PAVIA, ItalyIn 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.