Intermediate-dose methotrexate in the treatment of childhood acute lymphocytic leukaemia: lack of benefit during maintenance therapy following intensive induction therapy

Abstract

One hundred and fifty-one children with acute lymphocytic leukaemia (ALL) received multiple agent induction chemotherapy followed by intensive phase treatment. One hundred and thirty-seven patients were randomised for the first year of maintenance treatment to receive reinforcement therapy (pulses) with either intermediate-dose methotrexate (ID-MTX) and prednisone (PRED) or vincristine (VCR) and PRED. The probability of continuous complete remission (CCR) at 5.5 years is 0.80 for the ID-MTX group and 0.84 for the VCR group. Extramedullary relapses were not prevented either in the ID-MTX group nor in the VCR group. Since in previous studies VCR/PRED pulses did not increase CCR rates when given after intensive combination chemotherapy, it can be concluded from this study that neither did ID-MTX reinforcement therapy further improve treatment results in our patients with ALL when given after aggressive chemotherapy.

The problem of preventing testicular leukaemia

“…In our study 2 out of 72 (2.7%) patients in the vincristine group and 1 out of 65 (1.5%) patients in the methotrexate group developed an isolated testicular relapse [3].…”

Vitamin E in newborns surviving respiratory distress

“…However, results of clinical studies published up to now suggest that standard dose chemotherapy is unable substantially to reduce the testicular relapse rate, independent of the multi-drug schedule employed. In particular, the BFM 76-79 protocol, which is identical to that used for induction by JankaSchaub et al [4], has a testicular relapse rate of 5.6% [5], a figure comparable to that of less aggressive treatments [1,7]. In contrast, intermediate or high-dose MTX has almost abolished testicular relapses both in controlled [2,9] and in uncontrolled studies [3,6] supporting the hypothesis of a testicular sanctuary [10].…”

“…In contrast, intermediate or high-dose MTX has almost abolished testicular relapses both in controlled [2,9] and in uncontrolled studies [3,6] supporting the hypothesis of a testicular sanctuary [10]. The experience of Janka-Schaub et al [4] is at variance with the above studies. While the authors do not specifically discuss the implications for prevention of testicular leukaemia, the reader might easily assume that this aim can be accomplished with intensive multi-drug chemotherapy.…”

“…Sir, -We read with interest the article of Janka-Schaub et al [4] on "Intermediate-dose methotrexate in the treatment of childhood acute lymphocytic leukaemia: lack of benefit during maintenance therapy following intensive induction therapy".…”