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)

Eleven patients with hairy cell leukemia (HCL) were treated with YK-176 (2'-deoxycoformycin) at a dose of 5 mg/m2 by intravenous injection every week or every other week. Patients received a median of eight (range 4-19) injections of YK-176. Five patients had previously been untreated, four of whom had massive splenomegaly. Six patients had previously been treated, four with interferon-alpha (IFN-alpha) or IFN-alpha and chemotherapy and two with prednisolone. Two patients had had splenectomies. Five patients achieved complete remission (CR) and six, partial remission (PR) according to WHO criteria (remission rate 100%, 95% confidence interval (CI) 74-100%). All six neutropenic patients recovered > 1,500/microliters neutrophils, six of seven anemic patients recovered > 12.0 g/dl hemoglobin and five of nine thrombocytopenic patients recovered > 100,000/microliters platelets following the treatment. According to the response criteria for HLC, five patients achieved CR, two PR and four minor response. The overall remission (CR + PR) rate was 64% (95% CI 35-85%). The CR and PR have lasted from > 30 to > 718 days (median, > 281 days) so far with no relapses. Of four patients previously treated with IFN-alpha, two achieved CR and one, PR. All patients were alive with a median survival time of > 290 days from treatment (range > 50- > 763 days). The treatment was generally well tolerated. Mild to moderate nausea, vomiting, appetite loss and general fatigue were experienced in two patients, skin rash in one and a transient fever in three. YK-176 was a highly active agent in the treatment of HCL.
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PMID:Treatment of hairy cell leukemia with deoxycoformycin (YK-176). The Deoxycoformycin (YK-176) Study Group. 129 57

The Philadelphia (Ph1) chromosome is a specific structural abnormality in which the abl oncogene is activated due to the formation of the novel chimeric gene, bcr/abl. To investigate the clinicopathological role of bcr/abl in Ph1-positive chronic myelogenous leukaemia (CML), we studied the clonal origin of haematopoietic progenitors by detecting bcr/abl mRNA in a single haematopoietic colony using the polymerase chain reaction (PCR). Nine patients with CML were examined. In 5 chronic phase patients, all granulocyte/macrophage (CFU-GM) and erythroid (BFU-E) progenitor-derived colonies were positive for bcr/abl mRNA. Colonies in which the transcripts were not detectable were observed in 4 patients. These 4 patients included one patient with a normal karyotype and without splenomegaly, a patient with cyclic oscillation of her white blood cell level, a patient treated with busulfan and interferon-alpha (INF-alpha), and a patient relapsing after allogenic bone marrow transplantation (BMT). Our observations indicate that detection of Ph1-positive clones by PCR may be used to evaluate clinical stages and the effects of treatment in CML.
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PMID:Analysis of clonality at the level of progenitors in chronic myelogenous leukaemia using the polymerase chain reaction. 156 40

The cardinal features of hairy cell leukaemia are: (i) cytopenias, (ii) splenomegaly, and (iii) mononuclear cells of B-cell origin with cytoplasmic projections and tartrate-resistant acid phosphatase-positivity. The most common complication is infection. In the past, the mainstay of therapy has been splenectomy, and this procedure is still often suggested as a first-line approach. However, research during the last decade has resulted in three new, highly effective therapies for hairy cell leukaemia: interferon-alpha (IFN-alpha), 2'-deoxycoformycin (DCF) and 2-chlorodeoxyadenosine (2CDA). IFN-alpha is currently approved for this indication. About 90% of patients have a durable haematologic recovery, and complete remission rates range from less than 5% to greater than 40% in different series. It should be noted that patients with partial remissions generally have normal or near-normal blood counts, and can live indefinitely without disease-related problems, despite a few remaining hairy cells in the bone marrow. In this paper we will discuss the various therapeutic modalities available for patients with hairy cell leukaemia.
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PMID:Hairy cell leukaemia: review of treatment. 171 89

This study was undertaken to calculate the in vivo drug interactions between recombinant human interferon-alpha A/D (rHuIFN-alpha A/D) and 3'-azido-3'-deoxythymidine (AZT) in a quantitative model for retroviral viremia. When given as single agents, both AZT and rHuIFN-alpha A/D suppressed virus-induced splenomegaly in a dose-dependent fashion in mice inoculated with Rauscher murine leukemia virus (RLV). However, suppressive doses of single-agent AZT caused anemia after 20 days of therapy. Combining rHuIFN-alpha A/D with AZT allowed drastic dose reductions for each agent while maintaining greater than or equal to 93% inhibition of splenomegaly. No clinically significant toxicity was seen. Computer analysis with the isobologram technique and combination index method showed that these combination regimens were highly synergistic. A 20-day course of AZT + rHuIFN-alpha A/D started 4 h after virus exposure was protective against RLV viremia and disease. After cessation of therapy, the animals were resistant to rechallenge with fully infectious RLV. We conclude that prompt initiation of effective combination therapy after retroviral exposure prevented viremia and disease and led to protective immunity.
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PMID:Interferon-alpha and 3'-azido-3'-deoxythymidine are highly synergistic in mice and prevent viremia after acute retrovirus exposure. 215 92

Rauscher murine leukemia virus (R-MuLV) induces a rapidly developing erythroleukemia in BALB/c mice. Previously, we have shown that mouse interferon-alpha/beta (Mu IFN-alpha/beta) applied shortly after virus inoculation efficiently inhibits the leukemic process (Hekman et al., 1981). Here we describe the effect of Mu IFN-alpha/beta on an established leukemia. Varying doses of Mu IFN-alpha/beta were injected over 3 days, starting 8 to 12 days after virus inoculation. The effect of Mu IFN-alpha/beta on the leukemic process was monitored by measuring the spleen weight, reverse transcriptase activity in the serum and, in selected experiments, by microscopic examination of sections of the spleen using standard histological and immunological staining techniques. Depending on the spleen weight at the start of its application (maximal about 450 mg), Mu IFN-alpha/beta caused a dramatic reduction in the number of virus-infected erythroleukemic cells in the spleen. Also, R-MuLV disappeared from the serum within 3 days. If Mu IFN-alpha/beta was injected into R-MuLV-infected mice with an already 10-fold enlarged spleen, it could only stop further development of leukemia. Results obtained with crude Mu IFN-alpha/beta preparations were confirmed with absolutely pure Mu IFN-beta.
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PMID:The effect of murine interferon-alpha/beta on an established Rauscher murine leukemia virus-induced erythroleukemia in BALB/c mice. 258 Aug 3

A 32-year-old female was diagnosed as having Ph1-positive chronic myelocytic leukemia (CML) on March 6, 1985. She was intermittently treated with busulfan or 6-mercaptopurine. Her regimen was changed on February 27, 1987 to interferon-alpha (HLBI, Sumitomo) because of leukocytosis (46,200/microliters) with basophilia (45%) and splenomegaly refractory to conventional therapy. She was admitted to our hospital on November 27, 1987 because of blastic crisis. Cytogenetic analysis on peripheral cells was repeated six times during the treatment with HLBI. The sixth analysis was done on bone marrow cells as well. Nineteen to 22 metaphases were analyzed by the trypsin G-banding method after short-term culture. Cytogenetic analysis of peripheral cells revealed 46, XX, Ph1 in 9% of metaphases and 47, XX, Ph1, +8, i(17q) in 91% on March 2, 1987, and 47, XX, Ph1, +8, i(17q) in 95.2% of metaphases and 48, XX, Ph1, +8, i(17q), +19 in 4.8% on December 11, 1987. Karyotypes of bone marrow cells on December 11, 1987 were 48, XX, Ph1, +8, +8, 4(17q) in 73.7% of metaphases and 47, XX, Ph1, +8, i(17q) in 26.3%. It was speculated that abnormal clones might have developed in other sites than bone marrow.
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PMID:[Discrepancy in karyotypes between peripheral blood and bone marrow during blastic crisis in chronic myelocytic leukemia]. 281 Jul 87

Fourteen patients with Ph'-chromosome positive chronic myelogenous leukemia (CML) in first chronic phase were treated with recombinant interferon-alpha 2c. Interferon-alpha 2c 5 to 10 X 10(6) units s.c. was given for 12 weeks as an induction therapy. Maintenance treatment consisted of interferon-alpha 2c 5 X 10(6) units twice weekly s.c.. Two patients (14%) attained a complete clinical remission and 6 (43%) a partial remission, 3 of whom developed progressive disease during maintenance therapy. A complete disappearance of Ph'-chromosome was achieved in 1 patient. All patients had a more than 45% initial decline of the leukocyte count. Four out of ten patients with an initially enlarged spleen demonstrated reduction in spleen size. Influenza-like symptoms, anorexia, nausea, weight loss and fatigue were common side effects. Interferon-alpha is active in CML but additional clinical investigations are warranted to assess more precisely the therapeutic value of the interferons in this disease.
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PMID:Recombinant human interferon-alpha induced cytoreduction in chronic myelogenous leukemia. Results of a multicenter study. 328 12

Twelve evaluable patients with progressive hairy cell leukemia were treated with deoxycoformycin at a dose of 4 mg/m2 every 2 weeks. Five patients had not been splenectomized, and one had failed to respond to interferon-alpha. Complete remission, as defined by absence of hairy cells in the bone marrow and normalization of the peripheral blood and regression of splenomegaly, was obtained in 11 of 12 patients (92%). These patients have remained in unmaintained remission for 1+ to 13 months with an average of 7.5 months. Two of these patients had a bone marrow relapse at 8 and 12 months, respectively. During treatment the monocytopenia corrected, and, after complete remission was obtained, marrow was aspirable. Toxicity was mild and reversible. There were no significant infections associated with this treatment. It was of interest that we could treat two patients with creatinine clearance of 50 and 60 ml/min using lower doses (and 2-3 mg/m2) than our conventional therapy of 4 mg/m2 every 2 weeks. They obtained a complete remission after 6 and 10 treatments, respectively. Low-dose deoxycoformycin has proven to be an excellent treatment for hairy cell leukemia.
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PMID:Treatment of hairy cell leukemia: the Ohio State University experience with deoxycoformycin. 349 42

The anti-Friend leukemia virus (FLV) effects of interferon-alpha-A/D (IFN-alpha) and 2',3'-didehydro-2',3'-dideoxythymidine (stavudine) used alone and in combination were examined in Mus dunni cells using a checkerboard-type experiment design. Strong antiviral synergy and a suggested cytotoxic synergy were seen. In two experiments to evaluate the effect of combining therapy with IFN-alpha and stavudine against FLV disease in the hybrid mouse strain (B10.A x A.By)F1, which is a strong producer of cytotoxic T cells, the drug combination resulted in better inhibition of FLV disease than did either drug used alone. Combination therapy inhibited splenomegaly, splenic virus infectious centers, plasma virus, and the virus-induced increase in hematocrit to a greater degree than did either drug alone. These data indicate that combination therapy with stavudine and IFN-alpha is effective in the treatment of murine retrovirus infections and may be of value in the treatment of human AIDS.
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PMID:Effect of the combination of interferon-alpha and stavudine on Friend virus infections in (B10.A x A.By)F1 mice. 786 Oct 24

Chronic myelogenous leukemia is a clonal disorder of hematopoietic stem cells characterized by granulocytic leukocytosis, splenomegaly, and a specific chromosomal abnormality, the Philadelphia chromosome. Treatment options include the oral agents hydroxyurea or busulfan, subcutaneous interferon-alpha, and bone marrow transplantation. The recent publication of some large, randomized trials and the increased availability of bone marrow transplantation are changing the therapeutic approach to chronic myelogenous leukemia. This paper reviews these recent studies on the management of chronic myelogenous leukemia.
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PMID:Update on therapy for chronic myelogenous leukemia. 793 Aug 64


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