Treatment of acute lymphocytic leukemia in Down syndrome

Fumio Bessho,Mark Adrian Williams,Hiroshi Yoshino,Yuki Gemma

doi:10.1080/2331205x.2017.1304512

Fumio Bessho, Mark Adrian Williams + Show 2 more

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https://doi.org/10.1080/2331205x.2017.1304512

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Journal: Cogent Medicine	Publication Date: Jan 1, 2017
Citations: 2	License type: CC BY 4.0

Affiliation: Kyorin University

Abstract

AbstractDespite improvements in the prognosis of acute myelogenous leukemia in patients with Down syndrome, the prognosis of acute lymphocytic leukemia (DS-ALL) in these patients is still poorer than that of ALL in the general population. We compared treatment results between 4 patients with DS-ALL and 16 non-Down syndrome patients with ALL (NDS-ALL). Four patients with DS-ALL treated with TCCSG protocols achieved complete remission by the end of the induction phase. During the high-dose methotrexate (HD-MTX) phase, the dosage of MTX was reduced from 3 to 2 g/m2 after the syndrome of inappropriate ADH secretion developed in the first patient. All DS-ALL patients had severe mucositis and a longer period of anorexia than NDS-ALL patients, even after dose reductions, resulting in a longer HD-MTX phase in DS-ALL patients than in NDS-ALL patients. The mean dosages of 6-MP and MTX during the maintenance phase were significantly lower in DS-ALL patients than in NDS-ALL patients (6-MP 22.1 ± 9.9 mg/m2 and MTX 16....

Highlights

Patients with Down syndrome (DS) are at a high risk of developing leukemia (Ross, 2005)
In contrast to the improvements achieved in the prognosis of acute myelogenous leukemia in patients with DS (Creutzig, 2005; Kojima, 2000), the prognosis of acute lymphocytic leukemia (DS-ALL) in these patients is still poorer than that of ALL in the general population (NDS-ALL) (Arico et al, 2008; Buitenkamp et al, 2014; Lundin et al, 2014; Patrick et al, 2014; Xavier, Ge, & Taub, 2009)
The reason for this poorer prognosis is multifactorial, the main reasons appear to be the poor tolerance of DS-ALL patients to anti-leukemic drugs and high relapse rate

Summary

Introduction

Patients with Down syndrome (DS) are at a high risk of developing leukemia (Ross, 2005). The reason for this poorer prognosis is multifactorial, the main reasons appear to be the poor tolerance of DS-ALL patients to anti-leukemic drugs and high relapse rate. The high relapse rate may be not an independent factor, but secondary to poor tolerance to anti-leukemic drugs rather than decreases in the sensitivity of leukemic cells to these drugs (Izraeli, 2014; Whitlock, 2006). If the main factor of the poor tolerance of DS-ALL patients to anti-leukemic drugs is the sustained high blood levels of these drugs or the high sensitivity of DS-ALL cells to these drugs, titrations of the dosages of these drugs based on the degree of myelosuppression represent the best and easiest approach to avoid or minimize adverse effects, as reported previously for the maintenance of ALL remission in general (Bohnstedt et al, 2013; Schmiegelow, 2006).

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