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 occurrence of late events (beyond 2 years) in patients with acute leukaemia who received an allogeneic (BMT) (n = 1059), or an autologous bone marrow transplantation (ABMT) (n = 656) in Europe during the period from January 1979 to December 1990. Patients with no recurrence of leukaemia at 2 years had overall 82% chance of being alive in complete remission at 9 years following transplantation regardless of the nature of the leukaemia, the status at transplant, and the type of transplant. The incidence of late relapses continuously decreased with time. The latest relapses in acute myelogenous leukaemia (AML) were observed following BMT at 6.6 years in a patient transplanted in first remission (CR1) and at 3.7 years in a patient transplanted in second remission (CR2), and following ABMT at 6 years and 5.1 years respectively. The latest relapses in acute lymphoblastic leukaemia (ALL) were observed following BMT at 4 years in a patient transplanted in first remission (CR1) and at 6.8 years in a patient transplanted in second remission (CR2), and following ABMT at 5.3 years and 4.5 years respectively. Several factors predictive for late relapse or death were identified. Patients allografted experienced a lower frequency of late relapse than patients autografted. Of the numerous other prognostic factors studied, female sex in AML, the use of total body irradiation (TBI) in ALL and status in CR1, rather than CR2-3, for both ALL and AML allografted were correlated with a lower relapse incidence. The use of TBI in ALL was also associated with a better LFS and survival. The absence of acute graft-versus-host disease (GVHD) in allografted AML correlated with better LFS and better survival, but had no influence on the relapse incidence. This study indicates that patients alive and well at 2 years post transplant have a very high probability of being cured, but the possibility of late relapse still remains.
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PMID:Are patients with acute leukaemia, alive and well 2 years post bone marrow transplantation cured? A European survey. Acute Leukaemia Working Party of the European Group for Bone Marrow Transplantation (EBMT). 820 85

Use of the mother as mismatched marrow donor was assessed in 19 children with advanced leukemia. Patients were homogeneous for HLA incompatibility, age, donor, and conditioning regimen, and stage of disease. All received busulfan and cytoxan, combined with unmodified donor marrow, ALG given before and after transplant, and short MTX and cyclosporine as GVHD prophylaxis. Survival, LFS, and relapse respectively were 26, 26, and 33%. Incidence of overall and severe acute GVHD was 58 and 32%, respectively. Four patients had failure of engraftment, and two of these are alive with autologous reconstitution in complete remission. Probability of rejection was 21%. Results of haploidentical transplants were compared with those of children with advanced leukemia treated at the same institution, who received marrow from HLA-identical siblings. The probability of long-term leukemia-free survival was similar in the two groups. We thus propose using the mother as an alternative marrow donor in children with advanced leukemia.
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PMID:Haploidentical bone marrow transplantation from mother to child with advanced leukemia. 852 68

From October 1984 to December 1994, 142 patients from six IGCI-BMT centers (78 acute myelogenous leukemia and 64 acute lymphoblastic leukemia) received allogeneic bone marrow from their HLA-identical sibling. The probability of LFS at 60 months is 41% for AML patients and 39% for ALL patients. A better LFS was documented in patients allografted in first CR compared to the patients treated in advanced stage of the disease. The overall relapse rate is 27% for AML patients and 45% for ALL patients. The relapse rate is higher for patients allografted in advanced stage of the disease (47 vs 26% at 60 months for AML and 55 vs 38% at 60 months for ALL). The incidence of moderate to severe acute GVHD is between 45-50% for both AML and ALL patients. Chronic GVHD was documented in 30% of AML patients and 38% of ALL patients. Transplant-related mortality for both AML and ALL is about 25%. Relapse and GVHD with or without infection are the main causes of death. These results confirmed that allogeneic BMT is very effective therapy for patients with acute leukemia, especially for patients transplanted in first CR.
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PMID:Allogeneic bone marrow transplantation for acute leukaemia--IGCI experience. International Group for Chemo-Immunotherapy. 880 7

A total of 1634 recipients of HLA-identical sibling bone marrow with acute leukemia were treated with the combination of cyclosporin A (CsA) and methotrexate as prophylaxis against graft-versus-host disease (GVHD). The probability of relapse decreased with an increasing grade of acute GVHD, especially in patients grafted in first remission (CR-1): P < 0.01 and P < 0.001 for acute lymphoblastic leukemia and acute myeloid leukemia, respectively. Among patients surviving at least 3 months without a relapse, chronic GVHD was associated with a decreased incidence of relapse in CR-1 (P < 0.0001 for both diagnoses), and a better LFS. Among patients in CR-1, the probability of relapse was the same in those with limited or with extensive chronic GVHD. However, in patients with intermediate stage of the disease (> or = 2nd remission or 1st relapse) with previous acute GVHD, those with extensive chronic GVHD had a reduced probability of relapse (P = 0.05). The graft-versus-leukemia effect of acute and especially chronic GVHD was confirmed by multivariate analyses. Overall, the highest LFS was seen in patients with chronic GVHD and no or grades I-II acute GVHD. The lowest LFS was seen in patients having acute GVHD grades III-IV without chronic GVHD.
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PMID:Graft-versus-leukemia effect in allogeneic marrow transplant recipients with acute leukemia is maintained using cyclosporin A combined with methotrexate as prophylaxis. Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. 893 46

To assess the consequence of second BMT (BMT2) for leukemia relapse after allogeneic BMT, we analyzed the clinical course of 66 recipients who were treated by BMT2 in Japan. Diagnoses included 29 ANLL, 27 ALL, six CML and four MDS. Durations between the first BMT (BMT1) to relapse and BMT1 to BMT2 were 13.5 +/- 13.7 months and 17.4 +/- 13.9 months, respectively. Donors for BMT2 were replaced in 11 cases. Thirty-one patients were in CR (or CP) at BMT2. Earlier deaths were observed in those who received BMT2 within 12 months after BMT1, mostly caused by regimen-related toxicity and infections. Overall leukemia-free survival rate was 28% at 2 years and 16% at 4 years. Factors influencing the poor prognosis after BMT2 were early (<6 months) relapse, early (<12 months) BMT2, not in remission at BMT2, and ALL. Intensified conditioning did not affect either remission duration or LFS. Among the 39 cases observed for more than 100 days, 18 developed chronic GVHD (cGVHD) and showed longer remission duration than those without cGVHD. Our analysis indicates that BMT2 as treatment for leukemia relapse is effective in selected cases, and exploration of pre-BMT treatment and post-BMT immunotherapy is warranted.
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PMID:Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes. 905 12

Extension of allogeneic transplants to older patients has been limited by a high risk of transplant-related death and graft-versus-host disease. To evaluate the feasibility in older patients, a retrospective analysis of the procedure was performed for first remission acute leukemia in 192 patients aged over 40 years and compared with a group of 1119 recipients aged from 16 to 40 years reported to the EBMT from 1986 to 1992. Patient-, disease-, and treatment-related variables were compared between the two age groups using the chi2 statistical method for categorical variables. Variables differing significantly or recognized as potential prognostic factors were included in a multivariate analysis. Leukemia-free survival and relapse were comparable among the age groups in the two types of leukemias. Incidence of graft-versus-host disease was higher in the older group of ALL patients. Older patients with AML in first remission had a higher treatment-related mortality incidence, with no influence on survival. A pair-matched analysis of AML patients did not show any statistical difference in the probability of LFS, RI, TRM, and survival for the two age cohorts of patients. These results suggest that BMT should be considered for patients over 40 years of age.
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PMID:Allogeneic bone marrow transplantation for acute leukemia in patients over the age of 40 years. Acute Leukemia Working Party of the European Group for Bone Marrow Transplantation (EBMT). 906 82

One hundred and eighty-one consecutive patients with standard-risk leukaemia were transplanted with HLA-identical sibling grafts depleted of lymphocytes using counter-flow centrifugation. In 116 patients, standard conditioning was intensified by the addition of anthracyclines. Multivariate analysis revealed significantly more acute GVHD > or = grade 2 and a trend towards more chronic GVHD in patients conditioned with the addition of anthracyclines. For all patients the risk for chronic GVHD, but not for acute GVHD increased with a higher number of T cells in the graft. The projected 5-year probability of relapse was significantly lower in the group of patients conditioned with anthracyclines; 26% versus 52% (P = 0.015). In multivariate analysis the addition of anthracyclines to the conditioning regimen was the only significant factor contributing to a lower probability of relapse. The projected 5-year probability of leukaemia-free survival [LFS] in the patients conditioned with and without the addition of anthracyclines was 56% and 36%, respectively (P = 0.004). In multivariate analysis the addition of anthracyclines to the conditioning regimen correlated significantly with a lower number of mixed chimaeras in patients at 6 and 12 months after BMT. Mixed chimaerism at 6 months after transplantation did not significantly correlate with a higher incidence of relapse in further follow-up. In contrast, mixed chimaerism at 12 months after BMT was significantly associated with higher relapse rate. We conclude that the addition of anthracyclines to the conditioning regimen improves outcome of BMT using T-cell-depleted grafts.
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PMID:Outcome of transplantation for standard-risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen. 933 35

Outcome of allogeneic BMT for childhood ALL performed at a national centre was evaluated for the period between 1985 and 1996. Sixty-seven patients representing all Danish children and adolescents (1-19 years) transplanted for ALL, were evaluated. Patients transplanted with a family donor (n = 51) had a 3-year probability of leukaemia-free survival (P-LFS) of 56% (95% confidence limits 41-69%) and patients receiving marrow from a matched unrelated donor (MUD) (n = 16) had a 3-year P-LFS of 67% (34-86%) (P = 0.38). Relapse was responsible for 48% of the deaths and occurred with increasing frequency among children transplanted with marrow from HLA-identical siblings. Patients transplanted with family donors from 1985-1989 had P-LFS of 72% (54-84%) compared to patients transplanted after 1990 who revealed a significantly reduced P-LFS of 28% (10-49%, P = 0.01). Furthermore, the risk of relapse was increased (65% (24-88%)) (P = 0.02) in the later period. In contrast, patients transplanted with marrow from a MUD (1990-1996) had a lower risk of relapse (11%, 5-20%) (P = 0.002) but a comparable risk of transplant-related mortality. Children who experience relapse after modern, intensive treatment for ALL may have an increased propensity for relapse even after BMT. Therefore, when performing BMT for childhood ALL, there may be a benefit in overall survival from the increased graft-versus-leukaemia effect that follows less intensive GVHD prophylaxis or transplantation with a MUD.
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PMID:Outcome of acute lymphoblastic leukaemia in Danish children after allogeneic bone marrow transplantation. Superior survival following transplantation with matched unrelated donor grafts. 972 66

Allogeneic transplantation is a well recognized treatment strategy of leukemia. However, its use in advanced leukemia patients is a subject of some debate especially when donors are not HLA-identical siblings because of the toxicity and cost of the procedure. We reviewed retrospectively the outcome of patients (pts) who received allogeneic transplantation for advanced acute leukemia in our center between 09/86 and 11/97. Thirty-six pts (study group) who lacked a matched sibling donor received partially matched related donor (n=14: PMRD group) or matched unrelated donor transplantation (n=22: MUD group). Fifteen pts had AML and 21 ALL. Seventeen pts (47%) were in CR>1, 13 pts (36%) had refractory disease and six pts (17.7%) were in untreated relapse. The outcome was compared to that of 56 patients (AML: 45.5 %, ALL: 55.5 %, CR>1: 49.9 %, refractory disease: 37.5 %, untreated relapse 19.6 %) who received allogeneic transplantation from a matched sibling donor (control group). Various conditioning regimens and GVHD prophylaxis were used. The actuarial incidence of grade II to IV acute GVHD was significantly higher in the study group (57%) than in the control group (34%) (p=0.047). The actuarial risk of relapse at three years was 21% +/- 22% in the study group versus 65% +/- 16% in the control group (p= 0.04). The actuarial probability of transplant-related mortality at 3 years is 64 +/- 16% for the study group and 25 +/- 11% for the control group (p=0.001). The leading cause of death in the study group was infection (30%) followed by acute GVHD and relapse. Relapse was the major cause of death in the control group (54%), followed by infection, interstitial pneumonia, veno-occlusive disease and GVHD. The OS and probability of leukemia-free survival at 3 years were 28 % +/- 15% (95% CI) and 27% +/- 15% (95% CI) in the study group. The overall survival and probability of LFS at 3 years were respectively 28 +/- 12% (95% CI) and 23 +/- 12% (95% CI) in the control group (p = 0.08 and p=0.11 respectively). In multivariate analysis, transplant-related mortality was higher in the study group (p=0.04) and lower if both donor and recipient were seronegative for CMV (p=0.007). OS was significantly higher for seronegative couples (p=0.0001), and when CR was achieved before BMT (p=0.0022). These results suggest that all efforts in this field should be directed on lowering the transplant related mortality for non geno-identical transplants and the relapse rate in geno-identical transplants.
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PMID:Allogeneic transplantation for patients with advanced acute leukemia: a single center retrospective study of 92 patients. 1137 41

Eighty patients with chronic myeloid leukemia (CML) underwent T cell-depleted stem cell transplantation from an HLA-identical sibling, with add-back of donor T cells on days 30 to 45 and days 60 to 100 in patients in whom grade 2 or greater acute graft-versus-host disease (GVHD) developed. The outcomes for 54 patients with chronic-phase (CP) and 26 with advanced-phase (AP) disease were as follows: overall survival, 85% +/- 5% versus 36% +/- 10%; transplantation-related mortality (TRM), 13% +/- 5% versus 43% +/- 11%; and current leukemia-free survival, 76% +/- 6% versus 34% +/- 9%. The day-30 lymphocyte count (LC30) was strongly associated with outcome. For patients in CP with counts greater than the median of 0.30 x 10(9)/L, survival was 100% versus 70% +/- 9% (P = .003); current LFS 100% versus 56% +/- 9% (P = .002); and TRM 0% versus 26% +/- 8% (P = .006). Higher-than-median LC30 correlated significantly with molecular remission (MR) at 3, 6, and 12 months and with higher CD34 doses. Lymphocyte subset analysis performed in 20 patients available for phenotyping showed that LC30 was highly correlated with absolute CD56+CD3- natural killer cell numbers (NK30), which also predicted for survival and MR. CD34 cell dose, LC30, and NK30, but not day-30 CD3+ cell count, were highly correlated and were significant predictors of transplantation outcome. These results suggest that transplanted CD34 cell doses greater than 5 x 10(6)/kg may improve outcomes by increasing the early recovery of NK cells.
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PMID:Factors associated with early molecular remission after T cell-depleted allogeneic stem cell transplantation for chronic myelogenous leukemia. 1613 70


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