Hairy cell leukemia: an autopsy study.

Autopsy material from 5 patients with hairy cell leukemia was examined. In addition to the expected widespread involvement of the hematopoietic system and of the liver, all of the patients had various amounts of pulmonary infiltration by leukemic cells. This infiltration was so severe in one instance that the resulting pulmonary insufficiency was the cause of death. Other areas of hairy cell infiltration included the peripancreatic connective tissue in all cases, kidneys in 3 cases, pericardium in 2 cases, and skin in 1 case. Association of plasma cells with the infiltrating neoplastic cells was prominent. In one patient, foci of large, bizarre cells were found in several lymph nodes and in the pericardium. Whether these cells represent transformation of the hairy cells into a larger, less differentiated cell type, or the emergence of a second hematopoietic neoplasm, is unknown.     

Hairy cell leukemia and sarcoid.

A 45-year-old female simultaneously developed both hairy cell leukemia and acute sarcoid. A defect in suppressor T lymphocytes which allowed an unrestrained B-cell proliferation manifested as both hairy cell leukemia and sarcoid is proposed.     

Hairy cell leukemia

Hairy cell leukemia is a malignancy with a variable course that can be relatively indolent or rapidly fatal. Alterations in the immune system are responsible for much of the morbidity and mortality from hairy cell leukemia. More than 60% of patients die from infection, and infections are both pyogenic and nonpyogenic. Many patients have transfusion requirements, and bleeding complications can also occur. Treatment strategies for hairy cell leukemia have evolved and are being modified as more is learned about the disease. Splenectomy is the initial treatment when patients become symptomatic, and if the disease progresses after splenectomy, chlorambucil offers good control in many patients. Radiation can be used for local palliation, as when complications such as bulky adenopathy or bone lesions occur. Initial studies using interferon in the treatment of hairy cell leukemia look encouraging, but more investigation is necessary before the role of interferon in treatment of hairy cell leukemia is determined.     

Hairy cell leukemia

Opinion statement The standard therapy for hairy cell leukemia (HCL) is with the nucleoside analogs, 2’-deoxycoformycin (dCF) or 2-chlorodeoxyadenosine (CdA), which produce morphologic complete remissions (CRs) in the majority of patients, although residual hairy cells can frequently be detected by molecular or immunologic techniques. Relapses continue to occur over time, but most patients respond well to retreatment withthe same agent. The longest follow-up is for patients treated with dCF, where the 5- and 10-year relapse-free survival rates are 80% to 85% and 67% to 76%, respectively. dCF is usually administered as 4 mg/m2 intravenously every second week until CR followed by two additional treatments for consolidation. CdA is administered as 0.09 mg/kg/d × 7, by continuous intravenous infusion, although it may be equally effective when given as daily boluses or subcutaneously. More recent studies have suggested that CdA, 0.15 mg/kg intravenously weekly × 6, produces equivalent response rates, while reducing the risk of febrile neutropenia (which occurs in approximately 50% of patients using the standard regimen). We have found this to be a very simple, safe, and effective regimen. Both dCF and CdA should be used with caution in the presence of renal or hepatic dysfunction, and both are contraindicated in the presence of active infection. Interferon-alfa (3 × 10⁶ U subcutaneously three times per week for 12 months) produces inferior response rates but is less likely to cause febrile neutropenia. It can be considered for initial treatment for patients with active infection, patients at high risk of febrile neutropenia, and patients who cannot tolerate or are resistant to the nucleoside analogs. Splenectomy is now rarely performed in HCL, but it is required for splenic rupture and may be of value in “splenic” HCL or those with massive splenomegaly and hypersplenism. In preliminary studies, monoclonal antibodies directed against CD20 or CD25 also show activity in HCL, but their roles in this disease require further study.     

Hairy cell leukemia: clinical, pathological and ultrastructural findings in Asian-Indians

Background: Hairy-cell leukemia (HCL), lymphoproliferative disease of older age, is characterized by projections from surface of abnormal cells. Aim: The aim was to study the clinical presentation and ultrastructural changes in hairy cells (HCs) following cladribine treatment. Settings and Design: Clinical presentation, peripheral smear, bone marrow aspiration and biopsy of HCL cases diagnosed over a period of three years were reviewed. Materials and Methods: Consecutive HCL cases in Hematology clinic of a tertiary care center were enrolled. Tartarate-resistant acid phosphatase (TRAP) test was done to detect HCs and electron microscopy was done to demonstrate initial ultrastructural changes and alterations following cladribine therapy. Results: Fifteen cases of HCL, aged 32-57 years (median 47 years) were studied. The clinical presentation included splenomegaly in 15 (100%), fever in 10 (67%), hepatomegaly and pain abdomen in eight (53%), fatigue in nine (60 %) cases. The commonest laboratory features were monocytopenia in 13 (87%), neutropenia in 12 (80%), anemia in 10 (67 %) and pancytopenia in nine (60%). All patients showed symptomatic improvement on cladribine therapy. Electron microscopy after treatment (three months) showed loss of the finger like projections, characteristic bald lymphocytes, loss of ribosomal lamellar complexes, as well as decrease in mitochondria and vacuoles. Conclusions: Indian patients with HCL are younger. Cladribine is an effective therapy for these patients and leads to complete response in most of the patients. There is a significant improvement in the ultrastructural features following cladribine therapy.     

Hairy cell leukemia

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder characterized by pancytopenia and variable infiltration of the reticuloendothelial system with "hairy" lymphocytes. HCL is more common in men than women and has a median age of diagnosis of 52 yr. Typically, patients with HCL respond well to purine analog-based therapy. The purpose of this review will be to establish the current status of HCL with respect to its pathophysiology, diagnosis, management, and future directions.     

Hairy cell leukemia

Six patients of 'Hairy cell leukemia' (HCL) were seen by us between 1982 and 1987. Five patients had anaemia and two had leukopaenia. None of the patients had thrombocytopaenia at presentation. All the patients were positive for tartarate resistant acid phosphatase. Two had B and one had T cell surface markers. Characteristic cytoplasmic projections and ribosomal lamellar complexes were seen on electron microscopy in four patients. Three patients were treated with splenectomy with satisfactory results.     

Hairy cell leukemia

BACKGROUND:

Historically, the first treatment choices for hairy cell leukemia (HCL) were splenectomy and alpha‐interferon. Recently, purine analogues (pentostatin and cladribine) changed radically the treatment modality, inducing complete and durable responses in the majority of patients.

METHODS:

The authors analyzed the outcome of different lines of therapy in 121 HCL patients followed in their institute from 1986 to 2008, with a median follow‐up of 105 months. Patients were divided into subgroups according to the number of treatments; Group A included 121 patients who underwent a front‐line therapy, Group B patients (n =53) were treated with 2 lines, Group C patients (n = 34) with 3 lines, Group D patients (n = 17) with 4 lines, and Group E patients (n = 8) with 5 lines.

RESULTS:

In Group A, 92 (77%) patients obtained a complete response (CR), 23 (18%) a partial response, and the remaining 6 (5%) a minor or no response; median duration of response was 2.7 years. In Group B, 53 relapsed patients achieved a second CR rate of 73.5%; median duration of response was 2.5 years. Group C contained 34 patients in a second relapse, with a CR rate after the third line of treatment of 70.5% (median duration of response, 2.2 years). In Group D, 11 (64.7%) patients obtained a CR (median duration of response, 1.6 years), and in Group E 4 (50%) of 8 patients achieved a CR (median duration of response, 1.3 years).

CONCLUSIONS:

This study confirms the high risk (>40% of all patients) of retreatment of HCL patients and the need to maximize primary response. Cancer 2010. © 2010 American Cancer Society.     

Hairy cell leukemia

The diagnosis of 131 patients with hairy cell leukemia was based on the demonstration of characteristic cells in the blood and bone marrow in 105 males and 26 females between 23 and 87 years (mean 52) of age. Enlargement of the spleen was found in 71% of cases. Anemia was present in 78% of the patients, neutropenia below 1000/mm³ in 63%, thrombocytopenia below 100,000/mm³ in 73%.The median survival (m.s.) was 42 months. Of 41 documented causes of death, 33 were related to infection. Prognosis is the worst for patients with neutropenia below 500/mm³ or leukocytosis over 10,000/mm³.The patients without palpable spleen have the best survival. The 14 patients who received chemotherapy had a 20 months m.s. Eighty-four patients (with and without splenomegaly) received only supportive therapy: their m.s. was 50 months. In splenomegalic patients, survival was better when splenectomy was performed (m.s. 42 months) than when it was not (m.s. 34 months).     

Hairy cell leukemia

Hairy cell leukemia is a rare B-cell neoplasm. When treated with either pentostatin or cladribine, complete and durable remissions can be secured and life expectancy for most patients is normal. A small minority of patients require alternative treatment with monoclonal antibodies or immunotoxins. Patients who attain a complete response to first-line treatment have the best prognosis.     

Hairy cell leukemia. Current management

The long-term outlook for patients with HCL has brightened over the last 5 years with the development of two highly effective systemic therapies, pentostatin and alpha-interferon. Pentostatin can induce complete responses in over 75 per cent of patients and may offer cure in this disease. Splenectomy continues to have a role as first-line therapy in selected patients in whom it may offer a median remission duration of over 5 years. Alpha-interferon is the treatment of choice for patients requiring initial systemic therapy and can be used intermittently to re-induce remission in patients with disease progression off therapy. Outside of clinical trials pentostatin should be utilized only in appropriately selected patients refractory to interferon therapy.     

Hairy cell leukemia and human T cell leukemia virus

HCL is a lymphoproliferative disorder, primarily of B cells. T cell variant HCL is a rare clinical entity, which has a clinical picture similar to that of the common B cell HCL disease. HTLV-II has been isolated from a case of T cell variant HCL. This subtype of HTLV-II-associated disease is indolent in character in comparison to the very aggressive HTLV-I-associated disease. Investigation of the biology and molecular genetics of HTLV is in progress. It is hoped that better understanding of HTLV and the comparative differences between HTLV-I and HTLV-II will provide specific insights into the mechanisms of human leukemogenesis.     

Non-Hodgkin's lymphomas: an ultrastructural study correlating morphology with immunologic cell type.

Ultrastructural studies were performed on 40 B-cell and 14 T-cell lymphomas of non-Hodgkin's type (NHL). Most B-cell lymphomas were comprised of neoplastic cells with morphologic features compatible with a follicular center cell origin. Dendritic reticulum cells and their desmosome-associated processes, characteristic of germinal centers, were observed in all 11 cases of nodular poorly differentiated lymphocytic lymphoma and in one of two cases of nodular "histiocytic" lymphoma, but were not identified in the lymphomas with a diffuse growth pattern. Desmosomes were observed between dendritic reticulum cells and were not found between lymphoid cells. Large neoplastic cells comprising lymphomas of "histiocytic," mixed lymphocytic "histiocytic," and "undifferentiated" types were characterized ultrastructurally and immunologically as lymphoid cells. Malignant lymphomas of well and moderately well differentiated lymphocytic types (7 cases) revealed B-cell markers, and represented a distinct homogenous group of neoplasms, with electron microscopic features most closely resembling follicular cuff lymphocytes. T-cell malignancies included lymphoblastic lymphomas (3 cases), large cell ("histiocytic") lymphomas (4 cases), lymphoepithelioid cell ("Lennert's") lymphomas (2 cases), mycosis fungoides (3 cases) and diffuse poorly differentiated lymphocytic lymphomas (2 cases). A consistent finding in the T-cell proliferations was the presence of small and/or large lymphoid cells with extremely irregular and/or convoluted nuclei, which occurred in varying proportions and with variable degrees of nuclear complexity. The nuclear irregularity evident in the neoplastic T cells was distinguishable from that observed for lymphoid cells of B-cell lymphomas. In comparing the cytoplasmic features of the T- and B-cell neoplasms ultrastructurally, the only distinguishing feature was the presence of well developed granular endoplasmic reticulum with dilated cisternae, i.e., plasmacytoid features, predictive of a B cell origin.     

Hairy cell leukemia: treatment prospects

The recent advances in the management of hairy cell leukemia, a chronic and indolent B-cell lymphoproliferative disorder are reviewed. The introduction of α-interferon, purine analogs and recombinant monoclonal antibodies/immunotoxins has dramatically improved the outcome in a disease that once had a dismal prognosis. The underlying genetic defect remains unknown.     

Hairy cell leukemia: current concepts

Hairy cell Leukemia (HCL) is a chronic lymphoproliferative disorder that was characterized in the late 1950s. HCL is defined, according to the WHO classification, as a mature (peripheral) B-cell neoplasm (1). HCL accounts for between 2-3% of all leukemia cases, with about 600 new cases diagnosed in the U.S. each year (1). HCL occurs more commonly in males, with an overall male to female ratio of approximately 4:1. The median age of onset is 52 years. This disease is seen more commonly in Caucasians and appears to be especially frequent in Ashkenazi Jewish males, with rare occurrence in persons of Asian and African descents (1). Hairy cells are distinct, clonal B cells arrested at a late stage of maturation. They are small B lymphoid cells that possess oval nuclei and abundant cytoplasm with characteristic micro-filamentous ("hairy") projections. They strongly express CD103, CD22, and CD11c (2). These cells typically infiltrate the bone marrow, the spleen, and to a lesser extent the liver, lymph nodes, and skin. Many patients present with splenomegaly and pancytopenia. Other clinical manifestations include recurrent opportunistic infections and vasculitis. Historically, HCL was considered uniformly fatal (2). However, recent treatment advances, using purine analogues such as Cladribine and Pentostatin, led to a significant improvement in prognosis with achievement of high response rates and durable remissions (2).     

Hairy cell leukemia: treatment prospects

The recent advances in the management of hairy cell leukemia, a chronic and indolent B-cell lymphoproliferative disorder are reviewed. The introduction of alpha-interferon, purine analogs and recombinant monoclonal antibodies/immunotoxins has dramatically improved the outcome in a disease that once had a dismal prognosis. The underlying genetic defect remains unknown.     

Hairy cell leukemia in father and son

Hairy cell leukemia (HCL) is an uncommon B cell disorder, and familial HCL is rarely encountered among the first degree relatives of HCL patients. A father and son, both of whom developed hairy cell leukemia, is presented in this report. The HLA haplotype shared by the father and son was A2, B18, BW6, CW7, DR3, DR10, and DQ8. Among these haplotypes, HLA A2 and Bw6 have previously been reported.     

Hairy cell leukemia: diagnostic pathology

The pathology of HCL has been reviewed with a focus on the diagnostic hematopathology of this rare, but fascinating, disease. The discrimination of HCL from other B-cell lymphoproliferations, particularly HCL-V and SMZL, has been emphasized. The unique responsiveness of HCL to 2-CdA and other chemotherapeutic agents makes this distinction critical. Fortunately, HCL has consistent cytologic, histologic, cytochemical, and immunologic features that make classification reliable and reproducible. Less straightforward is the differential diagnosis of SMZL and HCL-V, problematic because of the rarity of both disorders, lack of discriminating evidence-based criteria, and perhaps a biologic kinship between these two disorders that share many clinical and pathologic features. Fortunately, this is not a clinically critical distinction.