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)

We describe a single center experience of 41 consecutive patients with poor prognosis acute myeloid leukemia (AML) who received a single course of FLAG regimen consisting of Fludarabine 30 mg/m2/day plus Cytarabine 2 gr/m2/day (days 1-5) and G-CSF 5 mg/Kg/day (from day 0 to polymorphonuclear recovery) as salvage therapy. Eleven patients were primarily refractory to previous chemotherapy, 10 patients were in first relapse, 2 patients in second relapse and 7 patients in relapse after transplants. Eleven cases were defined as secondary AML (diagnosis of AML made after a preexisting diagnosis of myelodysplastic syndrome). The median age was 52.6 years (range 16-72); 29 patients were males and 12 females. Overall, 23 (56%) patients reached complete remission (CR), 3 patients died of infection (2) or hemorrhage (1) during induction, and 15 (36%) patients had resistant disease. The highest CR rates (80%) were obtained in relapsed cases; de novo and secondary AML registered 60% and 45% of CR rates, respectively. Patients achieving CR received a second FLAG course as consolidation and were submitted to an individualized program post-remission therapy, depending on the age and performance status. Hematological and non hematological toxicities were acceptable. In conclusion, our data confirm that FLAG is a an high effective treatment for poor prognosis AML and in young patients allows intensive post remissional therapy including allogeneic BMT.
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PMID:Treatment of "poor risk" acute myeloid leukemia with fludarabine, cytarabine and G-CSF (flag regimen): a single center study. 1142 51

At the workshop on infections after stem cell transplantation (SCT) in children, the following topics were introduced by invited speakers and discussed with the audience: empirical antimicrobial therapy in the pre-engraftment period, early diagnosis of fungal and viral infections and possibilities to treat them and the possible role of G-CSF early post-SCT. Episodes of fever in the pre-engraftment period mostly are unexplained, and in about one quarter due to bacteremia, mostly by Gram-positive cocci. No single drug or combination of drugs used for antimicrobial therapy is superior, neither does it cover 100% of the pathogens. Close microbiological surveillance of the patients and knowledge of the local microbial epidemiology are requested for optimal therapy. Early fungal infections are reactivations of pre-SCT infections, late fungal infections mostly are associated with failure of engraftment or GvHD and its treatment. Except for suggestive ultrasound or CT-scan abnormalities, the possibilities for early diagnosis are limited c.q. not reliable. Fluconazol prophylaxis is recommended to prevent Candida albicans invasion. A number of new antifungal drugs are being tested in phase I and II studies. CMV, EBV and adenoviruses may reactivate after SCT, causing severe disease with a high mortality, especially in non-HLA-identical donor-recipient combinations. Frequent surveillance cultures for CMV and adenoviruses, pp65-CMV antigen detection in WBC and PCR techniques for CMV, EBV and adenoviruses all have their own contribution to the early diagnosis of dissemination of the viral infection. Therapeutical possibilities, except with respect to ganciclovir and foscarnet for CMV infection, are still limited. The effectiveness of cidofovir is under study. Adoptive therapy with virus-specific CTL's probably represents the new frontier. G-CSF administration early after SCT has a beneficial effect on PMN recovery, hospitalization time, use of antibiotics and total parenteral nutrition requirement in children undergoing allogeneic and autologous BMT. No benefit is observed in children undergoing peripheral blood SCT. The routine use of G-CSF in the latter group of patients is not justified.
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PMID:Infections after stem cell transplantation in children: state of the art and recommendations. 1157 29

Graft-versus-host disease (GVHD) and infection are major obstacles to successful allogeneic bone marrow transplantation (allo-BMT). In an attempt to improve the results of HLA-identical sibling BMT, we investigated the effect of accelerating hemopoietic reconstitution and reducing acute GVHD (aGVHD) in allo-BMT receiving G-CSF-stimulated donor marrow and the preliminary biological mechanism. The donors of 30 patients (study group) with leukemia were given G-CSF 3-4 microg/kg/d for 7 doses prior to marrow harvest. The results of subsequent engraftment in the recipients were compared with those of 18 patients without G-CSF (control group). Five donors themselves were studied to assess the effects of G-CSF on the hematopoietic progenitor cells and lymphocyte subsets in the bone marrow (BM). We observed that the stimulated BM yielded higher numbers of nucleated cells as well as CFU-GM and CD34+ cells (p<0.01), and that hemopoietic reconstitution was accelerated. The median number of days of granulocyte count exceeding 0.5x10(9)/L and platelet count exceeding 20x10(9)/L was 16 (range 10-23 d) and 18.5 (range 13-31 d), respectively (control group: median 22 d, range 13-29 d and median 23 d, range 17-34 d; p=0.001). The incidence of grade II-IV severe aGVHD was very low, with only 1 case (3.3%) with acute grade II aGVHD limited to the skin in the study group. Five of 18 patients in the control group manifested grade II-IV severe aGVHD (27.8%, p=0.02). The number of T-lymphocyte subsets in the harvested BM using G-CSF stimulation was changed. In the G-CSF-stimulated marrow group, CD4+ decreased and CD8+ increased significantly (p=0.02). The changes of progenitor cells and T-lymphocyte subsets in donors' BM from pre- and post-G-CSF stimulation showed that the percentage of CD4+ reduced (p=0.04) and that of CD8+ increased (p=0.06), while that of CD34+ also increased (p=0.002). The incidence of chronic GVHD and relapse had no significant difference between both groups. These results indicate that allo-BMT in BM G-CSF priming can accelerate engraftment and minimize the incidence of severe aGVHD. There is a trend in favor of improved transplantation-related mortality.
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PMID:The effect of G-CSF-stimulated donor marrow on engraftment and incidence of graft-versus-host disease in allogeneic bone marrow transplantation. 1167 57

A female patient with AML received an allogeneic BMT from her brother. She experienced two relapses managed with chemotherapy and donor leukocyte infusions. The patient subsequently developed extensive therapy-refractory chronic GVHD. Pseudoautologous blood stem cell transplantation was performed as a salvage treatment for chronic GVHD. Her blood stem cells were easily mobilized with cyclophosphamide and G-CSF. The conditioning regimen was well tolerated and consisted of 200 mg/kg cyclophosphamide and horse-derived antithymocyte globulin. A total of 4.03 x 10(6)/kg CD34+ cells were infused and hematological recovery was rapid. Chronic GVHD improved with the ability to taper steroids. Nine months post transplantation the patient died from leukemia.
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PMID:Pseudoautologous blood stem cell transplantation for refractory chronic graft-versus-host disease. 1218 Jan 18

Here, we report the first study assessing the helper T lymphocyte precursor (HTLp) frequency as a predictor of outcome in patients undergoing allogeneic PBSC transplantation. The HTLp assay uses limiting dilution analysis to measure the frequency, in PBMCs from the donor, of T lymphocytes capable of producing IL-2 in response to histocompatibility antigenic differences on PBMCs from the recipient. This assay has shown promise as a functional histocompatibility assessment used to predict the risk of recipients of HLA-matched donor bone marrow developing severe acute GVHD: the higher the HTLp frequency, the greater the significance of any histoincompatibility, and the greater the risk of severe acute GVHD. In the current report, the HTLp frequency was measured in 28 HLA-identical sibling pairs who subsequently underwent allogeneic PBSC transplantation for haematological malignancies. The HTLp frequency did not predict for acute GVHD (P = 0.38), chronic GVHD (P = 0.95), transplant-related mortality (P = 0.79), relapse (P = 0.39) or overall survival (P = 0.84). Converting the HTLp frequency to HTLp infused per kilogram of recipient body weight also did not predict for any of the outcome measures. We conclude that, although the HTLp assay may be useful for patients undergoing BMT, it does not predict for outcome after HLA-identical sibling donor G-CSF-mobilised PBSC transplantation.
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PMID:The helper T lymphocyte precursor (HTLp) frequency does not predict outcome after HLA-identical sibling donor G-CSF-mobilised peripheral blood stem cell transplantation. 1223 17

To explore the feasibility of using CD25 monoclonal antibody (Basiliximab) in T-cell undepleted allo-BMT with graft from haplotype-matched related donor for acute GVHD prophylaxis. Twenty-eight patients with leukemia received allo-BMT from HLA two or three loci mismatched related donors. The donors were given G-CSF (Lenograstim) 250 micro g/d for 7 doses prior to marrow harvest. CSA, MTX, ATG and mycophenolate mofetil (MMF) were combined for GVHD prophylaxis. ATG 5 mg/(kg.d) was infused from day 4 to day 1 before transplantation and MMF was administered from day 7. In the study group, the patients received additional CD25 monoclonal antibody for aGVHD prophylaxis. CD25 20 mg each by 30 min intravenous infusion on 2 hours before transplantation and day 4 after transplantation was administered while no application of CD25 in the controls. The outcomes of transplantation were compared between the stud y and control groups. The results showed that the median number of CD34(+) cell in graft was 5.9 x 10(6)/kg in the control group and 7.9 x 10(6)/kg in the study group. The median number of CD3(+) cell was 48 x 10(6)/kg and 52 x 10(6)/kg respectively (P > 0.05). All patients showed 100% donor-typed hematopoietic cells after transplantation by cytogenetic evidence. Five out of fifteen patients in the control group experienced II - IV acute GVHD. While none of thirteen in the study group developed the II - IV acute GVHD. However, none in both groups developed extensive cGVHD. The median follow-up duration was 8 (3-15) months in the study group and 26 (15-36) months in control. In the study group, one patient died from transplant related mortality (CMV infection); no one relapsed; and 12/13 patients survived in disease-free situation within the period of follow-up. In the control group, six patients died from transplant related mortality (3 GVHD, 2 infection and 1 relapsed) and 9/15 patients survived in disease-free situation. The one-year probabilities of disease-free survival (DFS) in two groups were significantly different (P < 0.05). It is concluded that the transplant from haploidentical donors used CD25 antibody is effective and feasible in preventing acute severe GVHD and improving DFS. The major histocompatibility barrier in the haploidentical related allo-BMT could be crossed by donors primed with G-CSF and GVHD prophylaxis with CD25 antibody in the hosts.
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PMID:[A clinical study of haploidentical and G-CSF primed bone marrow transplantation by using CD25 for aGVHD prophylaxis]. 1251 46

In this study, to investigate the effect on expression of IL-2 in lymphocytes from bone marrow and peripheral blood of normal donors after they were mobilized by G-CSF in allo-BMT, 7 normal donors bone marrow and peripheral blood were harvested before and after G-CSF administration. The separated lymphocytes were measured by FCM after they were stained intracellularly by anti-IL-2, and their expressions of IL-2 were compared. The degree of aGVHD in patients after bone marrow transplantation was evaluated clinically, and it was compared with the status of aGVHD of 15 patients whose donors didn't receive G-CSF administration in our department, and 2 groups of patients are comparable in age, types of diseases and status of donors. The results showed that the expression of IL-2 in lymphocytes in 7 G-CSF mobilized donors decreased significantly after G-CSF administration and more severe aGVHD than grade II didn't develop in these recipient patients, and comparing with 15 patients received the bone marrow from donors who didn't receive G-CSF, the incidence of aGVHD decreased. It is suggested that the expression of IL-2 in lymphocytes was influenced by donors' G-CSF administration, and it is likely that thereby reduces the incidence of aGVHD in patients after BMT.
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PMID:[Impact on IL-2 expression of lymphocytes in donors after G-CSF administration and its clinical significance]. 1251 17

We report a 39-year-old female patient who underwent HLA-identical sibling allogeneic BMT for CML in accelerated phase. Severe pancytopenia refractory to G-CSF associated with progressive splenomegaly and RBC/platelet transfusion dependency were present from day +60 after BMT. MRD assessed by FISH and RT-PCR multiplex for BCR-ABL rearrangement was negative, and complete chimerism was documented by VNTR on days +100, +180, +360 and 2 years after BMT. Splenectomy was performed on day +225 and pancytopenia resolved but chronic extensive graft-versus-host disease developed, with hepatic cholestasis, diffuse scleroderma and sicca-like syndrome. She was sequentially and progressively treated with different immunosuppressive therapy combinations with no clear benefit. On day +940, she presented with infection over the previously present ulcers on both limbs, which culminated in septic shock and death on day +1041. We conclude that, although splenectomy may reverse poor graft function after allogeneic BMT, hyposplenism may trigger or worsen chronic extensive GVHD leading to increased morbidity and mortality.
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PMID:Refractory chronic GVHD emerging after splenectomy in a marrow transplant recipient with accelerated phase CML. 1285 7

Haploidentical donors are available for most patients who need allografts but do not have matched donors. However, GVHD, rejection, delayed immune reconstitution, and infections have been significant barriers. We designed a haploidentical BMT protocol focusing on prevention of GVHD and rejection. A total of 53 leukemic patients underwent haploidentical G-CSF-primed BMT without ex vivo T-cell depletion. GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine, methotrexate, and mycophenolate mofetil. In all, 38 patients (the CD25 group) received additional anti-CD25 monoclonal antibody basiliximab. The results were compared to 15 patients who did not receive basiliximab. All patients achieved trilineage engraftment with full-donor chimerism. The incidence of acute II-IV GVHD was 11% in the CD25 group vs 33% in the control group (P=0.046). The overall incidence of extensive chronic GVHD was 15%. T, B, and NK cells recovered within 12 months post transplant. The disease-free survival at 2 years was 53% with a median follow-up of 31 months. In conclusion, G-CSF primed haploidentical BMT along with sequential immunosuppressive agents as described here deserves further study.
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PMID:Anti-CD25 monoclonal antibody (basiliximab) for prevention of graft-versus-host disease after haploidentical bone marrow transplantation for hematological malignancies. 1596 93

This is the first study to examine the outcomes in 54 patients with hematologic malignancies who received an HLA-matched related donor bone marrow (BM, n = 42) or GCSF-mobilized peripheral blood stem cells (PBSC, n = 12) following identical nonmyeloablative conditioning with the intention of induction of mixed chimerism (MC) followed by prophylactic donor leukocyte infusion (pDLI) to convert MC to full donor chimerism (FDC) and capture a graft-versus-tumor effect without clinical graft-versus-host disease (GVHD). Neutrophil and platelet recovery were faster and transfusion requirement was less in PBSC recipients (P < 0.05). A total of 48% of BMT recipients achieved FDC with a median conversion time of 84 days, including 13 following pDLI. In contrast, 83% (P = 0.04) in the PBSC group had spontaneous FDC at a median of 14 days, precluding the administration of pDLI. There was no significant difference in the incidences of acute or chronic GVHD, though the rates of chronic GVHD were considerably higher in PBSC group than in the BM group (6/7, 86% vs 10/24, 42%). CD4 and CD8 T-cell recovery was faster in PBSC recipients. In PBSC recipients, a higher number of CD34+ cells was associated with increased rates of severe, grade III-IV acute GVHD.
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PMID:Comparison of outcomes after transplantation of peripheral blood stem cells versus bone marrow following an identical nonmyeloablative conditioning regimen. 1746 73


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