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)

A 63-year-old white man had a history of recurrent pneumonia, pancytopenia, and splenomegaly when the diagnosis of hairy cell leukemia was made on bone marrow biopsy examination. Splenectomy confirmed that diagnosis and his pancytopenia moderately improved. Three years following the diagnosis, the patient developed an upper abdominal mass involving the stomach wall that was found to be an anaplastic "large cell" neoplasm. Palliative radiotherapy was started, but the patient died 2 months later. Cytochemical studies of the anaplastic gastric neoplasm revealed cytoplasmic tartrate resistant acid phosphatase activity. Electron microscopy showed no epithelial differentiation. These observations suggest that the gastric neoplasm represented an evolution of hairy cell leukemia into a more aggressive tumor analogous to the transformation that occurs in other B-cell neoplasms.
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PMID:Anaplastic neoplasm in a patient with hairy cell leukemia. 241 86

Hairy cell leukemia (HCL) is a rare chronic lymphoproliferative disorder which has been extensively studied over the past decade. Much has been learned regarding the diagnosis, natural history, biology, and treatment of this unique neoplasm. The disease most commonly affects middle aged men and characteristic clinical features include splenomegaly, cytopenias, and usually the presence in the peripheral blood of distinctive 'hairy cells' with irregular cytoplasmic projections. Diagnosis can usually be confirmed by bone marrow biopsy. Although the natural history can be extremely variable among patients, complications are usually referable to the cytopenias, with anemia and infection being most frequent. In addition to pyogenic infections, patients are susceptible to unusual organisms including atypical mycobacterium, legionella, and fungi. The requirement of red blood cell transfusion, severe granulocytopenia or thrombocytopenia, frequent infections, or painful splenomegaly are all indications for treatment. Splenectomy is the standard initial treatment of choice. However, in the past few years there have been exciting major advances in the therapeutic modalities for HCL. Recombinant alpha-interferon is highly effective, with beneficial responses occurring in close to 90% of patients. The Food and Drug Administration has recently approved the use of interferon for HCL. This represents the first time a biological response modifier has been approved for the treatment of human disease. In addition, preliminary results with the adenosine deaminase inhibitor, 2'deoxycoformycin (dcf), have been encouraging. Further clinical trials are required in order to determine the optimal sequential treatment strategy for HCL. The exact mechanisms of action of both interferon and dcf in HCL remain to be elucidated. A better understanding of the unusual features of the hairy cell and the underlying biological effect of these two agents in HCL may have important applications in other hematologic and non-hematologic malignancies.
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PMID:Hairy cell leukemia: clinical features and therapeutic advances. 244 91

The Italian Cooperative Group for Hairy Cell Leukaemia (ICGHCL), between April 1985 and June 1987, conducted a multicentre study using human lymphoblastoid alpha-interferon as primary therapy as an alternative to splenectomy. Forty-eight evaluable patients with HCL entered the study, 38 of them had splenomegaly, in five patients the spleen was not palpable and five were unfit for surgery because of age and general condition. Daily dose of 3 MU s.c. alpha-IFN was given for 12 weeks, or until a satisfactory and stable response was obtained. Among these 48 patients the response rate after 3 months of therapy was 63%, with seven patients (15%) achieving complete remission and 23 (48%) partial remission; 13 (27%) patients had a minor response. In five patients no response was observed and they died within 2 months of treatment. Five other patients, after an initial response, presented a re-expansion of the disease. Actuarial survival at 30 months was 88.8% for the entire group of 48 patients and 92% for the 38 patients who would normally be treated by splenectomy. Thus, alpha-IFN as primary treatment in HCL offered a reasonable therapy for splenomegalic patients. The timing and validity of splenectomy still remains an open question.
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PMID:Human lymphoblastoid interferon as initial therapy in hairy cell leukaemia: a multicentre study in non-splenectomized patients. Italian Cooperative Group for Hairy Cell Leukemia. 266 Sep 1

Since interferon (IFN-alpha) treatment has proven effective in hairy cell leukemia, its evaluation in chronic lymphocytic leukemia (CLL), a cytologically related disease, appeared reasonable. In our study, we have focused on previously untreated, early stage patients who are less than 60 years of age. All patients had less than 50,000 lymphocytes/microL and immunologic analysis revealed a CD20+, IgM+, IgD- phenotype for leukemic B cells in eight of nine patients. Recombinant interferon alpha 2b (IFN-alpha 2) at 5 x 10(6) U was given subcutaneously three times per week for 8 to 16 months. Consistent with earlier reports, side effects were minor with this low-dose protocol. All patients responded with a decrease of WBC count and lymphocyte count; in one patient, splenomegaly resolved such that he moved from Rai stage II to Rai stage I. On the average CD20+ B cells decreased from 14,312 to 3,995 cells/microL, indicating that no complete eradication of the leukemic cells was possible. A partial response, based on a greater than 50% reduction of CD20+ B cells was obtained in five of seven patients analyzed. The increased numbers of CD2+ T lymphocytes decreased in response to interferon treatment in six of seven patients. Furthermore, in a portion of the patients class II antigen expression was enhanced on LeuM3+ monocytes suggesting an in vivo activation of the monocytes by IFN-alpha 2. Immunoglobulin levels were substantially improved in that serum IgG increased by more than 3 g/L in three of seven patients. In one patient, lymphocyte counts increased in spite of continued therapy, whereas all others exhibited no increase of lymphocyte numbers while on therapy. Our study clearly demonstrates effects of IFN-alpha 2 treatment on both the leukemic cells and on the nonleukemic components of the immune system in peripheral blood. Whether IFN-alpha treatment will result in long-term beneficial effects in early stage CLL needs to be evaluated in a larger study.
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PMID:Favorable response of early stage B CLL patients to treatment with IFN-alpha 2. 271 86

A daily dose of 3 x 10(6) or 6 x 10(6) units of alpha-interferon was given during two 4- to 6-month periods to a 65-yr-old male patient with hairy cell leukemia, reducing splenomegaly and decreasing the number of hairy cells. Liver biopsy specimens taken during treatment revealed predominantly decreased hairy cell infiltration in the dilated sinusoids and enlarged or vacuolar nuclei of hepatocytes, compared with those in the liver before treatment. The ultrastructure of hepatocytes in specimens taken during treatment showed cytoplasmic vacuoles, weakly stained glycogen particles, and conspicuously decreased endoplasmic reticulum. Liver tests revealed decreased serum cholinesterase and total cholesterol levels in the early stage of treatment, low levels of total protein and albumin during treatment, and a very low value in the [13C]aminopyrine breath test. No clinical reports have been made on the decreased microsomal function during treatment with interferon. alpha-Interferon damaged the endoplasmic reticulum of hepatocytes, although it was effective for the reduction of hairy cells in the liver of hairy cell leukemia.
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PMID:The effect of alpha-interferon on the liver in a patient with hairy cell leukemia: light and electron microscopic studies. 275 86

2'-Deoxycoformycin (pentostatin [dCF]), a potent inhibitor of adenosine deaminase (ADA), was administered in a biweekly low-dose (2 to 4 mg/m2) intravenous (IV) schedule to patients with advanced hairy cell leukemia. Twenty-three patients were treated, including 12 patients previously treated by splenectomy and five patients treated with interferon. Twenty-one of 23 patients had objective responses, including 20 who achieved a complete remission (CR). Responses occurred rapidly, with an average time to CR of 5.4 months. Treatment was not continued once CR was achieved, and 15 of 20 patients remain in remission with an average duration of 12.6 months. CRs were achieved in both patients previously treated with interferon (three of five) and patients with marked splenomegaly (three of three). Relapses, when seen, have occurred in the bone marrow alone and the one patient who required retreatment was reinduced into CR. Toxicity has been mild and reversible, with nausea and vomiting, conjunctivitis, and skin rash as the main complications of treatment. dCF is the most effective single agent in the treatment of hairy cell leukemia, inducing a high percentage of CRs in all subgroups. Two multiinstitutional trials are now underway to compare its effectiveness v alpha interferon.
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PMID:Pentostatin in the treatment of advanced hairy cell leukemia. 278 31

In 10 HCL patients, who following treatment for more than 1 year with alpha-IFN, had achieved a normalization of the splenomegaly and a disappearance of circulating hairy cells together with a complete restoration of all peripheral hematological values, a multiple assessment of the apparent complete remission (CR) was carried out. The presence of residual disease was investigated by bone marrow histology, bone marrow immunohistochemistry, immunoglobulin (Ig) gene analysis and on the basis of the serum levels of the soluble form of the Interleukin-2 receptor (sIL-2R). Examination of bone marrow biopsies showed a pattern of CR in 5 cases; 4 of them revealed no evidence of Ig heavy chain gene rearrangement, as well as a near normalization of the serum levels of sIL-2R. Immunohistochemical studies were carried out on embedded paraffin sections with the monoclonal antibody 4KB5 (CD45R) and were assessable in 4 of the 5 patients considered in CR and in 3 of the 4 cases with no Ig gene rearrangement. In 2 the pattern of CR was confirmed, while in the 3rd a minimal but persistent disease (5%) was suspected.
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PMID:Evaluation of complete remission in hairy cell leukemia patients treated with alpha-IFN. 278 26

Two cell lines (EH and HK) were derived from two patients with hairy cell leukemia (HCL). Both patients exhibited a clinical picture characteristic of HCL, including splenomegaly, cytopenias, and tartrate-resistant acid phosphatase (TRAP)-positive "hairy" lymphocytes in blood and marrow. EH and HK were demonstrably of B lineage, as judged by cytochemistry and immunophenotype, including expression of B1, B2, and LEU-12 antigens and of monoclonal surface immunoglobulins (slgs). Monoclonality was confirmed by clonal karyotype abnormality demonstrated in cell line HK. HCL parentage suggested by cytochemistry and electron microscopy was confirmed by the immunophenotypic observation that HCL lines expressed antigens alpha S-HCL1, alpha S-HCL3, and cCLLa. While alpha S-HCL1 and alpha S-HCL3 are nonspecific, their co-expression is characteristic of HCL cells. The cCLLa is a novel 69-kd membrane HCL-associated polypeptide antigen not shared by circulating normal T or B lymphocytes nor by malignant cells from unrelated lymphoid or nonlymphoid malignancies. The doubling time of EH and HK was 24 and 36 hours, respectively. While HK included a small subset of Epstein-Barr virus (EBV) nuclear antigen-positive cells, EH cells were homogeneously negative for the presence of this antigen. Both cell lines were consistently implantable in irradiation-preconditioned immunodeficient mice giving rise to primary tumors and widespread metastasis.
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PMID:Cytochemical, cytogenetic, immunophenotypic and tumorigenic characterization of two hairy cell lines. 282 13

A low-dose interferon (IFN)-alpha regimen for the treatment of hairy cell leukemia (HCL) was evaluated by following changes in leukocyte differentiation antigens (LDA), natural killer cell (NK) and 2',5'-oligoadenylate (2-5A) synthetase activities. Due to hairy cells' (HC) weak expression of several antigens positive for T cells, B cells, NK cells and monocytes, the use of a double marker specific for hairy cells was needed to distinguish the different subpopulations. Analysis of LDA in peripheral blood (PB) showed a total normalization of the T cell and monocyte numbers within 90 days, the number of NK cells normalized in 90 to 180 d, whereas normalization of B cell number was seen only after 180 to 360 d of treatment. Mean pretreatment 2-5A synthetase activity was normal or low, but upon treatment the levels rose immediately to higher than normal values and remained high throughout the study. Pretreatment NK activity was low, but normalized after between 90 to 360 d, except in 2 patients with severe splenomegaly. In vitro incubation of peripheral blood mononuclear cells (PBMNC) with IFN-alpha induced activation of the NK and 2-5A synthetase activity in untreated patients, but with treatment these effects were gradually abolished, indicating an increasing effect of IFN-alpha in vivo with time. These results shows that the different PBMNC subpopulations and important immunological functions normalize with treatment. This normalization is, however, not seen until at least after 1 year of treatment, indicating that the treatment schedule should be longer. As no exhaustion to the effect of IFN was seen, as measured by the 2-5A synthetase activity, a continuing beneficial effect of treatment is anticipated. The increasing effect of IFN-alpha after the first signs of clinical effect suggests that the doses used in the present study were higher than necessary.
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PMID:Immunological recovery and dose evaluation in IFN-alpha treatment of hairy cell leukemia: analysis of leukocyte differentiation antigens, NK and 2',5'-oligoadenylate synthetase activity. 291 94

The association of neutropenia with an indolent chronic T-suppressor cell lymphoproliferative disorder (LPD) has been well documented. The morphologic features and course suggest that this is a benign disorder. The authors studied a 58-year-old man with a chronic T-cell LPD, splenomegaly, and neutropenia. Chromosomal analysis revealed multiple abnormalities which progressively increased in number as the marrow lymphocytosis became more prominent. Subsequently he developed small bowel infiltration. A splenectomy resulted in only brief improvement in the neutropenia. Immunopathologic examination of the spleen was consistent with a well-differentiated lymphocytic lymphoma of a mature peripheral T-cell type without subset specific markers. Granulocyte-monocyte colony (CFU-GM) formation from the patient's marrow was normal and not augmented by T-cell depletion. Neither the patient's splenic T-cells nor serum suppressed granulopoiesis. In contrast to previous T-LPD with neutropenia whose malignant nature has been questioned, the clinical, cytogenetic, and pathologic features and course in this case indicate a malignant lymphoid process which was effectively treated with chemotherapy. Although the histologic pattern of red pulp involvement simulated hairy cell leukemia, that diagnosis was excluded by this patient's clinical, morphologic, and cytochemical features.
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PMID:A unique malignant T-cell lymphoproliferative disorder with neutropenia simulating hairy cell leukemia. 293 14


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