Correspondence
Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia in Children
N Engl J Med 2000; 343:1043-1044October 5, 2000
- Article
To the Editor:
In the April 6 issue, Aricò et al.1 report on a retrospective study of the characteristics of and treatment for Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL) in children. The authors state that Ph-positive ALL is associated with a poor prognosis and that transplantation of bone marrow from HLA-matched related donors is superior to other types of transplantation and to intensive chemotherapy alone. The authors provide important information on Ph-positive ALL in childhood, but we would like to make some comments about the study design.
The study by Aricò et al. showed that postinduction therapy is the most important problem in the treatment of Ph-positive ALL. To investigate the optimal postinduction treatment, they retrospectively analyzed outcomes for 267 children who had a remission after induction therapy. We agree that a retrospective survey can collect a large amount of information, but such studies may easily be biased. For this reason, it is important to determine whether the study groups had similar characteristics. We assume that the chemotherapy group in the study by Aricò et al. included many patients who could not undergo transplantation because of early relapse, infections, or severe organ damage, even if suitable related donors were available. Considering that the interval between diagnosis and transplantation was approximately six months, on average, were there any differences between the condition of the patients at the time of transplantation in the group of children who underwent this treatment and the condition of those in the chemotherapy group six months after the diagnosis?
The era during which the treatment was given is another important factor, because important advances have been made in the treatment of acute leukemia and in supportive care.2,3 In the study by Aricò et al., 65 percent of the patients in the chemotherapy group and 37 percent of those in the transplantation group were treated before 1992, a difference that is statistically significant (P<0.001). The superiority of bone marrow transplantation to chemotherapy may be due to a temporal bias.
3 ReferencesYasuhiro Oki, M.D.
Yukiko Kishi, M.D.
Masahiro Kami, M.D.
Toranomon Hospital, Tokyo 105-8470, Japan1
Arico M ,Valsecchi MG ,Camitta B , et al. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med 2000;342:998-1066
Full Text | Web of Science | Medline2
Pui CH . Recent advances in the biology and treatment of childhood acute lymphoblastic leukemia. Curr Opin Hematol 1998;5:292-301
CrossRef | Medline3
Berman E . Recent advances in the treatment of acute leukemia. Curr Opin Hematol 1997;4:256-260
CrossRef | Medline
To the Editor:
In their otherwise superb article, Aricò et al. fail to mention the expression of myeloid antigens by leukemic cells as one of the variables that may influence responsiveness to therapy and overall survival.
In a prospective observational study of 236 patients, Wiersma et al.1 found that the expression in leukemic cells of at least one of three myeloid-associated antigens (CD33, CD13, and CD14) was an important predictor of relapse and was associated with a poor response to chemotherapy. In a multivariate analysis, myeloid-antigen expression was found to be the most significant prognostic factor with respect to event-free and overall survival.
1 ReferencesOren Fruchter, M.D.
29 Greenbaum St., Haifa 34987, Israel1
Wiersma SR ,Ortega J ,Sobel E ,Weinberg KI . Clinical importance of myeloid-antigen expression in acute lymphoblastic leukemia of childhood. N Engl J Med 1991;324:800-808
Full Text | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Oki et al. raise two important issues. There was no indication in our series that patients treated with chemotherapy were in worse clinical condition than those treated with transplantation. To adjust for differences in time to transplantation and other prognostic factors, we used a Cox regression model in the analysis. Treatment was considered to be a time-dependent factor, and each patient was included in the chemotherapy-only group until transplantation was performed (if it was performed), at which point the patient was shifted to the transplantation group. This is a well-accepted method of minimizing potential bias.
The difference in the proportion of patients treated with chemotherapy or transplantation before 1992 and the proportion treated more recently could have contributed to the improved outcome in the transplantation group. However, whereas improvements in the selection of donors and in supportive care have undoubtedly increased the rate of success of transplantation, there has been little, if any, change in the efficacy of chemotherapy for patients with Ph-positive ALL.
Dr. Fruchter asks about the prognostic importance of the expression of myeloid-associated antigens. We did not mention this factor in our article because virtually all recent studies have shown that it lacks prognostic importance in patients with ALL who receive current therapy.1-3
A list of the institutions that participated in the study was omitted from our article. Those institutions (and their representatives) were as follows: the Associazione Italiana di Ematologia ed Oncologia Pediatrica, Italy (M. Aricò, M.G. Valsecchi, G. Masera, V. Conter); the Berlin–Frankfurt–Münster Study Group, Germany (M. Schrappe, H. Riehm); the Children's Cancer Group, United States (P. Gaynon, N. Heerema); the Dana–Farber Cancer Institute, United States (L. Silverman, S. Sallan); the French Acute Lymphoblastic Leukemia Study Group, France (A. Baruchel, M.-F. Auclerc); the Pediatric Oncology Group, United States (B. Camitta, J. Pullen, J. Shuster, A. Carroll); St. Jude Children's Research Hospital, United States (C.-H. Pui, S. Raimondi); the Medical Research Council, United Kingdom Acute Lymphoblastic Leukaemia Study, United Kingdom (J. Chessells, S. Richards); the Cooperative Acute Lymphoblastic Leukemia Study, Germany (G. Janka-Schaub); and the Dutch Childhood Leukemia Study Group, The Hague, the Netherlands (W. Kamps).
3 ReferencesMaria Grazia Valsecchi, Ph.D.
University of Verona, 37134 Verona, ItalyMartin Schrappe, M.D.
Medizinische Hochschule, D-30625 Hannover, GermanyChing-Hon Pui, M.D.
St. Jude Children's Research Hospital, Memphis, TN 381051
Putti MC ,Rondelli R ,Cocito MG , et al. Expression of myeloid markers lacks prognostic impact in children treated for acute lymphoblastic leukemia: Italian experience in AIEOP-ALL 88-91 studies. Blood 1998;92:795-801
Web of Science | Medline2
Pui CH ,Rubnitz JE ,Hancock ML , et al. Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia. J Clin Oncol 1998;16:3768-3773
Web of Science | Medline3
Schrappe M ,Reiter A ,Ludwig WD , et al. Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. Blood 2000;95:3310-3322
Web of Science | Medline
