Clinical characteristics and outcome of refractory/relapsed myeloid leukemia in children with Down syndrome

Abstract

Myeloid leukemia in Down syndrome (ML-DS) is associated with good response to chemotherapy and favorable prognosis. Because little research has been focused on refractory/relapsed (R/R) cases, we conducted a retrospective analysis for R/R ML-DS. Among ML-DS patients diagnosed between 2000 and 2010 in Japan, 26 relapsed (25 in the BM and 1 in the skin), and 3 refractory patients were enrolled. The male/female ratio was 18/11. The median age at initial diagnosis of ML-DS was 2 years, and the median time to relapse was 8.6 months. Each patient initially had been treated with ML-DS-specific protocols. Thirteen of the 26 patients achieved complete remission with various kinds of reinduction chemotherapies; 2 of 8 survived without further recurrence after receiving allogeneic hematopoietic stem cell transplantation, and 4 of 5 maintained complete remissions with chemotherapy alone. Treatment failures mostly were associated with disease progression rather than treatment-related toxicities. The 3-year OS rate was 25.9% ؎ 8.5%. A longer duration from initial diagnosis to relapse was a significant favorable prognostic factor (P < .0001). We conclude that clinical outcome for patients with R/R ML-DS generally are unfavorable, even in those receiving hematopoietic stem cell transplantation. Novel methods to identify poor prognostic factors for ML-DS are necessary. (Blood. 2012; 120(9):1810-1815)

Improved outcomes for myeloid leukemia of Down syndrome: a report from the Children’s Oncology Group AAML0431 trial

“…17,18 Of 6 patients who received SCT, 4 are alive and 2 died. Thus, new therapies such as histone deacetylase inhibitors and Wee1 inhibitors need to be developed for patients with refractory or relapsed ML-DS.…”

“…[13][14][15] ML-DS patients with either refractory or relapsed disease have a very poor prognosis even after receiving stem cell transplants (SCTs). [16][17][18] Hence, identifying the optimal treatment intensity for ML-DS patients remains a challenge, balancing the need to use curative therapy while minimizing treatment-associated morbidity and mortality. The online version of this article contains a data supplement.…”

Therapy reduction in patients with Down syndrome and myeloid leukemia: the international ML-DS 2006 trial

“…19 In summary, we show that therapy reduction could be achieved in children with ML-DS without compromising the excellent outcome. The identification of clinical and cytogenetic prognostic markers in our study offers new possibilities for risk-adapted therapy for children with ML-DS.…”

“…14,15 In contrast, the prognosis of relapsed ML-DS patients is extremely poor. 12,19,20 This means that ML-DS treatment schemata have to particularly strive for the balance between appropriate chemotherapy dosage to avoid relapses and treatment-related toxicity. Despite substantial efforts, clear prognostic factors that identify those patients at high risk for relapse remain elusive precluding a risk-adapted treatment strategy.…”

Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study

“…6,11,32 ML-DS AMKL cases are characterized by mutations in the hematopoietic transcription factor GATA1, and these patients have a good prognosis when treated with reduced-intensity chemotherapy because of the unique sensitivity of leukemia cells to chemotherapeutic agents. 21,22,[32][33][34][35][36] Our group previously showed that RBM15/MKL1, CBFA2T3/GLIS2, NUP98/ KDM5A, and KMT2A rearrangements were not present in ML-DS. 5 GATA1 mutations have been described in non-Down syndrome AMKL, often seen with an acquired trisomy 21, and it was suggested that these cases fare well in terms of prognosis, although numbers were small.…”