Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report our findings in two cases of steroid-resistant severe acute GVHD after allogeneic BMT successfully treated with FK506 (tacrolimus). An 18-year-old female (patient 1) who underwent BMT from an HLA-identical sibling for ALL in first CR, developed generalized erythema and profuse watery diarrhea, which progressed to acute GVHD of grade III severity, resistant to steroid control. After continuous 24-h administration of FK506, the diarrhea improved within 10 days. Patient 2, a 9-year-old girl with AML who underwent unrelated BMT, had skin, gut and liver lesions of acute GVHD grade IV, which did not respond to high-dose steroid therapy. They were controlled, however, by continuous intravenous infusion of FK506. Both patients are still surviving after more than 1 year without any acute GVHD sequelae or signs of chronic illness. The adverse effects of FK506 were mild and tolerable in both cases. Comparison of our findings with those in the literature suggests that it is important to give FK506 at plasma concentrations as high as 25-35 ng/ml by continuous intravenous infusion for extended periods to control steroid-resistant severe acute GVHD.
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PMID:Successful treatment of steroid-resistant severe acute GVHD with 24-h continuous infusion of FK506. 908 43

In our BMT Unit, we have observed a high frequency of skin rash associated with fever and other clinical findings during engraftment of autologous BM and/or PBSC. Thirty patients with breast cancer and 12 patients with Hodgkin's or non-Hodgkin's lymphoma, treated with the same regimen, were analyzed retrospectively or prospectively to characterize the clinical syndrome, its frequency, and its clinical course, as well as to define the factors affecting its incidence. In patients developing skin rash, the median and range for time to onset of skin rash and for time to increase in WBC after reinfusion of stem cells were identical (8 days, range 5-13) and did not differ significantly (P = 0.533). Twenty-three patients (55%) had skin rash, 18 patients had fever. Other, less frequent manifestations include platelet transfusion refractoriness (PTR), diarrhea, diffuse alveolar hemorrhage, and autoimmune thrombocytopenia or hemolytic anemia. A higher proportion of breast cancer patients developed the syndrome in comparison to lymphoma patients (67% vs 25%, P = 0.051). Acute GVHD grade I-II was established histologically in six patients with the syndrome. Comparison of the incidence of the syndrome by different variables using Fisher's exact test revealed significance for disease category (P = 0.02) and number of previous treatment regimens (P = 0.002) as predictive factors for developing the autoaggression syndrome. In other words, patients with breast cancer and those with only one previous treatment regimen were more likely to develop the syndrome. This study suggests that an autoaggression GVHD-like syndrome accompanies the early phase of autologous engraftment and that a higher frequency of the syndrome might be seen in breast cancer patients undergoing high-dose chemotherapy and autologous stem cell transplantation.
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PMID:Increased frequency of autoaggression syndrome associated with autologous stem cell transplantation in breast cancer patients. 911 5

We treated 12 patients with leukemia relapse after allogenic bone marrow transplantation with a combination of interferon-alpha (IFN-alpha) ((2.5-5.0) x 10(6) u/m2 subcutaneously three times a week) and interleukin-2 (IL-2) ((1.8-3.6) x 10(6) IU/m2 subcutaneously five times a week) to determine the toxicity and efficacy of combination cytokine therapy in this setting. The median age of the patients was 39 years (range: 16-50). There were nine females and three males. The median time to relapse from BMT was 98 days (range: 0-963). At the time of relapse, six patients had AML, four patients had CML (two in blast crisis and two in chronic phase with clonal evolution), and one patient had lymphoblastic lymphoma. Combination cytokine therapy was started a median of 108 days post BMT (range: 37-2404). Nine patients treated at the higher dose level required a 50% dose reduction because of toxicity or GVHD (three CNS, two GVHD, one high fever, one diarrhoea with hypotension, and one pericarditis). At a lower dose level, 2 of 10 patients had their treatment discontinued because of toxicity or GVHD. Six patients developed clinical findings consistent with acute GVHD while on combination cytokine therapy. Two patients responded to combination cytokine therapy: one with CML and one with AML. Combination cytokine therapy is feasible in the setting of relapse post allogeneic BMT. The combination of IL-2 1.8 x 10(6) IU/m2 five times a week with IFN-2 2.5 x 10(6) U/m2 three times a week seems to be tolerable, and merits further study in this setting.
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PMID:Interferon-alpha and interleukin-2 as treatment for leukemia relapse after allogeneic bone marrow transplantation. 938 68

In our all patients, the antibodies to HHV-6 and -7 were positive before BMT. HHV -6 and -7 DNA were sometimes detected after BMT, and HHV-6 infection after BMT caused fever, interstitial peumonitis, diarrhea, and myelosuppression. However, HHV -7 didn't induce any clinical symptoms. For the diagnosis of the HHV-6 or -7 infection, we used the virus isolation, semiquantitative PCR, and 4-hold elevation of the antibodies to HHV-6 or -7. Ganciclovir, foscarnet, high dose gamma-globulin and high dose acyclovir were useful for the treatment of HHV-6 infection after BMT. HHV-6 is an important agent for the fever of unknown origin, interstitial peumonitis, diarrhea, and myelosuppression after BMT.
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PMID:[Human herpesvirus-6 and -7 infection and bone marrow transplantation (BMT)]. 946 92

In an effort to develop more effective therapy for patients with refractory or relapsed acute myelogenous leukemia (R-AML) we combined three drugs with proven activity in AML, that are not typically used in induction regimens, with cytosine arabinoside (ara-C). Twenty-five patients (3 primary refractory, 22 relapsed) were treated. Patients received 3 days of "CECA" therapy as follows: cyclophosphamide (CTX) 1 g/m2 i.v. over 2 hrs., etoposide (VP-16) 200 mg/m2 i.v. over 3 hr, carboplatin (CBP) 150 mg/m2 i.v. over 24 hours and ara-C 1 g/m2 over 2 hr. Peripheral circulating blasts cleared in 24 cases (96%), and marrow aplasia was achieved in 19 (76%). There were 3 complete remissions (CR), 1 patient died before day 14, 5 died aplastic 14 or more days from the start of therapy, 5 had primary resistant disease, and 10 had secondary resistance i.e., leukemia reappearing after developing aplasia and 1 was lost to follow up 6 weeks into therapy. Two of the patients achieving CR received allogeneic BMT in CR (at 18 and 22 weeks): one died of fungal infection on day 50 and the other, who had CNS involvement at relapse, is alive 24 months post transplant. Toxicity was tolerable: one patient each developed grade III diarrhea and mucositis, another had grade III cardiac toxicity, a fourth developed a grade IV bilirubin elevation. Single, 2, and 3 or more infectious episodes occurred in 10, 5 and 4 patients respectively. This regimen showed definite anti-leukemic activity: the 3 patients achieving CR were among 23 patients with a 1%, 10% or 20% expectation for second CR attainment. The CECA regimen should be investigated in better prognosis salvage groups.
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PMID:CECA-cyclophosphamide, etoposide, carboplatin and cytosine arabinoside--a new salvage regimen for relapsed or refractory acute myelogenous leukemia. 951 8

Twenty-six patients affected by acute myeloid leukemia (AML) who relapsed after autologous stem cell transplantation (ASCT) were treated with the FLAG regimen (fludarabine, cytarabine, and G-CSF). Their median age was 39 years (range 14-59). The median interval from achievement of CR to ASCT was 4 months (2-8). The conditioning regimen was BAVC (BCNU, amsacrine, VP-16, cytarabine) in eight patients, BuCy (busulfan, cyclophosphamide) in 13, and TBI-Cy (total body irradiation, cyclophosphamide) in five. Relapse occurred after a median of 7 months (2-18). ASCT had been performed in CR1 for 23 patients and in CR2 for three. Nineteen patients had been given bone marrow, seven peripheral blood stem cells collected following consolidation plus G-CSF. Overall, CR was obtained by 13 patients (50%), all remitters requiring a single course. The median time for hematological recovery of neutrophils >500/microl and platelets >20,000/microl was 24 and 30 days, respectively. The median duration of G-CSF administration was 25 days, while the median hospitalization was 31 days. There were four deaths in induction (15%), while nine patients (35%) were resistant. After achieving CR, two patients received allogeneic BMT, five a second ASCT, and four were consolidated with HD-ARA-C. Only two patients were judged unable to receive any further therapy. There were 14 documented infections, while nine patients experienced fever of unknown origin. WHO >2 nonhematological toxicity consisted of stomatitis (50%), hepatic dysfunction (11%), diarrhea (11%), and lethargy (4%). Median overall survival and disease-free survival were 6 and 13 months, respectively. Six patients are in CCR at present. We conclude that FLAG is effective in patients with AML who are relapsing after ASCT. The toxicity is acceptable, enabling most patients to receive further treatment, including second transplantation procedures.
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PMID:Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of acute myeloid leukemia relapsing after autologous stem cell transplantation. 1046 Mar 53

In recent years, significant improvements have been made in the management of neutropenia and thrombocytopenia and other potentially life-threatening complications of ablative chemotherapy. While these complications are of particular concern to physicians, patients receiving ablative therapy for bone marrow or blood stem cell transplants are often troubled by other side effects such as nausea, vomiting, diarrhea and mouth sores. The purpose of the study was to gain a better understanding of patients' experiences while undergoing a transplant. The same professional medical interviewer conducted in-depth interviews with 38 subjects (10 men, 28 women; mean age 46.9 years) who had received ablative therapy for bone marrow and/or peripheral blood stem cell transplants. Participants were consecutively identified through physician and patient referrals, cancer and BMT patient support groups, and newspaper advertisements. Twenty-eight patients (74%) received autologous stem cell transplants and 10 patients (26%) received allogeneic transplants. Participants reported mouth sores, nausea and vomiting, diarrhea, and fatigue as the most troubling side effects of their transplants. Mouth sores were selected as the single most debilitating side effect (42%), followed by nausea and vomiting (13%). Many patients mentioned that mouth sores made it difficult or impossible to eat (n = 23), swallow (n = 21), drink (n = 17), and/or talk (n = 8). Twenty patients reported pain in the mouth, throat, and/or esophagus. Two-thirds (66%) of patients reported receiving opioid analgesics, most frequently morphine, to relieve oral pain. For many, opioids caused incapacitating side effects, including hallucinations, a feeling of loss of control and a decrease in mental acuity. Patients receiving ablative chemotherapy identify oral mucositis as a significant cause of suffering and morbidity. Effective interventions to alleviate this complication are urgently needed.
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PMID:Patient reports of complications of bone marrow transplantation. 1065 Aug 95

Although the life-threatening cytomegalovirus (CMV) disease is a well known complication following allogeneic hematopoietic stem cell transplantation (HSCT), it has been considered infrequent after autologous peripheral blood stem cell transplantation (PBSCT). On the other hand, the massive involvement of the gastrointestinal (GI) tract as the primary site of fatal CMV disease is particularly rare after autologous PBSCT. We present the case of a woman who suffered from CMV disease after high-dose busulphan/melphalan/thiotepa (BuMelTT) and autologous PBSCT. The primary site of infection was the GI tract, which was extensively affected. During the fifth week post-transplant the patient started with epigastralgia, diarrhea, fever, GI bleeding, and thrombocytopenia, and she died on day +52. Another case of fatal CMV disease among the few patients treated with BuMelTT has been recently reported, which suggests that the immunodeficiency associated with that regimen can be as intense as that occurring after allogeneic BMT.
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PMID:Fatal upper and lower gastrointestinal cytomegalovirus disease following autologous peripheral blood stem cell transplantation. 1116 21

Thrombotic microangiopathy after bone marrow transplantation (post-BMT TMA) is a serious transplant-related complication. We identified 16 patients with TMA after allogeneic BMT who showed histopathological evidence of intestinal TMA in their gut specimens (six autopsies, 10 biopsies). In all, 14 patients had grade II-IV acute graft-versus-host disease (GVHD). The first seven patients were retrospectively diagnosed with TMA. Since six of them were diagnosed with progressive GVHD at that time because there was no awareness of the existence of intestinal TMA, they received more intensive treatment for GVHD, but all died between days +49 and +253. In contrast, the remaining nine patients were recently diagnosed with intestinal TMA on the basis of colonoscopic biopsies. For eight of these patients, the immunosuppressants were reduced, and the patients' intestinal symptoms improved gradually. Six of the nine patients were still alive 12 months after the diagnosis of TMA. Our findings suggest that the gut may be a site involved in post-BMT TMA, presenting as ischemic enterocolitis. Differentiating intestinal TMA from acute GVHD is important in patients suffering from severe and refractory diarrhea after BMT.
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PMID:Intestinal thrombotic microangiopathy after allogeneic bone marrow transplantation: a clinical imitator of acute enteric graft-versus-host disease. 1515 44

Graft failure and nonrelapse mortality (NRM) are major obstacles after the first unrelated-donor bone marrow transplantation (UD-BMT) with reduced-intensity conditioning. We evaluated UD-BMT with fludarabine (5 x 25 mg/m2) and melphalan (2 x 90 mg/m2) treatment combined with short-term methotrexate and tacrolimus (n = 20) or cyclosporine (n = 2) therapy for 22 patients with hematologic malignancies who were ineligible for conventional conditioning. Only 9 patients were in remission at transplantation. Seventeen patients underwent HLA-matched or DRB1 allele-mismatched transplantation, and 5 patients underwent HLA-A allele-mismatched or serologically HLA-DR-mismatched transplantation. Regimen-related toxicities were tolerable, although transient oral mucositis, hepatobiliary enzyme elevation, and diarrhea were observed frequently. All evaluable patients achieved sustained neutrophil engraftment, and all patients tested showed complete donor chimerism on day 28. With a median follow-up of 16 months, NRM and overall survival rates at 1 year were 19% and 81%, respectively, among the patients who underwent HLA-matched or DRB1 allele-mismatched transplantation. Acute graft-versus-host disease (GVHD) of grades II to IV occurred in 26% of the patients. The cumulative incidence of chronic GVHD was 44%. Despite the small number of patients and the short follow-up period, this reduced-intensity regimen enabled satisfactory engraftment and achievement of rapid complete donor chimerism with tolerable toxicities in the patients, including those who underwent HLA-mismatched UD-BMT.
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PMID:Stable engraftment after a conditioning regimen with fludarabine and melphalan for bone marrow transplantation from an unrelated donor. 1675 39


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