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

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.

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.

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.

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.

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).

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 integreted program (PIO), Programma di Ricerca Regione – Università 2007 – 2009.

Baccarani:NOVARTIS: Honoraria; BRISTOL MYERS SQUIBB: Honoraria. Martinelli:Novartis: Consultancy, Honoraria; BMS: Honoraria; Pfizer: Consultancy.