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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukaemia is relatively common in the elderly compared to the general population, with over half of all cases of leukaemia occurring in patients aged 65 and over. Special problems are associated with treating patients in this age group. The leukaemias may be intrinsically different, in part because of the high incidence of preceding myelodysplasia. There is increased likelihood of coincident disease. There is lower tolerance to toxic complications, such as infection and bleeding, associated with a decreased resilience of normal haematopoiesis. There is more difficulty in obtaining intravenous access in elderly patients. These problems render patients ineligible for marrow transplants. Myelodysplastic syndromes occur predominantly in the elderly. There are a number of myelodysplastic syndromes now identified, each with its characteristic natural history. Management decisions are based on accurate diagnosis of the specific syndrome, consideration of prognostic features, a period of observation, and conservative treatment principles. More than half the cases of acute myeloblastic leukaemia also occur in the elderly. Prognostic factors must be examined and the literature carefully scrutinized for results pertinent to the elderly patient. In some patients treatment may be justifiably withheld, others may benefit from low dose cytosine arabinoside and some patients should receive aggressive combination chemotherapy. Management of the chronic leukaemias in the elderly is a less controversial area. Chronic lymphocytic leukaemia is the most common of the leukaemias in this age group. Prognostic factors can be determined using staging criteria. observation alone is indicated in many patients. Chlorambucil and prednisone are the most widely used drugs for symptomatic disease. Aggressive combination chemotherapy may benefit a few patients with advanced or refractory CLL. Hairy cell leukaemia is a rare disorder but many of the patients are over age 65. The elderly male patient may have a particularly benign course and require no therapy. Splenectomy is the standard first line of therapy, but recombinant alpha-interferon is sufficiently effective and non-toxic that it should be the treatment of choice in some patients. Deoxycoformycin is also effective in preliminary trials and may soon be routinely indicated. It is not often appreciated that half of all patients with chronic myelogenous leukaemia are aged 65 and over.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The management of leukaemia in the elderly. 332 44

Laboratory and clinical data relating to the use of 2'-deoxycoformycin in human disease are reviewed. Pentostatin is an inhibitor of adenosine deaminase, an enzyme that is important for purine metabolism, but more than one mechanism may be involved in its cytotoxic action. Early studies with dCF employed large doses and for the most part were conducted in patients with acute lymphocytic leukaemia: responses were brief and relatively few, and severe renal, hepatic, and central nervous system toxicity were encountered, leading to temporary abandonment of clinical trials. More recently, it has been shown that dCF is effective in much smaller doses, with considerably less toxicity. It has proved to be more effective in low-grade lymphoid malignancies (chronic leukaemias, indolent lymphomas) than in more undifferentiated neoplasms (acute leukaemias, lymphoblastic and immunoblastic lymphomas), and is outstandingly effective in hairy cell leukaemia, both as initial therapy and after failure of splenectomy and interferon. Pentostatin is profoundly immunosuppressive: generally this is considered a disadvantage but its potential therapeutic exploitation merits investigation. Despite extensive knowledge of its biochemical effects, the optimal dose regimen of dCF and the value of combining it with purine antagonists remain to be defined.
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PMID:The role of pentostatin (2'-deoxycoformycin, dCF) in the management of lymphoproliferative malignancies. 333 90

The adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), at low concentrations (less than 10 microM), enhances the inhibitory activity of adenosine against lymphocyte-mediated cytolysis (LMC) without itself being inhibitory. At higher concentrations, EHNA alone is inhibitory to LMC with an IC50 of 160 microM. This inhibition is reversible upon washout, appears to affect an early stage of the lytic process, and does not appear to involve changes in basal levels of cyclic AMP (cAMP), ribonucleoside 5'-triphosphate pool sizes, S-adenosylhomocysteine levels, or protein carboxymethylation. EHNA does enhance the cAMP response of cytolytic lymphocytes (CL) to activators of adenylate cyclase such as prostaglandin E1. EHNA inhibits lymphocyte high-affinity cAMP phosphodiesterase at immunosuppressive levels, exhibiting hyperbolic mixed-type inhibition (Ki = 83 microM, alpha = 0.47, beta = 0.18). Whereas inhibition of intralymphocytic ADA is complete at low concentrations (less than 25 microM) of EHNA, inhibition of LMC and intralymphocytic cAMP phosphodiesterase increases linearly with EHNA concentration to at least 200 microM. The presence of 200 microM EHNA during the centrifugation of mixtures of CL and EL4 leukemia target cells leads to increased CL cAMP levels. 2'-Deoxycoformycin, a more potent ADA inhibitor than EHNA, is not inhibitory to LMC and shows none of these cAMP-related effects. These results suggest that CL-target cell contact stimulates adenylate cyclase in the CL and that EHNA inhibits LMC due to its enhancement of this target cell-stimulated elevation of cAMP.
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PMID:Inhibition of lymphocyte-mediated cytolysis and cyclic AMP phosphodiesterase by erythro-9-(2-hydroxy-3-nonyl)adenine. 629 34

Two men with advanced but previously untreated B cell hairy-cell leukemia were treated with low doses of pentostatin (2'-deoxycoformycin) in intermittent courses. There was prompt clearance of hairy cells from the blood, regression of splenomegaly and lymphadenopathy, and correction of anemia, thrombocytopenia, and granulocytopenia. Side effects were tolerable and myelosuppression was not observed. Both patients achieved complete remission documented by bone marrow aspiration and biopsy and radionuclide scans of liver and spleen. They remain in complete remission nine and six months, respectively, after their last treatment. Pentostatin (Warner-Lambert, Ann Arbor, Mich) is highly active in hairy-cell leukemia and merits more extensive evaluation in this disease. A woman with hairy-cell leukemia has begun treatment with pentostatin, and at ten weeks there is disappearance of gross splenomegaly and clearance of hairy cells from the blood. Bone marrow studies have not yet been repeated.
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PMID:Hairy-cell leukemia: induction of complete remission with pentostatin (2'-deoxycoformycin). 633 21

Deoxycoformycin (DCF) is a tight-binding inhibitor of adenosine deaminase (ADA) currently undergoing phase I--II evaluation. Neurological toxicity has been a frequent and occasionally severe complication of treatment with this drug. A T-cell leukemia patient with an Ommaya reservoir was treated with DCF, and the pharmacokinetics of the drug in the cerebrospinal fluid and plasma were studied. DCF penetrates the cerebrospinal fluid and achieves levels as high as 1/10 the concurrent plasma levels. The accumulation of adenosine and deoxyadenosine in plasma, cerebrospinal fluid, and urine was monitored; the neuropharmacological effect of these metabolites is discussed.
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PMID:Deoxycoformycin: neurological toxicity. 697 88

Pentostatin, a potent inhibitor of adenosine deaminase, is an antineoplastic agent which has been studied in the treatment of a variety of lymphoproliferative disorders. It is particularly effective in the treatment of hairy cell leukaemia, achieving complete remissions in 33 to 92% of patients, and has useful activity in treating B cell chronic lymphocytic leukaemia, prolymphocytic leukaemia, adult T cell leukaemia/lymphoma and cutaneous T cell lymphoma refractory to conventional chemotherapy. Initial results suggest that in the treatment of hairy cell leukaemia pentostatin achieves a more rapid response and higher frequency of complete remission with longer duration than interferon-alpha 2a, although it is still not known if some patients experiencing complete remission have been cured. The drug has yet to be directly compared with other promising purine analogues such as cladribine and fludarabine, and results of such comparisons are required before the ultimate role of pentostatin in the treatment of hairy cell leukaemia can be clearly established. However, pentostatin does produce a substantial response in a difficult therapeutic area and should be considered for initial treatment of hairy cell leukaemia.
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PMID:Pentostatin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in lymphoproliferative disorders. 750 51

Eighty-five hairy cell leukemia (HCL) patients who had failed initial therapy with recombinant alpha interferon were enrolled for pentostatin therapy. All had HCL confirmed by central pathology review and were eligible for evaluation. The median age was 55 years (range 31-83 years). Fifteen patients were between 31- and 40-years-old. There were 72 males (85%) and 13 females (15%). Fifty-four patients (64%) had prior splenectomy. All had been previously treated with interferon; nine had achieved a complete response (CR), 36 had a partial response (PR), 35 had stable disease (SD), and five patients had progressive disease. Patients with a CALGB performance status (PS) of 0-2 (78 patients) received 4 mg/m2 i.v. on days 1 and 15, repeated every 4 weeks. Patients with a performance status of 3 or 4 (seven patients) were started at 2 mg/m2 i.v. in the absence of grade 3 toxicity, the dose was escalated. Complete responses were seen in 36 patients (42.4%) and 35 patients had partial responses (41.2%) for an overall response rate of 83.6%. Median time to best response was 6.5 months. Eight patients had stable disease, and one patient had progressive disease. Three patients died early during the treatment phase and two were not evaluable due to treatment violations. Of seven patients with a CALGB performance status of 3 or 4, there were no CRs and only two PRs. Of 31 evaluable PS 0-2 patients who had previously achieved only stable disease on interferon, 13 had a CR on pentostatin and 12 had a PR. Based on PS 0-2 patients, the median follow-up is 44 months and 36 month remission duration and survival rates and 95% confidence intervals are 84% (CI 68-93%) and 91% (CI 81-96%). The 36 month survival rate was 29% (CI 10-58%) for PS 3-4 patients. Drug dosage was modified in 39 (51%) of 76 evaluable patients. Leukopenia and/or infection were the most frequent toxicities leading to a dose modification. Pentostatin is an effective agent and induces an excellent response in relapsed HCL patients previously treated with alpha-interferon (alpha-IFN).
Leukemia 1994 Dec
PMID:Pentostatin treatment for hairy cell leukemia patients who failed initial therapy with recombinant alpha-interferon: a report of CALGB study 8515. 780 91

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.
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PMID:Hairy cell leukaemia. 791 37

This is a review of current opinions on all aspects of diagnosis and treatment of hairy-cell leukemia. First, the authors report a concise but complete description of clinical and hematological characteristics of the disease with particular attention to peripheral blood and bone marrow morphological, cytochemical and cytogenetic features. Still concerning the diagnostic phase, the authors report a brief description of splenic, hepatic and lymph nodal histological pictures and some informations about immunophenotypic diagnosis with monoclonal antibodies. A space is then given to differential diagnosis and prognostic factors which have remarkably changed over the years. The second part of this review concerns current treatments for hairy-cell leukemia and analyses all the aspects of the different therapeutic strategies. Data, for this analysis were obtained from the Italian Cooperative Group's Studies and from other published series. Special attention was given to the impact of splenectomy, alpha-interferon therapy and new drugs such as purine analogues (2-CdA, 2-dCF) on the management of the disease. The last section concerns minimal residual disease, second neoplasia and the most common causes of death. A whole paragraph is dedicated to hairy-cell leukemia variants.
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PMID:[Hairy-cell leukemia]. 851 96

Although hairy-cell leukemia (HCL) is uncommon, remarkable progress has been made in the treatment of patients with this disease. Because of their unique mechanisms of action, the purine analogs, 2'-deoxycoformycin (2'-DCF) and 2-chlorodeoxyadenosine (2-CdA), are naturally targeted to lymphocytes and are cytotoxic to both resting and dividing cells. Both of these agents induce durable complete remissions (CRs) in the overwhelming majority of patients. Remarkably, equally high rates of durable CR are achieved in both untreated and previously treated patients. Furthermore, patients with large tumor burdens fare as well as those with minimal disease. Therefore, these agents have emerged as the treatments of choice for all patients with hairy-cell leukemia and have supplanted earlier treatments such as splenectomy and interferon-alpha (IFN-alpha). Since a single 7-day cycle of 2-CdA leads to excellent outcomes and is associated with few toxicities other than culture-negative fever, this agent is particularly attractive and may offer some advantages. However, given the indolent natural history of HCL, long-term follow-up study will be required to determine if one purine analog offers a survival advantage over the other.
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PMID:Treatment of hairy-cell leukemia: current views. 1031 84


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