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)

The study was devised to evaluate whether it was possible to collect Philadelphia-negative precursor cells in patients with chronic myeloid leukaemia. The approach was based on previous experience showing that complete remission (Ph-negative bone marrow cells) is rarely achieved after chemotherapy and is very short-lasting. We decided to explore whether it was possible to collect Ph-negative precursor cells in peripheral blood during the early phase of haemopoietic recovery. These data show that: the collection of Ph-negative precursor cells occurred in 12/16 (75%) patients mobilized within one year of diagnosis (group A) versus 12/33 (36%) in patients with a history of more than one year of disease (group B). Furthermore the numbers of Ph-negative precursor cells were significantly much higher at diagnosis. Ten patients mobilized at diagnosis were subsequently autografted with such Ph-negative precursor cells. Five of them remain Ph-negative from 4 to 12 months while the other five have percentages of Ph-positive cells in their marrow ranging from 20% to 70%. In this stage of the disease the procedure is safe and associated with a very good compliance. Occasional restoration of Ph-negative haemopoiesis could be observed up to 40 months after autograft, in patients of group B, but most of patients revert to Ph-positive haemopoiesis. in conclusion these data suggest that it is possible to restore Ph-negative haemopoiesis in 70% of patients mobilized at diagnosis. This percentage represent the highest one can obtain without allogeneic BMT, and this includes patients who never would have been cytogenetic responders to IFN-alpha. Whether and how long for Ph-negative status can be maintained is a matter for future observation and study.
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PMID:Autografting Ph-negative blood precursor cells in chronic myeloid leukaemia. 876 4

With the rationale that a significant reduction of the malignant clone in CML might prolong time to metamorphosis, intensive treatment was given to patients < or = 55 years. Six months of hydroxyurea and high dose interferon-alpha (IFN-alpha) was followed by one to three courses of intensive chemotherapy. Patients who had a donor were allotransplanted and patients who became Ph-negative in bone marrow were autotransplanted. On 1 May 1995, 160 patients were registered in the study. Fifty-one percent of the patients who received six months IFN-alpha and hydroxyurea had a significant Ph-reduction and 5% became Ph-negative. The corresponding figures after two intensive chemotherapy courses were 47 and 28%, respectively. Twenty-seven of 30 autotransplanted patients have been analysed for Ph. Seventeen have relapsed cytogenetically, while ten are Ph-negative 1-64 + months after ABMT. BMT was performed in 59 patients. The actuarial 6-year survival from diagnosis of all 160 registered patients is 68%, which seems to be better than for age-matched historical controls.
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PMID:Intensive treatment in order to minimize the Ph-positive clone in CML. Danish-Swedish CML Group. 876 5

A patient, who was treated twice with donor lymphocyte infusions for relapse of CML after an allogeneic BMT was given lymphoblastoid human alpha-IFN after a third relapse. Further donor lymphocyte infusions were followed by repeated courses of 30 days treatment with a low dosage of IL-2 subcutaneously, alternately with alpha-IFN. This treatment resulted in a hematologic and cytogenetic remission. He also developed a limited degree of chronic GVHD. At the latest follow-up at 20 months after the third course of lymphocyte infusions he is in continuous hematologic and cytogenetic remission. Furthermore, a qualitative PCR analysis for the bcr/abl translocation is negative.
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PMID:Lymphoblastoid human interferon and low dose IL-2 combined with donor lymphocyte infusion as therapy of a third relapse of CML--a case report. 883 27

Haematopoietic stem cell-supported myeloablative therapy appears to be a promising treatment modality for MM. It yields increased overall response and CR rates when compared with conventional chemotherapy, and seems to prolong the duration of survival. These conclusions, while encouraging, have mostly been drawn from uncontrolled studies carried out in select groups of patients and, obviously, need to be confirmed in controlled clinical trials. While the results of these studies are still awaited, the wider application of BMT should probably be encouraged. As in other malignancies, the best candidates appear to be those less heavily pre-treated, with chemosensitive disease, low tumour cell mass and other favourable prognostic features, for example low beta 2-microglobulin levels. Under these conditions, the chance of entering CR following BMT, be it autologous or allogeneic, is currently estimated to be of at least 50%, and the long-term probability of survival averages approximately 30%. However, while it appears that a plateau for progression-free survival cannot be ascertained following a single ABMT, reported observations of patients with continued disease-free survivals up to and beyond 10 years after allografting suggest that this latter procedure may be curative. It seems likely therefore that the higher mortality related to allogeneic BMT (which in recent years decreased from 50% to approximately 30% as the results of a better selection of patients and increasing experience in their management) may be offset by more durable control of the disease and cure in a certain proportion of patients. Recurrence of underlying malignant disease remains, however, a major problem and is the most common cause of treatment failure following BMT. For this reason, attempts to improve the impact of transplantation are warranted. Options currently under investigation include the development of more effective conditioning regimens, as applied in double auto-transplant or with targeted therapy using antibody-radionuclide conjugates, as well as post-transplant immunomodulation with either IFN-alpha, interleukin-2 or idiotype vaccines. In addition, many other problems regarding BMT for MM are still unresolved and could be properly addressed only in future clinical trials. The most important of these issues include the choice of the best conditioning regimen and the optimal source of haematopoietic stem cells, the nature of relapse after autografting, the need to purge or not to purge the autologous marrow, the existence of a 'graft-versus-myeloma' effect and its role in prolonging the duration of disease control and, finally, the likelihood of cure, especially for patients with molecularly-defined CR.
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PMID:The role of haematopoietic stem cell-supported myeloablative therapy for the management of multiple myeloma. 884 73

During the last decade, the availability of large numbers of cytokines and growth factors has greatly favoured the use of biotherapies in several haematological disease. For MM, the majority of clinical studies have dealt with the use of IFN-alpha. From these studies it appears that IFN-alpha has a definite role in the treatment of MM especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies or HDC followed by BMT procedures or PBSCI. Data on the use of EPO have consistently demonstrated the role of this growth factor in ameliorating the grade of anaemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Despite the large amount of experimental data indicating a role for IL-2 and IL-6 in controlling tumour growth, there are only a few clinical studies dealing with their use in MM. From these, it appears that IL-2 and anti-IL-6 antibodies should be further investigated as therapeutic tools useful in maintaining responses, because results show that they arrest tumour progression rather than aid, tumour regression. Finally, in the next years, there will be a wider diffusion of biotherapies in MM that should take into account the roles that IL-1 beta and TNF alpha play in myeloma cell proliferation and bone destruction and the finding that retinoic acid is capable of inhibiting the growth of human myeloma cells in vitro through modulation of IL-6 and its receptor.
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PMID:The role of biotherapies (interleukins, interferons and erythropoietin) in multiple myeloma. 884 74

Cytogenetic analysis is the gold standard for the follow-up of CML patients. The sensitivity of cytogenetics is fairly similar to that of Southern detection of M-BCR rearrangement (5%); this last technique has the potential advantage of being independent of cell division and yield of metaphases. IFN alpha treatment can induce lack of growth of hemopoietic precursors and poor yield of metaphases has been observed. For this reason we decided to study the grade of concordance and complementarity between analysis of karyotype and detection of M-BCR rearrangement of Southern blot. We studied 43 Ph1 positive, M-BCR positive pre-BMT CML patients (48 samples) treated with IFN alpha 2a. Karyotype was done on bone marrow cells by direct method, culture, and banding. Southern technique was performed onto DNA from peripheral blood leukocytes treated with BgIII (and Xbal if necessary) and hybridized with the universal probe (Ph1/bcr-3, Transprobe 1) labelled with dCTP32. A highly significant association between both tests was obtained. Of 48 samples analyzed, 34 were evaluable by both methods and 28 gave the same result for both tests. The concordance between the tests was good (kappa index: 0.63). Of total samples 27.1% was not evaluable by cytogenetics; this figure was 31.2% in samples from patients who were previously in complete cytogenetic response. All of the specimens not evaluable by karyotyping were evaluable by Southern. One sample was not analyzable by Southern but it was evaluable by cytogenetic analysis. The information obtained by Southern technique was clinically relevant, and decisions were made according to its results. We conclude that both tests show a significant association and a good concordance, although they are not interchangeable. Cytogenetic and molecular studies are complementary and must be employed together in CML patients treated with alpha-interferon.
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PMID:Southern technique and cytogenetics are complementary and must be used together in the evaluation of Ph1, M-BCR positive chronic myeloid leukemia (CML) patients treated with alpha interferon (IFN-alpha). 889 87

Soluble interleukin-6 receptor (sIL-6R) has previously been shown to potentiate the activity of interleukin-6 (IL-6) which may display antitumor activity. Therefore, we evaluated sIL-6R levels in the sera of 15 patients who received cytokine-mediated immunotherapy with (IL-2/IFN-alpha), and 15 patients who received cell-mediated immunotherapy post-BMT, in an attempt to reduce the relapse rate. sIL-6R levels were evaluated pre-, during and post-cytokine or cell-mediated immunotherapy, using IL-6R-specific monoclonal antibodies (McAb) and double-sandwich ELISA. In normal controls, sIL-6R levels were found to be 20 +/- 3 ng/ml. sIL-6R levels increased significantly during IL-2/IFN-alpha immunotherapy in comparison to pre- or post-immunotherapy levels (74 +/- 9 ng/ml vs 46 +/- 6 ng/ml, and 50 +/- 9 ng/ml, respectively) (n = 15) (P < 0.05). sIL-6R levels also significantly increased following donor lymphokine activated killer (LAK) cells, given in addition to IL-2, in comparison to base line levels (87 +/- 3 ng/ml vs 60 +/- 2 ng/ml) (n = 6) (P < 0.05). Increased levels of sIL-6R were observed in BMT patients treated with immunotherapy.
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PMID:Soluble IL-6 receptors (sIL-6R) in hematological patients receiving immunotherapy with IL-2/IFN-alpha or donor lymphocytes following bone marrow transplantation. 889 86

We treated 12 patients with leukemia relapse after allogenic bone marrow transplantation with a combination of interferon-alpha (IFN-alpha) ((2.5-5.0) x 10(6) u/m2 subcutaneously three times a week) and interleukin-2 (IL-2) ((1.8-3.6) x 10(6) IU/m2 subcutaneously five times a week) to determine the toxicity and efficacy of combination cytokine therapy in this setting. The median age of the patients was 39 years (range: 16-50). There were nine females and three males. The median time to relapse from BMT was 98 days (range: 0-963). At the time of relapse, six patients had AML, four patients had CML (two in blast crisis and two in chronic phase with clonal evolution), and one patient had lymphoblastic lymphoma. Combination cytokine therapy was started a median of 108 days post BMT (range: 37-2404). Nine patients treated at the higher dose level required a 50% dose reduction because of toxicity or GVHD (three CNS, two GVHD, one high fever, one diarrhoea with hypotension, and one pericarditis). At a lower dose level, 2 of 10 patients had their treatment discontinued because of toxicity or GVHD. Six patients developed clinical findings consistent with acute GVHD while on combination cytokine therapy. Two patients responded to combination cytokine therapy: one with CML and one with AML. Combination cytokine therapy is feasible in the setting of relapse post allogeneic BMT. The combination of IL-2 1.8 x 10(6) IU/m2 five times a week with IFN-2 2.5 x 10(6) U/m2 three times a week seems to be tolerable, and merits further study in this setting.
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PMID:Interferon-alpha and interleukin-2 as treatment for leukemia relapse after allogeneic bone marrow transplantation. 938 68

In a retrospective single centre study we examined the outcome of five different therapy approaches in 48 patients in whom a relapse of CML (13 cytogenetic relapses, 35 hematological relapses: 10 chronic phase (CP), nine accelerated phase, 16 blast crisis) occurred after allogeneic BMT. Cyclosporin A (CsA) withdrawal, interferon alpha-2b (IFN-alpha) therapy, donor leukocyte transfusions (DLT), second transplantation (2nd BMT), and chemotherapy (CTX) alone were used and studied for their response rates. Patients who achieved a complete hematologic and cytogenetic remission (CR) were studied for BCR-ABL transcripts and for their chimerism status by PCR. A strong antileukemic effect was observed after abrupt CsA withdrawal, with 10 of 20 patients achieving a CR (50%). All 10 patients with early stage (nine cytogenetic and one CP), but none of the patients with advanced disease recurrence, responded to CsA withdrawal. IFN-alpha induced in five of 11 patients (45%) a stable cytogenetic remission, whereas treatment with DLT induced a CR in only two of 14 patients (14%). A second transplant was performed in six patients. Three of six patients (50%) survive disease-free at a median of 19 months after the 2nd BMT (range 10-25). The use of CTX alone did not induce a remission.
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PMID:A retrospective single centre study of the outcome of five different therapy approaches in 48 patients with relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation. 946 77

We report a patient with CML who developed a reversible dilated cardiomyopathy with cardiac failure following 10 months of IFN therapy. Despite the previous cardiomyopathy, he tolerated subsequent allogeneic BMT without any adverse cardiac events. Reversible IFN-induced cardiomyopathy should not be considered a contraindication to bone marrow transplantation.
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PMID:Successful allogeneic bone marrow transplant for chronic myeloid leukaemia despite previous interferon-induced cardiomyopathy. 960 10


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