Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a double-blind, randomized study performed between 1988 and 1990, 40 patients undergoing allogeneic BMT from HLA-identical siblings for hematologic malignancies received 8 mg/kg/d rHuGM-CSF (molgramostim, n = 20) for 14 days. The median neutrophil count on day 14 was significantly higher in the GM-CSF group (1.90 vs 0.46 yen 10(9)/L, P < .0001). The incidence of acute GVHD and transplant-related mortality were comparable. Only two deaths occurred after 6 months; one due to pulmonary fibrosis in the GM-CSF group on day 1591, and one due to relapse on day 1590 in the placebo group. The Karnofsky score of the 10 survivors, 3 in the placebo group and 7 in the GM-CSF group, is 90-100% (median 100%), and none has chronic GVHD requiring therapy. There was no evidence of increased relapse in the GM-CSF group with only two relapses occurring; both in the placebo group. With a follow-up of 4.5-6.8 years (median 5.5 years), these patients are amongst the longest surviving patients to have received a recombinant growth factor post-allograft. We conclude that the administration of GM-CSF after allogeneic BMT does not appear to be associated with an increased incidence of chronic GVHD or relapse, or of other adverse effects such as the development of myelodysplasia.
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PMID:Long-term safety of GM-CSF (molgramostim) administration after allogeneic bone marrow transplantation for hematologic malignancies: five-year follow-up of a double-blind randomized placebo-controlled study. 915 59

To evaluate the chimeric status of mononuclear cells in the CSF after allogeneic BMT, cells were analyzed by FISH using satellite DNA probes for human X and Y chromosomes. CSF cells were obtained from five pediatric ALL patients who received BMT from sex-mismatched donors. All patients received TBI-containing conditioning regimens. We found that CSF cells showed complete donor type in 19-97 days after BMT, when complete donor type hematopoiesis was observed. The rapid entry of the donor leukocytes into the brain may exert beneficial effects to eradicate the residual CNS leukemic cells and prevent a CNS relapse in ALL patients after BMT.
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PMID:Chimerism analysis on mononuclear cells in the CSF after allogeneic bone marrow transplantation. 931 85

Pulmonary alveolar proteinosis (PAP) is a disease of unknown etiopathogenesis sometimes associated with malignant haematological disorders. The potential reversibility of the process in these cases seems to be related to recovery from the underlying disease. GM-CSF has acquired an important, potentially pathogenic role and BMT presents one therapeutic option effective in certain forms of human PAP. We present the case of a 43-year-old female patient with Ph+ CML. During pretransplantation evaluation, unexpected pulmonary infiltrates were noted in the chest X-ray, PAP being diagnosed on biopsy. In view of the progressive respiratory symptomatology and her CML being in accelerated phase, the patient underwent haematopoietic transplantation. She died on day +12 from invasive pulmonary aspergillosis before a response could be observed. Pathogenic implications in PAP and the role of haematopoietic transplantation in this disease are discussed.
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PMID:Haematopoietic transplantation in pulmonary alveolar proteinosis associated with chronic myelogenous leukaemia. 931 86

Several experimental autoimmune diseases (AID), including allergic encephalomyelitis, ie the multiple sclerosis (MS) model, respond to TBI and chemotherapy followed by BMT. Remissions of AID may also occur in patients with concomitant malignancies treated with allogeneic or autologous BMT. These observations have emphasized the possibility of treating AID with high-dose therapy and haematopoietic stem cell transplantation (HSCT). In a phase I/II pilot study, 15 patients with progressive MS were treated with BEAM followed by autologous blood SCT and antithymocyte globulin (ATG). Patients were severely disabled, with median EDSS and SNRS scores of 6 (5-7.5) and 42 (33-62), respectively. Cyclophosphamide (4 g/m2) and G/GM-CSF (5 microg/kg/day) were used for stem cell mobilization, which caused no neurotoxicity. On days +1 and +2, ATG (2.5-5 mg/kg) was given for in vivo T cell-depletion. Allergy (93%) and infections (87%) were the principal toxic complications. Mild, transient, neurotoxicity was observed in six patients in the immediate post-transplant period. The median follow-up time is 6 months (6-18). Durable neurologic improvements have been detected on both the EDSS (7/15) and SNRS (15/15) systems. One patient worsened at 3 months and two have relapsed. Autologous HSCT appears feasible in MS; it does not aggravate disability and seems to offer a clinical benefit. However, these observations need confirmation and long-term outcomes will show if benefits counterbalance toxicity and cost.
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PMID:Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. 938 25

We previously suggested that using a combined conditioning regimen including rhG-CSF with allogeneic BMT in refractory AML and CML in blast crisis might reduce the rate of relapse and improve disease-free survival, without any major side effects. In this study, we used the same protocol for 10 AML patients in complete remission (CR) and 6 CML patients in the chronic phase (CP). We compared disease-free survival as well as toxic side effects of the regimen with 6 AML patients in CR and 6 CML patients in CP treated with chemoradiotherapy without G-CSF. The conditioning regimen consisted of TBI and high-dose AraC. RhG-CSF was infused continuously at a dose of 5 microg/kg/day, starting 24 hr before the initial dose of total body irradiation (TBI) until the end of AraC therapy. In all 28 cases, there were no early stage deaths due to regimen-related toxicity (RRT). None of the 10 AML cases treated with the G-CSF combined regime relapsed. In 6 AML cases treated conventionally without G-CSF, one patient died of infection and another relapsed. There were no relapses in either CML group. In the combined G-CSF group, one patient died of interstitial pneumonitis 48 days after BMT, while the rest of the CML cases are still alive. There were no relapses with rhG-CSF and no serious adverse effects in terms of RRT, acute graft vs. host disease (GVHD), or leukocyte recovery.
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PMID:Recombinant human granulocyte colony-stimulating factor (G-CSF) combined conditioning regimen for allogeneic bone marrow transplantation (BMT) in standard-risk myeloid leukemia. 954 74

Marrow stromal cells were evaluated several months after autologous BMT for their capacity to support both normal hemopoiesis and secrete the main growth factors involved in its control, G-CSF, GM-CSF, IL-3 and SCF. Stromal layers (SL) were obtained by long-term marrow cultures (LTMC) established from 15 patients (9 with hematologic malignancies and 6 with solid tumors) 3 months after autologous BMT and were compared to pre-graft patients. After irradiation, both post-graft and pre-graft SL were recharged with the same inoculum of normal marrow cells. As compared to pre-graft values, CFU-GM production on post-graft SL was significantly increased during the first 2 weeks of culture whereas it was decreased from week 3 to week 8. These findings were only observed in patients with hematologic malignancies and not in patients with solid tumors. Growth factor secretion was evaluated by ELISA in the supernatants of unstimulated and IL-1-stimulated SL from 10 post-graft patients, 13 pre-graft patients and 5 normal controls. In any group of patients, IL-3 was undetectable either spontaneously or after IL-1-stimulation. As compared to controls, secretion by IL-1-stimulated SL was not different for GM-CSF in pre- and post-graft patients but tended to be decreased for G-CSF in post-graft patients. SCF secretion, which was not induced by IL-1, appeared dramatically decreased in both pre- and post-graft patients. The capacity of post-graft SL to support CFU-GM growth in LTMC was correlated at week 1 with G-CSF secretion and from week 3 to week 8 with SCF secretion. These results suggest that microenvironment remains qualitatively damaged several months after BMT involving a decreased capacity both to support early hemopoiesis and to secrete SCF, particularly in patients grafted for hemopoietic malignancies.
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PMID:Changes in the functional capacity of marrow stromal cells after autologous bone marrow transplantation. 964 67

We have established a murine model to compare the antileukemic effect of PBPC grafts obtained after treatment with SCF + G-CSF and G-CSF alone. C57/BL6, DBA and Balb/c mice were splenectomized and injected with optimal doses of rhG-CSF (250 microg/kg/day s.c.) or rrSCF (100 microg/kg/day s.c.) or with a combination thereof. On day 5, we determined the hematopoietic potential (number of CD34+ cells, CFUs, total CFC, CFU-gm), the proportion of lymphoid (T, NK and B cells) and myeloid components and graft-versus-leukemia activity after allogeneic and syngeneic PBPCT and BMT in Balb/c mice bearing a B-lymphoblastic leukemia cell line (A20). The absolute number of progenitor cells increased two-fold after administering a combination of G-CSF and SCF as compared to G-CSF alone (1500 vs 940 CD34+ cells/microl; 190 vs 70 total CFC/microl; 150 vs 50 CFU-gm/microl and 6600 vs 3000 CFUs/ml). Although no differences could be detected in the cellular composition, especially in the number of T cells, PBPC grafts mobilized by the combination of G-CSF + SCF demonstrated significantly higher antileukemic activity compared to G-CSF alone (94% vs 71% freedom from leukemia, P < 0.05). Because the incidence of lethal GVHD was similar in both groups, improved GVL activity resulted in superior overall survival. Our data suggest that the higher number of progenitor cells can be harvested after G-CSF + SCF and that grafts mobilized by G-CSF + SCF exert significantly enhanced antileukemic activity compared to those harvested after treatment with G-CSF alone.
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PMID:Superior antileukemic activity of murine peripheral blood progenitor cell (PBPC) grafts mobilized by G-CSF and stem cell factor (SCF) as compared to G-CSF alone. 971 86

One hundred and five consecutive primary high-risk myelodysplastic syndromes (MDS) or secondary acute myeloid leukaemia (sAML) evolving from MDS (performance status 0-3, ECOG) entered this study. Induction chemotherapy (CT) consisted of idarubicine 12 mg/m2 i.v. on days 1 and 2, etoposide 60 mg/m2/12h i.v. for 5d, Ara-C 120 mg/ m2/12h i.v. for 5d (one or two courses). Patients were randomized to receive or not G-CSF (5 microg/kg/d subcutaneously 48 h after the end of CT). 52 cases underwent CT alone and 53 CT+G-CSF. The CT+ G-CSF patients had a significantly shorter duration of neutropenia (8 nu 16d) with a lower incidence of infections and significantly better responses (CR+PR: 74% v 52%, P<0.05). 40 patients entered CR: 17 with CT and 2 3 with CT+G-CSF. Responders underwent two consolidation courses with the same CT, followed by high-dose Ara-C (2 g/m2 every 12h for 3 d). Most CRs were clonal. At present 21 responders have relapsed (median relapse-free survival 4 5 months). Eight responders received an allo-BMT, six are alive in CR 7-57 months post-transplant. Therefore allo-BMT only increases the chance of a long survival and possible cure. In conclusion, CT+G-CSF did not prolong either CR duration or survival; the growth factor support, however, increased the number of allo-transplantable cases by inducing higher remission rates and improving clinical conditions.
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PMID:Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia evolving from MDS. 972 93

We present a case of death likely to be directly due to cyclosporine (CsA) neurotoxicity. To date, there have been no reports of deaths directly due to CsA neurotoxicity, nor has an associated histological lesion been described independent of confounding processes. A 54-year-old male received an HLA-matched-unrelated BMT for CML. He developed progressive encephalopathy and on day +79 had a generalized seizure. All CSF studies were negative for infectious causes. MRI revealed diffuse, symmetrical white matter abnormalities located in the occipital sub-cortex, thalamus, mid brain, pons, and cerebellum which were typical of CsA toxicity. The patient died of central respiratory failure within 72 h of discontinuing CsA. Autopsy revealed diffuse patchy white matter edema and astrocytic injury without evidence of axonopathy, demyelination, microvascular injury, or infectious/inflammatory process. This case demonstrates previously undescribed lethal CsA neurotoxicity and may reveal an associated primary pathological lesion.
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PMID:Fatal outcome due to cyclosporine neurotoxicity with associated pathological findings. 1019 8

We studied the effects of an intensified induction/consolidation treatment containing fludarabine (ICE/FLAN/FLAN) on the mobilization and collection of peripheral blood stem cells (PBSC) in 31 consecutive untreated acute myeloid leukaemia (AML) patients. The complete remission (CR) rate was comparable to classic inductions (68% after ICE; 84% after ICE-FLAN I). To mobilize PBSC, 19 patients received 10 microg/kg/d of granulocyte-colony stimulating factor (G-CSF) starting at day 13 after FLAN, 13 (69%) of whom were found to be nonmobilizers. When a second G-CSF administration was performed in 10/13 patients mobilization was either not achieved (8/10) or was considered insufficient (<1 x 106 CD34+ cells/kg) (2/10) and all 13 were subsequently submitted to bone marrow harvest. The harvest was considered adequate in 12/13 (92%) patients and autologous BMT (ABMT) has so far been performed in 10/12 cases with a mean of 8.6 x 108/kg nucleated reinfused cells. The median times to neutrophil and platelet recovery after ABMT did not significantly differ from those of two previous series of patients treated with ABMT without fludarabine-containing regimens. Adequate amounts of PBSC were obtained in 6/19 (31%) patients, who were then reinfused. Median times for platelet recovery were significantly longer than in a previous series of 26 AML cases reinfused with PBSC after treatment with the ICE-NOVIA induction/consolidation regimen (125 v 20 d to 20 x 109 plt/l, P < 0.02; 218 v 37 d to 50 x 109 plt/l, P < 0.02). In addition, times for platelet recovery after ICE/FLAN/FLAN were not significantly different from those in a previous group treated with ABMT performed after ICE/NOVIA,without fludarabine. We conclude that fludarabine-containing regimens severely impair mobilization and collection of PBSC in AML patients and seem unsuitable when PBSC autotransplantation is programmed.
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PMID:Fludarabine-containing regimens severely impair peripheral blood stem cells mobilization and collection in acute myeloid leukaemia patients. 1035 46


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