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

This report presents the analysis of leukemic relapse of 52 patients who received allogeneic bone marrow transplantation between July 1984 and May 1990. Conditioning regimen consisted of TBI + CY and GVHD prophylaxis consisted of cyclosporin-A and methotrexate. The relapse ratios of chronic myelogenous leukemia (CML) (21 in chronic phase, 1 in accelerated phase, 1 in blastic crisis), acute nonlymphocytic leukemia (ANLL) (all 17 in 1st CR), acute lymphocytic leukemia (ALL) (all 12 in 1st CR) were 13%, 18%, 25%, respectively, and 3 year disease free survival (DFS) was as follows, CML 68%, ANLL 72%, ALL 49%. Regarding acute GVHD grading and chronic GVHD presence, 3 year DFS was as follows, acute GVHD 0 degree: 59%, I degree: 78%, II degree-IV degree: 53%, chronic GVHD (+): 82% GVHD (-): 77%. In our center leukemic relapse has been the major cause of death after BMT since 1984. Among 9 relapsed cases, one recurred more than 3 years after BMT, and another one got recurrent leukemia of donor origin.
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PMID:[The analysis of leukemic relapse after allogeneic bone marrow transplantation]. 175 50

The Polymerase Chain Reaction (PCR) was used to evaluate minimal residual disease in 21 Ph+ CML patients at various intervals after allogeneic bone-marrow transplantation (ABMT) by amplification of bcr-abl cDNA. All patients were cytogenetically Ph- at the moment of molecular analysis. Of these 76% were PCR negative, 24% positive for bcr-abl transcripts. 100% of the Cyclosporine A/Methotrexate treated patients (7/7) were negative. Severe chronic GvHD was twice as frequent in PCR positive patients (60%) than in negative ones (31%). The only patient who relapsed during follow up was PCR positive. The two longest survivors were PCR negative. These data are still insufficient for assessing the predictive value of PCR analysis in CML. Patients. 25 patients with Ph+ CML at diagnosis were enrolled in this study. Two died soon after BMT because of infection for failure of engraftment/early relapse, two were Ph chromosome positive and PCR+, and were therefore dismissed from this study. All remaining 21 patients were cytogenetically Ph- at the time of molecular analysis and underwent ABMT from matched donors. All patients were conditioned with cyclophosphamide and TBI: 330 cGy the three days prior to transplantation (990 cGy total, treatment B), or 200 cGy two times daily for three days (1200 cGy total, treatment A). In 3 cases the marrow was treated for GvHD prophilaxis with Campath alone or Campath plus BT 5/9 monoclonal antibodies (1). All patients were treated with Cyclosporin A (CS) 5 mg/kg i.v. from the day prior to transplantation until 25-30 days after; 9 of these were treated with CS plus Methotrexate (MTX).
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PMID:An assessment of chimeric transcript detection in CML patients after bone marrow transplantation. 187 98

One hundred eighty patients with chronic myelogenous leukemia, who received an unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180 patients, 126 were non-randomly assigned to single dose total body irradiation (STBI group) and, 54 to fractionated total body irradiation (FTBI group). With a median follow-up of 40 months, there is no statistically significant difference in the 5-year survival rate between the two groups (51% for the whole population). In a first step we demonstrate by multivariate analysis that total body irradiation fractionation can dramatically decrease the incidence of interstitial pneumonitis. However, a multivariate analysis of potent risk factors for relapse post-transplant strongly suggests that TBI fractionation is also linked to an increased relapse rate. So, a sparing effect of fractionation for lung tissue could be offset by a less effective leukemic stem cell kill. Those results from a retrospective, non-randomized, multi-institutional study clearly need additional clinical data, ideally from a randomized study.
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PMID:Influence of the fractionation of total body irradiation on complications and relapse rate for chronic myelogenous leukemia. The Groupe d'Etude des greffes de moelle osseuse (GEGMO). 199 23

Autologous bone marrow transplantation (ABMT) has developed considerably in the past 15 years and is now a routine procedure for the consolidation of acute leukemias, non-Hodgkin's lymphomas and Hodgkin's disease. In addition, ABMT has been tested in multiple myeloma (MM) and even considered in highly selected cases of chronic myelocytic leukemia (CML). Interest has resulted from the discovery of new purging procedures such as long-term cultures with or without serum-free media containing various lymphokines, the evaluation of cryoinjury on malignant cells, the increased detection of minimal residual disease using PCR, and the acceleration of hemopoietic recovery post-ABMT through the use of peripheral blood stem cells and/or lymphokines. Results presented include data from the international (ABMTR) and European (EBMT) registries, and our own unit in Paris. With respect to acute leukemias, (a) the EBMT listed 1,688 patients. The overall results were as follows: for patients autografted in complete remission (CR) 1, the leukemia-free survival and relapse rate at 7 years were 48 +/- 2% and 41 +/- 3% for AML and 44 +/- 5% and 45 +/- 5% in acute lymphoblastic leukemia (ALL), respectively. In CR2, the figures were 34 +/- 4% and 54 +/- 5% for AML and 32 +/- 3% and 62 +/- 4% for ALL, respectively. Patients not relapsing at 1 year post-ABMT had a probability of being cured at 7 years of 86 and 71% if autografted in CR1 and CR2 for AML and 81 and 59% for ALL, respectively. Multivariate analysis of relapse rates in several subpopulations confirmed the efficacy of marrow purging in AML CR1: in patients transplanted prior to January 1988 (minimum follow-up of 2 years), the relapse rate with purged marrow was 35 +/- 5% vs. 47 +/- 3% (p less than 0.005). (b) In Paris, St-Antoine, using TBI and marrow purged with mafosfamide at levels individually adjusted (Blood 1986;67:1367), the probability of remission and DFS were 84 and 62% in AML CR1 63 and 59% in ALL CR1, respectively. There was a statistically significant relationship between the relapse rate and the residual amount of CFUGM progenitors in the marrow after purging. The cutoff point was 0.3%, with a relapse rate of 54% in those receiving marrow containing the higher residual CFUGM fractions and only 29% in those receiving less. With respect to non-Hodgkin's lymphomas, the EBMT listed 698 patients. In intermediate or high grade lymphomas, the DFS at 6 years was 30% and 18% in sensitive and resistant relapses, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Autologous bone marrow transplantation in hematological malignancies. 204 65

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

In May 1979, Memorial Sloan-Kettering embarked on a programme of hyperfractionated TBI (HFTBI), 1320 cGy in 11 fractions over 4 days with partial lung shielding (1 HVL), followed by cyclophosphamide (60 mg/kg/d x 2d) for cytoreduction prior to allogeneic bone marrow transplantation (BMT). Anterior and posterior chest wall electron "boosts" were given to the areas blocked (600 cGy in 2 fractions) on the last two days of treatment. Since then, we have treated over 600 patients with HFTBI, the majority for allogeneic BMT. Several modifications have occurred over the years. We have added a "boost" electron dose of 400 cGy to the testes in all male leukemic patients; this reduced testicular relapses from a rate of 14% (4/28) to 0%. In an attempt to increase engraftment of T-depleted BMTs, we added one additional fraction; since our present dose/fraction was also increased to 125 cGy, we now deliver a total dose of 1500 cGy in 12 fractions over 4 days for allogeneic transplants. Tolerance to HFTBI has been excellent relative to the single dose (SD) regimen utilised prior to May, 1979. The incidence of fatal interstitial pneumonitis (IP) decreased from 50% in the SD regimen to 18% after the introduction of HFTBI. In children, the incidence of IP was only 4% with HFTBI. With the introduction of T-depleted marrows, fatal IP in adults has decreased also, e.g. to less than 10% in CML patients. With conventional BMT after HFTBI, relapse at 5 years has been exceedingly low (e.g. in children, 13% for ALL, 2nd remission and 0% for AML, 1st remission) and engraftment has been 100%. With matched T-depleted BMT, rejections have occurred in 15% overall; the incidence of graft failure has not been reduced by the higher dose of HFTBI. Relapses in this setting are equivalent to relapses with conventional BMT for AML, but appear to be increased for ALL. Radiobiological findings related to HFTBI will also be discussed.
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PMID:Total body irradiation for bone marrow transplantation: the Memorial Sloan-Kettering Cancer Center experience. 224 51

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

Bu and Cy is a bone marrow transplant preparative regimen that is effective for ANLL and certain genetic diseases. It has shown promise in CML. Its effectiveness in ALL and lymphomas remains to be explored. The substitution of Bu for TBI in marrow transplant regimens would seem to have a number of practical and theoretical advantages.
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PMID:Busulfan (Bu) and cyclophosphamide (Cy) for marrow transplantation. 265 11

From June 1981 to March 1987, 106 patients--59 with acute myeloid leukemia (AML) and 47 with chronic myelogenous leukemia (CML)--were treated with Cyclophosphamide 60 mg/kg X 2 d and total body irradiation (TBI-990 cGy/3fr/3d described dose) before allogeneic bone marrow transplantation. Seventy-nine patients are evaluable for risk of relapse: 32 with chronic myelogenous leukemia (23 in first chronic phase, 9 in accelerated phase) and 47 with acute myeloid leukemia (38 in first complete remission, 9 in subsequent phases). Actual TBI doses delivered to these patients varied between 839 and 1250 cGy (mean 956 +/- 101)/3 fr/3d, with dose rates between 2.7 and 7.25 cGy/min (mean 4.2 +/- 1.8). Patients receiving high (greater than 990 cGy) and low (less than or equal to 990) dose and/or dose rate (greater than 4 cGy/min and less than or equal to 4, respectively) have been evaluated overall and stratified by type of leukemia and phase of disease. When the patients are considered altogether, high total dose is significantly correlated with decreased risk of relapse (p = 0.0005) as well as high dose rate (p = 0.03). When considering specific subgroups, the influence of total dose on relapse rate is evident both for "early" and "advanced" leukemias, while an impact of dose rate appears only for chronic myelogenous leukemia in 1st chronic phase. Pertinent radiobiological and clinical literature is reviewed, and a possible role of dose fractionation and dose rate in leukemic control rate is evidenced; in this TBI setting, total dose not less than 990 cGy/3fr/3d and dose rate not less than 4 cGy/min have to be guaranteed.
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PMID:Total body irradiation in acute myeloid leukemia and chronic myelogenous leukemia: influence of dose and dose-rate on leukemia relapse. 267 77


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