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)

Granulocyte colony-stimulating factor (G-CSF) priming increases the number of progenitor cells in harvested bone marrow (BM) and has been used for allogeneic transplantation. Primed bone marrow (pBM) seems to offer faster engraftment than steady-state BM, but the stability of such engraftment has been questioned. The incidence of graft-versus-host disease (GVHD) and disease relapse after pBM, compared with such incidence after BM or peripheral blood progenitor allotransplantation, has not been established. We studied the long-term outcome (median follow-up, 24 months) of sibling matched allografting with G-CSF pBM. Seventeen patients received pBM from matched sibling donors primed with G-CSF 10 microg/kg per day for 2 days before BM harvest. Conditioning consisted of total body irradiation and cyclophosphamide (CY); busulfan and CY; or total lymphoid irradiation, CY, and antithymocyte globulin. All infused grafts contained > or = 3.5 to 4 x 10(8) mononuclear cells per kilogram. Ten of 17 patients received methotrexate as part of their GVHD prophylaxis. International Bone Marrow Transplant Registry definitions for engraftment were used. Control subjects consisted of 112 consecutive patients who received allogeneic transplantation at our institution with steady-state BM; control subjects for length of hospitalization consisted of the subset of patients who underwent transplantation during 1996. Neutrophil engraftment occurred a median of 7 days earlier in primed bone marrow transplantation (pBMT) patients when compared with steady-state BMT patients; this shortened hospitalization by a median of 11 days. The peritransplant mortality rate was 18% in pBMT patients and 25% in BMT patients (not significant). The rate of GVHD of grade > II and the rate of relapse were almost identical in pBMT and BMT patients (GVHD: 18% and 19%, respectively; relapse: 14% and 13%, respectively). There were 4 transplant-related deaths within the first 100 days; 1 patient died of disease relapse on day 470. Twelve patients remained alive on days 430 through 1522 after BMT. Results showed that pBM allografts resulted in more rapid engraftment and shorter hospitalization. All patients maintained stable donor engraftment. In this cohort of patients, G-CSF pBMT resulted in rates of GVHD, disease relapse, and peritransplant mortality that were similar to those produced by conventional BMT.
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PMID:Long-term follow-up after allogeneic granulocyte colony-stimulating factor--primed bone marrow transplantation. 1097 11

We studied the effect of the CD34+ cell dose on transplant-related mortality (TRM) and survival in 39 patients randomized to receive lenograstim-mobilized PBSCT (n = 20) or BMT (n = 19) from HLA-identical siblings. Both marrow and blood were harvested, and one infused in a double-blind fashion. The median nucleated (7.0 vs 3.2 x 10(8)/kg; P < 0.0001), CD34+ (3.7 vs 1.5 x 10(6)/kg; P = 0.002), CFU-GM (42 vs 19 x 10(4)/kg; P = 0.002), and CD3+ (1.9 vs 0.3 x 10(8)/kg; P < 0.0001) cell doses with PBSCT were higher. Thirteen patients (6 BMT and 7 PBSCT) experienced TRM at 15-733 days (median 57); 10 of 20 receiving <2 x 10(6) CD34+ cells/kg compared with three of 19 receiving > or =2. Eight of 20 patients receiving <2 x 10(6) CD34+ cells/kg are alive compared with 14 of 19 receiving > or =2. In Cox analysis, CD34+ cell dose > or =2 x 10(6)/kg was associated with lower TRM (RR 0.2, P = 0.01), and higher overall (RR 3.7, P = 0.01) and event-free (RR 3.2, P = 0.02) survival. Other cell populations and the source of stem cells did not affect TRM or survival. We conclude that 2 x 10(6) CD34+ cells/kg may be the ideal minimum cell dose for allogeneic transplantation although lower doses do not preclude successful therapy. Since the likelihood of obtaining this threshold CD34+ cell number is significantly greater from blood than marrow, PBSCT may be preferable to marrow for allografts from HLA-identical siblings.
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PMID:A low CD34+ cell dose results in higher mortality and poorer survival after blood or marrow stem cell transplantation from HLA-identical siblings: should 2 x 10(6) CD34+ cells/kg be considered the minimum threshold? 1101 37

Kostmann syndrome, severe congenital neutropenia, is often associated with life-threatening bacterial infections. A 5-year-old girl with Kostmann syndrome developed pulmonary abscesses. She was refractory to granulocyte colony-stimulating factor and antibiotics. She underwent unrelated HLA-matched BMT. Myeloablative conditioning consisted of 12-Gy TBI with lung shielding, antithymocyte globulin, etoposide, and cyclophosphamide. After successful engraftment, the pulmonary abscesses resolved by day 75 post-transplant. Although the option of transplantation is not established in the setting of unrelated HLA-matched BMT in Kostmann syndrome, this case may provide useful information. Furthermore, pre-transplant pulmonary bacterial abscesses may not be a contraindication for BMT in some patients with Kostmann syndrome.
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PMID:Successful unrelated BMT in a patient with Kostmann syndrome complicated by pre-transplant pulmonary 'bacterial' abscesses. 1157 17

Allogeneic peripheral blood stem cell transplantation (PBSCT) was performed in children and adolescents for the treatment of malignant (n = 49) and nonmalignant hematological disease (n = 8). Granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCs were apheresed from 57 HLA-matched siblings aged 9 months to 24 years (median, 8 years) without any serious adverse, effects. No abnormalities were found in these donors for a median follow-up of 25 months (range, 6-56 months). Patients were conditioned with a TBI-containing regimen (n = 17) or a non-TBI regimen (n = 40). GVHD prophylaxis consisted of methotrexate (MTX) plus cyclosporine A (CSP) for 23 patients, CSP plus methylprednisolone (mPDN) for 22 patients, MTX only for 7 patients, CSP only for 4 patients, and MTX plus CSP plus mPDN for 1 patient. Engraftment was prompt, with a median number of days to reach an absolute neutrophil count (ANC) above 0.5 x 10(9)/L of 13 days (range, 8-23 days), with 1 graft failure. Acute GVHD (grades II-IV) occurred in 8 (16%) of 49 evaluable patients, and chronic GVHD developed in 23 (64%) of 36 evaluable patients. Notably, two thirds of chronic GVHD was extensive. The Kaplan-Meier estimate of 3-year disease-free survival was 0% for refractory disease (n = 6), 37.2% +/- 11.8% for high-risk malignancies (n = 25), 81.4% +/- 9.7% for standard-risk malignancies (n = 18), and 100% for nonmalignant disease (n = 8). The estimated 100-day nonrelapse mortality rate was 9.9% +/- 4.2%. In conclusion, allogeneic PBSCT is feasible in a pediatric population. Although the grade of acute GVHD was set low, as in Japanese BMT studies, the incidence and severity of chronic GVHD appears to be relatively high. For nonmalignant disease, the question arises of whether the higher incidence and severity of chronic GVHD is a drawback of this procedure. For high-risk malignancies, whether or not a graft-versus-leukemia effect prevents relapse needs to be clarified in future comparative studies with BMT.
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PMID:HLA-identical sibling peripheral blood stem cell transplantation in children and adolescents. 1184 53

Granulocyte colony-stimulating factor (G-CSF) is widely used to accelerate neutrophil recovery after allogeneic BMT or PBSC transplantation. The optimal time to start G-CSF treatment is not known. Forty-two patients undergoing allogeneic BMT or PBSC transplantation for hematological malignancies received G-CSF either on day 6 or on day 9 post transplant. The time to hematological recovery was monitored and the two groups were compared with respect to peritransplant morbidity and mortality. Recovery of the neutrophil counts to >0.1 x 10(9)/l, > 0.5 x 10(9)/l and >1.0 x 10(9)/l were not significantly different in either group. There was no difference in recovery of red blood cell and platelet counts and no difference between the two groups with respect to the number of febrile days or number of days on antibiotic treatment. Documented bacterial, viral or fungal infections did not occur more often when G-CSF treatment was started on day 9. Delaying treatment with G-CSF resulted in a significant reduction in the length of treatment from 13 to 10 days (23.1% reduction). Reducing the length of the treatment by 3 days lowered the costs by 395.40 Euro per patient. Delaying G-CSF treatment and starting on day 9 after BMT or PBSC transplantation is safe and results in a clear economic benefit.
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PMID:Late G-CSF after allogeneic bone marrow or peripheral blood stem cell transplantation: a prospective controlled trial. 1237 87

Allogeneic peripheral blood progenitor cells (PBPCs) have mostly been mobilized by granulocyte colony-stimulating factor (G-CSF). There is neither clinical nor experimental data available addressing the question if other hematopoietic growth factors or combinations thereof might influence engraftment, graft-versus-host disease (GvHD), and graft-versus-leukemia (GvL) effects after allogeneic peripheral blood progenitor cell transplantation (PBPCT). We used a murine model to investigate these parameters after transplantation of PBPCs mobilized with G-CSF and SCF either alone or in combination. Treatment of splenectomized DBA and Balb/c mice with 250 microg/kg/day G-CSF for 5 days resulted in an increase of CFU-gm from 0 to 53/microl. The highest progenitor cell numbers (147/microl) were observed after treatment with 100 microg/kg/day SCF administered in conjunction with G-SCF. No differences were detected with regard to the number of T cells (CD3+), T cell subsets (CD4+, CD8+), B cells (CD19+) and NK cells (NK1.1+) in PBPC grafts mobilized by G-CSF plus SCF compared to those mobilized with G-CSF alone. The antileukemic activity of syngeneic and MHC-identical allogeneic PBPC grafts was investigated in lethally irradiated Balb/c mice bearing the B-lymphatic leukemia cell line A20. In this model, PBPCs mobilized by G-CSF plus SCF exerted a significantly higher antileukemic activity compared to grafts mobilized by G-CSF alone (94 vs 71% freedom from leukemia at day 100, P<0.05). The antileukemic effect was lowest after BMT (38% freedom from leukemia). Since significant differences in the incidence of lethal GvHD were not observed, improved GVL-activity resulted in superior overall survival. Our data demonstrate that the utilization of specific hematopoietic growth factors not only improve the yield of hematopoietic progenitor cells but can also significantly enhance the immunotherapeutic potential of allografts.
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PMID:Enhanced antileukemic activity of allogeneic peripheral blood progenitor cell transplants following donor treatment with the combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) in a murine transplantation model. 1281 78

Dendritic cells (DC) play a key role in initiating immune reactions after allogeneic stem cell transplantation. The two main peripheral blood DC populations are myeloid (DC1) and lymphoplasmacytoid (DC2). A new subset of myeloid DC, expressing CD16, has been identified. We analyzed the number and CD86 expression of DC subsets in peripheral blood of 18 healthy donors, before and after granulocyte colony-stimulating factor (G-CSF) and in the inoculum of allogeneic peripheral blood transplants (allo-PBT; n=100) and allogeneic bone marrow transplants (allo-BMT; n=22). Granulocyte colony-stimulating factor administration increased the median number of DC1 (P=0.0007), of DC2 (P<0.0001) and of DC CD16+ (P=0.0001). Granulocyte colony-stimulating factor administration was also associated with a significant decrease of CD86 expression on DC1 (P=0.0003) and with a trend for an increase on DC CD16+ (P=0.07). Recipients of allo-PBT received similar quantities of DC1 and higher doses of DC2 and DC CD16+ than recipients of allo-BMT (P=0.5; P=0.0001; P<0.0001, respectively). Granulocyte colony-stimulating factor modifies the number of DC in peripheral blood and the expression of the costimulatory molecule CD86. This resulted in a different composition of DC2 and especially of DC CD16+ in the harvests, which might explain some of the differences observed in allogeneic reactions after allo-PBT with respect to allo-BMT.
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PMID:G-CSF increases the number of peripheral blood dendritic cells CD16+ and modifies the expression of the costimulatory molecule CD86+. 1654 88

The management of adults presenting with aplastic anemia (AA) requires careful exclusion of other causes of bone marrow failure. Late-onset inherited forms of AA may present in adulthood with subclinical disease. Recent long-term studies of HLA identical sibling donor BMT show excellent survival for patients under the age of 40 years, but chronic graft-versus-host disease (GVHD) is still a major problem, impacting on quality of life. Recent improvements in outcome after matched unrelated donor BMT may reflect better donor matching and use of reduced intensity conditioning regimens. For patients treated with immunosuppressive therapy (IST), antithymocyte globulin (ATG) and cyclosporin (CSA) remain the standard regimen with excellent overall survival but less impressive failure-free survival due to nonresponse, relapse and later clonal disorders. The benefit of adding granulocyte colony-stimulating factor (G-CSF) to ATG and CSA is unclear and being assessed in a further prospective European study. Patients who are refractory to conventional IST and currently ineligible for BMT represent difficult management problems. For these patients, new approaches to transplantation are being evaluated, such as fludarabine-based conditioning regimens and the potential use of double umbilical cord blood transplants, but there is a need for new immunosuppressive agents. Improved supportive care is likely to be a major factor in improved outcome of all AA patients whether treated with IST or BMT. Robust predictive factors for response to IST are needed to help in decision making at diagnosis and to help justify exploring novel approaches to therapy.
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PMID:Making therapeutic decisions in adults with aplastic anemia. 1712 44

As of 1981, allogeneic bone marrow transplantation (allo-BMT) was applied in an acute leukaemia patient with success. Since then, the number of BMT has been increasing gradually, especially since the 1990s. Approximately 2000 BMTs per year have been performed in recent years in more than 100 BMT units in mainland China. A recent survey of 12 major BMT units indicates that the predominant types of transplantation performed are identical sibling (38.6%), related mismatched/haploidentical (19.4%), unrelated (17.2%), and autologous (24.5%). The indications of major disease entities are acute myeloid leukaemia (32.8%), acute lymphoblastic leukaemia (20%), chronic myeloid leukaemia (CML) [18.9%], and lymphoid malignancy (13.5%). The number of transplants from unrelated donor or related mismatched/haploidentical donor has been increasing significantly in recent 6 years. Granulocyte colony-stimulating factor-mobilised bone marrow plus peripheral blood are routinely used as a source of stem cells for haploidentical BMT. Umbilical cord blood is used less often. Although the total number of patients who received allo-BMT continues to increase, the increase in BMT for CML has been flattened since 2004. By the end of 2008, more than 960 000 volunteer's human leukocyte antigen (HLA) data are available in Chinese Marrow Donor Program (CMDP), and more than 1100 stem cell donations have been performed from it. Stem cells for unrelated BMT in mainland China are mainly from Taiwan Tzu Chi Stem Cell Center and CMDP. Related HLA-mismatched/haploidentical BMT has reached fairly good outcomes in terms of severe acute graft-versus-host disease (GVHD), chronic GVHD, relapse, treatment-related mortality, disease-free survival, and overall survival, which are comparable with HLA-identical-sibling BMT in the author's BMT units. Syngeneic BMT started successfully in 1964 and has still very good outcomes in more than 23 BMT units from the statistics of Chinese Society of Blood and Marrow Transplantation.
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PMID:Blood and marrow transplantation in mainland China. 1949 89

Human leukocyte antigen (HLA)-mismatched/haploidentical blood and marrow transplants (haplo-BMT) from family donors have been intensively studied because of the decreasing family size in mainland China, and also because the Chinese Marrow Donor Program is still not big enough. The protocol for unmanipulated haplo-BMT has been designated as 'GIAC' by Dr DP Lu--'G' represents granulocyte colony-stimulating factor mobilisation; 'I' stands for immunosuppression during pre-conditioning being prolonged and intensified; 'A' stands for the use of antithymocyte globulin; 'C' means combined use of bone marrow and peripheral blood as the graft. Haplo-BMT with GIAC regimen has been shown to be feasible for many applications as reported in 2004. Under this protocol, haplo-BMT has achieved comparable outcomes in terms of severe acute graft-versus-host disease (GVHD), chronic GVHD, relapse, treatment-related mortality (TRM), disease-free survival (DFS), and overall survival with HLA-identical sibling transplantation. The probabilities of DFS at 2 years in haplo-BMT setting were 70.7%, 49.6%, 22.2% in standard-risk, high-risk, advanced disease groups, respectively. As the third party cells, cord blood co-infusion could significantly reduce the incidence and severity of acute GVHD, and also 100-day TRM. The majority of refractory cytomegalovirus, Epstein-Barr virus and aspergillus infections can be controlled by adoptive cellular therapy. Many patients who early relapsed after BMT and failed, or are ineligible for standard therapy, have been salvaged with dendritic cell-primed cytokine-induced killer cells. With these new strategies, the lower TRM and improved DFS have been attained. Therefore, it is better to consider haplo-BMT for the patients with otherwise incurable haematological malignancies at earlier stage, when matched sibling or unrelated donors are not available.
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PMID:Unmanipulated haploidentical blood and marrow transplantation: where we are. 1949 93


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