Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematopoietic growth factors like G-CSF or GM-CSF have been shown to shorten the period of severe neutropenia after HD chemotherapy and autologous BMT, and are now widely used to mobilize hemopoietic stem cells into peripheral blood. In order to evaluate the possibility of delaying G-CSF administration after transplantation of G-CSF mobilized blood stem cells (BSC), we randomized 35 cancer patients to receive CSF at day 1 (group 1, n = 19) or at day 6 (group 2, n = 16) after transplantation and here we present their hematological reconstitution. BSC collection was performed by apheresis after G-CSF priming for 5 or 6 days (600 micrograms daily subcutaneously). Hematological recovery is comparable between the two groups: a median of 10 (range 7-16) vs 11 (range 9-18) days to reach an ANC > 0.5 x 10(9)/1 in group 1 (G-CSF day 1 after transplant) vs group 2 (G-CSF day 6 after transplant, P = NS). Median time to reach an unsupported platelet count of 25 x 10(9)/1 was 14 days in the two groups (range 8-110 and 10-40 respectively, P = NS); patients received less G-CSF after transplantation in group 2. No difference appeared in terms of transfusion support, number of days of fever of i.v. antibiotic treatment. Patients' hospital stay was the same in the two groups. Our data suggest that delaying G-CSF administration after infusion of mobilized blood cells is not detrimental to hematological recovery, while it lowers the overall cost of the procedure.
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PMID:Administration of G-CSF can be delayed after transplantation of autologous G-CSF-primed blood stem cells: a randomized study. 872 50

Twenty-five patients with hematologic malignancies were treated with busulfan (16 mg/kg) and cyclophosphamide (50 mg/kg x 3 days) as conditioning for bone marrow transplantation using marrow from serologically matched, DR locus genotypically identical unrelated donors. Previous studies of BuCy2 as conditioning for UD-BMT have reported a graft failure rate of up to 21% suggesting it may be insufficiently immunosuppressive in this setting. We elected not to use BuCy4 as it may have a higher incidence of extramedullary toxicity. In addition the patients received GM-CSF (500 mg/m2) from day 0, cyclosporine and short-course methotrexate (15 mg/m2 x 1, then 10 mg/m2 x 3) as GVHD prophylaxis and prophylactic ganciclovir at engraftment if either they or their donor were CMV antibody positive. The median age of the 25 patients was 41 years and the most common diagnosis was CML (76%). Seven patients were considered poor risk and eight males were recipients of marrow from female donors. Sixteen patients survive at a median of 435 days from transplant. The actuarial overall and disease-free survivals at 1 year in this group of older patients were 62 +/- 20% and 57 +/- 20% and 100-day survival was 70%. The engraftment rate was 100%; there have been no instances of secondary graft failure. Fifteen patients (60%) developed grade II-IV GVHD and 12 of 16 (75%) developed some chronic GVHD but only half of these were extensive. The performance status of survivors is good (median of 90); seven of 12 eligible patients are back at work. This study demonstrates that UD-BMT can be successfully performed in very closely HLA-matched older patients using a chemotherapy-only protocol and that low rates of severe acute GVHD can be achieved without T cell depletion.
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PMID:Unrelated donor bone marrow transplantation without T cell depletion using a chemotherapy only condition regimen. Low incidence of failed engraftment and severe acute GVHD. 872 53

G-CSF and GM-CSF have been shown in each clinical setting to reduce the duration of neutropenia, with the exception of the scant data available in the unrelated bone marrow transplant setting. These growth factors also have been shown to have no leukemogenic effect during the observation periods of the trials discussed. In MDS, one major randomized trial has demonstrated a reduction in incidence of infection. This has not yet been demonstrated in AML and allogeneic BMT. Data from ongoing and future trials will be helpful in elucidating their effect on treatment-related morbidity and overall survival.
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PMID:Clinical use of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in neutropenia associated with malignancy. 881 4

The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) as an adjunct to autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cell (PBPC) transplantation was evaluated in 59 lymphoma patients. Patients were divided into three groups. In group I (n = 21) patients received rhGM-CSF (5 micrograms/kg daily) at the time of PBPC collection and during the recovery phase post-infusion. In group II (n = 12) patients received rhGM-CSF as an adjunct to ABMT. In group III (n = 26) they were grafted with bone marrow without rhGM-CSF. Administration of rhGM-CSF (groups I and II) significantly reduced the time to myeloid engraftment, the number of febrile days and the median duration of antibiotics administration and of hospital stay when compared with the group in which patients did not receive rhGM-CSF. The only difference between ABMT and PBPC, given with rhGM-CSF support, was observed in the duration of hospitalization (group I > group II, P < 0.05). These data show that rhGM-CSF is highly effective in reducing the duration of aplasia following BMT and PBPC transfusion, and there appears to be little difference in efficacy between these techniques, provided that patients also receive rhGM-CSF.
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PMID:Granulocyte-macrophage colony-stimulating factor accelerates hematopoietic recovery after autologous bone marrow or peripheral blood progenitor cell transplantation and high-dose chemotherapy for lymphoma. 886 37

Treatment options for acute leukemia relapsing after allogeneic BMT include conventional chemotherapy or a second transplant; however, results are rather discouraging, the first option being associated with poor survival and the second with a high mortality rate. More recently, donor leukocyte infusion (DLI) from the original donor has been used for relapsed patients in an attempt to induce a graft-versus-leukemia (GVL) effect. This procedure is partially devoid of the toxicity inherent to a second BMT. At our Institution, a 36-year-old patient with biphenotypic AML in second complete remission after relapse following allogeneic BMT was treated with peripheral blood stem cell (PBSC)-enriched donor leukocytes, obtained after in vivo priming with rhG-CSF. The patient experienced extensive cGVHD but developed a testicular relapse while in full hematologic remission. After irradiation of the sanctuary site he remains free of disease, still with chronic GVHD, 21 months after bone marrow relapse. This case suggests that immunologically privileged sites are inaccessible to GVHD/GVL effect. This should be considered when planning salvage transplants procedures in patients at risk for extramedullary involvement.
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PMID:Testicular relapse of AML during chronic graft-versus-host disease induced by donor leukocyte infusion. 887 Mar 79

Rejection after allogeneic BMT for aplastic anemia is a complication with a high risk of mortality. We describe a patient who, following a second episode of rejection after a second BMT entered a third durable remission subsequent to treatment with ALG, donor lymphocyte infusions, GM-CSF, and erythropoietin. Therapy was well tolerated. At 5 years after rejection treatment, his hematopoiesis is of complete donor origin as determined by analyses of short tandem repeats. Thus, donor lymphocyte infusions can be considered as a therapy option for marrow rejection after allogeneic BMT for aplastic anemia.
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PMID:Rejection of the second allogeneic graft in a patient with severe aplastic anemia reversed by antilymphocyte globulin and donor lymphocyte infusions. 897 92

Since the early 80s, the EORTC Leukemia Group has included 3947 patients in 8 consecutive phase III studies on acute myelogenous leukemia, with stratification according to the age groups. Some of these patients were included by other cooperative groups (GIMEMA, HOVON), within intergroup studies. The main hypotheses tested by randomization were intensive chemotherapy consolidation, allogeneic and autologous bone marrow transplantation in the younger patients. In patients aged 60 years or more, a wait and see policy followed by a palliative chemotherapy was compared to an immediate conventional induction treatment, mitoxantrone was compared to daunorubicin, and, during remission, a low dose Ara-C maintenance treatment to no maintenance. The main results can be summarized as follows: Allogeneic BMT, and, relatively, autologous BMT do better than intensive chemotherapy consolidation with regards to the disease-free survival, but not for the overall survival after remission. In the elderly, an immediate induction and a low-dose Ara-C maintenance treatment are preferable to the other options tested. Mainly in patients aged more than 45, the supplementary toxicity of more intensive chemotherapy consolidation, with high dose Ara-C, counter balanced the increased anti-leukemic effect. Finally the trials randomizing GM-CSF during induction yielded disappointing results. The EORTC LCG is currently studying the relative value of various intercalating agents during induction, and of the G-CSF as well, and, during remission the autologous peripheral stem cells compared to bone marrow transplantation.
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PMID:The EORTC trials for acute myelogenous leukemia. EORTC Leukemia Cooperative Group. European Organisation of Research and Treatment of Cancer. 897 88

Allograft recipients are often unwell with significant organ dysfunction by the time delayed or failed engraftment is diagnosed. We attempted to identify factors associated with graft failure, or death due to infection, hemorrhage or graft failure in 712 patients undergoing allogeneic BMT. Low leukocyte counts between days 12 and 22 were strongly associated with subsequent graft failure or death. In multivariate analysis, a leukocyte count of < or = 0.2 x 10(9)/l on day 16 was the most powerful predictor of graft failure or death. Transplants from HLA-mismatched and unrelated donors were also associated with increased risk of both, and T cell depletion with increased risk of graft failure. On the basis of these findings, it may be possible to define graft failure in functional terms as early as 2 weeks after BMT rather than at 3 or 4 weeks. The use of growth factors can then be limited to patients most likely to benefit from them, and it may be possible to salvage patients at risk of complications of low counts early before their clinical condition deteriorates. We suggest that patients with leukocyte counts of 0.2 x 10(9)/l or less 14-16 days after BMT should be started on G-CSF or GM-CSF even if they are clinically well, and consideration should be given to a second infusion of cells.
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PMID:Early identification of patients at risk of death due to infections, hemorrhage, or graft failure after allogeneic bone marrow transplantation on the basis of the leukocyte counts. 905 Dec 45

Circulating anticoagulants protein C (PC) and antithrombin III (AT) are markers of, and possibly involved in the pathogenesis of, significant organ dysfunction, in patients undergoing autologous peripheral blood stem cell (PSBC) or autologous bone marrow (BM) transplantation. The effect of the stem cell source, the use of hematopoietic growth factors (GFs), and the specific preparative regimen on the incidence of organ system dysfunction or on post-transplant levels of circulating anticoagulants has not been well studied. We analyzed 205 patients in an attempt to correlate organ dysfunction and AT and PC deficiencies with these transplant-specific factors (78 BMT with GM-CSF after transplant, 95 PBSCT without GM-CSF after transplant, and 32 PBSCT with GM-CSF after transplant). Patients transplanted with PBSC had a lower incidence of pulmonary dysfunction (20 vs 40%, P = 0.006) and liver dysfunction (4 vs 13%, P = 0.05) than patients receiving BM. The use of GF after transplant did not influence the development of subsequent organ dysfunction. In multivariate analysis, the stem cell source was again predictive of pulmonary dysfunction. In contrast, although patients transplanted with PBSC also had a lower incidence of PC deficiency (50 vs 81%, P < 0.01) and AT deficiency (20 vs 54%, P < 0.01) as compared with patients receiving BM, use of GM-CSF after transplant was a more significant risk factor for the development of anticoagulant deficiency (PBSC with GF vs PBSC without GF: PC deficiency 50 vs 78%, P = 0.007; AT deficiency 20 vs 47%, P = 0.005). In the multivariate analysis GM-CSF use was the only significant risk factor for development of anticoagulant deficiency. Since the clinical significance of anticoagulant deficiency has been well shown, further studies examining these effects of hematopoietic GFs appear warranted.
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PMID:Factors predicting morbidity following hematopoietic stem cell transplantation. 905 18

A 19-year-old male underwent allogeneic BMT for severe aplastic anaemia (SAA) from his HLA- and blood group-identical sister. He was conditioned with cyclophosphamide (CY) and single fraction total lymphoid irradiation (TLI). GVHD prophylaxis consisted of FK506 and a short course of methotrexate. The patient failed to achieve durable trilineage hematopoietic engraftment. There was no significant myeloid response to GM-CSF or G-CSF. Evaluation of FACS-sorted peripheral T cells from the patient by fluorescence in situ hybridization (FISH) revealed mixed chimerism (44% host origin). Fifty-three days after the first BMT, he was treated with G-CSF primed, unmanipulated PBSC transfusions (5.28 x 10(8)/kg mononuclear, 4.28 x 10(6)/kg CD34+, 292.51 x 10(6)/kg CD3+ cells) from his original donor without reconditioning. FK506 was continued at the same dose. Neutrophil recovery to 0.5 x 10(9)/l and platelet engraftment to 20 x 10(9)/l was achieved 11 and 27 days following the first dose of allogeneic PBSC transfusion, respectively. On day 23 a repeat FISH on the patient's sorted peripheral T lymphocytes revealed 91% donor origin T cells. The patient is currently well with a stable engraftment 6 months following allogeneic PBSC transfusion, with no signs of acute of chronic GVHD.
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PMID:Successful engraftment after primary graft failure in aplastic anemia using G-CSF mobilized peripheral stem cell transfusions. 911 16


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