title: Nelarabine in the treatment of pediatric and adult patients with T-cell acute lymphoblastic leukemia and lymphoma.
abstract: T-cell acute lymphoblastic leukemia (ALL) and lymphoma (LBL) are aggressive hematologic neoplasms that are treated with combination chemotherapy in the frontline, but have limited options in the relapsed or refractory setting. Based on observations in patients with purine nucleoside phosphorylase (PNP) deficiency, a guanosine nucleoside analogue, arabinosylguanine (ara-G) was developed that provided T-cell specificity. Nelarabine was developed as the water-soluble, clinically useful-prodrug of ara-G and based on its activity was approved for the treatment of relapsed or refractory T-ALL/LBL. Areas covered: In this narrative review, we will summarize the preclinical studies, early dose-finding studies, and efficacy studies that led to approval of nelarabine. The review will succinctly cover response rates and safety signals reported during clinical development. We will also cover more recent work with nelarabine, including combination studies, modified dosing schedules, and frontline treatment approaches. Expert commentary: Based on evidence from the literature review and our own experience with nelarabine, we conclude that it is an effective agent in the treatment of T-cell malignancies. Understanding the factors that modulate the risk of dose-limiting neurotoxicity, how to mitigate this toxicity, and how to safely combine it with other active agents will continue to broaden its use.
authors.affiliation: a Departments of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Tapan M
authors.initials: TM
authors.lastname: Kadia
authors.affiliation: a Departments of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.|b Departments of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Varsha
authors.initials: V
authors.lastname: Gandhi
mesh_terms: D000328:Adult; D000367:Age Factors; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001087:Arabinonucleosides; C104457:nelarabine
keywords: GW506U78; Nucleoside analogue; T-cell; ara-G; arabinosylguanine; compound 506; nelarabine; pediatric ALL; purine nucleoside phosphorylase