This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weiss, M. A. Articles by Horgan, D. Search for Related Content PubMed PubMed Citation Articles by Weiss, M. A. Articles by Horgan, D. Social Bookmarking                            What's this?

Pentostatin and Cyclophosphamide: An Effective New Regimen in Previously Treated Patients With Chronic Lymphocytic Leukemia

Mark A. Weiss, Peter G. Maslak, Joseph G. Jurcic, David A. Scheinberg, Timothy B. Aliff, Nicole Lamanna, Stanley R. Frankel, Steven E. Kossman, Denise Horgan

From the Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, and Cornell University Medical College, New York, NY; and the Greenebaum Cancer Center, University of Maryland, Baltimore, MD.

Address reprint requests to Mark Weiss, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; email: weissm{at}mskcc.org.

Purpose: Purine analogs and alkylators are important agents in the treatment of chronic lymphocytic leukemia (CLL). Previously, combinations of fludarabine and chlorambucil were abandoned because of increased toxicity from overlapping myelosuppression and immunosuppression. Of the purine analogs active in CLL, pentostatin may be least myelosuppressive. We hypothesized that combining pentostatin with cyclophosphamide would have less myelotoxicity than combinations using other purine analogs.

Patients and Methods: We studied 23 patients with previously treated CLL. All patients received pentostatin 4 mg/m². Seventeen patients received cyclophosphamide 600 mg/m², and six patients received cyclophosphamide 900 mg/m². Both drugs were administered on day 1 of each cycle, and cycles were repeated every 3 weeks for six treatments. Filgrastim, sulfamethoxazole/trimethoprim, and acyclovir were administered prophylactically. The median number of prior treatment regimens was three (range, one to five) with 13 patients (57%) refractory to prior fludarabine therapy.

Results: The cyclophosphamide 900 mg/m² dose level was associated with moderate to severe nausea, and we chose cyclophosphamide 600 mg/m² as the dose for further study. There were 17 responses (74%; 95% confidence interval, 63% to 85%), including four complete responses. The response rate was 77% in fludarabine-refractory patients. Myelosuppression was acceptable with grade 3/4 neutropenia and thrombocytopenia, seen in 35% and 30% of patients, respectively. The relative sparing of thrombopoiesis can be seen in that only one patient (5%) with an initial platelet count of more than 20,000 required platelet transfusions while receiving therapy.

Conclusion: Pentostatin 4 mg/m² with cyclophosphamide 600 mg/m² is safe and effective in previously treated patients with CLL. On the basis of these results, we are currently studying pentostatin, cyclophosphamide, and rituximab (PCR) therapy in patients with CLL.

Supported in part by grants from Supergen, The Beatrice Renfield Foundation, The Michael Sweig Foundation, and the Archie W. and Grace S. Berry Charitable Foundation.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				N. E. Kay, S. M. Geyer, T. G. Call, T. D. Shanafelt, C. S. Zent, D. F. Jelinek, R. Tschumper, N. D. Bone, G. W. Dewald, T. S. Lin, et al. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia Blood, January 15, 2007; 109(2): 405 - 411. [Abstract] [Full Text] [PDF]

				V. A. Morrison Management of Infectious Complications in Patients with Chronic Lymphocytic Leukemia Hematology, January 1, 2007; 2007(1): 332 - 338. [Abstract] [Full Text] [PDF]

				P. Venugopal and S. A. Gregory Lymphoproliferative disorders ASH Self-Assessment Program, January 1, 2007; 2007(1): 265 - 297. [Full Text] [PDF]

				K. W. L. Yee and S. M. O'Brien Chronic Lymphocytic Leukemia: Diagnosis and Treatment Mayo Clin. Proc., August 1, 2006; 81(8): 1105 - 1129. [Abstract] [Full Text] [PDF]

				N. Lamanna, M. Kalaycio, P. Maslak, J. G. Jurcic, M. Heaney, R. Brentjens, A. D. Zelenetz, D. Horgan, A. Gencarelli, K. S. Panageas, et al. Pentostatin, Cyclophosphamide, and Rituximab Is an Active, Well-Tolerated Regimen for Patients With Previously Treated Chronic Lymphocytic Leukemia J. Clin. Oncol., April 1, 2006; 24(10): 1575 - 1581. [Abstract] [Full Text] [PDF]

				E. Montserrat, C. Moreno, J. Esteve, A. Urbano-Ispizua, E. Gine, and F. Bosch How I treat refractory CLL Blood, February 15, 2006; 107(4): 1276 - 1283. [Abstract] [Full Text] [PDF]

				B. L. Abbott Chronic Lymphocytic Leukemia: Recent Advances in Diagnosis and Treatment Oncologist, January 1, 2006; 11(1): 21 - 30. [Abstract] [Full Text] [PDF]

				M. L. Sorror, M. B. Maris, B. M. Sandmaier, B. E. Storer, M. J. Stuart, U. Hegenbart, E. Agura, T. R. Chauncey, J. Leis, M. Pulsipher, et al. Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning for Advanced Chronic Lymphocytic Leukemia J. Clin. Oncol., June 1, 2005; 23(16): 3819 - 3829. [Abstract] [Full Text] [PDF]

				J. G. Gribben Salvage Therapy for CLL and the Role of Stem Cell Transplantation Hematology, January 1, 2005; 2005(1): 292 - 298. [Abstract] [Full Text] [PDF]

				N. Lamanna, M. Kalaycio, P. Maslak, J. Jurcic, D. A. Scheinberg, A. N. Gencarelli, D. Horgan, and M. A. Weiss Pentostatin and Cyclophosphamide with or without Rituximab Has Significant Activity in Patients with Previously Treated Chronic Lymphocytic Leukemia and Other Low Grade Lymphoid Neoplasms. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 3484 - 3484. [Abstract]

				J. C. Byrd, S. Stilgenbauer, and I. W. Flinn Chronic Lymphocytic Leukemia Hematology, January 1, 2004; 2004(1): 163 - 183. [Abstract] [Full Text] [PDF]