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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)

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

The use of hematopoietic growth factors after allogeneic bone marrow transplantation (BMT) was investigated either in a preclinical canine model or in patients. G-CSF administration in dogs after high-dose total body irradiation (TBI) and transplantation of DLA-identical littermate marrow significantly accelerated recovery of peripheral blood neutrophils, monocytes and lymphocytes, but not of platelet counts, without significantly increasing the risks of graft failure or graft-versus-host disease (GVHD). GM-CSF given to patients after HLA-identical sibling BMT was well tolerated at doses < or = 250 micrograms/m2/day and resulted in significantly faster neutrophil recovery compared with matched historical controls. Risks of graft failure, GVHD or relapse were not increased. When GM-CSF was given after matched or 1-antigen mismatched unrelated BMTs, the number of febrile days and septic episodes within the first 28 days was reduced even though neutrophil recovery was not accelerated. Incidences of graft failure, GVHD or relapse were not increased. In recipients of BMT with invasive fungal infections, M-CSF in combination with conventional anti-fungal therapy may have a beneficial effect on survival. Treatment with GM-CSF in patients with graft failure appears to result in improved survival without increasing the risks of GVHD or relapse.
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PMID:Hematopoietic growth factors after allogeneic marrow transplantation in animal studies and clinical trials. 772 31

G-CSF-mobilized peripheral blood progenitor cells (PBPC) were utilized in a patient who failed to engraft after an unmanipulated HLA-matched allogeneic bone marrow transplant. Marrow engraftment occurred after repeated conditioning with high-dose cyclophosphamide and PBPC infusion. Severe graft-versus-host disease (GVHD) developed shortly after marrow engraftment. The role of PBPC in allogeneic transplant, the associated potential risk of GVHD, and the necessity of reconditioning before stem cell reinfusion are discussed.
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PMID:Successful engraftment using allogeneic peripheral blood progenitor cells in a patient with primary bone marrow graft failure. 775 98

We describe a case of cold agglutinin disease (CAD) following allogeneic bone marrow transplantation. This 36-year-old male developed CAD 3 weeks after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Cyclosporin A and methotrexate had been administered to prevent graft-versus-host disease. Other agents administered included cytomegalovirus hyperimmune globulin and recombinant human G-CSF. Pericarditis preceded the development of CAD. The characterization of cold agglutinin (CA) was monoclonal IgM-kappa with anti-Pr antigen specificity, probably derived from the engrafted donor lymphocytes. The administration of prednisolone led to transient improvement. The CA titer decreased without further treatment 12 weeks after transplant.
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PMID:Cold agglutinin disease following allogeneic bone marrow transplantation. 819 73

A 5-year-old boy with severe aplastic anemia failed to respond to cyclosporine (CYA), prednisolone and antilymphocyte globulin (ALG). No suitable sibling marrow donor was available, but an HLA-matched unrelated donor was identified. The patient was conditioned with cyclophosphamide (CY), 50 mg/kg/day for 4 days, total nodal irradiation (8 Gy), and ALG 30 mg/kg/day for 3 days. GVHD prophylaxis consisted of daily CYA, methotrexate (MTX) and ALG. The patient failed to achieve sustained engraftment. He was reconditioned with high-dose prednisolone and anti-T lymphocyte monoclonal antibody OKT3. The boy was reinfused with the same donor marrow on day 0 (+49/first BMT). No GVHD prophylaxis was given the second time. He received G-CSF on days 0 to +20 after the second transplant. Full engraftment was achieved on day +16 (+65). However, on day +31 (80) he developed a biopsy-proven B cell lymphoproliferative disorder (BLPD). After the OKT3 administration was stopped and treatment with ganciclovir and high-dose immunoglobulin was initiated, the BLPD resolved and the patient was discharged on day +50 (99). He is currently well with a functioning graft 266 (305) days posttransplant, with no sign of GVHD.
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PMID:Remission of a lymphoproliferative disorder occurring after second BMT from an unrelated donor in a 5-year-old boy with severe aplastic anemia. 853 24

We describe the case of a 41-year-old female who underwent allogeneic blood cell transplantation with CD34(+)-enriched cells from an HLA-matched unrelated donor for AML in second CR. The conditioning regimen consisted of TBI (12 Gy), VP16 (1800 mg), cyclophosphamide (7200 mg), and ATG (7200 mg). GVHD prophylaxis consisted of CsA and a short course of MTX. Receiving G-CSF from day +1, engraftment occurred on day +19 after stem cell infusion. Starting on day +10, GVHD grade II (skin and liver) developed that responded to high-dose steroid therapy. The patient died on day +38 due to suspected cerebral aspergillus infection. This case demonstrates the feasibility of primary transplantation of CD34(+)-enriched allogeneic peripheral stem cells from a matched unrelated donor leading to engraftment of donor cells.
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PMID:Transplantation of allogeneic rhG-CSF mobilized peripheral CD34+ cells from an HLA-identical unrelated donor. 854 73

We examined whether the use of G-CSF would affect the outcome of allogeneic marrow transplantation in humans and mice. Retrospective analysis of 24 patients who had received allogeneic marrow grafts from HLA-identical siblings revealed that the incidence of chronic but not acute graft-versus-host disease (GVHD) was lower in the patients receiving G-CSF than in those not given G-CSF (18% vs. 80%, P = 0.02). There was a difference in serum TNF-alpha levels during the first 3 months after transplant between these two groups. Four out of the ten patients who were not given G-CSF showed elevated serum TNF-alpha levels, whereas there was only one patients with an increased TNF-alpha level among eleven patients who were given G-CSF. With the use of murine acute and chronic GVHD models, we also observed that administration of G-CSF improved the survival of minor GVHD, but not major GVHD, mice. Taken together, these findings suggest that G-CSF down-regulates allogeneic immune responses and is active in modulating alloreactivity in vivo.
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PMID:Modulation of allogeneic immune responses by filgrastim (recombinant human granulocyte colony-stimulating factor) in bone marrow transplantation. 858 69

In order to obtain an additional graft versus leukemia effect (GVL) and rapid engraftment, donor leukocyte infusion (DLI) was added to unseparated, sex-mismatched allogeneic bone marrow transplantation in two male patients (age 21, 26) affected by high risk hematological malignancies (refractory T-ALL, refractory B-LBL in leukemic phase). Graft versus host disease (GVHD) prophylaxis consisted of methotrexate (MTX) alone. DLI were obtained after G-CSF 16 ug/kg/day sc. A total of 2.36 and 5.8 x 10(6)/kg MNC, 5.4 and 11 x 10(6)/kg CD34+ cells, 1.3 and 1.3 x 10(6)/kg CD3+ lymphocytes, respectively, were infused. Hemopoietic recovery occurred promptly. Complete chimerism was detected by cytogenetic examination. One patient developed an extramedullary relapse that first involved the cranial nerves, and then the testes, soft tissue and skin; the other patient developed central nervous system disease and then bilateral paravertebral masses with progressive paraplegia. Despite complete medullary remission with normal female karyotype, both patients died from extramedullary progression of their disease. Our observation shows that, at least in high risk patients, no additional GVHD or GVL effect was evident after donor leukocyte infusion. Extramedullary relapse was not prevented despite good control of medullary disease.
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PMID:Extramedullary relapse after allogeneic bone marrow transplantation plus buffy-coat in two high risk patients. 864 54

Over the past ten years, the availability of pharmacologic quantities of hematopoietic growth factors has opened many avenues of study in basic science and clinical investigation. Numerous studies performed to date have demonstrated significant benefits from the use of these cytokines. The side effect profiles, particularly for "later acting" growth factors, indicate that they are generally well tolerated by most patients. The table summarizes the potential indications for hematopoietic growth factor use as discussed in this article, as justified by current evidence of benefit, harm, and cost effectiveness resulting from their use in various clinical settings. It has been clearly demonstrated in standard-dose chemotherapy regimens that these agents shorten the duration of myelosuppression, reduce the incidence of significant infection, can shorten hospital stay, and reduce antibiotic use for most patients, although the cost/benefit ratio for growth factors such as G-CSF makes this a cost-effective approach only for regimens with a high (40 percent or more) incidence of febrile neutropenia. Limited indirect evidence supports the use of growth factors in patients with a prior episode of fever and neutropenia. The suppressive approach to growth factor use could potentially benefit patients with documented infection or clinical deterioration, but it has not otherwise been shown to be a particularly effective or cost-effective approach. Administration of hematopoietic growth factors has been instrumental in facilitating both autologous and allogeneic peripheral progenitor cell mobilization and techniques such as ex vivo expansion. There is an increasing body of data supporting the use of high-dose chemotherapy regimens with progenitor cell rescue for a number of malignancies and limited data supporting the benefits of maintaining dose-intensity for certain malignancies in standard-dose settings. Although of continuing concern, clinically significant evidence of disease stimulation and recurrence has not been unequivocally demonstrated in studies to date. A comprehensive set of evidence-based guidelines has recently been published by the American Society of Clinical Oncology. As often is the case, current studies have perhaps generated more questions than answers. Future investigation will undoubtedly focus on use of hematopoietic growth factors in conjunction with other techniques, such as outpatient-based treatment of febrile neutropenia, CD34-positive stem cell selection in autologous transplantation, selective manipulation of T-cell subsets (to decrease the incidence of severe graft-versus-host disease) in allogeneic transplantation, and high-dose therapy with stem cell transplantation.
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PMID:Hematopoietic growth factors. 864 43

Peripheral blood progenitor cells (PBPC) were mobilized by G-CSF in normal HLA identical siblings and used for allogeneic transplantation in eight patients with refractory or relapsed acute leukemias. G-CSF administration was well tolerated and no significant side-effects were registered. The number of circulating WBC peaked at day 5 after G-CSF (range: 22.6-74.6 x 10(9)/l) with a median of 65 CD34+ cells/microl (38-155). As a consequence of leukaphereses, platelets progressively decreased, reaching the nadir after the last procedure (84-205 x 10(9)/l). A mean of two aphereses (1-3) were performed between day +4 and +7 during which 10 liters of blood were processed each time by a cell separator. Conditioning regimens were: fractionated total body irradiation (FTBI) plus either HDAra-C (2 g/m2 x 2/day for 6 days) (n=5) or melphalan (110 mg/m2) (n= 1) and busulfan (4 mg/kg/day for 4 days) and melphalan (110 mg/m2) in two patients relapsed after a previous FTBI-based allogeneic or autologous BMT. At transplantation, a median of 6.9 x 10(6) CD34+ cells/kg (4.2-16.5) and 279 x 10(6) CD3+ cells/kg (161-786) were infused. Engraftment of both neutrophils (> or v=1.5 x 10(9)/l) and platelets (> or v=20 x 10(9)/l) was observed in all patients after a median time of 18 days (range: 11-20 and 10-26, respectively). The evaluation of engraftment after transplantation was accomplished by PCR analysis of four hypervariable genomic regions (VNTR) (ApoB, ApoC2, YNZ-22, and MCT 118) which allowed to demonstrate the condition of donor chimaera in all patients after transplantation. As far as the clinical outcome, two patients died of interstitial pneumonitis at day +243 and +69 and two patients died at day +62 and +152 of pulmonary aspergillosis. Four patients remain alive in remission between day +88 and +287 with grade 0-l GVHD. Allogeneic PBPC transplantation is associated with a complete hematologic recovery and despite the infusion of a large amount of mature CD3+ lymphocytes, apparently acute GVHD is not worse than expected after transplantation of bone marrow progenitors.
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PMID:G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation of resistant or relapsing acute leukemias. 865 84


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