Hepatotoxicity in the treatment of acute lymphoblastic leukaemia

Topley, J M; Benson, Jane M.; Squier, M. V.; Chessells, J M

doi:10.1002/mpo.2950070415

Cited by 35 publications

(18 citation statements)

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“…This may be related to the means of detection used; although light microscopic changes were minimal, electron microscopic examination of liver biopsy specimens from children given MTX and 6-MP showed significant abnormalities in all patients [166]. In another study, liver biopsy specimens from children receiving maintenance therapy with 6-MP and MTX revealed mild inflammatory and fatty changes in many, and early portal fibrosis in 3 of 16 biopsies after more than two years of therapy [167]. Interpretation of reported cases has been complicated by the fact that children who present at an older age and require more transfusions are more likely to develop increased ALT values in a pattern consistent with non-A, non-B hepatitis [168].…”

Section: Combination Chemotherapymentioning

confidence: 99%

Hepatotoxicity of Chemotherapy

2001

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After assessment of tumor histology, the next important factor to consider in the selection of a chemotherapy regime is organ function. Patients who are to receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate, and which drug doses should be modified. Following therapy abnormalities of liver function tests may be due to the therapy rather than to progressive disease, and this distinction is of critical importance. Furthermore, not all abnormalities in liver function are due to the tumor or its treatment, and other processes, such as hepatitis, must be kept in mind. This article reviews the hepatic toxicity of chemotherapeutic agents, and suggests dose modifications based upon liver function abnormalities. Emphasis is placed on agents known to be hepatotoxic, and those agents with hepatic metabolism.

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Section: Combination Chemotherapymentioning

confidence: 99%

Hepatotoxicity of Chemotherapy

2001

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“…Both drugs are well known to be hepatotoxic [ 1-41, and fibrosis of varying degree after prolonged use of these agents has been demonstrated on liver biopsy ; even cirrhotic changes [3,8] and the development of hepatoma [9] have been reported. However, routine liver function tests normalize promptly after the cessation of therapy in the majority of patients [l], and biopsy findings and liver function tests were not necessarily found to be correlated [5,6]. Since it is important to know the effects of these liver abnormalities on liver status after the cessation of therapy, we investigated liver function status in patients treated for ALL during childhood.…”

Section: Introductionmentioning

confidence: 99%

Liver function studies in children with acute lymphocytic leukemia after cessation of therapy

Bessho

Kinumaki

Yokota

et al. 1994

Med. Pediatr. Oncol.

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We investigated liver function in 27 children with acute lymphocytic leukemia (ALL) after cessation of therapy. Induction therapy consisted of prednisolone+vincristine (VP regimen) alone (16 patients) or with addition of daunorubicin (4 patients) or L-asparaginase (7 patients). Patients treated with VP regimen received short courses of VP regimen every 12 weeks for the first year of maintenance. Twenty-five patients remained in first complete remission and had completed 3-year maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6-MP) 1-7 years prior to this study. Twenty-three patients had received transfusions of packed red blood cells or fresh whole blood (1-11 units; median: 2 units) but none had evidence of either hepatitis B or hepatitis C. Alanine aminotransferase (ALT), which was measured every 3 months during maintenance therapy, had values more than three times the upper limit of the normal range in 25% of the measurements in more than half of the patients. However, by 3 months after the completion of maintenance therapy, ALT had normalized in all patients and remained normal in all but two patients until the time of this study. Serum bilirubin, serum albumin, and prothrombin time were all within normal limits. Fasting and 2-hour postprandial total serum bile acids were high in 5 of 13 patients and in 6 of 13 patients, respectively. The ratio of cholic acids+deoxycholic acids to chenodeoxycholic acids+lithocholic acids was below 1 in all but two patients, whereas this ratio was above 1 in all controls. Our bile acid profile results indicate the necessity of careful long-term follow-up of survivors of ALL treated with hepatotoxic chemotherapy during childhood.

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“…Whereas a number of these studies have set focus on the relation between pathological liver function tests and the presence of an abnormal liver histology (Nesbit et al, 1976;McIntosh et al, 1977;Topley et al, 1979), the main purpose of the present study was to explore the relation between relapse risk and the rise in serum AT, the most commonly applied test to detect liver dysfunction used by the departments participating in the study.…”

Section: Discussionmentioning

confidence: 99%

“…The rises in liver enzymes during MT are in most cases mild and transient with normalisation within a few months following the cessation of therapy. For patients with severe liver dysfunction with affected prothrombin time, jaundice or very high levels of liver enzymes, a liver biopsy may offer a guide to whether dose modifications should take place, though often no correlation exists between pathological liver function tests and histology (Topley et al, 1979). Parker et al (1980) suggested that analysing plasma concentration profiles of drugs could be helpful in determining dose modifications.…”

Section: Discussionmentioning

confidence: 99%

“…Methotrexate (MTX) and 6-mercaptopurine (6MP) are potential inducers of liver damage, and pathological liver function tests and biopsies are frequently encountered with oral MTX and 6MP maintenance therapy (MT) for childhood acute lymphoblastic leukaemia (ALL) (Nesbit et al, 1976;McIntosh et al, 1977;Topley et al, 1979;Parker et al, 1980;Menard et al, 1980;Harb et al, 1983). As the chance for long-term disease-free survival improves, chronic side effects of therapy like liver dysfunction gains increasing importance.…”

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confidence: 99%

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Prognostic significance of hepatotoxicity during maintenance chemotherapy for childhood acute lymphoblastic leukaemia

Schmiegelow

Pulczynska²

1990

Br J Cancer

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Summary In a population-based study of 115 children with non-B-cell acute lymphoblastic leukaemia, we analysed the relation of the degree of leukopenia and risk of relapse to the degree of hepatotoxicity (as measured by serum aminotransferase (AT)) during oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance chemotherapy (MT). Hepatotoxicity was calculated as a mean of all AT-measurements (mATMT). Lack of hepatotoxicity was defined as a mATMT < 40 IU I -. A highly significant correlation was demonstrated between the mean AT during the first, second, and third year of MT (r > 0.70, P < 0.00001). mATMT was not related to the mean WBC during MT (r = -0.03, P = 0.36), but was related to the rise in WBC following cessation of therapy (r = 0.24, P = 0.06). Patients with recurrent disease had significantly lower mATMT than patients staying in remission (P = 0.03 for both over-all and haematological relapse risk (Figure 1). One hundred and twenty-eight patients completed induction and consolidation therapy. Of these, 13 were excluded from this study due to major protocol violation during induction or consolidation therapy, refusal of MT by parents, AT not measured during MT, or lack of data (3, 1, 7 and 2 patients). Thus, 115 patients (67 boys and 48 girls) were eligible for analyses, with 56 cases of standard risk (SR), 39 cases of daily for 4 days); 6MP = oral 6-mercaptopurine (75 mg m-2 day-'); MTX = oral methotrexate (20 mg m-2 week-'); M = intrathecal methotrexate (12 mg m 2); pred/p = oral prednisone (60 mg m-2 day-'); -= 6-thioguanine (60 mg m 2 day-'); | / M = 500/1,000 mg MTX 24 h infusion with leucovorin rescue; V = vincristine (2 mg m2, max. 2 mg dose-'); XXXX = CNSirradiation (2,400 cGy).

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Hepatotoxicity in the treatment of acute lymphoblastic leukaemia

Cited by 35 publications

References 12 publications

Hepatotoxicity of Chemotherapy

Hepatotoxicity of Chemotherapy

Liver function studies in children with acute lymphocytic leukemia after cessation of therapy

Prognostic significance of hepatotoxicity during maintenance chemotherapy for childhood acute lymphoblastic leukaemia

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