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)

Marrow stromal cells were evaluated several months after autologous BMT for their capacity to support both normal hemopoiesis and secrete the main growth factors involved in its control, G-CSF, GM-CSF, IL-3 and SCF. Stromal layers (SL) were obtained by long-term marrow cultures (LTMC) established from 15 patients (9 with hematologic malignancies and 6 with solid tumors) 3 months after autologous BMT and were compared to pre-graft patients. After irradiation, both post-graft and pre-graft SL were recharged with the same inoculum of normal marrow cells. As compared to pre-graft values, CFU-GM production on post-graft SL was significantly increased during the first 2 weeks of culture whereas it was decreased from week 3 to week 8. These findings were only observed in patients with hematologic malignancies and not in patients with solid tumors. Growth factor secretion was evaluated by ELISA in the supernatants of unstimulated and IL-1-stimulated SL from 10 post-graft patients, 13 pre-graft patients and 5 normal controls. In any group of patients, IL-3 was undetectable either spontaneously or after IL-1-stimulation. As compared to controls, secretion by IL-1-stimulated SL was not different for GM-CSF in pre- and post-graft patients but tended to be decreased for G-CSF in post-graft patients. SCF secretion, which was not induced by IL-1, appeared dramatically decreased in both pre- and post-graft patients. The capacity of post-graft SL to support CFU-GM growth in LTMC was correlated at week 1 with G-CSF secretion and from week 3 to week 8 with SCF secretion. These results suggest that microenvironment remains qualitatively damaged several months after BMT involving a decreased capacity both to support early hemopoiesis and to secrete SCF, particularly in patients grafted for hemopoietic malignancies.
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PMID:Changes in the functional capacity of marrow stromal cells after autologous bone marrow transplantation. 964 67

Five years after the diagnosis of Ph chromosome-positive chronic myeloid leukemia (CML) a 31-year-old patient developed malignant nephrosclerosis with renal failure. He then underwent an allogeneic unrelated BMT in first chronic phase CML. The preparative regimen consisted of fractionated total body irradiation (TBI) and cyclophosphamide (CY). We studied the pharmacokinetics of cyclophosphamide on hemodialysis and compared clinical parameters including time to engraftment and toxicity with parameters of a patient with normal renal function who also received an unrelated marrow as treatment for CML in first chronic phase. Our results suggest that TBI/CY is a suitable conditioning regimen for allogeneic transplantation in patients with hematological malignancy and renal failure on hemodialysis.
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PMID:Total body irradiation and cyclophosphamide is a conditioning regimen for unrelated bone marrow transplantation in a patient with chronic myelogenous leukemia and renal failure on hemodialysis. 975 50

Nine of 56 (20% actuarial) patients receiving a T cell-depleted, HLA-identical sibling BMT for hematological malignancy developed hemorrhagic cystitis (HC) 15-368 days post BMT. Hematuria was severe and prolonged (median duration 18 days). In eight patients (89%), a viral etiology was confirmed (four adenovirus, four polyomavirus). HC was associated with significant morbidity, with all patients requiring continuous bladder irrigation and transfusion support for blood loss and thrombocytopenia. HC occurring before day 100 was significantly associated with a reduction in long-term survival: 1/7 (14.3%) patients developing HC before day 100 became long-term survivors vs 21/49 (42.8%) without HC by day 100 (P = 0.034). In univariate analysis, HC was associated with a diagnosis of multiple myeloma (P = 0.02). There was a trend towards a higher incidence of HC in patients reactivating cytomegalovirus (CMV) compared with those remaining CMV negative (18.4 vs 5.5% respectively, P = 0.17). HC was not associated with graft-versus-host disease, or with the transplant dose of CD34+ progenitors or CD3+ cells, patient age or sex. Life-threatening, viral-induced HC and the unusually high incidence of adenovirus-induced HC may have been caused by immune deficiency associated with T cell depletion in this series.
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PMID:High incidence of adeno- and polyomavirus-induced hemorrhagic cystitis in bone marrow allotransplantation for hematological malignancy following T cell depletion and cyclosporine. 982 17

Although T cell depletion of allografts used in BMT has reduced GVHD, it has been associated with inferior engraftment and an increased risk of relapse. We have found that T cell depletion by counterflow centrifugal elutriation (CCE) also results in depletion of CD34+ stem cells. In order to determine if the discarded CD34+ cells would improve engraftment, we undertook a phase II trial of allogeneic BMT in which 110 patients (median age 43) with a variety of hematologic malignancies received CD34+ stem cell augmented, elutriated marrow grafts. The T cell-depleted grafts were tightly controlled and contained a mean of 4.3 x 10(7) mononuclear cells/kg, 3.3 x 10(6) CD34+ cells/kg, 1.5 x 10(5) CFU-GM/kg and 5.5 x 10(5) CD3+ T cells/kg. Median time to engraftment of granulocytes (>500/microl) was 16 days and of platelets (>50000/microl) was 25 days, comparable to that seen with unmanipulated marrow. No mixed hematopoietic chimerism was observed that was not associated with disease relapse. The four patients (3.6%) who failed to engraft were all at high risk because of prior donor transfusions or underlying marrow disorders. The incidence of GVHD was dependent on the duration of cyclosporin A (CsA) immunosuppression. In patients who received CsA for > or = 80 days, the incidence of clinically significant acute GVHD (>stage 1) and extensive, chronic GVHD was 5% and 11%, respectively. Peritransplant (< or = 100 day post-BMT) mortality for this group of patients was 15%. Event-free survival in selected subsets of patients compared favorably to previous studies in which patients received unmanipulated marrow allografts.
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PMID:CD34+ stem cell augmentation of elutriated allogeneic bone marrow grafts: results of a phase II clinical trial of engraftment and graft-versus-host disease prophylaxis in high-risk hematologic malignancies. 984 91

One hundred and forty children with hematologic malignancies undergoing allogeneic BMT were reviewed in order to clarify the incidence, onset time, and risk factors for veno-occlusive disease (VOD) of the liver. Thirty-eight patients (27.1%) developed VOD diagnosed according to the Seattle clinical criteria. Seventeen patients developed VOD within 20 days of transplantation (early-onset) and in 21 patients developed after day 20 (late-onset) including eight patients with histological confirmation. Late-onset VOD occurred from day 21 to day 508 (median day 39). Moderate or severe VOD developed in 11 early-onset and 13 late-onset patients. Death occurred in eight early-onset and 10 late-onset patients. Serum albumin and cholinesterase levels prior to the start of pretransplant conditioning were significantly lower in early-onset VOD than in late-onset VOD. Multivariate analysis showed that low serum albumin levels (< or =3.7 g/dl) prior to the start of pretransplant conditioning was most strongly associated with the development of VOD. Donor mismatch (other than HLA-matched relatives), use of minocycline, and a long interval (> or =13 months) between diagnosis and BMT were also significantly associated with the development of VOD. In contrast, use of fosfomycin was associated with a decreased risk. Our data suggest that hepatic function reserve is important in the development and onset time of VOD. Veno-occlusive disease of the liver is a complication which may occur a long time after transplantation.
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PMID:Veno-occlusive disease of the liver after allogeneic bone marrow transplantation in children with hematologic malignancies: incidence, onset time and risk factors. 989 23

Marrow residual disease (RD) in patients with B-cell chronic lymphocytic leukemia (B-CLL) who are in complete remission (CR) after treatment with purine analogues is reported to have a prognostic value, but sample dilution, factors interfering with marrow aspiration, or undetectable immunoglobulin rearrangement can affect the assessment of RD by molecular or immunologic methods. As demonstrated for hairy cell leukemia and follicular lymphoma, bone marrow trephine biopsy specimen immunostaining (BMT/IS) can successfully detect residual malignant cells. The aim of this study was to use BMT/IS and computerized image analysis (CIMA) of bcl-2-positive cells to quantify RD in B-CLL patients in CR, after achievement of CR and more than 1 year later. This methodology was compared with other conventional techniques, i.e., cytologic, flow cytometric, cytogenetic, and molecular analysis. BMT/IS readily detected RD in every trephine biopsy specimen examined, either after CR or at distant follow-up. CIMA allowed an objective quantification of residual B-CLL cells, as evidenced by the correlation with semiquantitative polymerase chain reaction results. Both analyses indicated a progression of RD. This finding was also supported (but inconsistently) by the other techniques. CIMA with an interstitial labeling index, therefore, seems to be a reproducible and sensitive method to detect persistence and progression of RD in patients with B-CLL. This method could apply to other hematologic malignancies infiltrating the bone marrow.
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PMID:Use of image analysis and immunostaining of bone marrow trephine biopsy specimens to quantify residual disease in patients with B-cell chronic lymphocytic leukemia. 1022 4

CD34+ cell selection of PBPC after harvest from G-CSF-treated allogeneic donors results in a more than 200-fold depletion of T lymphocytes in the graft and has been used to reduce the incidence of acute GVHD post transplant. Since transplantation with T cell-depleted BM grafts is associated with a delay in immune reconstitution and an increase of opportunistic infections, we evaluated the immunological reconstitution of patients with hematologic malignancies after therapy followed by CD34+-selected PBPC34 transplantation from matched related donors. Lymphocyte subset reconstitution over the first 12 months post transplant and the incidence of infections were evaluated in 12 patients receiving PBPC34 grafts and compared to that of patients after transplantation with PBPC without CD34+ enrichment (n = 20) or unmanipulated bone marrow grafts (BM; n = 15). PBPC34 grafts contained 264-fold fewer T lymphocytes (median 0.53 x 10(6) kg/body weight) than PBPC grafts and 36-fold fewer than BM grafts (140 x 10(6)/kg and 19 x 10(6)/kg, respectively). Despite a two log depletion of T cells in the PBPC34 grafts, T lymphocyte reconstitution appeared comparable among the three transplant groups over the first 12 months. A positive patient CMV serostatus pretransplant was correlated with a faster T cell reconstitution in all transplant groups. GVHD prophylaxis with methylprednisolone delayed B lymphocyte reconstitution. The incidence of infections post transplant did not appear to be increased in the PBPC34 group compared with the PBPC and BMT groups. It remains to be shown in larger prospective trials, whether these promising preliminary data of lymphocyte reconstitution and the clinical course after transplantation with PBPC34 can be confirmed.
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PMID:Quantitative lymphocyte subset reconstitution after allogeneic hematopoietic transplantation from matched related donors with CD34+ selected PBPC grafts unselected PBPC grafts or BM grafts. 1045 69

Recently, hematopoietic stem cell transplantation has been diversified and classified into several types of transplants, including allogeneic bone marrow, peripheral blood stem cell and cord blood stem cell transplantation (BMT, PBSCT, CBSCT), from related or unrelated donors. In addition, autologous BMT or PBSCT can be used to facilitate hematologic reconstitution after marrow-ablative therapy for hematologic malignancies. At least 50% of patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) can be cured by treatment with allogeneic BMT. Autologous BMT has been studied in comparison with allogeneic BMT or intensive chemotherapy in the treatment of AML and ALL. A series of large-scale prospective randomized studies have provided controversial results: relapse rates are significantly low, but treatment-related mortality is significantly high, after allogeneic or autologous BMT as compared to intensive chemotherapy. At present, it is somewhat difficult to determine which treatment modality is indicated as a postremission therapy for AML and ALL. Therefore, risk factors such as leukemia subtype, age, karyotype, and initial response should be taken into consideration when deciding on a postremission therapy. In the 1990's, the use of autologous PBSCT has been replacing autologous BMT, as autologous PBSCT has several advantages over autologous BMT. Consequently, allogeneic PBSCT has come to be increasingly used instead of allogeneic BMT in the treatment of leukemia. Recent clinical data clearly indicate that allogeneic PBSCT can be used as an alternative to allogeneic BMT. With well-designed clinical trials, the places, of allogeneic or autologous BMT and PBSCT will be clarified in the treatment strategy for acute leukemia.
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PMID:[Hematopoietic stem cell transplantation for treatment of acute leukemia]. 1050 May 24

This study of adult patients of Thai cultural background compared the quality of life (QOL) of patients undergoing bone marrow and peripheral blood stem cell transplantation (BMT/PBSCT) with that of patients treated with conventional chemotherapy (CT). The study population comprised 59 patients who were transplant recipients (29 allogeneic, 29 autograft, and one syngeneic BMT/PBSCT) and 24 patients treated with CT for various hematologic malignancies. The participants completed a 50-item structured QOL questionnaire sent by mail. No significant differences were found between the two patient groups regarding their psychological, social, and treatment-related well-being or their overall QOL; all scores were above 75% of the total. The mean score regarding the physical domain, however, was significantly lower in BMT/PBSCT patients. Areas of highest concern in both groups were sexuality and financial burden. Happiness, functional ability, financial burden, and the degree of familial acceptance were the most important predictors of the self-rated QOL in BMT/PBSCT patients. Seventy-five percent of BMT/PBSCT patients would be willing to undergo the procedure again under the same circumstances. These results indicated that the QOL of Thai patients undergoing BMT/PBSCT was in general satisfactory and comparable to patients treated with conventional CT.
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PMID:Quality of life in Thai patients after bone marrow and peripheral blood stem cell transplantation: a comparison study with patients treated with conventional chemotherapy. 1056 12

We prospectively studied the reconstitution of lymphocyte subpopulations in a group of 22 children, who survived disease-free at least 6 months after allogeneic BMT for a haematological malignancy. Absolute counts of total lymphocytes, B lymphocytes, T lymphocytes, and CD4+ helper T lymphocytes reached the 5th percentile (p5) of age-matched reference values within 6 months after BMT in 15, 17, 7 and 2 patients, respectively. In particular, CD4+ helper T lymphocyte reconstitution was very slow. Unexpectedly, CMV reactivation had a profound positive influence upon the number of CD4+ helper T lymphocytes in the children. In five patients, absolute B lymphocyte counts above the 95th percentile were reached from 6 months after BMT onwards, mimicking normal ontogeny. Unlike normal ontogeny, the percentages of helper T lymphocytes expressing the 'naive' CD45RA isoform were low and those expressing the 'memory' CD45RO isoform were high in the first 3 months after BMT, as described before. Thereafter, the CD45RA:CD45RO ratio slowly normalised. Also, CD7 expression was absent on up to 90% of T lymphocytes in the first months after BMT, and on a steadily decreasing percentage thereafter, as recently described in adults. However, the absolute counts of CD45RO+/CD4+ and CD7-/CD4+ helper T lymphocytes did not change significantly. So, we found no evidence of peripheral expansion of previously primed donor-derived 'memory' T lymphocytes during the follow-up period which spanned 1-18 months after BMT. The absolute counts of 'naive' CD45RA+ helper T lymphocytes did not show a faster increase after BMT than in adults, despite the presumed presence of a non-involuted thymus in children. Bone Marrow Transplantation (2000) 25, 267-275.
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PMID:Reconstitution of lymphocyte subpopulations after paediatric bone marrow transplantation. 1067 98


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