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)

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

A male patient with CML received a BMT from his sister and developed chronic GVHD. The host-origin normal karyotype (46,XY) was identified for the first time in the 60th month after BMT. Detection of Y-chromosome-specific DNA in BM and peripheral blood (PB) showed that all BM samples obtained 6 months from BMT were positive for Y-specific DNA, while PB became positive in the 60th month after BMT. The BCR-ABL mRNA derived from leukemic cells was detected in the 36th month post-BMT, but not in the 60th month or thereafter. Fluorescence in situ hybridization revealed that 1.5% and 0.6% in BM and PB cells were Y-positive in the 70th month post-BMT, respectively. DNA analysis of hematopoietic progenitor colonies revealed 1 of 42 erythroid colonies to be host derived. These results indicate that host-origin hematopoietic cells survive chronic GVHD, while the Ph1 clone was eliminated.
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PMID:Hematopoietic recovery from host progenitors with normal karyotype devoid of Philadelphia chromosome in a patient with CML after allogeneic BMT. 837 40

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

(1) The polymerase chain reaction (PCR) was used to amplify Rh-related cDNAs from erythroid cells cultured by the selective two-phase liquid culture system for human erythroid progenitors in peripheral blood. Two Rh polypeptide cDNAs have been isolated from the PCR products and tentatively designated RhPI cDNA and RhPII cDNA. Both cDNA clones have an open reading frame composed of 1251 nucleotides. The RhPI cDNA clone shows a single nucleotide substitution with no amino acid substitution compared with the published sequence. The RhPII cDNA clone differs from the above by 41 nucleotide substitutions in the open reading frame, resulting in 31 amino acid substitutions. Besides these cDNA clones, eleven and five truncated isoforms of the RhPI and RhPII cDNAs, have been isolated, respectively. (2) The promoter region of the Duffy gene was cloned by IPCR of 1.1 kb SacI fragment and the 3' flanking sequence was cloned by IPCR of 1.9 kb EcoRI fragment. The IPCR products contained the known Duffy cDNA sequence without introns. By comparing the coding area of the Duffy gene in 28 Duffy positive individuals, we elucidated that one base change that results in an amino acid substitution (GAT(Asp44)-->GGT(Gly)) is in accordance with the Fya/Fyb polymorphism. This fact proves that the Duffy cDNA and its gene encode the Duffy blood group system. (3) Two common alleles in Esterase D (EsD) polymorphism, EsD1 and EsD2 were characterized by the substitution of one amino acid (Gly-Glu) caused by the point mutation of one nucleotide (G-A). The point mutation between cDNAs of EsD1 and EsD2 alleles was detectable as restriction fragment length polymorphism (RFLP) using Ssp1. The RFLP makes it possible to determine the EsD phenotypes using DNA samples from forensic materials without EsD enzymatic activity. (4) The authors report studies on 19 pairs of donors and recipients in bone marrow transplantation. A broad range of genetic markers at 42 gene loci, including one DNA marker 11 red blood cell markers, five human lymphocyte antigen types, 12 serum protein markers, five red cell enzyme markers, and eight salivary markers was evaluated before and after BMT over about 2 months. As a result, 11 out of 42 gene loci of genetic markers in recipients were transformed into the donor type.
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PMID:Molecular genetic basis of red cell markers and its forensic application. 869 Mar 20

Previous studies have shown that, unlike in patients submitted to allogeneic BMT, administration of recombinant erythropoietin (Epo) after autologous BMT (ABMT) had no significant effect on erythroid recovery and transfusional requirements. On the other hand, it has also been shown that combining Epo with recombinant granulocyte colony-stimulating factor (G-CSF) in patients with the acquired immunodeficiency syndrome (AIDS) and with myelodysplastic syndromes resulted in additive effects on erythropoiesis. To test the effects of combined G-CSF + Epo therapy on erythroid recovery after autologous bone marrow transplantation a pilot randomized, three-arm trial was designed. Thirty patients suffering from lymphoid malignancies submitted to ABMT were randomly assigned to receive G-CSF alone (5 micrograms/kg, from day + 1 up to reaching an ANC > or = 10(9)/1), G-CSF + Epo (150 U/kg, from day +1 to +21), or neither of these (controls). Patients receiving G-CSF + Epo had significantly more reticulocytes on day +21 and reached 30 x 10(9)/1 reticulocytes earlier when compared to both G-CSF and control patients; however, the number of red blood cell (RBC) transfusions was not modified by the addition of Epo to G-CSF, although both groups had significantly fewer units transfused than controls. No effect on platelet recovery or platelet transfusional requirements was observed. Myeloid recovery was comparable in the G-CSF and G-CSF+Epo groups, and significantly accelerated as compared to controls. We conclude that the addition of Epo to G-CSF causes a slight acceleration of erythroid recovery after ABMT, but is not associated with transfusional benefits. Therefore, the present data do not support the use of Epo in association with G-CSF to hasten erythroid recovery after ABMT.
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PMID:Combination therapy with G-CSF and erythropoietin after autologous bone marrow transplantation for lymphoid malignancies: a randomized trial. 872 49

A major concern with allogeneic BMT for treating most inherited diseases is the need to overcome graft rejection with conditioning chemotherapy which is associated with a relatively high morbidity and mortality. This can be eliminated if the transplant is done in utero when the fetus is unable to reject donor hematopoietic stem cells (HSC). We studied the efficacy of T cell-depleted (TCD) parental bone marrow as a source of HSC for transplantation into early gestation non-defective fetal rhesus monkeys. Thirteen opposite sexed TCD transplants were done into 44 day fetal recipients and 12 into 61 day recipients (165 day total gestation). The procedure-related mortality was 8%, all in the earlier age group. The overall survival was 60% at birth with a projected survival of 44 +/- 10% at 1.5 years with no difference between the two age groups. We used a PCR assay for the rhesus Y chromosome to detect male donor cells in female recipients (six animals transplanted at 44 days and five at 63 days). The overall engraftment rate was 73% with no difference as a function of gestational age at transplant. In six long-term surviving engrafted females we detected donor cells in the peripheral blood and bone marrow up to 3 years of age. We found a delay in the appearance of donor cells in the peripheral blood in engrafted animals, in some cases for up to 6 months post-BMT. In vitro mixed lymphocyte reaction and cell-mediated lymphocytotoxicity studies between the recipient and donor cells indicate that tolerance was induced to donor cells. Individual and pooled erythroid and myeloid marrow colonies grown in methyl cellulose were collected and analyzed for donor origin by PCR. The amount of donor cells in marrows from long-term engrafted animals was < 0.1%. In a fetal recipient studied at 35 days post-BMT, donor cells were detected in bone marrow and liver in both erythroid and myeloid lineages. These results indicate that TCD parental marrow can durably engraft in utero. While the engraftment rate is similar to that seen with fetal liver as the source of HSC, the degree of peripheral blood engraftment (percent donor cells) in this non-defective primate model is low. It will require increasing the percent pre-or postnatally for this approach to be clinically relevant in those disorders in which there is no selective survival advantage for normal engrafted donor cells.
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PMID:Long-term engraftment following in utero T cell-depleted parental marrow transplantation into fetal rhesus monkeys. 880 29

Recipients of bone marrow (BMT) or peripheral blood progenitor stem cells (PBSCT) transplant have in the period following transplantation a frequent need for red blood cell transfusions and therefore an increased risk of blood-transmitted infections. The anaemia is caused mainly by myelosuppression after high-dose chemotherapy, but an impaired erythropoietin (EPO) production and an inappropriate EPO response may also contribute. Since recombinant human erythropoietin (rHuEPO) has been established as a treatment for renal anaemia it has been of interest whether treatment may be of benefit in the transplant setting. This paper gives an overview of the studies conducted to date with rHuEPO treatment in patients receiving bone marrow transplants. Current data do not support any transfusional benefits when rHuEPO is used in patients receiving autologous transplants. However, in patients receiving allogeneic transplants several studies clearly indicate a therapeutic role for rHuEPO with patients showing accelerated erythroid engraftment, increased haemoglobin levels, a reduced requirement for red blood cell transfusions, and a shortened time to transfusion independence. Especially patients with immune haemolysis after transplantation seems to benefit from the treatment. In addition, rHuEPO treatment has been used for late-onset anaemia after BMT and to prevent the need for homologous red blood cell transfusions to the BMT donor. To reduce costs, it is important in future studies to identify not only the optimal dose and route of administration of rHuEPO but also the most effective combination with other haematopoietic growth factors and cytokines that are used before and after transplantation.
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PMID:Clinical use of rHuEPO in bone marrow transplantation. 1038 35

In industrialised countries, the use of regular blood transfusions and of chelation therapy with Deferoxamine (DFO) has led to the transformation of thalassemia major from a fatal disease in early childhood to a chronic illness associated with prolonged survival. Transfusion regimens maintaining pretransfusion hemoglobin > 9-10 g/dl are effective in suppressing erythroid marrow expansion. Long term DFO therapy using subcutaneous infusions at least 4-6 d a week have clearly demonstrated major effects on iron overload complications. DFO treatment reduces excessive iron and prevents cardiac, hepatic and endocrine diseases. Nonetheless, compliance is difficult for many patients and the cost of DFO limits its use in developing countries. The only oral iron chelating agent that has been investigated extensively is Deferiprone (L1). In France, this oral agent can be administered in patients experiencing toxic side effects under DFO treatment. Since 1981 more than 1500 bone-marrow transplants have been performed word-wide, mostly in Italy. Allogenic BMT is currently able to cure 85% of thalassemic children with an available HLA matched sibling donor.
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PMID:[Therapeuetic management of patients with thalassemia major]. 1147 36

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

ABO incompatibility in allogeneic bone marrow transplantation may be associated with incomplete or delayed erythroid engraftment, being pure red cell aplasia (PRCA) the most severe complication in this setting. Attempts for the treatment of PRCA have been made with erythropoietin or with plasmapheresis with relative success, and some authors have reported the reversibility of PRCA with antilymphocyte globulin (ALG or ATG), based on the assumption that PRCA might be immunologically mediated. We report herewith a patient with acute leukemia who developed post--BMT pure red cell aplasia. His sibling donor (sister) was HLA identical and ABO incompatible, having low agglutinin titers against donor's blood group. PRCA did not improve after treatment with erythropoietin or a boost of hematopoietic progenitor cells obtained from donor's peripheral blood but the problem was resolved completely after treatment with ALG.
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PMID:[Pure red cell aplasia after allogeneic transplantation of ABO incompatible hematopoietic stem cells]. 1253 94


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