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 V 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, Adele K Fielding, Jacob M Rowe, Susan M Richards, Georgina Buck, Anthony V 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

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 relapse-free 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.

Figures

Figure 1
Figure 1
Flow chart showing all patients and treatments received.
Figure 2
Figure 2
Kaplan-Meier plot of overall survival by treatment received. Patients who failed to achieve remission on protocol and chemotherapy-treated patients who relapsed or died within 12 weeks of the start of treatment (the scheduled time for transplantation) are excluded from the analysis.
Figure 3
Figure 3
Kaplan-Meier plot of overall survival by availability of sibling donor among those in whom tissue typing was carried out and reported.

Source: PubMed

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