Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irradiation of the mouse right or left hemithorax at 14 or 18 Gy produced a dose-dependent rise in breathing rate 16 weeks after irradiation without significant mortality. The measurement of breathing rate changes following right hemithoracic irradiation combined with the maximally tolerated dose of cytotoxic drugs was assessed as a method for qualitatively detecting drug-irradiation interactions which either exacerbate pneumonitis or alter its time course. Cyclophosphamide at 100 mg/kg accentuated and accelerated the rise in breathing rate, culminating in early mortality. BCNU 30 mg/kg delayed the appearance of the radiation response. Busulphan 30 mg/kg appeared to be radioprotective, but this was shown to be due to the DMSO-containing vehicle. Doxorubicin 6 mg/kg had no effect when combined with right or left hemithoracic irradiation. Carboplatin 100 mg/kg, vindesine 4 mg/kg and vinblastine 4 mg/kg had no substantial effect upon the changes in breathing rate.
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PMID:Mouse hemithoracic irradiation and its interaction with cytotoxic drugs. 141 May 72

We retrospectively reviewed the pulmonary toxicity of six high dose chemotherapy protocols using four chemotherapy regimens in the treatment of solid tumors. All protocols used either high dose cyclophosphamide or ifosfamide in combination with one to three additional chemotherapeutic agents. In each protocol autologous bone marrow was reinfused post chemotherapy to shorten the period of severe myelosuppression. Of 178 patients there were 20 cases of fatal or life-threatening pulmonary toxicity including nine cases of pneumonia, nine cases of interstitial pneumonitis and two cases of pulmonary hemorrhage. Pulmonary function tests revealed modest changes in FEV1 and DLCO in the majority of patients, although 24 patients had more dramatic changes in DLCO suggesting interstitial damage. Significant decrements in FEV1 were seen in the BCNU containing regimen. Statistically significant or nearly significant decreases in DLCO were seen after all cyclophosphamide containing regimens. A regimen containing ifosfamide, carboplatin, and etoposide had minimal associated pulmonary toxicity.
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PMID:Pulmonary toxicity associated with high dose chemotherapy in the treatment of solid tumors with autologous marrow transplant: an analysis of four chemotherapy regimens. 151 80

Fifteen patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who were ineligible for allogeneic bone marrow transplantation (BMT) or alpha-interferon therapy were included in this study. Eight patients were in the first late chronic phase, five were in the second chronic phase, one was in the accelerated phase, and one was in the blastic phase. Autologous bone marrow cells (median, 2.5 x 10(8) nucleated cells/kg) were stored at a median of 30 months after diagnosis. Patients were treated with cyclophosphamide (1.5 g/m2 daily for 4 days), carmustine (BCNU) (300 mg/m2), and etoposide (VP-16) (250 mg/m2 daily for 3 days) (CBV), followed by reinfusion of autologous bone marrow. Hematopoietic recovery was rapid, and toxicity was mild to moderate in 14 patients. One patient died of cytomegalovirus pneumonitis. Eight of 15 patients showed Ph suppression to less than 90% Ph-positive metaphases after autologous BMT. Major cytogenetic responses (Ph suppression to less than 35% Ph-positive metaphases) developed in four patients. Cytogenetic responses were observed in 4 of 11 patients infused with 100% Ph-positive marrows, and in all 4 patients infused with Ph-mosaic marrows (mixture of diploid and Ph-positive cells). Better results were observed when autologous BMT was performed in the chronic phase compared with the advanced phases. The major cytogenetic responses have lasted for 3, 4, 12, and 15+ months, whereas minor cytogenetic responses lasted for only a short time (less than 2 months). Three of seven patients (43%) in the chronic phase with previous resistance to alpha-interferon therapy became sensitive to alpha-interferon therapy after autologous BMT. The authors concluded that intensive chemotherapy followed by autologous BMT produced cytogenetic remissions in patients with Ph-positive CML and reinduced disease sensitivity to alpha-interferon therapy in patients previously resistant to it. This is particularly useful when treatment is given during the chronic phase and stem cells are collected at a time of previous cytogenetic remission.
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PMID:Intensive combination chemotherapy and autologous bone marrow transplantation leads to the reappearance of Philadelphia chromosome-negative cells in chronic myelogenous leukemia. 167 51

Fifty patients with advanced-stage Hodgkin's disease (HD) who relapsed or failed to respond to multiple regimens of combination chemotherapy were entered onto two autologous bone marrow transplantation (AuBMT) protocols. Twenty-eight patients who did not have prior radiation therapy were treated with protocol A. Protocol A consisted of reinduction with conventional doses of combination chemotherapy followed by boost local-field irradiation to areas of residual disease and hyperfractionated accelerated total lymphoid irradiation (TLI). Chemotherapy consisted of high-dose etoposide (VP-16) and cyclophosphamide followed by infusion of cryopreserved, unpurged autologous bone marrow. Twenty-two patients who have had prior radiation therapy were treated with protocol B. Protocol B consisted of reinduction with conventional doses of chemotherapy followed by involved field radiation therapy (when tolerance to residual disease has not been previously reached). High-dose chemotherapy regimen consisted of cyclophosphamide, carmustine (BCNU), and VP-16 (CBV) followed by autologous bone marrow transplantation. Of the 28 patients in protocol A, 5 patients died during the immediate peritransplant period, 5 patients progressed within six months, and 2 of them died. Two patients relapsed 13 and 39 months post transplant; 1 of them was reinduced into a complete remission (CR). Seventeen patients (61%) are disease free (16 patients in continuous complete remission), 12-54+ months (median 25+ months) following completion of therapy. Of the 22 patients in protocol B, 1 died of cytomegalovirus pneumonitis, and 11 relapsed. Ten patients (45%) are alive and disease free 16-42+ months (median 23+ months) after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autologous bone marrow transplantation for refractory or relapsed Hodgkin's disease: the Memorial Sloan-Kettering Cancer Center experience using high-dose chemotherapy with or without hyperfractionated accelerated total lymphoid irradiation. 204 22

Ten patients with plasma cell leukaemia (PCL), out of 259 cases of multiple myeloma diagnosed in the Haematology Service of the University Hospital of Barcelona in the last 18 years, are presented. Of the 10 PCL cases, 5 were primary and 5 were secondary. Anaemia and thrombocytopenia, along with massive plasma cell infiltration of the bone marrow, were the most striking findings. Osteolytic lesions were present in 9 of the cases and liver involvement in two. Chemotherapy including vincristine and prednisone was administered to eight patients, associated to alkylating agents (melphalan and/or cyclophosphamide) in six of them. Four of these patients received also adriamycin and BCNU. Two objective responses were achieved, lasting for 10 and 3 months, the remaining six patients failed to respond. The median survival for all the PCL patients was less than one month (ranging between 0.2 and 14 months). None of the secondary PCL patients survived for 2 months after diagnosis. Infection (3 cases of septicaemia and 3 of pneumonia), renal failure (2 cases) and liver insufficiency (1 case) were the causes of death in the nine deceased patients. The therapeutic possibilities for this severe haemopathy are discussed.
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PMID:[Plasma cell leukemia. Study of 10 cases]. 265 43

Employment of postoperative brain irradiation in the initial management of high-grade malignant glial tumors has now become standard. The addition of conventional chemotherapy to irradiation has not significantly improved median survival beyond 1 year. We treated 25 consecutive patients (13 pilot patients and 12 protocol patients) with histologically confirmed unresectable grade 3 or 4 malignant gliomas with high-dose BCNU (carmustine) followed by autologous bone marrow transplantation and whole brain irradiation. Within 3 weeks of initial surgery, each patient had autologous bone marrow stored (median 2 X 10(8) nucleated cells/kg), and then received BCNU 1,050 mg/m2 intravenously (IV). Peripheral granulocytes recovered (greater than 500/microL) at a median of 19 days (range, 10 to 37 days), and platelets recovered (greater than 20,000/microL) at a median of 18 days (range, 13 to 40 days), following bone marrow infusion. Patients received 60 Gy whole brain irradiation when granulocytes were greater than 1,500/microL. Toxicity was well tolerated. Nausea occurred in 19 patients (76%); however, only eight patients (32%) experienced vomiting (mild in three, moderate in five). Eleven patients (44%) did not require empiric antibiotics, six of whom never developed an absolute granulocyte count less than 500/microL. Three patients with a poor performance status died early (one seizure with vomiting and asphyxiation; one, klebsiella urinary tract infection (UTI) with bacteremia; one, candidal pneumonia), and one additional patient who was performing well died of pulmonary hemorrhage. The 13 pilot patients have now been followed for a median of 23 months, with a significant survival advantage compared with the 52 consecutive historical control patients who received similar surgery and radiotherapy without high-dose BCNU (P = .037). The overall study group of 25 patients also has a significant survival advantage when compared with the same historical control group, with a projected median survival of 26 months (P = .007). This new approach using early postoperative intensive therapy consisting of high-dose BCNU, autologous bone marrow transplantation, and whole brain irradiation appears to significantly improve survival.
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PMID:Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation. 355 37

Twenty-five adults who harbored malignant gliomas received 72 courses of intraarterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 mg/m2) and 67 courses of systemic vincristine (1.0 mg/m2) and procarbazine (100 mg/m2) as induction therapy (BVP) followed by 106 courses of systemic 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) (130 mg/m2), vincristine, and procarbazine as maintenance therapy (MVP). With a 6-week interval between each treatment, the median and range for the number of courses of BVP were 3 and 1 to 4 and those for MVP were 3 and 0 to 14, respectively. Fifteen patients (60%) responded to both BVP and MVP, and 10 (40%) did not. The overall median survival time was 12.7 months (range, 1.8 to 48.5+ months). Two of 3 patients who had recurrent gliomas responded and survived for 37+ to 45+ months. Seven of 10 who had nonirradiated glioblastomas responded and survived for 9 to 22 months. Four who had nonirradiated anaplastic astrocytomas all responded and survived for 38+ to 48.5+ months. Two who also received radiotherapy (1 glioblastoma and 1 primitive neuroectodermal tumor) benefited and survived for 16.9 and 28.5+ months. All who did not respond favorably died within 8 months. During the infusion of BCNU, complications included transient orbital and head pain, periorbital and scleral erythema in all patients, and a focal seizure in 1 (4%). During the 6-month induction periods, leukopenia and thrombocytopenia occurred in 1 (4%), deep vein thrombosis occurred in 9 (36%), pulmonary emboli occurred in 8 (32%), upper respiratory infections occurred in 6 (24%), pneumonia occurred in 9 (36%), and herpes zoster occurred in 1 (4%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraarterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and systemic chemotherapy for malignant gliomas: a follow-up study. 631 73

Simultaneous combination chemotherapy (CT) (BCNU 40 mg/m2, procarbazine 50 mg/m2, prednisone 40 mg/m2, and vincristine 1.4 mg/m2) with low-dose radiation therapy [(RT) 2000 rad] delivered to all areas of tumor involvement aside from the bone marrow was given to 28 patients with advanced Hodgkin's disease. Upon completion of RT and CT, the BCNU and procarbazine was increased by 100% until a total of six cycles of CT (with and without RT) were given. Eleven patients had received prior CT and had not achieved complete remission (CR) or had relapse from CT-induced CR within 1 year. Seventeen others had not had prior CT (7 had prior RT). Among the previously treated patients, one patient died in autopsy-proven CR during treatment. The other 10 patients achieved CR. Eight had relapsed at 4-36 months (median time to relapse, 6 months). Five patients died of Hodgkin's disease, three others died of status asthmaticus and pneumonia, radiation pneumonitis, and acute nonlymphocytic leukemia, respectively. Three patients are still alive (2 in continuous CR) at 28, 89, and 90 months. Among the previously untreated patients, four died during treatment, one of acute myocardial infarction, two of liver failure, and one of radiation pneumonitis. Twelve of the other 13 patients achieved CR. One of the CR died of pneumonia and sepsis 3 months after completion of treatment; two other patients relapsed at 10 and 15 months. Nine remain in continuous CR at 42-89 months of follow-up, (median follow-up, 81 months). Of 107 tumor areas treated with RT, in-field relapse occurred in two areas (1.9%). Hematologic tolerance to this treatment was good in both groups of patients. Radiation pneumonitis occurred in 50% of the patients whose lungs were irradiated, and it was fatal in two. By design or for other reasons, the median and mean doses of BCNU and procarbazine given to previously treated patients were 62% and 65.2%, respectively. In untreated patients, the median and mean doses of these two agents were 66.6% and 61.4%, respectively. There were no differences in dosage of these two agents between patients who remain alive in CR and those who relapsed and died. The potential of similar programs of radiation and chemotherapy is discussed.
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PMID:Simultaneous low-dose radiation and low-dose chemotherapy in the treatment of advanced Hodgkin's disease. 639 Nov 42

A patient who developed pneumonitis immediately after the administration of carmustine (BCNU), within exactly the same field as previous irradiation, is presented. The patient responded partially to corticosteroids. This case suggests that irradiation causes subclinical sensitisation of the lung and can therefore have an additive effect in precipitating lung damage when another pulmonary toxin is encountered at a later date.
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PMID:Recall lung pneumonitis due to carmustine after radiotherapy. 749 65

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


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