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 have evaluated the use of blood stem cell grafts for rapid hematopoietic recovery and tacrolimus (FK506) as GVHD prophylaxis to reduce early mortality after allogeneic transplantation. Eighty-five adults with advanced leukemia received high-dose thiotepa, busulfan, and cyclophosphamide as a preparative regimen in a prospective Phase II study. All donors were HLA-matched and related. Marrow (BMT) was used for 44 patients and filgrastim-mobilized blood stem cells (SCT) for 41 patients. GVHD prophylaxis consisted of cyclosporine (CsA) or FK506 with methotrexate (MTX) or methylprednisolone (MP). The median time to neutrophil recovery was earlier after SCT than after BMT (day 10 vs. 17, P<0.001), but this was due to the selective use of MTX only in the BMT patients. The risk of grades 2-4 GVHD was lower with FK506 than with CsA (16% vs. 45%, P=0.02) and was the same for SCT recipients as for BMT recipients (33% vs. 34%). Regimen-related toxicity was significantly lower after SCT than after BMT but did not differ between the FK506 and CsA patients. In comparison with those receiving the standard transplant (BMT with CsA and MTX), only the SCT recipients using FK506 and MP had a significantly higher survival at day 180 posttransplant (84% vs. 53%, P=0.014). In multivariate analyses, use of FK506 was associated with a lower risk of treatment-related mortality and a higher survival at day 180, while the diagnosis of acute lymphoblastic leukemia was associated with a higher risk of treatment-related mortality. These data suggest that the use of blood stem cell grafts and FK506 can reduce the early mortality after allogeneic transplantation for advanced leukemia.
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PMID:Allogeneic transplantation for advanced leukemia: improved short-term outcome with blood stem cell grafts and tacrolimus. 899 Mar 68

Several experimental autoimmune diseases (AID), including allergic encephalomyelitis, ie the multiple sclerosis (MS) model, respond to TBI and chemotherapy followed by BMT. Remissions of AID may also occur in patients with concomitant malignancies treated with allogeneic or autologous BMT. These observations have emphasized the possibility of treating AID with high-dose therapy and haematopoietic stem cell transplantation (HSCT). In a phase I/II pilot study, 15 patients with progressive MS were treated with BEAM followed by autologous blood SCT and antithymocyte globulin (ATG). Patients were severely disabled, with median EDSS and SNRS scores of 6 (5-7.5) and 42 (33-62), respectively. Cyclophosphamide (4 g/m2) and G/GM-CSF (5 microg/kg/day) were used for stem cell mobilization, which caused no neurotoxicity. On days +1 and +2, ATG (2.5-5 mg/kg) was given for in vivo T cell-depletion. Allergy (93%) and infections (87%) were the principal toxic complications. Mild, transient, neurotoxicity was observed in six patients in the immediate post-transplant period. The median follow-up time is 6 months (6-18). Durable neurologic improvements have been detected on both the EDSS (7/15) and SNRS (15/15) systems. One patient worsened at 3 months and two have relapsed. Autologous HSCT appears feasible in MS; it does not aggravate disability and seems to offer a clinical benefit. However, these observations need confirmation and long-term outcomes will show if benefits counterbalance toxicity and cost.
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PMID:Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. 938 25

In Epstein-Barr virus (EBV) infection, the virus immortalizes B lymphocytes and cytotoxic T lymphocytes (CTLs) are directed toward both latent and lytic viral antigens expressed on EBV-infected B-cells. Various EBV-associated diseases occur as a result of this disruption of immune surveillance. In the majority of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) cases, the major cell types containing EBV DNA are not B-cells, but clonally proliferating T-cells or NK-cells. Proliferation of these cells produces severe immune reactions in the host, and the clinical features related to massive cytokine production at the onset of disease are unique and distinct from other EBV-associated diseases. In the treatment of EBV-HLH, therapeutic infusion of EBV-specific CTLs appears to be ineffective, and eradication of EBV-containing cells is useful but not sufficient to save lives, because of high incidence of acute mortality due to cytokine-induced multiple organ failure and neutropenia-associated opportunistic infections. The optimal treatment strategy for this disease consists of three steps: (1) control of cytokine storm including coagulopathy and multiple organ failure, (2) control of opportunistic infections, and (3) eradication of clonally proliferating EBV-containing T- or NK- cells by immunochemotherapy and, if necessary, hemopoietic stem cell/bone marrow transplantation (SCT/BMT).
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PMID:Treatment strategies for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). 1097 82

Multiple myeloma is a relatively rare but severe hematologic malignancy. Marked depression in production of normal immunoglobulins, mild neutropenia, and alkylant/steroid therapy or BMT/SCT all produce major suppression of the immune system in the totality of patients. Recurrent bacterial, fungal, and viral infections are an important cause of morbidity and the most common cause of death in these subjects. Prompt diagnosis and appropriate anti-infective chemotherapy are essential in order to reduce the risk of mortality.
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PMID:Infections in multiple myeloma. 1144 1

The risk of Epstein-Barr virus lymphoproliferative disease (EBV-LPD) increases with the use of highly immunosuppressive therapies. Allogeneic BMT, especially supported by T-cell-depleted stem cell products, is a risk factor for EBV-LPD. Although the risk of EBV-LPD after autologous transplantation is low, case reports of this complication in the autologous setting exist. We report a higher incidence than previously described of EBV-LPD in children undergoing sequential high-dose chemotherapy supported with CD34 selected peripheral blood stem cells (CD34+ PBSC). The median time to LPD after tandem transplant was 3 months (range 1-5 months). Five patients out of 156 (3.5%) developed EBV-LPD while enrolled on two trials of tandem autologous SCT in high-risk pediatric malignancies. Both studies employed five cycles of induction therapy, followed by tandem autologous PBSC transplants. In all, 108 out of 156 patients received CD34+ PBSC; 48 received unselected PBSC. All patients contracting LPD were from the CD34 selected group. Treatment of EBV-LPD included rituximab in four out of five patients, i.v.Ig in two out of five patients, and gancyclovir in two out of five patients. EBV-LPD resolved in four out of five patients. We conclude that the combination of tandem SCT and CD34 selection may have increased immunosuppression in these patients to a point where there is an elevated risk of EBV-LPD.
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PMID:An unexpectedly high incidence of Epstein-Barr virus lymphoproliferative disease after CD34+ selected autologous peripheral blood stem cell transplant in neuroblastoma. 1473 Mar 39

Progress in allogeneic SCT will depend on several factors including the advances in the conventional treatment of diseases treated currently with allogeneic SCT, the expansion of the donor pool, the selective control of GVHD, the development of more effective and less toxic preparative regimens to eradicate the neoplastic cell population, the characterization of a new generation of hematopoietic growth factors and cytokines and the development of newer and safer techniques for ex-vivo manipulation of stem cells. The use of hematopoietic growth factor-mobilized donor progenitor cells collected from the peripheral blood has been associated with a rapid hematopoietic engraftment without an increase in the incidence of acute GVHD compared to allogeneic BMT, an increased donor acceptance, elimination of the risk of general anesthesia and a decreased cost. The use of nonmyeloablative conditioning regimens prior to SCT represents a novel treatment approach that may lead to reduced toxicity and an extended use of this treatment in older patients and those with co-morbid conditions and in the treatment of malignant and non-malignant disorders. This approach may play a role in inducing tolerance for solid organ transplantation and in utilizing the GVM effect to treat solid tumors that are not fully responsive to myeloablative cytotoxic regimens. The optimal intensity of cytoreduction and immunosuppression is not well defined. GVHD and disease recurrence remain a challenge. Promising results have been reported in patients with refractory hematologic malignancies as well as in metastatic renal cell cancer, but the ultimate role of this treatment modality remains to be defined pending prospective, well designed, randomized trials.
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PMID:Current concepts in allogeneic hematopoietic stem cell transplantation. 1498 67

Hickman catheter site infections are known to increase transplant-related mortality (TRM). A retrospective analysis of 103 patients who received allogeneic SCT (stem cell transplants) was performed to define the incidence and outcomes of Hickman infections. Seventy-six patients received peripheral blood stem cells (PBSCs) (73.8%) and 29 patients (28.2%), nonmyeloablative conditioning. During the median follow-up of 9 months, Hickman infections were observed in 10 patients (9.7%) at a median onset of 32 days posttransplantation (range, 2-102 days). The causative organisms were identified in 5 cases, including Staphylococcus species (n=4) and Pseudomonas aeruginosa (n=1). Six events were successfully resolved with antibiotic treatment, whereas the other 4 events required the removal of the Hickman catheters with subsequent death in 2 cases. The survival duration for the Hickman infection group was shorter than that for the Hickman no infection group (83 days vs 366 days, respectively; P <.001). Myeloid engraftment was delayed in the Hickman infection group (18.0 days vs 15.0 days, respectively; P=.038), plus Hickman infections were more frequent among BMT compared with PBSCT group (22.2% vs 5.3%, respectively, P=.019). Hickman infections were associated with TRM, especially during the first 3 months posttransplantation. As such, the current results emphasize both the importance of Hickman catheter care and the need for surveillance cultures after SCT.
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PMID:Hickman catheter site infections after allogeneic stem cell transplantation: single-center experience. 1568 29

Allogeneic SCT remains the only potential cure for patients with thalassemia. However, most BMT candidates lack a suitable family donor and require an unrelated donor (UD). We evaluated whether BMT using UDs in high-risk adult thalassemia patients can offer a probability of cure comparable to that reported employing an HLA-compatible sibling as donor. A total of 27 adult thalassemia patients (15 males and 12 females, median age 22 years) underwent BMT from a UD selected by high-resolution HLA molecular typing. The conditioning regimen consisted of Busulphan (BU, 14 mg/kg) plus Cyclophosphamide (CY, 120 or 160 mg/kg) in 12 cases and BU (14 mg/kg), Thiotepa (10 mg/kg) and CY (120-160 mg/kg) in the remaining 15 cases. Cyclosporine-A and short-term Methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. In all, 19 patients (70%) are alive and transfusion-independent after a median follow-up of 43 months (range 16-137). A total of 10 patients (37%) developed grade II-IV acute GVHD and six (27%) chronic GVHD. Eight patients (30%) died from transplant-related causes. UD-BMT can cure more than two-thirds of adult thalassemia patients, and is a particularly attractive option for patients who are not compliant with conventional treatment.
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PMID:Unrelated donor stem cell transplantation in adult patients with thalassemia. 1620 30

We retrospectively analyzed our results of 30 patients with three distinctive primary immunodeficiency diseases (PIDs)--severe combined immunodeficiency (SCID, n = 11), Wiskott-Aldrich syndrome (WAS, n = 11) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n = 8)--who underwent hematopoietic SCT (HSCT) during the past 20 years. Until 1995, all donors were HLA-haploidentical relatives with T-cell depletion (TCD) (n = 8). Since 1996, the donors have been HLA-matched related donors (MRD) (n = 8), unrelated BM (UR-BM) (n = 7) and unrelated cord blood (UR-CB) (n = 7). Twenty-seven of 30 patients had various pre-existing infections with or without organ damages before HSCT. Conditioning regimen and GVHD prophylaxis were determined according to disease, donor and pretransplant status. Although one of eight patients transplanted with TCD is alive with full engraftment, the other seven died. On the other hand, 18 of 22 patients transplanted without TCD are alive and well, including six of eight transplanted from MRD, seven of seven from UR-BM and five of seven from UR-CB. All 19 survivors did not require Ig supplementation after HSCT. These results indicate that UR-CBT as well as UR-BMT provides good results for PID comparable to MRD-SCT, and that early diagnosis, HSCT at early stage, careful supportive therapy and monitoring for various pathogens are important for the successful HSCT.
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PMID:Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team. 1643 16

A 34-year-old female was referred to our hospital for the evaluation of atypical lymphocytosis. Leukocyte count at diagnosis was 17,900/microl with 58% atypical lymphocytes having a convoluted nucleus and prominent nucleoli. Because the leukocyte count increased to 43,600/microl, the patient was treated with 2'deoxycoformycin followed by CHOP combination chemotherapy. However, both treatments failed to achieve remission. We planned an allogeneic bone marrow transplantation from an HLA-matched unrelated donor. The patient was treated with Ara-C and etoposide before conditioning to decrease the high leukemia burden. After administration of total body irradiation (12 Gy in six fractions) and cyclophosphamide (total dose of 120 mg/kg) unmanipulated marrow cells were infused. Under prevention of GVHD by CsA and short-term MTX, leukocyte engraft was prompt at day 16, and acute GVHD grade II was observed. Because 9.4% of residual recipient type T-cells was seen with STR analysis on day 22, we decreased the dose of Cs'A. After the occurrence of mild acute GVHD, the residual T-cell number decreased. The patient is still in complete remission for up to 22 months after BMT. We conclude that allogeneic SCT is effective for the treatment of T-PLL.
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PMID:[Allogeneic bone marrow transplantation for chemotherapy-resistant T-prolymphocytic leukemia]. 1644 Jul 47


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