Page 176 - Haematologica April 2020

M. Kroll et al.
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Together, these findings point to an increased awareness of the higher susceptibility of DS-ALL patients to MTX- related toxicity and the need of MTX dose modifications in recent years.
In DS-ALL patients who received a MTX dose of 5 g/m2 in the first course we observed significantly higher rates of grade 3/4 leukopenia, thrombocytopenia, infection and stomatitis compared to NDS-ALL. Similar results in small- er cohorts of heterogeneously treated DS-ALL patients have also been observed by other groups.5,8,15,16 However, here we showed for the first time that the administration of a low MTX dose of 0.5 g/m2 to patients with DS-ALL leads to a significant reduction of grade 3/4 toxicity. Furthermore, the MTX dose could subsequently be esca- lated to 1.0 g/m2 in more than half of the patients without resulting in higher rates of grade 3/4 toxicities after the second course compared to the initial course. These data support the study group’s recommendation to increase the MTX dose if no severe toxicity occurrs in the previous course. However, since reduced doses still bear a risk of severe side effects in individual DS-ALL patients, consoli-
dation treatment should be administered cautiously and under close clinical control.
Dose reduction of chemotherapeutic drugs during can- cer treatment may raise the concern of impairing long- term outcomes in the affected patients. Here, we did not find any differences in the 5y-CIR in DS-ALL patients who started consolidation with 5 g/m2 MTX compared to patients who received 0.5 g/m2 MTX. These findings raise the question whether DS-ALL patients require a high MTX dose in consolidation or whether a low dose between 0.5-1.0 g/m2 might be sufficient to optimize their outcome by balancing treatment-related complications with relapse rates. While others found impaired outcome of DS-ALL patients who were treated with reduced drug doses,2,5 two studies described no differences in event free and overall survival between patients with or without dose reductions.15,16 The authors speculate that modern, more effective ALL therapy and supportive treatment may contribute to an improved outcome in DS patients treated with a reduced dose. Other groups also described a trend towards a better outcome for DS-ALL in recent times.6,14
P=0.51
P=0.42
Figure 3. Five-year-cumulative incidence risk of relapse in Down syndrome acute lymphoblastic leukemia. (A) Comparison of the 5-year-cumulative incidence risk (5y-CIR) of Down syndrome acute lym- phoblastic leukemia (DS-ALL) patients who received a first high dose methotrex- ate (HD-MTX) course of 0.5 g/m2 (blue) or 5 g/m2 MTX (red). No significant differ- ences according to Gray’s test. (B) Comparison of the 5y-CIR of DS-ALL who initially received 0.5 g/m2 MTX in the first course and were eventually dose escalat- ed in the course of consolidation with DS- ALL who received 0.5 g/m2 MTX through- out the whole consolidation therapy. No significant differences were found accord- ing to Gray’s test.
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haematologica | 2020; 105(4)