Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group.
ABSTRACT Children's Oncology Group study AALL00P2 was designed to assess the feasibility and safety of adding nelarabine to a BFM 86-based chemotherapy regimen in children with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL).
In stage one of the study, eight patients with a slow early response (SER) by prednisone poor response (PPR; ≥ 1,000 peripheral blood blasts on day 8 of prednisone prephase) received chemotherapy plus six courses of nelarabine 400 mg/m(2) once per day; four patients with SER by high minimal residual disease (MRD; ≥ 1% at day 36 of induction) received chemotherapy plus five courses of nelarabine; 16 patients with a rapid early response (RER) received chemotherapy without nelarabine. In stage two, all patients received six 5-day courses of nelarabine at 650 mg/m(2) once per day (10 SER patients [one by MRD, nine by PPR]) or 400 mg/m(2) once per day (38 RER patients; 12 SER patients [three by MRD, nine by PPR]).
The only significant difference in toxicities was decreased neutropenic infections in patients treated with nelarabine (42% with v 81% without nelarabine). Five-year event-free survival (EFS) rates were 73% for 11 stage one SER patients and 67% for 22 stage two SER patients treated with nelarabine versus 69% for 16 stage one RER patients treated without nelarabine and 74% for 38 stage two RER patients treated with nelarabine. Five-year EFS for all patients receiving nelarabine (n = 70) was 73% versus 69% for those treated without nelarabine (n = 16).
Addition of nelarabine to a BFM 86-based chemotherapy regimen was well tolerated and produced encouraging results in pediatric patients with T-ALL, particularly those with a SER, who have historically fared poorly.
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ABSTRACT: To review and summarize the available evidence on factors predicting prognosis of children with relapsed acute lymphoblastic leukemia (ALL) and on the currently used treatment strategies, as well as on the most promising and innovative molecular or cellular therapies. Relapse still represents the most common cause of treatment failure, occurring in approximately 15-20% of childhood ALL. Risk-oriented standard salvage regimens are mostly based on combinations of the same agents incorporated in frontline therapies. Allogeneic hematopoietic stem cell transplantation (HSCT) is largely employed as postremission therapy, being superior to chemotherapy in high-risk patients. With conventional therapies including HSCT, 40-50% of children with relapsed ALL can be rescued. Thus, innovative approaches are needed to further improve the outcome of patients, especially when carrying poor prognostic factors. The last decade has witnessed the development of novel agents, including nucleoside analogues, anti-CD22 monoclonal antibodies and bi-specific, anti-CD3/CD19 antibodies, together with new formulations of existing chemotherapeutic agents and targeted molecules, such as tyrosine kinase inhibitors and FLT3 inhibitors. A significant proportion of children with relapsed ALL are salvaged by risk-oriented therapies. Novel agents should be integrated into combination regimens with the aim of further improving outcome of patients.Current opinion in oncology 09/2013; · 3.76 Impact Factor
- Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 10/2013; · 10.16 Impact Factor
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ABSTRACT: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications.Medicina Clínica 03/2014; · 1.25 Impact Factor