Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era

Results from the International ALL Trial MRC UKALLXII/ECOG2993

Adele K. Fielding, Jacob M. Rowe, Susan M. Richards, Georgina Buck, Anthony Moorman, I. Jill Durrant, David I. Marks, Andrew K. McMillan, Mark R. Litzow, Hillard M. Lazarus, Letizia Foroni, Gordon Dewald, Ian M. Franklin, Selina M. Luger, Elisabeth Paietta, Peter H. Wiernik, Martin S. Tallman, Anthony H. Goldstone

Research output: Contribution to journalArticle

Abstract

Prospective data on the value of allogeneic hematopoietic stem cell transplantation (alloHSCT) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) are limited. The UKALLXII/ECOG 2993 study evaluated the outcome of assigning alloHSCT with a sibling (sib) or matched unrelated donor (MUD) to patients younger than 55 years of age achieving complete remission (CR). The CR rate of 267 patients, median age 40, was 82%. Twenty-eight percent of patients proceeded to alloHSCT in first CR. Age older than 55 years or a pre-HSCT event were the most common reasons for failure to progress to alloHSCT. At 5 years, overall survival (OS) was 44% after sib alloHSCT, 36% after MUD alloHSCT, and 19% after chemotherapy. After adjustment for sex, age, and white blood count and excluding chemotherapy-treated patients who relapsed or died before the median time to alloHSCT, only relapsefree survival remained significantly superior in the alloHSCT group (odds ratio 0.31, 95% confidence interval 0.16-0.61). An intention-to-treat analysis, using the availability or not of a matched sibling donor, showed 5-year OS to be nonsignificantly better at 34% with a donor versus 25% with no donor. This prospective trial in adult Ph+ ALL indicates a modest but significant benefit to alloHSCT. This trial has been registered with clinicaltrials.gov under identifier NCT00002514 and as ISRCTN77346223.

Original languageEnglish (US)
Pages (from-to)4489-4496
Number of pages8
JournalBlood
Volume113
Issue number19
DOIs
StatePublished - Nov 19 2009
Externally publishedYes

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Philadelphia Chromosome
Chemotherapy
Hematopoietic Stem Cell Transplantation
Homologous Transplantation
Chromosomes
Stem cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug Therapy
Siblings
Unrelated Donors
Tissue Donors
Survival
Imatinib Mesylate
Intention to Treat Analysis
Blood
Odds Ratio
Outcome Assessment (Health Care)
Availability
Confidence Intervals

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era : Results from the International ALL Trial MRC UKALLXII/ECOG2993. / Fielding, Adele K.; Rowe, Jacob M.; Richards, Susan M.; Buck, Georgina; Moorman, Anthony; Durrant, I. Jill; Marks, David I.; McMillan, Andrew K.; Litzow, Mark R.; Lazarus, Hillard M.; Foroni, Letizia; Dewald, Gordon; Franklin, Ian M.; Luger, Selina M.; Paietta, Elisabeth; Wiernik, Peter H.; Tallman, Martin S.; Goldstone, Anthony H.

In: Blood, Vol. 113, No. 19, 19.11.2009, p. 4489-4496.

Research output: Contribution to journalArticle

Fielding, AK, Rowe, JM, Richards, SM, Buck, G, Moorman, A, Durrant, IJ, Marks, DI, McMillan, AK, Litzow, MR, Lazarus, HM, Foroni, L, Dewald, G, Franklin, IM, Luger, SM, Paietta, E, Wiernik, PH, Tallman, MS & Goldstone, AH 2009, 'Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: Results from the International ALL Trial MRC UKALLXII/ECOG2993', Blood, vol. 113, no. 19, pp. 4489-4496. https://doi.org/10.1182/blood-2009-01-199380
Fielding, Adele K. ; Rowe, Jacob M. ; Richards, Susan M. ; Buck, Georgina ; Moorman, Anthony ; Durrant, I. Jill ; Marks, David I. ; McMillan, Andrew K. ; Litzow, Mark R. ; Lazarus, Hillard M. ; Foroni, Letizia ; Dewald, Gordon ; Franklin, Ian M. ; Luger, Selina M. ; Paietta, Elisabeth ; Wiernik, Peter H. ; Tallman, Martin S. ; Goldstone, Anthony H. / Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era : Results from the International ALL Trial MRC UKALLXII/ECOG2993. In: Blood. 2009 ; Vol. 113, No. 19. pp. 4489-4496.
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abstract = "Prospective data on the value of allogeneic hematopoietic stem cell transplantation (alloHSCT) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) are limited. The UKALLXII/ECOG 2993 study evaluated the outcome of assigning alloHSCT with a sibling (sib) or matched unrelated donor (MUD) to patients younger than 55 years of age achieving complete remission (CR). The CR rate of 267 patients, median age 40, was 82{\%}. Twenty-eight percent of patients proceeded to alloHSCT in first CR. Age older than 55 years or a pre-HSCT event were the most common reasons for failure to progress to alloHSCT. At 5 years, overall survival (OS) was 44{\%} after sib alloHSCT, 36{\%} after MUD alloHSCT, and 19{\%} after chemotherapy. After adjustment for sex, age, and white blood count and excluding chemotherapy-treated patients who relapsed or died before the median time to alloHSCT, only relapsefree survival remained significantly superior in the alloHSCT group (odds ratio 0.31, 95{\%} confidence interval 0.16-0.61). An intention-to-treat analysis, using the availability or not of a matched sibling donor, showed 5-year OS to be nonsignificantly better at 34{\%} with a donor versus 25{\%} with no donor. This prospective trial in adult Ph+ ALL indicates a modest but significant benefit to alloHSCT. This trial has been registered with clinicaltrials.gov under identifier NCT00002514 and as ISRCTN77346223.",
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AU - Fielding, Adele K.

AU - Rowe, Jacob M.

AU - Richards, Susan M.

AU - Buck, Georgina

AU - Moorman, Anthony

AU - Durrant, I. Jill

AU - Marks, David I.

AU - McMillan, Andrew K.

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AU - Lazarus, Hillard M.

AU - Foroni, Letizia

AU - Dewald, Gordon

AU - Franklin, Ian M.

AU - Luger, Selina M.

AU - Paietta, Elisabeth

AU - Wiernik, Peter H.

AU - Tallman, Martin S.

AU - Goldstone, Anthony H.

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N2 - Prospective data on the value of allogeneic hematopoietic stem cell transplantation (alloHSCT) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) are limited. The UKALLXII/ECOG 2993 study evaluated the outcome of assigning alloHSCT with a sibling (sib) or matched unrelated donor (MUD) to patients younger than 55 years of age achieving complete remission (CR). The CR rate of 267 patients, median age 40, was 82%. Twenty-eight percent of patients proceeded to alloHSCT in first CR. Age older than 55 years or a pre-HSCT event were the most common reasons for failure to progress to alloHSCT. At 5 years, overall survival (OS) was 44% after sib alloHSCT, 36% after MUD alloHSCT, and 19% after chemotherapy. After adjustment for sex, age, and white blood count and excluding chemotherapy-treated patients who relapsed or died before the median time to alloHSCT, only relapsefree survival remained significantly superior in the alloHSCT group (odds ratio 0.31, 95% confidence interval 0.16-0.61). An intention-to-treat analysis, using the availability or not of a matched sibling donor, showed 5-year OS to be nonsignificantly better at 34% with a donor versus 25% with no donor. This prospective trial in adult Ph+ ALL indicates a modest but significant benefit to alloHSCT. This trial has been registered with clinicaltrials.gov under identifier NCT00002514 and as ISRCTN77346223.

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