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)

Allogeneic HSCT is a curative treatment for high-risk leukemia. In Europe, approximately 15% of children have an HLA-matched sibling, but in 65-70% HLA allele-matched (9-10/10) unrelated donors (UD) can be identified. Transplantation using an HLA partially mismatched donor, unrelated cord blood or haploidentical family donor with graft manipulation is then considered with preference on the basis of local experience and/or availability. Here we evaluate the outcomes of 87 consecutive patients with leukemia transplanted with unmanipulated graft from matched or partially mismatched UD or cord blood (CB) at our institution between January 2001 and December 2007. Within the median follow-up of 30 months, the acute GVHD grade II was diagnosed in 70.9% patients; grades III-IV only in 4.6%. The overall incidence of chronic GVHD was 43.3% (extensive in 34.9%). The probability of 3-year EFS was 59.5% and that of 3-year overall survival was 66.9%. TRM at day +100 was 4.5%, and overall it was 13.8%. Fourteen patients (16.1%) died as a consequence of post-transplant leukemia relapse. We conclude that the prognosis of patients transplanted for leukemia using unmanipulated grafts from HLA-matched or partially mismatched UD or CB is comparable and satisfactory. TRM and relapse rate are lower than in the earlier period.
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PMID:Allo-SCT in children with high-risk leukemia using unmanipulated grafts from alternative donors. 1897 35

Nowadays, different treatment options are available for an extending list of lysosomal storage diseases (LSDs). Hematopoietic stem cell transplantation (HSCT) can benefit selected subsets of patients with some LSDs, but results have been poor in several other disorders, including metachromatic leukodystrophy (MLD), outlining the need for innovative therapeutic approaches in this field. Enzyme replacement therapy has been developed recently for MLD, and a Phase I/II trial is ongoing. However, the blood-brain barrier limits the access of the recombinant product to the nervous tissues. Autologous hematopoietic stem/progenitor cells can be genetically modified to constitutively express supra-physiological levels of arylsulfatase-A and may become a quantitatively more effective source of functional enzyme than normal donor cells when transplanted in patients with MLD, thus possibly overcoming the limits of HSCT. Moreover, autologous transplantation might be associated with a significantly reduced transplant-related morbidity and TRM avoiding the risk of GVHD. Therefore, such a gene therapy strategy could represent a significant advance in comparison to conventional allogeneic HSCT.
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PMID:Metachromatic leukodystrophy: an overview of current and prospective treatments. 1897 39

Transplantation of haploidentical stem cells has become a well-established approach, which makes a potential donor available for almost all patients. This review focuses on current results and new strategies, especially in pediatric patients with malignant diseases. CD34(+) positive selection was the most common procedure for graft manipulation in the past years, whereas T and B cell depletion is a promising new method. GVHD could herewith be effectively reduced and primary engraftment was reported in 83-100% of patients after transplantation of high stem cell doses. For patients with ALL in remission, disease-free survival at 3 years ranged between 22 and 48%. TRM, mainly because of viral infections, was improved by the use of reduced-intensity conditioning (which helped to speed up T cell recovery) and by close monitoring of viral loads and prophylactic/preemptive therapy. The role of donor-derived Ag-specific T cells against viral and fungal antigens is currently under investigation. Patients with active disease at the time of transplantation had a poor outcome and several attempts to improve these results are currently evaluated, such as co-infusion of natural killer cells, co-transplantation of MSC, use of new antileukemic drugs and post-transplant immunotherapy.
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PMID:Haploidentical SCT in children: an update and future perspectives. 1897 46

The aim of the present study was to assess the influence of socioeconomic status (SeS) on the outcome of allo-SCT at a Brazilian SCT center. In total, 201 patients receiving HLA-identical related allo-SCTs were studied. The median age was 30 years. Overall, 163 patients had malignancies (CML 68, ALL/AML 63, myelodysplastic syndrome 12 and others 20). SeS was defined according to the Brazilian Association of Market Research Agencies classification, where people are clustered in groups A-E (richest to poorest). In total, 146 patients (72%) were classified as richest (A+B+C) and 55 (28%) as poorest (D+E). The D+E SeS group was associated with a higher incidence of chronic GVHD and acute GVHD (hazard ratio (HR)=2.61; P=0.001 and HR=2.62; P=0.001, respectively), better platelet and neutrophil engraftment (HR=1.94; P=<0.001 and HR=2.12; P=0.001) and with a higher TRM in multivariate analysis (HR=1.92; P=0.039). Estimated overall survival at 5 years was 55.2%. A D+E SeS (HR=2.13; P=0.001) was associated with a worse survival on multivariate analysis. In conclusion, a lower SeS is a strong prognostic factor in patients undergoing allo-SCT in Brazil, influencing engraftment, TRM and overall survival.
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PMID:Patient socioeconomic status as a prognostic factor for allo-SCT. 1897 20

Opinions are divided regarding the best prophylactic regimen for GVHD. The aim of this study was to evaluate potential survival benefit of different prophylactic regimens for acute GVHD (aGVHD). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) including patients undergoing Allo-SCT. We included trials that assessed the addition of MTX, compared CsA and tacrolimus and evaluated the addition of steroids. Outcomes assessed were all-cause mortality (ACM) at the longest follow-up, aGVHD, chronic GVHD, TRM, relapse rate and regimen-specific adverse events. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled. The regimen of MTX-CsA vs CsA alone (four trials) yielded no statistically significant difference in ACM (RR=0.84 (0.61-1.14)), but a significant decrease in aGVHD (RR=0.52 (0.39-0.7)). There was no difference in ACM for the comparison of MTX-CsA and MTX-tacrolimus (three trials); however, MTX-tacrolimus was superior to MTX-CsA in the reduction of aGVHD (RR=0.62 (0.52-0.75)) and severe aGVHD (RR=0.67 (0.47-0.95)). The addition of steroids did not affect the outcomes (four trials). We conclude that MTX-CsA and MTX-tacrolimus are both acceptable alternatives for GVHD prophylaxis, although MTX-tacrolimus may be superior in terms of aGVHD reduction.
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PMID:Prophylaxis regimens for GVHD: systematic review and meta-analysis. 1970 Dec 49

Fractionated TBI (FTBI) followed by allogeneic hematopoietic SCT results in donor engraftment and improves survival in children with high-risk hematologic malignancies. However, acute toxicities (skin, lung and mucosa) are common after FTBI. Late complications include cataracts, endocrine dysfunction, sterility and impaired neurodevelopment. Instead of FTBI, we used low-dose single fraction TBI (550 cGy) with CY as transplant conditioning for pediatric hematologic malignancies. GVHD prophylaxis included CYA and short-course MTX; methylprednisolone was added for unrelated donor transplants. A total of 55 children in first (40%) or second remission and beyond (60%) underwent transplantation from BM (65%) or peripheral blood; 62% from unrelated donors; 22% were mismatched. Median follow-up was 18.5 months (1-68). Overall survival and disease-free survival at 1 year were 60 and 47%, respectively. Acute toxicities included grade 3-4 mucositis (18%), invasive infections (11%), multiorgan failure/shock (11%), hemolytic anemia (7%), veno-occlusive disease (4%) and renal failure (4%). TRM was 11% at 100 days. Non-relapse mortality was 6% thereafter. Graft rejection occurred in 2%. Three patients (5%) died of GVHD. The regimen was well tolerated even in heavily pretreated children and supported donor cell engraftment; long-term follow up is in progress.
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PMID:Early outcomes after allogeneic hematopoietic SCT in pediatric patients with hematologic malignancies following single fraction TBI. 1901 66

We reviewed 26 consecutive patients with AML who were transplanted in second CR2 between 1994 and 2005. The most common conditioning regimen was CY and TBI. Median age at transplant was 8.9 yr (range 2.2-18.2). Nine patients received related donor, 16 patients received unrelated donors, and one patient received unrelated cord stem cells. Acute grade III-IV and chronic extensive GVHD occurred in eight (30%) and nine (35%) patients, respectively. Six patients (23%) relapsed, four of them died. Six patients (23%) died from TRM. Estimate of three-yr EFS was 0.53 (95% CI; 0.34-0.72). Including the two relapsed patients who were salvaged by DLI and second transplantation, three-yr OS was 0.61 (95% CI; 0.41-0.78) with a median follow-up of three and a half yr (range 1.5-11.2 yr). When entering remission, children with relapsed AML have a reasonable survival with HSCT, but relapse and TRM remain a concern.
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PMID:Outcome of allogeneic hematopoietic stem cell transplantation for children with acute myelogenous leukemia in second complete remission: single center experience. 1903 10

Do some patients benefit from an unrelated donor (URD) transplant because of a stronger graft-versus-leukemia (GVL) effect? We analyzed 4099 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) undergoing a myeloablative allogeneic hematopoietic cell transplantation (HCT) from an URD (8/8 human leukocyte antigen [HLA]-matched, n=941) or HLA-identical sibling donor (n=3158) between 1995 and 2004 reported to the CIBMTR. In the Cox regression model, acute and chronic GVHD were added as time-dependent variables. In multivariate analysis, URD transplant recipients had a higher risk for transplantation-related mortality (TRM; relative risk [RR], 2.76; P< .001) and relapse (RR, 1.50; P< .002) in patients with AML, but not ALL or CML. Chronic GVHD was associated with a lower relapse risk in all diagnoses. Leukemia-free survival (LFS) was decreased in patients with AML without acute GVHD receiving a URD transplant (RR, 2.02; P< .001) but was comparable to those receiving HLA-identical sibling transplants in patients with ALL and CML. In patients without GVHD, multivariate analysis showed similar risk of relapse but decreased LFS for URD transplants for all 3 diagnoses. In conclusion, risk of relapse was the same (ALL, CML) or worse (AML) in URD transplant recipients compared with HLA-identical sibling transplant recipients, suggesting a similar GVL effect.
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PMID:The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation. 1905 78

Various polymorphisms of non-HLA genes have recently been investigated as candidate risk factors in allogeneic haematopoietic SCT (aHSCT). Our study aimed at exploring possible associations of IL6 and CCL2 single nucleotide polymorphisms (SNP) with aHSCT outcome. A total of 166 HLA-identical aHSCT pairs recruited in were genotyped for IL6 -174 G/C, IL6 -597 G/A, CCL2 -2518 A/G and CCL2 -2076 A/T SNPs by PCR with sequence-specific primers (PCR-SSP). The association between IL6 -174 GG genotype and increased risk of acute GVHD was found in whole study group (P=0.03) and in the subgroup of related aHSCT (P=0.01), association between IL6 -597 GG genotype and the occurrence of acute GVHD was detected only in the related aHSCT pairs (P=0.02). Furthermore, reduction in OS was revealed among recipients possessing IL6 -174(*)G allele in the group of related aHSCT pairs (P=0.04). Presence of CCL2 -2076 TT genotype was associated with decrease of OS (P=0.04) and increase of TRM (P=0.02) in patients transplanted by related donor. These results, in the context of previous findings, suggest that IL6 gene polymorphisms may be associated with aHSCT outcome, particularly in patients transplanted from a related donor.
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PMID:Association of IL6 and CCL2 gene polymorphisms with the outcome of allogeneic haematopoietic stem cell transplantation. 1923 9

As unrelated allogeneic umbilical cord blood transplantation (UCBT) has been developed for 20 years already since 1988, more than ten thousands cases have cumulatively undergone UCBT over the world. A huge number of clinical data confirmed that UCBT had unique characters with low rate of severe GVHD. The efficacy and data on TRM, relapse and EFS of allogeneic UCBT with HLA 0-1 mismatched are similar to those in HLA matched BMT. UCBT has become the optimal choice for source of hematopoietic stem cells for allogeneic stem cell transplant especially when HLA-matched or haploidentical donors are not available in time. In most developed countries, unrelated allogeneic UCBT developed successively, and in recent years HLA mismatched UCBT with double units performed in adults increased even more rapidly than in children. Another recent trend of UCBT has been extending to treat some non-malignant but refractory diseases in pediatrics, such as severe combined immunodeficiency, thalassemia major, bone marrow failure syndrome and metabolic disorders. The clinical successful practice of double units for cord blood transplantation inspires to ponder over questions remaining mystery. What is the conflict like between two mismatched donor cells in vivo, which does not spoil the whole transplantation but enable the patient to be engrafted successfully without any increment of the dosage by the sum of two doses together? How can they both be taken at the same time firstly by the recipient, but why does only one predominate later? What are the factors enable the donor cells of the winner to sustain? With the references of the international experiences, how to solve the clinical encountered problems, perspective of unrelated allogeneic UCBT and proper strategies to be enacted are reviewed.
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PMID:[Unrelated allogeneic umbilical cord blood transplantation: present status, problems and countermeasures]. 1923 36


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