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)

Results from phase I/II studies of Granulocyte-colony stimulating factor (G-CSF) for bone marrow transplantation were reported. G-CSF in 200-800 micrograms/m2 was administered from day 3 or 5 daily for 14 days. A very rapid recovery of granulocytes was observed in most cases. Stem cell exhaustion was considered not serious. Stimulation on myeloid leukemic cells was observed in vitro tests, but relapse was observed in only 2 out of 17 myeloid leukemia patients. There was no marked difference in the grade and incidence of GVHD from historical control patients. As side effects, 3 cases of bone pain and 2 of skin rash were observed. All these symptoms were slight, reversible and tolerated for further administration. As a whole, courses of BMT with G-CSF seemed very smooth and uneventful with very rapid and steady recovery of granulocytes. G-CSF seemed promising for bone marrow transplantation in which the severe granulocytopenic stage is inevitable and normal stem cells without contact with cytostatic agents are procured.
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PMID:[Granulocyte colony stimulating factor for bone marrow transplantation]. 247 38

A 23-year-old woman gravely ill with Pseudomonas septicemia secondary to presumed drug-induced bone marrow aplasia received marrow transplantation from two male HL-A identical sibling donors. She had a successful engraftment with excellent but temporary clinical improvement. Subsequently she succumbed to graft-versus-host disease manifested by Pseudomonas and Candida albicans septicemia, cytomegalovirus pneumonitis, three phases of dermatitis, nausea, vomiting, dysphagia, diarrhea, fever, edema and bone pain, with gradual but complete graft suppression by the 74th day after the transplantation. A second marrow transplant on the 70th day was unsuccessful.
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PMID:Bone marrow transplantation in a patient with drug-induced aplastic anemia. 440 93

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.
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PMID:Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor. 769 Dec 44

Most children with acute lymphoblastic leukemia (ALL) are successfully treated by chemotherapy. For those patients, who relapse on therapy, bone marrow transplantation (BMT) is considered most appropriate after a subsequent remission is achieved. Three boys with ALL aged from 9 to 13 years met these criteria and received BMT from their HLA-compatible sisters after marrow ablation with total body irradiation 12 Gy plus high dose cytosine arabinoside 3 gm/m2/12h x 12 doses and graft-versus-host disease (GVHD) prophylaxis with cyclosporine plus short course methotrexate from March 10, 1989 to May 23, 1992. Filgrastim (rhG-CSF) was used to hasten the recovery of granulocyte in one patient. All three patients got full engraftment and two had grade 1 acute GVHD. None of them developed chronic GVHD. Two patients have disease-free survival over 51 and 12 months respectively post BMT without further chemotherapy. One patient died of recurrent refractory leukemia 5 months after BMT. The toxicity of this conditioning regimen included photophobia, conjunctivitis and erythematous skin rashes. One patient who received filgrastim from day 1 to 21 developed severe bone pain. However, this patient had faster recovery of granulocyte count than the other two patients. The preliminary results of this work favors BMT for children with recurrent ALL whose ultimate survival is usually poor when treated with chemotherapy. Further efforts are necessary to investigate new methods for reducing leukemic relapse in ALL patients undergoing BMT.
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PMID:Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in second remission or relapse. 783 80

Six patients with high-risk leukaemia received a myeloablative regimen followed by allogeneic peripheral blood progenitor cells transplantation (PBPCT) from an HLA-identical sibling donor. Donors received 10-12 mu g/kg/day of G-CSF subcutaneously for 5 days. G-CSF was well tolerated except for moderate bone pain. Peripheral blood leukapheresis product contained 1-4 times more CD34+ cells and approximately a log more of T lymphocytes than marrow grafts from normal donors. In the two first cases the leukapheresis product was partially depleted of T-lymphocytes using counterflow centrifugation. No growth-factors were administered post-transplant. GVHD prophylaxis consisted of cyclosporin A (CyA) in one case, and CyA and methotrexate in five cases. All patients engrafted with a neutrophil count reaching more than 0.5 x 10(9)/L by day 12 to 21 post-transplant and a platelet count above 20 x 10(9)/L by day 6 to 41 post-transplant. Acute GVHD was clinical grade 0 (n = 2), I (n = 1), II (n = I), grade III (n = I) and grade IV (n = 1). One case presents an extensive chronic cutaneous GVHD and is currently being treated with methylprednisolone. In conclusion, allogeneic transplants using PBPC can be performed safely. This may result in a rapid neutrophil and platelet engraftment, without an apparent increased risk of GVHD.
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PMID:Allogenic transplants with peripheral blood progenitor cells: a report of six cases. 883 5

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.
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PMID:[Allogeneic transplant of peripheral blood hematopoietic progenitors. Preliminary experience]. 894 58

Fifteen patients with hematological malignancies [9 acute nonlymphoblastic leukemia (ANLL), four chronic myelogenous leukemia (CML), two acute lymphoblastic leukemia (ALL)] received allogeneic peripheral blood stem cell transplantation (alloPBSCT) from HLA-identical sibling donors. Donors received 2.5-15 micrograms/kg/day of recombinant human granulocyte colony stimulating factor (rhG-CSF) for 5-10 days. Administration of rhG-CSF was well tolerated except for mild to moderate bone pain occurring in all the donors which was relieved by oral paracetamol. A total of 40 leukaphereses were performed for the 15 donors using the bilateral antecubital veins. None of the donors needed central venous line insertion. The median number of apheresis procedures for each patient was 3 (2-3). A median of 7.7 (4-38.2) x 10(8)/kg mononuclear cells, 35 (2.4-90.0) x 10(6)/kg CD34+ cells, 1.85 (0.45-4.8) x 10(8)/kg CD3 and 0.3 (0.16-1.01) x 10(8)/kg natural killer cells were given without any manipulation. Cyclosporin A (CsA) plus short-course methotrexate (MTX) (12 patients) and CsA alone (3 patients) were used for graft versus host disease (GVHD) prophylaxis. Median granulocyte and platelet engraftments were done on days 11 (10-31) and 16 (11-54) respectively. Grades II-IV GVHD occurred in 62% of the patients and grades III-IV in 15%. Twelve patients are still alive with full engraftment and disease-free. In conclusion, alloPBSCT is an alternative to allogeneic bone marrow transplantation, because of the ease of collection and rapid hematological recovery. However, there is a trend for increased acute GVHD in our leukemia patients compared to allogeneic bone marrow.
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PMID:Allogeneic peripheral blood stem cell transplantation: is there an increased risk of graft vs host disease in leukemia patients? 937 93

Mobilization of stem cells with pegylated granulocyte colony-stimulating factor (peg-G-CSF) modulates donor T- and natural killer T-cell (NKT-cell) functions, thus separating graft-versus-host from graft-versus-leukemia disease in animal models. We report a phase I/II study that analyzed the feasibility of mobilizing stem cells from normal donors with peg-G-CSF and the ability of these cells to restore hematopoiesis in allogeneic transplant recipients after myeloablative conditioning. Administration of 6 mg of peg-G-CSF resulted in suboptimal stem cell mobilization, with a peak peripheral blood CD34+ count of 29+/-5/microL. Apheresis 4 days after peg-G-CSF yielded 2.7+/-.4x10(6) CD34+ cells/kg recipient weight, and all donors required a second collection on day 5 to yield a total of 4.2+/-.5x10(6) CD34+ cells/kg recipient weight. After escalation of the dose to 12 mg, the peak CD34+ count was 99+/-11/microL and 12 of 13 donors collected sufficient stem cells for transplantation in a single apheresis (8.9+/-1.4x10(6) CD34+ cells/kg recipient weight). Late transient increases in serum hepatic transaminases were noted, but other side effects (predominantly bone pain) were otherwise similar to those seen in donors mobilized with standard G-CSF. Median neutrophil and platelet engraftments occurred on days 18 and 14, respectively, after transplantation and were identical to those seen with in recipients of grafts mobilized with standard G-CSF. With a median follow-up of 357 days, the incidence of grade II-IV acute graft-versus-host disease was 50% and there have been no relapses to date. Mobilization of stem cells with peg-G-CSF in normal donors is feasible and 12 mg results in mobilization characteristics similar to those of standard G-CSF.
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PMID:Allogeneic stem cell transplantation with peripheral blood stem cells mobilized by pegylated G-CSF. 1673 33

Granulocyte colony-stimulating factors (G-CSF) are established prerequisites for the mobilization of peripheral blood stem cells (PBSC). Pegylated filgrastim (pegfilgrastim) has a substantially increased elimination half-life due to decreased serum clearance. A single-dose of pegfilgrastim is equivalent in enhancing neutrophil recovery after chemotherapy compared to daily filgrastim administrations. Several clinical trials also investigated chemotherapy plus single-dose pegfilgrastim in the mobilization of autologous PBSC in patients with lymphoma or myeloma. The results indicated similar efficacy compared to unconjugated G-CSF in terms of blood CD34+ cell count, stem cell yields as well as engraftment of after reinfusion. However, the number of patients in these trials were limited and there were non-randomized controls only. Furthermore, the mobilization of 12 mg pegfilgrastim was not superior over the 6 mg dose, and in one trial insufficient results were observed in heavily pretreated patients. In allogeneic stem cell donors a single-dose of 12 mg pegfilgrastim has been shown to induce a sufficient increase of blood CD34+ cells with a similar kinetics as known from conventional G-CSF. Adequate numbers of PBSC for transplantation could be harvested mostly by a single apheresis. Bone pain and headaches appeared to be more severe and about 90% of donors required analgetics. Additional concerns are due to spleen enlargement and hyperleukocytosis. Promising insights were reported from preclinical studies which revealed a modulating impact on both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after transplantation of pegfilgrastim mobilized PBSC. Further trials are needed which carefully evaluate the issues of donor safety, but also the impact on graft composition and recipients' outcome.
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PMID:The role of pegfilgrastim in mobilization of hematopoietic stem cells. 1849 Jan 97

Donor lymphocyte infusions (DLIs) after allo-SCT displayed limited use in CLL and highly malignant non-Hodgkin's lymphoma (NHL). Here we studied whether Bi20 (FBTA05), a novel trifunctional bispecific antibody targeting CD20 on lymphoma cells and CD3 on T cells, could induce GVL responses in combination with DLI or mobilized PBSCT after allogeneic transplantation in these diseases. Six patients (three cases with p53-mutated CLL and three with high-grade NHL (HG-NHL)) refractory to standard therapy were treated with escalating doses of Bi20 (range 10-2000 microg) followed by DLI or SCT. Thereby, all CLL patients showed a prompt but transient clinical and hematological response. In one patient with HG-NHL, we observed a halt in progression for almost 4 months. Side effects (fever, chills and bone pain) were tolerable and appeared at antibody dose levels between 40 and 200 microg. The cytokine profile was characterized by transient increases of IL-6, IL-8 and IL-10. Neither human anti-mouse antibodies nor GVHD developed, allowing repeated treatment courses. In summary, the trifunctional antibody Bi20 induced prompt antitumor responses in extensively pretreated, p53-mutated alemtuzumab and rituximab refractory patients indicating its therapeutic potential.
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PMID:Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 x anti-CD20 antibody and donor lymphocyte infusion. 1885 12


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