Hairy cell leukemia medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

Overview

There is no curative treatment for hairy cell leukemia. The mainstay of therapy for hairy cell leukemia patients is chemotherapy. Pharmacological agents used for the treatment of hairy cell leukemia patients include cladribine, pentostatin, rituximab, and vemurafenib.

Medical Therapy

First Line Therapy

  • The preferred pharmacological agent used for the initial management of hairy cell leukemia could be either cladribine or pentostatin.[5][6][7][8]
  • Cladribine is administered by a single daily IV infusion for a period of 5-7 days.
  • Pentostatin is administered by a single IV infusion every 2 weeks for a period of 3-6 months.
  • Common side effects of such agents may include:
  • Hairy cell leukemia patients who demonstrate a complete response following initial medical therapy should be followed-up with close observation for any signs of relapse.
  • A complete response to medical therapy among patients with hairy cell leukemia is defined by:
  • Resolution of the patient's symptoms
  • The absence of splenomegaly on physical exam
  • Recovery of the patients blood counts to the normal limits
  • The absence of malignant leukemic cells on blood smear or bone marrow aspiration

Relapsed Therapy

  • The optimal therapy for patients who relapse after a complete response depends on the duration of disease-free period following the initial medical therapy.
  • Hairy cell leukemia patients who relapse after one year or more are be managed by the same initial purine analogue ± rituximab.
  • Hairy cell leukemia patients who relapse before a period of one year are managed by an alternative purine analogue ± rituximab.

Refractory Therapy

  • Rituximab is administered by a single IV infusion every week for a period of 8 weeks.
  • Interferon alpha is administered subcutaneously (3 million units) three times a week for a period of 12-18 months.
  • The major side effect of rituximab treatment is serum sickness, whereas the major side effects of interferon alpha are flu-like symptoms and depression.
  • Patients with progressive hairy cell leukemia, who do not demonstrate a complete response to any of the aforementioned medical therapies, should be managed with a BRAF kinase inhibitor, such as vemurafenib.[15]


The algorithm below summarizes the management approach for hairy cell leukemia patients:

 
 
 
 
 
Initial patients evaluation
 
 
 
 
 
 
 
 
 
 
History
Physical examination
Complete blood count
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Asymptomatic patients with no therapeutic indications
 
Symptomatic patients or evidence of therapeutic indications
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients managed by observation and close follow-up
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete response
 
No evidence of complete response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Follow-up and close observation
 

Retuximab alone
Interferon alpha alone

Alternative purine analogue ± rituximab
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Relapse after one year: same initial purine analogue ± rituximab

Relapse before one year: alternative purine analogue ± rituximab
 
No evidence of complete response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


References

  1. Zinzani, Pier Luigi; Pellegrini, Cinzia; Stefoni, Vittorio; Derenzini, Enrico; Gandolfi, Letizia; Broccoli, Alessandro; Argnani, Lisa; Quirini, Federica; Pileri, Stefano; Baccarani, Michele (2010). "Hairy cell leukemia". Cancer. 116 (20): 4788–4792. doi:10.1002/cncr.25243. ISSN 0008-543X.
  2. 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 (June 2009). "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. 145 (6): 733–40. doi:10.1111/j.1365-2141.2009.07668.x. PMID 19344416.
  3. Dearden CE, Matutes E, Hilditch BL, Swansbury GJ, Catovsky D (August 1999). "Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine". Br. J. Haematol. 106 (2): 515–9. PMID 10460614.
  4. Grever MR (January 2010). "How I treat hairy cell leukemia". Blood. 115 (1): 21–8. doi:10.1182/blood-2009-06-195370. PMC 2803689. PMID 19843881.
  5. Grever MR, Lozanski G (February 2011). "Modern strategies for hairy cell leukemia". J. Clin. Oncol. 29 (5): 583–90. doi:10.1200/JCO.2010.31.7016. PMID 21220590.
  6. Grever M, Kopecky K, Foucar MK, Head D, Bennett JM, Hutchison RE, Corbett WE, Cassileth PA, Habermann T, Golomb H (April 1995). "Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study". J. Clin. Oncol. 13 (4): 974–82. doi:10.1200/JCO.1995.13.4.974. PMID 7707126.
  7. Dearden CE, Matutes E, Hilditch BL, Swansbury GJ, Catovsky D (August 1999). "Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine". Br. J. Haematol. 106 (2): 515–9. PMID 10460614.
  8. Grever MR (January 2010). "How I treat hairy cell leukemia". Blood. 115 (1): 21–8. doi:10.1182/blood-2009-06-195370. PMC 2803689. PMID 19843881.
  9. Grever MR, Lozanski G (February 2011). "Modern strategies for hairy cell leukemia". J. Clin. Oncol. 29 (5): 583–90. doi:10.1200/JCO.2010.31.7016. PMID 21220590.
  10. Bastie, J. N.; Cazals-Hatem, D.; Daniel, M. T.; D'agay, M. F.; Rabian, CL.; Glaisner, S.; Noel-Walter, M. P.; Dabout, D.; Flandrin, G.; Dombret, H.; Poisson, D.; Degos, L.; Castaigne, S. (2010). "Five Years Follow-Up after 2-Chloro Deoxyadenosine Treatment in Thirty Patients with Hairy Cell Leukemia: Evaluation of Minimal Residual Disease and CD4+ Lymphocytopenia after Treatment". Leukemia & Lymphoma. 35 (5–6): 555–565. doi:10.1080/10428199909169620. ISSN 1042-8194.
  11. Gotić M, Rolović Z, Radosević N, Draguljac N, Jovanović V, Bogdanović A, Bosković D (2000). "[Results of treatment in patients with hairy cell leukemia with splenectomy, alpha-interferon and deoxycoformycin]". Srp Arh Celok Lek. 128 (7–8): 262–70. PMID 11089434.
  12. Grever M, Kopecky K, Foucar MK, Head D, Bennett JM, Hutchison RE, Corbett WE, Cassileth PA, Habermann T, Golomb H (April 1995). "Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study". J. Clin. Oncol. 13 (4): 974–82. doi:10.1200/JCO.1995.13.4.974. PMID 7707126.
  13. Chihara D, Kantarjian H, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Poku R, Jain P, Thompson P, Brandt M, Luthra R, Burger J, Keating M, Ravandi F (September 2016). "Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial". Br. J. Haematol. 174 (5): 760–6. doi:10.1111/bjh.14129. PMC 5396841. PMID 27301277.
  14. Ravandi F, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Koller C, Challagundla P, York S, Brandt M, Luthra R, Burger J, Thomas D, Keating M, Kantarjian H (October 2011). "Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia". Blood. 118 (14): 3818–23. doi:10.1182/blood-2011-04-351502. PMC 4081440. PMID 21821712.
  15. Cornet E, Damaj G, Troussard X (2015). "New insights in the management of patients with hairy cell leukemia". Curr Opin Oncol. 27 (5): 371–6. doi:10.1097/CCO.0000000000000214. PMID 26154707.


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