Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute graft-versus-host disease (GVHD) has recently been associated with endothelial cell injury. The potential clinical significance was explored here in an autopsy review. Thirty-seven allogeneic bone marrow recipients were identified in the autopsy files at The Johns Hopkins Hospital with no evidence of systemic infection. Forty-one percent (15/37) of these patients were found to have extensive recent pulmonary hemorrhage at autopsy which was thought to have led to terminal respiratory failure and death. The 37 patients were divided into 2 groups: those with significant acute GVHD (stage 2 or greater) and those without GVHD (stage 0 or 1). Fifty-nine percent (10/17) of the patients with significant acute GVHD died of acute respiratory failure due to recent pulmonary hemorrhage as opposed to 25% (5/20) of those without acute GVHD (P = 0.032, Fisher's exact test). Terminal pulmonary hemorrhage was also associated with preparation for BMT, with 67% (12/18) of those prepared with total body irradiation (TBI) having pulmonary hemorrhage as opposed to 15% (3/19) of those prepared with chemotherapy using Busulphan (P = 0.002). There was no significant difference in posttransplant survival, engraftment, or final platelet count between the patients stratified by GVHD or preparative protocol. The data support a strong association between significant acute GVHD and terminal hemorrhage, as well a possible association between TBI and pulmonary hemorrhage. Analysis of variance demonstrates that GVHD and TBI are independently associated with increased pulmonary hemorrhage (P < 0.01 for GVHD, P < 0.001 for TBI). We propose that GVHD contributes to terminal pulmonary hemorrhage by injuring the endothelium. However, this association could also be a secondary effect, i.e., toxicity from therapy for GVHD, or an abnormality in cytokines or growth factors. The pathogenic relationship between significant GVHD and terminal hemorrhage is discussed briefly.
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PMID:Pulmonary hemorrhage as a cause of death in allogeneic bone marrow recipients with severe acute graft-versus-host disease. 829 Nov 20

Fiberoptic bronchoscopy (FOB) has been reported to have a high diagnostic yield and to be safe in BMT patients with pulmonary infiltrates. At our institution, BMT patients with respiratory symptoms and/or pulmonary infiltrates had a thoracic CT and bronchoalveolar lavage (BAL). Transbronchial biopsy (TBBx) was considered if the platelet count could be raised to >30 x 10(9)/l. From March 1993 to August 1995, 52 patients had 68 FOBs (42 BAL + TBBx, 26 BAL only) for 60 episodes of clinical pneumonia. Patients' characteristics were: 38 males, mean age 42 years, and 39 allogeneic BMTs. Of the 68 FOBs, 47 were performed to evaluate diffuse infiltrates, 10 were done on mechanically ventilated patients, and 50 of the FOBs were preceded by a platelet transfusion. Thirty-one percent of FOBs (21 FOBs, 19 patients) were diagnostic. Twenty-four percent of FOBs (11 diagnostic FOBs, six nondiagnostic FOBs) changed therapy. Ten complications (15%) occurred in 10 FOBs (five acute respiratory failure, three pneumothoraces, one nose bleed, one death). Hospital and 6-month survival based on episodes of clinical pneumonia were 47 and 32%, respectively. Patients who had a diagnostic FOB or a FOB that changed treatment did not have better hospital or 6-month survival compared to patients who had FOBs that were nondiagnostic or did not change treatment. FOB in our BMT patient population, had a low diagnostic yield (31%), infrequently changed treatment (24%), a significant complication rate (15%) and was not associated with improved patient survival. The role of routine diagnostic FOB in BMT patients with pulmonary infiltrates and/or respiratory symptoms should be reevaluated.
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PMID:Utility of fiberoptic bronchoscopy in bone marrow transplant patients. 938 32

The role of support measures in the Intensive Care Unit for bone marrow transplant recipients has been controversial. Data from 176 pediatric bone marrow transplants were retrospectively analyzed to ascertain the probability, causes, risk factors and survival for life-threatening complications requiring intensive care. Ninety-two patients underwent allogeneic BMT and 84 autologous BMT between January 1991 and December 1995. Thirty-one ICU admissions were recorded. The most frequent causes were acute respiratory failure (n = 15, mostly interstitial pneumopathies), septic shock (n = 5) neurological disorders (n = 5) and heart failure (n = 2). The cumulative incidence of an ICU admission at 20 months post-transplant in patients with an allogeneic BMT was 25.7% (CI: 16.4-35.1), compared with 10.8% (CI: 4.2-17.5) in those with an autologous graft (P = 0.04). ICU admission frequency was maximum during the first 2 months post-transplant. All complications in patients with autologous transplants appeared during the first 5 months post-transplant. Among patients with allogeneic grafts, four were later admitted to the ICU, at 7, 9, 12 and 20 months post-transplant, respectively. The main risk factor for ICU admission was acute GVHD grades III-IV. No differences were found between patients with allogeneic transplants with GVHD grades 0-II and those undergoing autologous transplant. In contrast, differences were highly significant between patients undergoing allogeneic transplants with GVHD grades III-IV and those with GVHD grades 0-II or autologous transplants. No differences were observed between allogeneic and autologous transplants in terms of causes for ICU admission, duration of stay, hours on mechanical ventilation, hours on inotropic drug therapy and numbers of organs failing. Neither were differences found in ICU discharge survival between patients with allogeneic (50%, CI: 29.1-70.9) and autologous (66.7%, CI: 29.9-89.1) transplants. ICU discharge survival in patients admitted for lung disease was 28.6% (CI: 12.1-65.6) but 76.5% (CI: 41.9-87.8) in patients admitted for other causes (P = 0.007). ICU discharge survival in mechanically ventilated patients was 46.2% (CI: 27.0-65.4), significantly lower than nonventilated patients (100%). Three-year survival in all transplanted patients admitted to the ICU was 29.7% (CI: 13.1-45.0) compared with 70.2% (CI: 62.7-77.6) in patients not requiring ICU admission (P<0.001). Although a complication requiring admission to the ICU is, as confirmed by multivariate analysis, an unfavorable factor in long-term survival of transplanted patients, it must be emphasized that three of every 10 patients admitted to the ICU were alive and well at 3 years. Intensive care support in these patients can be life-saving.
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PMID:Role of the intensive care unit in children undergoing bone marrow transplantation with life-threatening complications. 1045 44

INK4A/ARF mutations are acquired in bcr/abl(+) lymphoid blast phase chronic myelogenous leukemia (CML) and bcr/abl(+) acute lymphoblastic leukemia (ALL). Donor lymphocyte infusion and graft-versus-leukemia (GVL) are generally ineffective in such ALLs, whereas GVL is highly active against bcr/abl(+) CML, which does not have a lesion in the INK4A/ARF locus. The mechanisms for the ineffectiveness of GVL are not fully known, and it is possible that intrinsic resistance of acute lymphoid leukemias to immune effectors associated with allogeneic GVL may contribute to ineffectiveness. This work tested the hypothesis that INK4A/ARF mutations that are associated with transformation of bcr/abl(+) CML to an ALL phenotype, and that are associated with increased resistance to apoptosis render ALL cells insensitive to allogeneic immune responses to minor histocompatibility antigens (mHA). Murine acute pre-B ALLs were induced by transfer of the human p210 bcr/abl gene into bone marrow of INK4A/ARF null mice. These ALL lines were then studied in a murine model of MHC-matched, mHA-mismatched allogeneic BMT. In vivo growth of these ALLs was inhibited in allogeneic transplants characterized by active allogeneic immune responses compared to their behavior in syngeneic transplants. In vitro ALLs with INK4A/ARF, p210 bcr/abl, or p190 bcr/abl mutations remained sensitive to anti-mHA cytolytic T cells. In addition, the ALLs were capable of inducing primary immune responses to mHAs in vivo. Thus, ALLs with INK4A/ARF or bcr/abl mutations are not intrinsically resistant to allogeneic T cell responses, suggesting that active immunotherapies against mHA have the potential to control such acute lymphoblastic leukemias.
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PMID:High-risk acute lymphoblastic leukemia cells with bcr-abl and INK4A/ARF mutations retain susceptibility to alloreactive T cells. 1848 87