Introduction. T-ALL represents 15% of childhood and 25% of adult ALL. Despite a cure rate of almost 80% in children and adolescents, adult ALL remains a difficult disease to cure, due to a high risk of relapse. Effective treatment of relapsed acute T-ALL is limited with a low CR rate, a high treatment-related mortality, and a very low prolonged disease-free survival. Nelarabine is a pro-drug of ara-G, approved by the FDA for the treatment of T-ALL and T-LBL that have not responded to or has relapsed after treatment with at least 2 chemotherapy regimens. Similar to other nucleoside analogues, Nelarabine acts by inhibiting DNA synthesis and inducing apoptosis in malignant cells. Our aim was to evaluate safety profile and efficacy of Nelarabine treatment as savage therapy in 9 adult relapsed or refractory T-ALL or T-LBL. Methods. After obtaining an informed consent, ten patients (median age 31 years, range 19-37, M/F=9/0) affected by T-ALL (N=6) and T-LBL (N=4) received a savage therapy with Nelarabine (median cycle=1, range 1-3). Nelarabine was administered at standard adult dosage (1500 mg2 on days 1, 3 and 5, every 21). Eight patients were relapsed after two previous chemtotherapy regimens, including allogeneic bone marrow transplantation; the remaining two patients were primary resistant to standard induction treatment. Results. Five out of ten patients obtained a complete morphological remission (4 T-ALL patients and 1 T-LBL patient), whereas a partial remission was documented in three cases, with an overall response rate of 80%. Median duration of complete response was 6 weeks (range 3-6 weeks). Nelarabine was well tolerated, and no significant adverse events were registered. Extra- hematological neurological toxicity, not clearly related to the drug, occurred in two cases, determining, in one patient a complete and irreversible paraplegia, and in the second one a condition of mental confusion (grade III), which resolved after few days. Conclusions. In our experience Nelarabine was successfully administered in such a high risk patients population. The drug showed a relevant efficacy and a good safety profile. Acknowledgments. This work was supported by European LeukemiaNet, AIL, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, PRIN 2008, Ateneo RFO grants, Project of integrated program (PIO), Programma di Ricerca Regione - Università 2007-2009.
EFFICACY, FEASIBILITY AND SAFETY OF NELARABINE SAVAGE THERAPY IN ADULT RELAPSED OR REFRACTORY T CELL ACUTE LYMPHOBLASTIC LEUKEMIA (T-ALL) OR LYMPHOBLASTIC LYMPHOMA (T-LBL): THE BOLOGNA EXPERIENCE
PAPAYANNIDIS, CRISTINA;IACOBUCCI, ILARIA;ABBENANTE, MARIACHIARA;PAOLINI, STEFANIA;Parisi S;LONETTI, ANNALISA;OTTAVIANI, EMANUELA;TESTONI, NICOLETTA;BALDAZZI, CARMEN;CURTI, ANTONIO;CLISSA, CRISTINA;MARTINELLI, GIOVANNI
2010
Abstract
Introduction. T-ALL represents 15% of childhood and 25% of adult ALL. Despite a cure rate of almost 80% in children and adolescents, adult ALL remains a difficult disease to cure, due to a high risk of relapse. Effective treatment of relapsed acute T-ALL is limited with a low CR rate, a high treatment-related mortality, and a very low prolonged disease-free survival. Nelarabine is a pro-drug of ara-G, approved by the FDA for the treatment of T-ALL and T-LBL that have not responded to or has relapsed after treatment with at least 2 chemotherapy regimens. Similar to other nucleoside analogues, Nelarabine acts by inhibiting DNA synthesis and inducing apoptosis in malignant cells. Our aim was to evaluate safety profile and efficacy of Nelarabine treatment as savage therapy in 9 adult relapsed or refractory T-ALL or T-LBL. Methods. After obtaining an informed consent, ten patients (median age 31 years, range 19-37, M/F=9/0) affected by T-ALL (N=6) and T-LBL (N=4) received a savage therapy with Nelarabine (median cycle=1, range 1-3). Nelarabine was administered at standard adult dosage (1500 mg2 on days 1, 3 and 5, every 21). Eight patients were relapsed after two previous chemtotherapy regimens, including allogeneic bone marrow transplantation; the remaining two patients were primary resistant to standard induction treatment. Results. Five out of ten patients obtained a complete morphological remission (4 T-ALL patients and 1 T-LBL patient), whereas a partial remission was documented in three cases, with an overall response rate of 80%. Median duration of complete response was 6 weeks (range 3-6 weeks). Nelarabine was well tolerated, and no significant adverse events were registered. Extra- hematological neurological toxicity, not clearly related to the drug, occurred in two cases, determining, in one patient a complete and irreversible paraplegia, and in the second one a condition of mental confusion (grade III), which resolved after few days. Conclusions. In our experience Nelarabine was successfully administered in such a high risk patients population. The drug showed a relevant efficacy and a good safety profile. Acknowledgments. This work was supported by European LeukemiaNet, AIL, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, PRIN 2008, Ateneo RFO grants, Project of integrated program (PIO), Programma di Ricerca Regione - Università 2007-2009.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
