment failure (relapse or death, inverse of leukemia-free survival) were more frequent in the Bu/CY group (RR, 1.39; P = .017 for death; RR, 1.42; P = .006 for treatment failure). Conclusion: These data indicate superior survival with CY/TBI conditioning, compared with Bu/CY conditioning, for HLA-identical sibling bone marrow transplants in children with ALL.",
author = "Davies, {Stella M.} and Ramsay, {Norma K C} and Klein, {John P.} and Weisdorf, {Daniel J.} and Brian Bolwell and Cahn, {Jean Yves} and Camitta, {Bruce M.} and Gale, {Robert Peter} and Sergio Giralt and Carsten Heilmann and Henslee-Downey, {P. Jean} and Herzig, {Roger H.} and Raymond Hutchinson and Armand Keating and Lazarus, {Hillard M.} and Milone, {Gustavo A.} and Steven Neudorf and Perez, {Waleska S.} and Powles, {Ray L.} and Prentice, {H. Grant} and Gary Schiller and G{\'e}rard Soci{\'e} and Marcus Vowels and Joseph Wiley and Yeager, {Andrew M} and Horowitz, {Mary M.}",
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TY - JOUR

T1 - Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia

AU - Davies, Stella M.

AU - Ramsay, Norma K C

AU - Klein, John P.

AU - Weisdorf, Daniel J.

AU - Bolwell, Brian

AU - Cahn, Jean Yves

AU - Camitta, Bruce M.

AU - Gale, Robert Peter

AU - Giralt, Sergio

AU - Heilmann, Carsten

AU - Henslee-Downey, P. Jean

AU - Herzig, Roger H.

AU - Hutchinson, Raymond

AU - Keating, Armand

AU - Lazarus, Hillard M.

AU - Milone, Gustavo A.

AU - Neudorf, Steven

AU - Perez, Waleska S.

AU - Powles, Ray L.

AU - Prentice, H. Grant

AU - Schiller, Gary

AU - Socié, Gérard

AU - Vowels, Marcus

AU - Wiley, Joseph

AU - Yeager, Andrew M

AU - Horowitz, Mary M.

PY - 2000/1

Y1 - 2000/1

N2 - Purpose: Preparative regimens involving total-body irradiation (TBI) produce significant late toxicities in some children who receive bone marrow transplants, including impaired growth and intellectual development. Busulfan is often used as an alternative to TBI, but there are few data regarding its relative efficacy. Patients and Methods: We compared outcomes of HLA- identical sibling transplants for acute lymphoblastic leukemia (ALL) in children (< 20 years of age) who received cyclophosphamide plus TBI (CY/TBI) (n = 451)versus those who received busulfan plus cyclophosphamide (Bu/CY) (n = 176) for pretransplant conditioning. Patients received transplants between 1988 and 1995 and their results were reported to the International Bone Marrow Transplant Registry by 144 participating institutions. The CY/TBI and Bu/CY groups did not differ in gender, immune phenotype, leukocyte count at the time of diagnosis, chromosome abnormalities, remission status, or length of initial remission. T-cell depletion was used more frequently in the CY/TBI group; the Bu/CY group included a higher proportion of children who were less than 5 years of age. The median follow-up period was 37 months. Results: The 3-year probabilities of survival were 55% (95% confidence interval [CI], 50% to 60%) with TBI/CY and 40% (95% CI, 32% to 48%) with Bu/CY (univariate P = .003). The 3-year probabilities of leukemia-free survival were 50% (95% CI, 45% to 55%) and 35% (95% CI, 28% to 43%), respectively (univariate P = .005). In a multivariate analysis, the risks of relapse were similar in the two groups (relative risk [RR], 1.30 for Bu/CY v CY/TBI; P = .1). Treatment- related mortality was higher in the Bu/CY group (RR, 1.68; P = .012). Death and treatment failure (relapse or death, inverse of leukemia-free survival) were more frequent in the Bu/CY group (RR, 1.39; P = .017 for death; RR, 1.42; P = .006 for treatment failure). Conclusion: These data indicate superior survival with CY/TBI conditioning, compared with Bu/CY conditioning, for HLA-identical sibling bone marrow transplants in children with ALL.

AB - Purpose: Preparative regimens involving total-body irradiation (TBI) produce significant late toxicities in some children who receive bone marrow transplants, including impaired growth and intellectual development. Busulfan is often used as an alternative to TBI, but there are few data regarding its relative efficacy. Patients and Methods: We compared outcomes of HLA- identical sibling transplants for acute lymphoblastic leukemia (ALL) in children (< 20 years of age) who received cyclophosphamide plus TBI (CY/TBI) (n = 451)versus those who received busulfan plus cyclophosphamide (Bu/CY) (n = 176) for pretransplant conditioning. Patients received transplants between 1988 and 1995 and their results were reported to the International Bone Marrow Transplant Registry by 144 participating institutions. The CY/TBI and Bu/CY groups did not differ in gender, immune phenotype, leukocyte count at the time of diagnosis, chromosome abnormalities, remission status, or length of initial remission. T-cell depletion was used more frequently in the CY/TBI group; the Bu/CY group included a higher proportion of children who were less than 5 years of age. The median follow-up period was 37 months. Results: The 3-year probabilities of survival were 55% (95% confidence interval [CI], 50% to 60%) with TBI/CY and 40% (95% CI, 32% to 48%) with Bu/CY (univariate P = .003). The 3-year probabilities of leukemia-free survival were 50% (95% CI, 45% to 55%) and 35% (95% CI, 28% to 43%), respectively (univariate P = .005). In a multivariate analysis, the risks of relapse were similar in the two groups (relative risk [RR], 1.30 for Bu/CY v CY/TBI; P = .1). Treatment- related mortality was higher in the Bu/CY group (RR, 1.68; P = .012). Death and treatment failure (relapse or death, inverse of leukemia-free survival) were more frequent in the Bu/CY group (RR, 1.39; P = .017 for death; RR, 1.42; P = .006 for treatment failure). Conclusion: These data indicate superior survival with CY/TBI conditioning, compared with Bu/CY conditioning, for HLA-identical sibling bone marrow transplants in children with ALL.

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