pentostatin and Pancytopenia

Hairy cell leukemia is a mature B-cell non-Hogkin lymphoma characterized by unique clinical, morphological and immunhistochemical features. Patients with hairy cell leukemia usually present with splenomegaly, progressive pancytopenia and a relative indolent clinical course. The diagnosis does not always indicate immediate treatment, as treatment depends on the clinical stage of the leukemia. Asymptomatic disease without progression requires a watchful waiting policy, while other categories usually need treatment. The treatment of choice is purine nucleoside analogues (pentostatin, cladribine) which can achieve complete remission even for decades. Interferon and monoclonal CD20 antibodies can also significantly prolong event-free survival. Unfortunately, only the latter two therapies are easily available in Hungary. Splenectomy, which was suggested as first line treatment before the era of purine nucleoside analogues, is only recommended as a last resort. Although hairy cell leukemia is a well-defined lymphoproliferative disease, sometimes it is difficult to differentiate it from other similar entities such as hairy cell leukema variant, splenic marginal zone lymphoma, small lymphocytic lymphoma etc. Making the correct diagnosis is of utmost importance because of the great difference in treatment modalities. Recently, a somatic mutation was found in all analysed hairy cell leukemia samples, but not in other splenic B-cell lymphomas. This article reviews the significance of this observation and presents the different types of methods for the detection of this mutation.

Topics: Antibodies, Monoclonal; Antigens, CD20; Antineoplastic Agents; Cladribine; Diagnosis, Differential; Disease-Free Survival; Humans; Hungary; Interferons; Leukemia, Hairy Cell; Mutation; Neoplasm Staging; Pancytopenia; Pentostatin; Purine Nucleosides; Remission Induction; Splenectomy; Splenomegaly; Watchful Waiting

Hairy-cell leukaemia (HCL) is an uncommon B-cell chronic lymphoproliferative disorder that accounts for about 2% of all leukaemias. Although the disease is generally indolent in its natural course, the majority of patients require treatment for life-threatening infections due to pancytopenia or symptomatic splenomegaly. During the past 20 years, remarkable progress has been made in the treatment of HCL. Since the introduction of interferon-alpha, splenectomy, which was formerly the standard therapy, has been rarely used. With the purine analogues cladribine and pentostatin, response rates are even better than with interferon-alpha and long-lasting remissions can be achieved in most patients. Therefore, these agents are now considered the treatment of choice. Recently, immunotherapeutic approaches which use monoclonal antibodies have increased the number of therapeutic options for HCL and offer promising salvage strategies for patients who relapse or who are refractory to treatment with purine analogues. In this review the different treatment options available are discussed and recommendations for the clinical management of the HCL are summarised.

Topics: Antibiotics, Antineoplastic; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Antineoplastic Agents; Cell Adhesion Molecules; Cladribine; Humans; Interferon-alpha; Lectins; Leukemia, Hairy Cell; Neoplasm, Residual; Neoplasms, Second Primary; Pancytopenia; Pentostatin; Receptors, Interleukin-2; Rituximab; Sialic Acid Binding Ig-like Lectin 2; Spleen; Splenectomy; Splenomegaly; Treatment Outcome; Vidarabine

Hairy cell leukaemia is a rare chronic lymphoproliferative disease, characterized by splenomegaly, pancytopenia and recurrent infection. The characteristic 'hairy cells', present in the peripheral blood and bone marrow, are the hallmark of this leukaemia. The disease has a chronic, progressive course, and the majority of patients afflicted by it require therapy. The most common reason to initiate treatment is neutropenia with or without associated infectious complications, or the development of severe thrombocytopenia. Therapeutic options in hairy cell leukaemia include splenectomy, interferon administration, or the use of chemotherapeutic agents such as pentostatin (2'-deoxycoformycin) and 2-chlorodeoxyadenosine. Splenectomy is still indicated in the treatment of young patients with significant splenomegaly and only minimal bone marrow involvement. Interferon treatment induces remission in approximately 90% of patients with hairy cell leukaemia, but complete remission is obtained in only 5-10%. The development of antibodies against interferon was initially considered a major problem, but longer follow-up of patients who developed antibodies has shown that it is transient and does not have a significant impact on the overall response to treatment. Pentostatin induces complete remission in 60-70% of patients and partial remission in 20-40%. 2-Chlorodeoxyadenosine is a very promising drug in the treatment of this rare leukaemia, inducing long-lasting complete remission in approximately 80% of patients. While interferon does not cure the disease, it is possible that a subset of patients treated with pentostatin or 2-chlorodeoxyadenosine are cured. Longer follow-up of these patients will determine whether this is true.

Topics: Adult; Cladribine; Clinical Trials as Topic; Female; Humans; Immunologic Deficiency Syndromes; Immunologic Factors; Interferon-alpha; Leukemia, Hairy Cell; Male; Middle Aged; Pancytopenia; Pentostatin; Prognosis; Remission Induction; Splenectomy; Splenomegaly; Treatment Outcome

The rationale for antileukemic therapy in hairy cell leukemia is to reduce the significant risk of infection and other potential serious complications. Corticosteroids have limited value; both corticosteroids and chemotherapy are associated with substantial risks of infection. The mainstay of therapy has been splenectomy. Improvement is seen in 50% to 70% of patients with cytopenias; although the impact of splenectomy on survival has not been clearly demonstrated, prolonged hematologic improvement can occur. Splenectomy presumably alleviates the pancytopenic effect of hypersplenism by removing the preferred site of leukemic cell proliferation. Human interferon represents a major advance in management. Favorable results with natural leukocyte alpha interferon have been confirmed by data with biosynthetic (recombinant) alpha interferon. Importantly, the incidence of infection has been clearly shown to decrease, suggesting improved survival in patients with advanced hairy cell leukemia. Many questions regarding interferon therapy remain unanswered, including optimal dose, optimal duration, and maintenance therapy after maximal response. The mechanism of action is unclear, but possibly interferon modulates as yet unidentified lymphokines or growth factors. In vitro evidence suggests a direct antiproliferative effect of type I interferon on hairy cells. Preliminary data suggest that although toxicity issues, including induction of immunodeficiency and renal insufficiency require further clarification, deoxycoformycin, an adenosine deaminase inhibitor, is also highly effective and holds substantial promise as an important therapeutic modality.

Topics: Adrenal Cortex Hormones; Antibiotics, Antineoplastic; Antineoplastic Agents; Humans; Hypersplenism; Interferon Type I; Interferon-alpha; Leukemia, Hairy Cell; Pancytopenia; Pentostatin; Recombinant Proteins; Risk Factors; Splenectomy; Survival Rate

The case of a patient with the aplastic variant of hairy cell leukaemia, successfully treated with the drug Deoxycoformycin(Pentostatin), is presented. It is very important to be aware of this rare variant of a rare disease so that the right treatment can be offered.

Topics: Anemia, Aplastic; Antimetabolites, Antineoplastic; Bone Marrow; Diagnostic Errors; Female; Humans; Leukemia, Hairy Cell; Middle Aged; Pancytopenia; Pentostatin; Remission Induction; Splenomegaly; Sweating

Hairy cell leukemia (HCL) is a chronic lymphoproliferative disease of B-cell origin manifested by pancytopenia and splenomegaly. Before 1980 the only effective treatment for HCL was splenectomy, which resolved the cytopenia but did not eliminate the disease from the bone marrow. In addition, the majority of patients progressed after splenectomy and required further treatment. Pentostatin (Nipent; SuperGen, San Ramon, CA) is a purine antimetabolite that was found in phase I studies to induce profound lymphocytopenia Although in vitro studies suggested that T lymphocytes were most sensitive to pentostatin, patients with B-cell chronic lymphatic leukemia and low-grade non-Hodgkin's lymphoma responded to treatment in the initial phase I trials. Due to evidence that the drug was effective in lymphoproliferative disease, patients with HCL were treated with pentostatin. The promising initial results led to phase II studies in both untreated and previously treated patients. These studies demonstrated that pentostatin was highly effective as a single agent, with complete responses seen in 60% to 90% of patients. These responses were durable without maintenance chemotherapy and were seen in patients previously treated with interferon or chemotherapy. Toxicity was usually mild, with nausea and skin rashes predominating. When seen, infections resulting from neutropenia occurred early in treatment. The high response rates and low toxicity suggest that pentostatin should be considered as one of the standard treatments for HCL.

Topics: Adenosine Deaminase Inhibitors; Antibiotics, Antineoplastic; Clinical Trials, Phase II as Topic; Disease Progression; Drug Eruptions; Enzyme Inhibitors; Exanthema; Humans; Immunosuppressive Agents; Leukemia, B-Cell; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Nausea; Neutropenia; Pancytopenia; Pentostatin; Remission Induction; Splenomegaly