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)

We investigated the hypothesis that gemtuzumab ozogamicin (GO), an anti-CD33 immunotoxin would improve the efficacy of fludarabine/melphalan as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/II trial. Toxicity was defined as grades III-IV organ damage, engraftment failure or death within 30 days. 'Response' was engraftment and remission (CR) on day +30. We sought to determine the GO dose (2, 4 or 6 mg m(-2)) giving the best trade-off between toxicity and response. All patients were not candidates for myeloablative regimens. Treatment plan: GO (day -12), fludarabine 30 mg m(-2) (days -5 to -2), melphalan 140 mg m(-2) (day -2) and HSCT (day 0). GVHD prophylaxis was tacrolimus and mini-methotrexate. Diagnoses were AML (n=47), MDS (n=4) or CML (n=1). Median age was 53 years (range, 13-72). All but three patients were not in CR. Donors were related (n=33) or unrelated (n=19). Toxicity and response rates at 4 mg m(-2) were 50% (n=4) and 50% (n=4). GO dose was de-escalated to 2 mg m(-2): 18% had toxicity (n=8) and 82% responded (n=36). 100-day TRM was 15%; one patient had reversible hepatic VOD. Median follow-up was 37 months. Median event-free and overall survival was 6 and 11 months. GO 2 mg m(-2) can be safely added to fludarabine/melphalan, and this regimen merits further evaluation.
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PMID:Phase I/II study of gemtuzumab ozogamicin added to fludarabine, melphalan and allogeneic hematopoietic stem cell transplantation for high-risk CD33 positive myeloid leukemias and myelodysplastic syndrome. 1798 20

Transplantation from unrelated donors (URD) is increasingly being used as treatment for hematological malignancies, including acute myeloid leukemia (AML). This increase is the consequence of the availability of more than 11 million URD volunteers and the more efficient donor search process in the recent years. Median time to identify a suitable URD is now 2 months. More than 50% of Caucasian patients have an human leukocyte antigen (HLA)-allele donor match and a one-antigen or allele HLA-mismatched donor may also be acceptable. Complications of URD transplants are particularly frequent and severe, with long-term OS in the registries being 10-20% inferior to HLA-identical sibling transplantation. High resolution DNA techniques for donor and recipient HLA matching have contributed to the survival in experienced centres after unrelated donor SCT approaching that achieved with sibling donors. The introduction of reduced intensity conditioning (RIC) has extended URD transplants to elderly and/or debilitated patients with AML. With this approach, TRM decreases, although graft-versus-host disease-related morbidity and mortality remain a problem. Despite this complication, results after URD transplantation in this age group seem better than those achieved with chemotherapy and/or autologous transplantation. To confirm this possibility, prospective multicenter comparisons of URD transplants after RIC with other treatment options for elderly AML patients have recently been started.
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PMID:Hematopoietic transplantation from adult unrelated donors as treatment for acute myeloid leukemia. 1820 27

In this study, we utilized a conditioning regimen with fludarabine and myeloablative dose i.v. BU (12.8 mg/kg) (FluBU) in 36 adult patients (median age: 44 years, range: 18-61) with myeloid or lymphoid malignancies at standard risk (n=10) or high risk of relapse (n=26), who received an allogeneic hematopoietic SCT (HSCT) from HLA-matched related (n=16) or unrelated (n=20) donors. The source of hematopoietic stem cells was peripheral blood in 28 and marrow in 8 cases. Rabbit-antithymocyte globulin at 7 mg/kg was utilized in 21 patients. Acute GVHD grade II-IV was observed in 19% of the patients (grade III-IV in 14% of patients) and chronic GVHD in 11 of 30 evaluable patients (37%). At median follow-up of 737 days (range: 152-1,737) for alive patients, overall survival rates in standard- and high-risk patients were 80 and 35%, respectively, and event-free survival rates were 70 and 31%, respectively. TRM was 10% in standard-risk and 19% in high-risk patients. Post transplant relapse was observed in 20% standard-risk and in 46% high-risk patients. FluBU conditioning regimen is associated with a limited hematologic and extrahematologic toxicity and with an antitumor activity comparable to other standard myeloablative regimens.
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PMID:Fludarabine/i.v. BU conditioning regimen: myeloablative, reduced intensity or both? 1826 44

Recent studies have pointed towards an association between certain single nucleotide polymorphisms (SNPs) in the NOD2/CARD15 gene, and negative outcome of Allo-SCT. In this study, 198 patients and their corresponding donors were analyzed retrospectively for the occurrence of NOD2/CARD15 mutations to evaluate the impact on clinical results after Allo-SCT. In all, 7.6% of the patients and 11% of the donors were heterozygous for one of three SNPs 8, 12 or 13. Contrary to earlier findings, we found no significant impact on incidence of acute GVHD or TRM following Allo-SCT. These differences in results could be due to a lower mutation frequency in the studied population and/or a lower overall incidence of severe GVHD. On the basis of these findings we conclude that a consideration to NOD2/CARD15 mutation status is not pertinent when selecting a donor for Allo-SCT at our centre.
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PMID:No impact of NOD2/CARD15 on outcome after SCT. 1869 58

We have reported a lower incidence of acute graft-versus-host disease (aGVHD) with a novel conditioning regimen using low-dose rabbit antithymocyte globulin (ATG; Thymoglobulin [TG]) with fludarabine and intravenous busulfan (FluBuTG). To assess further this single-center experience, we performed a retrospective matched-pair analysis comparing outcomes of adult patients transplanted using the FluBuTG conditioning regimen with matched controls from patients reported to the CIBMTR receiving a first allogeneic hematopoietic stem cell transplant (HCT) after standard oral busulfan and cyclophosphamide (BuCy). One hundred twenty cases and 215 matched controls were available for comparison. Patients receiving FluBuTG had significantly less treatment related mortality (TRM; 12% versus 34%, P < .001) and grades II-IV aGVHD (15% versus 34%, P < .001) compared to BuCy patients. The risk of relapse was higher in the FluBuTG patients (42% versus 20%, P < .001). The risks of chronic GVHD (cGVHD) and disease free survival (DFS) were similar in the cases and controls. These results suggest that the novel regimen FluBuTG decreases the risk of aGVHD and TRM after HLA-identical sibling HSCT, but is associated with an increased risk of relapse, resulting in similar DFS. Whether these conditioning regimens may be more suitable for specific patient populations based on relapse risk requires testing in prospective randomized trials.
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PMID:Outcomes following HSCT using fludarabine, busulfan, and thymoglobulin: a matched comparison to allogeneic transplants conditioned with busulfan and cyclophosphamide. 1872 62

Hematopoietic SCT (HSCT) has become a curative therapeutic strategy for several malignant and nonmalignant diseases. We report the comprehensive results of the first 10 years of experience in HSCT from the two major BMT units in Lebanon: Makassed University Hospital and the American University of Beirut Medical Center. The median and the 5-year overall survival (OS) were 97 months and 58%, respectively, for the 84 patients who received allogeneic HSCT, and 60 months and 50%, respectively, for the 228 patients who received autologous BMT. The results for myeloablative allogeneic transplantation were as follows: AML (n=28, 5-year OS 58%, 5-year disease-free survival (DFS) 48%), CML (n=9, 5-year OS 66%, 5-year DFS 52%), ALL (n=13, 2-year OS 10%, 2-year DFS 10%), thalassemia (n=10, 5-year transfusion-free survival 67%). The results for autologous HSCT were as follows: diffuse large B-cell lymphoma (DLBCL) in relapse (n=37, 5-year OS 68%, 5-year progression-free survival (PFS) 65%), Hodgkin's lymphoma (n=55, 5-year OS 55%, 5-year PFS 36%), and first-line multiple myeloma (n=71, 5-year OS 53%, 5-year PFS 24%). For allogeneic transplanted patients, the cumulative TRM was 23% and the incidence of acute GVHD was 23%. For autografted patients, TRM was 2.6%. These results indicate that despite the relatively low socioeconomic status of the Lebanese population, both allogeneic and autologous HSCT are feasible with outcomes similar to developed countries.
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PMID:Hematopoietic stem cell transplantation in Lebanon: first comprehensive report. 1872 16

Disease relapse following an allogeneic transplant remains a major cause of treatment failure, often with a poor outcome. Second allogeneic transplant procedures have been associated with high TRM, especially with myeloablative conditioning. We hypothesized that the use of reduced-intensity conditioning (RIC) would decrease the TRM. We performed a retrospective national multicentre analysis of 71 patients receiving a second allogeneic transplant using RIC after disease relapse following an initial allogeneic transplant. The majority of patients had leukaemia/myelodysplasia (MDS) (N=57), nine had lymphoproliferative disorders, two had myeloma and three had myeloproliferative diseases. A total of 25% of patients had unrelated donors. The median follow-up was 906 days from the second allograft. The predicted overall survival (OS) and TRM at 2 years were 28 and 27%, respectively. TRM was significantly lower in those who relapsed late (>11 months) following the first transplant (2 years: 17 vs 38% in early relapses; P=0.03). Two factors were significantly associated with a better survival: late relapse (P=0.014) and chronic GVHD following the second transplant (P=0.014). These data support our hypothesis that the second RIC allograft results in a lower TRM than using MA. A proportion of patients achieved a sustained remission even when relapsing after a previous MA transplant.
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PMID:Outcome of second allogeneic transplants using reduced-intensity conditioning following relapse of haematological malignancy after an initial allogeneic transplant. 1872 93

The aim was to evaluate two transplant strategies for patients who lack HLA-identical donors, namely HLA-A, HLA-B or -DR beta 1 mismatched unrelated donor (MM URD) transplants (n=14) and umbilical cord blood transplants (UCB, n=27). Diagnosis, disease stage and age were similar in the two groups. Cell dose was lower in the UCB group (P<0.001). Median time to ANC of >0.5 x 10(9)/l was 30 days in the UCB group and 17 days in the MM URD group (P=0.002). Engraftment of plt was delayed in the UCB group (P=0.03). The UCB patients required fewer erythrocyte transfusions (P=0.001). At 100 days, complete donor chimerism for CD3 was 63 and 44% in the UCB and MM URD groups, respectively. Acute GVHD of grades II-IV were 30% in the UCB group and 21% in the MM URD group. The corresponding figures for chronic GVHD were 9 and 20%, respectively. TRM was 30% in the UCB patients and 50% in the MM URD patients. Three-year survival was 66% in the UCB group and 14% in the MM URD group (P=0.006). Although the material is small and heterogeneous, engraftment was delayed, leukocyte chimerism was not significantly different and survival was superior using UCB rather than MM URD transplants.
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PMID:Unrelated cord blood and mismatched unrelated volunteer donor transplants, two alternatives in patients who lack an HLA-identical donor. 1876 60

The utility of imatinib in either the pre- or post-transplant period for Ph chromosome-positive (Ph+) ALL is uncertain. In addition, there have been recent concerns regarding imatinib and cardiac toxicity. We investigated the outcome of 32 patients with Ph+ ALL who received an allo-hematopoietic cell transplant (HCT) at the University of Minnesota between 1999 and 2006. The median age at HCT was 21.9 years (range: 2.8-55.2). All patients were conditioned with CY and TBI. GVHD prophylaxis was CsA based. Of the 32 patients, 15 received imatinib therapy pre- or post-HCT (imatinib group) and 17 patients received either no imatinib (n=11) or only after relapse (n=6) (non-imatinib group). Overall survival, relapse-free survival and relapse at 2 years was 61, 67 and 13% for the imatinib group as compared with 41, 35 and 35% for the non-imatinib group (P=0.19, 0.12 and 0.20, respectively). Cardiac toxicity and TRM at 2 years were similar between groups. Thus, patients treated with imatinib in either the pre- or post-transplant setting had trends toward improved outcomes and no increase in cardiac toxicity. We suggest that imatinib be included in the peri-transplant management of all patients with Ph+ ALL.
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PMID:Allo-hematopoietic cell transplantation for Ph chromosome-positive ALL: impact of imatinib on relapse and survival. 1877 28

Unrelated umbilical cord blood (UCB) is an alternative stem cell source for paediatric patients lacking a matched related or unrelated marrow donor. We report the results of all paediatric unrelated UCB transplants performed in Australia and New Zealand over a 10-year period. A total of 135 patients were transplanted, 100 for malignant disease (74%) and 35 for non-malignant disorders. The majority (88%) of patients received an HLA-mismatched graft. The median infused total nucleated cell dose was 4.7 x 10(7)/kg and CD34+ count 1.9 x 10(5)/kg. Neutrophil engraftment occurred in 83% of patients by day 42 (median 23 days) and platelet engraftment in 55% by day 60 (median 56 days). Grades II-IV and III-IV acute GVHD occurred in 41 and 18% of patients, respectively. TRM and overall survival 1-year post transplant were 32 and 61%, respectively. A higher probability of neutrophil recovery (P=0.004) and faster time to recovery (median 18 days vs 26 days, P=0.008) were observed in recipients of a cord unit with a CD34 cell dose >or=1.7 x 10(5)/kg. Our results support selection of cord units with CD34 cell doses >or=1.7 x 10(5)/kg to promote faster engraftment, improve survival and lower TRM.
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PMID:Outcome following unrelated cord blood transplant in 136 patients with malignant and non-malignant diseases: a report from the Australian and New Zealand children's haematology and oncology group. 1880 37


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