Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with herpesvirus infections were given intravenous injections of 10-20 mg of adenine arabinoside (ara-A)/kg per day. When given the higher dosage, some patients with chronic hematologic conditions showed mild to moderate additional depressions in the level of hemoglobin. The number of neutrophils and platelets did not decrease, even when numbers were low at the onset of treatment with ara-A. Two patients with Hodgkin's disease who received 20 mg of ara-A/kg per day developed a transient motor aphasia resembling akinetic mutism. With the regimens of ara-A used and challenge inocula of approximately 50 plaque-forming units of virus, the minimal inhibitory concentrations of ara-A and hypoxanthine arabinoside for herpesviruses are usually not achieved in serum but may be attained in body fluids (urine and vesicular fluid). Antiviral activity in vesicular fluids is likely to involve a combination of ara-A, hypoxanthine arabinoside, and interferon.
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PMID:Microbiologic assays and neurological toxicity during use of adenine arabinoside in humans. 18 99

Fludarabine phosphate is the 2-fluoro, 5'-monophosphate derivative of vidarabine (ara-A) with the advantages of resistance to deamination by adenosine deaminase (ADA) and improved solubility. The mechanism of cytotoxic action of the compound appears to involve metabolic conversion to the active triphosphate. Fludarabine phosphate has substantial activity against lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). Its single-agent activity in CLL appears at least comparable to those of other conventional combination regimens. Its activity in Hodgkin's disease, mycosis fungoides, and macroglobulinemia, although suggestive, needs to be further defined and clinical trials are warranted in hairy cell leukemia, prolymphocytic leukemia, and previously untreated myeloma. The compound does not appear active against most common solid tumors. Early clinical trials indicated significant myelosuppression and the potential for severe neurotoxicity. Toxicity on the currently used low-dose schedules includes transient and reversible myelosuppression, nausea and vomiting, diarrhea, somnolence/fatigue, and elevations of liver enzymes and/or serum creatinine. Possible pulmonary toxicity has been suggested in several patients. The currently used low-doses of fludarabine phosphate, even with repeated administration, are well tolerated and appear safe with a negligible risk for severe neurotoxicity. Based on its single-agent activity and tolerability, the Food and Drug Administration recently granted group C designation of the drug for the treatment of patients with refractory CLL outside the clinical trials setting. The use of fludarabine phosphate in combination regimens and its impact on the natural history of the lymphoid malignancies is yet to be determined. Fludarabine phosphate may well occupy a pivotal role in the management of CLL and low-grade NHL.
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PMID:Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. 170 43

This paper describes the properties of a continuous cell line derived from the blast cells of a patient with acute myeloblastic leukemia (AML), secondary to the treatment of Hodgkin's disease. The line grows slowly without stimulation but responds to interleukin-3 (IL-3), GM-CSF and mast cell growth factor (MGF), a ligand for the receptor encoded by the c-kit oncogene. When OCI/AML-4 cells are exposed to MGF with IL-3 or GM-CSF, additive or synergistic effects are seen. Combinations of MGF and G-CSF, IL-6 or CSF-1 give less growth than MGF alone. OCI/AML-4 cells are sensitive to retinoic acid; a dose related decrease in clonogenic cells is observed when OCI/AML-4 cells are exposed to retinoic acid in suspension culture. OCI/AML-4 cells are sensitive to cytosine arabinoside (ara-C), but the ara-C dose-response curve can be changed by altering the regulatory milieu in suspension culture. The cells are more ara-C sensitive in MGF or G-CSF than in IL-3 or GM-CSF. Following a 24 h exposure to retinoic acid, the ara-C sensitivity increases; in contrast, after a similar exposure to hydrocortisone, the cells become less ara-C sensitive. These changes in ara-C sensitivity occur in cells that are actively making DNA, as indicated by the reduction in colony formation after exposure to tritiated thymidine. Since OCI/AML-4 cells respond to many of the regulators that affect the growth of freshly obtained AML blast cells, it is proposed that this cell line may be useful for the study of regulation on AML in general and the interaction between different regulators in particular.
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PMID:OCI/AML-4 an acute myeloblastic leukemia cell line: regulation and response to cytosine arabinoside. 171 61

We report the results of two phase II trials of ifosfamide in very high risk patients with either partially responsive or recurrent non-Hodgkin's lymphomas. In the first study, in which patients were extremely heavily pretreated (50 per cent had received a very intensive salvage regimen containing very high dose cyclophosphamide), there were two complete responses, two partial responses and one objective (minimal) response among 14 patients treated. Toxicity was acceptable even in this end-stage patient group. We concluded that ifosfamide is an active agent even in patients with tumours resistant to cyclophosphamide. The second trial was a pilot study in 13 patients of a regimen incorporating VP16, ifosfamide/mesna, and high dose ara-C (VIPA). There were four complete responses, five partial responses and two objective responses. Two patients died in complete remission from toxic complications, while a third, with a stably regressed mediastinal mass died after completion of the protocol. While very toxic, we considered that this regimen was highly effective, and have since incorporated a slightly less intensive combination of the same drugs into the primary therapy of high risk patients. Since the primary toxicity of the VIPA combination was myelosuppression, the use of a modified protocol incorporating colony stimulating factors to ameliorate the side-effects and possibly increase dose rate is worthy of further exploration in patients with recurrent B cell tumours.
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PMID:Ifosfamide in the treatment of high-grade recurrent non-Hodgkin's lymphomas. 174 29

Twenty-one patients with high risk non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) underwent autologous bone marrow transplantation (ABMT). Nine out of 21 patients received in addition to bone marrow (BM) cells also peripheral blood (PB) cells collected by leucapheresis performed in the recovery phase after high-doses of either cyclophosphamide or etoposide (7 patients), or after ara-C (2 patient). All patients receiving BM + PB cells had ABMT as salvage therapy following extensive relapse or progression of their disease. The addition of PB cells to BM cells allowed a significantly faster recovery after ABMT. Median time to reach WBC greater than 1,000/microL was 14 days versus 20.5 days for patients receiving BM only. Furthermore, a reduced requirement of supportive care and a shorter period of isolation was observed. These results confirm that PB cells combined with BM cells allow a prompt hematopoietic reconstitution after myeloablation. In addition, the data demonstrate the efficacy of PB cells collected after various cytotoxic drugs, even in patients previously exposed to cytoreductive regimens.
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PMID:Use of peripheral blood stem cells to accelerate hemopoietic recovery following autologous bone marrow transplantation. 197 37

A 32-year-old man with an 18-year history of protein losing enteropathy (PLE) was admitted to hospital for abdominal distention. On physical examination, he had massive pleural effusion, ascites and edema of the right leg, but no superficial lymphadenopathy or organomegaly. Laboratory studies revealed mild microcytic anemia and hypoproteinemia. alpha 1-antitrypsin clearance was elevated (316 ml/day). Examination of ascites disclosed numerous lymphoblastoid cells of B cell phenotype with mu chain and lambda light chain of immunoglobulin (Ig) in the cytoplasm. Southern blot analysis showed monoclonal rearrangement of mu chain and lambda chain genes. No evidence of lymphomatous involvement of lymph nodes and non-lymphoid organs was found by CT scan, ultrasound echography and gallium scan of the chest and abdomen. Bone marrow biopsy was negative. Thus, a diagnosis of non-Hodgkin lymphoma (NHL) stage IVB limited in the pleural and peritoneal cavities was made. He was treated with the combination chemotherapy of BACOD with high dose ara-C or methotrexate followed by 4 doses of autologous LAK cell infusion resulting in no significant response. The massive pleural effusion, ascites and edema of the leg have not been improved. We consider this to be a rare case of NHL associated with PLE which is extremely resistant to chemotherapy or LAK therapy.
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PMID:[Non-Hodgkin lymphoma associated with a long history of protein losing enteropathy]. 262 5

Twenty-eight patients with poor prognosis acute myeloid leukemia (AML) received therapy with two courses of fludarabine 30 mg/m2/day + ara-C 2 g/m2/day (days 1-5) and G-CSF 5 mg/kg/day (FLAG) (from day 0 to polymorphonuclear recovery). Eighteen patients were considered 'refractory' (eight primarily resistant, five relapsing within 6 months of initial remission, or at a second relapse; five relapsing after an autologous bone marrow transplantation procedure. Ten cases were defined 'secondary' AML (diagnosis of AML made after a preexisting diagnosis of: myelodysplastic syndrome: five cases; myelodysplastic syndrome after therapy for breast cancer: one case; previously untreated, and concomitant, non-Hodgkin's lymphoma: two cases; Hodgkin's disease treated with chemoradiotherapy: one case). Overall, 15 patients (58%) achieved a complete remission (CR). Two patients died of infection during induction, and 11 had resistant disease. Analyzing the data in relation to selected host and disease characteristics, the response varied widely. The highest CR rates (89%) were obtained in secondary AML; in particular, two cases of 'second-primary' (concomitant with low-grade non-Hodgkin's lymphoma) AML obtained CR for both diseases. Refractory AML differed widely for response: high CR rate (75%), although with short mean CR duration for primary resistance AML, and very poor response (11% CR) for relapsed (early, second, after ABMT) cases. Interestingly, a slow kinetic of leukemic growth in vivo before FLAG administration was significantly related to the response and outcome (p = 0.0002). Hematological and nonhematological toxicities were acceptable. In conclusion, the FLAG regimen has significant antileukemic activity and acceptable toxicity especially in secondary AML, both with and without coexisting lymphoid malignancy.
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PMID:FLAG (fludarabine + high-dose cytarabine + G-CSF): an effective and tolerable protocol for the treatment of 'poor risk' acute myeloid leukemias. 752 88

The bcl-2 gene is expressed in many types of human tumours and becomes transcriptionally deregulated in the majority of non-Hodgkin's lymphomas as the result of t(14;18) chromosomal translocations. The 26-kDa Bcl-2 protein has been shown to block programmed cell death (apoptosis) induced by many types of stimuli, including a wide variety of chemotherapeutic drugs and radiation. The presence of bcl-2 in tumor cells has been correlated with poor responses to therapy in patients with some types of cancer. To explore further the relevance of bcl-2 to drug resistance, we used antisense (As) approaches to achieve reductions in the levels of steady state Bcl-2 protein levels in t(14;18)-containing human lymphoma cell lines. Both synthetic bcl-2-As oligonucleotides and inducible expression plasmids that produce bcl-2-As transcripts induced reductions in bcl-2 expression, resulting in a marked enhancement in the sensitivity of neoplastic cells to conventional chemotherapeutic drugs such as cytosine arabinoside (ara-C) and methotrexate (MTX). These results suggest that novel therapeutics targeted against bcl-2 could provide the means for improved treatment of cancer by affecting physiological pathways distal to the targets of cytotoxic drugs.
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PMID:Reversal of chemoresistance of lymphoma cells by antisense-mediated reduction of bcl-2 gene expression. 795 Mar 2

Fifty-one consecutive patients with Hodgkin's disease (HD) have been treated with high-dose chemotherapy (HDT) and transplantation of autologous bone marrow (BM) (n = 44), autologous BM plus peripheral blood stem cells (PBSC) (n = 2), PBSC (n = 1), syngeneic (n = 1), or allogeneic BM (n = 3). All patients had received standard salvage chemotherapy prior to HDT and were classified as sensitive (n = 33) or resistant (n = 17) to this treatment; one patient was in untreated relapse prior to BMT. The preparative regimens for patients receiving autologous BM and/or PBSC consisted of cyclophosphamide, VP 16, and BCNU (CVB) (n = 44) or BCNU, etoposide, ara-C, and melphalan (BEAM) (n = 3). The patients receiving allogeneic transplants were treated with the CVB regimen (n = 2) or busulfan (16 mg/kg body wt.) and cyclophosphamide (200 mg/kg body wt.). With a median follow-up of 12 months, overall survival for 44 patients grafted with autologous BM is 61% +/- 9%, progression-free survival for patients with sensitive disease is 44% +/- 11%; no patient with resistant relapse survived beyond 1 year post transplant. Two of three patients grafted with allogeneic BM still survive 15 and 24 months after BMT with Karnofsky performance scores of 70% and 100%, respectively. The main toxicity encountered with the CVB regimen was interstitial pneumonia (IP), seen in four of 15 patients (27%) receiving > or = 600 mg/m2 of BCNU. Three of these patients have died. The results show that HDT followed by hematopoietic stem cell rescue may effectively salvage an important fraction of patients with relapsed HD who respond to standard chemotherapy. The same approach is largely unsuccessful in patients with proven refractoriness to standard chemotherapy. Whether HDT followed by BMT or PBSC support is superior to intensive chemotherapy without stem cell support can be answered only by a prospectively randomized trial.
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PMID:High-dose chemotherapy and hematopoietic stem cell rescue in patients with relapsed Hodgkin's disease. 809 2

The authors report a case of primary ovarian non Hodgkin malignant lymphoma in a 41-year-old multiparous woman. An ovarian tumor was diagnosed in a context of hypogastric distention and discomfort. A total hysterectomy was performed with bilateral uterine appendectomy. The intra-abdominal organs were not affected and there were no internal adenopathies. The pathology examination concluded that this was a highly malignant, non-Hodgkin lymphoma. The findings of the extension assessment were negative. Five cycles of drastic chemotherapy combining bleomycin, adriamycin, cyclophosphamide, vincristine, methotrexate, iphosphamide, cisplatyl, VP-16 and ara-C have been administered and will be followed by abdominal radiotherapy. The patient is considered to be in a state of complete remission with a follow-up period of four years.
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PMID:[Malignant non-Hodgkins lymphoma with primary ovarian location. Observations apropos of a case]. 846 63


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