Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An extensive series of experimental investigations has shown that both inherited and induced autoimmune diseases in laboratory animals may be transferred and, conversely, cured by stem cell transplantation. In man, the evidence is mainly anecdotal, originating both from the transmission of autoimmune conditions following allogeneic BMT from carrier donors to non-autoimmune recipients transplant-requiring diseases, and from the resolution of autoimmune diseases (mainly rheumatoid arthritis) of the recipients after allogeneic BMT from healthy donors. Will it be possible to cure severe autoimmune diseases with powerfully immunosuppressive conditioning regimens followed by the administration of hematopoietic stem cells? If the reconstitution of a naive immune system is necessary, allogeneic stem cells will be necessary, but the procedure is still saddled with its attending problems, with TRM in the foreground. When utilizing autologous stem cells in conjunction with TCD the patients' tolerance will be significantly better, but remissions are to be anticipated rather than cures. However, some special manipulations may be expected to ameliorate results in those selected autoimmune patients not or badly responding to conventional immunosuppressive therapy, for whom this type of treatment can be offered.
...
PMID:Stem cell transplantation for severe autoimmune diseases: new proposals but still unanswered questions. 852 63

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.
...
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.
...
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

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.
...
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

One hundred and thirty-one patients were transplanted for AML-CR1, ALL-CR1 or CML-CP1 after conditioning with 120 mg/kg body weight cyclophosphamide and 2 x 4.5 Gy TBI. Conditioning was intensified with the addition of 42 mg/m2 idarubicin. Grafts were T cell-depleted using counterflow centrifugation. Donors were HLA-identical siblings. We compared outcome of BMT in 109 patients aged less than 50 (median, 35) years with that of 22 patients with an age of 50 years or more (median, 53 years). For the patients aged <50 years, 2-year probabilities of treatment-related mortality, relapse, survival and leukemia-free survival were 26% (95% CI, 17% to 35%), 26% (95% CI, 17% to 35%), 64% (95% CI, 55% to 73%), and 56% (95% CI, 47% to 65%). For the patients aged > or =50 years, these figures were 13% (95% CI, 0% to 30%), 24% (95% CI, 6% to 42%), 66% (95% CI, 46% to 86%), and 67% (95% CI, 47% to 87%), respectively. Outcome did not differ significantly between the two age groups. TRM was within the range of that reported in the literature for recipients of T cell-depleted grafts. We conclude that T cell-depleted transplantation after a conditioning regimen that was intensified with the addition of idarubicin is feasible in patients aged > or =50 years. For this age group of patients, results of nonmyeloablative regimens should be compared with that obtained with T cell-depleted grafts.
...
PMID:Outcome of T cell-depleted transplantation after conditioning with an intensified regimen in patients aged 50 years or more is comparable with that in younger patients. 1091 1

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.
...
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.
...
PMID:Matched-pair analysis comparing allogeneic PBPCT and BMT from HLA-identical relatives in childhood acute lymphoblastic leukemia. 1210 71

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.
...
PMID:Hematopoietic stem cell transplantation in Lebanon: first comprehensive report. 1872 16

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.
...
PMID:[Unrelated allogeneic umbilical cord blood transplantation: present status, problems and countermeasures]. 1923 36

When compared with BMT, umbilical cord blood transplantation (UCBT) is associated with a lower rate of engraftment and delayed hematological/immunological recovery. This leads to increased risk of TRM in the early post transplantation period due to infection. Acute GVHD, although occurring less frequently in UCBT compared with BMT, is also significantly associated with increased rate of early TRM. BM MSCs are known to support normal in vivo hematopoiesis, and co-transplantation of MSCs has been shown to enhance engraftment of human cord blood hematopoietic cells in nonobese diabetic/SCID mice. In 13 children with hematological disorders (median age 2 years) undergoing UCBT, we co-transplanted paternal, HLA-disparate MSCs with the aim of improving hematological recovery and reducing rejection. We observed no differences in hematological recovery or rejection rates compared with 39 matched historical controls, most of whom received G-CSF after UCBT. However, the rate of grade III and IV acute GVHD was significantly decreased in the study cohort when compared with controls (P=0.05), thus resulting in reduced early TRM. Although these data do not support the use of MSCs in UCBT to support hematopoietic engraftment, they suggest that MSCs, possibly because of their immunosuppressive effect, may abrogate life-threatening acute GVHD and reduce early TRM.
...
PMID:Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation. 2040 Sep 83


1 2 Next >>

---