Childhood Philadelphia-chromosome-positive B-lymphoblastic leukaemia

Abstract

The role of tyrosine-kinase inhibitors of BCR-ABL1 for treatment of de novo Philadelphia-chromosome-positive B-lymphoblastic leukaemia has changed since the inclusion of imatinib in front-line chemotherapy regimens. Results of several phase 2 studies have shown improved outcomes for adults, with long-term survival averaging 50–75% in patients aged 60 years or younger. 1 Thomas DA Faderl S Cortes J et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004; 103: 4396-4407 Crossref PubMed Scopus (453) Google Scholar , 2 Yanada M Takeuchi J Sugiura I et al. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol. 2006; 24: 460-466 Crossref PubMed Scopus (359) Google Scholar , 3 Wassmann B Pfeifer H Goekbuget N et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2006; 108: 1469-1477 Crossref PubMed Scopus (263) Google Scholar , 4 de Labarthe A Rousselot P Huguet-Rigal F et al. Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood. 2007; 109: 1408-1413 Crossref PubMed Scopus (270) Google Scholar , 5 Ribera JM Oriol A Gonzalez M et al. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial. Haematologica. 2010; 95: 87-95 Crossref PubMed Scopus (136) Google Scholar , 6 Bassan R Rossi G Pogliani EM et al. Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00. J Clin Oncol. 2010; 28: 3644-3652 Crossref PubMed Scopus (205) Google Scholar Randomised trials that include a treatment group not taking tyrosine-kinase inhibitors during any phase of treatment have not been done in adults because of the poor prognosis of chemotherapy only; expected 2-year survival is 20–25% in the absence of allogeneic stem-cell transplantation in first complete remission. For childhood Philadelphia-chromosome-positive B-lymphoblastic leukaemia—which accounts for only 3–5% of cases of paediatric acute lymphoblastic leukaemia (ALL)—survival is 45–50% with chemotherapy, which is better than survival in adults but worse than in paediatric patients with Philadelphia-chromosome-negative ALL, for whom survival is more than 85%. 7 Arico M Schrappe M Hunger SP et al. Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between 1995 and 2005. J Clin Oncol. 2010; 28: 4755-4761 Crossref PubMed Scopus (163) Google Scholar Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup studyOur results suggests that imatinib in conjunction with intensive chemotherapy is well tolerated and might be beneficial for treatment of children with Philadelphia-chromosome-positive ALL. Full-Text PDF Open Access