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Matched Donor Transplant Best Strategy for Ph-Positive ALL

Matched Donor Transplant Best Strategy for Ph-Positive ALL

PAVIA, Italy—In a retrospective study of children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL), bone marrow transplantation from an HLA-matched related donor proved superior to other types of transplantation and to intensive chemotherapy alone in prolonging initial complete remissions.

Although the overall cure rate for childhood ALL is 75% or higher, Ph-positive ALL “has a dire prognosis,” said Maurizio Arico, MD. Event-free survival rates for Ph-positive patients are 25% to 30% in children and less than 20% in adults.

Lack of consensus on the optimal therapy for Ph-positive ALL was a motivating factor for the current multicenter, international study, led by Dr. Arico, of the Clinica Pedi-atrica, IRCCS Poli-clinico San Matteo, Pavia, Italy.

The study included 267 children and young adults with Ph-positive ALL who were in complete remission after induction chemotherapy. The patients were all registered in clinical trials between 1986 and 1996.

After induction, the patients were stratified into three subgroups: best prognosis (leukocyte count less than 50,000/mm³ and age less than 10); intermediate prognosis; and worst prognosis (leukocyte count of more than 100,000/mm³). Estimates of disease-free survival at 5 years for the three groups were 49%, 30%, and 20%, respectively.

Compared with the group of patients treated with chemotherapy alone, patients who underwent bone marrow transplantation from a matched related donor had a significantly lower risk of treatment failure (relative risk of death or adverse events, 0.3, P < .001) (N Engl J Med 342:998-1006, 2000). “The advantage of transplantation of bone marrow from matched related donors became more apparent with each successive year of follow-up,” Dr. Arico said, “suggesting greater protection against late relapses than with chemotherapy alone in patients who survived the early toxic effects of treatment.”

The superiority of transplantation was seen in each of the prognostic subgroups. None of the other types of bone marrow transplantation showed a therapeutic advantage over chemotherapy alone.

“Further cooperation among leukemia specialists worldwide will be needed to generate and test relevant hypotheses pertaining to Ph-positive ALL and other uncommon subtypes of acute leukemia,” Dr. Arico concluded.

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