Subcutaneous and Intravenous Cladribine Treatment of Hairy Cell Leukemia Patients: Do We Still Need Intravenous Cladribine?

Abstract

Background Hairy cell leukemia (HCL) is an uncommon neoplasm representing approximately 2% leukemias and <1% lymphoid neoplasms. Although HCL remains an incurable disease, first-line treatment with intravenous (IV) or subcutaneous (SC) cladribine (2-CdA) often leads to long-term remissions. Although long-term data are available for IV administration, similar comparable data for SC administration are lacking. Material and Methods Demographic data, laboratory and clinical parameters of 20 patients with HCL, and IV and SC administrations of cladribine in primary treatment were analyzed. Results All patients were administered 2-CdA as the first-line therapy. 2-CdA was administered intravenously to 11 patients and subcutaneously to 9 patients. The hospitalization times were shorter in the SC route, and the incidence of febrile neutropenia was less; therefore, statistical significance could not be determined. There was no difference between the route of administration and the treatment response. A correlation was recorded between the level of anemia before treatment and the time to treatment response. In addition, a correlation was recorded between the level of anemia before treatment and minimal residual disease status after treatment. The median overall survival (OS) was 43.5 months (confidence interval 95%: 1.5-79 months), and 2- and 5-year OS was 95%. There was no increase in the incidence of second primary cancer. Conclusions The outcomes of HCL patients treated with SC 2-CdA are quite good, and, in most patients, one cycle of SC 2-CdA was adequate for long-term disease control. SC 2-CdA is an easily applicable option for outpatients, and their side effects are often easily manageable.

Keywords

• hairy cell leukemia
• 2-chlorodeoxyadenosine
• 2-CdA
• subcutaneous cladribine

References

1. Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood. 2006 Jan 1;107(1):265-76. doi: 10.1182/blood-2005-06-2508.
2. Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer. 2011 Nov 22;105(11):1684-92. doi: 10.1038/bjc.2011.450.
3. Frassoldati A, Lamparelli T, Federico M, Annino L, Capnist G, Pagnucco G, Dini E, Resegotti L, Damasio EE, Silingardi V. Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia. Leuk Lymphoma. 1994 Apr;13(3-4):307-16. doi: 10.3109/10428199409056295.
4. Catovsky D. Hairy-cell leukaemia and prolymphocytic leukaemia. Clin Haematol. 1977 Feb;6(1):245-68.
5. Golomb HM, Catovsky D, Golde DW. Hairy cell leukemia: a clinical review based on 71 cases. Ann Intern Med. 1978 Nov;89(5 Pt 1):677-83. doi: 10.7326/0003-4819-89-5-677.
6. Cornet E, Delmer A, Feugier P, Garnache-Ottou F, Ghez D, Leblond V, Levy V, Maloisel F, Re D, Zini JM, Troussard X; French Society of Haematology. Recommendations of the SFH (French Society of Haematology) for the diagnosis, treatment and follow-up of hairy cell leukaemia. Ann Hematol. 2014 Dec;93(12):1977-83. doi: 10.1007/s00277-014-2140-y.
7. Jones G, Parry-Jones N, Wilkins B, Else M, Catovsky D. Revised guidelines for the diagnosis and management of hairy cell leukaemia and hairy cell leukaemia variant*. Br J Haematol. 2012 Jan;156(2):186-95. doi: 10.1111/j.1365-2141.2011.08931.x.
8. Broccoli A, Argnani L, Cross M, Janus A, Maitre E, Troussard X, Robak T, Dearden C, Else M, Catovsky D, Zinzani PL. A 3-decade multicenter European experience with cladribine as upfront treatment in 384 patients with hairy cell leukemia. Blood Adv. 2022 Jul 26;6(14):4224-7. doi: 10.1182/bloodadvances.2022007854.

9. Yousaf M, Khan MA, Iftikhar R, Chaudary QU, Shahbaz N, Ahmad U, Javed H. Treatment outcomes of patients with hairy cell leukaemia; A 16-year experience at a tertiary care center in Pakistan. J Ayub Med Coll Abbottabad. 2022 Oct-Dec;34(4):797-801. doi: 10.55519/JAMC-04-10177.
10. Juliusson G, Heldal D, Hippe E, Hedenus M, Malm C, Wallman K, tolt CM, Evensen SA, Albertioni F, Tjønnfjord G, et al. Subcutaneous injections of 2-chlorodeoxyadenosine for symptomatic hairy cell leukemia. J Clin Oncol. 1995 Apr;13(4):989-95. doi: 10.1200/JCO.1995.13.4.989.
11. Liliemark J, Juliusson G. Cellular pharmacokinetics of 2-chloro-2'-deoxyadenosine nucleotides: comparison of intermittent and continuous intravenous infusion and subcutaneous and oral administration in leukemia patients. Clin Cancer Res. 1995 Apr;1(4):385-90.
12. Grever MR, Abdel-Wahab O, Andritsos LA, Banerji V, Barrientos J, Blachly JS, Call TG, Catovsky D, Dearden C, Demeter J, Else M, Forconi F, Gozzetti A, Ho AD, Johnston JB, Jones J, Juliusson G, Kraut E, Kreitman RJ, Larratt L, Lauria F, Lozanski G, Montserrat E, Parikh SA, Park JH, Polliack A, Quest GR, Rai KR, Ravandi F, Robak T, Saven A, Seymour JF, Tadmor T, Tallman MS, Tam C, Tiacci E, Troussard X, Zent CS, Zenz T, Zinzani PL, Falini B. Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia. Blood. 2017 Feb 2;129(5):553-60. doi: 10.1182/blood-2016-01-689422.
13. Piro LD, Carrera CJ, Carson DA, Beutler E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med. 1990 Apr 19;322(16):1117-21. doi: 10.1056/NEJM199004193221605.
14. Else M, Ruchlemer R, Osuji N, Del Giudice I, Matutes E, Woodman A, Wotherspoon A, Swansbury J, Dearden C, Catovsky D. Long remissions in hairy cell leukemia with purine analogs. Cancer. 2005 Dec 1;104(11):2442-8. doi: 10.1002/cncr.21447.
15. Chadha P, Rademaker AW, Mendiratta P, Kim B, Evanchuk DM, Hakimian D, Peterson LC, Tallman MS. Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University experience. Blood. 2005 Jul 1;106(1):241-6. doi: 10.1182/blood-2005-01-0173.
16. Saven A, Burian C, Koziol JA, Piro LD. Long-term follow-up of patients with hairy cell leukemia after cladribine treatment. Blood. 1998 Sep 15;92(6):1918-26.
17. Ellison DJ, Sharpe RW, Robbins BA, Spinosa JC, Leopard JD, Saven A, Piro LD. Immunomorphologic analysis of bone marrow biopsies after treatment with 2-chlorodeoxyadenosine for hairy cell leukemia. Blood. 1994 Dec 15;84(12):4310-5.
18. Hakimian D, Tallman M, Kiley C, Peterson L. Detection of minimal residual disease by immunostaining of bone marrow biopsies after 2-chlorodeoxyadenosine for hairy cell leukemia. Blood. 1993 Sep 15;82(6):1798-802.
19. Wheaton S, Tallman MS, Hakimian D, Peterson L. Minimal residual disease may predict bone marrow relapse in patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine. Blood. 1996 Feb 15;87(4):1556-60.
20. NCCN Clinical Practice Guidelines in Oncology, Guidelines for Treatment of Cancer by Site. Version 1.2013. Hairy Cell Leukemia.
21. Tiacci E, Park JH, De Carolis L, Chung SS, Broccoli A, Scott S, Zaja F, Devlin S, Pulsoni A, Chung YR, Cimminiello M, Kim E, Rossi D, Stone RM, Motta G, Saven A, Varettoni M, Altman JK, Anastasia A, Grever MR, Ambrosetti A, Rai KR, Fraticelli V, Lacouture ME, Carella AM, Levine RL, Leoni P, Rambaldi A, Falzetti F, Ascani S, Capponi M, Martelli MP, Park CY, Pileri SA, Rosen N, Foà R, Berger MF, Zinzani PL, Abdel-Wahab O, Falini B, Tallman MS. Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia. N Engl J Med. 2015 Oct 29;373(18):1733-47. doi: 10.1056/NEJMoa1506583.
22. Kreitman RJ. Immunoconjugates and new molecular targets in hairy cell leukemia. Hematology Am Soc Hematol Educ Program. 2012;2012:660-6. doi: 10.1182/asheducation-2012.1.660.
23. Park JH, Levine RL. Targeted immunotherapy for hairy cell leukemia. J Clin Oncol. 2012 May 20;30(15):1888-90. doi: 10.1200/JCO.2011.39.8313.
24. Divino V, Karve S, Gaughan A, DeKoven M, Gao G, Knopf KB, Lanasa MC. Characteristics and treatment patterns among US patients with hairy cell leukemia: a retrospective claims analysis. J Comp Eff Res. 2017 Sep;6(6):497-508. doi: 10.2217/cer-2017-0014.
25. Dinmohamed AG, Posthuma EFM, Visser O, Kater AP, Raymakers RAP, Doorduijn JK. Relative survival reaches a plateau in hairy cell leukemia: a population-based analysis in The Netherlands. Blood. 2018 Mar 22;131(12):1380-1383. doi: 10.1182/blood-2017-12-820381.
26. Hacioglu S, Bilen Y, Eser A, Sivgin S, Gurkan E, Yildirim R, Aydogdu I, Dogu MH, Yilmaz M, Kayikci O, Tombak A, Kuku I, Celebi H, Akay MO, Esen R, Korkmaz S, Keskin A. Multicenter retrospective analysis regarding the clinical manifestations and treatment results in patients with hairy cell leukemia: twenty-four year Turkish experience in cladribine therapy. Hematol Oncol. 2015 Dec;33(4):192-8. doi: 10.1002/hon.2177.
27. Inbar M, Herishanu Y, Goldschmidt N, Bairey O, Yuklea M, Shvidel L, Fineman R, Aviv A, Ruchlemer R, Braester A, Najib D, Rouvio O, Shaulov A, Greenbaum U, Polliack A, Tadmor T. Hairy Cell Leukemia: Retrospective analysis of demographic data and outcome of 203 patients from 12 medical centers in Israel. Anticancer Res. 2018 Nov;38(11):6423-6429. doi: 10.21873/anticanres.13003.
28. Dearden CE, Else M, Catovsky D. Long-term results for pentostatin and cladribine treatment of hairy cell leukemia. Leuk Lymphoma. 2011 Jun;52 Suppl 2:21-4. doi: 10.3109/10428194.2011.565093.
29. Benz R, Arn K, Andres M, Pabst T, Baumann M, Novak U, Hitz F, Hess U, Zenhaeusern R, Chalandon Y, Mey U, Blum S, Rauch D, O'Meara Stern A, Cantoni N, Bargetzi M, Bianchi-Papina E, Rossi D, Passweg J, Lohri A, Berardi S, Li Q, Feller A, Stussi G. Prospective long-term follow-up after first-line subcutaneous cladribine in hairy cell leukemia: a SAKK trial. Blood Adv. 2020 Aug 11;4(15):3699-3707. doi: 10.1182/bloodadvances.2020002160.
30. Maevis V, Mey U, Schmidt-Wolf G, Schmidt-Wolf IG. Hairy cell leukemia: short review, today’s recommendations and outlook. Blood Cancer J. 2014 Feb 14;4(2):e184. doi: 10.1038/bcj.2014.3.
31. Khorshid O, Namour AE, El-Gammal MM, Mahmoud TY, Fortpied C, Abdel-Malek R, Ramadan S. Efficacy and safety of cladribine: subcutaneous versus intravenous administration in hairy cell leukemia patients. Mediterr J Hematol Infect Dis. 2015 Oct 16;7(1):e2015058. doi: 10.4084/MJHID.2015.058.
32. Sarvaria A, Topp Z, Saven A. Current therapy and new directions in the treatment of hairy cell leukemia. JAMA Oncol. 2016 Jan;2(1):123-9. doi: 10.1001/jamaoncol.2015.4134.
33. Zheng G, Chattopadhyay S, Sud A, Sundquist K, Sundquist J, Försti A, Houlston R, Hemminki A, Hemminki K. Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia. Br J Haematol. 2019 Apr;185(2):232-239. doi: 10.1111/bjh.15777.
34. Watts JM, Kishtagari A, Hsu M, Lacouture ME, Postow MA, Park JH, Stein EM, Teruya-Feldstein J, Abdel-Wahab O, Devlin SM, Tallman MS. Melanoma and non-melanoma skin cancers in hairy cell leukaemia: a surveillance, epidemiology and end results population analysis and the 30-year experience at Memorial Sloan Kettering Cancer Center. Br J Haematol. 2015 Oct;171(1):84-90. doi: 10.1111/bjh.13528.
35. Else M, Dearden CE, Matutes E, Garcia-Talavera J, Rohatiner AZ, Johnson SA, O'Connor NT, Haynes A, Osuji N, Forconi F, Lauria F, Catovsky D. Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis. Br J Haematol. 2009 Jun;145(6):733-40. doi: 10.1111/j.1365-2141.2009.07668.x.
36. Au WY, Klasa RJ, Gallagher R, Le N, Gascoyne RD, Connors JM. Second malignancies in patients with hairy cell leukemia in british columbia: a 20-year experience. Blood. 1998 Aug 15;92(4):1160-4.
37. Cheson BD, Vena DA, Barrett J, Freidlin B. Second malignancies as a consequence of nucleoside analog therapy for chronic lymphoid leukemias. J Clin Oncol. 1999 Aug;17(8):2454-60. doi: 10.1200/JCO.1999.17.8.2454.
38. Kurzrock R, Strom SS, Estey E, O'Brien S, Keating MJ, Jiang H, Adams T, Talpaz M. Second cancer risk in hairy cell leukemia: analysis of 350 patients. J Clin Oncol. 1997 May;15(5):1803-10. doi: 10.1200/JCO.1997.15.5.1803.