Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 16-year-old white male with acute biphenotypic leukemia developed evidence of the eosinophilia myalgia syndrome associated with total parenteral nutritional support with solutions containing tryptophan, which were given during his initial induction chemotherapy and also after autologous marrow transplantation. He developed pronounced eosinophilia and a vasculitic skin rash, myalgias of the abdomen, upper trunk, and neck, and died of respiratory distress with no evidence of an infectious etiology. Autopsy revealed diffuse vasculitis involving the heart, lungs, kidneys, testes, spleen, liver, skin, gut wall and marrow with neuritis of gut wall nerves and ganglia. Thus, the eosinophilia myalgia syndrome can be associated with parenteral tryptophan administration.
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PMID:Fatal eosinophilia myalgia syndrome in a marrow transplant patient attributed to total parenteral nutrition with a solution containing tryptophan. 843 65

A 33-year-old woman with AML (M4) resistant to chemotherapy received syngeneic marrow graft from her identical twin following high dose busulfan and etoposide. However, the relapse was confirmed on the 60th day after the procedure. Since she failed to achieve remission despite intensive chemotherapy, a second BMT from the same donor was performed following total body irradiation and high dose etoposide on the 126th day after the initial BMT. At this time, cyclosporine (1 mg/kg/day) was administered to induce graft-versus-host disease (GVHD). Skin rash appeared on the 18th day after the 2nd BMT, and biopsy from the rash on the 23rd day showed a typical picture of cutaneous GVHD (grade 2) and there was no evidence of viral infection. On the 36th day after the 2nd BMT, the patient died of veno-occlusive disease. Although graft-versus-leukemia effect in this patient could not be evaluated because of early death, the induction of GVHD with cyclosporine might be effective to reduce the relapse rate after syngeneic or autologous BMT. Further studies are required to confirm this effect.
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PMID:[Cyclosporine-induced graft-versus-host disease in a syngeneic bone marrow transplantation]. 845 Jun 5

Generalized or localized itch without primary skin manifestations may be the presenting symptom of serious internal diseases. Five characteristic cases of pruritus are discussed: Hodgkin's disease, primary sclerosing cholangitis, polycythemia vera, iron deficiency (with pica), and uremia. Other important causes must be considered; all forms of cholestasis, including primary biliary cirrhosis, drug-induced, pregnancy-related, and extrahepatic cholestasis; other hematologic and malignant disorders such as non-Hodgkin's lymphoma, leukemia, multiple myeloma, solid tumors, and myelodysplastic syndromes; metabolic and endocrine diseases, most notably diabetes mellitus, hyperthyroidism, hypothyroidism, and carcinoid syndrome; focal neurologic diseases such as brain tumors, cerebral infarctions and multiple sclerosis; adverse drug reactions without rash; infectious diseases, especially parasitic and HIV infections. A diagnostic laboratory screening for pruritus of undetermined origin is suggested.
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PMID:[Pruritus--also a challenge in internal medicine]. 852 44

Patients with AML who relapse after an initial remission, have a poor prognosis. Administration of hemopoietic growth factors (HGFs) such as interleukin-3 (IL-3) during chemotherapy may result in an increased cell kill by cytotoxic agents. In addition, administration of IL-3 following chemotherapy may potentially accelerate hemopoietic recovery from chemotherapy-induced bone marrow hypoplasia. We performed an open labelled, phase I/II study in which patients received IL-3 by continuous infusion from 24 h before the beginning of chemotherapy until day 28. Chemotherapy included daunorubicin or mitoxantrone days 1-3 and cytarabine 200 mg/m2 days 1-7. IL-3 was given at a dose of 5 microgram(s)/kg/day in 10 patients, 7.5 microgram(s)/kg /day in six patients and 10 microgram(s)/kg/day in four patients. Complete remissions (CR) after one cycle of this treatment were obtained in 5/10 patients and 5 microgram(s)/ kg group, 2/6 in the 7.5 microgram(s)/kg group and 3/4 in the 10 microgram(s)/kg group). Thus, 50% (10/20) of all individuals and 45% (5/11) of the elderly patients attained CR. Eight of 20 patients entered PR, and 2/20 patients died during the hypoplastic phase from infectious complications. Neutrophils and platelets recovered to 0.5 x 10(9)/l at day 25 (median) and to 50 x 10(9)/l at day 32, respectively. Adverse events during IL-3 and concomitant chemotherapy were fluid retention (4/20), rash (14/20), bone pain (2/20), headache (10/20), chest pain (1/20), arthritis (1/20), fever and nausea. IL-3 (at the dose of 10 microgram(s)/kg) was discontinued in two patients because of side-effects (fluid retention, fever, rash and chest pain), and in two other patients the high IL-3 dose was tolerated with no problems for 29 days. Thus, IL-3 applied to patients with high-risk AML at dosages of 5-10 microgram(s)/kg is tolerated with acceptable toxicity and results in a satisfactory frequency of complete responses following a single treatment cycle.
Leukemia 1996 Jan
PMID:Recombinant human interleukin-3 (rH IL-3) in combination with remission induction chemotherapy in patients with relapsed acute myelogenous leukemia (AML): a phase I/II study. 855 36

Fifty-eight cases of bacteremia due to Moraxella catarrhalis, including seven that occurred in patients treated at our facilities, are analyzed. The host's medical history plays a major role in the presentation and outcome of M. catarrhalis bacteremia. Bacteremia is typically accompanied by pneumonia in adults with underlying respiratory disease. Many neutropenic patients do not manifest a focus of infection; in contrast, the source identified in healthy, immunocompetent patients is usually the upper airway or the ears. In the recent literature, it has been reported that a rash is typically absent in adults with bacteremic pneumonia and in immunocompetent hosts and that only some neutropenic patients have a rash. The prognosis is grave for patients with endocarditis and for patients with immunoglobulin deficiency or neutropenia not related to a hematologic malignancy. In addition, mortality is substantial among bacteremic patients with respiratory conditions or other chronic debilities, especially when respiratory copathogens are present. The prognosis is good for febrile neutropenic patients with underlying leukemia or lymphoma when the neutropenia resolves. When healthy, immunocompetent individuals are affected with M. catarrhalis bacteremia, their presentations range from self-limited febrile illness to life-threatening disease.
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PMID:Spectrum and significance of bacteremia due to Moraxella catarrhalis. 856 49

A 43-year-old male with newly diagnosed hairy cell leukaemia underwent a single course of 2-chlorodeoxyadenosine (2-CdA). Skin rash, facial swelling and marked eosinophilia developed 20 d after treatment and were resolved by 7 d of steroid therapy. Eosinophil peak in peripheral of the eosinophil population showed a high expression of the IL-2 receptor alpha-chain (CD25), representing up to 94% of gated cells. HLA-DR and CD4 antigens were constantly negative; eosinophils strongly reacted with the secretory form of the eosinophil cationic protein (ECP), recognized by EG2 monoclonal antibody. IL-5 serum levels were markedly elevated at the onset of eosinophilia, returned to normal levels after its disappearance and positively correlated with eosinophil count (r = 0.94, P = 0.016). Eosinophilia is an uncommon finding after treatment with 2-CdA. It is unclear whether these phenomena represented a true allergic reaction to the drug or the effect of massive tumour cell lysis and haemopoietic pancytopenia with immunosuppression, which induced the release of IL-5 and possibly other cytokines.
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PMID:Hypereosinophilia during 2-chlorodeoxyadenosine treatment for hairy cell leukaemia. 860 11

A number of cytokines are used as haemopoietic growth factors and this review focuses on toxicities associated with granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1, IL-3, IL-4, IL-6 and macrophage colony-stimulating factor (M-CSF). Both GM-CSF and G-CSF, currently approved for clinical use, are generally well tolerated by the majority of patients during short term administration. Constitutional symptoms and bone pain are the most frequently reported adverse effects, but they are rarely treatment-limiting. Reactivation of rheumatoid symptoms, and exacerbation of autoimmune thyroiditis or autoimmune haematological disorders have sometimes been described. Severe cardiovascular complications include the possibility for arterial thromboses and the vascular leak syndrome, which is more specifically observed with GM-CSF. Reports of several cases and small series of patients have suggested that growth factors might increase the pulmonary toxicity of chemotherapy, a possibility that remains debated and requires further attention. Generalised or local cutaneous reactions are frequently noted with GM-CSF. Leukocytoclastic vasculitis was observed with both growth factors, while neutrophilic dermatoses have been mostly described with G-CSF. Exacerbation of psoriasis and isolated anaphylactic reactions have appeared with GM-CSF and G-CSF. The hepatotoxic potential of the growth factors is not clearly established, but the occurrence of coagulation abnormalities has recently been reported. Renal and biological disturbances are usually transient. Long term treatment with GM-CSF and G-CSF also seems to be well tolerated, but the possible occurrence of several adverse events, i.e. bone disorders, leukaemia, unmasking or acceleration of underlying disease, require further investigation in patients receiving prolonged treatment, as in myelodysplasia. Finally, antibodies against growth factors have been reported only with GM-CSF. Other cytokines are still under investigation. Flu-like and constitutional symptoms, sometimes dose-limiting, have been reported with IL-1, IL-3, IL-4 and IL-6, while M-CSF was occasionally associated with such adverse effects. More specific adverse events, also frequently considered as dose-limiting toxicities, include hypotension with IL-1, severe headache or skin rash with IL-3, and nasal congestion and gastroduodenal lesions with IL-4. Severe capillary leak syndrome has been reported only with IL-4. M-CSF toxicity is minimal and limited to reversible but sometimes dose-limiting thrombocytopenia and ophthalmological symptoms with the recombinant product. Again, the safety of long term administration of these cytokines has not yet been determined, and IL-3-induced disease progression in myelodysplastic patients has been suggested.
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PMID:Clinical toxicity of cytokines used as haemopoietic growth factors. 865 81

The high relapse rate of hematologic malignancy treated with autologous bone marrow transplantation (ABMT) may reflect the absence of a graft-versus-leukemia (GVL) effect usually associated with graft-versus-host disease (GVHD). The purpose of this study was to determine whether administration of interleukin-2 (IL-2) early after ABMT might induce or exacerbate acute skin GVHD. Fourteen patients at high risk for post-transplant relapse, eight with NHL and six with AML > or = first relapse, were conditioned with chemotherapy and total body irradiation (13) or chemotherapy alone (1), and received purged (10) or unpurged (4) marrow. A median of 35 days (range 25-58) after ABMT, they received a 5-day induction course of Roche IL-2 (9 x 10(6) U/m2/day) followed by apheresis, reinfusion of LAK cells, and a 10-day maintenance course of IL-2 (0.9 x 10(6) U/m2/day), all by continuous i.v. infusion. Serial skin biopsies were obtained before and after IL-2 therapy and were read blindly. Patients were studied prospectively for the development of acute cutaneous GVHD as reflected by rash ( > or = 25% body surface area), skin biopsy ( > or = grade II histologic changes) and T cell infiltration as assessed by staining of the biopsy with antibodies UCHL-1 and TIA-1. No patient had a rash before IL-2 therapy, but 12 of 14 (85%) developed a rash during the IL-2 induction course. Before IL-2 therapy, biopsies from three of 10 patients (30%) revealed histologic GVHD; after induction IL-2, biopsies from 11 of 14 patients (79%) revealed grade II acute GVHD. Biopsies from all patients with histologic GVHD after IL-2 therapy contained TIA-1 positive T cells. HLA-DR was negative in the keratinocytes of these paraffin-embedded sections. One patient died early of sepsis, one patient required and responded to topical corticosteroids and 12 had spontaneous resolution of the rash. Six patients relapsed at 3-13 months, while seven remain in complete remission 32+ to 41+ months after ABMT. The results demonstrate that IL-2 therapy after ABMT can induce effects which histologically and clinically mimic cutaneous acute GVHD in most patients. Prospective, randomized trials of IL-2 vs observation after transplantation of autologous marrow or stem cells for high-risk NHL and AML have been initiated which may allow us to determine whether this phenomenon is associated with a clinical GVL effect as reflected by a decreased relapse rate.
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PMID:Close simulation of acute graft-versus-host disease by interleukin-2 administered after autologous bone marrow transplantation for hematologic malignancy. 870 86

Because of its exanthem, the disease varicella has been known since antiquity. Even late in the 19th century, however, there remained considerable confusion between mild smallpox and chickenpox. The name varicella itself is an irregular diminutive form of variola. Yet, early in the 20th century, detailed histologic studies began to differentiate the exanthems. The investigation of the varicella vesicle by Tyzzer 90 years ago remains a classic example (see Fig. 2). Although the pathogenesis of varicella vaccine virus infection appears to mimic that of wt VZV infection, a vaccine virus-related exanthem is more common in immunized children with an underlying immunosuppressive condition, such as leukemia, than in normal children. Those immunized children who never develop a rash presumably have an abrogated infection in which the host immune response has eliminated the virus prior to a major viremic spread. There may be a correlation between the presence of an exanthem and the ability of an immunized child to spread the varicella vaccine virus. The differences in capsid structure and assembly may explain in part the attenuation of the vaccine strain. Because the majority of varicella vaccine virus particles in the nucleus have aberrant cores lacking an electron-dense center, they are never enveloped. Therefore, they do not become infectious virions. In a recent article, Grose et al applied the technique of three-dimensional (3-D) computer modeling in an attempt to reconstruct an aberrant VZV capsid with the hubcap or pinwheel core. Each 3-D model was then sliced by computer to obtain a series of two-dimensional models that represented the images commonly seen by traditional electron microscopy. The 3-D model that best represented the capsid with a pinwheel core contained particulate matter in each of the 12 vertices of the icosahedral capsid (Fig. 14). This model strongly suggested that VZV may form in the nucleus an intermediary or end-stage capsid with an aberrant distribution of assembly protein or viral DNA within its core. Herpes simplex viral particles with pinwheel cores are rarely seen in cell culture, so this type of aberrant capsid appears to be associated mainly with VZV replication. Thus, the strategy of Takahashi and colleagues to serially passage the varicella vaccine virus in human embryonic lung cells, guinea pig embryo cells, and Wistar Institute strain 38 (WI-38) cells may have exploited in as yet unknown ways the profound cell-associated nature of VZV to achieve an end product with attenuated pathogenic potential.
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PMID:Pathogenesis of infection with varicella vaccine. 885 49

Varicella vaccine in immunocompromised children was clinically evaluated in 575 US and Canadian children with leukemia in remission by the Varicella Vaccine Collaborative Study. Most children had chemotherapy stopped 1 week before and 1 week after immunization. Steroids were stopped for 3 weeks (1 week before to 2 weeks after vaccination). Varicella vaccine was safe, immunogenic, and effective in leukemic children at risk for serious disease or death from chickenpox. The major side effect was mild rash in 50% approximately 1 month after immunization. About 40% of children who developed rash were treated with acyclovir. Vaccine efficacy was judged by the degree of protection after a household exposure to varicella; of 123 exposed children, 17 (14%) developed a mild form of varicella. The vaccine protected completely against severe varicella. Leukemic vaccines were less likely to develop zoster than were comparable children with leukemia who had wild type varicella. Thus, varicella vaccine, administered carefully with close follow-up, is extremely beneficial for leukemic children.
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PMID:Varicella vaccine for immunocompromised children: results of collaborative studies in the United States and Canada. 889 39


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