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)

The outcomes of bone marrow transplantation (BMT) performed at the Institute of Haematology and Blood Transfusion from April 1988 to December 1994 in 31 patients with chronic myelogenous leukemia are presented. Age of the patients range from 18 to 49 years, median 34 years. Male:female ratio was 1.58:1. The conditioning regimen consisted of Cyclophosphamide and total body irradiation (TBI) or Busulfan and Cyclophosphamide. The results are evaluated as of January 1, 1995. Nineteen patients (61.3%) are alive, 12 patients (38.7%) died. The causes of death are discussed. The median time of follow up all patients is 10.4 months, range 0.3-81.5. The median time of follow up of surviving patients is 21.8 months, range 2.5-81.5. Probability of 2 years survival by Kaplan-Meier analysis is 58 +/- 10%. Of the 24 transplanted in the first chronic phase, 18 patients are alive. Of the 7 transplanted in advanced phase of the disease, 1 patient is alive. Of the 27 patients, who received bone marrow from an HLA identical sibling, 19 are alive. Of the 4 patients who received bone marrow from other donor than an HLA identical sibling, none is alive. Acute GvHD III.-IV. grade developed in 5 patients (16.1%), moderate and severe chronic GvHD developed in 11 patients (31.5%). Cytogenetic relapse was diagnosed in 1 patient, hematological relapse in 2 patients. Karnofsky scores of patients surviving after BMT range from 30% to 100%, median 90%.
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PMID:[Treatment of chronic myeloid leukemia with bone marrow transplantation at the Institute of Hematology and Blood Transfusion in Prague]. 857 99

This study reviews results of a radiation-free preparative regimen consisting of busulfan and cyclophosphamide in 65 unrelated allogeneic bone marrow transplant recipients. Thirty-eight patients had chronic myelogenous leukemia (17 patients chronic phase, 13 patients accelerated phase, eight patients blast phase), 19 patients had acute leukemia (second complete remission or relapse) and eight patients had myelodysplasia. The patients were transplanted at four different medical centers from July 1988 to November 1992. Ages ranged 4-48 years (median 32). Fifty-seven patients received busulfan 16 mg/kg and cyclophosphamide 120 mg/kg, and eight received busulfan at doses between 15 and 17 mg/kg and cyclophosphamide at doses 100-200 mg/kg as preparative regimens. All patients received cyclosporine for graft-versus-host disease prophylaxis; in addition 46 patients received corticosteroid, 38 methotrexate, six anti-CD5 ricin A-immunotoxin, and four T cell-depleted bone marrow. Median follow-up of survivors was 53 months (range 15-68 months). Four year actuarial survival was 24 +/- 12%. Four-year survival based on disease was 29 +/- 27% for chronic myelogenous leukemia (CML) in chronic phase, 20 +/- 9% for chronic myelogenous leukemia in accelerated phase, 0% for chronic myelogenous leukemia in blast phase, 32 +/- 40% for acute leukemia, and 38 +/- 34% for myelodysplasia. Actuarial survival was 66 +/- 40% in patients age < 20 years, vs 23 +/- 13% for patients ages 20 to 40, and 10 +/- 14% for patients age > 40 years. Fifty patients (88%) engrafted. Graft failure occurred in eight patients. Acute graft-versus-host disease grade II-IV occurred in 36 (72%). Two patients relapsed after engraftment with the donor cells and died of leukemia within a month of relapse. The most common causes of death were graft-versus-host disease (37%), and transplant-related toxicity (59%); relapse (4%) was a rare cause of death. Busulfan/cyclophosphamide is an effective preparative regimen in unrelated bone marrow transplantation permitting adequate engraftment and a low relapse rate. Best results are observed in patients less than 20 years old.
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PMID:Unrelated allogeneic bone marrow transplantation using high-dose busulfan and cyclophosphamide (BU-CY) for the preparative regimen. 873 82

A retrospective analysis of the treatment with Interferon alpha in 18 patients with Ph positive chronic myeloid leukaemia is presented and compared with the results of peroral chemotherapy with Hydroxyurea or Busulphan in 20 patients. Patients treated with Interferon were significantly younger than the control group (median age 40.5 versus 55.5) (p = 0.01) and were followed-up for shorter period of time (median 10.5 months versus 36.5 months) ( p = 0.002), but did not differ in other parameters. Despite the shorter period of observation and treatment, significantly more complete haematological remissions were achieved with Interferon (86%) than with peroral chemotherapy (25%) (p = 0.03). 6 major and 2 minor (44%) cytogenetic responses were observed after Interferon, despite the fact that 8 patients had been treated for less than one year. Interferon was not the optimal therapy in the patients with additional or complex cytogenetic abnormalities at the time of diagnosis, which were the most significant negative prognostic factor. In general, our short-term results confirm the importance and effectiveness of Interferon in the patient with CML providing the therapy was started early, with an effective dose and with simultaneous cytogenetic monitoring. Longer observation of the patients is needed to confirm the impact of Interferon on the survival of patients.
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PMID:[Interferon-alpha in the treatment of patients with chronic myeloid leukemia]. 922 59

Busulfan is an alkylating agent commonly used in the treatment of chronic myelogenous leukemia and in combination with cyclophosphamide in preparation for allogeneic bone marrow transplantation. Serial treatment of a childhood high-grade glioma xenograft (D-456 MG) with busulfan resulted in a busulfan-resistant xenograft, D-456 MG(BR). Cross-resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea was seen but not resistance to cyclophosphamide or CPT-11. Cytoplasmic levels of glutathione in D-456 MG(BR) were approximately one-half those found in D-456 MG. This depletion could not be explained by levels of glutathione-S-transferase, or by amplification, rearrangement, or increased levels of transcript of gamma-glutamylcysteine synthetase. Furthermore, depletion of glutathione in D-456 MG did not alter busulfan activity. Quantitation of busulfan levels in D-456 MG and D-456 MG(BR) xenografts following treatment of mice at the dose lethal to 10% of the animals demonstrated that significantly lower levels of drug were achieved in D-456 MG(BR). These studies suggest that alterations in drug transport or metabolism of busulfan may play a role in the resistance of D-456 MG(BR) to this alkylator.
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PMID:Characterization of the mechanisms of busulfan resistance in a human glioblastoma multiforme xenograft. 927 17

The treatment of chronic myeloid leukaemia has become extremely complex in recent years. Busulphan has been displaced by hydroxyurea where rapid control of the leukocyte count is required. It is generally accepted that interferon-alpha (IFN-alpha) prolongs life for those who achieve a major or complete cytogenetic response and it may also prolong life for those who achieve only a haematological response. Thus routinely most newly diagnosed patients are started on treatment with IFN-alpha alone or in combination with other agents and this agent is continued if possible for 2 or more years. Because allografting is the only way of curing patients with CML, those under the age of 50 or 60 years who have HLA-identical siblings should be offered treatment by allogeneic haemopoietic stem cell transplantation; however, the risks of morbidity and mortality remain appreciable. Transplants with stem cells from phenotypically HLA-matched donors should also be considered for younger patients. The role of autografting is not yet clearly established; a series of controlled studies comparing autografting with IFN-alpha have therefore been activated. Because patients usually retain in their blood and marrow substantial numbers of Ph-negative stem cells a variety of methods designed to favour collection in vivo or isolation in vitro of Ph-negative stem cells are currently under investigation. To integrate these different approaches to treating patients with CML in chronic phase a variety of algorithms or flow charts have been proposed but many of the criteria on which the recommended treatment decisions are based remain controversial or ill-defined.
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PMID:Treatment of chronic myeloid leukaemia: some topical questions. 937 72

The choice of dose and fractionation for total body irradiation is made difficult by the large number of considerations to be taken into account. The outcome of bone marrow transplantation after total body irradiation can be understood in terms of tumour cell killing, engraftment, and normal tissue damage, each of these endpoints being influenced by irradiation-, disease-, transplant-, and patient-related factors. Interpretation of clinical data is further hampered by the overwhelming influence of logistic constraints, the small numbers of randomised studies, and the concomitant variations in total dose and fraction size or dose rate. So far, three cautious conclusions can be drawn in order to tentatively adapt the total body irradiation schedule to clinically-relevant situations. Firstly, the organs at risk for normal tissue damage (lung, liver, lens, kidney) are protected by delivering small doses per fraction at low dose rate. This suggests that, when toxicity is at stake (e.g., in children), fractionated irradiation should be preferred, provided that interfraction intervals are long enough. Secondly, fractionated irradiation should be avoided in case of T-cell depleted transplant, given the high risk of graft rejection in this setting. An alternative would be to increase total (or fractional) dose of fractionated total body irradiation, but this approach is likely to induce more normal tissue toxicity. Thirdly, clinical data have shown higher relapse rates in chronic myeloid leukaemia after fractionated or low dose rate total body irradiation, suggesting that fractionated irradiation should not be recommended, unless total (or fractional) dose is increased. Total body irradiation-containing regimens, primarily cyclophosphamide/total body irradiation, are either equivalent to or better than the chemotherapy-only regimens, primarily busulfan/cyclophosphamide. Busulfan/cyclophosphamide certainly represents a reasonable alternative, especially in patients who may not be eligible for total body irradiation because of prior irradiation to critical organs.
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PMID:[Total body irradiation: current indications]. 974 22

Busulfan is an alkylating agent commonly used to ablate marrow before hematopoietic stem cell transplantation. High levels have been shown to increase the chance for severe hepatic veno-occlusive disease, for which there is no treatment and which can be fatal. Low levels are associated with recurrence of chronic myeloid leukemia, whereas even lower levels are associated with graft rejection. The therapeutic window for busulfan is narrow and disease and graft-source dependent. Busulfan concentration in plasma is readily assayed by gas chromatography. In the authors' center, busulfan levels determined from the first dose of the drug are used to adjust the dose to that selected to achieve the desired therapeutic outcome by the third dose of the 16-dose regimen. Thus, turnaround time is less than 6 hours. Analytical and pharmacokinetic aspects of busulfan therapeutic monitoring are described. The cost of pharmacokinetically targeting busulfan concentration is < or = 1% of the cost of hematopoietic stem cell transplantation.
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PMID:Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. 978 Jan 33

We describe a pediatric case of acute promyelocytic leukemia with an i(17q) after treatment of BCR/ABL positive chronic myeloid leukemia (CML) for 3.5 years. The patient was treated with Busulphan, alpha-2a interferon, hydroxyurea, and cytosine arabinoside at various times in the course of the chronic phase of CML, because he had no HLA-identical donor for bone marrow transplantation. Hematologic remission was achieved for a short time, but cytogenetic remission was never possible. When promyelocytic blast crisis was diagnosed according to the French-American-British classification, cytogenetic studies revealed an i(17q) as a new feature in our patient. The promyelocytic transformation was associated with the appearance of an i(17q) preceding CML are discussed in the light of recent literature.
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PMID:Development of acute promyelocytic leukemia with isochromosome 17q after BCR/ABL positive chronic myeloid leukemia. 1008 49

Leukemic patients receiving marrow from HLA-identical sibling donors were randomized to treatment with either busulfan 16 mg/kg (n = 88) or total body irradiation ([TBI] n = 79) in addition to cyclophosphamide 120 mg/kg. The patients were observed for a period of 5 to 9 years. Busulfan-treated patients had an increased risk of veno-occlusive disease (VOD) of the liver (12% v 1%, P =.01) and hemorrhagic cystitis (32% v 10%, P =.003). Acute graft-versus-host disease (GVHD) was similar in the two groups, but the 7-year cumulative incidence of chronic GVHD was 59% in the busulfan-treated group versus 47% in the TBI group (P =.05). Death from GVHD was more common in the busulfan group (22% v 3%, P <.001). Obstructive bronchiolitis occurred in 26% of the busulfan patients but in only 5% of the TBI patients (P <.01). Complete alopecia developed in 8 busulfan patients and partial alopecia in 17, versus five with partial alopecia in the TBI group (P <.001). Cataracts occurred in 5 busulfan-treated patients and 16 TBI patients (P =.02). The incidence of relapse after 7 years was 29% in both groups. Seven-year transplant-related mortality (TRM) in patients with early disease was 21% in the busulfan group and 12% in the TBI group. In patients with more advanced disease, the corresponding figures were 64% and 22%, respectively (P =.004). Leukemia-free survival (LFS) in patients with early disease was 68% in busulfan-treated patients and 66% in TBI patients. However, 7-year LFS in patients with more advanced disease was 17% in the busulfan group versus 49% in the TBI group (P <.01). In patients with chronic myeloid leukemia (CML) in first chronic phase, 7-year LFS was 72% and 83% in the two groups, respectively.
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PMID:Increased risk of chronic graft-versus-host disease, obstructive bronchiolitis, and alopecia with busulfan versus total body irradiation: long-term results of a randomized trial in allogeneic marrow recipients with leukemia. Nordic Bone Marrow Transplantation Group. 1062 26

Graft versus host disease (GVHD) and recurrence of basic disease are major obstacles to a successful allogeneic bone marrow transplantation (BMT) outcome. One of the possibilities of maintaining the therapeutic potential of marrow allografting in the absence of GVHD is to intensify the conditioning regimen administered pre-T-cell depleted BMT in order to compensate for the loss of GVH related graft versus leukemia (GVL) effect. In order to do so we used a preparative regimen consisting of three alkylating agents-Busulfan (BU), Thiotepa (TTP) and Cyclophosphamide (CY)-for T-cell depleted allogeneic stem cell transplantation (SCT) instead of the standard BU-CY protocol. The effect of this intensified regimen was investigated in 30 consecutive leukemia patients who underwent T-cell depleted SCT from HLA identical siblings. Sixteen of the patients were males and 14 females, of median age 24 (5-43) years. Fourteen patients had acute myelogenous leukemia (AML), ten acute lymphoblastic leukemia (ALL), four chronic myelogenous leukemia (CML) and two myelodysplastic syndrome. The conditioning regimen consisted of BU 4 mg/kg x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1). Engraftment was normal, with WBC >1.0x10(9)/l at day +18 (10-32), ANC >0.5x10(9)/l at day +21 (9-33) and platelets >25x10(9)/l at day +30 (14-69). Regimen related toxicity (RRT) was moderate and transplant related complications comparable to other conventional conditioning protocols. Overall survival and disease free survival (DFS) at 60 months follow up was 50%. Only three patients (10%), with ALL, relapsed and subsequently died. From the current data it would appear that TTP does not significantly improve BMT outcome in patients with leukemia, when compared to the standard BU-CY conditioning. However, our results with the BU-TTP-CY combination followed by T-cell depleted allogeneic SCT could provide the basis for a prospective randomized study comparing this protocol with the standard BU-CY regimen.
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PMID:The role of thiotepa in allogeneic stem cell transplantation in patients with leukemia. 1057 41


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