Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following bone marrow transplantation employing conditioning including 'high-dose' cyclophosphamide, 65 patients were studied for the subsequent development of symptomatic haemorrhagic cystitis. There was no protection from the urothelial toxicity of cyclophosphamide metabolites afforded by the concurrent administration of 2-mercaptoethane sodium sulphonate (mesna) if timing errors in administration were made. Other factors which might increase the risk of haemorrhagic cystitis due to cyclophosphamide administration include the prior administration of busulphan to patients with chronic granulocytic leukaemia, in whom the incidence of haemorrhagic cystitis was 36% compared with 4% in all other patients. We have also investigated the use of intravesical prostaglandin E2 as a treatment for haemorrhagic cystitis in eight patients, two of whom appeared to obtain major benefit.
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PMID:Haemorrhagic cystitis in bone marrow transplantation patients: possible increased risk associated with prior busulphan therapy. 313 13

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

Cyclophosphamide is the most commonly prescribed alkylating agent in clinical medicine. The usefulness of cyclophosphamide is often limited, however, by its propensity to cause hemorrhagic cystitis especially in children or patients receiving concomitant radiotherapy. Administration i.p. of cyclophosphamide at doses of 100 mg/kg or more to mice produced a significant increase in urinary bladder weight within 48 hr of treatment. The present studies demonstrate that disulfiram prevented cyclophosphamide-induced bladder damage when administered p.o. within 1 hr of cyclophosphamide treatment. Diethyldithiocarbamate, a sulfhydryl-containing metabolite of disulfiram, had identical uroprotective activity. Unlike disulfiram, diethyldithiocarbamate was effective only when administered 2 to 4 hr after cyclophosphamide. Disulfiram augmented slightly the antitumor activity of cyclophosphamide against L1210 murine leukemia in vivo when administered 30 min prior to cyclophosphamide. In contrast, diethyldithiocarbamate had no effect on the antitumor activity of cyclophosphamide when administered 4 hr after cyclophosphamide.
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PMID:Effect of disulfiram (tetraethylthiuram disulfide) amd diethyldithiocarbamate on the bladder toxicity and antitumor activity of cyclophosphamide in mice. 629 38

Since 1976, 16 adult patients with acute leukemia have been treated by chemotherapy, total body irradiation (TBI) and allogeneic bone marrow transplantation (BMT) in the medical school hospital and the satellite hospitals of Nagoya University. The first group of 10 patients were given marrow grafts at the time of leukemic relapse and the second group of six patients were given the grafts in the period of remission of their disease. For the first group (ALL/ANLL 2:8, age (median) 33, M/F 8:2), HLA-identical donor cells (25 x 10(7)/kg [median]) were infused after the patients were conditioned with NSC D 245382 (ACNU) or daunorubicin, cyclophosphamide (CY) and a single shot of 1000 rad of TBI. For the second group (ALL/ANLL 4:2, age (median) 20, M/F 5:1), HLA-identical donor cells (22 x 10(7)/kg [median]) were infused after the patients were conditioned with CY and fractionated (250 rad x 4) TBI. All the patients were isolated in a laminar air flow room (LAF) after gut and skin decontamination. Engraftment of donor cells was confirmed in 15 out of the 16 patients. Febrile periods in LAF and the days required for platelet transfusion were prolonged in the first group. All the patients in the first group died within 12-214 days after BMT because of interstitial pneumonitis (7 patients) or bacterial infection (3 patients). On the other hand, five out of six patients in the second group are alive 84-540 days after BMT. For the surviving patients, the complications of chronic graft versus host disease, viral infections, tuberculosis, hepatitis, hemorrhagic cystitis and recurrence of leukemia are now the problems. It can be stated that the patient's clinical condition at the time of BMT is one of the most essential factors for the success of BMT although the effects of other variables, such a change in the conditioning regimens of the supportive care, must also be carefully analyzed.
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PMID:Sixteen adult patients with acute leukemia treated by chemotherapy, total body irradiation and allogeneic marrow transplantation. 639 11

Sixty patients consisting of 56 cases with leukemia, 3 with lymphoma and 1 with neuroblastoma were treated with various kinds of hematopoietic stem cell transplantation. The conditioning regimen consisted of mainly cyclophosphamide (CTX) and total body irradiation (TBI) with the addition of 1-3 doses of other antitumor drugs e.g. cytarabine, daunomycin, etoposide, 6-MP etc. The overall incidence of hemorrhagic cystitis in the course of transplantation was 23.3% (14 out of 60 patients). The time of onset of hematuria in 6 of 14 patients was within 1-4 days following high-dose CTX during conditioning and in the remaining 8 cases occurred 10-30 days after transplantation. The duration of hematuria lasted 2-31 days (mean, 4 days). Thirteen patients recovered and one patient died from the complication.
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PMID:[Hemorrhagic cystitis in the course of hematopoietic stem cell transplantation]. 790 67

We report a successful ereated case of acute megakaryoblastic leukemia (AMKL) with myelofibrosis (MF), which achieved a disease free condition, with disappearance of MF, for over 24 months after allogeneic bone marrow transplantation (BMT) and summarized cases of MF receiving BMT reported in Japan to evaluate the influence of MF on engraftment of bone marrow (BM). A 40-year-old man was admitted on Jan. 29, 1991 due to anemia and thrombocytopenia. BM aspiration resulted in a dry tap and MF and cells stained positive with anti-GPIIb/IIIa (CD41a) antibody were demonstrated by BM the biopsy specimen. Complete remission was achieved by multi-drug chemotherapy including behenoylcytosine arabinoside, etoposide, mitoxantrone and prednisolone (PLS). After preconditioning with little BU+CY, BMT was performed from an HLA-identical brother on Jan. 16, 1992. From day 9 of post BMT, acute skin graft versus host disease (grade 1) was observed, which was controlled by 60 mg/day of PSL. Engraftment was achieved on day 12. Although cystitis developed, he was discharged on Apr. 5, 1992 and remains disease free. Including the present case, seven allogeneic BMT patient with MF have been reported so far in Japan. Four cases in whom MF recovered before BMT showed better results than other three cases that still showed MF at BMT. Reversal of MF seems to be a favorable pre-transplant factor for successful BMT in patients with MF.
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PMID:[Reversal of myelofibrosis is an important pre-transplant factor for bone marrow grafting--a successful case of allogeneic bone marrow transplantation for an acute megakaryoblastic leukemia]. 813 12

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

Water-soluble derivatives of camptothecin, and active topoisomerase I inhibitor, have shown a broad spectrum of activity against human tumors. Early clinical trials with the water-soluble sodium salt of camptothecin were hindered by significant cystitis, gastroenteritis, and leukopenia. Furthermore, the sodium salt of camptothecin has been shown to have significantly less activity than the water-insoluble lactone form of the compound. We describe a formulation of lipid-complexed CPT (LC-CPT; particle size range 20.8-208.1 nm) that is very easy to prepare and allows for intravenous administration in vivo in clinically relevant lipid-drug ratios (12.5:1 w/w). The lipid formulation had in vitro antitumor activity similar to that of CPT formulated without lipids and displayed similar cytotoxicity against MDR-1-negative and -positive tumor cells. The biodistribution of CPT was profoundly affected by lipid complexation; free CPT achieved the greatest concentration in the pulmonary parenchyma while LC-CPT achieved the highest concentration in the gastrointestinal tract. LC-CPT had significant antitumor activity in vivo against intraperitoneal L1210 and P338 leukemia and appeared to be more potent then free CPT.
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PMID:Lipid-complexed camptothecin: formulation and initial biodistribution and antitumor activity studies. 861 6

We retrospectively compared the outcome in patients in the EBMT database transplanted for acute leukaemia from January 1987 to January 1994 who received busulphan and cyclophosphamide (BU/CY) as a pretransplant regimen versus those who received cyclophosphamide and total-body irradiation (CY/TBI). The patients were matched for type of transplant (autologous bone marrow transplantation (ABMT) versus allogeneic (BMT)), diagnosis (acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML)), status (early (first complete remission, CR-1) versus intermediate (second or later remission, first relapse)), age, FAB classification for AML, prevention of graft-versus-host disease and year of transplantation. In ABMT recipients (matched paired 530 x 2) with ALL CR-1, AML CR-1 and AML intermediate disease, transplant-related mortalities (TRM) relapse incidence (RI) and leukaemia-free survival (LFS) did not differ significantly in patients treated with BU/CY or CY/TBI. However, in ABMT recipients with ALL intermediate disease, the probability of relapse was 82 +/- 5% (+/- 95% confidence interval) in the BU/CY group compared to 62 +/- 6% in the CY/TBI group (P = 0.002) and the 2-year leukaemia-free survival 14 +/- 4% and 34 +/- 6%, respectively (P = 0.002). In BMT recipients of bone marrow from HLA-identical siblings (matched paired 391 x 2), the TRM, RI and LFS did not differ significantly between the two treatments in all groups. In particular, the 2-year LFS in patients with AML CR-1 was 64 +/- 3% in those treated with BU/CY (n = 237) compared to 66 +/- 3% in those given CY/TBI (n = 237). In all groups the findings were confirmed in a multivariate analysis of prognostic factors. Veno-occlusive disease (VOD) of the liver (P < 0.05) and haemorrhagic cystitis (P < 0.001) was more common in the BU/CY group compared to the CY/TBI group for ABMT and BMT patients. In conclusion, BU/CY and CY/TBI as pretransplant regimens gave similar results in all situations, except ABMT for ALL intermediate stages with more than 2 years from diagnosis to transplantation, where a lower RI and a higher LFS were associated with CY/TBI.
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PMID:A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). 865 85


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