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 order to further improve the cure rate in AML we investigated the effect of more chemotherapy--in terms of its intensity and its duration--in 2 studies. In our 1981 study patients received TAD 1-2 courses for induction, 1 course for consolidation and randomly no further treatment or monthly myelosuppressive maintenance for 3 years. Evaluating 213 responders remission duration was clearly longer in the maintenance group with 24% CCR after 5 and 10 years. In our 1985 study the same successful strategy was further intensified by a second induction course given regardless of response to the first course to all patients up to 60 years of age while older patients received standard induction as before. This age-adapted concept resulted in a further increase of 5 years CCR in the 461 responders to as much as 34% not achieved for unselected patients in other multicenter trials. 20 patients receiving auto-BMT in first CR show the same relapse free survival as their counterparts receiving chemotherapy according to the 1985 protocol in a matched-pair analysis. We conclude that both very early intensification and prolonged maintenance contribute to a higher cure rate that is not further improved even by a maximum intensity short-term treatment. The limits of chemotherapy in AML may be overcome by modulating its myelotoxicity and antileukemic potency using GM-CSF as shown in 2 studies of our group.
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PMID:Longterm effects of prolonged maintenance and of very early intensification chemotherapy in AML: data from AMLCG. 157 46

We describe an exceptional case of Candida tropicalis sepsis in a patient submitted to allogeneic BMT; the diagnosis was made on a peripheral blood smear, when the pt was neutropenic and only mildly febrile. The combination of GM-CSF to accelerate hematological recovery and the possibility of administering large doses of a liposomal form of Amphotericin B were the contributing factors to the resolution of the infection.
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PMID:An unusual case of Candida tropicalis sepsis in a patient submitted to allogeneic bone marrow transplantation. 209 67

It appears that part of the confusion surrounding the lineage of NS cells could be due, in part, to the presence of more than one cell population in normal BM. Whether other cell populations exist in other organ compartments, or can be induced, is presently unknown. This is of particular interest in allogeneic BMT where various lymphocyte depletion techniques have been employed to reduce the incidence of AGVHD. When CCE is used for depletion, the NS lymphocyte component is entirely removed. Since the incidence of AGVHD is significantly reduced with CCE lymphocyte-depleted rat and human BM, it appears that this subpopulation need not be present to abrogate AGVHD. Quite surprisingly, preliminary studies in rats indicates that this lymphocyte subpopulation may actually induce acute syngeneic GVHD (Fischer et al., 1989). That a cell(s) in the clonogenic compartment has the ability to suppress or down-regulate a variety of immune responses is not altogether surprising. This cell is better thought of as an auto-regulatory cell which has the ability to control the cellular interactions in its immediate micro-environment. Indeed, R/O NSCA can be augmented by GM-CSF, IL-3, and CsA (NoGa et al., 1988a). In vitro, this cell differentiates into the mono-myeloid series using a variety of stimulatory agents and can acquire tumoricidal activity. The ability to express NSCA is lost however, being present only during a brief window of early maturation. Only IL-3 can sustain NSCA in culture.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elutriation of bone marrow delineates two distinct natural suppressor cell populations. 213 33

Purified human urinary CSF-1 was used for production of polyclonal CSF antibodies in rabbits. The purified CSF was iodinated by a modified chloramine-T technique with retention of biologic activity. Dilutions of anti-CSF were reacted with 15,000 cpm of 125I-CSF in EDTA-phosphate buffer for 48 hr. Sheep antirabbit serum was added for 3 hr to precipitate the tracer-anti-CSF complex. A 1:1000 dilution of anti-CSF caused 60-90% precipitation of tracer; optimal conditions were observed with a 1:30,000 dilution. Linear displacement curves were obtained with 2-50 U of pure CSF-1. Related hormones did not cross-react in the assay; no displacement was seen with human GM-CSF, IL-1, IL-2, IL-3, EP, LH or FSH. Reactivity was also not observed with murine GM-CSF or IL-3. Ten normal human sera yielded CSF values of 91-138 U/ml in 5 assays. Urine values were 72-105 U/ml. When 32 U of pure CSF-1 was added to normal serum and urine samples, quantitative recovery was observed. Serial assays revealed a rise in serum and urinary CSF during marrow aplasia in a patient undergoing autologous BMT; CSF values returned to normal during the recovery phase. This sensitive and specific radioimmunoassay should prove useful in the further study of CSF-1 responses in vivo.
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PMID:Development of a radioimmunoassay for human macrophage colony-stimulating factor (CSF-1). 266 Jun 70

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

Bone marrow transplantation improves the chances of survival in a variety of hematological malignancies. However, infectious complications during the post-transplant phase contribute significantly to morbidity and mortality. To reduce the duration of granulocytopenia, which is approximately 20 days after BMT, in this study patients with ALL, relapsed or high-grade NHL, relapsed or refractory HD, or Neuroblastoma stage III/IV, were given rh GM-CSF to assess the effects on hematological and immunological reconstitution after conditioning therapy and BMT. The results of 9 patients are presented. After autologous BMT and subsequent rh GM-CSF therapy, a peripheral blood neutrophil count of 500/microliters was reached within 8-12 days, i.e., between 7 and 10 days earlier than would have been expected without rh GM-CSF. Furthermore, it appeared that rh GM-CSF was useful in case of insufficient bone marrow regeneration post autologous transplant. The influence of rh GM-CSF after allogeneic BMT is not yet clear. Further studies will be necessary to evaluate the potential of this promising new drug after BMT.
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PMID:Recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) after bone marrow transplantation. 307 46

G-CSF and GM-CSF enhance the rate of neutrophil engraftment in autologous bone marrow transplantation (ABMT) without significantly affecting platelet engraftment. Peripheral blood progenitor cells (PBPC) may enhance rates of engraftment of both neutrophils and platelets. We treated 49 patients undergoing ABMT with a course of G-CSF to obtain PBPC and infused these cells post-transplant with G-CSF in an attempt to determine factors which might correlate with enhanced BM engraftment. Forty-nine patients with Hodgkin's disease, non-Hodgkin's lymphoma or breast cancer undergoing unpurged ABMT were studied. G-CSF priming consisted of an outpatient 8 day course of 5 micrograms/kg/day followed by three leukaphereses (on day 5, 7 and 8) to collect PBPC. Patients then received a chemotherapeutic BMT preparative regimen followed by an infusion of PBPC, autologous BM and the reinstitution of G-CSF (16 micrograms/kg/day). BM engraftment was rapid. The median time to achieve 0.5 x 10(9)/l neutrophils was 10 days compared with a historical BMT control patient population receiving the same preparative regimens of 19 days (p = 0.001). Time to achieve a platelet count of 20 x 10(9)/l was 16 days compared with a historical control of 22 days (p = 0.001). Neutrophil engraftment occurred in all patients by day +14. Marrow engraftment correlated with the total number of CD34+ cells infused as well as the total number of mononuclear cells infused but not the total number of CD34+/CD33- cells infused. The amount of total blood volume pheresed significantly correlated with yield of total mononuclear cells. Prior exposure to radiation therapy negatively correlated with progenitor cell yield.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:G-CSF primed peripheral blood progenitor cells in autologous bone marrow transplantation: parameters affecting bone marrow engraftment. 751 Oct 16

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

This retrospective study evaluates the impact of GM-CSF and interleukin 3 (IL-3) on bone marrow (BM) and peripheral blood (PB) cell recovery following autologous bone marrow transplantation (ABMT) with mafosfamide-purged BM in patients with lymphoid malignancies compared with a control group receiving no colony-stimulating factor. GM-CSF was administered at 250 micrograms/m2/day (8 patients) as a continuous infusion from day of autologous BMT until the absolute neutrophil count (ANC) reached 0.5 x 10(9)/l for 7 days or until day 30, whichever was first. IL-3 was administered daily starting on the first day of transplant at a dose of 1 microgram/kg/day (6 patients) and 5 micrograms/kg/day (6 patients) for 30 days. CFU-GM and BFU-E were sequentially evaluated in BM and PB at days 7, 14, 21, 28, and 56 post-graft. The neutrophil recovery (ANC > 0.5 x 10(9)/l) was significantly faster in the GM-CSF group compared with IL-3 5 micrograms, IL-3 1 microgram and control group (respectively, days 15, 21, 22, 24) (p < 0.05 to p < 0.01). Similarly, leukocyte recovery was faster in the GM-CSF group compared with control and IL-3 1 microgram groups (p < 0.01 and p < 0.05). No difference was noticed between the two IL-3 groups. Although no difference was observed in platelet recoveries (> 50 x 10(9)/l), it appeared that the GM-CSF group required more units of platelets than either the IL-3 1 microgram or 5 micrograms groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo effects of GM-CSF and IL-3 on hematopoietic cell recovery in bone marrow and blood after autologous transplantation with mafosfamide-purged marrow in lymphoid malignancies. 799 41


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