UMLS:C0018133 - FACTA Search

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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)

Granulocyte colony-stimulating factor (G-CSF) priming increases the number of progenitor cells in harvested bone marrow (BM) and has been used for allogeneic transplantation. Primed bone marrow (pBM) seems to offer faster engraftment than steady-state BM, but the stability of such engraftment has been questioned. The incidence of graft-versus-host disease (GVHD) and disease relapse after pBM, compared with such incidence after BM or peripheral blood progenitor allotransplantation, has not been established. We studied the long-term outcome (median follow-up, 24 months) of sibling matched allografting with G-CSF pBM. Seventeen patients received pBM from matched sibling donors primed with G-CSF 10 microg/kg per day for 2 days before BM harvest. Conditioning consisted of total body irradiation and cyclophosphamide (CY); busulfan and CY; or total lymphoid irradiation, CY, and antithymocyte globulin. All infused grafts contained > or = 3.5 to 4 x 10(8) mononuclear cells per kilogram. Ten of 17 patients received methotrexate as part of their GVHD prophylaxis. International Bone Marrow Transplant Registry definitions for engraftment were used. Control subjects consisted of 112 consecutive patients who received allogeneic transplantation at our institution with steady-state BM; control subjects for length of hospitalization consisted of the subset of patients who underwent transplantation during 1996. Neutrophil engraftment occurred a median of 7 days earlier in primed bone marrow transplantation (pBMT) patients when compared with steady-state BMT patients; this shortened hospitalization by a median of 11 days. The peritransplant mortality rate was 18% in pBMT patients and 25% in BMT patients (not significant). The rate of GVHD of grade > II and the rate of relapse were almost identical in pBMT and BMT patients (GVHD: 18% and 19%, respectively; relapse: 14% and 13%, respectively). There were 4 transplant-related deaths within the first 100 days; 1 patient died of disease relapse on day 470. Twelve patients remained alive on days 430 through 1522 after BMT. Results showed that pBM allografts resulted in more rapid engraftment and shorter hospitalization. All patients maintained stable donor engraftment. In this cohort of patients, G-CSF pBMT resulted in rates of GVHD, disease relapse, and peritransplant mortality that were similar to those produced by conventional BMT.
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PMID:Long-term follow-up after allogeneic granulocyte colony-stimulating factor--primed bone marrow transplantation. 1097 11

HLA-identical bone marrow or stem cell transplantation from a sibling is the preferred treatment for patients with chronic myelogenous leukemia, bone marrow failure syndromes, relapsed acute leukemia, and specific inborn errors of metabolism. Several groups have shown that granulocyte colony-stimulating factor (G-CSF)--mobilized peripheral blood progenitor cells (PBPCs) obtained from HLA-matched siblings are effective in reconstitution of marrow function after marrow ablative conditioning therapy. To evaluate whether G-CSF treatment before bone marrow harvest leads to enhanced recovery of PBPC counts and recovery from limited graft-versus-host disease (GVHD), we assessed the outcome of a sequential cohort of patients treated identically and then given either G-CSF--mobilized PBPCs or G-CSF--stimulated bone marrow from HLA-identical siblings. We show that the time to neutrophil engraftment is identical in the 2 cohorts, whereas platelet engraftment is earlier with the use of PBPCs. The incidence of acute GVHD was decreased, and that of chronic GVHD significantly decreased, in the group receiving bone marrow. Overall survival was not different between the 2 groups. Thus, G-CSF--stimulated bone marrow offers a source of stem cells that allows for early neutrophil engraftment with a decreased risk of GVHD.
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PMID:Comparison of granulocyte colony-stimulating factor (G-CSF)--mobilized peripheral blood progenitor cells and G-CSF--stimulated bone marrow as a source of stem cells in HLA-matched sibling transplantation. 1097 12

Six patients with advanced Hodgkin's disease in which multiple conventional treatments (median prior chemotherapy regimens: seven), radiation therapy, and a prior autologous stem cell transplantation (SCT) had failed underwent allogeneic SCT following a fludarabine-based conditioning regimen. Median age was 29 years (22-30). Median time to progression after autologous SCT was 6 months (4-21). Disease status at transplant was refractory relapse (n = 3) and sensitive relapse (n = 3). Cell source was filgrastim-mobilized peripheral blood stem cells from an HLA-identical sibling (n = 4) or matched unrelated donor marrow (n = 2). Conditioning regimens were fludarabine-cyclophosphamide-antithymocyte globulin (n = 4), fludarabine-melphalan (n = 1) and fludarabine-cytarabine-idarubicin (n = 1). Myeloid recovery was prompt, with an absolute neutrophil count > or =500/microl on day 12 (11-15). Median platelet recovery to > or =20000/microl was on day 9 (0-60). Chimerism studies on day 30 indicated 100% donor-derived hematopoiesis in 4/5 evaluable patients (4/4 non-progressors). All responders (3/3) have ongoing 100% donor-derived chimerism. Acute graft-versus-host disease (GVHD) was diagnosed in 4/6 evaluable patients. Chronic GVHD was present in 2/4 evaluable patients. There were no regimen-related deaths. Overall day 100 transplant-related mortality was 2/6 (33%). Three patients have expired and three are alive and progression-free with a median follow-up of 9 months (6-26) post transplant. We conclude that allogeneic stem cell transplantation with fludarabine-based preparative regimens is feasible in these high-risk, heavily pretreated HD patients.
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PMID:Allogeneic stem cell transplantation with fludarabine-based, less intensive conditioning regimens as adoptive immunotherapy in advanced Hodgkin's disease. 1104 66

We have employed a new cytoreductive regimen to transplant two patients with Fanconi anaemia (FA), using T cell-depleted two HLA-allele disparate related peripheral blood stem cell transplants (PBSCTs). Patient 1, a 5-year-old male with FA and aplastic anaemia, initially received an HLA two-antigen mismatched unrelated cord blood transplant and failed to engraft. He received fludarabine (Flu) and cyclophosphamide (Cy), followed by a CD34(+) E-rosette(-) (CD34(+)E(-)), T cell-depleted, granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCT from his HLA B-DRB1 mismatched father. He received anti-thymocyte globulin (ATG), steroids, FK506 and G-CSF after transplant for rejection and graft-versus-host disease (GVHD) prophylaxis. The patient is now 23 months after SCT with no evidence of GVHD and with full haematopoietic and immune reconstitution. Patient 2, a 10-year-old boy with FA and myelodysplastic syndrome, received single-dose total body irradiation (SDTBI), Flu and Cy followed by a CD34(+)E(-), T-cell-depleted, G-CSF-mobilized PBSCT from his HLA B-DRB1 mismatched sister. He also received ATG, steroids, FK506 and G-CSF after transplant. The patient is now 12 months after SCT in complete remission with no evidence of GVHD. Absolute neutrophil counts (ANC) of > 1 x 10(9)/l were achieved on day 11 and day 10 post transplant respectively. Both patients are fully engrafted. In summary, we report two successful T-cell-depleted stem cell transplants from mismatched related donors for the treatment of Fanconi anaemia, using a fludarabine-based cytoreduction. Both patients experienced minimal toxicity, rapid engraftment and no GVHD.
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PMID:Stem cell transplantation for the treatment of Fanconi anaemia using a fludarabine-based cytoreductive regimen and T-cell-depleted related HLA-mismatched peripheral blood stem cell grafts. 1116 55

Recovery of immune function following stem cell transplantation is necessary for a good outcome. Immune recovery is facilitated by transplanting higher numbers of cells than neutrophil or platelet reconstitution requires. Estimates from studies in the allogeneic setting suggest the minimum stem cell dose to achieve optimal lymphocyte recovery is about 10(7) CD34+ cells/kg. Increasing the number of autologous stem cells infused potentially increases the risk of reinfusing tumor cells. Transplanted mature immune cells apparently have very limited early contribution to cellular immune recovery. Mobilizing cytokines permit collection of greater numbers of stem cells, but they also can polarize T cells with potentially significant consequences, for example, granulocyte colony-stimulating factor (G-CSF) decreases the antitumor cytotoxic effector functions of cells. Although this could be a disadvantage in the autologous setting, it might decrease graft versus host disease in the allogeneic setting. Thus, identification of cytokines, which alone or in combination provide the most potent mobilizing effect to permit the collection of the highest number of stem cells without inadvertent detrimental polarization of the responses of immune cells, and employment of cytokines posttransplantation, which direct differentiation of the stem cells along the most desirable pathways, for example, to generate antitumor immune responses, might improve immunological outcome. A future emphasis should be to better define the cytokines and target cell populations that provide optimal immune reconstitution rather than focusing solely on rapid hematological recovery. More complete immunological reconstitution in a greater proportion of patients should be accompanied by improvements in outcomes of blood stem cell transplantation.
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PMID:Blood stem cell transplantation: factors influencing cellular immunological reconstitution. 1117 12

We describe a single-center experience of 23 consecutive patients (median age, 35 years) with hematologic malignancies who received allogeneic peripheral blood stem cell transplants (alloPBSCTs) from HLA-identical siblings. Ten patients had standard-risk disease and 13 had high-risk disease. Twenty-one patients received alloPBSCT as a primary transplant, and the remaining 2, with high-risk disease, as a second transplant after posttransplantation relapse. All donors received daily subcutaneous injections of granulocyte colony-stimulating factor at a dose of 10 microg/kg, and peripheral blood stem cells were collected by 1 to 3 aphereses. Median numbers of CD34+ and CD3+ cells infused were 5.8 x 10(6)/kg (range, 1.3-19.7 x 10(6)/kg) and 4.9 x 10(8)/kg (range, 1.9-8.6 x 10(8)/kg), respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A (CyA) and methotrexate (18 patients) or CyA and methylprednisolone (5 patients). Rapid hematologic engraftment was observed in 20 of the 23 patients. Median days to absolute neutrophil counts >0.5 x 10(9)/L and platelet counts >20 x 10(9)/L were 12 (range, 9-18 days) and 14 (range, 10-128 days), respectively. Acute GVHD of grade 2-4 was observed in 6 of 20 evaluable patients (30%) and extensive chronic GVHD in 8 of 15 evaluable patients (53%). Ten of the 23 patients (44%) were surviving in continuous complete remission 191 to 1492 days (median, 643 days) posttransplantation. Treatment-related death within 100 days posttransplantation was observed in 6 of the 23 patients (26%). Six of the 23 patients (26%) developed relapse at a median 81 days (range, 38-160 days) posttransplantation. Further study is needed to assess the precise benefits of alloPB-SCT compared with allogeneic bone marrow transplantation.
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PMID:Allogeneic peripheral blood stem cell transplantation in 23 adult patients with hematologic malignancies: a single-center experience. 1118 96

In human leukocyte antigen haplotype-mismatched transplantation, extensive T-cell depletion prevents graft-versus-host disease (GVHD) but delays immune recovery. Granulocyte colony-stimulating factor (G-CSF) is given to donors to mobilize stem cells and to recipients to ensure engraftment. Studies have shown that G-CSF promotes T-helper (Th)-2 immune deviation which, unlike Th1 responses, does not protect against intracellular pathogens and fungi. The effect of administration of G-CSF to recipients of mismatched hematopoietic transplants with respect to transplantation outcome and functional immune recovery was investigated. In 43 patients with acute leukemia who received G-CSF after transplantation, the engraftment rate was 95%. However, the patients had a long-lasting type 2 immune reactivity, ie, Th2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4- and IL-10-producing CD4(+) cells not expressing the IL-12 receptor beta(2) chain. Similar immune reactivity patterns were observed on exposure of donor cells to G-CSF. Elimination of postgrafting administration of G-CSF in a subsequent series of 36 patients with acute leukemia, while not adversely affecting engraftment rate (93%), resulted in the anticipated appearance of IL-12-producing dendritic cells (1-3 months after transplantation versus > 12 months in transplant recipients given G-CSF), of CD4(+) cells of a mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Moreover, CD4(+) cell counts increased in significantly less time. Finally, elimination of G-CSF-mediated immune suppression did not significantly increase the incidence of GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients of T-cell-depleted hematopoietic transplants was associated with abnormal antigen-presenting cell functions and T-cell reactivity. Elimination of postgrafting administration of G-CSF prevented immune dysregulation and accelerated functional immune recovery.
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PMID:Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants. 1129 May 77

We studied the effects of recombinant human granulocyte colony-stimulating factor (G-CSF) on hematopoietic recovery and clinical outcome in patients undergoing allogeneic peripheral blood stem cell (PBSC) transplantation. Fifty-six patients with hematological malignancies who underwent allogeneic PBSC transplantation between 1995 and 1998 were entered into this study. Twenty-eight patients who received daily G-CSF from day +1 after allogeneic PBSC transplantation until the absolute neutrophil count (ANC) reached >0.5 x 10(9)/l for 3 consecutive days were compared with 28 patients (control group) who did not receive G-CSF in a non-randomized manner. The study group and the control group were comparable with respect to baseline patient and transplantation characteristics. Median times to ANC of >0.5 x 10(9)/l and 1 x 10(9)/l with or without G-CSF were 12 days (range 8-21), 13 days (10-32) (P = 0.04) and 13 days (9-21), 15 days (11-44) (P = 0.02), respectively. Median times to reach a platelet count of >20 x 10(9)/l with and without G-CSF were 11 days (0-20) and 13 days (9-26), respectively (P = 0.03). The incidence of febrile episodes was significantly lower with G-CSF, 75% vs 100% (P = 0.008). Patients receiving G-CSF had less grade III-IV mucositis than those who did not receive G-CSF (P = 0.01). There was also no increase in the incidence and severity of acute GVHD in patients using G-CSF (P = 0.22). Although the number of relapsing patients was greater in the G-CSF group (seven vs three patients), this was not statistically significant (P = 0.24). Disease-free and overall survival rates did not differ between the two groups (P = 0.58 and 0.53, respectively). The administration of G-CSF after allogeneic PBSC transplantation provided faster neutrophil and platelet engraftment associated with less severe mucositis and less febrile episodes.
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PMID:Recombinant human granulocyte colony-stimulating factor (rh-G-CSF) may accelerate hematopoietic recovery after HLA-identical sibling allogeneic peripheral blood stem cell transplantation. 1131 83

The rapid recovery of hematopoiesis after allogeneic blood stem cell transplantation has been attributed to the quality and quantity of hematopoietic progenitors in the blood stem cell grafts from filgrastim-stimulated donors. To determine whether further stimulation with filgrastim after transplantation would affect hematopoietic recovery, a prospective, randomized, controlled study was performed. Forty-two adult recipients of allogeneic blood stem cells from human leukocyte antigen-matched related donors were randomized to receive 10 microg/kg per day filgrastim subcutaneously from day 1 through neutrophil recovery or no growth factor support after transplantation. There was no significant difference between the 2 groups in the number of CD34(+) cells infused (median, 4.8 vs 4.3 x 10(6)/kg). Graft-versus-host (GVHD) disease prophylaxis consisted of tacrolimus and steroids for 9 patients and tacrolimus and minimethotrexate for 33 patients. The group receiving filgrastim had a shorter time to neutrophil levels greater than 0.5 x 10(9)/L (day 12 vs day 15, P =.002) and to neutrophil levels greater than 1.0 x 10(9)/L (day 12 vs day 16, P =.01). The filgrastim group also had a trend for earlier discharge (day 16 vs 20, P =.05). There was no significant difference between the groups in time to platelet recovery, number of transfusions, regimen-related toxicity, infection, incidence of GVHD, relapse, survival, or hospital charges. It can be concluded that the administration of filgrastim after allogeneic blood stem cell transplantation shortens the time to neutrophil recovery. (Blood. 2001;97:3405-3410)
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PMID:Controlled trial of filgrastim for acceleration of neutrophil recovery after allogeneic blood stem cell transplantation from human leukocyte antigen-matched related donors. 1136 30

The effect of granulocyte colony-stimulating factor (G-CSF) on peripheral blood lymphocytes (PBL) and CD34+ cell frequency in the apheresis product has been determined in 25 healthy stem cell donors. Peripheral blood mononuclear cells (PBMNC) were collected after five days of G-CSF 10 microg/kg/day s.c., which was well tolerated. The median number of leukocytes increased eight-fold over that of pretreatment levels. Collection of PBMNC lasted a median of two (range, 1-3) days. The mean mononuclear cell (MNC) count and total lymphocyte percentage were 6.69 x 10(8)/kg and 59.08%, respectively, and the frequency of CD34+ cell expression was 2.1% in the apheresis product. The frequency of CD3+, CD4+, CD25+, NK and CD122+ cell expressions in mobilized PBMNC and PBL showed no significant difference. However, the frequency of CD8+, CD8+28+, CD3+DR+, CD19+, CD20+ and CD22+ B cells expression in the apheresis product increased significantly compared to steady-state PBL. In contrast, the frequency of the CD11 a+ and CD8+38+ cell expressions in the apheresis product was decreased compared to the steady-state PBL. The mean yield of CD34+ and CD3+ cells were 13.6 x 10(6) and 2.69 x 10(8)/kg of recipient body weight (RBW), respectively. Following allograft all patients engrafted with >0.5 x 10(9)/l neutrophil and < or = 20 x 10(9)/l platelets on a median of day 13 and 12, respectively. Nine patients had grade II-IV acute GVHD and chronic GVHD occurred in eight patients. Four patients died due to transplant-related complications. There was one late engraftment failure which occurred on the fifth month. Thirteen patients are still alive. In conclusion, these results indicate that administration of G-CSF at 10 microg/kg/day in normal donors alters the lymphocyte subsets and there are significant differences in the lymphocyte contents of the recipients before apheresis and in apheresis product.
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PMID:The effect of G-CSF on lymphocyte subsets and CD34+ cells in allogeneic stem cell transplantation. 1151 7

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