Efficacy and Feasibility of Nelarabine Savage Therapy In Adult Relapsed or Refractory T Cell Acute Lymphoblastic Leukemia (T-ALL) and Lymphoblastic Lymphoma (T-LBL) Strongly Indicates the Introduction of a Nelarabine-Based First Line Regimen

Background.: 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. Aims of the study.: To evaluate the safety profile and the efficacy of Nelarabine treatment as savage therapy, administered to 9 out of 13 adult relapsed or refractory T-ALL or T-LBL patients. Patients and Methods.: After obtaining an informed consent, nine patients (median age 31 years, range 19–37, M/F= 9/0) affected by T-ALL (N=6) and T-LBL (N=3) received a savage therapy with Nelarabine (median cycle=1, range 1–3). Nelarabine was administered at standard adult dosage (1500 mg/sqm on days 1, 3 and 5, every 21). Seven 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 nine patients obtained a complete morphological remission (4 T-ALL patients and 1 T-LBL patient), whereas a partial remission was documented in two cases, with an overall response rate of 78%. 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. Conclusion.: 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, strongly suggesting a good rational for its introduction in first-line chemotherapeutic regimens. This strategy is being explored in our Institution as well as in other ones (Faderl S, MD Anderson).