Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of peripheral blood stem cells (PBSC) for allogeneic transplantation (PBSCT) is increasing steadily so that it cannot be considered an experimental practice any longer. Collection of PBSC requires the treatment of donors with G-CSF. With this drug, 10 to 16 mg/kg/day, side-effects are acceptable, but thrombocytopenia may follow the PBSC harvest. After transplant, allogenic PBSC engraft quickly in comparison with marrow. This has been shown for platelets, and to a lesser extent for granulocytes. Stability of graft has been documented by DNA analysis. With PBSC a high number of T- and NK-cells is infused, with a possible increase of GVL effect. However, we only have experimental evidence in the mouse that this may be the case. Incidence of acute GVHD equals that after BMT, but data on chronic GVHD are controversial, with an increased incidence reported in some studies. There is currently no indication for T-cell depletion of PBSC in HLA-identical sibling pair transplants. Experiments with CD34+ cell selection have sometimes produced a paradoxical increase of acute GVHD. The challenge of allogeneic PBSCT is improvement in survival, but available data only show that results are no worse than BMT. Prospective studies of allogeneic PBSCT versus bone marrow transplantation are in progress in Europe and USA.
 ...
PMID:Peripheral blood stem cells for allogeneic transplantation. 893 24

Between October 1991 and May 1994, 42 patients were treated with cyclophosphamide, thiotepa, and total body irradiation followed by an allogeneic transplantation of marrow depleted of T cells with soybean agglutinin and E-rosetting. Patients included in this study had acute myelogenous leukemia (13), chronic myelogenous leukemia (12), acute lymphocytic leukemia (nine), Hodgkin's disease or non-Hodgkin's lymphoma (four), multiple myeloma (three), or myelodysplastic syndrome (one). The mean age was 34 (range 8 to 51 years). Nineteen patients had a matched sibling donor and 18 received marrow from 6/6 matched unrelated donors while five received transplants from unrelated donors disparate at one DR locus (5/6 match). Time to granulocyte engraftment (AGC > or = 500/mm3) occurred at a mean of 16.5 days for related and 11.4 days for unrelated transplant recipients, and was related to the increased use of G-CSF in the unrelated population. There was no correlation with number of mononuclear cells, T cells, or CD34-positive cells infused, the rate of engraftment or the incidence of transplant complications. Multivariate analysis determined that G-CSF administration and a diagnosis other than ALL were the only factors associated with a faster rate of engraftment. Patients receiving unrelated donor transplants, those with ALL, or those who had a low T cell number infused (< or = 8.0 x 10(3) cells/kg) experienced delayed hospital discharge. The regimen resulted in excellent rates of engraftment (95.2%) with only one failure to engraft and one graft rejection. The incidence of grade III-IV acute graft-versus-host disease was 0% with sibling and 26.1% with unrelated donors. There were no cases of veno-occlusive disease. Fifty percent of patients are alive with a mean follow-up of 26.4 months. We conclude that this regimen is well tolerated and results in excellent engraftment with a low incidence of severe graft-versus-host disease and few therapy-related toxicities.
 ...
PMID:Minimizing graft rejection in allogeneic T cell-depleted bone marrow transplantation. 893 45

Myeloablative treatment followed by allogeneic transplantation of peripheral blood hemopoietic progenitors (alloPBT) was administered to five leukemia patients with a high risk of relapse. The donors subcutaneously received 10 micrograms/kg/day of G-CSF for five days. The tolerance to this medication was good with only complaints of moderate bone pain. Two of the peripheral blood donors had previously been bone marrow donors and both expressed their preference for the new method. The product of peripheral blood leukapheresis contained from one to four-fold more hemopoietic progenitors and approximately ten-fold more T-lymphocytes than the bone marrow received from normal donors. Prophylaxis of the graft versus host disease (GVHD) consisted of cyclosporine A (CsA) in one case and CsA and methotrexate (MTX) in four cases. The bone marrow implantation was verified with a neutrophil count of up to more than 0.5 x 10(9)/l between days 12 to 21 after transplant and a platelet count higher than 20 x 10(9)/l from days 11 to 41 after transplant. Acute GVHD was clinical grade O (two cases), II (one case) and grade III (two cases). In conclusion, alloPBT may be more safely and comfortably performed to the donor. This method may provide rapid recovery of neutrophils and platelets in patients without an apparent increase in the risk of developing graft versus host disease.
 ...
PMID:[Allogeneic transplant of peripheral blood hematopoietic progenitors. Preliminary experience]. 894 58

Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has been increasingly used as an alternative to allogeneic bone marrow transplantation (allo-BMT). In comparison with allo-BMT, preliminary results indicate that rapid hematopoietic engraftment can be obtained, and there is no increase in the incidence and severity of acute GVHD after allo-PBSCT. Furthermore, general anesthesia is not required to collect a sufficient number of PBSCT, which are usually mobilized by G-CSF administration. Therefore, allo-BMT will be replaced by allo-PBSCT in near future.
 ...
PMID:[Allogeneic peripheral blood stem cell transplantation]. 897 90

Peripheral blood stem cells (PBSCs) are gaining increasing acceptance as an alternative to bone-marrow (BM)-derived stem cells for allografting. Although scarce under steady-state conditions, CD34+ progenitor cells can be effectively mobilized into the peripheral blood (PB) in the vast majority of normal donors with a brief (3-4 days) course of recombinant human (rHu)G-CSF. Those cytokine-peripheralized progenitor cells and, among them, pluripotent stem cells, are collected by apheresis in sufficient amounts to achieve complete and permanent alloengraftment after myeloablative treatment in patients with primarily malignant hematologic disorders. The short-term tolerability profile of PBSC mobilization and apheresis in normal donors appears to be acceptable, although continued monitoring is necessary to ensure long-term safety. When compared with BM progenitor cells, mobilized PBSCs seem to exhibit a more primitive phenotype and a different clonogenic potential. The impact of factors affecting the efficiency of PBSC mobilization, such as rHuG-CSF dose, duration of cytokine treatment, and, to a lesser extent, donor age is now being recognized. Potential ways to optimize and possibly "engineer" PBSC collection, such as the use of cytokine/chemokine combinations (e.g., thrombopoietin, stem cell factor, etc.) and monoclonal antibodies directed against integrin receptors on CD34+ progenitor cells, are now being explored as well. In the clinical setting, engraftment after PBSC allografting is rapid and probably faster than after BM allografting. PBSC allografting seems to be associated with an incidence and severity of acute graft-versus-host disease (GVHD) comparable to the ones observed after BM allografting, although the incidence of chronic GVHD after allogeneic PBSC transplantation is still controversial. The infusion of a larger number of lymphoid cells appears to translate into a more rapid immunologic recovery and may lead to an enhanced graft-versus-leukemia effect. The collection of large numbers of mobilized PBSCs should provide ample opportunities for graft engineering and gene therapy. PBSCs may eventually replace, at least in part, BM as the preferred source of stem cells for both auto- and allotransplantation.
 ...
PMID:The use of mobilized peripheral blood stem cells from normal donors for allografting. 900 18

We report on five children with haematological malignancies who underwent allogeneic peripheral blood progenitor cell (PBPC) transplantation. PBPC were harvested from HLA-identical sibling donors after G-CSF (10 micrograms/kg/d s.c.) mobilization. Aphereses were carried out on day 5 after G-CSF using a Cobe Spectra blood cell separator. All PBPC allografts were cryopreserved before transplantation. The median of CD34+ cells and CD3+ cells infused were 14.1 x 10(6)/kg recipient body weight (range 4.92-22.3) and 2.40 x 10(8)/kg recipient body weight (range 0.54 4.82), respectively. Engraftment occurred in all cases. The median time to a neutrophil count > 0.5 x 10(9)/l and a platelet count > 20 x 10(9)/l were 15 and 14 d, respectively. The incidence of severe acute graft-versus-host disease was 20%. These data suggest that allogeneic PBPC transplantation might be an alternative to bone marrow transplantation in children.
 ...
PMID:Allogeneic peripheral blood progenitor cell (PBPC) transplantation in children with haematological malignancies. 901 2

We have carried out an analysis of 44 patients undergoing allogeneic PBSC transplants from fully HLA-matched related donors with particular emphasis on engraftment kinetics and the incidence and severity of GVHD. The recipients had a median age of 37 years (range 5-56 years), 16 patients had standard-risk disease and 28 had poor-risk disease. GVHD prophylaxis was with cyclosporin A and methotrexate (n = 41), cyclosporin A alone (n = 2) or cyclosporin A and methyl-prednisolone (n = 1). Stem cells were mobilised using G-CSF, collecting a median of 5.75 x 10(6) CD34+ cells/kg recipient weight (range 0.94-35 x 10(6) CD34+ cells/kg). Engraftment times to a neutrophil count > 0.5 x 10(9)/1 and platelets > 20 x 10(9)/1 were achieved at a median of day +14 (range 10-25) and day +14 (range 9-130) respectively. Patients receiving > or = 4 x 10(6) CD34+ cells/kg had significantly accelerated neutrophil and platelet engraftment and this number of CD34+ cells would appear to be a prerequisite for maximum engraftment using PBSC. Acute GVHD occurred in 25 of 43 evaluable patients although in only 12 was this clinically significant (grades II-IV). Chronic GVHD has occurred in 17 out of 36 evaluable patients, there was no significant difference between the standard- and poor-risk groups in incidence of either acute or chronic GVHD. In conclusion, these results confirm the feasibility of using PBSC for allogeneic transplantation without evidence for increased risk of either acute or chronic GVHD and provide further evidence supporting the potential of PBSC to replace bone marrow as the major source of haemopoietic cells for allogeneic transplantation.
 ...
PMID:Allogeneic peripheral blood stem cell transplantation for haematological malignancies--an analysis of kinetics of engraftment and GVHD risk. 901 25

A patient with CML in accelerated phase received G-CSF-mobilized PBPC from an unrelated HLA genotypically matched donor. The blood groups of the patient and donor were bidirectionally incompatible. Hematologic recovery was rapid with > 500 PMN/microliter on day +9. Starting on day +5 bilirubin levels increased from 1.3 mg/dl up to a maximum of 18 mg/dl on day +14. Clinical signs and laboratory tests supported major hemolysis. Blood typing on day +16 revealed early blood-group change, consistent with donor-derived antibodies produced by passenger-lymphocytes which may have mediated severe hemolysis. The early onset and strong intensity of the hyperbilirubinemia could be a specific feature of ABO-incompatible allogeneic PBPC transplantation which would be difficult to differentiate from GVHD or VOD.
 ...
PMID:Rapid engraftment after allogeneic ABO-incompatible peripheral blood progenitor cell transplantation complicated by severe hemolysis. 902 62

In the present single institution study of 66 leukaemia patients (28 AML, 23 ALL, 15 CML), the factors influencing haematological recovery after allogeneic bone marrow transplantation (alloBMT) were analysed retrospectively in order to identify the optimal conditions required for a rapid haematological recovery after alloBMT. All patients received GVHD prophylaxis with cyclosporine A plus methotrexate. The mean number of days required to achieve > or = 0.5 x 109/l neutrophil count after alloBMT was 17 (median 17, range 9 to 27 days) and 19 patients (28.8%) had rapid neutrophil recovery within 15 days after alloBMT. The haematological recovery was more rapid in the 38 patients without GVHD or with only grade I GVHD. Furthermore, 50% and 40% of patients receiving 10 (n = 18) or 5 (n = 20) micrograms/kg/day G-CSF had rapid neutrophil recovery within 15 days after alloBMT, versus only 7.1% of patients not receiving G-CSF post-transplant (n = 28), p < 0.001. The neutrophil recovery was similar in patients receiving either fresh or cryopreserved allografts and either TBI-containing or busulfan-containing conditioning regimen. A significant correlation was found between neutrophil recovery and either the MNC or CFU-GM content of the allografts, r = 0.33, p < 0.01. The mean number of days required for neutrophil recovery was only 16 days (median 16, range 9 to 24 days) in patients receiving allografts containing > 1 x 10(5) CFU-GM/kg (n = 28) versus 19 days (median 19, range 13 to 27 days) in patients receiving allografts containing < 1 x 10(5) CFU-GM/kg (n = 35). Three patients receiving allografts containing less than 0.5 x 10(5) CFU-GM/kg had primary neutrophil engraftment failure. The mean number of days required to achieve 20 x 109/l platelet count was 21 (median 20, range 11 to 50 days) and 30 patients (46.9%) had platelet recovery within 20 days after alloBMT. The platelet recovery after alloBMT was not significantly affected by the type of leukaemia, conditioning regimen, or G-CSF administration. The mean number of days required for platelet recovery after alloBMT was only 20 days (median 18 days) in patients receiving allografts containing > 1.0 x 10(5) BFU-E/kg (n = 35) versus 23 days (median 20 days) in patients receiving allografts containing < 1.0 x 10(5) BFU-E/kg (n = 24). Seven patients receiving allografts containing less than 0.5 x 10(5) BFU-E/kg had primary platelet engraftment failure. The present study has identified the high number of progenitor cells in the allografts infused and the daily administration of G-CSF post-transplant as the optimal combination for a rapid neutrophil recovery after alloBMT. More significantly, the number of BFU-E in allografts was the most significant factor to determine platelet recovery after alloBMT. The development of GVHD of grade II or more during the first weeks after alloBMT was associated with slower haematological recovery and longer period of fever during neutropenia and hospitalisation.
 ...
PMID:Factors influencing the haematological recovery after allogeneic bone marrow transplantation in leukaemia patients treated with methotrexate-containing GVHD prophylaxis: a single-centre experience. 906 85

A 44-year-old woman with AML, while receiving a conditioning treatment with BU-CY for an allogeneic sibling transplant, developed septic shock with pulmonary embolism and heart failure. Conditioning was stopped at the end of the busulfan course and cyclophosphamide omitted. After antibiotics, dopamine and steroids the patient was allografted, using the donor's G-CSF-primed PBSC. She recovered her peripheral blood counts promptly and developed an acute GVHD grade II that responded to steroids. The DNA microsatellite analysis showed full donor engraftment up to a year from transplantation. This case suggests that the use of PBSC may facilitate engraftment in the absence of an effective immunosuppression during conditioning.
 ...
PMID:Successful engraftment of allogeneic PBSC after conditioning with busulfan alone. 908 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>