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)

Fifty patients affected by sickle cell anaemia underwent transplantation of HLA-identical haematopoietic stem cells (bone marrow, 48; cord blood, 2). Two groups of patients were considered for transplantation. Group 1 included 36 permanent residents of a European country who, retrospectively, met the inclusion criteria accepted at a consensus conference held in Seattle in 1990, wherein children were selected because they already had evidence of a morbid course. Group 2 included 14 patients who were transplanted earlier, had not received more than three blood transfusions and were transplanted because they had decided to return to their country of origin. Kaplan-Meier estimates of overall survival, event-free survival and disease-free survival at 11 years of the whole grafted population are 93, 82 and 85%, respectively. In group 1, overall survival, EFS and DFS were 88, 76 and 80% and in group 2, 100, 93 and 93%, respectively. Clinical manifestations of the disease, as well as disease associated haemolytic anaemia, disappeared in all successfully treated patients. Recovery of spleen function was present in seven out of 10 evaluated patients. Adverse events (death, absence of engraftment, mixed chimerism and relapse) occurred more frequently in group 1 than in group 2 (25% vs 7%, P< 0.001). Acute graft-versus-host disease (GVHD) was present in 20 patients (grade I or II, 19; grade III, 1), chronic GVHD in 10 (limited, 7; extensive, 3). One patient developed an acute myeloid leukaemia. Gonadal dysfunction was present in all patients (six boys and eight girls) transplanted close to or after puberty, although transient in one adolescent girl.
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PMID:Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium. 967 88

Over the past decade, allogeneic cord blood transplantation (CBT) has been widely used for treating patients with malignant disorders. However, the reported low incidence of GVHD observed after allogeneic CBT might be a major drawback in leukemic recipients and at present it is not clear whether CBT really predisposes patients to an increased risk of leukemia relapse. In order to further elucidate the role of CBT in children with hematological malignancies, 54 patients with ALL or AML given either a related (31 cases) or an unrelated (23 cases) CBT in 25 centers participating in the Eurocord Registry were analyzed. Overall survival of related and unrelated CBT recipients was substantially similar, the most important factor influencing patients' outcome being disease state at time of transplantation. In fact, due to a markedly increased relapse rate, poor-risk children (ie patients transplanted in more advanced disease) experienced a significantly worse EFS than those given CBT in a more favorable disease phase (ie CR1 or CR2). These data confirm that allogeneic CBT from either a related or an unrelated donor is a feasible procedure able to cure a significant proportion of children with acute leukemia, especially if transplanted in a favorable phase of disease.
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PMID:Cord blood transplantation for children with acute leukemia. Eurocord Transplant Group. 971 98

Relapsed or very aggressive high-grade NHL and refractory low-grade NHL have a poor clinical outcome. Autologous BMT may be used but is of limited efficacy in these cases. Allogeneic BMT offers the advantage of tumour-free bone marrow and a possible GVL effect. Between 1987 and 1996, 13 patients (median age 31 years) suffering from lymphoid malignancies underwent allo-BMT. Four patients had low-grade NHL, three intermediate-grade and six high-grade NHL. Three patients were grafted with evolutive disease, four were in partial remission after several courses of chemotherapy, two were in CR2 and four were in CR1 after initial therapy. The mean number of prior treatments was 2.7 (1-6). Median time from diagnosis to BMT was 25 months (4-90). The conditioning regimen consisted of cyclophosphamide (120 mg/kg/day for all, plus VP16 in one case) and total body irradiation. Five out of the seven patients who were not in CR at the time of transplantation entered CR after BMT. Eight patients developed acute GVHD grade > or = II and four had chronic GVHD. Nine patients are alive, eight in CR with a median follow-up of 49.8 months post BMT (2-125). Overall survival is 67.3% and the median time for EFS is 102 months. Two patients with low-grade NHL relapsed 61 and 102 months post BMT and were treated with DLI. One patient with a stage IV SLL had a partial remission and one with multiple cutaneous localisation of FL entered CR after grade IV acute GVHD. Allo-BMT is a highly effective treatment for advanced poor prognosis lymphoid malignancies with acceptable toxicity. Moreover, DLI can be effective in relapsing patients.
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PMID:Long-term follow-up of allogeneic bone marrow transplantation in patients with poor prognosis non-Hodgkin's lymphoma. 1010 May 76

A retrospective, case-matched analysis of the short-term toxicity, risk of GVHD and relapse as well as outcome in pediatric unrelated marrow transplantation was conducted by comparing recipients of T-replete and -depleted grafts in a two-center setting. Both groups contained 30 patients with acute leukemia matched by age at transplant, gender, primary diagnosis and disease status. Acute (90% vs 53%) and chronic (48% vs 0%) GVHD were more common among recipients of T-replete grafts. No significant differences in graft rejection/failure or viral infections were encountered between the two groups. Relapses were more prevalent (37% vs 15%) among recipients of T-depleted grafts. Outcome (EFS) was similar in the two groups. Consequently, in the analysis of transplant outcome, the higher risk of procedure-related, toxic complications among pediatric recipients of T-replete marrow grafts appears to be balanced by an increased risk of relapse among the recipients of T-depleted grafts.
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PMID:Pediatric marrow transplantation for acute leukemia using unrelated donors and T-replete or -depleted grafts: a case-matched analysis. 1072 82

A total of 11 high-risk Korean acute myeloid leukemia (AML) patients received stem cell transplantation from human leukocyte antigen (HLA) haploidentical donors. Specifically, for eight patients with 2-3 mismatched antigens and bidirectional vectors, we used a newly designed conditioning regimen that consists of total body irradiation, busulfex, ATG, and fludarabine. The median number of CD34+ cells infused was 15.4 x 10(6)/kg (range, 8-21.2). These patients received neither graft-versus-host disease (GvHD) prophylaxis nor post transplantation G-CSF. All of the patients who were followed up for a median of 6 months (range, 17 days-28 months) showed stable primary engraftment and had no acute GvHD or transplant-related mortality for 100 days post transplant. Three patients with high-risk or refractory disease eventually died in relapse, even with GvH-directed NK alloreactivity. However, the patients in complete remission (CR), with the exception of one patient who is alive at 18 months EFS, died at 4, 6, and 8 months post transplantation due to infections that were associated with delayed immune recovery. Our findings suggest that haploidentical transplantation represents a feasible treatment for patients with high-risk AML in CR, provided that a plan for the enhancement of immune recovery is implemented.
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PMID:Haplotype mismatched transplantation using high doses of peripheral blood CD34+ cells together with stratified conditioning regimens for high-risk adult acute myeloid leukemia patients: a pilot study in a single Korean institution. 1577 30

The results of blood or marrow transplantation in patients with chemorefractory aggressive lymphoma, that is, those not responding to conventional-dose chemotherapy at the time of transplant, have been poor. The relapse rate has been high after autologous bone marrow transplant, whereas allogeneic transplantation has been associated with excessive transplant-related toxicity. Administration of cyclosporine after autologous transplantation can induce an autoreactive syndrome that resembles graft-versus-host disease (GVHD). This syndrome, named autologous graft-versus-host disease, has clear antitumor activity in animal models that can be enhanced by the addition of cytokines such as gamma-interferon and interleukin-2. A randomized, prospective study was conducted to evaluate the antitumor effect of autologous graft-versus-host disease induced with cyclosporine, and augmented by the administration of gamma-interferon and interleukin-2 in patients with chemorefractory Hodgkin and aggressive non-Hodgkin lymphomas. Fifty-one patients were randomized, 24 to the autologous GVHD induction arm, and 27 to the noninduction arm after autologous transplant using mobilized peripheral blood stem cell (PBSC) grafts. There were no differences in treatment-related mortality, overall and event-free survival (OS, EFS) between both groups; however, in the induction arm, GVHD developed only in 4 patients. The administration of oral cyclosporine followed by interleukin-2 and gamma-interferon is generally not well tolerated, and does not appear to be an effective method to induce autologous GVHD in patients receiving autologous PBSC grafts.
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PMID:Induction of autologous graft-versus-host disease: results of a randomized prospective clinical trial in patients with poor risk lymphoma. 1788 55

The data of allogeneic HSCT in nine children with acquired AA between June 1998 and July 2006 were analyzed retrospectively. The median duration of time to neutrophil and platelet engraftment was 18 and 25 days, respectively. None of the patients had primary graft failure. Two (22.2%) patients developed acute GVHD and of these, one (11.1%) was Grade 1, and the other (11.1%) was Grade 3. Although the study group was composed of higher risk patients, including six of nine resistant to previous immunosuppressive treatment, eight had multiple not irradiated or filtered transfusion histories and one of the cases was only 5/6 HLA-compatible with his donor, the five-yr overall and EFS was 100%, and all recipients are alive without any graft failure. This may be attributed to the dose adjusted use of ATG according to individual transfusion history and gradual tapering of CsA and cessation at least nine months after allogeneic HSCT.
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PMID:Favorable outcome with allogeneic hematopoietic stem cell transplantation in pediatric acquired aplastic anemia patients. 1791 Jun 58

We reviewed 70 consecutive children with AML who received hematopoietic stem cell transplantation (HSCT) in our institution between 1994 and 2005. Forty-seven children were transplanted in CR1 and 23 were transplanted in CR2. BU/CY was the most common pretransplant conditioning regimen for CR1 patients and a TBI-based conditioning regimen was the most common regimen for CR2 patients. Most patients transplanted in CR1 (81%) received related donor HSCT, whereas most of the CR2 patients (74%) received unrelated donor HSCT. Expectedly, there was a significant increase in acute GVHD incidence in CR2 patients (40 vs 25% for grades I-II and 30 vs 10% for grades III-IV; P=0.02) and a significant increase in transplant-related mortality (38 vs 11%; P=0.01). Although the difference between 3-year EFS for CR1 and CR2 was not statistically significant, there was a significantly superior 3-year overall survival for CR1 patients (74 vs 51%; P=0.05). Children with relapsed AML who achieve and maintain remission until HSCT, have a reasonable survival, but the outcome of children receiving HSCT in CR1 remains superior.
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PMID:A comparison of the outcomes of children with acute myelogenous leukemia in either first or second complete remission (CR1 vs CR2) following allogeneic hematopoietic stem cell transplantation at a single transplant center. 1826 41

Impact of pretransplant splenectomy in patients with beta-thalassemia major undergoing an allogeneic SCT has never been addressed. Twenty-seven class III patients (29 transplants) had a pretransplant splenectomy. The outcome of these 29 transplants was compared with 76 transplants in class III who did not have a splenectomy. Patients in the splenectomy group were older (11.7 +/- 5.0 vs. 8.5 +/- 3.5 yr; p = 0.003) and had a larger liver size (5.7 +/- 1.8 vs. 4.4 +/- 1.6 cm; p = 0.000). Splenectomized patients had a significantly faster time to ANC >500/mm(3) (15.4 +/- 5.9 vs. 17.5 +/- 4 days; p = 0.002) and platelet >20 000/mm(3) (22.5 +/- 6.7 vs. 32.5 +/- 13.6 days; p = 0.000). The splenectomized group had a significantly reduced requirement of blood transfusion in the first 100 days post-transplant (5.5 +/- 5.1 vs. 7.2 +/- 5.4 units; p = 0.017). There were significantly more deaths related to peri-transplant infections in the post-splenectomy group (24% vs. 5.3%; p = 0.0001). The graft rejections were comparable between the two groups (20.7% vs. 14.5%; p = 0.55). The incidence of acute and chronic GVHD, late infections, and deaths from RRT was not significantly different between the two groups. The five-yr EFS (31.0 +/- 8.6 vs. 60.8 +/- 5.98; p = 0.003) and OS (39.7 +/- 9.3 vs. 71.8 +/- 5.5; p = 0.002) was significantly worse in the splenectomized group. In conclusion, pretransplant splenectomy among patients with beta-thalassemia major was associated with faster engraftment, reduced transfusion support, a higher incidence of peri-transplant infection related deaths, and a reduced EFS and OS.
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PMID:Impact of pretransplant splenectomy on patients with beta-thalassemia major undergoing a matched-related allogeneic stem cell transplantation. 1906 21

In the current study, we have analyzed the efficacy of cyclosporine A (CSA) plus mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis in the fludarabine plus melphalan or busulfan reduced intensity regimen (RIC) setting in a series of 44 patients receiving allogeneic transplantation from an unrelated donor. Only 23% were in the first complete remission at the time of transplant. Cumulative incidence of grades II-IV and III-IV acute GVHD (aGVHD) was 53% and 23%, respectively. Fifty-six percent had equal to or greater than grade 2 gut involvement. Cumulative incidence of overall and extensive chronic GVHD (cGVHD) was 93% and 63%, respectively. Ninety-two percent of patients who were evaluable +100 days after transplant were in complete remission. Relapse rate was 25% at 2 years. Event free (EFS) and overall survival (OS) at 2 years were 52%. Pharmacokinetic assays of mycophenolic acid (MPA) showed a therapeutic area under the curve (AUC) at the dosage of 3 g daily, although a large inter- and intraindividual variations of MPA plasma levels were found. In conclusion, the combination of CSA plus MMF in the fludarabine plus melphalan or busulfan RIC setting is feasible. Regarding GVHD, this combination allowed to control aGVHD but lead to a high incidence of cGVHD, so that newer strategies are required, especially in trying to decrease gastrointestinal involvement.
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PMID:Reduced-intensity conditioning allogeneic transplantation from unrelated donors: evaluation of mycophenolate mofetil plus cyclosporin A as graft-versus-host disease prophylaxis. 1848 92


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