Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow transplantation is the only treatment that can result in long-term disease-free survival and possible cure in a significant number of patients with CML. Several prognostic features influence relapse and survival following allogeneic BMT for CML. The most important factor is treatment of patients during chronic phase. The timing of BMT in chronic phase CML remains controversial, because the Seattle findings that BMT done within a shorter interval from diagnosis to transplant was associated with improved survival has not been confirmed by the IBMTR. No factor can predict in the individual patient the timing of transformation, even in patients with low-risk chronic phase CML, but we believe that allogeneic BMT should be offered as soon as possible for newly diagnosed patients who have histocompatible siblings. More widespread application of BMT in CML is possible because of effective methods for preventing GVHD, the major cause of morbidity after allogeneic BMT. However, in vitro techniques for the depletion of donor marrow T cells have resulted in higher graft failure and relapse rates. More precise understanding of the immune mechanisms involved may permit more selective depletion techniques which not only abrogate GVHD but also permit sustained engraftment and preserve GVL effect. This may extend application of BMT for patients with mismatched related or histocompatible unrelated donors. It is of interest that cytogenetic relapse after BMT is not invariably followed by hematologic relapse. It is likely that the use of polymerase chain reaction techniques which detect the bcr-abl rearrangement at a very low level will identify the persistence of the malignant clone after allogeneic BMT in even more patients. At present, the significance of such findings is unclear, but further study of the kinetics of disappearance of the CML clone post-BMT may increase our understanding of the immune mechanisms involved in suppression of the malignant clone and determine whether in fact CML can be cured using BMT approaches.
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PMID:The evolving role of bone marrow transplantation in the treatment of chronic myelogenous leukemia. 218 97

BMT is the only curative therapy for CML, a uniformly lethal malignant disorder of the hematopoietic stem cell. Younger patient age and transplant in CP are associated with better outcome. Transplant within 1 year of diagnosis may provide a greater chance of survival than transplant at a longer interval from diagnosis. T-cell depletion of donor BM significantly reduces the incidence of acute and chronic GVHD, but is associated with an increased risk of graft failure and a marked increase in rate of relapse. Early results suggest that HLA-matched or partially HLA-mismatched unrelated donors may be used successfully in cases in which a suitably matched related donor is not available. Autologous transplantation of BM or PB stem cells can result in successful engraftment and possibly prolonged survival in some patients with CML. Following allogeneic BMT, some patients relapse cytogenetically without progressing to hematologic relapse. The use of PCR methodology to amplify bcr-abl transcripts has revealed persistence of the malignant clone in a substantial number of patients who are in hematologic and cytogenetic remission. The clinical significance and biologic mechanism(s) of this form of molecular relapse remain to be defined.
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PMID:Treatment of chronic myelogenous leukemia with bone marrow transplantation. 219 13

We analysed probability of disease free survival (DFS) and remaining in remission (POR) in evaluable patients with hematological malignancies undergoing allogeneic bone marrow transplantation by Nagoya BMT groups between 1976 and August 1989 according to conditioning regimens retrospectively. Patients were divided into good risk patients with acute leukemia in first remission or CML in chronic phase and high risk patients with advanced disease. The results are as follows: 1. DSF and POR in good risk patients was 45% and 68% at 7 1/2 years for thirty nine patients treated by CY + TBI, 63% and 78% at 5 2/3 years for thirty nine patients treated by CA + CY + TBI, 84% and 84% at 2 years for sixteen patients treated by preconditioning regimens without TBI respectively. 2. DFS and POR in high risk patients was 21% and 45% at 6 years for twenty nine patients treated by CY + TBI, 23% and 48% at 4 5/6 years for forty patients treated by CA + CY + TBI, 64% and 74% at 2 years for eight patients treated by preconditioning regimens without TBI respectively. 3. There were no statistical differences among these conditioning regimens in good and high risk patients. These results show that more effective and stronger preconditioning regimens are needed especially for high risk patients for prevention of posttransplant leukemia relapses.
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PMID:[Comparison among three preconditioning regimens for allogeneic bone marrow transplantation in hematological malignancies]. 220 18

Since 1976 in Genoa, 291 TBI treatments were performed. Before allogeneic BMT, 1000 cGy/1 fx were prescribed in the first 22 patients, and then 990 cGy/3 fx/3 d in AML and CML, and the same or 1200 cGy/6 fx/3 d in ALL. Survival (S) and probability of remaining in remission (PRR) were 54% and 69% at 80 months in 80 AML; in 62 CML 45% and 60% at 60 months; in 69 ALL, 32% and 45% at 82 months. Differences in favour of higher doses and dose rates were observed and are presented. Before autologous BMT, 1000 cGy/1 fx were prescribed to AML and NHL, and 1200 cGy/3 fx/3 d to ALL patients. Disease free survival (DFS) was 71% and 13% at 82 months in 21 AML treated in first R and 9 ALL, respectively; 81% at 32 months in 11 NHL treated in R.
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PMID:Total body irradiation before allogeneic and autologous bone marrow transplantation: a ten year Genoa experience. 224 39

20 CML patients with hematological (5 pts) or only cytogenetic (15 pts) relapse occurring after allogeneic BMT have been treated with alpha-2b-interferon (IFN) at a starting dose of 5 x 10(6) IU/m2, subcutaneously, three times a week. All 5 patients with hematological relapse achieved hematological remission without reduction of bone marrow Ph1-positive cells. With a median follow-up of 43 months (range 6-48) from the hematological relapse, 3 patients are alive and 2 patients died from non-lymphoid blast crisis. 7 out of 15 patients with only cytogenetic relapse remain in hematological remission at a median of 37 months (range 3-45) from cytogenetic relapse, with 2 patients achieving complete cytogenetic remission confirmed at the molecular level by disappearance of the bcr rearranged band. With a median follow-up of 21 months (range 6-46), 8 patients progressed from cytogenetic to hematological relapse: 4 patients died from blast crisis and the other 4 patients are currently alive in chronic phase. For the 15 patients, the actuarial survival from BMT is 71% at 5 years.
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PMID:Alpha-2b-interferon as single therapy for patients with chronic myeloid leukemia relapsing after T-cell depleted allogeneic bone marrow transplantation. 227 45

A 31-year-old woman with Philadelphia (Ph) chromosome-positive chronic myeloid leukaemia (CML) underwent allogenic bone marrow transplantation during accelerated phase. Non-T-cell-depleted marrow from a male sibling mismatched at one Class 2 histocompatibility locus was infused after conditioning with total body irradiation and intravenous cyclophosphamide. Cyclosporin and methotrexate were given for prevention of graft-versus-host disease (GVHD). Prompt engraftment occurred with donor karyotype cells, followed by transient moderate acute GVHD. However, by day 60 after BMT, haematological relapse occurred with increasing splenomegaly, leucocytosis, increasing marrow fibrosis, and cytogenetic mosaicism, consisting of 47% donor metaphases with 53% Ph-positive host metaphases, some containing additional structural changes. Thirty days later further cytogenetic progression was evident. A slowly progressive fungal pneumonia concurrently present was treated with intravenous amphotericin and gradual reduction of cyclosporin. Subsequently, without further cytotoxic chemotherapy, pancytopenia and bone marrow hypoplasia developed, and on day 144 only donor karyotype marrow cells were seen. Chromosomes have remained of donor type on subsequent occasions, and the patient has a normal performance status 25 months after BMT. The patient's course illustrates that factors operating after allogeneic BMT contribute to longterm control of CML. The factors potentially responsible for this spontaneous remission, after early relapse, are discussed.
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PMID:Spontaneous complete remission of chronic myeloid leukaemia following haematological relapse after allogeneic bone marrow transplantation. 228 87

We treated a patient with chronic granulocytic leukemia (CGL), in the accelerated phase by intensive chemotherapy followed by the infusion of cryopreserved peripheral blood buffy-coat cells. The cells had been stored for 32 months. The chemotherapy consisted of daunorubicin 40 mg X 2 days, vincristine 2 mg X 1 day, cytosine arabinoside (Ara-C) 200 mg X 6 days and prednisolone 30 mg X 7 days in the first week, then Ara-C 3 g/m2 X 3 days and cyclophosphamide 60 mg/kg X 2 days in the second week, but reversion to the chronic phase was not achieved. Therefore, total body irradiation (TBI) was added to repeated intensive chemotherapy followed by infusion of the remaining cells. Marrow recovery was good. The patient is currently alive and has been in the chronic phase for 22 months. This preliminary result indicates that this therapy may be tried soon after transformation in CGL and that TBI is an important part of therapy in BMT in the accelerated or blastic phase of CGL.
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PMID:Treatment of chronic granulocytic leukemia in the accelerated phase by transfusion of autologous buffy-coat cells--a case report. 233 Aug 6

The polymerase chain reaction (PCR) allows the detection of minimal amounts of nucleic sequences and has been successfully used to test for the chronic myeloid leukemia-specific bcr/abl transcripts. We studied blood samples from 17 patients who had undergone allogeneic bone marrow transplantation for CML, using a modified polymerase chain reaction-based assay for the detection of leukemic mRNA. This nested PCR technique was found to be highly sensitive, detecting the chimeric bcr/abl transcript in 16 of 17 patients including several long-term survivors. Cytogenetic techniques failed to detect Ph mitoses. The clinical significance of the persisting bcr/abl transcript for long periods following BMT is poorly understood and remains to be elucidated by further studies.
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PMID:Frequent detection of minimal residual disease by use of the polymerase chain reaction in long-term survivors after bone marrow transplantation for chronic myeloid leukemia. 240 20

In acute leukaemias there was a stable plateau in the survival curve at 45% after two years if grafted in first complete remission (n = 20) but only 13% of the patients are disease-free alive if grafted in a more advanced stage of the disease (n = 8). In 16 patients transplanted for chronic myeloid leukaemia the overall survival is 40%, in cases with graft-versus-host disease (GVHD) prevention by cyclosporine survival rate could be improved. Only 8 patients with severe aplastic anaemia, partially in low performance status were able to be transplanted; three died of infections, another by acute GVHD. The fatal complications in our study characterize the international well-known major problems in BMT: GVHD, interstitial pneumonitis, infections, graft failure in aplastic anaemia and recurrence of leukaemia, especially in more advanced leukaemia stage.
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PMID:Allogeneic bone marrow transplantation for leukaemia and aplastic anaemia. Results of the Leipzig BMT Group. 248 Feb 78

With increasing survival rates of children grafted for different malignancies concerns about the longterm side effects of this treatment are growing. Therefore, investigations on the function of endocrine systems were conducted in a total 28 patients grafted for various reasons: ALL (N = 18), AML (N = 1), SAA (N = 3), CML(N = 4), neuroblastoma (N = 2). The results can be summarized as follows: 1. The extent of hormonal derangements is primarily dependent on the extent of irradiation prior to BMT. Integrity of hormonal systems was found in cases without irradiation (SAA) or if TBI did not exceed 3 Gy. 2. Primary hypogonadism was present in 18 patients. 3. Primary hypothyroidism was present in 2 patients. 4. Growth impairment was observed in 8 patients. In four of these cases growth hormone deficiency was the cause. In four other cases with graft-versus-host-disease and hepatic involvement SmC/IGF I levels were severely diminished. The data suggest that in most cases BMT itself has relatively few negative effects on the endocrine regulatory system. However, more detailed investigations before and after BMT will be needed to further validate these observations.
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PMID:Influence of allogeneic bone marrow transplantation on the endocrine system in children. 248 Mar 5


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