Hepatic ultrastructure in leukemic children treated with methotrexate and 6-mercaptopurine

Jm, Harb; Sl, Werlin; Bm, Camitta; Oechler, Herbert W.; Ba, Kamin; El, Blank

doi:10.1097/00043426-198324000-00001

Cited by 26 publications

(13 citation statements)

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“…They found fibrosis in 67 out of 72 (93%) and hepatitis in 26 out of 72 patients (36%) studied after therapy for childhood ALL. Several small studies in the 1970s and 1980s have reported hepatic fibrosis to occur more rarely than Guido et al [26], namely in about 18-63% [10,35,36]. We detected mild fibrosis in only three out of 27 patients (11%) and none had histological or serological hepatitis.…”

Section: Discussioncontrasting

confidence: 46%

“…There are earlier studies that have not even reported fatty change to be present [26], and in many of the studies only patients with clinical and laboratory evidence of liver dysfunction, and not consecutive patients, have undergone a liver biopsy. In some of the previous studies fatty change has been found to exist in $10-50% of children with ALL [10,12,35,36].…”

Section: Discussionmentioning

confidence: 90%

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Liver histology after current intensified therapy for childhood acute lymphoblastic leukemia: microvesicular fatty change and siderosis are the main findings

Halonen

Mattila

Ruuska

et al. 2003

Med. Pediatr. Oncol.

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Section: Discussioncontrasting

confidence: 46%

Section: Discussionmentioning

confidence: 90%

Liver histology after current intensified therapy for childhood acute lymphoblastic leukemia: microvesicular fatty change and siderosis are the main findings

Halonen

Mattila

Ruuska

et al. 2003

Med. Pediatr. Oncol.

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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].…”

Section: Combination Chemotherapymentioning

confidence: 97%

“…King, Perry 166 When MTX was used for maintenance therapy in children with acute leukemia, it led to the development of hepatic cirrhosis and fibrosis [70][71][72]. Fatty change, focal hepatitis, or portal fibrosis in previously untreated patients made the evaluation of MTX's role in the production of hepatotoxicity difficult.…”

Section: Antimetabolitesmentioning

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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“…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.…”

mentioning

confidence: 99%

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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Hepatic ultrastructure in leukemic children treated with methotrexate and 6-mercaptopurine

Cited by 26 publications

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Liver histology after current intensified therapy for childhood acute lymphoblastic leukemia: microvesicular fatty change and siderosis are the main findings

Liver histology after current intensified therapy for childhood acute lymphoblastic leukemia: microvesicular fatty change and siderosis are the main findings

Hepatotoxicity of Chemotherapy

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

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