Journal of Clinical Oncology, Vol 10, 364-370, Copyright © 1992 by American Society of Clinical Oncology

ARTICLES

2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia

VM Santana, J Mirro Jr, C Kearns, MJ Schell, W Crom and RL Blakley
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38101.

PURPOSE: The purine analog 2-chlorodeoxyadenosine (2-CDA) was well tolerated and showed promising anti-leukemic activity in a phase I trial conducted at St Jude Children's Research Hospital. To substantiate and extend this result, we performed a phase II trial in a representative group of children and young adults with relapsed acute leukemia. PATIENTS AND METHODS: Twenty-four patients (median age, 11 years) with acute myeloid or lymphoid leukemia in first or later relapse (acute myeloid leukemia [AML], 17; acute lymphoid leukemia [ALL], seven) were given continuous infusion 2-CDA for 5 days at 8.9 mg/m2/d. Patients with residual blast cells 10 days after treatment received a second course of 2-CDA that was identical to the first. Detailed pharmacokinetic studies were performed on plasma collected from five patients. RESULTS: Eight (47%) of the 17 patients with AML had complete hematologic remissions (four after the initial course of 2- CDA), and two (12%) had partial remissions, for a total response rate of 59%. Only one child with ALL achieved remission. Seven of the responding patients underwent allogeneic or autologous bone marrow transplantation, with six remaining free of leukemia for a median of 7 months (range, 1 to 11 months). The major form of drug-induced toxicity was hematologic, with severe neutropenia and thrombocytopenia (National Cancer Institute [NCI] grade 3 or 4) developing in 34 of the 36 courses of 2-CDA. In responding patients, the median times to recovery of neutrophil counts greater than 0.5 x 10(9)/L and platelet counts greater than 50 x 10(9)/L were 18 and 21 days, respectively. There were no deaths due to toxicity. The mean steady-state plasma concentration of 2-CDA was 34.6 nmol/L (range, 20 to 54 nmol/L). CONCLUSION: 2-CDA given by prolonged continuous infusion has clinically significant activity against AML and merits further testing in multidrug regimens for this disease.

This article has been cited by other articles:

				G. J.L. Kaspers and C. M. Zwaan Pediatric acute myeloid leukemia: towards high-quality cure of all patients Haematologica, November 1, 2007; 92(11): 1519 - 1532. [Abstract] [Full Text] [PDF]

				S. Jeha, V. Gandhi, K. W. Chan, L. McDonald, I. Ramirez, R. Madden, M. Rytting, M. Brandt, M. Keating, W. Plunkett, et al. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia Blood, February 1, 2004; 103(3): 784 - 789. [Abstract] [Full Text] [PDF]

				R. J. Wells, M. T. Adams, T. A. Alonzo, R. J. Arceci, J. Buckley, A. B. Buxton, K. Dusenbery, A. Gamis, M. Masterson, T. Vik, et al. Mitoxantrone and Cytarabine Induction, High-Dose Cytarabine, and Etoposide Intensification for Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia: Children's Cancer Group Study 2951 J. Clin. Oncol., August 1, 2003; 21(15): 2940 - 2947. [Abstract] [Full Text] [PDF]

				K. R. Crews, V. Gandhi, D. K. Srivastava, B. I. Razzouk, X. Tong, F. G. Behm, W. Plunkett, S. C. Raimondi, C.-H. Pui, J. E. Rubnitz, et al. Interim Comparison of a Continuous Infusion Versus a Short Daily Infusion of Cytarabine Given in Combination With Cladribine for Pediatric Acute Myeloid Leukemia J. Clin. Oncol., October 15, 2002; 20(20): 4217 - 4224. [Abstract] [Full Text] [PDF]

				R. A. Krance, C. A. Hurwitz, D. R. Head, S. C. Raimondi, F. G. Behm, K. R. Crews, D. K. Srivastava, H. Mahmoud, W. M. Roberts, X. Tong, et al. Experience With 2-Chlorodeoxyadenosine in Previously Untreated Children With Newly Diagnosed Acute Myeloid Leukemia and Myelodysplastic Diseases J. Clin. Oncol., June 1, 2001; 19(11): 2804 - 2811. [Abstract] [Full Text] [PDF]

				K. Lotfi, E. Mansson, T. Spasokoukotskaja, B. Pettersson, J. Liliemark, C. Peterson, S. Eriksson, and F. Albertioni Biochemical Pharmacology and Resistance to 2-Chloro-2'-arabino-fluoro-2'-deoxyadenosine, a Novel Analogue of Cladribine in Human Leukemic Cells Clin. Cancer Res., September 1, 1999; 5(9): 2438 - 2444. [Abstract] [Full Text] [PDF]

				A. Saven and C. Burian Cladribine Activity in Adult Langerhans-Cell Histiocytosis Blood, June 15, 1999; 93(12): 4125 - 4130. [Abstract] [Full Text] [PDF]

				A. K Morris, J. M Kolesar, and J. G Kuhn Review : Purine nucleoside analogs: fludarabine, entostatin and cladribine: Part 3: cladribine Journal of Oncology Pharmacy Practice, June 1, 1997; 3(2): 94 - 109. [PDF]

				J Gruber, F Geisen, R Sgonc, A Egle, A Villunger, G Boeck, G Konwalinka, and R Greil 2',2'-Difluorodeoxycytidine (gemcitabine) induces apoptosis in myeloma cell lines resistant to steroids and 2-chlorodeoxyadenosine (2-CdA) Stem Cells, May 1, 1996; 14(3): 351 - 362. [Abstract]