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 series of 198 patients we compared various methods of prevention of GVHD. One hundred and thirty-three patients were treated with CSA alone, 44 with the combination of CSA and MTX, and 21 with CSA after marrow T cell depletion. The incidence of GVHD greater than or equal to II was 35% in the CSA group, 22% in the CSA+MTX group and 14% in the T depleted group. The actuarial survival was 55.4%, 52.3% and 55.1% respectively. These results show that the improvement of methods of prevention of GVHD did not affect significantly long term survival after BMT.
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PMID:Role of immunosuppressive drugs for prevention of graft-v-host disease after bone marrow transplantation. 267 32

CSA toxicity includes renal impairment, microangiopathic hemolytic anemia (MAHA), thrombocytopenia (T), and consumptive coagulopathy (CC). We report five BMT patients who developed CSA-associated hematological toxicity. All were conditioned with Ara-C, Cyclophosphamide, Methylprednisolone, TBI, and in two cases busulfan. IV CSA was started the day after marrow infusion and, when practicable, changed to the enteral route. Five patients developed MAHA and T resulting in significantly increased transfusion requirements. All patients had renal impairment and red cell fragmentation. In all patients fragmentation was noted before renal impairment. All developed disproportionate increases in BUN relative to serum creatinine consistent with decreased renal perfusion. Hypertension followed renal impairment in four cases and occurred at the same time as the renal impairment in one case. Two developed CC, prolongation in APTT, and marked decreases in plasma fibrinogen. All patients improved on reduction of the CSA dose. BMT recipients receiving CSA at variable doses may develop evidence of a TTP-like syndrome and/or CC.
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PMID:Coagulation defects in cyclosporine A treated allogeneic bone marrow transplant patients. 304 63

Sera from 11 patients undergoing autologous or allogeneic BMT were tested for their content of megakaryocytic, granulocytic and erythrocytic colony stimulating factors. During the first week after BMT, all patients sera revealed a low/inadequate production of granulocytic, erythrocytic and megakaryocytic colony-stimulating activity (defined as the number of colonies per plate induced by 30% test serum from monocyte and T-lymphocyte depleted bone marrow cells). Thereafter an increase of colony-stimulating activity for all cell lineages tested was observed with peak levels between days 8 to 14 after BMT. The peak level was followed by a decline of colony stimulating activity, which shows an inverse correlation to basal blood leukocyte counts suggesting an adequate counter-regulation during this period. The GM colonies grown in the presence of patient serum were found to consist largely of neutrophilic granulocytes with only single monocytic colony, but without eosinophilic colony formation, suggesting that granulopoietic colony formation during this period is mediated predominantly by G-CSF and not by GM-CSF. All patients undergoing autologous BMT revealed a low/inadequate endogenous CSF production. rh GM-CSF addition in vitro was able to compensate from the impaired endogenous granulopoietic CSA in all patients and resulted in a constant augmentation of granulopoietic colony formation. The percentage of eosinophilic colony formation showed an inverse correlation to endogenous CSF production also suggesting that G-CSF is secreted during this period. In contrast to the granulopoietic colony formation, erythropoietic and megakaryopoietic colony formation was not enhanced by GM-CSF addition in vitro and even showed a slight reduction in some experiments. Our results suggest the treatment with recombinant GM-CSF might be beneficial for a faster reconstitution of granulo-monocytopoiesis after BMT, that rh GM-CSF therapy should be started immediately after bone marrow transplantation and that G-CSF is the main factor secreted in allogeneic bone marrow transplantations in the regeneration period.
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PMID:Serum colony stimulating factors in patients undergoing bone marrow transplantation: enhancing effect of recombinant human GM-CSF. 307 43

Aplastic anaemia is characterized by multilineage bone marrow failure resulting in pancytopenia. We have successfully treated a young woman with severe aplastic anaemia (SAA) who was resistant to antilymphocyte globulin (ALG) and corticosteroids, with a combination therapy consisting of erythropoietin, cyclosporin A and granulocyte-colony stimulating factor (G-CSF). The patient received erythropoietin and CSA for a period of 10 months without success before G-CSF treatment was started. After 6 weeks of G-CSF therapy she responded with a sustained trilineage recovery. This suggests that immunosuppression together with haemopoietic growth factors may be an effective treatment in patients with SAA who are ALG resistant and cannot be treated by BMT.
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PMID:Sustained trilineage response in a patient with ALG-resistant severe aplastic anaemia after treatment with G-CSF, erythropoietin and cyclosporin A: association of recovery with marked elevation of serum alkaline phosphatase. 751 Sep 93

Fifteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 3/y) vaso-occlusive crises (VOC) associated with recurrent acute chest syndrome episodes (n = 10), osteitis (n = 3), osteonecrosis (n = 3), strokes (n = 3) or frequent massive deglobulisation (n = 2). Two children undergone splenectomy, two were chelated and two had an erythroid allo-immunization. Ethnic origins were from various countries in Africa (n = 11), North-Africa (n = 3) or West Indies (n = 1). At BMT, they were 2y 3m to 14y 9m old (mean: 8y 7m). Donors were AS (n = 11) or AA (n = 4). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n = 13) or 260 mg/kg (n = 2); BU: 14 mg/kg (n = 1), 16 mg/kg (n = 9), > 16 mg/kg (n = 5); one patient received also TLI and the last two anti-thymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n = 4) or CSA plus short-term MTX (n = 11). Median follow-up is 28 months (5 m to 53 m). All patients had an engraftment (d12 to d32) with a stable total chimerism in 10/14 patients. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (35 m follow-up) without any manifestation of SCD, with a high stable 22% Hb F level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of severe forms of sickle cell anemia with bone marrow allograft: French experience (15 cases). SFGM]. 833 53

Fourteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 4/y) vasoocclusive crises (VOC) and recurrent acute chest syndrome episodes (n:10), osteitis (n:3), osteonecrosis (n:3), strokes (n:3) or frequent massive deglobulisation (n:2). Two children undergone splenectomy, 2 were chelated and 2 had erythroid allo-immunization. Ethnic origins were from various countries in Africa (n:10), North-Africa (n:3) or West Indies (n:1). At BMT, they were 2y 3m to 14y 9m old (mean:8y 7m). Donors were AS (n:11) or AA (n:3). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n:12) or 260 mg/kg (n:2); BU:14 mg/kg (n:1), 16 mg/kg (n:9), > 16 mg/kg (n:4); 1 patient received also TLI and one other antithymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n:4) or CSA plus short-term MTX (n:10). Median follow-up was 23 months (8 m. to 48 m.). All patients had an engraftment (d13 to d32) with a stable total chimerism in 10/14 patients who are cured. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (28 m. follow-up) without any manifestation of SCD, with a high stable 22% Hb F level. One patient developed an aplastic anaemia 15 m after BMT: a second BMT was achieved 21 m after the first one with engraftment and total chimerism. Two patients have a relatively stable partial chimerism with still undergoing CSA therapy (11 m. and 23 m. follow-up).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation (BMT) in 14 children with severe sickle cell disease (SCD): the French experience. GEGMO. 837 51

Initial studies of FK506 combined with methotrexate (MTX) in patients receiving unrelated donor BMT have demonstrated a possible-decrease in the incidence of severe GVHD but high rates of severe stomatitis and nephrotoxicity. With this background, we undertook a pilot study evaluating FK506 in combination with a lower than usual dose of MTX in an attempt to improve the tolerability of this immunoprophylaxis regimen. Between July 1993 and October 1994, 26 consecutive adults receiving unrelated donor BMT at Emory University Hospital were enrolled on this study. All patients received FK506 intravenously at an initial dose of 0.03 mg/kg/day beginning day -1 and continuing until oral FK506 was tolerated. Patients also received MTX intravenously at 5 mg/m2 on days 1, 3, 6, and 11. The preparative regimen administered to all but one patient included cyclophosphamide at 200 mg/kg over 4 days followed by total body irradiation (TBI) at 1400 cGy in twice daily fractions over 4 days. The median age of patients was 31 years (range: 19 to 52). Sixteen donor/recipient pairs were matched for HLA-A, -B, and -DR by serology and molecular typing. Ten paris were minor mismatches at either class I or class II. Twenty-two of 26 patients (85%) completed four doses of MTX on schedule. Nephrotoxicity was the most common adverse event associated with the administration of FK506: 88% of patients experienced a doubling of their serum creatinine. One patient died of central nervous system hemorrhage prior to engraftment. Twenty-four of the remaining 25 patients (96%) engrafted. Fourteen of 24 patients (50%) evaluable developed grades 2-4 acute GVHD. The rate of severe (grades 3-4) acute GVHD was 25%. Chronic GVHD developed in 11 of 20 (55%) evaluable patients. At a median follow-up of 461 days, 14 patients (54%) are alive. All are relapse-free with a median Karnofsky performance status of 90% (range: 70-100%). The cumulative probability of 2-year disease-free survival is 50% (95% confidence interval [CI]: 0.33 to 0.77); for low risk patients 67% (95% CI: 0.47 to 0.95) and for high risk patients 23% (95% CI: 0.049 to 1.00). These preliminary data indicate that FK506-based immunosuppression following unrelated donor BMT is effective in preventing severe acute GVHD and warrants comparison to CSA-based regimens.
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PMID:The outcome of unrelated donor bone marrow transplantation in patients with hematologic malignancies using tacrolimus (FK506) and low dose methotrexate for graft-versus-host disease prophylaxis. 920 38

Fifty-two BMT institutions were sent a questionnaire asking for details of dosing for busulphan, cyclophosphamide (bu-cy), cyclosporin and methotrexate (CSA-MTX). The following data were requested: (a) the method used to determine the body weight for dosage calculations (b) the actual dose per weight and (c) the schedule of administration. Thirty-six (69%) institutions responded and 33 were evaluable. There was substantial variation in the method used to determine weight for bu-cy. No single method was used in more than 30% of units, although most units made some allowance for discrepancies between actual and ideal body weight. There was more uniformity in the method of weight determination for CSA-MTX, with the majority of units using actual body weight. Conversely, there was much more variation in the dose per weight formulae and schedules used for CSA-MTX than for bu-cy. These substantial differences highlight the importance of specifying these criteria when the toxicity and efficacy of chemotherapy regimens is reported and the need for further studies to determine the optimal weight formulae for dosage calculations.
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PMID:Variability in determination of body weight used for dosing busulphan and cyclophosphamide in adult patients: results of an international survey. 925 Aug 19

Three hundred and six patients with low- and intermediate-risk leukaemias undergoing allogeneic BMT between 1980 and March 1996 were studied regarding transplantation-related mortality (TRM), relapse, and leukaemia-free survival (LFS). Among the patients were 262 recipients of marrow from HLA-identical siblings and 44 patients receiving marrow from HLA-A, -B, and -DR identical unrelated donors. Between 1986 and 1993, 153 adult patients received ciprofloxacin continuously during Cy conditioning, but since November 1993 ciprofloxacin has not been given until after Cy treatment. TRM at 5 yr showed an incidence of 30%. Significant risk factors in Cox regression multivariate analysis comprised acute GVHD grades II-IV (p < 0.0001), seropositivity for 3-4 herpes viruses prior to BMT (p = 0.002), intermediate risk disease (p = 0.008), female donor to male recipient (p = 0.015), and a donor age over 17 yr (p = 0.025). The risk of relapse was studied from 90 d after BMT, and the overall 5-yr incidence was 32%. Significant risk factors comprised acute leukaemia, as compared to CML (p = 0.003), total body irradiation (TBI) compared to busulphan treatment (p = 0.011), gram-negative prophylaxis with ciprofloxacin during cyclophosphamide (Cy) conditioning (p = 0.024), GVHD prophylaxis using a combination of methotrexate (MTX) and cyclosporine (CSA), compared to monotherapy (p = 0.037) and absence of chronic GVHD (p = 0.050). The 5-yr probability of relapse in patients receiving ciprofloxacin prophylaxis during Cy conditioning was 40%, compared to 24% in patients not receiving this treatment (p = 0.01). Overall, LFS at 5 yr was 49%. LFS was evaluated from day 30 after BMT until relapse or death of the patient. We found no difference in TRM, relapse or LFS between recipients of HLA-identical sibling or unrelated bone marrow, risk factors significantly associated with an inferior LFS included acute GVHD grades II-IV (p = 0.0002), intermediate risk disease (p = 0.003), donor seropositivity for 3-4 herpes viruses (p = 0.046), and TBI conditioning (p = 0.048).
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PMID:Risk factors in bone marrow transplant recipients with leukaemia. Increased relapse risk in patients treated with ciprofloxacin for gut decontamination. 957 94

Unrelated donor (UD) transplantation is the only potentially curative therapy for many leukaemia patients but is associated with a high mortality and morbidity. We sought to identify factors that could be optimised to improve outcome following UD transplantation in adults. Data was retrospectively analysed on 55 patients sequentially receiving UD transplants for CML or acute leukaemia (AL), all of whom received serotherapy for the prevention of GVHD and rejection. All patients received standard conditioning regimens. The first 28 patients transplanted also received combined pre- and post-transplant serotherapy with Campath 1G (days -5 to +5) and standard dose CsA plus MTX as GVHD prophylaxis (protocol 1). The subsequent 27 patients received a 5-day course of pre-transplant serotherapy alone either with ATG (CML patients) or Campath 1G (AL patients) on days -5 to -1 inclusive, with high-dose CSA plus MTX (protocol 2). The incidence of acute GVHD was low with no patient receiving either protocol developing > grade 2 disease. The use of protocol 2 and the administration of a bone marrow cell dose above the median (2.17 x 10(8)/kg) were the most important factors predicting engraftment (P = 0.03 and P = 0.001, respectively) but this only remained significant for cell dose in multivariate analysis (P = 0.03). Overall survival for the group was 45% at 3 years and was influenced by both age (P = 0.02) and disease status at transplantation (P = 0.001). Receiving a cell dose above the median was also associated with a trend towards better survival (P = 0.08), due primarily to a reduction in the TRM to 8.2% compared with 54.5% in those receiving a lower cell dose (P = 0.002). We conclude that pre-transplant serotherapy alone is highly effective at preventing acute GVHD following UD BMT and that additional post-transplant serotherapy does not confer any benefit. Furthermore, a high marrow cell dose infused has a major effect in reducing transplant related mortality following UD BMT.
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PMID:The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia. 1072 85


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