Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-six patients with hairy cell leukemia (HCL) were treated with 2-chlorodeoxyadenosine (2-CdA), a purine analogue resistant to adenosine deaminase, at 0.1 mg/kg/d for 7 days by continuous intravenous infusion. Fifteen patients were previously untreated, while 11 patients had received prior treatment with splenectomy alone (three patients), interferon alpha alone (four), splenectomy, then interferon alpha (two), or splenectomy, interferon alpha, then 2-deoxycoformycin (2-DCF) (two). Sixteen (80%) of 20 patients evaluable at 3 months achieved complete remission (CR), and four (20%) achieved partial remission (PR) following a single cycle of therapy. All four patients in PR had complete recovery of their peripheral blood counts (except one patient whose platelet count remained 84,000/microL), but had residual HCL in the bone marrow (three patients) or residual splenomegaly (one). Patients with bulky adenopathy, massive splenomegaly, and severe pancytopenia responded as well as those with only modest marrow involvement. The three patients with residual marrow disease received a second cycle of 2-CdA, and two have attained CR. Therefore, 18 of 20 (90%) achieved CR with either one or two cycles of therapy. No patient achieving CR has relapsed at a median follow-up of 12 (+/- 2.1) months. Toxicities included myelosuppression and culture-negative fever. A community-acquired pneumonia was the only infectious complication. Since a single cycle of 2-CdA induces sustained CR in the vast majority of patients with minimal toxicity, this agent is emerging as the treatment of choice for all patients with HCL.
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PMID:A single cycle of 2-chlorodeoxyadenosine results in complete remission in the majority of patients with hairy cell leukemia. 135 62

We report the case of a patient with prolymphocytic leukemia in whom a lengthy survival of 5 years was observed after treatment with splenic irradiation and chemotherapy. The patient obtained a surprising improvement with a significant reduction in the absolute count of the prolymphocytes and considerable reduction in splenomegaly after 3 months' therapy with interferon alpha.
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PMID:Prolymphocytic leukemia: a very satisfactory response to treatment with recombinant interferon alpha. 139 2

2 patients with myelofibrosis and myeloid metaplasia had symptomatic splenomegaly and were treated with interferon alpha-2c (IFN alpha-2c). The splenic pain and pressure symptoms disappeared, accompanied by a decrease in the size of the spleen. However, the peripheral blood count worsened and no improvement in the bone marrow fibrosis could be observed.
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PMID:Alpha interferon in the treatment of symptomatic myelofibrosis with myeloid metaplasia. 367 74

Hairy-cell leukemia is a well-characterized, pathologic disorder. The majority of cases are B lymphocyte in origin with circulating hairy cells, splenomegaly, and, not infrequently, pancytopenia included in the clinical findings. Observation, splenectomy, glucocorticoids (ie, for vasculitic manifestations), and alkylating agents are the currently recommended treatment for this disease. Recombinant interferon alpha may become the treatment of choice for individuals with progressive disease after splenectomy. An understanding of the mechanism of action of recombinant interferon alpha may shed light on the pathways of interferons in general, as well as provide insights into the pathogenesis of this particular proliferative disorder.
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PMID:Therapeutic options in hairy-cell leukemia. 390 17

In 1985, Cancer and Leukemia Group B initiated a multi-institutional study to define the role of interferon alpha in therapy of previously untreated active hairy cell leukemia (HCL). This is a long-term follow-up report of the study. Fifty-five evaluable patients were treated with recombinant interferon-2b 2 million units/m2 subcutaneously three times a week for 1 year. Treatment was well tolerated; toxicity mainly consisted of flu-like syndrome and pancytopenia, both of a transient nature. Seventy-three percent of patients had objective beneficial responses with 8.3 months median time to achieve at least a partial response (PR). After 1 year of therapy, the patients have been observed for a median of 5 years. There was a continual trend towards relapse throughout this period but 28% have remained in remission beyond 6 years. Forty-six patients (83%) are alive at 6 years. Among the 40 patients who achieved at least a PR, there were 28 with splenomegaly at the beginning of study: the spleen size was reduced in all with interferon alpha therapy and none required splenectomy. This study confirms the results of other investigators, and demonstrates that recombinant alpha interferon-2b is an effective agent for treatment of hairy cell leukemia.
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PMID:Recombinant alpha-2b-interferon in therapy of previously untreated hairy cell leukemia: long-term follow-up results of study by Cancer and Leukemia Group B. 763 Jan 81

We retrospectively analysed the results of interferon alpha-2 (IFN) treatment in 93 patients with hairy-cell leukaemia, of which 31 had previously undergone splenectomy. Induction treatment (3 x 10(6) U three times weekly for 12 months) was completed in 84 cases (90%). Peripheral hematological response was observed in 76 patients. Two patients had persistent splenomegaly, and response was observed in both cases after splenectomy. Five additional patients were responsive after 18-24 months of induction treatment and 1 was unresponsive. Of 28 patients on maintenance treatment (1 x 10(6) U 3 x per week), no patient relapsed after a median follow-up of 30 months. The toxicity level was acceptable and IFN resistance was not observed. On the other hand, of 56 patients without maintenance treatment, 37 relapsed at a median of 19 months. Thirty of 32 evaluable patients remained responsive to a second course of IFN. Of 19 patients without relapse, 11 had undergone splenectomy compared to 0/37 patients who relapsed (p < 0.001). In conclusion, the study shows the following, (1) IFN, provides excellent palliation without major toxic side effects; (2) long term maintenance was well tolerated and prevented peripheral haematological relapse; (3) lack of maintenance treatment was associated with peripheral haematological relapse requiring a second treatment; and (4) certain previously splenectomized patients may not require maintenance treatment. These long term results must be compared with the effectiveness and toxicity of new drugs, such as pentostatin and 2-chloro-deoxy-adenosine.
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PMID:Hairy cell leukemia. An update on a cohort of 93 patients treated in a single institution. Effects of interferon in patients relapsing after splenectomy and in patients with or without maintenance treatment. 782 62

C57/BL/6 mice infected with LP-BM5 MuLV virus developed an AIDS-like disease (MAIDS) with splenomegaly, leukopenia, thrombocytopenia, anemia, decreased numbers of helper/inducer and suppressor/cytotoxic T-cells and decreased production of interferon alpha. We have shown previously that HIV-associated Kaposi's sarcoma tissue contains high levels of prostaglandin E2 (PgE2), and this inhibits interferon synthesis through a cAMP-dependent second-messenger process. In this study we treated groups of MAIDS-infected mice with combinations of pentoxifylline, an agent which increases cAMP and inhibits phosphodiesterases, and sodium meclofenamic acid, a PgE2 inhibitor. Treated mice showed: 1) significantly higher total leukocyte and platelet counts, 2) higher total L3T4+ (helper/inducer) and Lyt-2+ (suppressor-cytotoxic) T-cell population. Pathologic examination also showed significantly less hepatosplenomegaly and lymphadenopathy in animals treated with pentoxifylline and meclofenamic acid. Partly, PgE2-induced suppression of interferon alpha production may mediate expression of retrovirus infection in this murine model of AIDS.
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PMID:Pentoxifylline and meclofenamic acid treatment reduces clinical manifestations in a murine model of AIDS. 830 44

The case of an 11 year old girl with three line type of polycythaemia vera, with 4 cm splenomegaly and a plethoric complexion is presented. Peripheral blood values were as follows: RBC: 7.75 x 10(12)/l, Hb: 18.8 g/l, WBC: 15.2 x 10(9)/l, platelets: 920 x 10(9)/l. Serum erythropoietin level: < 1 mU/ml. In vitro, erythroid colonies developed from the bone marrow in the absence of added erythropoetin. For three years the haematocrit value has been controlled by regular venesections. Since extreme thrombocytosis developed, the treatment was continued with interferon alpha. Different treatment protocols are discussed.
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PMID:[Polycytemia vera in an 11-year old girl]. 872 60

We report major responses in 4 of 4 patients with hairy cell leukemia (HCL) who have recently been treated on a phase I trial with the recombinant immunotoxin LMB-2. The immunotoxin, designed to target CD25(+) malignancies, is composed of the Fv portion of the anti-Tac (anti-CD25) antibody, fused to a 38-kD truncated form of Pseudomonas exotoxin A, and has previously been called anti-Tac(Fv)-PE38. All 4 HCL patients were resistant to standard and salvage therapies for HCL, including 2-chlorodeoxyadenosine (CdA) and interferon alpha, and all patients responded to LMB-2 after a single cycle. One patient treated with 2 cycles had a complete remission (CR), with regression of HCL cells from the blood and marrow and resolution of splenomegaly and pancytopenia. As is typical for patients in CR after treatment with CdA, minimal residual disease was detectable by flow cytometry of the bone marrow aspirate. This patient has not relapsed after 11 months. Three other patients had 98% to 99.8% reductions in malignant circulating cells. These results represent a proof of principal that targeted therapy with recombinant Fv-containing proteins can be clinically useful. LMB-2 may be an effective new therapy for patients with chemotherapy-resistant CD25(+) HCL.
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PMID:Responses in refractory hairy cell leukemia to a recombinant immunotoxin. 1055 43

In the last half of this century, hairy cell leukemia was recognized as a distinct B-cell malignancy, accounting for 2% of all leukemias. Characteristics include splenomegaly, pancytopenia, a usually indolent course, and responsiveness to both interferon and purine analog therapy. Accurate diagnosis requires the demonstration of malignant cells in the bone marrow and peripheral blood which contain cytoplasmic projections and characteristic surface antigens. Splenectomy was identified early as a palliative therapy, and in 1984 systemic treatment with interferon alpha was first reported to induce complete remissions. Soon thereafter, the purine analog deoxycoformycin was found to induce more durable complete remissions in a higher percentage of patients. In 1990, 2-Chlorodeoxyadenosine, a new purine analog therapy, was reported to be capable of inducing long-term durable responses in most patients after a single cycle. Current challenges include identifying which purine analog is the least toxic since both appear similarly effective, and neither appear to add to the already increased rate of second malignancies occurring in these patients. Moreover, up to 25% of patients with hairy cell leukemia fail initially or eventually to respond to standard therapy, making the development of new approaches necessary. The characteristic bright expression of several B-cell antigens on the malignant cells, including CD20, CD22 and CD25, has led to the development of targeted biotherapeutic approaches. A recombinant immunotoxin targeting CD25 has recently been reported to induce major responses and it is likely that other successful targeted approaches will be reported early in the new century.
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PMID:Malignancy: Current Clinical Practice: Treatment of Hairy Cell Leukemia at the Close of the 20th Century. 1139 70


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