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)

We studied whether treatment of dogs with recombinant human granulocyte colony-stimulating factor (rhG-CSF), after 920 cGy total body irradiation (TBI) and transplantation of 3.3 +/- 1.0 x 10(8) bone marrow cells per kilogram from a DLA-identical littermate, accelerated hematopoietic recovery and influenced the incidence of subsequent marrow graft failure or graft-versus-host disease (GVHD). Ten animals were treated with 100 micrograms rhG-CSF/kg/d from days 1 through 10 after TBI. Results were compared with those of historical control of 14 dogs not administered rhG-CSF. Neither group of dogs received GVHD prophylaxis. The median time to recovery of 1,000 neutrophils/mm3 was 8 days for dogs administered rhG-CSF compared with 14 days in controls (logrank test: P less than .03). The median time to reach 100 monocytes/mm3 was 17 days in G-CSF-treated dogs compared with 49 days in controls (P less than .002). The median time to attain 500 lymphocytes/mm3 was 15 days versus 31 days, respectively (P less than .01). The median time to reach 20,000 platelets/mm3 was 26 versus 20 days (P = .68). Graft failure occurred in 1 of 10 G-CSF-treated dogs versus 2 of 14 controls (two-tailed Fisher's exact test: P = 1.00). GVHD was seen in 4 of 9 rhG-CSF-treated dogs compared with 1 of 12 controls (P = .12). Two G-CSF-treated dogs died of GVHD versus none of the controls (P = .17). No unusual toxicities were seen in dogs receiving rhG-CSF. In summary, rhG-CSF significantly accelerated recovery of neutrophils, monocytes, and lymphocytes after DLA-identical littermate marrow transplantation without altering platelet recovery. Graft failure was not seen more often than in controls, but there was a trend toward an increased incidence of GVHD.
 ...
PMID:Recombinant human granulocyte colony-stimulating factor accelerates hematopoietic recovery after DLA-identical littermate marrow transplants in dogs. 169 48

We cultured bone marrow cells from patients receiving bone marrow transplantation (BMT) to assay bone marrow fibroblast colony-forming cells (CFU-F) and hematopoietic progenitors (CFU-mix, CFU-C, BFU-E and CFU-E), and compared the mean values obtained from patients with and without graft-versus-host disease (GVHD). The value of CFU-F colonies from 15 patients was always less in patients with acute GVHD Grade II,III than in those with Grade 0,I over the period 30 to 110 days after BMT. The CFU-F colonies from patients with Grade 0,I consisted of approximately the same number of small and large colonies, whereas virtually all CFU-F colonies from patients with Grade II,III were small. Fibroblasts collected from bone marrow cells cultured for 2-3 weeks were incubated with IL-1 (50 U/ml) for 24 h. The concentrations of G-CSF in the culture supernatants from patients with Grade II,III were higher than in those with Grade 0,I. The results of assays of hematopoietic progenitors from 48 patients showed that the number of hematopoietic progenitors decreased as the severity of acute GVHD increased. These results suggest that the myelosuppression seen in GVHD may be associated with reduced numbers of CFU-F in bone marrow.
 ...
PMID:Stromal fibroblastic and hematopoietic progenitors in patients with graft-versus-host disease (GVHD). 172 15

Prevention of graft-versus-host disease by depletion of CD6-positive T cells was studied in the dog. Donors were DLA-homozygous, recipients DLA-heterozygous with one DLA haplotype identical to the donor. Seven control dogs received untreated marrow and died of GvHD after full hemopoietic recovery within 28 days of transplantation. For prevention of GvHD, immunomagnetic separation of T cells with a monoclonal antibody against human CD6 that crossreacted with canine T cells was evaluated. Depletion of CD6-positive cells depleted CD4-positive cells completely, but only part of CD8-positive cells and DR-positive cells. CD6-depleted marrow exhibited strong nonspecific "natural" suppression of the generation of cytotoxic T cells in vitro. Eleven dogs received CD6-depleted marrow. Only 1 dog developed GvHD and died. Sustained engraftment was seen in 8 dogs. Hemopoietic recovery was delayed and slower after transplantation of CD6-depleted marrow than after transplantation of untreated marrow. Four of these dogs were treated with G-CSF, and this accelerated the recovery of leukocytes, but did not prevent rejection. Chimerism was mixed in 7 of 10 evaluable dogs and 1 dog recovered its own hemopoiesis 2 years after transplantation. CD6 depletion prevents GvHD across a DLA-haplotype difference, but rejection and mixed chimerism may occur. Treatment with G-CSF accelerates leukocyte recovery, but cannot prevent rejection.
 ...
PMID:Prevention of graft-versus-host disease in DLA-haplotype mismatched dogs and hemopoietic engraftment of CD6-depleted marrow with and without cG-CSF treatment after transplantation. 752 57

The use of the recombinant hematopoietic growth factors G-CSF and GM-CSF have shortened the period of neutropenia, or avoided this problem, in many cancer patients who have received cytotoxic therapy. Although these benefits have been particularly striking in the autologous bone marrow and/or autologous peripheral blood progenitor cell transplant setting, most data suggest that the use of G-CSF and GM-CSF only marginally enhance recovery of the neutrophil count when administered after allogeneic bone marrow infusion. Furthermore, in the allograft setting these expensive agents have not provided benefit in the form of enhanced platelet count recovery, lessening the incidence of graft-versus-host disease, or improvement in overall survival. These data do not justify routine widespread use of G-CSF and GM-CSF and suggest that these agents should be reserved for patients who experience delay in engraftment after allogeneic bone marrow infusion. Administration of erythropoietin, on the other hand, may reduce the need for homologous red blood cell transfusions, and may increase the safety margin for both the allogeneic bone marrow recipient and as well as the donor. Recombinant hematopoietic growth factors targetted specifically to enhance platelet recovery after transplantation (such as interleukin-3, interleukin-6, and interleukin-11) have shown promise after autotransplantation and after conventional dose chemotherapy, and likely will be evaluated in the allogeneic transplant patient.
 ...
PMID:Clinical use of hematopoietic growth factors in allogeneic bone marrow transplantation. 752 6

The treatment effect of immunoselected allogeneic CD34+ blood cells was evaluated in two patients with poor graft function following BMT without evidence for immune-mediated rejection. Patient A had no signs of hematopoietic recovery up to day +34 post-BMT and patient B had normal leukocyte counts only with G-CSF support and remained platelet transfusion-dependent for > 200 days post-BMT. PBPC from the HLA-identical sibling BM donors were mobilized with G-CSF (2 x 5 micrograms/kg sc daily) for 5 days. Aphereses were performed on days 4 and 5 of G-CSF administration. CD34+ cells were separated from the pooled PBPC concentrates by immunoadsorption with the anti-CD34 moAb 12.8 in a biotin-avidin system. Patient A received 0.4 x 10(6) CD34+ and 4.3 x 10(5) CD3+ cells/kg body weight and patient B 3.4 x 10(6) CD34+ and 1.4 x 10(5) CD3+ cells/kg body weight. The trilineage repopulation of BM and the rapid improvement of peripheral blood parameters correlated with CD34+ cell infusion. Patients' blood and BM cell analyses proved the donor origin. Patient A died from CMV pneumonitis and multiorgan failure 27 days after CD34+ cell infusion (day +61 post-BMT). Patient B is still stable and in remission 260 days after CD34+ cell infusion (day +478 post-BMT). Neither patient suffered further exacerbation of GVHD). Thus, immunoselected allogeneic CD34+ blood cells might be appropriate for treatment of post-BMT graft failure.
 ...
PMID:Treatment of poor marrow graft function with allogeneic CD34+ cells immunoselected from G-CSF-mobilized peripheral blood progenitor cells of the marrow donor. 753 62

A 25-year-old man with AML, who relapsed 21 months after his first allogeneic bone marrow transplant (BMT), underwent a second transplant with peripheral blood progenitor cells (PBPC) obtained from his HLA-identical sibling. The donor cells were collected through four aphereses after G-CSF mobilization with 5 micrograms/kg/d for 5 days. The patient received BAVC conditioning regimen followed by non-T cell-depleted PBPC. Successful engraftment occurred with rapid hematopoietic recovery (time to reach 0.5 x 10(9)/L neutrophils and 50 x 10(9) platelets/L was 15 and 19 days, respectively). A bone marrow aspirate on day +19 showed trilineage engraftment. Erythrocyte phenotype showed that erythropoiesis was of donor origin. The patient developed grade II acute GVHD that responded to prednisone. Seven months after PBPC transplantation he remains in complete remission, alive and well, with just limited chronic GVHD. Allogeneic peripheral blood progenitor cell transplantation may be considered a suitable alternative to marrow transplant.
 ...
PMID:Allogeneic peripheral blood progenitor cells mobilized by G-CSF (filgrastim) for a second transplant in a patient with acute myeloid leukemia in relapse. 753 99

There is a growing interest in the use of peripheral blood stem cells (PBSC) for allogeneic transplantation. This is due in part to the idea that, as with autologous transplantation, increasing the number of allogeneic hemopoietic progenitors infused may lead to reduced complications. However, introducing the PBSC technique into allogeneic transplants implies theoretical as well as ethical problems involving both patient and donor. We are still uncertain whether the PBSC technique will result in an increase of GVHD or (better) of GVL. G-CSF, necessary for effective PBSC mobilization, is safe but its use in normal subjects should be regarded with caution. For this reason, a Study Committee promoted by the GITMO (Gruppo Italiano Trapianto di Midollo Osseo) evaluated the key aspects of allogeneic PBSC collection and transplantation. The present paper summarizes the scientific data and suggests some guidelines for the introduction of allogeneic PBSC transplantation into clinical practice. The procedure should be considered experimental and the Committee strongly recommends the use of allogeneic PBSC in experienced centers, initially in patients with advanced disease. The donor should be given a complete explanation of the advantages and risks of G-CSF therapy, leukapheresis and general anesthesia. A careful monitoring of both patient and donor should also be included to watch for short-term and long-term side effects.
 ...
PMID:Allogeneic transplants of rhG-CSF-mobilized peripheral blood stem cells (PBSC) from normal donors. GITMO. Gruppo Italiano Trapianto di Midollo Osseo. 753 68

The positive role of G-CSF in hastening the myeloid recovery of patients undergoing allogeneic bone marrow transplantation (ALLO-BMT) or autologous bone marrow transplantation (ABMT) has recently been established. Considerable knowledge about adequate doses and route of administration has been accumulated in the past few years. Nonetheless, the optimal time to start growth-factor administration remains undetermined. We have performed a stratified study according to the source of hematopoietic progenitors (ALLO-BMT or ABMT), underlying disease and its stage, and acute graft-versus-host disease (GVHD) prophylaxis regimen and randomized patients in two arms: group A, which started G-CSF on day 0 (36 patients), and group B, which started on day +7 post-BMT (39 patients). The same dose (5 micrograms/kg/day) and route of administration were employed in both groups. We found no significant differences in the time to reach an absolute neutrophil count (ANC) of 0.1, 0.5, and 1 x 10(9)/l and 50 x 10(9) platelets/l (medians: 10 and 11, 14.5 and 14, 17 and 16, 23 and 24 days, respectively, in groups A and B). We did not find differences in the days of fever or days on antibiotic treatment with less than 1 x 10(9)/l ANC, rate of bacteriemia, or days of hospitalization in both groups. In contrast, a considerable saving of G-CSF in B group was found (mean days of infusion in group A, 18, versus 11 in group B) (p < 0.0001). This is equivalent to a saving of 1120 $US per patient.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Optimal timing of granulocyte colony-stimulating factor (G-CSF) administration after bone marrow transplantation. A prospective randomized study. 754 28

Growing attention has been focused on cord blood as a source of transplantable hematopoietic stem cells. However, clinical experience is rather limited. In this study we describe a child with advanced acute lymphoblastic leukemia who received an HLA-haploidentical cord blood transplant. The patient was transplanted in third complete remission after conditioning with fractionated total body irradiation, thiotepa and cyclophosphamide. Forty-one milliliters of cryopreserved umbilical cord blood, containing 0.15 x 10(8) nucleated cells/kg and 0.25 x 10(4) CFU-GM/kg, were infused. Cyclosporine and prednisone were administered for graft-versus-host disease (GVHD) prophylaxis. The patient received G-CSF from day +1 to day +35, but no improvement in granulocyte counts was observed. Therefore, administration of GM-CSF was started on day +36 to day +59, which resulted in a significant increase in white blood cells and granulocyte counts. Sustained myeloid engraftment was evidenced by a granulocyte count > 0.5 x 10(9)/l by day +41. The presence of donor-derived cells could be documented in the peripheral blood and bone marrow of the patient by cytogenetic analysis, HLA phenotyping and DNA studies. Forty-one days after transplant, clonogenic bone marrow assays showed the presence of low frequencies of primitive hematopoietic progenitor cells (BFU-E = 19/10(5) and CFU-GM = 8/10(5)). The chimerism was complete and no host-derived cells could be detected. However, the engraftment was restricted to the myeloid lineage whereas lymphoid and megakaryocytic engraftments were inadequate. The immunophenotype of the patient's peripheral blood showed the presence of T lymphocytes expressing an immature phenotype (CD2+ CD3-) at day +21.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:HLA-haploidentical umbilical cord blood stem cell transplantation in a child with advanced leukemia: clinical outcome and analysis of hematopoietic recovery. 758 Nov 41

We describe a 42-year-old man with ANLL-M4 in relapse after allogeneic BMT, in whom a new CR was obtained by conventional chemotherapy followed by the infusion of his female donor PBSC. At the time of BMT he was in CR. Six months later a full hematological relapse occurred an a three drug 5-day regimen was started. Two days after the end of chemotherapy he received donor PBSC collected by two leukaphereses after mobilization with G-CSF, given subcutaneously at 5 micrograms/kg/day for 7 days. The mononuclear PBSC were 4.2 x 10(8)/kg; the CD34 positive cells were 8.2 x 10(6)/kg and the CFU-GM were 14 x 10(4)/kg. Two days after PBSC infusion the patient received G-CSF at a dose of 5 micrograms/kg/day. Hemopoietic recovery occurred promptly on day + 13 and Y-FISH revealed 14% of Y-spot positive cells in the marrow. On day +20 hematological and cytogenetic remission was documented. The percentage of recipient cells decreased from day +36 onwards following the occurrence of a grade II GVHD, from which the patient recovered 1 week later with oral cyclosporin A and intravenous high-dose steroids. At present (day +200 from relapse) the patient is still in CR with 3% of Y-spot positive cells.
 ...
PMID:Intensive chemotherapy followed by donor PBSC in ANLL relapsed after allogeneic BMT. 765 95


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