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Previous Volume 342:998-1006 April 6, 2000 Number 14 Next

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ABSTRACT

Background Children with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph-positive ALL) have a poor prognosis, and there is no consensus on the optimal treatment for this variant of ALL.

Methods We reviewed the medical records of patients with Ph-positive ALL who were treated with intensive chemotherapy, with or without bone marrow transplantation, by 10 study groups or large single institutions from 1986 to 1996. Data on 326 children and young adults, who ranged in age from 0.4 to 19.9 years (median, 8.1), were analyzed to determine the rate of complete remission and the probability of event-free, disease-free, and overall survival according to standard prognostic factors and type of treatment.

Results The 267 patients who had a complete remission after induction chemotherapy (82 percent) were stratified into three subgroups according to the age and leukocyte count at the time of diagnosis: those with the best prognosis (a leukocyte count of less than 50,000 per cubic millimeter and an age of less than 10 years; 95 patients); those with an intermediate prognosis (intermediate-risk features; 92 patients); and those with the worst prognosis (a leukocyte count of more than 100,000 per cubic millimeter; 80 patients). The estimates of disease-free survival at five years (±SE) were 49±5 percent (for patients with the best prognosis), 30±5 percent (for those with an intermediate prognosis), and 20±5 percent (for those with the worst prognosis) (P<0.001 for the overall comparison). We also found that transplantation of bone marrow from an HLA-matched related donor offered significantly greater benefit than intensive chemotherapy alone in terms of protecting patients from relapse or other adverse events (relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). This finding was consistent in all three subgroups.

Conclusions Unlike the usual type of ALL, Ph-positive ALL is associated with a poor prognosis. Nevertheless, in some patients with favorable prognostic features, the disease can be controlled by intensive chemotherapy. Transplantation of bone marrow from an HLA-matched related donor is superior to other types of transplantation and to intensive chemotherapy alone in prolonging initial complete remissions.

Source Information

From the Department of Pediatrics, Istituto Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo, Pavia, Italy (M.A.); the Department of Public Health, University of Verona, Verona, Italy (M.G.V.); the Department of Pediatrics, Midwest Children's Cancer Center, Medical College of Wisconsin, Milwaukee (B.C.); the Department of Pediatric Hematology–Oncology, Medizinische Hochschule, Hannover, Germany (M.S.); the Leukemia Research Fund, Hematology–Oncology, Institute of Child Health, London (J.C.); Service de Pédiatrie Hématologique, Hôpital Saint Louis, Paris (A.B.); Children's Hospital of Los Angeles and University of Southern California, Los Angeles (P.G.); the Department of Pediatric Oncology, Dana–Farber Cancer Institute and Harvard Medical School, Boston (L.S.); the Department of Pediatric Hematology and Oncology, University of Hamburg, Hamburg, Germany (G.J.-S.); the Department of Pediatric Oncology, Beatrix Children's Hospital, Groningen, the Netherlands (W.K.); St. Jude Children's Research Hospital and the University of Tennessee College of Medicine, Memphis (C.-H.P.); and the Department of Pediatrics, University of Milan and Ospedale San Gerardo, Monza, Italy (G.M.). Other authors were V. Conter, M.D. (Associazione Italiana di Ematologia ed Oncologia Pediatrica); H. Riehm, M.D. (Berlin–Frankfurt–Münster Study Group); N. Heerema, Ph.D. (Children's Cancer Group); S. Sallan, M.D. (Dana–Farber Cancer Institute, Boston); M.-F. Auclerc, M.D. (French Acute Lymphoblastic Leukemia Study Group); J. Pullen, M.D., J. Shuster, Ph.D., and A. Carroll, Ph.D. (Pediatric Oncology Group); S. Raimondi, Ph.D. (St. Jude Children's Research Hospital, Memphis, Tenn.); and S. Richards, M.D. (Medical Research Council, United Kingdom Acute Lymphoblastic Leukaemia).

Address reprint requests to Dr. Aricò at the Clinica Pediatrica, IRCCS Policlinico San Matteo, 27100 Pavia, Italy, or at aricom{at}unipv.it.

Full Text of this Article

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Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia in Children
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N Engl J Med 2000; 343:1043-1044, Oct 5, 2000. Correspondence

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