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)

Various techniques are applied to assess chimerism after allogeneic bone marrow transplantation. The polymerase chain reaction (PCR) of donor- and/or host-specific gene sequences provides a rapid and highly sensitive technique. We describe the characterization and application of PCR for the amplification of Y-chromosome-specific DNA in blood cells recovered from stored slides. Four different primer pair combinations were used. PCR can be rapidly performed on stained or unstained slide material with varying sensitivity--depending on the primer combination. The lowest limit of detection is one male cell in 500-1000 female cells. The technique was applied to follow the early post-transplant course of 15 male patients who received grafts from female donors and found a high incidence of mixed chimerism during the first three months after BMT and a striking fluctuation between positive and negative results in the follow-up of individual patients. We conclude that PCR for the detection of male-specific DNA sequences can be successfully performed with high sensitivity on material recovered from stored blood slides.
Leukemia 1993 Jan
PMID:Demonstration of chimerism after allogeneic bone marrow transplantation by polymerase chain reaction of Y-chromosome-specific nucleotide sequences--characterization of a new technical approach. 841 73

Peripheral blood progenitor cells (PBPC) were mobilized by G-CSF in normal HLA identical siblings and used for allogeneic transplantation in eight patients with refractory or relapsed acute leukemias. G-CSF administration was well tolerated and no significant side-effects were registered. The number of circulating WBC peaked at day 5 after G-CSF (range: 22.6-74.6 x 10(9)/l) with a median of 65 CD34+ cells/microl (38-155). As a consequence of leukaphereses, platelets progressively decreased, reaching the nadir after the last procedure (84-205 x 10(9)/l). A mean of two aphereses (1-3) were performed between day +4 and +7 during which 10 liters of blood were processed each time by a cell separator. Conditioning regimens were: fractionated total body irradiation (FTBI) plus either HDAra-C (2 g/m2 x 2/day for 6 days) (n=5) or melphalan (110 mg/m2) (n= 1) and busulfan (4 mg/kg/day for 4 days) and melphalan (110 mg/m2) in two patients relapsed after a previous FTBI-based allogeneic or autologous BMT. At transplantation, a median of 6.9 x 10(6) CD34+ cells/kg (4.2-16.5) and 279 x 10(6) CD3+ cells/kg (161-786) were infused. Engraftment of both neutrophils (> or v=1.5 x 10(9)/l) and platelets (> or v=20 x 10(9)/l) was observed in all patients after a median time of 18 days (range: 11-20 and 10-26, respectively). The evaluation of engraftment after transplantation was accomplished by PCR analysis of four hypervariable genomic regions (VNTR) (ApoB, ApoC2, YNZ-22, and MCT 118) which allowed to demonstrate the condition of donor chimaera in all patients after transplantation. As far as the clinical outcome, two patients died of interstitial pneumonitis at day +243 and +69 and two patients died at day +62 and +152 of pulmonary aspergillosis. Four patients remain alive in remission between day +88 and +287 with grade 0-l GVHD. Allogeneic PBPC transplantation is associated with a complete hematologic recovery and despite the infusion of a large amount of mature CD3+ lymphocytes, apparently acute GVHD is not worse than expected after transplantation of bone marrow progenitors.
Leukemia 1996 May
PMID:G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation of resistant or relapsing acute leukemias. 865 84

The outcome of a cohort of 218 consecutive patients who failed to respond to a single course of standard daunorubicin plus ARAC (three + seven) induction regimen has been retrospectively evaluated to assess the characteristics of this group of AML patients and the effectiveness of second-line induction programs. Seventy-four of the 218 patients (33.9%) attained complete remission with salvage chemotherapies. The multivariate analysis of pretherapy characteristics of the patients showed that peroxidase positivity and age were the most important factors in determining whether or not the patient would have a favorable response to second-line induction regimen. In addition, comparison of marrow characteristics at diagnosis with those of marrow after the first-line therapy (marrow leukemic index, MLI) provided the greatest differences between second-line CR and resistant patients. Finally, peroxidase positivity and MLI predicted for remission duration and overall survival. Allogeneic BMT, however, appeared the most important factor for survival and event-free survival of remitting patients. These results are of importance when considering that better defined prognostic factors provide an objective rationale for selecting appropriate strategies for the treatment of patients who do not respond to a single course of induction regimen.
Leukemia 1996 Sep
PMID:Outcome of patients with acute myeloid leukemia who failed to respond to a single course of first-line induction therapy: a GIMEMA study of 218 unselected consecutive patients. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. 875 60

The Leukemia Cooperative Groups of the EORTC and the GIMEMA conducted a prospective randomized phase III trial, in order to assess the value of autologous BMT (ABMT) vs a second intensive consolidation course (IC2), following a common intensive consolidation course (IC1) for patients with AML. Patients with an HLA-identical sibling donor were not randomized, but were included in an allogeneic BMT (alloBMT) program. This is an analysis of prognostic factors which influence the outcome of treatment after alloBMT in first complete remission (CR). The study included 730 patients < 46 years of age in CR, 270 having a histocompatible sibling donor. In 169 of these patients alloBMT was performed in first CR. Early remitters (122 patients achieving CR with one course of treatment) had a DFS at 3 years of 67%, significantly longer than that of 44% for late remitters (47 patients achieving CR after more than one course of treatment) (P = 0.006). The relapse risk for early vs late remitters was 16 and 40% at 3 years (P = 0.001) and the treatment-related mortality (TRM) at 2 years was 21 vs 27%. Age appeared to be a prognostic factor for TRM, WBC for DFS, whereas the FAB classification was not of prognostic importance. Patients with poor risk cytogenetic abnormalities showed a trend towards a higher relapse risk. Patients transplanted shortly after achieving CR appeared to have a worse prognosis than those transplanted further into remission. Overall, the number of courses of induction therapy needed to achieve CR was the most important prognostic factor for outcome after allogeneic BMT.
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PMID:Prognostic factors of patients with acute myeloid leukemia (AML) allografted in first complete remission: an analysis of the EORTC-GIMEMA AML 8A trial. The European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell' Adulto (GIMEMA) Leukemia Cooperative Groups. 880 5

Since the early 80s, the EORTC Leukemia Group has included 3947 patients in 8 consecutive phase III studies on acute myelogenous leukemia, with stratification according to the age groups. Some of these patients were included by other cooperative groups (GIMEMA, HOVON), within intergroup studies. The main hypotheses tested by randomization were intensive chemotherapy consolidation, allogeneic and autologous bone marrow transplantation in the younger patients. In patients aged 60 years or more, a wait and see policy followed by a palliative chemotherapy was compared to an immediate conventional induction treatment, mitoxantrone was compared to daunorubicin, and, during remission, a low dose Ara-C maintenance treatment to no maintenance. The main results can be summarized as follows: Allogeneic BMT, and, relatively, autologous BMT do better than intensive chemotherapy consolidation with regards to the disease-free survival, but not for the overall survival after remission. In the elderly, an immediate induction and a low-dose Ara-C maintenance treatment are preferable to the other options tested. Mainly in patients aged more than 45, the supplementary toxicity of more intensive chemotherapy consolidation, with high dose Ara-C, counter balanced the increased anti-leukemic effect. Finally the trials randomizing GM-CSF during induction yielded disappointing results. The EORTC LCG is currently studying the relative value of various intercalating agents during induction, and of the G-CSF as well, and, during remission the autologous peripheral stem cells compared to bone marrow transplantation.
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PMID:The EORTC trials for acute myelogenous leukemia. EORTC Leukemia Cooperative Group. European Organisation of Research and Treatment of Cancer. 897 88

Adoptive immunotherapy with donor-derived buffy coat cells for relapsed hematological malignancies after allogeneic BMT is an established and highly effective treatment. We report a patient who relapsed on day +330 after allogeneic sibling BMT for multiple myeloma with multiple solid subcutaneous tumors consisting of plasma cells. Histology and immunocytology of the bone marrow did not show plasma cell infiltration. After cessation of the immunosuppression consisting of cyclosporine and methylprednisolone, a total of 6.2 x 10(7)/kg recipient body weight CD3+ T cells derived from the donor by leukapheresis were transfused on 4 consecutive days. To enhance the T cell effect six doses of 5 million units alpha interferon were given subcutaneously. Five days later the tumors started to shrink and have completely vanished since day x400 after BMT. The patient developed acute GVHD grade III of the liver and gut which was treated by reinduction of various immunosuppressive drugs. Up to now there is no evidence for relapse of the multiple myeloma, but the patient suffers from extensive chronic GVHD (gut and liver). This is the first report to demonstrate a graft-versus-myeloma effect for relapse with solid tumor manifestation after sibling BMT with donor-derived buffy coat cells as adoptive immunotherapy.
Leukemia 1997 Feb
PMID:Adoptive immunotherapy for relapsed multiple myeloma after allogeneic bone marrow transplantation (BMT): evidence for a graft-versus-myeloma effect. 900 93

Extension of allogeneic transplants to older patients has been limited by a high risk of transplant-related death and graft-versus-host disease. To evaluate the feasibility in older patients, a retrospective analysis of the procedure was performed for first remission acute leukemia in 192 patients aged over 40 years and compared with a group of 1119 recipients aged from 16 to 40 years reported to the EBMT from 1986 to 1992. Patient-, disease-, and treatment-related variables were compared between the two age groups using the chi2 statistical method for categorical variables. Variables differing significantly or recognized as potential prognostic factors were included in a multivariate analysis. Leukemia-free survival and relapse were comparable among the age groups in the two types of leukemias. Incidence of graft-versus-host disease was higher in the older group of ALL patients. Older patients with AML in first remission had a higher treatment-related mortality incidence, with no influence on survival. A pair-matched analysis of AML patients did not show any statistical difference in the probability of LFS, RI, TRM, and survival for the two age cohorts of patients. These results suggest that BMT should be considered for patients over 40 years of age.
Leukemia 1997 Mar
PMID:Allogeneic bone marrow transplantation for acute leukemia in patients over the age of 40 years. Acute Leukemia Working Party of the European Group for Bone Marrow Transplantation (EBMT). 906 82

Donor CD4+ and CD8+ T cells mediate graft-vs.-leukemia (GVL) responses in the allogeneic bone marrow transplantation (alloBMT) setting. To evaluate the role of functional T cell subsets in the mediation of GVL, alloreactive donor CD4+ (Th1/Th2) and CD8+ (Tc1/Tc2) T cells of defined cytokine phenotype were generated by in vitro culture. A leukemia/transplantation model (B6 into B6C3F1; 1050 cGy host irradiation) was established using the bcr/abl-transfected myeloid leukemia line, 32Dp210 (P210; H-2k). Leukemia control mice (1X10(4) P210 cells per recipient) died at day 12.0 post-BMT. Recipients of the CD4+, Th1-type or CD8+, Tc1-type populations were conferred a survival advantage (death at 20.7 and 23.5 days post-BMT, respectively). In contrast, the CD4+, Th2-type population did not mediate GVL (death at 12.3 days). Furthermore, cell mixing experiments demonstrated that the Th2 subset abrogated both Th1- and Tc1-mediated GVL. The CD8+, Tc2 population, which secreted type II cytokines and lysed the P210 leukemia target in vitro, mediated GVL in some experiments; interestingly, the magnitude of Tc2-mediated GVL was inversely related to the level of interleukin-10 (IL-10) secreted in vitro by the Tc2 population. These studies therefore indicate that alloreactive T cells of type I phenotype maximally generate GVL, and that type I/type II interactions are an important consideration for allogeneic transplantation in the setting of leukemic hosts.
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PMID:Allospecific CD4+, Th1/Th2 and CD8+, Tc1/Tc2 populations in murine GVL: type I cells generate GVL and type II cells abrogate GVL. 919 54

It has previously been reported that the use of mitobronitol (dibromomannitol, DBM) instead of busulphan (BU) for myelosuppression is associated with significantly decreased risk for several complications of allogeneic bone marrow transplantation in accelerated chronic granulocytic leukemia. In exploring the pharmacologic basis for this observation, we have compared the acute and subacute cytotoxicities of DBM and BU on the spleen and thymus of mice. While there was comparable early (day 3) weight loss in both organs following these treatments, splenic B cells exhibited significantly less damage, and thymic regeneration (over weeks) was significantly faster following DBM treatment than with BU. These observations raise the possibility that improved post-BMT immune recovery could contribute to the clinical benefits observed with DBM-preconditioning.
Leukemia 1997 Oct
PMID:Comparison of the lymphoid toxicities of mitobronitol and busulphan in mice: reduced B cell toxicity and improved thymic recovery as possible contributors to the reduced risk for complications following BMT with mitobronitol preconditioning. 932 99

Graft-versus-host disease (GVHD) remains a major immunological complication after allogeneic bone marrow transplantation (allo-BMT), but also favors development of the beneficial graft-versus-leukemia (GVL) effect. A patient with AML-M4 (inv (16)) is described, who was given non-myeloablative remission reinduction therapy for leukemic relapse (inv (16), trisomy 8) diagnosed on day 184 after HLA-compatible sibling BMT. On day 236, ie about 6 weeks after completion of this course, a clinical syndrome suggestive of acute GVHD grade 3 had developed. Skin biopsy confirmed the clinical diagnosis of GVHD, with a compatible liver biopsy. Transfusion-associated GVHD was ruled out by analysis of short tandem repeat (STR) alleles in the skin biopsy, revealing alleles from donor and recipient but not from third party origin. Cyclosporin A (CsA) therapy, which had been tapered between days 150 and 175, was resumed, resulting in a favorable response and gradual transition to limited chronic GVHD. The patient has since remained in complete remission with an excellent performance status for more than 40 months, without further chemotherapy. Thus this biopsy proven case of GVHD was induced by marrow donor lymphocytes more than 200 days after transplantation and apparently triggered by remission reinduction chemotherapy. The case indicates that intensive non-myeloablative chemotherapy can cure AML relapsing after allo-BMT. The therapeutic effect in this case probably involved a direct pharmacological suppression of the leukemic clone followed by a GVL effect initiated by donor-derived alloreactive T lymphocytes.
Leukemia 1997 Oct
PMID:A single course of remission reinduction chemotherapy for acute myelogenous leukemia relapsing after allogeneic bone marrow transplantation is complicated by graft-versus-host disease and followed by sustained complete remission. 932


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