Hairy cell leukemia

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Section editor
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Sanjai Sharma, MD
Sequoia Regional Cancer Center
Visalia, CA
11 regimens on this page
16 variants on this page


Guidelines

ESMO

Hairy Cell Leukemia Foundation

NCCN

Untreated

Cladribine monotherapy

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

Study Years 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 Evidence
Piro et al. 1990 Pilot, <20 pts
Tallman et al. 1996 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 Years 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 Years 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 Evidence
Damasio et al. 1998 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 contains dosing details in abstract 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 contains dosing details in manuscript 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 contains dosing details in abstract 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 contains dosing details in manuscript 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 contains dosing details in manuscript PubMed NCT00003746

Cladribine & Rituximab

Protocol

Study Evidence
Ravandi et al. 2011 Phase 2

Chemotherapy

Supportive medications

All were administered at the discretion of the treating physician.

5-day course

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

Targeted therapy

8-week course

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. link to original article contains dosing details in manuscript 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

Pentostatin monotherapy

Regimen variant #1

Study Evidence
Spiers et al. 1987 Non-randomized

Chemotherapy

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

Regimen variant #2

Study Years 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

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

  • Pentostatin (Nipent) 4 mg/m2 IV rapid injection once on day 1
    • 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.

Supportive medications

  • 1.5 liters of IV fluid hydration with every dose

14 day cycles (see note)

References

  1. Spiers AS, Moore D, Cassileth PA, Harrington DP, Cummings FJ, Neiman RS, Bennett JM, O'Connell MJ. Remissions in hairy-cell leukemia with pentostatin (2'-deoxycoformycin). N Engl J Med. 1987 Apr 2;316(14):825-30. link to original article contains dosing details in manuscript 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 contains dosing details in abstract 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 contains dosing details in manuscript 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 contains dosing details in manuscript PubMed

Relapsed or refractory

Bendamustine & Rituximab (BR)

BR: Bendamustine, Rituximab

Regimen

Study Evidence
Burotto et al. 2013 Pilot, <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 PubMed

Cladribine & Rituximab

Protocol

Study Evidence
Ravandi et al. 2011 Phase 2, <20 pts in this cohort

Chemotherapy

Supportive medications

All were administered at the discretion of the treating physician.

5-day course

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

Targeted therapy

8-week course

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. link to original article contains dosing details in manuscript 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 Years of enrollment Evidence
Quesada et al. 1986 (N2752) 1984-NR Non-randomized (RT)

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 Years of enrollment Evidence
Quesada et al. 1984 NR Pilot, <20 pts
Golomb et al. 1986 1983-1984 Non-randomized
Golomb et al. 1988 1985-1987 Non-randomized portion of RCT (RT)

Of historic interest. Most patients had previously undergone splenectomy.

Immunotherapy

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 Years 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 contains dosing details in abstract 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 Years of enrollment Evidence
Nieva et al. 2003 2000-2002 Phase 2

Targeted therapy

Supportive medications

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. link to original article contains dosing details in manuscript PubMed

Vemurafenib monotherapy

Regimen

Study Evidence Efficacy
Tiacci et al. 2015 (MSKCC 12-200) Phase 2 ORR: 96-100%

Note that a pooled analysis of two phase II trials is reported; they have slightly different durations - please see original text for details.

Targeted therapy

28-day cycle for up to 4 cycles (Italian trial) or 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 contains dosing details in manuscript link to PMC article PubMed NCT01711632

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

Protocol

Study Evidence
Ravandi et al. 2011 Phase 2, <20 pts in this cohort

Chemotherapy

Supportive medications

All were administered at the discretion of the treating physician.

5-day course

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

Targeted therapy

8-week course

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. link to original article contains dosing details in manuscript 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