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)

One-hundred-and-forty-three patients with haematological malignancy or severe aplastic anaemia received HLA-identical sibling bone marrow transplants. In 111 of these patients who had haematological malignancy and who were prepared for transplant with cyclophosphamide 120 mg/kg and fractionated total body irradiation 12-14 Gy, the incidence of haemorrhagic cystitis and hepatic veno-occlusive disease was 13% and 3%, respectively. In contrast, the incidence in 15 leukaemic patients prepared for transplant with chemotherapy regimens containing high-dose busulphan was 47% and 20%, respectively (p less than 0.001). Two patients in this latter group who developed fatal veno-occlusive disease had chronic myeloid leukaemia and had received long-term low-dose busulphan pre-transplant. Neither complication occurred in 26 patients prepared by cyclophosphamide alone (20 patients with severe aplastic anaemia) or with cyclophosphamide and melphalan (six patients with leukaemia). The regimen of busulphan 16 mg/kg in combination with cyclophosphamide 120 mg/kg was associated with a short duration of total leucopenia with a significantly higher leucocyte count on the day of marrow transplant compared to other regimens. Furthermore, oro-pharyngeal mucositis was not severe even when methotrexate was utilised as post-transplant prophylaxis for graft-versus-host disease. Thus, while the busulphan-cyclophosphamide regimen appeared useful, we suggest that (1) high-dose busulphan should not be used as a preparative regimen for patients previously exposed to busulphan, and (2) bladder irrigation (as well as intravenous hydration) is necessary to minimise haemorrhagic cystitis in patients given regimens that incorporate high-dose busulphan.
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PMID:Preparative regimens for marrow transplantation containing busulphan are associated with haemorrhagic cystitis and hepatic veno-occlusive disease but a short duration of leucopenia and little oro-pharyngeal mucositis. 333 86

Allogeneic bone marrow transplantations were carried out between March 1983 and July 1985 in 31 patients aged 7 to 45 years (median 18 years). Acute lymphoblastic leukaemia in 1st to 5th remission was present in 8 patients, acute myeloblastic leukaemia in 1st and 2nd remission in 4 patients, chronic myeloid leukaemia, with various remission status, in 6 patients, 3 patients had severe aplastic anaemia and there were single cases of myelodysplasia and immature cell megakaryocytic myelosis. Transplantation was carried out during relapse in 8 patients with either acute myeloid or lymphoblastic leukaemia. Phenotypic HLA-identical mothers (n = 2) as well as genotypic HLA-identical siblings (n = 27), and in two cases HLA-non-identical mothers, served as bone marrow donors. In leukaemia patients the conditioning treatment consisted of fractionated total body irradiation and high dose cyclophosphamide or etoposide. Patients with severe aplastic anaemia received cyclophosphamide (4 X 50 mg/kg) and fractionated total nodal irradiation (total dose 8 Gy). 19 patients (61%) survived 14 to 605 days after bone marrow transplantation. 15 patients (48%) continue to remain in complete remission with Karnofsky indices of greater than or equal to 90%. Causes for death were infection (n = 3), interstitial pneumonia (n = 3), relapse (n = 3) as well as single cases involving acute graft-versus-host-disease, non-engraftment of donor marrow and veno-occlusive disease of the liver.
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PMID:[Allogeneic bone marrow transplantation after fractionated whole body irradiation. Results at the Kiel transplantation center]. 389 27

Indicine N-oxide is the first member of the large class of compounds comprised of pyrrolizidine alkaloids and their N-oxides to be studied in the treatment of cancer in humans. Twenty-two patients with refractory acute leukemia received indicine N-oxide daily for 5 consecutive days in a dose-seeking study. Of eight patients with refractory acute lymphocytic leukemia, one had a complete remission, and one had a partial remission. Of 11 patients with refractory acute nonlymphocytic leukemia, 2 patients had complete remissions. Of three patients with blast crisis of chronic granulocytic leukemia, one patient had a partial remission. Five patients had severe hepatic toxicity, probably due to veno-occlusive disease induced by the drug. Whether hepatotoxicity and antileukemic activity are a result of the same mechanism of action of indicine N-oxide is not known.
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PMID:Hepatocellular toxicity during the treatment of refractory acute leukemia with indicine N-oxide. 659 Jan 15

Conditioning regimens for BMT are important in determining transplant outcome. A radiation-free protocol containing Mitobronitol (DBM), Cytarabine (Ara-C) and Cyclophosphamide (Cy) was used for conditioning of patients with chronic granulocytic leukemia (CGL). Using this conditioning treatment, fewer transplant related complications, including acute GVHD, VOD and severe infections, were observed. Acute GVHD did not develop, but chronic GVHD, accompanied with graft-versus leukemia, was present in half of the cases. To determine the clinical effect of the DBM/Ara-C/Cy conditioning, the recovery of peripheral blood lymphocytes was examined after allogeneic BMT for patients with CGL in comparison with TBI/Cy conditioning. The lymphocyte subsets of 11 DBM patients were followed and analyzed periodically (30-90 days, 4-12 months and > 13 months) using ten monoclonal antibodies and flow cytometry. Decreased percentage of total T cells as well as CD4+ and CD8+ subpopulations, significantly decreased T cell activation and increased proportion of TCR gamma delta + cells were found to be characteristic in the early post-transplant period in the DBM group. Early recovery and consistently higher percentage of B cells were observed for the whole follow-up period of patients receiving DBM conditioning. A high proportion of NK cells was observed in all transplant recipients. These findings suggest that the characteristic pattern of recovering lymphocytes is associated with the lack of severe transplant-related clinical complications following DBM/Ara-C/Cy conditioning.
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PMID:Lymphocyte subset reconstitution after allogeneic bone marrow transplantation using radiation-free conditioning regimen for patients with chronic granulocytic leukemia. 767 5

The outcomes of 39 patients with hematological disorders who had undergone allogeneic bone marrow transplantation (BMT) from September 1986 to March 1992 were reported. The length of follow-up was six to 50 months. Twenty patients with acute leukemia, eight patients with aplastic anemia, seven patients with chronic myelogenous leukemia, two patients with non-Hodgkin's lymphoma, and two patients with myelodysplastic syndrome were included. Major complications were acute graft-versus-host disease (GVHD) (17 cases out of 36 evaluable cases; 47 percent), chronic GVHD (13/25; 52 percent), sepsis (20/41; 49 percent), interstitial pneumonitis (IP) (10/30; 33 percent), and veno-occlusive disease (VOD) of the liver (5/41; 12 percent). Acute and chronic GVHD were well managed with cyclosporin, methotrexate, and steroids. VOD of the liver seemed to be associated with the pretransplant regimen including busulfan and cyclophosphamide. The overall probability of disease free survival of 39 patients who had undergone allogeneic BMT was 0.56. This includes nine high risk cases such as HLA antigen mismatch between the donor and the recipient, and as in the second or subsequent remission or in relapsed cases. The probability of disease free survival in patients with acute leukemia, chronic myelogenous leukemia, and aplastic anemia including high risk cases was 0.55 (n = 20), 0.71 (n = 7), and 0.50 (n = 8) respectively. These results indicate that allogeneic BMT is the major therapeutic strategy for patients whose survival could not be expected by conventional chemotherapy and that drug intensification for conditioning regimen is also important.
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PMID:Allogeneic bone marrow transplantation as a therapeutic modality for hematological disorders: a report based on 39 cases. 786 58

Seventy-three BMT procedures (42 allogeneic-BMT, 30 autologous-BMT, 1 syngeneic transplant) were undertaken at the Shariati Hospital in Tehran between March 1991 and November 1993. Allogeneic-BMT was performed for thalassaemia major (n = 23), AML in complete remission (n = 3), severe aplastic anaemia (n = 7), CML (n = 7), dyskeratosis congenita (n = 2) and Fanconi anaemia (n = 1). Conditioning regimens comprised busulphan (BU) plus cyclophosphamide (CY) or CY only. Thirty-two (78%) of the 43 patients remain alive 1-34 months after BMT. Twelve patients died: the causes of death were haemorrhagic cystitis (n = 1), CMV pneumonitis (n = 1), GVHD (n = 3), infection (n = 3), rejection (n = 1), VOD (n = 2) and hepatitis (n = 1). Autologous-BMT was performed for patients with AML in CR (n = 16), ALL in CR (n = 9), lymphoma in relapse (n = 3), Ewing sarcoma (n = 1) and multiple myeloma (n = 1). The median age was 18 years. Conditioning regimens were Ara C plus CY, etoposide plus CY and high-dose melphalan. Sixteen (54%) of the 30 patients survive, 14 in continuous complete remission. The causes of death were relapse (AML (n = 7), ALL (n = 4), lymphoma (n = 1)), VOD (n = 1) and infection (n = 1).
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PMID:Bone marrow transplantation in Iran. 792 Mar 8

Between September 1987 and May 1991, 21 children aged 10 months to 15 years (median 9 years) underwent bone marrow transplantation (BMT) for advanced haematological malignancies using a conditioning regimen consisting of total body irradiation (TBI), etoposide 1.8 g/m2 by continuous infusion, and cyclophosphamide 2 g/m2 on 3 consecutive days. The patients included 14 with acute lymphoblastic leukaemia (ALL), 1 with chronic myeloid leukaemia (CML), 1 with juvenile CML, 4 with non-Hodgkin's lymphoma and 1 with acute nonlymphocytic leukaemia. Eleven had an allogeneic BMT from an HLA-matched sibling, and 1 from an unrelated donor. Nine patients received 4-hydroperoxycyclophosphamide purged autologous marrow. Median time to myeloid engraftment (ANC > 500/microliters) was 19 days in allogeneic BMT patients and 28 days in autologous BMT patients (P < .01). Mucositis was the major regimen-related toxicity (RRT). GI toxicity in the form of diarrhoea affected ten patients and five had veno-occlusive disease of the liver. Two patients had mild bladder toxicity and one died of renal toxicity. There was no CNS or cardiac toxicity. There was no significant difference in the incidence of toxicity according to the type of BMT (autologous or allogeneic), total dose, or sequence of TBI. With a median follow-up of 44 months, ten patients are alive (6/12 allogeneic BMT patients and 4/9 autologous BMT patients). Of the 11 deaths, four were related to toxicity (2 aspergillus, 1 haemorrhage following liver biopsy, and 1 from haemolytic-uraemic syndrome), and 4/12 allogeneic and 4/9 autologous BMT patients died from relapsed disease. This conditioning regimen is well tolerated in children, demonstrating mild and reversible RRT.
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PMID:Intensive conditioning regimen for bone marrow transplantation in children with high-risk haematological malignancies. 793 71

Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus-host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan-treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.
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PMID:A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. 816 51

Between 1980 and 1988, 126 patients with leukemia were treated with piperazinedione and fractionated total body irradiation (TBI) followed by allogeneic bone marrow transplantation from HLA matched siblings. Sixty-one patients had acute myelogenous leukemia, 46 acute lymphoblastic leukemia, and 19 chronic myelogenous leukemia. Patients with acute leukemia in first complete remission were transplanted only if perceived to have a low probability of remaining in remission with conventional therapy. The toxicity from the preparative regimen was similar to that of cyclophosphamide and TBI except that none of the patients in the study had hemorrhagic cystitis or veno-occlusive disease. After a median follow up of 114 months, 29 patients (23%) are still alive without relapse. The survival of patients with acute myelogenous or lymphoblastic leukemia transplanted in their first remission were 35% and 43%, respectively. The survival of patients transplanted in their first chronic phase of chronic myelogenous leukemia was 60%. The results of this preparative regimen are comparable to those of cyclophosphamide and TBI.
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PMID:Allogeneic bone marrow transplantation for leukemia following piperazinedione and fractionated total body irradiation. 817

Successful allogeneic peripheral blood progenitor cell (PBPC) transplantation has recently been reported by several transplant centers. This is a first report describing allogeneic PBPC transplantation in five patients using related pediatric donors between the ages of 4 and 13 years. Donors underwent 3 or 4 days of rhG-CSF treatment (6 micrograms/kg q 12 h) for stem cell peripheralization prior to PBPC collection, which was performed by continuous-flow apheresis on day 4 or 5. Venous access was exclusively by ante-cubital veins. A median of 2.2 times (range 1.4-3.6) the donor's total blood volume (TBV) was processed per procedure. In cases where the donor's TBV was < 2 liters, the blood cell separator was primed with human serum albumin (HSA-5%), and anticoagulation was performed using a combination of heparin (pre-apheresis bolus + continuous infusion (CI)) and/or ACD-A (CI at a reduced rate). The median number of CD34+ cells collected per kg of donor body weight (b.w.) and per liter of donor blood processed during each procedure was 128 x 10(4) (range 58 x 10(4)-314 x 10(4)). Between one and two aphereses were sufficient to collect a safe CD34+ cell engraftment dose of 3 or 4 x 10(6)/kg of recipient b.w. Two PBPC recipients were parents, and three were siblings. After freezing and thawing, the median number of CD34+ cells per kg of recipient b.w. thawed and transfused was 8.5 x 10(6) (range 3.2 x 10(6)-9.7 x 10(6)). The time to PMN > 1000/microliters was between 10 and 16 days (four out of five evaluable patients), and platelets > 20000/microliters were reached between day 13 and 14 post-transplantation (three out of five evaluable patients). Two out of three evaluable patients developed grades one and three acute GVHD, and one out of three developed chronic GVHD. Two patients died of sepsis and VOD at day 10 and 19, respectively. Two adult patients are alive and in cytogenetic and molecular remission of CML at +339 and +227 days post-allotransplantation. One 3-year-old girl with hemophagocytic lymphohistiocytosis is in remission at +304 days post-transplantation. Using pediatric donors for allogeneic PBPC transplantation appears to be safe, yields a sufficient amount of progenitors for prompt engraftment, and results in clinical outcome similar to adult PBPC allotransplantation.
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PMID:Allogeneic peripheral blood stem cell transplantation using normal patient-related pediatric donors. 893 41


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