PS952 NELARABINE AS SALVAGE THERAPY FOR PEDIATRIC PATIENTS WITH RELAPSED T‐ALL
Authors: L. Vinti, L. Strocchio, K. Girardi, L. Antonetti, F. Locatelli
Journal: HemaSphere (2019)

Background: Despite improvements in first‐line treatment of childhood T‐cell‐lineage acute lymphoblastic leukemia (T‐ALL), refractory/relapsed T‐ALL is usually associated with a dismal prognosis, mostly due to a failure to achieve a 2 nd morphological/molecular complete remission (CR). Long‐term survival can be obtained through the use of allogeneic hematopoietic stem cell transplantation (HSCT). Nelarabine is a purine nucleoside antimetabolite with high T‐cell cytotoxicity, shown to be effective in relapsed T‐ALL both as a single agent and in combination with other chemotherapeutic drugs. Aims: In an attempt to obtain CR, while reducing chemotherapy‐related toxicity in 16 pretreated pediatric patients with resistant/relapsed T‐ALL, we explored the use of Nelarabine in addition to a standard AIEOP‐BFM‐based Consolidation IB Protocol backbone, as a salvage/reinduction treatment. Methods: The treatment schedule was based on the backbone of the front‐line Consolidation IB Protocol of the AIEOP‐BFM ALL2009 Trial (6‐mercaptopurine for 28 days, with 2 pulses of cyclophosphamide 1000 mg/m 2 on the first and last days, and four 4‐day courses of low dose‐cytarabine 75 mg/m 2 /day), with the addition of Nelarabine, administered in 1 or 2 courses of 3 days each (after the second and fourth cytarabine courses) at a dose of 4.5 gr/m 2 four each course Results: Between March 2010 and October 2018, 16 children with relapsed/resistant T cell‐lineage acute leukemia were treated with ‘IB Protocol+Nelarabine’ course at the Pediatric Hematology/Oncology Department of the IRCCS Bambino Gesù Childrens’ Hospital, Rome, Italy. All but one patients were male; age ranged from 2 to 15 years (median 11) at time of diagnosis and from 5 to 16 (median 11,5) at relapse. Four patients had Central Nervous System (CNS) involvement at diagnosis. Two patients received fase IB + Nelarabine as first‐line treatment because of molecularly resistant disease (MRD) while in 14 patients IB + Nelarabine was employed after full‐blown relapse. Six of these 14 relapsed patients experienced a combined bone marrow (BM) and extramedullary relapse (CNS involvement in 4), 2 extramedullary relapse, the remaining 6 showing isolated BM relapse. Ten patients obtained complete remission after IB+ Nelarabine treatment; 2 patients experienced partial response; 1 stable disease; 1 progressive disease. Twelve patients underwent allogeneic HSCT. The remaining 4 patients were not transplanted because of persistent disease (3) or neurological toxicity (1)Eleven patient are currently alive, 10 in CR and 1 with persistent disease. Five patients died for progressive disease. Neurological toxicity (self‐limiting grade 2 peripheral motor/sensory neuropathy) occurred in 4 patients, while 1 patient had grade 4 peripheral motor neuropathy and central neurotoxicity. Summary/Conclusion: A polychemotherapy regimen based on the use of Consolidation IB protocol, in combination with the T‐cell‐specific agent Nelarabine over a 6 week‐period, instead of intensive high‐dose multidrug short‐courses, can be a safe option to achieve 2 nd CR, in pretreated patients with relapsed T‐cell‐lineage acute leukemia, providing a bridge to allogeneic HSCT. A larger number of patients with long‐term follow‐up is needed to assess the effectiveness and safety of this approach image