eMedicine Specialties > Hematology > Stem Cells and Disorders
Hairy Cell Leukemia
Updated: Nov 24, 2008
Introduction
Background
Hairy cell leukemia (HCL) is a chronic lymphoid leukemia that was originally described in 1958 by Bouroncle and colleagues.1,2 Hairy cell leukemia is a B-cell disease, and the abnormal cell has hairlike cytoplasmic projections on its surface.
Hairy cell leukemia is recognized as a clonal B-cell malignancy as identified by immunoglobulin gene rearrangements that result in a phenotype B-cell expression of surface antigens, which reflect the differentiation between the immature B-cell of chronic lymphocytic leukemia and the plasma cell of multiple myeloma.
For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Leukemia.
Pathophysiology
The abnormal cell in hairy cell leukemia is a clonal B-cell lymphocyte (see Image 1). This cell infiltrates the patient's reticuloendothelial system and interferes with bone marrow function, resulting in bone marrow failure or pancytopenia. The hairy cell also infiltrates the liver and spleen, resulting in organomegaly.
The etiology of hairy cell leukemia has not been determined, although some investigators suggest that exposures to benzene, organophosphorus insecticides, or other solvents may be related to disease development. This hypothesis has not been confirmed by other reports, although a French study that evaluated occupational exposure to pesticides and lymphoid neoplasms among men appears to support the hypothesis that occupational pesticide exposures may not only be involved in hairy cell leukemia, Hodgkin lymphoma, and multiple myeloma, but also may play a role in non-Hodgkin lymphoma.3 Further research is needed.
Exposure to radiation, agricultural chemicals, and wood dust, and a previous history of infectious mononucleosis have been suggested as etiologic associations in previous reports.
Overexpression of cyclin D1 protein, an important cell-cycle regulator, has been observed in hairy cell leukemia and may play a role in the molecular pathogenesis of the disease.
Accumulation of hairy cells in the bone marrow, liver, and spleen, with very little lymph node involvement, is characteristic of hairy cell leukemia. This pattern probably results from the expression of the integrin receptor alpha4-beta1 by the hairy cells and the interaction of the receptor with the vascular adhesion molecule-1 (VCAM-1) found in splenic and hepatic endothelia, bone marrow, and splenic stroma.
Frequency
United States
Hairy cell leukemia is relatively uncommon and accounts for 2% of all leukemia cases, which is about 600-800 new patients diagnosed each year.2
International
Some geographic variations have been observed with hairy cell leukemia, such as an extremely low incidence in Japan.
Mortality/Morbidity
- Symptoms of pancytopenia in hairy cell leukemia are related to anemia (fatigue and weakness), thrombocytopenia (bleeding or easy bruising), and neutropenia (infections).
- Abdominal discomfort is a common symptom, resulting from hepatosplenomegaly. It is usually controlled with new effective drug therapy, although late recurrences may occur. Recurrences are usually responsive to medications.
Race
- This disease is observed more commonly in whites. It has been reported to occur in Ashkenazi Jewish males, and it is rare in Japan and in those of African descent.2
Sex
- Hairy cell leukemia is observed mostly in males, with a male-to-female ratio of 4:1 to 5:1.2
Age
- Hairy cell leukemia occurs predominantly in middle-aged men, with a median age of 52 years.2
Clinical
History
- The most common symptoms and presenting complaints in hairy cell leukemia are weakness and fatigue due to anemia. Approximately one third of patients have bleeding from thrombocytopenia, and another one third have fever and infections from neutropenia.
- Symptoms related to organ infiltration of the reticuloendothelial system may occur. Abdominal discomfort from an enlarged spleen is present in one quarter of patients.
- Some patients may present with weight loss, fever, and night sweats, similar to other lymphoproliferative disorders.
- Hairy cell leukemia is associated with gram-positive and gram-negative bacterial infections, as well as atypical mycobacterial and invasive fungal infections. Other opportunistic infections, such as Legionella, toxoplasmosis, and listeriosis, have been reported.
- Hairy cell leukemia is associated with other systemic immunologic disorders including scleroderma, polymyositis, polyarteritis nodosa, erythematous maculopapules, and pyoderma gangrenosum.
- Other uncommon conditions may be associated with hairy cell leukemia, such as acquired factor VIII antibodies, paraproteinemia, and systemic mast cell disease.
Physical
- Splenomegaly is the most common physical finding in virtually every patient with hairy cell leukemia, and it is massive in more than 80% of patients.
- Hepatomegaly with mild liver function abnormalities is found in 20% of cases, and lymphadenopathy is found in 10%.
- A low-grade fever is part of the disease, but it may be due to an infection from the resulting neutropenia. In more than half of the cases, it is from a gram-negative organism. Atypical mycobacterial infections are common. Disseminated fungal infections and Pneumocystis carinii may occur in some cases of hairy cell leukemia.
- Peripheral lymphadenopathy is uncommon, with fewer than 10% of patients presenting with peripheral nodes larger than 2 cm in diameter. However, internal adenopathy may develop after a prolonged disease course and was found in 75% of patients at autopsy.
Causes
Hairy cell leukemia is due to proliferation of a clonal malignant B cell that infiltrates the reticuloendothelial cells, particularly the bone marrow, resulting in bone marrow failure.
Differential Diagnoses
| Agnogenic Myeloid Metaplasia With
Myelofibrosis | Myelophthisic Anemia |
| Anemia | Myeloproliferative Disease |
| Aplastic Anemia | |
| Chronic Lymphocytic Leukemia | |
| Myelodysplastic Syndrome |
Other Problems to Be Considered
Agnogenic myeloid metaplasia
Chronic lymphocytic leukemia
Low-grade lymphoma
Myelosclerosis
Pancytopenia and marrow fibrosis
Prolymphocytic leukemia
Splenic marginal zone lymphoma
Systemic mastocytosis
Workup
Laboratory Studies
- The typical hairy cells of hairy cell leukemia are so named because of their characteristic cytoplasmic projections, which appear as fine (hairlike) microvilli when seen by light microscopy, phase-contrast microscopy, and electron microscopy. These are mononuclear cells with eccentric or centrally placed nuclei.
- Hairy cells have a mature B-cell phenotype and typically express single or multiple immunoglobulin light chains and pan–B-cell antigens, such as CD19, CD20, CD22, and CD79b, but not CD21 (late B-cell marker). The cells also typically express CD103, CD11c, and CD25 but usually not CD5, CD10, or CD23. Hairy cells strongly express CD45, seen as a bright signal, with increased forward and side scatter resembling large lymphocytes and monocytes. Immunophenotypic analysis helps distinguish hairy cell leukemia from other low-grade B-cell malignancies.
- Monoclonal BLy-7 has high sensitivity and specificity for HCL. CD22 stains at higher intensity in hairy cells than in normal B cells. Hairy cells can be identified immunophenotypically in 92% of cases, even when the cells represent less than 1% of the circulating lymphocytes.
- Cytochemical evaluation is important for diagnostic confirmation of the morphologic findings. Hairy cells demonstrate strong positivity for tartrate-resistant acid phosphatase (TRAP) staining (see Image 3). A positive TRAP stain in conjunction with a characteristic bone marrow biopsy is essentially diagnostic of hairy cell leukemia.
- The peripheral blood cell counts show pancytopenia with decreased cell counts in all 3 cell lines.
- Anemia is usually severe and normochromic-normocytic in character.
- Neutropenia and monocytopenia are usually present in hairy cell leukemia, but an elevated white blood cell count (hairy cells) is found in 20% of cases.
- Thrombocytopenia is found in more than 80% of patients.
- The bone marrow aspirate is usually unsuccessful due to a "dry tap." Infiltration of the bone marrow by hairy cell leukemia makes aspirating cells through a needle difficult.
- Core biopsy of the bone marrow shows a pattern of hairy cell infiltration with a single round or oval nucleus separated by abundant cytoplasm in a fine fibrillar network.4
- The cell appears separated, resulting in the characteristic fried-egg appearance.4
- Clonal cytogenetic abnormalities are present in two thirds of patients, and the involvement of chromosomes 1, 2, 5, 6, 11, 14, 19, and 20 have been described. Chromosome 5 abnormality is most frequent (in 40% of patients) with trisomy 5 and pericentric inversions and interstitial deletions of band 5q13.
Imaging Studies
- Most patients with hairy cell leukemia have massive splenomegaly such that imaging studies are unnecessary to appreciate its presence.
- In milder forms, a liver and spleen scan or ultrasound measurement may detect some mild forms of organomegaly that may be missed by abdominal palpation.
Other Tests
- Difficult cases can be confirmed by using immunophenotypic analysis of the buffy coat cells or by performing electron microscopy on suspected cells.
- Soluble interleukin-2 receptor levels are elevated in patients with hairy cell leukemia and may provide additional supportive data for the diagnosis.
Histologic Findings
The findings of pancytopenia and splenomegaly in the presence of circulating cells that are TRAP positive and a dry bone marrow aspirate with biopsy material showing infiltration with a mononuclear cells that have a fried-egg appearance are diagnostic of hairy cell leukemia.
Treatment
Medical Care
Chemotherapeutic approaches
The first-line therapy for hairy cell leukemia is 2-chlorodeoxyadenosine (2-CdA) 0.1 mg/kg/d (Cladribine, Leustatin) by continuous intravenous infusion for 7 days, which can be performed on an outpatient basis with a pump, using a percutaneous intravenous central catheter (PICC).5,6 Growth factors are not routinely given but may be added in patients with febrile neutropenia. The response is usually first observed in the platelet counts (in 2-4 wk) followed by white blood cell counts and neutrophils and, finally, hemoglobin levels. Bone marrow biopsy is repeated in 3 months, but minimal residual disease does not need therapy.
With one course of therapy of 2-CdA, 80% of patients obtain a complete remission (CR), and the remainder obtains a partial remission (PR). Several long-term studies have been reported. Chadha et al reported that, although the overall survival rate at 12 years was 87%, the progression-free survival at 12 years was only 54%.7 In addition, 17% of patients had developed another malignancy during that time.
For increased convenience, some groups have given 2-CdA as a 2-hour infusion (0.14 mg/kg/d) for 5 days. Zinzani et al reported a CR rate of 81% and a PR rate of 19% using this schedule.8 The 13-year overall survival rate was 96%, and the relapse-free survival rate was 52%.8 No randomized study comparing the 24-hour infusional versus the 2-hour infusional schedules is available.
A current trend is the significance of minimal residual disease following treatment with 2-CdA. Ravandi et al administered rituximab to patients with residual disease following 2-CdA.9 Eleven of 12 patients had eradication of minimal residual disease with this treatment. Whether this will alter the natural history of hairy cell leukemia or prevent relapse is unclear. Currently, the standard therapy for patients with minimal residual disease is observation.
For patients with relapsed hairy cell leukemia who have previously been treated with splenectomy, interferon, or 2-deoxyformycin (2'-DCF, Pentostatin), retreatment with 2-CdA in the same manner is indicated, especially if their disease had previously responded to 2-CdA. In patients previously treated with 2-CdA, response rates of 50% are typical.
Rituximab is a monoclonal antibody against CD20. In patients with relapsed or refractory hairy cell leukemia, response rates of 50% are reported.
- Hairy cell leukemia may behave as a chronic leukemia without causing any symptoms. Approximately 10% of cases, usually in elderly men with moderate splenomegaly and mild decrease in blood counts, never require therapy.
- The standard criteria for initiating therapy include the following:
- Symptoms or blood transfusion requirement
- Significant anemia with hemoglobin of 8-10 g/dL or less
- Thrombocytopenia with platelet counts of 50,000-100,000/mL or less
- Neutropenia with an absolute neutrophil count (ANC) of 500-1000/mL or less
- Less common indications for therapy include the following:
- Leukocytosis with a high proportion of hairy cells
- Repeated life-threatening infections
- Symptomatic splenomegaly
- Bulky or painful lymphadenopathy
- Vasculitis
- Bony involvement
- For patients with hairy cell leukemia that is refractory to 2-CdA, or if relapse occurs after 2 cycles of 2-CdA, the authors recommend treatment with 2'-deoxycoformycin (2'DCF, Pentostatin) 4 mg/m2 intravenously every 2 weeks for 3-6 months.10
- Alpha interferon at 2 million U/m2 subcutaneously 3 times a week for 12-18 months can be used to salvage relapsed or refractory hairy cell leukemia.
Surgical Care
- Splenectomy was the first standard treatment modality and was used commonly in the past, but this propcedure has been replaced by the newer agents available. Cytopenia improved rapidly in most patients. Although splenectomy does not produce pathologic remissions in the bone marrow, the peripheral blood cell counts improve in all 3 cell lines in approximately 40-70% of patients. This response usually lasts for a median of 20 months in approximately two thirds of patients, with an overall survival rate of 70% in 5 years.
- Splenic size does not predict response to splenectomy.
- Effective medical therapy has replaced splenectomy as the first-line treatment for hairy cell leukemia.
- Splenectomy is currently reserved for patients whose conditions fail to respond to systemic therapy or for those with bleeding from thrombocytopenia. Patients undergoing splenectomy require appropriate vaccination.
- Laparoscopic splenectomy has decreased the morbidity and duration of the postsurgical recovery period.
Medication
Systemic therapy has changed rapidly in the past 10 years because of new biologic agents (eg, interferons) and new purine analogues. Also, the availability of recombinant human hematopoietic growth factors has improved supportive care during life-threatening infections in those with hairy cell leukemia.
Purine Analogues
Gibbett and coworkers observed that patients with severe combined immunodeficiency (SCID) were deficient in the purine catabolic enzyme adenosine deaminase. This deficiency causes intracellular accumulation of deoxyadenosine triphosphate and results in lymphocytotoxicity. Purine analogues mimic this condition by irreversibly binding to adenosine deaminase or by fostering resistance to deamination in the purine salvage pathway.
Cladribine or 2-chlorodeoxyadenosine (Leustatin)
Synthetic antineoplastic agent for continuous IV infusion. The enzyme deoxycytidine kinase phosphorylates this compound into active 5'-triphosphate derivative. This, in turn, breaks DNA strands, inhibits DNA synthesis, disrupts cell metabolism, and causes death to resting and dividing cells.
Most active among the purine analogues in the treatment of hairy cell leukemia. Has a 94% overall response and 84% complete response in hairy cell leukemia.
Patients whose disease does not respond to the initial regimen likely will not have a response to retreatment.
Dosing
Adult
0.1 mg/kg/d IV for 7 d
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with a history of hematologic or immunologic dysfunction; neurotoxicity may occur; allopurinol can be used prophylactically to prevent hyperuricemia secondary to tumor lysis
Pentostatin or 2-deoxycoformycin (Nipent)
Approved by the FDA for hairy cell leukemia but is less active than 2-CDA for this disease. Treatment results in a 79% overall response rate and a 64% complete response rate in patients with hairy cell leukemia. Response rates (CR + PR) of more than 90% have been reported.
Dosing
Adult
4 mg/mm3 IV bolus weekly for 3-6 mo until complete response achieved
Pediatric
Not established
Interactions
Vidarabine, allopurinol, and fludarabine may increase toxicity.
Contraindications
Documented hypersensitivity; severely suppressed bone marrow ( <3,000 white blood cells/mm3)
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in the presence of hepatic or renal insufficiency
Interferons
Interferons are naturally produced proteins with antitumor and immunomodulatory effects.
Interferon alfa-2a (Roferon)
Protein product manufactured by recombinant DNA technology. First systemic drug shown to partially eradicate hairy cells from bone marrow, and first approved indication was for this disease. The mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of the host immune response may play important roles.
Roferon and Intron A differ from the natural product only in amino acid residue at position 23 and achieve similar results in hairy cell leukemia. Response rates are 65% overall, with 10% of patients achieving a complete remission.
Dosing
Adult
2 million U/m2 SC 3 times/wk until the maximum response is achieved
Pediatric
Not established
Interactions
Theophylline may increase the toxicity; cimetidine may increase the antitumor effects; zidovudine and vinblastine may increase the toxicity.
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients with brain metastases, severe hepatic or renal insufficiencies, seizure disorders, multiple sclerosis, or a compromised CNS
Interferon alfa-2b (Intron A)
Protein product manufactured by recombinant DNA technology. First systemic drug shown to partially eradicate hairy cells from bone marrow, and first approved indication was for this disease. The mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of the host immune response may play important roles.
Roferon and Intron A differ from the natural product only in amino acid residue at position 23 and achieve similar results in hairy cell leukemia. Response rates are 65% overall, with 10% of patients achieving a complete remission.
Dosing
Adult
2 million U/m2 SC 3 times/wk until the maximum response is achieved
Pediatric
Not established
Interactions
Potential risk of renal failure when administered concurrently with interleukin-2; theophylline may increase interferon alfa toxicity by reducing clearance; cimetidine may increase the antitumor effects of interferon alfa; zidovudine and vinblastine may increase the toxicity of interferon alfa
Contraindications
Documented hypersensitivity; patients who have anaphylactic sensitivity to mouse immunoglobulin (IgG), egg protein or neomycin; autoimmune hepatitis
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Depression and suicidal ideation may be side effects of the treatment; infrequently, severe or fatal GI hemorrhage has been reported in association with alfa interferon therapy; before the initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cells, and bone marrow hairy cells; monitor periodically (eg, monthly) during treatment to determine the response to treatment; if the patient's condition does not respond within 6 mo, discontinue the treatment; if a response occurs, continue treatment until no further improvement is observed; it is not known whether continued treatment after that time is beneficial
Recombinant Granulocyte Colony-Stimulating Factors (G-CSFs)
Because treatment of hairy cell leukemia is associated with neutropenia, use of G-CSF may be helpful in reducing the toxicity of treatment for hairy cell leukemia.
Filgrastim or G-CSF (Neupogen)
Shortens the early myelosuppressive effects of alfa interferon and reverses neutropenia in some patients with hairy cell leukemia.
Dosing
Adult
5 mcg/kg/d SC until the ANC has reached 10,000/µL
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not use 12-24 h before or 24 h after administering cytotoxic chemotherapy, because this will increase the sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy.
Follow-up
Further Inpatient Care
- Hyperuricemia may occur during therapy in patients with hairy cell leukemia with leukocytosis and high tumor burden. Add allopurinol at 300 mg per day orally.
- The risk of second malignancies has been observed in affected patients either through hairy cell leukemia disease itself or secondary from the immunosuppressive effects of the therapy, including melanoma, prostate cancers, gastrointestinal malignancies, non-Hodgkin lymphomas, and nonmelanomatous cancers.
- A 20-year follow-up in 117 patients in British Columbia showed 31% developed a second malignancy, of which 30% were diagnosed before hairy cell leukemia was found.11 On the other hand, MD Anderson reported no excess of second malignancies among 350 patients with hairy cell leukemia who were treated with interferon, 2'-CdA, or 2'-DCF.12
Further Outpatient Care
- Hairy cell leukemia is usually indolent and protracted; late relapses occur.
- Long-term outpatient follow-up is often necessary in most patients.
- The overall survival rate with 2'DCF up front or after alpha interferon failure in 241 patients was 80-85% at 10 years.
- Evaluation of minimal residual disease by posttreatment bone marrow biopsies using anti-CD20 by flow cytometry reveals that 13-51% of patients in apparent CR had minimal residual disease and appears to predict clinical relapse. Because a majority respond very well to retreatment (92% response) or salvage treatment (80% response), no evidence supports treatment of minimal residual disease.
- Newer therapies, such as anti-CD20 monoclonal antibody rituximab, had been tested in patients with hairy cell leukemia that was refractory to standard treatment. Several studies with small numbers of patients who received rituximab showed an overall response of 64%, with a median duration of response of 14 months, to 100% response and a duration of 73 months, indicating that this form of therapy is active against hairy cell leukemia.
Prognosis
- Hairy cell leukemia behaves like a chronic leukemia. With new therapies, most patients achieve clinical remissions and, sometimes, long-term cures.
- Although relapses are known to occur after 5-10 years, they are usually responsive to the same treatment.
- Most of the difficulty is in making the diagnosis.
Patient Education
Multimedia
Media file 1: Blood film at × 400 magnification. This image demonstrates a lymphocytosis and an absence of any other type of blood cell (pancytopenia). The characteristic cytoplasmic projections are already visible. Photographed by U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Media file 2: Blood film at × 1000 magnification. This image demonstrates lymphocytes with characteristic cytoplasmic projections. Photographed by U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Media file 3: Blood film at × 1000 magnification. This image demonstrates tartrate-resistant acid phosphatase (TRAP) activity of lymphocytes. Photographed by U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
References
Bouroncle BA, Wiseman BK, Doan CA. Leukemic reticuloendotheliosis. Blood. Jul 1958;13(7):609-30. [Medline]. [Full Text].
Cannon T, Mobarek D, Wegge J, Tabbara IA. Hairy cell leukemia: current concepts. Cancer Invest. Oct 2008;26(8):860-5. [Medline].
Orsi L, Delabre L, Monnereau A, et al. Occupational exposure to pesticides and lymphoid neoplasms among men: results of a French case-control study. Occup Environ Med. Nov 18 2008;epub ahead of print. [Medline].
Katayama I. Bone marrow in hairy cell leukemia. Hematol Oncol Clin North Am. Dec 1988;2(4):585-602. [Medline].
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. Apr 19 1990;322(16):1117-21. [Medline].
Goodman GR, Burian C, Koziol JA, Saven A. Extended follow-up of patients with hairy cell leukemia after treatment with cladribine. J Clin Oncol. Mar 1 2003;21(5):891-6. [Medline]. [Full Text].
Chadha P, Rademaker AW, Mendiratta P, et al. Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University experience. Blood. Jul 1 2005;106(1):241-6. [Medline]. [Full Text].
Zinzani PL, Magagnoli M, Bendandi M, et al. Long-term follow-up of hairy cell leukemia patients treated with 2-chlorodeoxyadenosine. Haematologica. Sep 2000;85(9):922-5. [Medline]. [Full Text].
Ravandi F, Jorgensen JL, O'Brien SM, et al. Eradication of minimal residual disease in hairy cell leukemia. Blood. Jun 15 2006;107(12):4658-62. [Medline]. [Full Text].
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. Nov 1 2000;96(9):2981-6. [Medline]. [Full Text].
Au WY, Klasa RJ, Gallagher R, et al. Second malignancies in patients with hairy cell leukemia in british columbia: a 20-year experience. Blood. Aug 15 1998;92(4):1160-4. [Medline]. [Full Text].
Kurzrock R, Strom SS, Estey E, et al. Second cancer risk in hairy cell leukemia: analysis of 350 patients. J Clin Oncol. May 1997;15(5):1803-10. [Medline].
Glaspy JA, Baldwin GC, Robertson PA, et al. Therapy for neutropenia in hairy cell leukemia with recombinant human granulocyte colony-stimulating factor. Ann Intern Med. Nov 15 1988;109(10):789-95. [Medline].
Monnereau A, Orsi L, Troussard X, Berthou C, et al. Cigarette smoking, alcohol drinking, and risk of lymphoid neoplasms: results of a French case-control study. Cancer Causes Control. Dec 2008;19(10):1147-60. [Medline].
Ratain MJ, Golomb HM, Vardiman JW, et al. Relapse after interferon alfa-2b therapy for hairy-cell leukemia: analysis of prognostic variables. J Clin Oncol. Nov 1988;6(11):1714-21. [Medline].
Keywords
hairy cell leukemia, hairy cell, leukemic reticuloendotheliosis, HCL, chronic lymphoid leukemia, lymphoproliferative disorders, B-cell disease, clonal B-cell lymphocyte, pancytopenia, anemia, thrombocytopenia, neutropenia, hepatosplenomegaly
Contributor Information and Disclosures
Author
Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.
Coauthor(s)
Ulrich Woermann, MD, Consulting Staff, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland
Disclosure: Nothing to disclose.
Medical Editor
Rodger L Bick, MD, PhD, FACP, Clinical Professor of Medicine, University of Texas Southwestern Medical Center; Director, Dallas and Pacific Thrombosis Hemostasis and Vascular Medicine Clinical Center
Rodger L Bick, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Blood Banks, American Cancer Society, American College of Angiology, American College of Physicians, American Geriatrics Society, American Heart Association, American Medical Association, American Society for Clinical Pathology, American Society of Hematology, Association of Clinical Scientists, California Medical Association, California Thoracic Society, International College of Angiology, International Society of Hematology, International Society on Thrombosis and Haemostasis, New York Academy of Sciences, and Southwest Oncology Group
Disclosure: Nothing to disclose.
Pharmacy Editor
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment
Managing Editor
Troy H Guthrie, Jr, MD, Director of Cancer Institute, Baptist Medical Center
Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association
Disclosure: Nothing to disclose.
CME Editor
Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.
Chief Editor
Koyamangalath Krishnan, MD, FRCP, FACP, Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, James H Quillen College of Medicine at East Tennessee State University
Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians
Disclosure: Nothing to disclose.