Background: Precursor T cell LBL/ALL occurs most frequently in late childhood, adolescence, and young adulthood, with a 2:1 male predominance; it comprises 15 and 25 percent of childhood and adult ALL, respectively, and 2 percent of adult non-Hodgkin lymphoma. Nelarabine is an anticancer prodrug of arabinofuranosylguanine (ara-G); it inhibits DNA synthesis and leads to high molecular weight DNA fragmentation and cell death. Aims: Nelarabine has showed relevant efficacy in phase II clinical trials, both in pediatric and in adult LBL/ALLpopulations. Methods:We report clinical outcome results of 9 newly diagnosed and younger than 60 yearsT-ALL patients (median age 29 years, range 22-45 years, 3/6 M/F, 8 T-ALL, 1 T-LBL) treated according to pediatric-like adapted schedule. Cytogentics data and molecular biologic features will be provided on site. Induction cycle included Vincristine, daunoblastine, L-asparaginase and Prednisone. After induction, all the patients received consolidation therapy with cyclophosphamyde, L-asparaginase, Cytarabine and 6-Mercaptopurine. Subsequently all the patients receveid Nelarabine 1500 mg/sqm (days 1-3-5 every 21) for two cycles. All the patients shared the same strategy for intensification, which consisted in allogenic stem cell transplantation, if available, or additional courses of consolidation chemotherapy. Durations of complete remission (CR) and overall survival (OS) were estimated according to the Kaplan-Meier method. The CR duration was dated from start of CR to first evidence of disease recurrence. Results: After a single induction course, 9/9 patients obtained a CR (100%). Eight patients underwent an allogenic bone marrow transplantation. Aftera median follow-up of 24 months, 7/9 patients (78%) are alive in CR. The median CR duration and OS were 13.4 and 24.4 months, respectively. Neurological toxicity of grade 3has not been reported. We did not observe grade 3-4 haematological toxicity. Summary / Conclusion: Nelarabine is a promising drug, which induces a remarkable complete remission rate at the expense of a very low and manageable toxicity.
Sartor, C., Abbenante, M., Papayannidis, C., Iacobucci, I., Paolini, S., Ottaviani, E., et al. (2013). NELARABINE FRONT-LINE THERAPY FOR ADULT T-LYMPHOBLASTIC LEUKAEMIA/LYMPHOMA (T-LBL/ALL): PRELIMINARY RESULTS OF A SINGLE CENTRE EXPERIENCE.
NELARABINE FRONT-LINE THERAPY FOR ADULT T-LYMPHOBLASTIC LEUKAEMIA/LYMPHOMA (T-LBL/ALL): PRELIMINARY RESULTS OF A SINGLE CENTRE EXPERIENCE
LONETTI, ANNALISA;
2013
Abstract
Background: Precursor T cell LBL/ALL occurs most frequently in late childhood, adolescence, and young adulthood, with a 2:1 male predominance; it comprises 15 and 25 percent of childhood and adult ALL, respectively, and 2 percent of adult non-Hodgkin lymphoma. Nelarabine is an anticancer prodrug of arabinofuranosylguanine (ara-G); it inhibits DNA synthesis and leads to high molecular weight DNA fragmentation and cell death. Aims: Nelarabine has showed relevant efficacy in phase II clinical trials, both in pediatric and in adult LBL/ALLpopulations. Methods:We report clinical outcome results of 9 newly diagnosed and younger than 60 yearsT-ALL patients (median age 29 years, range 22-45 years, 3/6 M/F, 8 T-ALL, 1 T-LBL) treated according to pediatric-like adapted schedule. Cytogentics data and molecular biologic features will be provided on site. Induction cycle included Vincristine, daunoblastine, L-asparaginase and Prednisone. After induction, all the patients received consolidation therapy with cyclophosphamyde, L-asparaginase, Cytarabine and 6-Mercaptopurine. Subsequently all the patients receveid Nelarabine 1500 mg/sqm (days 1-3-5 every 21) for two cycles. All the patients shared the same strategy for intensification, which consisted in allogenic stem cell transplantation, if available, or additional courses of consolidation chemotherapy. Durations of complete remission (CR) and overall survival (OS) were estimated according to the Kaplan-Meier method. The CR duration was dated from start of CR to first evidence of disease recurrence. Results: After a single induction course, 9/9 patients obtained a CR (100%). Eight patients underwent an allogenic bone marrow transplantation. Aftera median follow-up of 24 months, 7/9 patients (78%) are alive in CR. The median CR duration and OS were 13.4 and 24.4 months, respectively. Neurological toxicity of grade 3has not been reported. We did not observe grade 3-4 haematological toxicity. Summary / Conclusion: Nelarabine is a promising drug, which induces a remarkable complete remission rate at the expense of a very low and manageable toxicity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
