Diffuse Interstitial Pulmonary Fibrosis After Busulphan Therapy

Leake, Eleanor; Smith, Walter G.; Woodliff, H. J.

doi:10.1016/s0140-6736(63)92173-1

Cited by 46 publications

(13 citation statements)

References 2 publications

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“…The action of BU on cells is mainly limited to the bone marrow. However, other reported side effects of BU therapy are interstitial pulmonary fibrosis (busulphan lung), hyperpigmentation of the skin, ovarian suppression and amenorrhea, and cataract formation (Leake et al 1963;Burns et al 1970;Oakhill et al 1981;Reynolds 1993;Dollery 1999). BU is potentially teratogenic and carcinogenic (Feingold and Koss 1969;IARC 1987;Reynolds 1993;Dollery 1999).…”

Section: Discussionmentioning

confidence: 99%

Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

et al. 2010

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Many anticancer drugs are myelotoxic and cause bone marrow depression; however, generally, the marrow/blood returns to normal after treatment. Nevertheless, after the administration of some anti-neoplastic agents (e.g. busulphan, BU) under conditions as yet undefined, the marrow may begin a return towards normal, but normality may not be achieved, and late-stage/residual marrow injury may be evident. The present studies were conducted to develop a short-term mouse model (a 'screen') to identify late-stage/residual marrow injury using a brief regimen of drug administration. Female BALB/c mice were treated with BU, doxorubicin (DOX), cisplatin (CISPLAT) or cyclophosphamide (CYCLOPHOS) on days 1, 3 and 5. In 'preliminary studies', a maximum tolerated dose (MTD) for each drug was determined for use in 'main studies'. In main studies, mice were treated with vehicle (control), low and high (the MTD) dose levels of each agent. Necropsies were performed, and blood parameters and femoral/humeral nucleated marrow cell counts (FNCC/HNCC) were assessed on six occasions (from days 1 to 60/61 post-dosing). Late-stage/residual changes were apparent in BU-treated mice at day 61 post-dosing: RBC, Hb and haematocrit were reduced, mean cell volume/mean cell haemoglobin were increased and platelet and FNCC counts were decreased. Mice given DOX, CISPLAT and CYCLOPHOS, in general, showed no clear late-stage/residual effects (day 60/61). It was concluded that a brief regimen of drug administration, at an MTD, with assessment at day 60/61 post-dosing was a suitable short-term method/screen in the mouse for detecting late-stage/residual marrow injury for BU, a drug shown to exhibit these effects in man.

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Section: Discussionmentioning

confidence: 99%

Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

et al. 2010

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“…Sterility and hyperpigmentation are seen frequently and are usually overlooked. On rare occasions dangerous sideeffects are encountered, such as pulmonary fibrosis (Oliner, Schwartz, Rubio, and Dameshek, 1961;Leake, Smith, and Woodliff, 1963;Koss, Melamed, and Mayer, 1965;Harrold, 1966;Smalley and Wall, 1966). The present study is concerned with this complication.…”

mentioning

confidence: 98%

Busulphan lung

Heard¹,

Cooke²

1968

Thorax

103

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“…Comhaire et al (1972) found no correlations between the total dosage of busulphan (ranging from 212 to 1400 mg) and the vital capacity in 23 patients. Littler and Ogilvie (1970) found no association between dosage (ranging from 93 to more than 6000 mg) and transfer factor in 23 patients suffering from myeloproliferative disease. On the other hand, Woodliff and Finlay-Jones (1972) reported that three (12%) patients, including two with radiographic abnormalities, of 26 receiving 'longterm' busulphan showed histological features of busulphan lung in specimens obtained at necropsy or lung biopsy compared with none of 13 who had received 'short-term' busulphan.…”

Section: Discussionmentioning

confidence: 86%

“…The patients were due to receive busulphan daily for two years but because of a high mortality from carcinoma of the lung during the period and the need to lower the maintenance dose and sometimes interrupt or terminate chemotherapy on account of toxicity, the mean total dosage received was 464 mg over a mean period of just over one year. This is considerably less than the mean total dosage of 3000 to 4000 mg received over a period of approximately four years by 25 patients reviewed in the literature with 'typical' radiographic and histological appearances of busulphan lung (Oliner et al, 1961;Leake et al, 1963;Koss et al, 1965;Harrold, 1966;Smalley and Wall, 1966;Min and Gyorkey, 1968;Heard and Cooke, 1968;Feingold and Koss, 1969;Korbitz and Reiquam, 1969;Littler et al, 1969;Burns, McFarland, and Matthews, 1970;Comhaire et al, 1970;Kolarz, Pietschmann, and Regele, 1970;Pintos Fuentes and Reissenweber, 1970;Massachusetts General Hospital Case Records, 1971;Batzenschlager et al, 1972;Jeanmart et al, 1972;Brynes et al, 1973;Etcheberry et al, 1973;Podoll and Winkler, 1974). Moreover, none of these 25 patients received less than 600 mg of busulphan, whereas only 13 (7%) of the patients in the present series received more than this.…”

Section: Discussionmentioning

confidence: 86%

“…There have been reports of the occurrence of what is now commonly termed 'busulphan lung', characterized by cough, dyspnoea, fever, and usually bilateral diffuse infiltrations in patients under treatment with busulphan (Oliner et al, 1961;Leake et al, 1963;Heard and Cooke, 1968). The opportunity was therefore taken to investigate radiographic abnormalities occurring in the five-year period in the lungs of patients receiving busulphan in comparison with those receiving cyclophosphamide or placebo.…”

Section: In 1964 a Medical Research Council Workingmentioning

confidence: 99%

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