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Information from PDQ -- for Health Professionals
Hairy cell leukemia
208/01651
** GENERAL INFORMATION **
Hairy cell leukemia is a chronic lymphoproliferative disorder that is easily
controlled. Decision to treat is based on symptomatic cytopenias, massive
splenomegaly, or the presence of other complications. About one-tenth of all
patients will never require therapy.
** STAGE INFORMATION **
There is no generally accepted staging system that is useful both for prognosis
and therapy.
For the purpose of treatment decisions, it is best to consider this disease in
two broad categories: untreated hairy cell leukemia and progressive hairy cell
leukemia, either post-splenectomy or post-systemic therapy.
-- Untreated --
Untreated hairy cell leukemia is characterized by splenomegaly, varying degrees
of leukopenia (occasionally leukocytosis) and/or pancytopenia, and bone marrow
infiltration by an atypical cell with prominent cytoplasmic projections ("hairy
cells"). The bone marrow is usually fibrotic and is not easily aspirated.
Bone marrow biopsies are therefore required for diagnosis and evaluation of the
degree of hairy cell infiltration.
-- Progressive --
Progressive hairy cell leukemia, post-splenectomy (or following any systemic
therapy) is characterized by progressive bone marrow replacement by hairy
cells, with pancytopenia refractory to treatment. For patients with advanced
hairy cell leukemia treated with cladribine (2-chlorodeoxyadenosine, 2-CdA),
pentostatin, or interferon alfa, the survival rate appears to be greater than
85% at 5 years after the initiation of any one of these therapies.[1,2]
References:
1. Frassoldati A, Lamparelli T, Federico M, et al.: Hairy cell leukemia: a
clinical review based on 725 cases of the Italian Cooperative Group
(ICGHCL): Italian Cooperative Group for Hairy Cell Leukemia. Leukemia
and Lymphoma 13(3-4): 307-316, 1994.
2. Kurzrock R, Strom SS, Estey E, et al.: Second cancer risk in hairy cell
leukemia: analysis of 350 patients. Journal of Clinical Oncology 15(5):
1803-1810, 1997.
** TREATMENT OPTION OVERVIEW **
The initial therapies of choice are either cladribine (2-chlorodeoxyadenosine,
2-CdA) or pentostatin.[1] These drugs have comparable response rates but have
not been compared in phase III trials. Cladribine is administered as a one-
time continuous infusion or series of subcutaneous injections, and is
associated with a high rate of febrile neutropenia.[2-4] Rarely, more than 1
course of treatment is required to induce a desirable response. Treatment
should be discontinued once complete remission or stable partial remission with
normalization of peripheral blood counts is reached. The presence of residual
disease may be predictive of relapse but does not seem to affect survival.[5]
The role of consolidation or maintenance therapy in preventing relapse or
progression of the disease following treatment with purine analogs has not been
evaluated and remains unproven. Pentostatin is administered intermittently for
a longer treatment duration but may result in a lower incidence of febrile
complications.[6,7] While most patients remain disease-free 10 years after
treatment with these purine analogues, no patient has been followed long enough
to assess cure.[8] Both nucleoside analogues cause profound suppression of CD4
counts which may last for a year. With use of cladribine, there may be an
increased risk of second malignancies among patients with hairy cell leukemia
(observed to expected ratio of about 1.8 in several series after 6 years).[4,9]
Several series using pentostatin did not report an increased risk of second
malignancies.[8,10,11] For a few patients, such as those with severe
thrombocytopenia, splenectomy can be considered.[12] After splenectomy,
one-half of patients will require no additional therapy and long-term survivors
are common. Therapy with interferon alfa is another treatment option,
especially for patients with intercurrent infection.[7,13]
The designations in PDQ that treatments are "standard" or "under clinical
evaluation" are not to be used as a basis for reimbursement determinations.
References:
1. Tallman MS, Peterson LC, Hakimian D, et al.: Treatment of hairy-cell
leukemia: current views. Seminars in Hematology 36(2): 155-163, 1999.
2. Hoffman MA, Janson D, Rose E, et al.: Treatment of hairy-cell leukemia
with cladribine: response, toxicity, and long-term follow-up. Journal
of Clinical Oncology 15(3): 1138-1142, 1997.
3. Cheson BD, Sorensen JM, Vena DA, et al.: Treatment of hairy cell leukemia
with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the
National Cancer Institute: a report of 979 patients. Journal of
Clinical Oncology 16(9): 3007-3015, 1998.
4. Saven A, Burian C, Koziol JA, et al.: Long-term follow-up of patients
with hairy cell leukemia after cladribine treatment. Blood 92(6):
1918-1926, 1998.
5. Fayad L, Kurzrock R, Keating M, et al.: Treatment of hairy-cell leukemia
(HCL) with 2-CdA: long term follow-up at M.D. Anderson Cancer Center.
Blood 90(suppl 1): A2363, 1997.
6. Ribeiro P, Bouaffia F, Peaud PY, et al.: Long term outcome of patients
with hairy cell leukemia treated with pentostatin. Cancer 85(1): 65-71,
1999.
7. Grever M, Kopecky K, Foucar MK, et al.: Randomized comparison of
pentostatin versus interferon alfa-2a in previously untreated patients
with hairy cell leukemia: an intergroup study. Journal of Clinical
Oncology 13(4): 974-982, 1995.
8. Flinn IW, Kopecky KJ, Foucar MK, et al.: Long-term follow-up of remission
duration, mortality, and second malignancies in hairy cell leukemia
patients treated with pentostatin. Blood 96(9): 2981-2986, 2000.
9. Au WY, Klasa RJ, Gallagher R, et al.: Second malignancies in patients
with hairy cell leukemia in British Columbia: a 20-year experience.
Blood 92(4): 1160-1164, 1998.
10. Kurzrock R, Strom SS, Estey E, et al.: Second cancer risk in hairy cell
leukemia: analysis of 350 patients. Journal of Clinical Oncology 15(5):
1803-1810, 1997.
11. Ribeiro P, Bouaffia F, Peaud PY, et al.: Long term outcome of patients
with hairy cell leukemia treated with pentostatin. Cancer 85(1): 65-71,
1999.
12. Golomb HM, Vardiman JW: Response to splenectomy in 65 patients with hairy
cell leukemia: an evaluation of spleen weight and bone marrow
involvement. Blood 61(2): 349-352, 1983.
13. Capnist G, Federico M, Chisesi T, et al.: Long term results of interferon
treatment in hairy cell leukemia. Leukemia and Lymphoma 14(5-6):
457-464, 1994.
** UNTREATED HAIRY CELL LEUKEMIA **
-- Initial treatment --
Hairy cell leukemia is a highly treatable disease. Since it is easily
controlled, many patients have prolonged survival with sequential therapies.
The decision to treat is based on cytopenias (especially if symptomatic),
increasing splenomegaly, indications that the disease is progressing, or the
presence of other, usually infectious complications. It is reasonable to offer
no therapy if the patient is asymptomatic and blood counts are maintained in an
acceptable range.[1]
-- Progressive hairy cell leukemia --
Standard treatment options:
1. Cladribine (2-Chlorodeoxyadenosine, 2-CdA) given intravenously by continuous
infusion or as daily subcutaneous injections for one week results in a complete
response rate of 50% to 80% and an overall response rate of 85% to 95%.[1-8]
The response rate was lower in 979 patients treated with the Group C mechanism
of the National Cancer Institute (50% complete remission rate, 37% partial
remission rate).[5] Responses are durable with this short course of therapy
and patients who relapse often respond to retreatment with cladribine. This
drug may cause fever and immunosuppression, with documented infection in one-
third of treated patients.[5] In a retrospective study of patients with
cladribine-associated neutropenic fever, filgrastim (G-CSF) did not demonstrate
a decrease in the percentage of febrile patients, number of febrile days, or
frequency of admissions for antibiotics.[9] A potential increased risk for
second malignancies with this agent remains controversial.
2. Pentostatin given intravenously every other week for 3 to 6 months produces
a 50% to 76% complete response rate and an 80% to 87% overall response
rate.[10,11] Complete remissions are of substantial duration. In two trials
with 9-year median follow-up, relapse-free survival ranged from 56% to
67%.[12,13] Side effects include fever, immunosuppression, cytopenias, and
renal dysfunction. A randomized comparison of pentostatin and interferon alfa
demonstrated higher and more durable responses to pentostatin.[10]
3. Interferon alfa given subcutaneously three times per week for 1 year yields
a 10% complete response rate and an 80% overall response rate. The drug
frequently produces an influenza-like syndrome early in the course of
treatment. Late effects include depression and lethargy. Responding patients
who relapse usually respond to retreatment with interferon alfa.[14] Remission
can be prolonged with a low-dose maintenance regimen.[15] A randomized
comparison of pentostatin and interferon alfa demonstrated significantly higher
and more durable responses to pentostatin.[10]
4. Splenectomy will partially or completely normalize the peripheral blood in
the vast majority of patients with hairy cell leukemia.[16] There is usually
little or no change in the bone marrow after splenectomy, and virtually all
patients have progressive disease within 12 to 18 months. Therefore, since a
number of more effective alternatives are available, splenectomy is playing a
decreasing role in the treatment of this disease.
References:
1. Saven A, Piro L: Newer purine analogues for the treatment of hairy-cell
leukemia. New England Journal of Medicine 330(10): 691-697, 1994.
2. Juliusson G, Heldal D, Hippe E, et al.: Subcutaneous injections of
2-chlorodeoxyadenosine for symptomatic hairy cell leukemia. Journal of
Clinical Oncology 13(4): 989-995, 1995.
3. Tallman MS, Hakimian D, Variakojis D, et al.: A single cycle of
2-chlorodeoxyadenosine results in complete remission in the majority of
patients with hairy cell leukemia. Blood 80(9): 2203-2209, 1992.
4. Hoffman MA, Janson D, Rose E, et al.: Treatment of hairy-cell leukemia
with cladribine: response, toxicity, and long-term follow-up. Journal
of Clinical Oncology 15(3): 1138-1142, 1997.
5. Cheson BD, Sorensen JM, Vena DA, et al.: Treatment of hairy cell leukemia
with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the
National Cancer Institute: a report of 979 patients. Journal of
Clinical Oncology 16(9): 3007-3015, 1998.
6. Saven A, Burian C, Koziol JA, et al.: Long-term follow-up of patients
with hairy cell leukemia after cladribine treatment. Blood 92(6):
1918-1926, 1998.
7. Lauria F, Bocchia M, Marotta G, et al.: Weekly administration of
2-chlorodeoxyadenosine in patients with hairy-cell leukemia: a new
treatment schedule effective and safer in preventing infectious
complications. Blood 89(5): 1838-1839, 1997.
8. Robak T, Blasinska-Morawiec M, Krykowski E, et al.:
2-chlorodeoxyadenosine (2-CdA) in 2-hour versus 24-hour intravenous
infusion in the treatment of patients with hairy cell leukemia.
Leukemia and Lymphoma 22(1-2): 107-111, 1996.
9. Saven A, Burian C, Adusumalli J, et al.: Filgrastim for
cladribine-induced neutropenic fever in patients with hairy cell
leukemia. Blood 93(8): 2471-2477, 1999.
10. Grever M, Kopecky K, Foucar MK, et al.: Randomized comparison of
pentostatin versus interferon alfa-2a in previously untreated patients
with hairy cell leukemia: an intergroup study. Journal of Clinical
Oncology 13(4): 974-982, 1995.
11. Ribeiro P, Bouaffia F, Peaud PY, et al.: Long term outcome of patients
with hairy cell leukemia treated with pentostatin. Cancer 85(1): 65-71,
1999.
12. Johnston JB, Eisenhauer E, Wainman N, et al.: Long-term outcome following
treatment of hairy cell leukemia with pentostatin (Nipent): a National
Cancer Institute of Canada study. Seminars in Oncology 27(2 suppl 5):
32-36, 2000.
13. Flinn IW, Kopecky KJ, Foucar MK, et al.: Long-term follow-up of remission
duration, mortality, and second malignancies in hairy cell leukemia
patients treated with pentostatin. Blood 96(9): 2981-2986, 2000.
14. Golomb HM, Ratain MJ, Fefer A, et al.: Randomized study of the duration
of treatment with interferon alfa-2b in patients with hairy cell
leukemia. Journal of the National Cancer Institute 80(5): 369-373,
1988.
15. Capnist G, Federico M, Chisesi T, et al.: Long term results of interferon
treatment in hairy cell leukemia. Leukemia and Lymphoma 14(5-6):
457-464, 1994.
16. Golomb HM, Vardiman JW: Response to splenectomy in 65 patients with hairy
cell leukemia: an evaluation of spleen weight and bone marrow
involvement. Blood 61(2): 349-352, 1983.
** REFRACTORY HAIRY CELL LEUKEMIA **
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Cladribine (2-Chlorodeoxyadenosine, 2-CdA) and pentostatin are both highly
efficacious in the treatment of patients with disease refractory to interferon
alfa.[1-4] Patients who relapse after cladribine or pentostatin often respond
to retreatment with the same or another purine analogue.[5-8] Evidence
suggests that fludarabine may also be active in patients who are refractory to
interferon alfa or pentostatin.[9] An anti-CD22 recombinant immunotoxin can
induce complete remissions in patients resistant to re-treatment with purine
analogues.[10][Level of evidence: 3iiiDiii] An anecdotal response to rituximab
(anti-CD20 monoclonal antibody) has been reported.[11]
Allogeneic bone marrow transplantation may be considered for selected patients
in rare instances. The patients should be in good health and have an
HLA-identical sibling. The high mortality of this procedure justifies its use
only in refractory cases.[12]
Aggressive, high-dose chemotherapy has been beneficial in some cases, but the
associated morbidity and mortality are high. It should not be considered
unless other more frequently effective therapies have been exhausted.
References:
1. Blick M, Lepe-Zuniga JL, Doig R, et al.: Durable complete remissions
after 2'-deoxycoformycin treatment in patients with hairy cell leukemia
resistant to interferon alpha. American Journal of Hematology 33(3):
205-209, 1990.
2. Piro LD, Carrera CJ, Carson DA, et al.: Lasting remissions in hairy-cell
leukemia induced by a single infusion of 2-chlorodeoxyadenosine. New
England Journal of Medicine 322(16): 1117-1121, 1990.
3. Estey EH, Kurzrock R, Kantarjian HM, et al.: Treatment of hairy cell
leukemia with 2-chlorodeoxyadenosine (2-CdA). Blood 79(4): 882-887,
1992.
4. Tallman MS, Hakimian D, Variakojis D, et al.: A single cycle of
2-chlorodeoxyadenosine results in complete remission in the majority of
patients with hairy cell leukemia. Blood 80(9): 2203-2209, 1992.
5. Hoffman MA, Janson D, Rose E, et al.: Treatment of hairy-cell leukemia
with cladribine: response, toxicity, and long-term follow-up. Journal
of Clinical Oncology 15(3): 1138-1142, 1997.
6. Saven A, Burian C, Koziol JA, et al.: Long-term follow-up of patients
with hairy cell leukemia after cladribine treatment. Blood 92(6):
1918-1926, 1998.
7. Ribeiro P, Bouaffia F, Peaud PY, et al.: Long term outcome of patients
with hairy cell leukemia treated with pentostatin. Cancer 85(1): 65-71,
1999.
8. Zinzani PL, Magagnoli M, Bendandi M, et al.: Long-term follow-up of hairy
cell leukemia patients treated with 2-chlorodeoxyadosine. Haematologica
85(9): 922-925, 2000.
9. Kantarjian HM, Schachner J, Keating MJ: Fludarabine therapy in hairy cell
leukemia. Cancer 67(5): 1291-1293, 1991.
10. Kreitman RJ, Wilson WH, Bergeron K, et al.: Efficacy of the anti-CD22
recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell
leukemia. New England Journal of Medicine 345(4): 241-247, 2001.
11. Zinzani PL, Ascani S, Piccaluga PP, et al.: Efficacy of rituximab in
hairy cell leukemia treatment. Journal of Clinical Oncology 18(22):
3875-3877, 2000.
12. Cheever MA, Fefer A, Greenberg PD, et al.: Treatment of hairy cell
leukemia with chemoradiotherapy and identical-twin bone marrow
transplantation. New England Journal of Medicine 307(8): 479-481, 1982.
Date Last Modified: 02/2002
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* but this information is not available through CancerMail. For more *
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