Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Graft-versus-host disease (GVHD), graft rejection, disease recurrence and long-term toxicity remain significant obstacles to successful allogeneic bone marrow transplantation (BMT) in children with genetic diseases. In an attempt to improve results, we used a preparative regimen consisting of three alkylating agents, busulfan (BU), thiotepa (TTP) and cyclophosphamide (CY), for T cell-depleted allogeneic bone marrow transplantation instead of the conventional BU-CY protocol. The effect of this intensified regimen was investigated in 26 consecutive children with genetic diseases who underwent T cell-depleted BMT from HLA-identical siblings. Sixteen patients were males and 10 females, of median age 5 (0.2-14) years. The diseases included beta-thalassemia major, osteopetrosis, severe combined immunodeficiency, Wiskott-Aldrich syndrome, familial agranulocytosis, congenital idiopathic hemolytic anemia (CIHA), Gaucher's disease, Niemann-Pick disease, Hurler's syndrome, and adrenoleukodystrophy. The conditioning regimen consisted of BU 4 mg/kg x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1). Engraftment was as expected, with WBC >1.0 x 10(9)/l at day +19 (10-33), ANC >0.5 x 10(9)/l at day +22 (10-56) and platelets >25 x 10(9)/l at day +32 (18-131). Transplant-related mortality was 19%. Overall survival and disease-free survival (DFS) at 60 months follow-up were both 77%. Our results with the BU-TTP-CY regimen followed by T cell-depleted BMT in genetic diseases may provide a basis for prospective comparison with the standard conditioning regimen of BU-CY in the management of children suffering from these conditions.
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PMID:The role of thiotepa in allogeneic bone marrow transplantation for genetic diseases. 1033 39

Candidemia is a serious complication in patients following allogeneic blood, marrow, and organ transplantation. Fourteen patients developed nosocomial fungemia among 204 allogeneic marrow transplants performed during 1997-1999. Incidence of hematogenous candidiasis was 6.8 per 100 allogeneic BMT. All 14 had an indwelling central venous catheter (CVC) and fluconazole (100-200 mg daily) was given prophylactically. In 11 (78.5%) neutropenic patients, duration between agranulocytosis and diagnosis of fungemia was (median, +/- s.d.) 10 +/- 8 days. Candida glabrata (53.3%) was the most common yeast species, followed by C. krusei (33.3%), and C. parapsilosis (13.3%). Candida albicans was conspicuously absent. Ten patients (71.4%) had primary transplant-related complication (>2 days) including hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) (n = 5), severe hemorrhagic cystitis (n = 3), and bacteremia (n = 2). Seven (50.0%) patients expired and in three (21.4%) deaths were attributed to fungemia. The impact of a primary transplant-related complication on short-term survival in this setting was not significant (P = 0.07) (HUS/TTP (P > 0.5); neutropenia (P > 0.5); GVHD (P = 0.35)). Removal of CVC did not alter outcome in our group (P > or = 0.5) although in patients with persistent fungemia (>72 h), and those with preceding bacteremia, mortality was significantly higher (P = 0.002). Conventional prognosticators of poor outcome did not adversely effect short-term survival in our transplant recipients with hematogenous candidiasis. The predominance of C. glabrata and C. krusei breakthrough infections was similar to what is seen with high-dose fluconazole (400 mg) prophylaxis, and no adverse effects of low-dose fluconazole in terms of increased incidence of non-susceptible Candida species was seen.
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PMID:Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome. 1178 48

Despite significant advances in the management of immunosuppressed patients, invasive aspergillosis remains an important life-threatening complication. In the past two decades, the incidence of invasive aspergillosis in this population has continued to increase. Factors that predispose patients to develop invasive aspergillosis include prolonged granulocytopenia, the development of graft-versus-host disease, immunosuppressive therapy, the use of adrenal corticosteroids, and the prolonged impairment of host defenses associated with diseases such as chronic granulomatous disease. Environmental factors also play a key part in the pathogenesis of this infection, and therefore, infection control measures play a critical role in reducing exposure of patients to Aspergillus. New exciting developments in the early diagnosis of invasive aspergillosis and the acceleration of antifungal drug discovery offer promise for the future.
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PMID:Invasive aspergillosis in 2002: an update. 1195 17

Blood and marrow transplantation (BMT) is increasingly used to treat malignant and nonmalignant diseases. Despite significant advances in the management of transplant recipients, however, fungal infections remain important life-threatening complications of BMT. Over the past two decades, the incidence of fungal infections in this population has continued to rise. Several factors predispose BMT recipients to invasive fungal infections. These include but are not limited to use of intensive myeloablative chemotherapy and radiation therapy combined with prolonged granulocytopenia; development of acute and chronic graft-versus-host disease; administration of immunosuppressive therapy, particularly using corticosteroids; use of central venous catheters; and prolonged impairment of cell-mediated immunity secondary to the underlying disease and post-transplant immunodeficiency. Environmental factors also play a key part in the pathogenesis of fungal infections. Therefore, infection-control measures are critical to the prevention of such infections. In addition, although Candida and Aspergillus species are still the major culprits, other opportunistic fungi have emerged in recent years.
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PMID:Risk factors for the development of invasive fungal infections in allogeneic blood and marrow transplant recipients. 1212 20

Fungal infection is one of the most important causes of morbidity and mortality in bone marrow transplant (BMT) recipients. The growing incidence of these infections is related to several factors including prolonged granulocytopenia, use of broad-spectrum antibiotics, conditioning regimens, and use of immunosuppression to avoid graft-versus-host disease (GvHD). In the present series, we report five cases of invasive mold infections documented among 64 BMT recipients undergoing fluconazole antifungal prophylaxis: 1) A strain of Scedosporium prolificans was isolated from a skin lesion that developed on day +72 after BMT in a chronic myeloid leukemic patient. 2) Invasive pulmonary aspergillosis (Aspergillus fumigatus) was diagnosed on day +29 in a patient with a long period of hospitalization before being transplanted for severe aplastic anemia. 3) A tumoral lung lesion due to Rhizopus arrhizus (zygomycosis) was observed in a transplanted patient who presented severe chronic GvHD. 4) A tumoral lesion due to Aspergillus spp involving the 7th, 8th and 9th right ribs and local soft tissue was diagnosed in a BMT patient on day +110. 5) A patient with a history of Ph1-positive acute lymphocytic leukemia exhibited a cerebral lesion on day +477 after receiving a BMT during an episode of severe chronic GvHD. At that time, blood and spinal fluid cultures yielded Fusarium sp. Opportunistic infections due to fungi other than Candida spp are becoming a major problem among BMT patients receiving systemic antifungal prophylaxis with fluconazole.
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PMID:Fungal infections in marrow transplant recipients under antifungal prophylaxis with fluconazole. 1213 18

Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic stem cell transplantation (SCT) received imatinib mesylate (400-1000 mg/d). Disease was in chronic phase in 5 patients, accelerated in 15, and blastic in 8 (7 medullary, 1 extramedullary); median time from transplantation to relapse was 9 months (range, 1-137 months). Thirteen patients had undergone salvage donor lymphocyte infusion (DLI) (median time from DLI to imatinib mesylate therapy, 4 months [range, 2-39 months]). The overall response rate was 79% (22 of 28 patients); the complete hematologic response (CHR) rate was 74% (17 of 23 patients), and the cytogenetic response rate was 58% (15 of 26 patients; complete response in 9 [35%] patients). CHR rates were 100% for chronic phase, 83% for accelerated phase, and 43% for blastic phase. The patient with extramedullary blastic disease achieved complete response. Cytogenetic response rates were 63% (12 of 19 patients) for chronic or accelerated phases (complete cytogenetic response in 8) and 43% for blastic phase (3 of 7 patients). At median follow-up of 15 months, 19 patients were alive, 9 with no evidence of disease. The 1-year estimated survival rate was 74%. Five patients had recurrence of grade 3 (3 patients) or grades 1 to 2 (2 patients) graft-versus-host disease (GVHD). Severe granulocytopenia developed in 43% of patients and thrombocytopenia in 27%; both conditions reversed with dose adjustments of imatinib mesylate. We conclude that imatinib mesylate effectively controlled CML that recurred after allogeneic SCT, but it was associated with side effects including myelosuppression and recurrence of severe GVHD.
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PMID:Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. 1252 95

Bone marrow transplant is currently the treatment of choice for a number of haematological neoplasms. High doses of antiblastic drugs, immunosuppressive agents and acute graft versus host disease before and after bone marrow transplant cause toxic damage to the liver and to the gastrointestinal tract. Related acute abdominal complications often need emergency surgical treatment with a 30-60% mortality rate. In these patients the surgical strategy is complex and hard to schematise. Ninety-one patients undergoing bone marrow transplantation showed acute abdominal symptoms requiring thorough surgical monitoring: 51 had ileocolitis, 17 pancreatitis, 9 cholangitis, 6 cholecystitis, 6 appendicitis, and 2 gastric perforation. Nine patients needed an emergency operation (2 gastroduodenal resections, 1 ileal resection, 2 right hemicolectomies, 2 total colectomies, 1 cholecystectomy and one appendectomy. The operative mortality was 22.2%. Positive blood cultures were quite frequent (63.7%). Moderate granulocytopenia was observed (neutrophils: 500 x mm3) in about 40% of cases, and severe granuloctopenia in only one patient (neutrophils: 100 x mm3) with ileotyphlitis. Moderate thrombocytopenia (PLTS < 50,000 x mm3) was observed in 43.9% of cases while in three cases (all submitted to surgical treatment) the platelet count was < 5,000 x mm3. The recent increase in bone marrow transplants has led to a progressive rise in the number of patients with acute abdominal complications. When deciding the surgical strategy in treating acute abdominal complications the surgeon must consider that surgical intervention is indicated only after unsuccessful medical treatment and that the intestinal segment involved must always be removed as far as possible; severe neutropenia, thrombocytopenia (< 10,000 x mm3) and positive blood cultures, especially for CMV, are unfavourable prognostic factors.
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PMID:[Acute abdominal complications in bone marrow transplant recipients]. 1223 61

Good prognosis after imatinib mesylate treatment has been reported if cytogenetic clonal evolution (CE) is the only criterion of accelerated phase (AP) chronic myelogenous leukemia (CML). To evaluate the impact of CE upon imatinib treatment in post-transplant settings, responses and toxicities in the relapsed AP-CE were analyzed in comparison with those in the relapsed chronic phase (CP). Both CP (n=7) and AP-CE patients (n=6) received imatinib mesylate in an oral dose of 400 mg/day. Complete cytogenetic responses were obtained in six patients of each group, CP (86%) and AC-CE (100%), while molecular remission was seen in 43 and 50%, respectively. Granulocytopenia or thrombocytopenia of grade III or more occurred in four (57%) and two (33%) patients with CP and AP-CE, respectively. Nonhematological adverse events were mild and tolerable in both groups and only one (7%) of the 13 patients experienced recurrent graft-versus-host disease after imatinib treatment. Although this is a relatively small group of patients, we suggest that imatinib mesylate should be considered as a front-line treatment for relapsed CML as it showed the high response rate and low toxicity. We also suggest that CE alone is not an important factor in the induction of cytogenetic and molecular remissions in post-transplant relapse.
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PMID:Cytogenetic clonal evolution alone in CML relapse post-transplantation does not adversely affect response to imatinib mesylate treatment. 1462 81

This study was aimed to investigate the relation of reinfused hematopoietic stem cell volume and recipient's leukocyte count at reinfusion with prognosis of disease in allo-hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 37 patients received allo-HSCT in our hospital were analyzed retrospectively. The 37 patients were divided into agranulocytosis and non-agranulocytosis groups according to the recipient's leukocyte count at reinfusion, and were divided into the high dose and low dose groups according to the median number of reinfused mononuclear cells (MNC) and CD34(+) cells. Then, hematopoietic reconstructions,GVHD, relapse and death rates of patients were compared. The results showed that the hematopoietic reconstruction of patients in non-agranulocytosis group and high dose MNC group were earlier than that in agranulocytosis group and low dose MNC group. There was no significant difference of hematopoietic reconstruction between the groups of high dose CD34(+) cells and low dose CD34(+) cells. The GVHD incidence was higher in high dose MNC group and non-agranulocytosis group than that in low dose MNC group and agranulocytosis group (P < 0.05). There were no statistical differences of relapsed and death rates between different reinfused number of HSC and recipient's leukocyte count at reinfusion.It is concluded that the infused MNC number and the recipient's leukocyte count at reinfusion in allo-HSCT correlated with hematopoietic reconstruction, the GVHD incidence is high in high dose MNC and non-agranulocytosis groups, the reinfused HSC volume and the recipient's leukocyte count at reinfusion not significantly relate with relapse and death rates.
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PMID:[Relation of reinfused hematopoietic stem cell volume and recipient's leukocyte count at reinfusion with prognosis of disease in allo-hematopoietic stem cell transplantation]. 2437 43

A 64-year-old woman underwent reduced-intensity conditioning cord blood transplantation (RIC-CBT) for refractory acute myeloid leukemia (AML). A 6/6 antigen-level HLA-identical cord blood from a male infant was transfused. After successful engraftment with complete donor chimerism, the patient developed mixed chimera (XX 8.8%) on day 82. Tapering of tacrolimus was started on day 96. Bone marrow chimerism analysis showed a decreasing recipient cell population (XX 2.2%) on day 117 and tacrolimus was discontinued with no clinical signs of GVHD on day 123. However, pancytopenia with agranulocytosis was detected on day 138. She was diagnosed as having secondary graft failure associated with Coombs-positive immune hemolytic anemia and immune thrombocytopenia (ITP). At the same time, the percentage of recipient T cell chimerism in peripheral blood was about 50% and the B cell population showed lambda light chain restriction. On day 180, she received a second RIC-CBT due to lack of improvement of agranulocytosis. A single dose of rituximab was administered on day - 11 before the second CBT to eliminate the activated B cells. Prompt neutrophil engraftment was achieved and both hemolytic anemia and ITP also showed resolution. She is currently well (30 months after the second CBT), showing normal blood cell counts and complete second donor chimerism of marrow cells.
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PMID:[Successful second cord blood transplantation (CBT) for late graft failure associated with several immune disorders after the initial CBT in a patient with acute myeloid leukemia]. 2625 Nov 54


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