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)

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

In this retrospective study, 23 recipients of peripheral blood progenitor cells (PBPC) were compared to 23 recipients of bone marrow (BM). The donors were 12 HLA-A-B-DR identical siblings and 11 HLA-A-B-DR identical unrelated donors in the PBPC and BM groups, respectively. Diagnoses in the PBPC group were CML seven, AML, nine, ALL three, lymphoma one, myeloma two and aspartylglucosaminuria (AGU) one. The median age was 40 (5-55) years. The BM group was matched for diagnosis, age, conditioning therapy, GVHD prophylaxis and G-CSF treatment after BMT. A higher number of MNC (P<0.001), CD34+ (P = 0.05), CD3+ (P<0.001) and CD56+ (P<0.001) cells in the graft, a reduced number of platelet transfusions (P = 0.03) and a significant hastening of neutrophil and platelet recovery were seen in the PBPC group compared to the BM group. In logistic regression analysis, the following factors were important for engraftment of ANC >0.5 x 10(9)/l: peripheral blood progenitor cell transplantation (PBPCT) (P = 0.003) and mononuclear cells (MNC) > or =2.5 x 10(8)/kg recipient in the graft (above median) (P = 0.009) in univariate analysis. For recovery of platelets >30 x 10(9)/l: PBPCT (P = 0.03) and HLA-identical sibling donors (P = 0.05) were significant in multivariate analysis. A trend towards a lower incidence of bacteremia was seen in the PBPC group, ie 22 vs 48% (P = 0.06) in the BM group. GVHD, TRM and survival did not differ between the two groups.
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PMID:Faster neutrophil and platelet engraftment, but no differences in acute GVHD or survival, using peripheral blood stem cells from related and unrelated donors, compared to bone marrow. 970 19

Three different types of anti-T cell antibody were used in patients undergoing haematopoietic stem cell transplantation (HSCT) with an HLA-A, -B and -DR compatible unrelated donor: ATG-Fresenius (ATG-F) (n = 26), Thymoglobuline (TMG) (n = 61) and OKT-3 (n = 45). The groups were comparable regarding diagnosis, stage, age, conditioning and GVHD prophylaxis, Adverse events were less frequent after ATG-F treatment. Levels of IL-2, IL-6, IFN-gamma, TNF-alpha and GM-CSF were increased after OKT-3 infusion. In multivariate analysis OKT-3 treatment (P = 0.01), G-CSF treatment (P = 0.02) and a cell dose >/=2.7 x 108/kg (P = 0.03) gave a faster engraftment. Acute GVHD grades II-IV occurred in 25% of the ATG-F patients, 12% of the TMG-patients and 43% (P < 0.001 vs TMG) of the OKT-3 patients. OKT-3 was associated with acute GVHD in multivariate analysis. TRM was 26% using TMG as compared to 43% in the OKT-3 group (P = 0.03). Patient survival at 4 years was 63%, 50% and 45% in the ATG-F, TMG and OKT-3-treated patients, respectively (NS). Relapses were 8%, 49% and 34%, respectively (ATG-F vs TMG, P = 0.03). Relapse-free survivals were 61%, 40% and 37% (NS). Among CML patients the probability of relapse was 61% in TMG-treated patients, while no patients relapsed in the other two groups. To conclude, the type of anti-T cell antibody affects GVHD and relapse after HSCT using unrelated donors.
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PMID:Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation. 1051 91

Allogeneic hematopoietic stem cell transplantation (alloHCT) is considered as a treatment of choice for many malignant hematologic disorders and genetic diseases. Unfortunately toxicities of conventional alloHCT remain a major limitation to successful application of the procedure. A radically new approach for alloHCT has been developed. Nonmyeloablative preparative regimen allows to establish mixed hematopoietic chimerism after alloHCT. A state of stable mixed chimerism may represent a starting point for induction of full donor derived hematopoiesis. A published results of several clinical trials have confirmed potential benefits of this new approach such as less procedure--related toxicity, protection from severe acute GVHD (graft versus host disease), lower TRM (transplant related mortality). Intensive investigations are done to replace in the future pretransplant chemotherapy and/or radiation by nontoxic anti-T-cell agents. These include antibody to the T-cell receptor alpha beta and blockers of T-cell costimulation (e.g. CTLA4lg).
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PMID:[Nonmyeloablative allogeneic hematopoietic stem cell transplantation: minitransplantation]. 1069 76

Unrelated donor (UD) transplantation is the only potentially curative therapy for many leukaemia patients but is associated with a high mortality and morbidity. We sought to identify factors that could be optimised to improve outcome following UD transplantation in adults. Data was retrospectively analysed on 55 patients sequentially receiving UD transplants for CML or acute leukaemia (AL), all of whom received serotherapy for the prevention of GVHD and rejection. All patients received standard conditioning regimens. The first 28 patients transplanted also received combined pre- and post-transplant serotherapy with Campath 1G (days -5 to +5) and standard dose CsA plus MTX as GVHD prophylaxis (protocol 1). The subsequent 27 patients received a 5-day course of pre-transplant serotherapy alone either with ATG (CML patients) or Campath 1G (AL patients) on days -5 to -1 inclusive, with high-dose CSA plus MTX (protocol 2). The incidence of acute GVHD was low with no patient receiving either protocol developing > grade 2 disease. The use of protocol 2 and the administration of a bone marrow cell dose above the median (2.17 x 10(8)/kg) were the most important factors predicting engraftment (P = 0.03 and P = 0.001, respectively) but this only remained significant for cell dose in multivariate analysis (P = 0.03). Overall survival for the group was 45% at 3 years and was influenced by both age (P = 0.02) and disease status at transplantation (P = 0.001). Receiving a cell dose above the median was also associated with a trend towards better survival (P = 0.08), due primarily to a reduction in the TRM to 8.2% compared with 54.5% in those receiving a lower cell dose (P = 0.002). We conclude that pre-transplant serotherapy alone is highly effective at preventing acute GVHD following UD BMT and that additional post-transplant serotherapy does not confer any benefit. Furthermore, a high marrow cell dose infused has a major effect in reducing transplant related mortality following UD BMT.
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PMID:The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia. 1072 85

Preparative regimens without total body irradiation (TBI) have been reported for alternative donor hemopoietic stem cell transplants (HSCT). Between 7 September 1994 and 7 June 1999 48 patients with advanced hematologic malignancies were conditioned with thiotepa (THIO) 15 mg/kg, cyclophosphamide (CY) 150 mg/kg and antithymocyte globulin (ATG). Donors were HLA mismatched family members (1-2 antigens) (FAM) (n = 24, median age 31 years) or HLA matched unrelated donors (UD) (n = 24, median age 34 years). GVHD prophylaxis was cyclosporine and methotrexate. Stem cell source was peripheral blood (n = 8) or bone marrow (n = 40). Hematologic recovery was seen in 42/46 (91%) evaluable patients and complete chimerism in 31/37 patients (85%). Acute GVHD grades III-IV were seen in 10/46 patients surviving 10 days (21%) and extensive chronic GVHD in 2/36 patients surviving 100 days (5%). Twenty-six patients died (54%), eight of recurrent disease (17%) and 18 of transplant-related complications (37%): main causes of TRM were GVHD (15%), infections (15%) and graft failure (4%). Twenty-two patients (46%) survive with a median follow-up of 877 days (287-1840). The actuarial 3-year survival is 49% for FAM and 42% for UD transplants. Results obtained with this regimen in unrelated grafts for advanced CML (n = 15) were not significantly different when compared to 21 concurrent UD grafts for advanced CML prepared with CY-TBI. In conclusion, the combination of THIO-CY-ATG allows engraftment of alternative donor hemopoietic stem cells. Results are similar when using unrelated matched donors or partially mismatched family donors, and not significantly different when compared to patients conditioned with CY-TBI.
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PMID:Alternative donor transplants for patients with advanced hematologic malignancies, conditioned with thiotepa, cyclophosphamide and antithymocyte globulin. 1122 70

Helper T lymphocyte precursor (HTLp) frequencies determined by limiting dilution analysis were studied in the graft-versus-host direction to assess the predictive value for outcome in allogeneic BMT. The HTLp frequencies correlated with the degree of HLA disparity. HTLp frequencies from 28 HLA-identical sibling BMT pairs had a median of 1:557 362 (range 1:9511 to <1:2 500 000). The HTLp frequencies from 20 HLA-matched unrelated and partially HLA-matched related BMT pairs had a median of 1:88 110 (range 1:4139-1:736 123). The HLA-identical sibling BMT pairs were split evenly into high and low HTLp frequency groups above and below 1:500 000. There was a trend towards a higher risk for acute GVHD > or =grade II (P = 0.075) in the high frequency group. There was no difference in TRM. The high HTLp frequency group had a significantly higher risk for chronic GVHD (P = 0.04), a significantly lower risk for relapse (P = 0.01), as well as a significantly better overall survival (P = 0.045) and leukaemia-free survival (P = 0.008). The HLA-matched unrelated and partially HLA-matched related BMT pairs were split evenly into high and low HTLp frequency groups above and below 1:90 000. There was a significantly higher risk for acute GVHD > or = grade II (P = 0.007) in the high HTLp frequency group. There was a trend towards a higher TRM in the high HTLp frequency group (P = 0.05). There were no differences in chronic GVHD, risk of relapse, overall survival and leukaemia-free survival. Analyzing all 48 patients the risk of acute GVHD > or = grade II and TRM was significantly higher (P = 0.012 and 0.021, respectively) with HTLp frequencies >1:100 000 and there was a trend towards a higher risk of relapse (P = 0.058) with low HTLp frequencies <1:400 000. Patients in the intermediate HTLp frequency group 1:100 000-1:400 000 had a trend towards improved survival (P = 0.059). The HTLp frequency seems to detect clinically significant differences in alloreactivity, that can be useful in donor selection and graft engineering.
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PMID:The predictive value of helper T lymphocyte precursor frequencies for graft-versus-host disease and graft-versus-leukaemia effects in allogeneic bone marrow transplantation. 1143 5

This multicenter study was designed to evaluate whether allo-PBPCT provides some advantages, if any, over BMT in terms of engraftment kinetics, acute and chronic GVHD incidence, TRM, relapse incidence and survival in acute lymphoblastic leukemia patients (ALL). From January 1995 to December 1999, 67 ALL patients (34 in the PBPCT group and 33 in the BMT group) were included in this study. Median age for both groups was 8 years (range, 1-18). There were 24 patients in first or second CR in the PBPCT group and 28 such patients in the BMT group. Preparatory regimens were TBI-based in 26/34 in the PBPC group and 25/33 in the BMT group. GVHD prophylaxis was CsA alone in 38 patients (18 PBPCT vs 20 BMT) and CsA plus short Mtx in 29 (16 PBPCT vs 13 BMT). Engraftment was achieved in all cases. Median days to neutrophil recovery was 10 (range, 7-18) after PBPCT vs 14 (range, 9-21) after BMT (P < 0.0001). Platelet engraftment (>50 x 10(9)/l) was also faster for PBPCT patients (median 13 days, range, 9-40 vs 23 days, range, 15-165) (P < 0.0001). Acute GVHD grade II-IV incidence was similar in both groups (46.4 +/- 8.8% vs 42.7 +/- 8.6%) (P = 0.45). Probability of chronic GVHD was 50.6 +/- 12.2% after PBPCT vs 27.8 +/- 9.2% after BMT (P = 0.1). Probability of relapse was similar (28.7 +/- 9.2% for PBPCT vs 27.1 +/- 8.2% for BMT) (P = 0.89). There were eight patients who died from transplant-related complications after PBPCT vs 5 after BMT (P, NS). With a median follow-up of 25 months the event-free survival probability was 53 +/- 8.9% for PBPCT vs 54.9 +/- 9.7% for BMT (P = 0.54). Using PBPC for allogeneic transplantation in childhood ALL results in faster hematopoietic recovery compared to BM, with a similar incidence of aGVHD, TRM, relapse and disease-free survival. However, the issue of cGVHD remains unresolved.
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PMID:Matched-pair analysis comparing allogeneic PBPCT and BMT from HLA-identical relatives in childhood acute lymphoblastic leukemia. 1210 71

According to recent reports, fast engraftment with minimal transplant-related toxicity and mortality (TRT, TRM) can be achieved by using reduced-intensity preparative regimens in allogeneic hematopoietic stem cell transplantation (HSCT). We report our experience with related (39%) and unrelated (61%) HSCT in 44 high risk patients (AML, ALL, CML, CLL) receiving either busulfan/fludarabine or busulfane/fludarabine/ATG or TBI/fludarabine as reduced-intensity preparative regimens. Organ toxicity was minimal with mild mucositis and no major bleeding. Acute GVHD was recorded in 64% of the patients. Twenty-three patients achieved complete remission after transplantation, and complete chimerism was obtained in all patients with stable engraftment (35 patients). Twenty-nine patients died: 15 due to relapse/progression, 14 due to TRM. Survival with median follow-up of 18.5 months was significantly better in patients with matched related transplants compared to patients with other transplants. However, there was no difference between related and unrelated transplants with regard to engraftment, TRM and GVHD. In conclusion, our results in high-risk patients transplanted in CR or with smoldering leukemia from a related donor are encouraging, although a longer follow-up and a larger group of patients is needed in order to evaluate the role of different reduced-intensity preparative regimens in unrelated and related HSCT.
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PMID:Reduced intensity preparative regimens for allogeneic hematopoietic stem cell transplantation: a single center experience. 1242 Feb 3

A total of 30 multiple myeloma patients (M=23, F=7; age 31-55 years, median 48) were allografted with peripheral blood stem cells (PBSC) from HLA-identical siblings. Time to transplantation was 3-107 months (median 8). Prior chemotherapy lines varied from 1 to 6 (median 1). Four patients were in complete remission (CR), 11 in partial remission (PR), 13 were considered to be nonresponders, and two had progressive disease. Most were conditioned with busulfan-melphalan. PBSC were collected by apheresis after G-CSF or sequential GM-CSF and G-CSF. The patients were grafted with 4.4-24.1 x 10(6)/kg CD34+ (median 7.9) and 0.9-7.9 x 10(8)/kg CD3+ cells (median 2.3). GVHD prophylaxis was methotrexate-cyclosporine. Engraftment was complete and rapid. Grades II-IV acute GVHD (aGVHD) developed in 16 (53%), but was grade III-IV only in five (17%); chronic GVHD (cGVHD) developed in 17 out of the 24 evaluable patients (71%). A total of 18 patients (71%) attained CR after transplantation. TRM was 30% overall, 16% at 100 days. There was only one relapse. Overall survival and event-free survival at 73 months were 60% and 67%, respectively. PCR negativity for IgH-gene rearrangement occurred in all persistently CR patients studied. PBSC allograft can induce long remissions, because of profound suppression of the neoplastic clone that is probably linked to the antitumor effect of cGVHD.
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PMID:High rate of remission and low rate of disease recurrence in patients with multiple myeloma allografted with PBSC from their HLA-identical sibling donors. 1273 83


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