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)

Infection, hemorrhage and adult respiratory distress syndrome (ARDS) are pulmonary complications occurring after remission induction therapy for acute leukemia. The aim of this study was to analyze the incidence of these causes by serial roentgenogram, clinical, microbiological and laboratory tests in 21 patients (pts) with relapsed acute leukemia (18 X myeloid, 3 X lymphoblastic), an AML-pt (acute myeloid leukemia) suffering from secondary leukemia, and three pts with primary refractory leukemia following treatment with intermediate (IM) and high-dose cytosine arabinoside (HD-Ara C), in combination with amsacrine (AMSA)(n = 19), etoposide (VP 16) (n = 5) or Mitoxantrone (n = 1). Eleven out of 25 pts developed pulmonary complications, one of them with massive hemoptysis and roentgenographic signs of pulmonary bleeding, one suffering from protracted shock after a tumor lysis syndrome, two pts showing symptoms of a cardiogenic pulmonary edema complicating severe Candida pneumonia in one case and legionnaires' disease in the other. Seven of the eleven pts had a non-cardiogenic pulmonary edema with respiratory failure 1-14 days after cessation of induction or consolidation therapy. In six of the seven, there were no signs of cardiogenic, infectious or metabolic reasons, including fluid overload, for the pulmonary edema, one had as a contributing factor a Candida infection of the lung. Three of the seven patients recovered, four died (two following IM and two after HD-Ara C). Other adverse side effects, clearly attributable to HD-Ara C, included delirious state (n = 3), generalized erythema (n = 3), acute pancreatitis (n = 2), acute abdomen (n = 1) and conjunctivitis in almost all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Non-cardiogenic pulmonary edema complicating intermediate and high-dose Ara C treatment for relapsed acute leukemia. 336 72

35 patients were treated for acute myeloid leukaemia or acute lymphoblastic leukaemia with allogeneic bone-marrow grafts from a parent, child, or sibling who was mismatched at the major histocompatibility complex (MHC). 11 of these patients are alive at least 6 months after grafting, 5 of them after more than 2 years. Of the 15 patients aged under 20 at the time of the graft, 8 are alive and well 6 months to 3 years later. Cyclosporin A was given to all patients after grafting. 1 patient died of acute graft-versus-host disease and in 2 other cases this was a major factor in their death. Graft failure caused the death of 2 patients. 4 patients died of recurrent leukaemia. A fatal complication in 12 patients was pulmonary oedema, often associated with convulsions, intravascular haemolysis, and renal failure. Some of these patients had viral or bacterial infections, but in the majority the syndrome was not associated with demonstrable infection. This syndrome, in which the essential lesion appears to be vascular, was much more common in recipients of mismatched than matched grafts. 3 others died from lung disease in which infection was a factor.
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PMID:Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia. 613

Fatal pulmonary toxicity can be consistently produced in L1210 leukemia-bearing mice by single therapeutic doses of cyclophosphamide, BCNU, and mitomycin C but not by adriamycin. Lung toxicity is principally determined by an existing tumor burden at the time of drug administration. Thus when any of the four chemotherapeutic agents was given 5 days after L1210 transplantation there was no mortality. Pulmonary pathology in these mice was equivalent to that noted in normal mice receiving identical drug treatment or to that noted in untreated L1210-bearing mice sacrificed 7, 8, or 10 days after tumor transplantation. When chemotherapy was delayed to day 7 after L1210 transplantation for mitomycin C or to day 8 after transplantation for BCNU and cyclophosphamide, more severe pulmonary toxicity was found. Mortality within the first 5 days of treatment was 38, 50, and 80%, respectively. Pulmonary pathology included moderate to severe vascular congestion and interstitial pneumonitis, diffuse pulmonary hemorrhage often involving the entire pulmonary parenchyma, pulmonary edema, and alveolar cell metaplasia. A unique finding, associated with cyclophosphamide treatment, was the occurrence of perivascular-intramural edema of the walls of medium-size pulmonary vessels. It is hypothesized that stasis within the pulmonary capillary circulation, resulting from advanced tumor growth and from drug treatment, may contribute to the development of chemotherapy-related toxicity.
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PMID:Chemotherapy-induced pulmonary toxicity in mice bearing L1210 leukemia. 640 46

Ten pediatric patients with refractory leukemia received continuous infusion high-dose cytosine arabinoside (ara-C) according to one of two escalating dosage schedules: (1) a 500-mg/m2 rapid infusion loading dose followed by 3.5 g/m2 per day continuous infusion daily for four consecutive days, or (2) a 600-mg/m2 rapid infusion loading dose followed by 5.0 g/m2 per day continuous infusion daily for four consecutive days. Major toxicity at the lower dosage level was grade IV hematopoietic aplasia of three weeks' duration. At the higher dosage level, there was a prohibitive toxicity in multiple organ systems including transient noncardiogenic pulmonary edema, fungal infections, peritonitis, severe diarrhea, transaminase elevations, and one treatment-related death due to acute renal failure. In contrast to other methods of administration of high-dose ara-C, no CNS toxicity occurred. Oncolytic responses were seen in all patients and two achieved brief, partial remissions. Steady-state plasma ara-C concentrations were 13 to 40 mumol/L at the 3.5-g/m2 dosage level and 10 to 225 mumol/L at the 5-g/m2 dosage level; CSF concentrations at both dosages ranged from 2 to 5 mumol/L. Intracellular levels and ratios of 1-beta-D-arabinofuranosylcytidine-5' triphosphate and endogenous deoxycytidine 5' triphosphate in marrow blasts varied widely at steady state during infusion. No positive correlation existed between steady-state plasma ara-C levels, toxicity, oncolytic effect, or intracellular nucleotide concentration.
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PMID:Continuous infusion high-dose cytosine arabinoside in refractory childhood leukemia. 659 35

A patient with angioimmunoblastic lymphadenopathy, immunoblastic leukaemia, pulmonary immunoblastic infiltration, and multiple antihaemocytic antibodies in his serum deteriorated rapidly after chemotherapy due to severe progressive respiratory of dysfunction. The haematological and immunological changes that accompanied this are described and discussed in the light of the pulmonary changes observed at necropsy of pulmonary oedema, fibrinous thrombi within venules, and immunoblastic infiltration of these thrombi and the venule walls. A pathophysiological mechanism is postulated in an attempt to rationalise these findings, and to act as a guide for the future assessment and management of similar cases.
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PMID:Rapidly fatal respiratory failure and angioimmunoblastic lymphadenopathy: possible contributions of immunoblastic leukaemia, chemotherapy, and multiple antibodies directed against mature blood cells. 725 91

Unexplained fatal pulmonary edema observed at autopsy in leukemic patients treated with cytosine arabinoside (Ara-C) suggested a possible role of the drug in causing increased alveolar capillary permeability. We reviewed clinical and pathologic features of the 181 patients with leukemia who were examined at autopsy at The Johns Hopkins Hospital in the past 12 years, 93 (51 percent) of whom had received intravenous Ara-C in doses of 7.5 to 30 mg/kg/day (average dose, 16 mg/kg/day). Fifty-one patients had received their last treatment within 30 days, and 42 patients between 31 and 894 days, prior to death. Among the 181 patients examined at autopsy 43 (24 percent) had massive edema, 59 (33 percent) had moderate edema, and 79 (44 percent) had either slight edema or no pulmonary edema. The 51 patients who had received Ara-C within 30 days of their death, compared to the other 130, had a highly significant increase in the frequency of pulmonary edema (p less than 0.001), which was massive in 24 and moderate in 18. In these 42 patients, causative or contributing factors that explained the edema were present in 14 (33 percent) of them, but in 28 (67 percent) there was no apparent explanation. In contrast, 60 of the 130 patients who had no or remote Ara-C therapy had massive (19 patients) or moderate (41 patients) pulmonary edema, which was explained in 55 (92 percent) and unexplained in only five (8 percent) (p less than 0.001). The unexplained pulmonary edema, a highly proteinaceous interstitial and intra-alveolar infiltrate, correlated with gastrointestinal lesions typical of Ara-C toxicity (p less than 0.001). Multivariate regression analysis showed that unexplained pulmonary edema was predicted by the recent administration of Ara-C, but by no other chemotherapeutic agent, including daunomycin, a potential cardiotoxin frequently given in conjunction with Ara-C. The study suggests that increased alveolar capillary permeability may result from the intravenous administration of cytosine arabinoside and that this complication should be considered when pulmonary edema develops in leukemic patients treated with Ara-C.
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PMID:Ara-C lung: noncardiogenic pulmonary edema complicating cytosine arabinoside therapy of leukemia. 746 13

The increased survival rate of malignant diseases due to more aggressive treatments contributes to the occurrence of drug-induced pulmonary diseases (DIPD). We reviewed, retrospectively over a 10-year period, 15 children (8 girls) who presented a DIPD. Their mean age was 9 years (range, 1 to 17 years), with an underlying malignant disease in 14 (9 leukemias). Three typical patterns have emerged from this analysis: (1) acute hypersensitivity lung disease caused by methotrexate (in 6 patients) or azathioprine (in 1 patient). This acute syndrome consisted of alveolar-interstitial infiltrate with a hypercellularity on bronchoalveolar lavage (BAL) (mean, 714,286 cells/mL; range, 180,000-2,940,000 cells/mL) and an increase of lymphocyte counts (mean, 39%; range 11-64%) with predominantly CD8-suppressor/cytotoxic lymphocytes. Inhibition of leukocyte migration or leukocyte aggregation in the presence of low drug concentrations was positive in the 5 cases tested. Lung function tests showed a restrictive pattern and the outcome of DIPD was always favorable. (2) Chronic pneumonitis/fibrosis was seen in 6 patients who received a variable association of cyclophosphamide (3 patients), bleomycin (2 patients), BCNU (2 patients), and melphalan (1 patient). Symptoms of an alveolar-interstitial pneumonitis developed progressively. BAL showed a moderate increase of total cell numbers (mean, 495,000 cells/mL; range, 150,000-900,000 cells/mL). Lung function tests showed a restrictive pattern. Despite corticosteroid treatment in 4 children, one died after bleomycin lung injury and 2 had functional lung impairment. (3) Noncardiogenic pulmonary edema occurred in 2 patients with leukemia treated with recombinant interleukin II. BAL showed hypercellularity and outcome was rapidly favorable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytotoxic drug-induced pulmonary disease in infants and children. 789 68

In order to strengthen the anti-leukemia effect, we developed a new conditioning regimen with high dose busulfan, VP-16 and ACNU (BVA) for cytoreduction before stem cell transplantation. Fourteen patients with refractory acute leukemia received allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) after conditioning with the BVA regimen, 7; allogeneic BMT, 1; syngeneic BMT, 6; PBSCT. # Seven patients were transplanted in the first complete remission, and 8 patients were in their second or third remission. Although total body irradiation or cyclophosphamide was not included in this regimen, engraftment was obtained in all cases. Two patients suffered relapse, and one patient died of cytomegalovirus interstitial pneumonitis (IP) 64 days after PBSCT. The other 11 patients are alive and free of disease at a median follow up time of 647 days (98-1235 days). Major regimen-related toxicity was pulmonary complications such as IP (3 cases) and pulmonary edema (2 cases). However, all patients recovered rapidly following steroid therapy. The results indicate that this conditioning regimen is highly effective for the treatment of childhood acute leukemia.
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PMID:[High-dose busulfan, VP-16 and ACNU therapy with stem cell transplantation for the treatment of children with acute leukemia]. 810 Feb 84

Twenty-five consecutive leukemia patients (21 AML, 4 ALL) with either primary resistance (n = 22) or resistant relapse (n = 3) of all FAB subtypes were treated with 1 or 2 cycles of ID-ara C (1 g/m2 i.v. q 12 h, days 1-6) and AMSA (120 mg/m2 i.v., days 5-7). Patients reaching CR received 1 cycle of intensive consolidation using ara C 3 g/m2 i.v. q 12 h, days 1-4 and AMSA 120 mg/m2 i.v., day 5. Two patients received an allograft thereafter and are still alive and in CCR. CR was achieved in 12/25 patients (48%), ten after 1 cycle of induction and two after 2 cycles; 10/22 patients with primary resistant disease reached CR, and 2/3 with resistant relapse. Nine patients remained refractory (36%) and four died during hypoplasia (16%). Median DFS of the 12 responders was 2.9 months, median survival from time of CR 8.9 months. Median overall survival of responders and nonresponders was 6 months from time of resistance. Survival advantage of responding patients (n = 12) as compared with nonresponders (n = 13) was 10.7 vs. 3.2 months (p = 0.002). Toxicity of chemotherapy was acceptable: one patient experienced pulmonary edema due to ara C; two patients developed life-threatening systemic fungal infections, one of whom died while in CR.
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PMID:Phase-II study of treatment of refractory acute leukemia with intermediate-dose cytosine arabinoside and amsacrine. 847 58

Myeloablative chemo (+/- radio) therapy and rescue with ABMT has been used as final consolidation therapy in 18 patients with AML in first remission. In seven (6 autologous, 1 syngeneic) marrow reinfusion was followed by iv IL-2. One patient, who commenced IL-2 4 days after BMT, died from pulmonary oedema due to the capillary leak syndrome. Thereafter, treatment with IL-2 was delayed until the platelet count reached 30 x 10(9)/l. All patients developed reversible hypotension (treated with infusion of colloid), but treatment was otherwise well tolerated. With 21-58 months (median 32 months) from the time of ABMT there has been one relapse (actuarial risk 17%, 95% confidence intervals (CI) 3-31%). The disease-free survival is 71% (95% CI 38-100%). Eleven patients with comparable remission induction and consolidation therapy, and an identical interval between diagnosis and ABMT (5-11 months, median 6 months) received an autograft without immunotherapy. With 24-45 months (median 29 months) follow-up the actuarial disease-free survival is 36% (95% CI 8-64%), the actuarial relapse risk is 54% (95% CI 18-90%). We conclude that immunotherapy given after ABMT to patients with AML in first remission when the platelet count exceeds 30 x 10(9)/l is safe and may induce an immunological environment which results in the elimination of residual leukaemia.
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PMID:Immunotherapy with interleukin 2 after ABMT in AML. 850 74


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