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 Cladribine

cladribine is a purine nucleoside antimetabolite analogue. Cladribine triphosphate, a phosphorylated metabolite of cladribine, incorporates into DNA, resulting in single-strand breaks in DNA, depletion of nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP), and apoptosis. Because this agent is resistant to adenosine deaminase, an enzyme that inactivates some antineoplastic agents, it is selectively toxic to lymphocytes and monocytes which exhibit little deoxynucleotide deaminase activity. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Cladribine (Leustatin) is a drug used to treat hairy cell leukemia (leukemic reticuloendotheliosis) and multiple sclerosis. Its chemical name is 2-chlorodeoxyadenosine (2CDA). As a purine analog, it is a synthetic anti-cancer agent that also suppresses the immune system. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. It is easily destroyed by normal cells except for blood cells, with the result that it produces relatively few side effects and results in very little non-target cell loss.

Cladribine is indicated for the treatment of symptomatic hairy cell leukemia (HCL). It is under investigation for other B cell leukemias and lymphomas, such as mantle cell lymphoma,[2], and for use in the treatment of multiple sclerosis. In January 2010, a large clinical trial involving more than 1000 patients documented significant reduction in relapse rates in multiple sclerosis patients with use of oral cladribine and thus making its use as the first oral medication in multiple sclerosis patients, most likely in year [2011].
According to the Histiocytosis Association of America, cladribine is used to treat histiocytosis. See http://en.wikipedia.org/wiki/Cladribine.

DRUG DESCRIPTION

LEUSTATIN (cladribine) Injection (also commonly known as 2-chloro-2 -deoxy- β -D-adenosine) is a synthetic antineoplastic agent for continuous intravenous infusion. It is a clear, colorless, sterile, preservative-free, isotonic solution. LEUSTATIN Injection is available in single-use vials containing 10 mg (1 mg/mL) of cladribine, a chlorinated purine nucleoside analog. Each milliliter of LEUSTATIN Injection contains 1 mg of the active ingredient and 9 mg (0.15 mEq) of sodium chloride as an inactive ingredient. The solution has a pH range of 5.5 to 8.0. Phosphoric acid and/or dibasic sodium phosphate may have been added to adjust the pH to 6.3±0.3.

LEUSTATIN Injection is indicated for the treatment of active Hairy Cell Leukemia as defined by clinically significant anemia, neutropenia, thrombocytopenia or disease-related symptoms. 

 1: El-Osta H, Janku F, Kurzrock R. Successful treatment of Castleman's disease with interleukin-1 receptor antagonist (Anakinra). Mol Cancer Ther. 2010 Jun;9(6):1485-8. Epub 2010 May 25. PubMed PMID: 20501803.

2: Sigal DS, Sharpe R, Burian C, Saven A. Very long-term eradication of minimal residual disease in patients with hairy cell leukemia after a single course of cladribine. Blood. 2010 Mar 11;115(10):1893-6. Epub 2010 Jan 7. PubMed PMID: 20056789.

3: Robak T, Jamroziak K, Robak P. Current and emerging treatments for chronic lymphocytic leukaemia. Drugs. 2009;69(17):2415-49. doi: 10.2165/11319270-000000000-00000. PubMed PMID: 19911856.

4: Grever MR, Zinzani PL. Long-term follow-up studies in hairy cell leukemia. Leuk Lymphoma. 2009 Oct;50 Suppl 1:23-6. Review. PubMed PMID: 19814694.

5: Arons E, Suntum T, Stetler-Stevenson M, Kreitman RJ. VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy. Blood. 2009 Nov 19;114(21):4687-95. Epub 2009 Sep 10. PubMed PMID: 19745070; PubMed Central PMCID: PMC2780305.

6: Spurgeon S, Yu M, Phillips JD, Epner EM. Cladribine: not just another purine analogue? Expert Opin Investig Drugs. 2009 Aug;18(8):1169-81. Review. PubMed PMID: 19604118.

7: Bosanquet AG, Richards SM, Wade R, Else M, Matutes E, Dyer MJ, Rassam SM, Durant J, Scadding SM, Raper SL, Dearden CE, Catovsky D. Drug cross-resistance and therapy-induced resistance in chronic lymphocytic leukaemia by an enhanced method of individualised tumour response testing. Br J Haematol. 2009 Aug;146(4):384-95. Epub 2009 Jun 22. PubMed PMID: 19552723.

8: Lech-Maranda E, Korycka A, Robak T. Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12. Review. PubMed PMID: 19519505.

9: Larson ML, Venugopal P. Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009 Jun;10(8):1353-7. Review. PubMed PMID: 19463072.

10: Cheson BD. Novel therapies for peripheral T-cell non-Hodgkin's lymphomas. Curr Opin Hematol. 2009 Jul;16(4):299-305. Review. PubMed PMID: 19367159.

11: Harned TM, Gaynon PS. Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. PubMed PMID: 18728851; PubMed Central PMCID: PMC2504075.

12: Inwards DJ, Fishkin PA, Hillman DW, Brown DW, Ansell SM, Kurtin PJ, Fonseca R, Morton RF, Veeder MH, Witzig TE. Long-term results of the treatment of patients with mantle cell lymphoma with cladribine (2-CDA) alone (95-80-53) or 2-CDA and rituximab (N0189) in the North Central Cancer Treatment Group. Cancer. 2008 Jul 1;113(1):108-16. PubMed PMID: 18470909.

13: Robak T, Wierzbowska A, Robak E. Recent clinical trials of cladribine in hematological malignancies and autoimmune disorders. Rev Recent Clin Trials. 2006 Jan;1(1):15-34. Review. PubMed PMID: 18393777.

14: Sotlar K. [Therapeutically relevant mutations in the receptor tyrosine kinase KIT in mastocytosis]. Verh Dtsch Ges Pathol. 2007;91:169-76. German. PubMed PMID: 18314612.

15: Kelner MJ, McMorris TC, Rojas RJ, Estes LA, Suthipinijtham P. Synergy of Irofulven in combination with various anti-metabolites, enzyme inhibitors, and miscellaneous agents in MV522 lung carcinoma cells: marked interaction with gemcitabine and 5-fluorouracil. Invest New Drugs. 2008 Oct;26(5):407-15. Epub 2008 Jan 29. PubMed PMID: 18227973.

16: Robak T. Recent progress in the management of chronic lymphocytic leukemia. Cancer Treat Rev. 2007 Dec;33(8):710-28. Epub 2007 Sep 27. Review. PubMed PMID: 17904294.

17: Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S. Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. Review. PubMed PMID: 17852710.

18: Zhong Y, Bakke AC, Fan G, Braziel RM, Gatter KM, Leis JF, Maziarz RT, Huang JZ. Drug resistance in B-cell chronic lymphocytic leukemia: predictable by in vitro evaluation with a multiparameter flow cytometric cytotoxicity assay. Cytometry B Clin Cytom. 2007 May;72(3):189-95. PubMed PMID: 17226861.

19: Robak P, Linke A, Cebula B, Robak T, Smolewski P. Cytotoxic effect of R-etodolac (SDX-101) in combination with purine analogs or monoclonal antibodies on ex vivo B-cell chronic lymphocytic leukemia cells. Leuk Lymphoma. 2006 Dec;47(12):2625-34. PubMed PMID: 17169808.

20: Robak T, Lech-Maranda E, Korycka A, Robak E. Purine nucleoside analogs as immunosuppressive and antineoplastic agents: mechanism of action and clinical activity. Curr Med Chem. 2006;13(26):3165-89. PubMed PMID: 17168705.

21: Goy A. New directions in the treatment of mantle cell lymphoma: an overview. Clin Lymphoma Myeloma. 2006 Oct;7 Suppl 1:S24-32. Review. PubMed PMID: 17101070.

22: Grever MR. Pentostatin: impact on outcome in hairy cell leukemia. Hematol Oncol Clin North Am. 2006 Oct;20(5):1099-108. Review. PubMed PMID: 16990110.

23: Robak T, Smolewski P, Cebula B, Szmigielska-Kaplon A, Chojnowski K, Blonski JZ. Rituximab combined with cladribine or with cladribine and cyclophosphamide in heavily pretreated patients with indolent lymphoproliferative disorders and mantle cell lymphoma. Cancer. 2006 Oct 1;107(7):1542-50. PubMed PMID: 16948126.

24: Quintas-Cardama A, Aribi A, Cortes J, Giles FJ, Kantarjian H, Verstovsek S. Novel approaches in the treatment of systemic mastocytosis. Cancer. 2006 Oct 1;107(7):1429-39. Review. PubMed PMID: 16948123.

25: Steurer M, Pall G, Richards S, Schwarzer G, Bohlius J, Greil R. Purine antagonists for chronic lymphocytic leukaemia. Cochrane Database Syst Rev. 2006 Jul 19;3:CD004270. Review. PubMed PMID: 16856041.

26: Gandhi V, Plunkett W, Bonate PL, Du M, Nowak B, Lerner S, Keating MJ. Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment. Clin Cancer Res. 2006 Jul 1;12(13):4011-7. PubMed PMID: 16818700.

27: Steurer M, Pall G, Richards S, Schwarzer G, Bohlius J, Greil R; Cochrane Haematologic Malignancies Group. Single-agent purine analogues for the treatment of chronic lymphocytic leukaemia: a systematic review and meta-analysis. Cancer Treat Rev. 2006 Aug;32(5):377-89. Epub 2006 Jun 21. Review. PubMed PMID: 16793209.

28: Robak T. New agents in chronic lymphocytic leukemia. Curr Treat Options Oncol. 2006 May;7(3):200-12. Review. PubMed PMID: 16615876.

29: Robak T. Therapy of chronic lymphocytic leukaemia with purine nucleoside analogues: facts and controversies. Drugs Aging. 2005;22(12):983-1012. Review. PubMed PMID: 16363884.

30: Kline JP, Larson RA. Clofarabine in the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia: a review. Expert Opin Pharmacother. 2005 Dec;6(15):2711-8. Review. PubMed PMID: 16316309.

31: Sipe JC. Cladribine for multiple sclerosis: review and current status. Expert Rev Neurother. 2005 Nov;5(6):721-7. Review. PubMed PMID: 16274330.

32: McClain KL. Drug therapy for the treatment of Langerhans cell histiocytosis. Expert Opin Pharmacother. 2005 Nov;6(14):2435-41. Review. PubMed PMID: 16259575.

33: Hubeek I, Peters GJ, Broekhuizen AJ, Sargent J, Gibson BE, Creutzig U, Kaspers GJ. Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia. Br J Haematol. 2005 Oct;131(2):219-22. PubMed PMID: 16197453.

34: Tallman MS, Zakarija A. Hairy cell leukemia: survival and relapse. Long-term follow-up of purine analog-based therapy and approach for relapsed disease. Transfus Apher Sci. 2005 Feb;32(1):99-103. Review. PubMed PMID: 15737878.

35: Robak T. Therapy of chronic lymphocytic leukemia with purine analogs and monoclonal antibodies. Transfus Apher Sci. 2005 Feb;32(1):33-44. Review. PubMed PMID: 15737872.

36: Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP. Diagnosis and management of Waldenstrom's macroglobulinemia. J Clin Oncol. 2005 Mar 1;23(7):1564-77. Review. PubMed PMID: 15735132.

37: Miehlke S, Morgner A, Ehninger G. [Gastric MALT lymphoma and gastrointestinal stromal tumors (GIST)]. Praxis (Bern 1994). 2004 Dec 22;93(51-52):2143-50. Review. German. PubMed PMID: 15672765.

38: Dimopoulos MA, Merlini G, Leblond V, Anagnostopoulos A, Alexanian R. How we treat Waldenström's macroglobulinemia. Haematologica. 2005 Jan;90(1):117-25. Review. PubMed PMID: 15642678.

39: Cooper T, Kantarjian H, Plunkett W, Gandhi V. Clofarabine in adult acute leukemias: clinical success and pharmacokinetics. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1417-23. PubMed PMID: 15571270.

40: Robak T. The place of cladribine in the treatment of chronic lymphocytic leukemia: a 10-year experience in Poland. Ann Hematol. 2005 Feb;84(2):63-70. Epub 2004 Nov 19. Review. PubMed PMID: 15558283.

41: Greyz N, Saven A. Cladribine: from the bench to the bedside--focus on hairy cell leukemia. Expert Rev Anticancer Ther. 2004 Oct;4(5):745-57. Review. PubMed PMID: 15485311.

42: Tobinai K, Hotta T. Clinical trials for malignant lymphoma in Japan. Jpn J Clin Oncol. 2004 Jul;34(7):369-78. Review. PubMed PMID: 15342663.

43: Wendtner CM, Eichhorst BF, Hallek MJ. Advances in chemotherapy for chronic lymphocytic leukemia. Semin Hematol. 2004 Jul;41(3):224-33. Review. PubMed PMID: 15269882.

44: Nakagawa T, Kami M, Hori A, Kim SW, Murashige N, Hamaki T, Kishi Y, Fujimoto H, Matsuoka N, Okajima E, Komiyama M, Tobisu K, Wakayama T, Uike N, Tajima K, Makimoto A, Mori S, Tanosaki R, Takaue Y, Kakizoe T. Allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen for treatment of metastatic renal cell carcinoma: single institution experience with a minimum 1-year follow-up. Exp Hematol. 2004 Jul;32(7):599-606. PubMed PMID: 15246155.

45: Densmore JJ, Williams ME. Mantle cell lymphoma. Curr Treat Options Oncol. 2003 Aug;4(4):281-7. PubMed PMID: 12943608.

46: Robak T. Purine nucleoside analogues in the treatment of myleoid leukemias. Leuk Lymphoma. 2003 Mar;44(3):391-409. Review. PubMed PMID: 12688309.

47: Lindemalm S, Liliemark J, Gruber A, Eriksson S, Karlsson MO, Wang Y, Albertioni F. Comparison of cytotoxicity of 2-chloro- 2'-arabino-fluoro-2'-deoxyadenosine (clofarabine) with cladribine in mononuclear cells from patients with acute myeloid and chronic lymphocytic leukemia. Haematologica. 2003 Mar;88(3):324-32. PubMed PMID: 12651272.

48: Tsimberidou AM, Alvarado Y, Giles FJ. Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies. Expert Rev Anticancer Ther. 2002 Aug;2(4):437-48. Review. PubMed PMID: 12647987.

49: Ogura M. [Cladribine]. Gan To Kagaku Ryoho. 2003 Feb;30(2):309-17. Review. Japanese. PubMed PMID: 12610885.

50: Takaue Y. Mini-transplantation strategy for solid tumors. Int J Hematol. 2002 Aug;76 Suppl 2:13-4. PubMed PMID: 12430894.

51: Stathopoulos GP. Molecular characterization as a target for cancer therapy in relation to orphan status disorders (Review). Oncol Rep. 2002 Nov-Dec;9(6):1257-9. Review. PubMed PMID: 12375030.

52: Robak T, Boński JZ, Kasznicki M, Góra-Tybor J, Hellmann A, Konopka L, Dmoszyńska A, Dwilewicz-Trojaczek J, Wołowiec D; Polish Leukemia Study Group. Re-treatment with cladribine-based regimens in relapsed patients with B-cell chronic lymphocytic leukemia. Efficacy and toxicity in comparison with previous treatment. Eur J Haematol. 2002 Jul;69(1):27-36. PubMed PMID: 12270059.

53: McKenna JA. Waldenström's macroglobulinemia. Clin J Oncol Nurs. 2002 Sep-Oct;6(5):283-6. Review. PubMed PMID: 12240489.

54: Szmigielska-Kaplon A, Ciesielska E, Szmigiero L, Robak T. Anthracyclines potentiate activity against murine leukemias L1210 and P388 in vivo and in vitro. Eur J Haematol. 2002 Jun;68(6):370-5. PubMed PMID: 12225395.

55: Itälä M, Remes K. [Nucleoside analogues--new drugs for the treatment of lymphatic cancers]. Duodecim. 2001;117(2):162-9. Review. Finnish. PubMed PMID: 12092367.

56: Densmore JJ, Williams ME. Mantle cell lymphoma. Curr Treat Options Oncol. 2000 Aug;1(3):281-5. Review. PubMed PMID: 12057172.

57: Savoie L, Johnston JB. Hairy cell leukemia. Curr Treat Options Oncol. 2001 Jun;2(3):217-24. Review. PubMed PMID: 12057121.

58: Desikan KR, Dhodapkar MV, Barlogie B. Waldenström's macroglobulinemia. Curr Treat Options Oncol. 2000 Jun;1(2):97-103. Review. PubMed PMID: 12057047.

59: Robak T, Kasznicki M. Alkylating agents and nucleoside analogues in the treatment of B cell chronic lymphocytic leukemia. Leukemia. 2002 Jun;16(6):1015-27. Review. PubMed PMID: 12040433.

60: Armitage JO. The role of mitoxantrone in non-Hodgkin's lymphoma. Oncology (Williston Park). 2002 Apr;16(4):490-502, 507-8; discussion 511-2, 514. Review. PubMed PMID: 12017536.

61: Robak T. The role of nucleoside analogues in the treatment of chronic lymphocytic leukemia-lessons learned from prospective randomized trials. Leuk Lymphoma. 2002 Mar;43(3):537-48. Review. PubMed PMID: 12002757.

62: Tortorella C, Rovaris M, Filippi M. Cladribine. Ortho Biotech Inc. Curr Opin Investig Drugs. 2001 Dec;2(12):1751-6. Review. PubMed PMID: 11892941.

63: Owen RG. Treatment options in Waldenström's macroglobulinaemia: the role of the purine analogues. Expert Opin Pharmacother. 2001 Jun;2(6):945-52. Review. PubMed PMID: 11585010.

64: Johnson SA. Nucleoside analogues in the treatment of haematological malignancies. Expert Opin Pharmacother. 2001 Jun;2(6):929-43. Review. PubMed PMID: 11585009.

65: Ogura M. [Recent progress in the treatment of malignant lymphoma]. Gan To Kagaku Ryoho. 2001 Sep;28(9):1213-35. Review. Japanese. PubMed PMID: 11579632.

66: Robak T. Cladribine in the treatment of chronic lymphocytic leukemia. Leuk Lymphoma. 2001 Feb;40(5-6):551-64. Review. PubMed PMID: 11426528.

67: Krance RA, Hurwitz CA, Head DR, Raimondi SC, Behm FG, Crews KR, Srivastava DK, Mahmoud H, Roberts WM, Tong X, Blakley RL, Ribeiro RC. Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases. J Clin Oncol. 2001 Jun 1;19(11):2804-11. PubMed PMID: 11387351.

68: Robak T, Błoński JZ, Kasznicki M. Does intensive treatment with high dose chlorambucil and prednisone as first line and cladribine as second line influence the survival of the patients with chronic lymphocytic leukemia? Leuk Lymphoma. 2001 May;41(5-6):545-57. PubMed PMID: 11378572.

69: Hamblin TJ. Achieving optimal outcomes in chronic lymphocytic leukaemia. Drugs. 2001;61(5):593-611. Review. PubMed PMID: 11368285.

70: Weiss MA. Novel treatment strategies in chronic lymphocytic leukemia. Curr Oncol Rep. 2001 May;3(3):217-22. Review. PubMed PMID: 11296131.

71: Johnson SA, Thomas W. Therapeutic potential of purine analogue combinations in the treatment of lymphoid malignancies. Hematol Oncol. 2000 Dec;18(4):141-153. Review. PubMed PMID: 11135355.

72: Gordon MS, Young ML, Tallman MS, Cripe LD, Bennett JM, Paietta E, Longo W, Gerad H, Mazza J, Rowe JM. Phase II trial of 2-chlorodeoxyadenosine in patients with relapsed/refractory acute myeloid leukemia: a study of the Eastern Cooperative Oncology Group (ECOG), E5995. Leuk Res. 2000 Oct;24(10):871-5. PubMed PMID: 10996206.

73: Shoji N, Mineishi S. [Non-myeloablative stem cell transplant]. Gan To Kagaku Ryoho. 2000 Jun;27(6):795-800. Review. Japanese. PubMed PMID: 10897204.

74: Cabanillas F. Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5. Review. PubMed PMID: 10887639.

75: Kipps TJ. Chronic lymphocytic leukemia. Curr Opin Hematol. 2000 Jul;7(4):223-34. Review. PubMed PMID: 10882178.

76: Ahmad I, Al-Katib AM, Beck FW, Mohammad RM. Sequential treatment of a resistant chronic lymphocytic leukemia patient with bryostatin 1 followed by 2-chlorodeoxyadenosine: case report. Clin Cancer Res. 2000 Apr;6(4):1328-32. PubMed PMID: 10778958.

77: Dimopoulos MA, Panayiotidis P, Moulopoulos LA, Sfikakis P, Dalakas M. Waldenström's macroglobulinemia: clinical features, complications, and management. J Clin Oncol. 2000 Jan;18(1):214-26. Review. PubMed PMID: 10623712.

78: Ohnishi K, Ohno R. [New antitumor drugs for non-Hodgkin's lymphoma]. Gan To Kagaku Ryoho. 1998 Dec;25(14):2223-8. Review. Japanese. PubMed PMID: 9881079.

79: Cheson BD. Therapy for previously untreated chronic lymphocytic leukemia: a reevaluation. Semin Hematol. 1998 Jul;35(3 Suppl 3):14-21. Review. PubMed PMID: 9685175.

80: Cheson BD. New prospects in the treatment of indolent lymphomas with purine analogues. Cancer J Sci Am. 1998 Jul;4 Suppl 2:S27-36. PubMed PMID: 9672772.

81: Rai KR. Cladribine for the treatment of hairy cell leukemia and chronic lymphocytic leukemia. Semin Oncol. 1998 Jun;25(3 Suppl 7):19-22. Review. PubMed PMID: 9671325.

82: Betticher DC, Hsu Schmitz SF, Ratschiller D, von Rohr A, Egger T, Pugin P, Stalder M, Hess U, Fey MF, Cerny T. Cladribine (2-CDA) given as subcutaneous bolus injections is active in pretreated Waldenström's macroglobulinaemia. Swiss Group for Clinical Cancer Research (SAKK). Br J Haematol. 1997 Nov;99(2):358-63. PubMed PMID: 9375754.

83: Mitterbauer M, Hilgenfeld E, Wilfing A, Jäger U, Knauf WU. Is there a place for 2-CDA in the treatment of B-CLL? Leukemia. 1997 Apr;11 Suppl 2:S35-7. Review. PubMed PMID: 9178836.

84: Bergmann L. Present status of purine analogs in the therapy of chronic lymphocytic leukemias. Leukemia. 1997 Apr;11 Suppl 2:S29-34. Review. PubMed PMID: 9178835.

85: Pott C, Hiddemann W. Purine analogs in the treatment of chronic lymphocytic leukemia. Leukemia. 1997 Apr;11 Suppl 2:S25-8. Review. PubMed PMID: 9178834.

86: Cheson BD. Perspectives on purine analogues. Hematol Cell Ther. 1996 Dec;38 Suppl 2:S109-16. Review. PubMed PMID: 9137964.

87: Saven A, Piro LD. 2-Chlorodeoxyadenosine: a potent antimetabolite with major activity in the treatment of indolent lymphoproliferative disorders. Hematol Cell Ther. 1996 Dec;38 Suppl 2:S93-101. Review. PubMed PMID: 9137962.

88: Plunkett W, Begleiter A, Liliemark JO, Reed JC. Why do drugs work in CLL? Leuk Lymphoma. 1996 Oct;22 Suppl 2:1-11. Review. PubMed PMID: 9021705.

89: Fabianowska-Majewska K, Wyczechowska D. 2-Chloro-2'-deoxyadenosine (2CdA) biochemical aspects of antileukemic efficacy. Acta Pol Pharm. 1996 Jul-Aug;53(4):231-9. Review. PubMed PMID: 9415193.

90: Gruber J, Geisen F, Sgonc R, Egle A, Villunger A, Boeck G, Konwalinka G, Greil R. 2',2'-Difluorodeoxycytidine (gemcitabine) induces apoptosis in myeloma cell lines resistant to steroids and 2-chlorodeoxyadenosine (2-CdA). Stem Cells. 1996 May;14(3):351-62. PubMed PMID: 8724701.

91: Bosanquet AG, Bell PB. Novel ex vivo analysis of nonclassical, pleiotropic drug resistance and collateral sensitivity induced by therapy provides a rationale for treatment strategies in chronic lymphocytic leukemia. Blood. 1996 Mar 1;87(5):1962-71. PubMed PMID: 8634445.

92: O'Brien S, Kantarjian H, Keating MJ. Purine analogs in chronic lymphocytic leukemia and Waldenström's macroglobulinemia. Ann Oncol. 1996;7 Suppl 6:S27-33. Review. PubMed PMID: 9010576.

93: Hoffman MA. Cladribine for the treatment of indolent non-Hodgkin's lymphomas. Semin Hematol. 1996 Jan;33(1 Suppl 1):40-4. Review. PubMed PMID: 8714616.

94: Piro LD. Cladribine in the treatment of low-grade non-Hodgkin's lymphoma. Semin Hematol. 1996 Jan;33(1 Suppl 1):34-9. Review. PubMed PMID: 8714615.

95: Saven A. The Scripps Clinic experience with cladribine (2-CdA) in the treatment of chronic lymphocytic leukemia. Semin Hematol. 1996 Jan;33(1 Suppl 1):28-33. Review. PubMed PMID: 8714614.

96: Tallman MS, Hakimian D. Current results and prospective trials of cladribine in chronic lymphocytic leukemia. Semin Hematol. 1996 Jan;33(1 Suppl 1):23-7. Review. PubMed PMID: 8714613.

97: Nelson MC, Hogan DK. The role of cladribine in the treatment of lymphoid malignancies. Oncol Nurs Forum. 1995 Oct;22(9):1395-400. Review. PubMed PMID: 8539180.

98: Becker CC, Gidal BE, Fleming JO. Immunotherapy in multiple sclerosis, Part 2. Am J Health Syst Pharm. 1995 Oct 1;52(19):2105-20; quiz 2132-4. Review. PubMed PMID: 8535945.

99: Tallman MS, Hakimian D. Purine nucleoside analogs: emerging roles in indolent lymphoproliferative disorders. Blood. 1995 Oct 1;86(7):2463-74. Review. Erratum in: Blood 1996 Mar 1;87(5):2093. PubMed PMID: 7670093.

100: Becker CC, Gidal BE, Fleming JO. Immunotherapy in multiple sclerosis, Part 1. Am J Health Syst Pharm. 1995 Sep 15;52(18):1985-2000. Review. PubMed PMID: 8528866.

101: Molica S, De Rossi G, Luciani M, Levato D. Prognostic features and therapeutical approaches in B-cell chronic lymphocytic leukemia: an update. Haematologica. 1995 Mar-Apr;80(2):176-93. Review. PubMed PMID: 7628755.

102: O'Brien S, del Giglio A, Keating M. Advances in the biology and treatment of B-cell chronic lymphocytic leukemia. Blood. 1995 Jan 15;85(2):307-18. Review. PubMed PMID: 7811987.

103: Depenbrock H, Wenger M, Peter R, Fellbaum C, Block T, Rastetter J, Hanauske AR. Investigation of the comparative effects of 2-chlorodeoxyadenosine on tumor colony forming units in vitro. Invest New Drugs. 1995;13(2):117-23. PubMed PMID: 8617573.

104: Delannoy A, Ferrant A, Martiat P, Montfort L, Doyen C, Sokal G, Michaux JL. 2-Chlorodeoxyadenosine therapy in advanced chronic lymphocytic leukaemia. Nouv Rev Fr Hematol. 1994 Aug;36(4):311-5. PubMed PMID: 7971251.

105: Kumagai M, Manabe A, Coustan-Smith E, Blakley RL, Beck WT, Santana VM, Behm FG, Raimondi SC, Campana D. Use of stroma-supported cultures of leukemic cells to assess antileukemic drugs. II. Potent cytotoxicity of 2-chloro-deoxyadenosine in acute lymphoblastic leukemia. Leukemia. 1994 Jul;8(7):1116-23. PubMed PMID: 7913512.

106: Anderson N, Lokich JJ. Cancer chemotherapy and infusional scheduling. Oncology (Williston Park). 1994 May;8(5):99-111; discussion 111, 115-6. Review. PubMed PMID: 8025010.

107: Saven A, Piro L. Newer purine analogues for the treatment of hairy-cell leukemia. N Engl J Med. 1994 Mar 10;330(10):691-7. Review. Erratum in: N Engl J Med 1994 Apr 28;330(17):1247. PubMed PMID: 7906385.

108: Larsson R, Fridborg H, Liliemark J, Csoka K, Kristensen J, de la Torre M, Nygren P. In vitro activity of 2-chlorodeoxyadenosine (CdA) in primary cultures of human haematological and solid tumours. Eur J Cancer. 1994;30A(7):1022-6. PubMed PMID: 7946567.

109: Platanias LC, Golomb HM. Hairy cell leukaemia. Baillieres Clin Haematol. 1993 Dec;6(4):887-98. Review. PubMed PMID: 7913637.

110: Saven A, Piro LD. The newer purine analogs. Significant therapeutic advance in the management of lymphoid malignancies. Cancer. 1993 Dec 1;72(11 Suppl):3470-83. Review. PubMed PMID: 7902205.

111: Baltz JK, Montello MJ. Cladribine for the treatment of hematologic malignancies. Clin Pharm. 1993 Nov;12(11):805-13; quiz 860-2. Review. PubMed PMID: 7903917.

112: Saven A. Comparative efficacy of the newer nucleosides (fludarabine, 2'-deoxycoformycin, and 2-chlorodeoxyadenosine) in the treatment of indolent lymphoid malignancies. Semin Hematol. 1993 Oct;30(4 Suppl 6):31-3. Review. PubMed PMID: 7908757.

113: Piro LD. 2-Chlorodeoxyadenosine: treatment of hairy cell leukemia, chronic lymphocytic leukemia, and lymphocytic lymphoma. Semin Hematol. 1993 Oct;30(4 Suppl 6):28-30. Review. PubMed PMID: 7908756.

114: Saven A, Piro LD. 2-Chlorodeoxyadenosine in the treatment of hairy cell leukemia and chronic lymphocytic leukemia. Leuk Lymphoma. 1993;11 Suppl 2:109-14. Review. PubMed PMID: 7907251.

115: Cheson BD. New antimetabolites in the treatment of human malignancies. Semin Oncol. 1992 Dec;19(6):695-706. Review. PubMed PMID: 1361080.

116: Pentostatin and 2-chlorodeoxyadenosine for hairy-cell leukemia. Med Lett Drugs Ther. 1992 Sep 18;34(879):89-90. PubMed PMID: 1355592.

117: Cheson BD. Clinical trials referral resource. Clinical trials with 2-chlorodeoxyadenosine. Oncology (Williston Park). 1992 May;6(5):95-8. PubMed PMID: 1350917.

118: Kay AC, Saven A, Carrera CJ, Carson DA, Thurston D, Beutler E, Piro LD. 2-Chlorodeoxyadenosine treatment of low-grade lymphomas. J Clin Oncol. 1992 Mar;10(3):371-7. PubMed PMID: 1346801.

119: Santana VM, Mirro J Jr, Harwood FC, Cherrie J, Schell M, Kalwinsky D, Blakley RL. A phase I clinical trial of 2-chlorodeoxyadenosine in pediatric patients with acute leukemia. J Clin Oncol. 1991 Mar;9(3):416-22. PubMed PMID: 1671875.

120: Gribbin TE. New purine analogues for the treatment of chronic B-cell malignancies. Henry Ford Hosp Med J. 1991;39(2):98-102. Review. PubMed PMID: 1679757.

121: Plunkett W, Saunders PP. Metabolism and action of purine nucleoside analogs. Pharmacol Ther. 1991;49(3):239-68. Review. PubMed PMID: 1675805.

122: Lill MC, Golde DW. Treatment of hairy-cell leukemia. Blood Rev. 1990 Dec;4(4):238-44. Review. PubMed PMID: 1706207.

123: Hutton JJ, Von Hoff DD. Cytotoxicity of 2-chlorodeoxyadenosine in a human tumor colony-forming assay. Cancer Drug Deliv. 1986 Spring;3(2):115-22. PubMed PMID: 2871921.