Treatment of acute lymphocytic leukemia in Down syndrome

Abstract

Despite 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 16.1 ± 4.5 mg/m² vs. 6-MP 43.5 ± 23.1 mg/m² and MTX 25.2 ± 8.8 mg/m², respectively). All DS-ALL patients have been in complete remission for a median of 10 years 0 month (range: 8 years 10 months-14 years 1 month) as of January 1, 2017. DS-ALL patients may receive the same treatment protocol as that for NDS-ALL patients with adequate care and few modifications, and this strategy may result in the expansion of treatment protocols suitable for DS-ALL patients in the future.

Keywords:

• Down syndrome
• acute lymphocytic leukemia
• methotrexate toxicity
• 6-mercaptopurine
• dose adjustment

Public Interest Statement

Persons with Down syndrome are identified as vulnerable individuals. They develop leukemia 20 times more than people at large. Acute lymphocytic leukemia is one type of leukemia (ALL). Although prognosis of ALL is excellent in general population, it is still unfavorable in Down syndrome. There are many reasons for this. Persons with Down syndrome often have various congenital anomalies such as heart defects, obstruction of digestive tract, immunological weakness, etc. In addition to the fact that these conditions are likely to hinder adequate treatment, persons with Down syndrome are sensitive to anti-leukemic drugs and are often unable to tolerate modern treatment. On the assumption that main reason of this poor prognosis is inadequate treatment, we treated them with meticulous supportive care as intensively as they can tolerate. The result of our strategy seems satisfactory and all Down syndrome children with ALL are doing well for more than 8 years.

Competing Interests

The authors declare no competing interest.

Additional information

Funding

Funding. The authors received no direct funding for this research.

Notes on contributors

Yuki Gemma

Authors of this paper belong to Tokyo Children’s Cancer Study Group (TCCSG) and work at the University Hospital, where number of staff belonging to each specialty is very few. TCCSG consists of more than 30 institutes. Each institute can take care of only small number of patients and experience of the staff at each institute is limited and it is difficult to provide quality care. However, there are some merits, too, in this situation. The staff are obliged to care not only children with diseases in the field of their specialty, that is, children’s cancers in this case, but also children with diseases of almost all fields. Under this situation, the staff become familiar to many kinds of children’s diseases even out of their specialties and thus they can provide comprehensive care to their limited number of patients.