Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between 1995 and 2005 - PubMed (original) (raw)

. 2010 Nov 1;28(31):4755-61.

doi: 10.1200/JCO.2010.30.1325. Epub 2010 Sep 27.

Martin Schrappe, Stephen P Hunger, William L Carroll, Valentino Conter, Stefania Galimberti, Atsushi Manabe, Vaskar Saha, André Baruchel, Kim Vettenranta, Keizo Horibe, Yves Benoit, Rob Pieters, Gabriele Escherich, Lewis B Silverman, Ching-Hon Pui, Maria Grazia Valsecchi

Affiliations

Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between 1995 and 2005

Maurizio Aricò et al. J Clin Oncol. 2010.

Abstract

Purpose: In a previous analysis of 326 children with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL) treated between 1986 and 1996, hematopoietic stem-cell transplantation from HLA-matched related donors, but not from unrelated donors, offered a superior outcome than chemotherapy alone. To evaluate the impact of recent improvements in chemotherapy and transplantation, we performed a similar analysis on patients treated in the following decade.

Patients and methods: We analyzed 610 patients with Ph-positive ALL treated between 1995 and 2005 without tyrosine kinase inhibitor therapy. The median follow-up duration was 6.3 years.

Results: Complete remission was achieved in 89% of patients. The 7-year event-free survival and overall survival rates were superior in the present cohort compared with the previous cohort (32.0% ± 2.0% v 25.0% ± 3.0, respectively, P = .007; and 44.9% ± 2.2% v 36.0% ± 3.0%, respectively, P = .017). Compared with chemotherapy alone, transplantation with matched related donors or unrelated donors in first remission (325 patients) showed an advantage with increasing follow-up, suggesting greater protection against late relapses (hazard ratio at 5 years, 0.37; P < .001). In the multivariate Cox regression analysis accounting for treatment (transplantation v no transplantation), age, leukocyte count, and early response had independent impact on treatment outcome.

Conclusion: Clinical outcome of children and adolescents with Ph-positive ALL has improved with advances in transplantation and chemotherapy. Transplantations with matched related donors and unrelated donors were equivalent and offered better disease control compared with chemotherapy alone. Age, leukocyte count, and early treatment response were independent prognostic indicators. The results of this study will serve as a historical reference to evaluate the therapeutic impact of tyrosine kinase inhibitors on the outcome of Ph-positive ALL.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Fig 1.

Estimates of (A) disease-free survival and (B) overall survival (± SE) in 542 patients treated with hematopoietic stem-cell transplantation (HSCT) or chemotherapy only. The curves have been adjusted for waiting time to transplantation, so that the zero on the time axis corresponds to the median time from first complete remission to transplantation (5.1 months); patients were assigned to this treatment group in a time-dependent fashion. Five-year estimates (from remission) are shown.

Fig 2.

Fig 2.

Estimates of disease-free survival (± SE) in 281 patients with Philadelphia chromosome–positive childhood acute lymphoblastic leukemia treated with hematopoietic stem-cell transplantation from HLA-matched related or unrelated donors before or after year 2000. Five-year estimates are shown.

Fig 3.

Fig 3.

Estimates of disease-free survival (± SE) in good or poor responders as defined by (A) day 8 peripheral blood or (B) day 8 to 21 bone marrow evaluation. Five-year estimates are shown. CR1, first complete remission.

Fig 4.

Fig 4.

Estimates of disease-free survival (± SE) in 540 patients with Philadelphia chromosome–positive childhood acute lymphoblastic leukemia. The patients were classified according to modified Rome–National Cancer Institute criteria as follows: better prognosis (10 years of age or younger with a leukocyte count of < 50,000/μL), intermediate prognosis (intermediate-risk features), and worst prognosis (any age with a leukocyte count of > 100,000/μL). Five-year estimates are shown.

Fig A1.

Fig A1.

Estimates of (A) disease-free survival and (B) overall survival (± SE) in 149 patients with good early response and better modified Rome–National Cancer Institute criteria treated with hematopoietic stem-cell transplantation (HSCT) or chemotherapy only. The curves have been adjusted for waiting time to transplantation, so that the zero on the time axis corresponds to the median time from first complete remission to transplantation (5.1 months); patients were assigned to this treatment group in a time-dependent fashion. Five-year estimates (from remission) are shown.

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