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)

Homogeneous immunoglobulins are frequently detected in the serum of patients undergoing allogeneic bone marrow transplantation (BMT). The aim of the present study was to further characterize the incidence of this phenomenon and its correlations with laboratory and clinical data. Serum samples were gathered from 29 patients undergoing allogeneic or syngeneic BMT for chronic myeloid leukemia (CML), and serial protein (IgG, IgA and IgM) quantification, electrophoresis and immunofixation were performed. Transient mono- or oligoclonal gammopathies were observed in 23 out of 29 patients between days 20 and 1,750 following transplantation. The presence of homogeneous immunoglobulins was not correlated with the following clinical parameters: graft-versus-host disease, bacterial sepsis, Epstein-Barr virus or cytomegalovirus infection or invasive fungal infection. Therefore, the development of mono- or oligoclonal immunoglobulins may represent a complex disorder of B cell regeneration which may be caused by an intrinsic B cell defect, or a failure in the regenerating T cell system, or both, manifesting itself in a restricted antibody diversity after allogeneic BMT.
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PMID:Homogeneous immunoglobulins following allogeneic bone marrow transplantation. 1271 21

We report the feasibility and efficacy of a fludarabine/busulfan-based dose-reduced conditioning regimen followed by stem cell transplantation from related ( n=19) or unrelated HLA-matched donors ( n=18) in 37 patients with myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) who were not eligible for a standard myeloablative conditioning regimen. The conditioning regimen consisted of fludarabine (120-180 mg/m(2)), busulfan (8 mg/kg p.o. or 6.4 mg/kg i.v.), and antithymocyte globulin ( n=25). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine ( n=36) and a short course of methotrexate ( n=29) or mycophenolate mofetil ( n=3). The median age of the patients was 55 years (range: 23-72). The reasons to perform a dose-reduced conditioning were reduced performance status ( n=14), age ( n=12), prior autologous ( n=5) or allogeneic ( n=1) transplantation, or prior/active fungal infection ( n=5). Diagnoses at transplantation were refractory anemia (RA) ( n=8), refractory anemia with excess of blasts (RAEB) ( n=6), RAEB in transformation (RAEB-T) ( n=13), chronic myelomonocytic leukemia (CMML) ( n=3), and sAML ( n=7). Stem cell sources were peripheral blood stem cells (PBSC) ( n=29) or bone marrow ( n=8). One patient received a T-cell-depleted peripheral stem cell graft. Two primary graft failures were observed (6%). Engraftment of leukocytes (>1.0x10(9)/l) and platelets (>20x10(9)/l) was seen after a median of 14 days. Acute GVHD grade II-IV was seen in 37%, while severe grade III/IV GVHD was observed in six patients (17%). Chronic GVHD was seen in 13 patients (48%). There were ten deaths (27%) due to treatment (TRM). The probability of TRM was higher in patients with unrelated donors (45 vs 12%, p=0.03) and in patients with poor cytogenetics in comparison to those with a low or intermediate karyotype (75 vs 20%, p=0.009). During follow-up 12 patients relapsed (32%). Patients without chronic GVHD had a significantly higher probability of relapse compared to those with chronic GVHD (70 vs 15%, p=0.02). After a median follow-up of 20 months, the 3-year estimated disease-free survival (DFS) is 38% [95% confidence interval (CI): 21-55%] and the overall survival (OS) is 39% (95% CI: 22-56%). The OS and DFS after related and unrelated transplantations was 45% (95% CI: 19-71%) vs 31% (95% CI: 9-53%) (n.s.) and 51% (95% CI: 29-73%) vs 25% (95% CI: 4-47%) (n.s.), respectively. We conclude that dose-reduced conditioning followed by allogeneic stem cell transplantation from related or unrelated donors is an effective treatment approach in patients with MDS/sAML and might cure a substantial number of patients who are not eligible for a standard allogeneic transplantation.
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PMID:Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. 1272 37

The possible advantage of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a graft-versus-lymphoma effect. We explored the feasibility and efficacy of allo-HSCT with reduced-intensity (RI) regimens in advanced malignant lymphoma (ML). A total of 20 patients with indolent (n=9) or aggressive lymphoma (n=11) received allo-HSCT with an RI regimen (RIST). The preparative regimen consisted of a combination of purine analog and alkylating agent with or without antithymocyte globulin. A total of 11 patients had chemorefractory disease, seven had chemosensitive relapsed disease and two had residual disease. All of the patients received G-CSF-mobilized blood stem cells from HLA-matched siblings. Of the 20 patients, 19 achieved engraftment with acceptable regimen-related toxicities. Seven patients developed grade II-IV acute GVHD and 15 developed chronic GVHD. Of the 15 patients with evaluable disease, 12 achieved a complete response. One died of invasive fusariosis, four subsequently died of GVHD complicated with fungal infection and one died of progressive disease. With a median follow-up of 358 days, the Kaplan-Meier estimates for 1-year overall and progression-free survival were both 70%. The high response rate with low relapse observed in this study suggests that RIST may be an effective alternative curative treatment for patients with advanced ML.
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PMID:High complete response rate after allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimens in advanced malignant lymphoma. 1283 76

Morbidity and mortality in patients with malignancies, especially leukemia and lymphoma, are increased by invasive fungal infections. Since diagnosis of invasive fungal infection is often delayed, antifungal prophylaxis is an attractive approach for patients expecting prolonged neutropenia. Antifungal prophylaxis has obviously attracted much interest resulting in dozens of clinical trials since the late 1970s. The non-absorbable polyenes are probably ineffective in preventing invasive fungal infections, but may reduce superficial mycoses. Intravenous amphotericin B and the newer azoles were used in clinical trials, but their role in antifungal prophylaxis is still not well defined. Allogeneic stem cell transplant recipients are at particularly high risk for invasive fungal infections. Other well described risk factors are neutropenia >10 days, corticosteroid therapy, sustained immunosuppression, graft versus host disease, and concomitant viral infections. The enormous study efforts are contrasted by a scarcity of risk stratified evidence based recommendations for clinical decision making. The objective of this review accumulating information on about 10.000 patients is to assess evidence based criteria primarily regarding the efficacy of antifungal prophylaxis in neutropenic cancer patients.
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PMID:Prophylaxis of invasive fungal infections in patients with hematological malignancies and solid tumors--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). 1368 Jan 64

Five lymphoma patients relapsed from allogeneic hematopoietic stem cell transplantation (HSCT). Three patients who received myeloablative conditioning had full donor chimerism at relapse, whereas two who received nonmyeloablative conditioning had partially or completely lost the graft. All received mini-BEAM [carmustine (BCNU), etoposide, cytarabine (AraC), melphalan], followed by infusion of HSC (four peripheral blood, one marrow) from the initial donor. Neutropenia and thrombocytopenia were brief, and full donor chimerism was established in all cases. There were four complete and one partial remissions. Graft-versus-host disease occurred in three cases, all with full donor chimerism at relapse. Two patients died subsequently of disease relapse or progression. Another two patients died from fungal infection, one of whom was still in remission at death. One patient had remained in remission 47 months after treatment. Mini-BEAM/HSC is an effective treatment for lymphoma relapses after allogeneic HSCT, but optimal strategies of remission consolidation and prevention of treatment-related complications are needed to improve outcome.
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PMID:Treatment of lymphoma relapses after allogeneic hematopoietic stem cell transplantation with intensive chemotherapy followed by infusion of hematopoietic stem cell from the original donor. 1450 11

CMV disease remains a major infectious complication after allogeneic hematopoietic stem cell transplantation (HSCT). To investigate the relationship between CMV antigenemia, treatment with ganciclovir (GCV), and outcome, we retrospectively analyzed 241 consecutive patients at risk for CMV infection who underwent allogeneic HSCT. Antigenemia-guided pre-emptive strategy with GCV was used for all patients. CMV antigenemia developed in 169 patients (70.1%), and CMV disease in 18 patients (7.5%). Multivariate analysis showed that acute GVHD (grades II-IV) was the only risk factor for developing antigenemia, and acute GVHD and advanced age for CMV disease. GCV use, as well as acute GVHD and advanced age, significantly increased the risk for bacterial and fungal infection after engraftment. Those who developed CMV antigenemia had a poorer outcome than those who did not (log-rank, P=0.0269), although the development of CMV disease worsened the outcome with only borderline significance (log-rank, P=0.0526). In conclusion, detection of antigenemia proved to be a poor prognostic factor for HSCT patients, which may be attributed to a combination of factors, including CMV disease itself, the effect of treatment, and a host status that allows for reactivation of CMV. Optimal pre-emptive strategy needs to be determined.
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PMID:Cytomegalovirus antigenemia and outcome of patients treated with pre-emptive ganciclovir: retrospective analysis of 241 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation. 1452 Apr 25

Invasive fungal infections are typically difficult to prevent, diagnose, and treat; consequently, fungal infection-related mortality has become high, particularly among patients with prolonged neutropenia and severe graft-versus-host disease. However, much recent progress has been made in understanding the immune response to fungi and the epidemiology of infection, and new diagnostic tests and antifungal drugs have become available. This review will describe these most recent developments with the goal of evaluating new approaches to prevent, diagnose, and treat invasive fungal infections.
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PMID:New approaches to invasive fungal infections. 1456 76

Nonmyeloablative hematopoietic stem cell transplantation (NST) has been explored in hematological malignancies and solid tumors in an attempt to minimize treatment-related toxicity. Whether this approach is associated with reduced risk of infectious complications is unclear. The aim of the current study was to evaluate the infectious complications in a series of 32 consecutive adult patients who received NST at our institution. Peripheral blood stem cell grafts (n=30) or marrow grafts (n=2) were infused from human leukocyte antibody (HLA)-matched sibling (n=30), partially matched related (n=1), or unrelated (n=1) donors. Neutropenia developed in two-thirds of patients and lasted 16 days. Acute graft-versus-host disease (GVHD) grade II to IV was observed in 25% of patients, whereas 35% of patients had signs of extensive chronic GVHD. Twenty-two patients (69%) had at least one significant infectious episode. Bacteremia occurred in 19% of patients (n=5 gram-positive, n=1 gram-negative microorganisms). Cytomegalovirus (CMV) infection was observed in 10 out of 28 (36%) evaluable patients; 4 of these had recurrent or persistent CMV antigenemia requiring a second-line treatment, but eventually the viremia cleared. No patients experienced CMV disease. Fungal infections were documented in five (16%) patients, comprising invasive fungal infections in two cases and mucosal fungal infections in three. Four patients died of transplant-related causes, and three of these died before day +100. Infection was considered the primary cause of death in one patient (pulmonary aspergillosis) and contributed to death in another two. The actuarial probability of nonrelapse mortality at 100 days was 10% (95% confidence interval, 3-26%). Our preliminary results suggest that NST is associated to a low incidence of bacteremia or fungal and viral infections. Whether these findings would translate into an improved overall survival needs to be confirmed in larger prospective studies.
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PMID:Infectious complications following nonmyeloablative allogeneic hematopoietic stem cell transplantation. 1461 1

We conducted a multi-center phase I/II trial of nonmyeloablative stem cell transplantation for patients with hematologic malignancies. The aim of this trial was to assess the safety and feasibility of this treatment modality for older or younger patients with significant organ dysfunction, who could not be treated with conventional high dose chemoradiotherapy. Twelve patients were treated with a conditioning regimen consisting of fludarabine and cyclophosphamide, followed by peripheral blood stem cell transplantation from human leukocyte antigen (HLA) identical siblings. Nonhematologic toxicities were mild. Median time to absolute neutrophils above 0.5 x 10(9)/l, 1.0 x 10(9)/l and platelets above 50 x 10(9)/l were 8, 10 and 12 days, respectively. Donor dominant hematopoiesis was achieved in all patients, with or without donor leukocyte infusion. The cumulative incidence of acute and chronic graft-versus-host disease (GVHD) was 75 and 56%, respectively. Only one patient experienced early death within 100 days, caused by acute GVHD complicated by fungal infection. All patients except one achieved complete remission. With a median follow-up of 330 days, expected progression-free survival is 75%. Overall survival is 76%. Our study confirms that nonmyeloablative stem cell transplantation with cyclophosphamide and fludarabine conditioning is a safe and promising treatment for elderly patients with hematologic malignancies. A further study in large-scale setting is warranted.
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PMID:Nonmyeloablative stem cell transplantation with fludarabine and cyclophosphamide for patients with hematologic malignancies. 1464 Nov 43

From January 1978 to December 2001, 133 patients with severe aplastic anemia (SAA) underwent non-T cell-depleted allogeneic bone marrow transplantation from an HLA-identical sibling donor, at the Hospital Saint Louis using either the combination of cyclophosphamide (Cy) and thoracoabdominal irradiation (TAI; n=100) or Cy and antithymocyte globulin (ATG; n=33), as a conditioning regimen. With 13.6 years of follow-up, the 10-year survival estimate was 64%. Four factors were associated with lower survival: older age, use of Cy-TAI, any form of treatment prior to transplantation (either androgens or immunosuppressive therapy, [IST]), and grade II to IV acute graft-versus-host disease (GvHD). TAI was the sole factor associated with the occurrence of acute GvHD. The risk of cancers (15-year cumulative incidence, 10.9%) was associated with older age and with the use of cyclosporine as IST before transplantation. Cumulative incidences and risk factors of nonmalignant late effect including avascular osteonecrosis and late bacterial, viral, and fungal infection were also analyzed. Improved results using Cy-ATG as conditioning can lead to more than 90% chance of cure in patients with SAA. Even if, in our experience, the role of Cy-ATG versus that of Cy-TAI remained inextricably related to the year of transplantation, the major detrimental role of the GvHD disease in the long-term outcome and its relation to TAI supports avoidance of irradiation in the conditioning regimen. Furthermore, avoidance of any IST before transplantation in patients with a sibling donor is a prerequisite for attaining such excellent results.
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PMID:Long-term outcome after bone marrow transplantation for severe aplastic anemia. 1465 84


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