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)

A 36-year-old man was diagnosed as having RAEB in 1986, and required blood transfusion regularly because of severe anemia. He received the first bone marrow transplantation following total-body irradiation and etoposide infusion in October 1987. He was found to be relapsed into RAEB on 106th day after BMT. And the second BMT was planned. According to the conditioning regimen of Tutschka, et al, we administrated busulfan and cyclophosphamide before re-transplantation. On 26th day after BMT, the WBC count exceeded 1,000/microliters and anemia was improved, while thrombocytopenia persisted until 50th day. Normal hematopoiesis in the bone marrow was confirmed on the 29th day. No severe side effect except for a little fevering and bleeding was found during the clinical course. Unfortunately he died of pneumonia following graft versus host disease on the 166th day after re-BMT. This new conditioning regimen is considered to be a choice for the high risk patients on re-transplantation.
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PMID:[Bone marrow re-transplantation following a busulfan and cyclophosphamide regimen]. 221 94

8 patients with severe and 4 with non-severe aplastic anaemia, aged 7 to 46 years, whose suppressor lymphocyte activity was in most cases elevated and who had no histocompatible sibling donor, underwent 1-2 courses of ALG/ATG treatment. 6 patients got CR and 1 PR and during 1-4 years they live with sustaining haemopoiesis, independent of blood transfusion (except one in PR). Among these seven responders increased suppressor lymphocyte activity normalized in 6. The adverse effects of the treatment were granulocyto- and thrombocytopenia, subfebrile states, hepatotoxicity, serum sickness and skin allergy. Five patients died because of early or late complications of the treatment or it's failure. Our results, similar to other authors', are like after BMT and supports the immunological mechanism of A.A. Immunosuppressive treatment with ALG/ATG has many advantages: no need to have identical bone marrow donor, no GVHD, possibility of treatment of patients over 30, even pretreated with blood transfusions, and finally much lower costs and efforts.
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PMID:ALG/ATG treatment--a useful alternative for BMT in selected aplastic anaemia patients. 248 Feb 77

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

This article has outlined the special problems associated with evaluation of bone marrow before and after BMT. Marrow grafting has become a major form of therapy in oncology and hematology whose potential is only beginning to be fully realized. The transplantation of healthy hematopoietic and lymphoid cells has made possible the use of otherwise superlethal doses of radiation and chemotherapy in preparing the patient for engraftment. In the case of tumors, this allows massive doses of tumorocidal therapy prior to rescue with a BMT. In the case of aplastic anemia, it allows massive immunosuppression and ablation of the residual host marrow in preparation for replacement by the healthy donor marrow. The complications of this procedure include the toxicity of chemotherapy and irradiation upon the liver, lung, and gut as well as less serious toxicity to skin and other organs. The double barrier associated with marrow transplantation consists of rejection and GVHD. Marrow graft failure occurs by two distinct mechanisms, graft resistance and graft rejection. The former is marked by a total failure of any evidence of engraftment and the latter by engraftment followed by disappearance of the graft. GVHD is the immunologic attack upon host tissues by donor lymphoid cells (predominantly mature T cells). In the acute phase, it attacks liver, skin, and gut, with the latter producing the most life-threatening syndrome. Chronic GVHD resembles scleroderma. Treatment of GVHD includes the use of prednisone, cyclosporin A, ATG, and monoclonal antilymphoid antibodies. Prevention includes the attempt to remove T cells from the donor marrow with monoclonal antibodies using complement-mediated cytolysis and other approaches such as conjugation of antibodies to ricin and other toxins. GVHD also produces severe immunosuppression in and of itself added to that produced by chemoirradiation therapy. As a result, the marrow transplant recipient is extremely susceptible to infections. During the early period, the patient is granulocytopenic and susceptible to bacterial and fungal infections, which are dealt with by antibiotics and isolation procedures. Later, viral infections become very important, particularly CMV and other herpes viruses. The relative success in dealing with bacterial and, to some extent, viral infections has brought fungal infections to the fore as major causes of death, especially in higher risk categories of patients. Hemorrhage is a frequent complication owing to delayed megakaryocyte engraftment and thrombocytopenia during the early period and is a serious problem in patients with GVHD of the gut.
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PMID:Pathology of bone marrow in transplant recipients. 306 26

Administration of G- and GM-CSF increases the neutrophil counts in a number of clinical situations. GM-CSF shows the additional effect of increasing the number of monocytes and eosinophil granulocytes. Both G- and GM-CSF affect of neutrophil functions, in the case of GM-CSF there are some potentially negative effects on neutrophil migration and adhesiveness. The clinical relevance of the various effects on mature haematopoietic cells is not fully understood. Clinical data with G-CSF treatment indicate that increased levels of neutrophil granulocytes following cytotoxic chemotherapy may translate into clinical benefit such as a decreased rate of neutropenic infection and an increased cytotoxic chemotherapy dose even though the data are conflicting and the risk of "laboratory cosmetics" is apparent. Regarding treatment with GM-CSF following chemotherapy, the clinical benefit is unclear. The clinical benefit of GM-CSF-induced monocytes and eosinophils is unknown. G- and GM-CSF accelerates neutrophil recovery following autologous or allogeneic BMT. The influence on neutropenic infections is, however, less impressive. Pretreatment with G- or GM-CSF increases the yield of peripheral stem cell harvest, thereby reducing the number of leukaphereses needed. Transplantation of G- and GM-CSF primed autologous peripheral stem cells tends to reduce the period of post-transplant cytopenia, particularly thrombocytopenia, in comparison with traditional ABMT. In patients with MDS, G- and GM-CSF appear to increase the number of neutrophil granulocytes and there is some evidence that patients with severe infectious problems will benefit from this treatment. However, little influence was seen on the main clinical problems with these patients, which are anaemia and thrombocytopenia. In conclusion, G- and GM-CSF are two different proteins with different properties in vivo and in vitro. GM-CSF has, compared with G-CSF, more complex pharmacological effects and a more trouble-some side-effect profile. Early clinical development indicates that both compounds have a substantial influence on the levels of certain blood cells. Whether the increases in different blood cells translate into long-term clinical benefit for greater patient groups is the focus of ongoing research. The effects of G- and GM-CSF may be potentiated by other cytokines, an area which is presently being explored.
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PMID:G- and GM-CSF in oncology and oncological haematology. 751 79

Myelosuppressive toxicity is dose-limiting for radioimmunotherapy. We have reported on the use of cytokine intervention (rhIL-1 and rmGM-CSF) to stimulate differentiation of progenitor cells and reduce radioantibody-induced leukopenia and thrombocytopenia (J. Natl. Cancer Inst. 84:399, 1992; Cancer 73:1073, 1994). As an alternative to the use of cytokines, we investigated the effect of syngeneic bone marrow transplantation on the ability to dose-escalate radioantibody. Injection of 10(7) bone marrow cells from a donor mouse 6 to 8 days after a 340- to 360-microCi dose of radioantibody (LD100/28)--a 25 to 30% increase above the maximal tolerated dose--resulted in 100% survival. This observation is associated with a recovery in neutrophil and thrombocyte counts within 21 days of therapy (normal recovery after 275 microCi takes 42 days). None of the mice survived when BMT was done at either 4 or 11 days after radioantibody. Marrow from normal donor mice was more effective than that from cytokine-primed mice whose marrow cells were actively cycling after a 5-day course of IL-1/GM-CSF. The combination of the two myeloprotective approaches, BMT plus a 14-day schedule of IL-1 (2 x 10(3) U/d) and GM-CSF (1 microgram/d) intervention, provided a greater stimulation of peripheral WBC counts than either approach alone; however, further dose escalation under these conditions was not feasible. The 30% intensification in radioantibody dose offers a therapeutic advantage for both bulky disease (GW-39 subcutaneous nude mouse model) and micrometastatic disease (GW-39 intrapulmonary model). In the bulky tumor model, the increase in administered dose resulting from BMT extends the 8-week growth delay observed at 275 microCi 131I-MN-14 IgG by an additional 7 weeks. In the metastatic model, dose intensification increased median animal survival from 15 to 23 weeks. Therefore, by optimizing the use of BMT, a greater therapeutic benefit can be derived from radioantibody therapy in a solid tumor model. This study represents a proof of principle, that BMT can be effective for low-dose-rate therapy as it has been for short-duration intense chemotherapy and radiation therapy. It also highlights several important issues to consider when attempting to apply the method in the clinic.
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PMID:Improved experimental cancer therapy by radioantibody dose intensification as a result of syngeneic bone marrow transplantation. 765 29

We have previously demonstrated an inverse relationship between circulating endogenous G-CSF levels and myeloid engraftment post-BMT. A new early-acting hematopoietic growth factor, Steel factor (SLF), has recently been demonstrated to induce the proliferation of early hematopoietic progenitor cells and synergistically stimulate committed progenitor cells in the presence of lineage-specific CSFs. In this pilot study, we determined the temporal relationship between endogenous SLF levels and the circulating absolute neutrophil count (ANC) (myeloid engraftment) in both children and adults undergoing both allogeneic and autologous BMT. Pre-BMT SLF levels were 2600 +/- 100 pg/ml compared to significantly lower levels of G-CSF (30-50 pg/ml). The circulating SLF level was significantly decreased throughout the post-BMT period (ANC < or = 200 x 10(6)/l: 1500 +/- 600 pg/ml; ANC 200-500 x 10(6)/l: 1780 +/- 130 pg/ml; ANC > or = 500 x 10(6)/l: 1690 +/- 110 pg/ml) (p < 0.001). There was a lack of an inverse relationship between the circulating SLF level and the ANC (r = -0.43) (p = NS). For comparison, SLF levels from immune thrombocytopenia (platelet < = or 20 x 10(9)/l) and chemotherapy-induced neutropenia patients (ANC < or = 200 x 10(6)/l) were similar to pre-BMT levels but significantly higher than post-BMT levels (p < or = 0.02 and < or = 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased endogenous circulating Steel factor (SLF) levels following allogeneic and autologous BMT: lack of an inverse correlation with post-BMT myeloid engraftment. 767 98

Twenty-four patients with a variety of malignant diseases (13 lymphoma, 4 myeloma, 1 ALL, 6 solid tumours) were treated with the alkylating agents busulphan and melphalan as a preparative regimen for autologous BMT. Thirteen males and 11 females, aged 27-53 years (median 39.5 years) received oral busulphan 1 mg/kg q6 h on days -6 to -3, followed by i.v. melphalan 140 mg/m2 on day -2 and infusion of cryopreserved haemopoietic cells on day 0. The major toxicity seen was gastrointestinal with nausea, vomiting and diarrhoea in 17 patients and severe mucositis in 22. There was no evidence of cardiotoxicity, nephrotoxicity, haemorrhagic cystitis or clinical signs of hepatic veno-occlusive disease. Twenty-three patients engrafted with the median duration of neutropenia (< 0.05 x 10(9)/l) 10 days (range 5-63 days) and thrombocytopenia (< 50 x 10(9)/l) 43 days (range 5-350 days). Three patients died of transplant-related complications. Of 15 evaluable patients with active disease at BMT, 9 responded and 6 were refractory. Sixteen evaluable patients were in CR after BMT. Seven relapsed, 1 died in remission and 8 remain in CR 12-46 months (median 29 months) later. Of the group of 13 lymphomas, overall and relapse-free actuarial survival at 36 months was 64% and 58%, respectively, while for the entire group of 24 patients these values were 39% and 34%. Busulphan and melphalan is a safe and inexpensive conditioning regimen for autologous BMT with acceptable toxicity and substantial antitumour activity particularly against lymphomas.
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PMID:Busulphan and melphalan prior to autologous bone marrow transplantation. 827 31

A 12 year-old female patient suffering from multifocal Ewing's Sarcoma underwent bone marrow transplantation in March 1992. The donor was the patient's HLA-identical brother. On day 38 following BMT, an occluding catheter thrombosis of the superior vena cava was diagnosed. Lysis therapy using rt-PA was initiated. During therapy, serious bleeding occurred and administration was temporarily discontinued. Normalisation of previously high fibrinogen levels during an acute phase reaction was seen concomitantly with systemic fibrin and probably also fibrinogen fragments as demonstrated using the Western blot technique. Lysis therapy resulted in regained catheter patency, while thrombosis of the superior vena cava persisted. The reduction in the need for the transfusion of packed thrombocytes following lysis was seen as being a positive result. The use of rt-PA following BMT should be carefully weighed against the risks and requires careful patient observation. Due to the systemic fibrinolytic and fibrinogenolytic effects combined with mucositis and thrombocytopenia as a result of transplantation therapy, a high risk of bleeding complications seems likely.
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PMID:[Use of recombinant tissue plasminogen activator (rt-PA) in occluding thrombosis of a Hickman catheter after bone marrow transplantation: clinical and coagulation physiologic aspects]. 830 9

Despite intensification of treatment with high-dose chemotherapy (HDC) and autologous bone marrow transplantation (AMBT), the prognosis of poorly responding metastatic neuroblastoma remains bad. Recombinant IL-2 (rIL-2) was used after ABMT to enhance the immune response against the tumor and thereby to improve survival of these patients. In this study, five courses of rIL-2 were administered as a continuous intravenous infusion every 2 weeks, the first course lasting 5 days, and the other four 2 days. rIL-2 treatment was to begin within 120 days of BMT. This study demonstrates the feasibility of rIL-2 soon after HDC and ABMT. The maximum tolerated dose (MTD) was 12 x 10(6) U/m2/day. Clinical toxicity was similar to that observed in adults, moderately increased by the proximity of ABMT; in a previous study we demonstrated that the MTD in non-grafted children was 18 x 10(6) U/M2/day. Nevertheless, half of the patients were not able to receive rIL-2 therapy after ABMT, and only 6/12 received 100% of the planned dose, mainly because of thrombocytopenia. If peripheral stem cell transplantation is demonstrated to enhance platelet recovery, more patients could be treated with rIL-2 with the present schedule. Earlier administration of low-dose rIL-2 after BMT associated with ex vivo rIL-2 treatment of the graft could be a more valid way of using rIL-2 to improve survival.
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PMID:Phase I-II study of interleukin-2 after high-dose chemotherapy and autologous bone marrow transplantation in poorly responding neuroblastoma. 852 66


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