Hairy cell leukemia

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Section editor
Sanjai Sharma, MD
Sequoia Regional Cancer Center
Visalia, CA, USA
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Last updated on 2024-07-23:
12 regimens on this page
17 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ESMO


Hairy Cell Leukemia Foundation


NCCN


Untreated

Cladribine monotherapy

Regimen variant #1, 0.09 mg/kg/day x 7 days

Study Dates of enrollment Evidence
Saven et al. 1998 1986-1993 Non-randomized (RT)

Chemotherapy

  • Cladribine (Leustatin) 0.09 mg/kg/day IV continuous infusion over 7 days, started on day 1 (total dose: 0.63 mg/kg)

7-day course


Regimen variant #2, 0.1 mg/kg/day x 7 days

Study Dates of enrollment Evidence
Piro et al. 1990 1986-1989 Pilot, fewer than 20 pts
Tallman et al. 1996 1991-1995 Phase 2

Chemotherapy

  • Cladribine (Leustatin) 0.1 mg/kg/day IV continuous infusion over 7 days, started on day 1 (total dose: 0.7 mg/kg)

7-day course


Regimen variant #3, 0.12 mg/kg/day x 5 days

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Robak et al. 1999 1991-1997 Phase 2
Robak et al. 2007 1998-2005 Phase 3 (C) Cladribine; weekly Did not meet primary endpoint of CR rate

Chemotherapy

5-day course


Regimen variant #4, 0.14 mg/kg/day x 5 days

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Zenhäusern et al. 2009 (SAKK 32/98) 1998-2005 Phase 3 (C) Cladribine; weekly Did not meet primary endpoint of average leukocyte count within 6 weeks from randomization

Chemotherapy

5-day course


Regimen variant #5, 0.15 mg/kg/day x 5 days

Study Dates of enrollment Evidence
Damasio et al. 1998 Not reported in abstract Phase 2

Chemotherapy

5-day course

References

  1. 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. link to original article dosing details in abstract have been reviewed by our editors PubMed
  2. Tallman MS, Hakimian D, Rademaker AW, Zanzig C, Wollins E, Rose E, Peterson LC. Relapse of hairy cell leukemia after 2-chlorodeoxyadenosine: long-term follow-up of the Northwestern University experience. Blood. 1996 Sep 15;88(6):1954-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
    1. Update: 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. Epub 2005 Mar 10. link to original article dosing details in abstract have been reviewed by our editors PubMed content property of HemOnc.org
  3. Damasio EE, Resegotti L, Masoudi B, Bruni R, Cerri R, Isaza A, Clavio M, Risso M, Rossi E, Spriano M, Truini M; Italian Group for the Hairy Cell Leukemia. Five day intermittent vs seven day continuous 2-chlorodeoxyadenosine infusion for the treatment of hairy cell leukemia: a study by Italian Group for the Hairy Cell Leukemia. Recenti Prog Med. 1998 Feb;89(2):68-73. PubMed
  4. 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. link to original article PubMed
  5. Robak T, Błasińska-Morawiec M, Błoński J, Hellmann A, Hałaburda K, Konopka L, Kotlarek-Haus S, Potoczek S, Hansz J, Dmoszyńska A, Urasiński I, Zdziarska B, Dwilewicz-Trojaczek J, Hołowiecki J, Skotnicki AB. 2-chlorodeoxyadenosine (cladribine) in the treatment of hairy cell leukemia and hairy cell leukemia variant: 7-year experience in Poland. Eur J Haematol. 1999 Jan;62(1):49-56. link to original article PubMed
  6. Robak T, Jamroziak K, Gora-Tybor J, Blonski JZ, Kasznicki M, Dwilewicz-Trojaczek J, Wiater E, Zdunczyk A, Dybowicz J, Dmoszynska A, Wojtaszko M, Zdziarska B, Calbecka M, Kostyra A, Hellmann A, Lewandowski K, Stella-Holowiecka B, Sulek K, Gawronski K, Skotnicki AB, Nowak W, Zawilska K, Molendowicz-Portala L, Kloczko J, Sokolowski J, Warzocha K, Seferynska I, Ceglarek B, Konopka L; PALG. Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial. Blood. 2007 May 1;109(9):3672-5. Epub 2007 Jan 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
  7. SAKK 32/98: Zenhäusern R, Schmitz SF, Solenthaler M, Heim D, Meyer-Monard S, Hess U, Leoncini L, Bargetzi M, Rufener B, Tobler A. Randomized trial of daily versus weekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: a multicenter phase III trial (SAKK 32/98). Leuk Lymphoma. 2009 Sep;50(9):1501-11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003746


Cladribine & Rituximab

Regimen

Study Dates of enrollment Evidence
Ravandi et al. 2011 2004-2009 Phase 2

Note: 28 days after administration of cladribine, bone marrow examination was repeated, and then rituximab was started.

Chemotherapy, first portion (course 1)

Supportive therapy, first portion (course 1)

All were administered at the discretion of the treating physician.

Targeted therapy, second portion (cycles 2 to 9)

28-day course, then 7-day cycle for 8 cycles

References

  1. 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. Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia. Blood. 2011 Oct 6;118(14):3818-23. Epub 2011 Aug 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
    1. Update: 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. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial. Br J Haematol. 2016 Sep;174(5):760-6. Epub 2016 Jun 15. link to original article link to PMC article PubMed


Interferon alfa-2a monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Grever et al. 1995 (SWOG 8691) 1986-1989 Phase 3 (C) Pentostatin Inferior RFS (co-primary endpoint)

Immunotherapy

7-day cycle for 26 cycles

References

  1. SWOG 8691: Grever M, Kopecky K, Foucar MK, Head D, Bennett JM, Hutchison RE, Corbett WE, Cassileth PA, Habermann T, Golomb H, Rai K, Eisenhauer E, Appelbaum F, Cheson BD. Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol. 1995 Apr;13(4):974-82. link to original article dosing details in manuscript have been reviewed by our editors PubMed
    1. Update: Flinn IW, Kopecky KJ, Foucar MK, Head D, Bennett JM, Hutchison R, Corbett W, Cassileth P, Habermann T, Golomb H, Rai K, Eisenhauer E, Appelbaum F, Cheson B, Grever MR. Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin. Blood. 2000 Nov 1;96(9):2981-6. link to original article PubMed


Pentostatin monotherapy

Regimen variant #1

Study Dates of enrollment Evidence
Spiers et al. 1987 1984-1987 Non-randomized

Chemotherapy

14-day cycles, continued to the point of maximal response or treatment failure


Regimen variant #2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Grever et al. 1995 (SWOG 8691) 1986-1989 Phase 3 (E-RT-switch-ooc) Interferon alfa-2a Superior RFS (co-primary endpoint)

Note: patients who had complete response before 6 months were given 2 additional cycles of pentostatin, and then treatment was stopped. Patients with objective partial response after 6 months of treatment received an additional 6 months of additional therapy, until they had a complete response or progression of disease.

Chemotherapy

Supportive therapy

  • 1.5 liters of IV fluid hydration with every dose

14-day cycles (see note)

Dose and schedule modifications

  • Patients with performance status of 3 received an initial dose of 2 mg/m2 IV rapid injection once on day 1, which would be increased in later cycles to 4 mg/m2 IV rapid injection once on day 1 if patients had no adverse reactions.
  • Doses of pentostatin were held for patients who had an increase in the serum creatinine concentration greater than 20% above their baseline. Pentostatin was not given until renal function returned to baseline or if 24-hour creatinine clearance was greater than 50 mL/min/1.73m2.

References

  1. Spiers AS, Moore D, Cassileth PA, Harrington DP, Cummings FJ, Neiman RS, Bennett JM, O'Connell MJ; ECOG. Remissions in hairy-cell leukemia with pentostatin (2'-deoxycoformycin). N Engl J Med. 1987 Apr 2;316(14):825-30. link to original article dosing details in manuscript have been reviewed by our editors PubMed
    1. Update: Cassileth PA, Cheuvart B, Spiers AS, Harrington DP, Cummings FJ, Neiman RS, Bennett JM, O'Connell MJ. Pentostatin induces durable remissions in hairy cell leukemia. J Clin Oncol. 1991 Feb;9(2):243-6. link to original article dosing details in abstract have been reviewed by our editors PubMed
  2. SWOG 8691: Grever M, Kopecky K, Foucar MK, Head D, Bennett JM, Hutchison RE, Corbett WE, Cassileth PA, Habermann T, Golomb H, Rai K, Eisenhauer E, Appelbaum F, Cheson BD. Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol. 1995 Apr;13(4):974-82. link to original article dosing details in manuscript have been reviewed by our editors PubMed
    1. Update: Flinn IW, Kopecky KJ, Foucar MK, Head D, Bennett JM, Hutchison R, Corbett W, Cassileth P, Habermann T, Golomb H, Rai K, Eisenhauer E, Appelbaum F, Cheson B, Grever MR. Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin. Blood. 2000 Nov 1;96(9):2981-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Relapsed or refractory

Bendamustine & Rituximab (BR)

BR: Bendamustine, Rituximab

Regimen

Study Dates of enrollment Evidence
Burotto et al. 2013 Not reported Pilot, fewer than 20 patients

Note: this was a dose-escalation study and the bendamustine dose was selected for further study based on absence of DLT.

Chemotherapy

Targeted therapy

28-day cycle for 6 cycles

References

  1. Burotto M, Stetler-Stevenson M, Arons E, Zhou H, Wilson W, Kreitman RJ. Bendamustine and rituximab in relapsed and refractory hairy cell leukemia. Clin Cancer Res. 2013 Nov 15;19(22):6313-21. Epub 2013 Oct 28. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed


Cladribine & Rituximab

Regimen

Study Dates of enrollment Evidence
Ravandi et al. 2011 2004-2009 Phase 2, fewer than 20 pts in this cohort

Note: 28 days after administration of cladribine, bone marrow examination was repeated, and then rituximab was started.

Chemotherapy, first portion (course 1)

Supportive therapy, first portion (course 1)

All were administered at the discretion of the treating physician.

Targeted therapy, second portion (cycles 2 to 9)

28-day course, then 7-day cycle for 8 cycles

References

  1. 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. Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia. Blood. 2011 Oct 6;118(14):3818-23. Epub 2011 Aug 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
    1. Update: 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. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial. Br J Haematol. 2016 Sep;174(5):760-6. Epub 2016 Jun 15. link to original article link to PMC article PubMed


Interferon alfa-2a monotherapy

Regimen

Study Dates of enrollment Evidence
Quesada et al. 1986 (N2752) 1984 to not reported Non-randomized (RT)

Note: This is of historic interest. It is not completely clear whether the cited study is the same as N2752, which is cited by the FDA in the package insert.

Immunotherapy

References

  1. N2752: Quesada JR, Hersh EM, Manning J, Reuben J, Keating M, Schnipper E, Itri L, Gutterman JU. Treatment of hairy cell leukemia with recombinant alpha-interferon. Blood. 1986 Aug;68(2):493-7. link to original article PubMed


Interferon alfa-2b monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Quesada et al. 1984 Not reported Pilot, fewer than 20 pts
Golomb et al. 1986 1983-1984 Non-randomized
Golomb et al. 1988 1985-1987 Randomized (E-RT-de-esc) Inteferon alfa-2b x 18 mo Seems to have lower incidence of fatigue

Note: This is of historic interest. Most patients had previously undergone splenectomy.

Immunotherapy

12-month course

References

  1. Quesada JR, Reuben J, Manning JT, Hersh EM, Gutterman JU. Alpha interferon for induction of remission in hairy-cell leukemia. N Engl J Med. 1984 Jan 5;310(1):15-8. link to original article PubMed
  2. Golomb HM, Jacobs A, Fefer A, Ozer H, Thompson J, Portlock C, Ratain M, Golde D, Vardiman J, Burke JS, Brady J, Bonnem E, Spiegel R. Alpha-2 interferon therapy of hairy-cell leukemia: a multicenter study of 64 patients. J Clin Oncol. 1986 Jun;4(6):900-5. link to original article PubMed
  3. Golomb HM, Ratain MJ, Fefer A, Thompson J, Golde DW, Ozer H, Portlock C, Silber R, Rappeport J, Bonnem E, Spiegel R, Tensen L, Burke JS, Vardiman JW. Randomized study of the duration of treatment with interferon alfa-2B in patients with hairy cell leukemia. J Natl Cancer Inst. 1988 May 4;80(5):369-73. link to original article PubMed


Moxetumomab pasudotox monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Kreitman et al. 2018 (Study 1053) 2013-2016 Phase 2 (RT)

Targeted therapy

28-day cycle for up to 6 cycles

References

  1. Study 1053: Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Karlin L, Robak T, Gladstone DE, le Coutre P, Dietrich S, Gotic M, Larratt L, Offner F, Schiller G, Swords R, Bacon L, Bocchia M, Bouabdallah K, Breems DA, Cortelezzi A, Dinner S, Doubek M, Gjertsen BT, Gobbi M, Hellmann A, Lepretre S, Maloisel F, Ravandi F, Rousselot P, Rummel M, Siddiqi T, Tadmor T, Troussard X, Yi CA, Saglio G, Roboz GJ, Balic K, Standifer N, He P, Marshall S, Wilson W, Pastan I, Yao NS, Giles F. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018 Aug;32(8):1768-1777. Epub 2018 Jul 20. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT01829711
    1. Update: Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Robak T, le Coutre PD, Gjertsen BT, Troussard X, Roboz GJ, Karlin L, Gladstone DE, Kuptsova-Clarkson N, Liu S, Patel P, Rotolo F, Mitry E, Pastan I, Giles F; Study 1053 investigators. Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial. J Hematol Oncol. 2021 Feb 24;14(1):35. link to original article link to PMC article PubMed


Rituximab monotherapy

Regimen

Study Dates of enrollment Evidence
Nieva et al. 2003 2000-2002 Phase 2

Targeted therapy

Supportive therapy

4-week course

References

  1. Nieva J, Bethel K, Saven A. Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. Blood. 2003 Aug 1;102(3):810-3. Epub 2003 Mar 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Vemurafenib monotherapy

Regimen

Study Dates of enrollment Evidence Efficacy
Tiacci et al. 2015 (MSKCC 12-200) 2013-2015 Phase 2 ORR: 96-100%
Tiacci et al. 2015 (HCL-PG01) 2013-2015 Phase 2 ORR: 96-100%

Note: a pooled analysis of two phase 2 trials is reported in Tiacci et al. 2015; they have slightly different durations - please see original text for details.

Targeted therapy

28-day cycle for varying durations: 4 cycles (HCL-PG01); 6 cycles (MSKCC 12-200)

References

  1. MSKCC 12-200: 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. Epub 2015 Sep 9. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01711632
  2. HCL-PG01: 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. Epub 2015 Sep 9. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed EudraCT 2011-005487-13


Hairy cell leukemia variant (HCLv), all lines of therapy

Note: this is a distinct disease process from hairy cell leukemia, but will be included on this page for now given the similarities. We may create a dedicated page in the future.

Cladribine & Rituximab

Regimen

Study Dates of enrollment Evidence
Ravandi et al. 2011 2004-2009 Phase 2, fewer than 20 pts in this cohort

Note: 28 days after administration of cladribine, bone marrow examination was repeated, and then rituximab was started.

Chemotherapy, first portion (course 1)

Supportive therapy, first portion (course 1)

All were administered at the discretion of the treating physician.

Targeted therapy, second portion (cycles 2 to 9)

28-day course, then 7-day cycle for 8 cycles

References

  1. 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. Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia. Blood. 2011 Oct 6;118(14):3818-23. Epub 2011 Aug 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
    1. Update: 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. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial. Br J Haematol. 2016 Sep;174(5):760-6. Epub 2016 Jun 15. link to original article link to PMC article PubMed


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