title: High single-drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation.
abstract: Nelarabine, a purine analog with T-cell specific action, has been approved for relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma (ALL/LBL). This is a report of a single-arm phase 2 study conducted in adults (18-81 years of age) with relapsed/refractory T-ALL/LBL. After 1 or 2 cycles, 45 of 126 evaluable patients (36%) achieved complete remission (CR), 12 partial remission (10%), and 66 (52%) were refractory. One treatment-related death was observed, and 2 patients were withdrawn before evaluation. A total of 80% of the CR patients were transferred to stem cell transplantation (SCT). Overall survival was 24% at 1 year (11% at 6 years). After subsequent SCT in CR, survival was 31% and relapse-free survival 37% at 3 years. Transplantation-related mortality was 11%. Neurologic toxicities of grade I-IV/grade III-IV were observed in 13%/4% of the cycles and 16%/7% of the patients. This largest study so far with nelarabine in adults showed impressive single-drug activity in relapsed T-ALL/T-LBL. The drug was well tolerated, even in heavily pretreated patients. A high proportion of CR patients were transferred to SCT with low mortality but a high relapse rate. Exploration of nelarabine in earlier stages of relapse (eg, increasing minimal residual disease), in front-line therapy, and in combination is warranted.
authors.affiliation: Department of Medicine II, Hematology/Oncology, Goethe University Hospital, Frankfurt, Germany. goekbuget@em.uni-frankfurt.de
authors.forename: Nicola
authors.initials: N
authors.lastname: Gökbuget
authors.forename: Nadezda
authors.initials: N
authors.lastname: Basara
authors.forename: Herrad
authors.initials: H
authors.lastname: Baurmann
authors.forename: Joachim
authors.initials: J
authors.lastname: Beck
authors.forename: Monika
authors.initials: M
authors.lastname: Brüggemann
authors.forename: Helmut
authors.initials: H
authors.lastname: Diedrich
authors.forename: Björn
authors.initials: B
authors.lastname: Güldenzoph
authors.forename: Gernot
authors.initials: G
authors.lastname: Hartung
authors.forename: Heinz-August
authors.initials: HA
authors.lastname: Horst
authors.forename: Andreas
authors.initials: A
authors.lastname: Hüttmann
authors.forename: Guido
authors.initials: G
authors.lastname: Kobbe
authors.forename: Ralph
authors.initials: R
authors.lastname: Naumann
authors.forename: Richard
authors.initials: R
authors.lastname: Ratei
authors.forename: Albrecht
authors.initials: A
authors.lastname: Reichle
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelljes
authors.forename: Andreas
authors.initials: A
authors.lastname: Viardot
authors.forename: Mohammed
authors.initials: M
authors.lastname: Wattad
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D011355:Prodrugs / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D033581:Stem Cell Transplantation / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D011355:Prodrugs; C104457:nelarabine