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)

Platelet recovery after allogeneic bone marrow transplantation for treatment of different haematologic disorders was monitored by ability of sera from BMT recipients to support the clonal growth of normal megakaryocyte progenitors. The resultant megakaryocyte colonies were expressed as a Serum Factor Index-Megakaryocyte (SFI-Mk). In two patients with whole and in one with partial haematological reconstitution SFI-Mk was normal, and in others SFI-Mk value was increased. Our results indicate that sera from BMT recipients contain megakaryocytopoietic activity which inversely correlate with recovery of megakarycytic lineage following bone marrow transplantation.
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PMID:Serum megakaryocytopoietic activity after allogeneic bone marrow transplantation (BMT). 170 16

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

The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. To determine the relationship of endogenous thrombopoietic cytokine levels and circulating platelet (PLT) counts, we measured the levels of thrombo-poietin (TPO), interleukin-11 (IL-11), and interleukin-6 (IL-6) in patients with significant thrombocytopenia secondary to both marrow hypoplasia and increased PLT destruction. Increased endogenous levels of TPO and IL-11, but not IL-6, were detected in bone marrow transplant patients with thrombocytopenia following myeloablative therapy (BMT/MAT) (TPO: 1,455.5 +/- 87.3 pg/mL, [PLT 39,600 +/- 7,800/microL], P < .001, n = 12; IL-11: 227.9 +/- 35 pg/mL, [PLT 32,900 +/- 57,000/microL], P < .05, n = 19; IL-6: 25.8 +/- 8.4 pg/mL, [PLT 32,800 +/- 5,057/microL], P > .05, n = 4] v normal donors [TPO < 150 pg/mL, n = 8; IL-11 < 50 pg/mL, n = 9; IL-6 < 10 pg/mL, n = 5 [PLT 203,000 +/- 7,500/microL]. There was a significant inverse correlation between endogenous levels of TPO and IL-11, but not IL-6, and PLT counts in the MAT/BMT patients (TPO: r = -0.57, P < .0001, n = 188; IL-11: r = -0.329, P < .0001, n = 249; IL-6: r = -0.1147, P > .05, n = 62). In patients with immune thrombocytopenia purpura (ITP), with decreased PLT survival, but intact bone marrow megakaryocytopoiesis, endogenous IL-11 levels were significantly increased (328.0 +/- 92.6 pg/mL, [PLT: 20,900 +/- 3,000/microL], P < .05, n = 25). However, endogenous TPO levels remained undetectable (< 150 pg/mL, [PLT 30,500 +/- 5,500/microL], n = 15). These results suggest that there may be differential mechanisms regulating endogenous TPO, IL-11, and IL-6 levels during acute thrombocytopenia and suggest that the absolute number of circulating PLTs may not always be the sole regulator of endogenous TPO levels. Other mpl-expressing cells of the megakaryocyte lineage may contribute to the regulation of circulating TPO levels as well. Our results also suggest IL-11 levels may in part, be regulated by a negative feedback loop based on circulating PLT counts, but also may, in part, be regulated by a variety of inflammatory agonists. Both TPO and IL-11, therefore, appear to be active thrombopoietic cytokines regulating, in part, megakaryocytopoiesis during states of acute thrombocytopenia.
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PMID:Differential mechanisms in the regulation of endogenous levels of thrombopoietin and interleukin-11 during thrombocytopenia: insight into the regulation of platelet production. 889

A retrospective immunohistological and morphometric study was performed on bone marrow trephine biopsies derived from 113 patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph(1+)-CML) before and at standardized intervals following allogeneic transplantation (BMT) with full unmanipulated marrow specimens. The purpose of this investigation was to quantify CD34+ progenitor cells and to determine their dynamics during the post-transplant period. Moreover, we tried to correlate their number with corresponding changes in the amount of nucleated erythroid precursors and megakaryocytes including pro- and megakaryoblasts and the fiber content. Monitoring the quantity of precursors after BMT revealed a very rapid recovery in comparison to a control group. However, a more detailed evaluation showed that at day 22 +/- 6 a higher number of progenitor cells was significantly associated with an earlier independence for platelet transfusion and also with a more pronounced growth of erythro- and megakaryopoiesis including their precursor cells. Furthermore, a slight increase in the density of the fibrous matrix (reticulin fibers) was present in these patients that were characterized by a more favorable engraftment. The latter feature sheds some light on the complex pathomechanisms of homing and differentiation of progenitors. In confirmation with in vitro findings, this phenomenon is dependent on proper anchoring sites to the fibrous bone marrow stroma. Finally, the size of a full BM graft exerted a distinctive influence on the number of CD34+ precursors in the early post-transplant period. In conclusion, the present study has validated a number of BM features by focusing on the CD34+ progenitor cells and associated hematopoietic reconstitution including reticulin fibers and precursor cells of the erythroid and megakaryocyte lineage, which are not readily evaluable by fluorescence-activated cell sorting (FACS) analysis.
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PMID:Dynamics of CD34+ progenitor cells following allogeneic bone marrow transplantation in Ph1+CML--an immunohistochemical study on 113 patients with sequential trephine biopsies. 1218 41

The BMT program at Princess Margaret Hospital performed 105 transplants using cryopreserved peripheral blood stem cells (PBSC) from related allogeneic donors. The outcomes were compared with those of a historic control of 106 patients transplanted with freshly procured PBSC. The infusions were tolerated with limited toxicity related to nausea/vomiting or bradycardia, correlated with the total amount of DMSO infused. The average viability of the total nucleated cell (TNC) population after thawing was 71%. The survival of clonogenic progenitors amounted to 75% for colony-forming unit-granulocyte-macrophage (CFU-GM), 69% for burst-forming units erythroid (BFU-E), and 78% for colony-forming units granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM). In contrast, colony-forming units megakaryocyte (CFU-MEG) was significantly more cryosensitive with recovery rates of 39%. The number of viable CD34(+) cells transplanted was correlated with the number of transplanted viable CFU-GM (P < .001), BFU-E (P < .001), CFU-MEG (P < .001), and CFU-GEMM (P = .049), but not with the TNC dose. The number of transplanted CD34(+) cells was correlated with engraftment of neutrophils (P = .012) and platelets (P = .013). The outcomes of cryopreseved or fresh PBSC transplants (PBSCT) with respect to engraftment of neutrophils (P = .178) and platelets (P = .785), lymphocyte recovery (P = .926), acute (P = .113), and chronic graft-versus-host disease (P = .673), recurrence (P = .295), nonrelapse mortality (P = .340), and overall survival (P = .668) were not significantly different. It is therefore reasonable to consider the option of cryopreserved allografts.
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PMID:Similar outcomes of cryopreserved allogeneic peripheral stem cell transplants (PBSCT) compared to fresh allografts. 1788 61