Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a preliminary feasibility study to assess the pharmacokinetics and efficacy of pentostatin in a patient undergoing dialysis. Pentostatin is a safe and well-tolerated medication, but a dose reduction is required for patients with renal insufficiency. We present a patient with chronic adult T-cell leukemia, whose white blood cell count exceeded 100 X 10(9)/l, and end-stage renal disease, receiving long-term thrice-weekly dialysis. The initial treatment with oral cyclophosphamide or with oral etoposide resulted in no response. After informed consent was obtained, pentostatin (1, 2, or 3mg/m2) was administered. 1 or 2 hours after injection, the patient received hemodialysis over 4 hours to remove any of the drug remaining in his system. Plasma concentrations of pentostatin were calculated with the known pharmacokinetics parameters. The differential equations describing a 2-compartment open-infusion pharmacokinetic model were fitted to the measured concentration-time data. Tumor lysis syndrome occurred 4 days after the course of the highest dose (3mg/m2), and the patient achieved complete remission. Anorexia, graded as 2 according to the NCI-CTC classification system, occurred and continued for four weeks. Pentostatin therapy consisting of the decreased dose (2mg/m2) was then administered every other week and provided a transient partial response with mild anorexia. Consequently, pentostatin can be considered as one of the chemotherapeutic regimens available for a patient undergoing dialysis.
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PMID:[Pentostatin treatment for a patient with chronic type adult T-cell leukemia undergoing hemodialysis]. 1644 Aug 2

Host conditioning prior to allogeneic bone marrow transplantation (BMT) has traditionally involved the use of high-dose, myeloablative chemotherapy and irradiation, focusing on maximal tumor cytoreduction as well as adequate immunosuppression to allow engraftment of allogeneic stem cells. High-dose chemoradiation conditioning regimens have been associated with a significant incidence of organ toxicity and acute and chronic graft-versus-host disease (GVHD). Recent efforts to diminish the acute transplant-associated toxicities have focused on the development of relatively nontoxic, nonmyeloablative, or less myeloablative conditioning regimens, with the emphasis being predominantly on induction of immunosuppression to enable engraftment. Without ablative chemotherapy, disease control in these regimens is largely relegated to the graft-versus-leukemia/lymphoma (GVL) effect. While the evolution these regimens has resulted in successful engraftment of allogeneic stem cells with minimal toxicity, acute and chronic GVHD occurs in 20% to 50% of patients and remains a major cause of transplant-associated morbidity. Strategies to lower the incidence of acute GVHD have primarily focused on more precise molecular donor/recipient matching, alternative stem cell sources, and T-cell depletion of the graft. While successful in lowering the frequency and severity of GVHD, T-cell-depleted grafts have been associated with compromised the graft-versus-disease effect. Recent studies have suggested that, in addition to T-effector cells within the graft, donor and host dendritic cells may play a role in GVHD. Purine analogues have been evaluated as part of these regimens. While fludarabine and cladribine have been shown to be effective, these agents have been associated with an increased incidence of serious infection and severe acute GVHD. Pentostatin has a different mechanism of action and was also investigated as part of these preparative regimens. Regimens using pentostatin/extracorporeal photopheresis (ECP)/total body irradiation (TBI) have been shown to be well tolerated and associated with early full donor engraftment with a predominance of donor dendritic cell (DC)2 cells and a low incidence of acute GVHD. Further investigation evaluating this preparative regimen is warranted.
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PMID:The role of purine analogues in low-intensity regimens with allogeneic hematopoietic stem cell transplantation. 1654 13

Major advances in the management of patients who have hairy cell leukemia have been made following the use of purine nucleoside analogs. Pentostatin and cladribine are equally effective, and have impressive long-term effectiveness. Although the degree of myelosuppression may be less with the use of pentostatin, this may reflect differences in the schedule and dose of drug administration between these agents. The gradual, but relentless, improvement in the peripheral blood counts enables out-patient management with pentostatin in most patients. Cladribine affords the convenience of a single course of administration. A direct comparative study with these two agents is unlikely to yield the optimal management of patients who have minimal residual disease following the administration of either agent is warranted in the context of a clinical trial. Patients do relapse, and the overall survival curves have not reached a plateau, which indicates that cure has not been secured. The satisfaction of having improved the outcome for patients who have this previously untreatable leukemia should not give way to complacency for further improvement in the management of this disease. Future studies should be directed to optimizing the therapy for minimal residual disease as well as clearer definition of supportive care.
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PMID:Pentostatin: impact on outcome in hairy cell leukemia. 1699 Jan 10

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).
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PMID:Hairy cell leukemia: current concepts. 1879 68

Large granular lymphocyte leukemia (T-LGL) is an indolent T lymphoproliferative disorder that was difficult to diagnose with certainty until clonality testing of the T cell receptor gene became routinely available. We studied the natural history and response to treatment in 25 consecutive patients with T-LGL diagnosed between 2004 and 2008 in which the diagnosis was confirmed by molecular analysis, to define an effective treatment algorithm. The median age at diagnosis was 61 years (range 27-78), with a male to female ratio of 1:1.8 and presenting features of fatigue (n = 13), recurrent infections (n = 9), and/or abnormal blood counts (n = 5). Thirteen patients with symptomatic disease were treated as follows: pentostatin (nine patients), cyclosporine (six patients), methotrexate (three patients), and alemtuzumab in two patients in whom pentostatin was ineffective. Pentostatin was the single most effective therapy, with a response rate of 75% and minimal toxicity. The overall survival (OS) and progression-free survival (PFS) 37 months from diagnosis were 80% and 52%, respectively. Treatment of T-LGL should be reserved for patients with symptomatic disease, but in this series, pentostatin treatment was less toxic and more effective than cyclosporine or methotrexate.
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PMID:Large granular lymphocyte leukemia: natural history and response to treatment. 2036 69

The adenosine deaminase inhibitor 2'-deoxycoformycin (DCF) has been used to treat 40 patients with hairy cell leukaemia (HCL) who have been followed up for a minimum of 6 months. 21 patients had previously undergone splenectomy. 33 had received treatment with alpha-interferon (IFN), half of whom had relapsed and the remainder had either been partially treated due to intolerance or had an incomplete response. Deoxycoformycin was administered by slow intravenous injection at a dose of 4 mg/m(2) weekly for 4 consecutive weeks and then 2-weekly for 4 doses followed by 4-weekly injections until a complete remission was achieved. No maintenance therapy was given. The overall response rate was 97yi, with 82% complete remission (CR) and 15% partial remission (PR). CR have lasted from 3+ to 30+ months (median 12 +) with no relapses recorded so far. Only one evaluable patient, suffering from a variant form of HCL, failed to respond to DCF, whilst two other HCL-variant cases who had been resistant to alpha-IFN have achieved a PR and are still on treatment. DCF was generally well tolerated, the major toxicity being related to cytopenia and associated infection. Four patients developed severe infections, one of whom died of septicaemia before it was possible to evaluate the response to DCF. A group of 12 patients who had received alpha-IFN immediately prior to treatment with DCF and had obtained clinical and haematological benefit had fewer infections with DCF than the group who had either not received IFN immediately before or who had failed to respond to it. In view of the infections associated with DCF, we would now recommend initial therapy for HCL patients with alpha-IFN for 2-4 months to obtain clinical and haematological improvement, followed by DCF given 2-weekly, to eradicate residual disease. This approach may achieve a higher proportion of sustained CR with a short treatment time and minimal toxicity.
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PMID:Treatment of Hairy Cell Leukaemia with 2'-Deoxycoformycin. 2746 84


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