Faculty Opinions recommendation of Post-induction MRD by FCM and GATA1-PCR are significant prognostic factors for myeloid leukemia of Down syndrome.

Key Points Reducing therapy intensity in the ML-DS 2006 trial did not impair the excellent prognosis in ML-DS compared with the historical control. Early treatment response and gain of chromosome 8 are independent prognostic factors.

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Prognostic factors in children and adolescents with acute myeloid leukemia (excluding children with Down syndrome and acute promyelocytic leukemia): univariate and recursive partitioning analysis of patients treated on Pediatric Oncology Group (POG) Study 8821

Leukemia ◽

10.1038/sj.leu.2401832 ◽

2000 ◽

Vol 14 (7) ◽

pp. 1201-1207 ◽

Cited By ~ 50

Author(s):

M Chang ◽

SC Raimondi ◽

Y Ravindranath ◽

AJ Carroll ◽

B Camitta ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Down Syndrome ◽

Prognostic Factors ◽

Myeloid Leukemia ◽

Recursive Partitioning ◽

Promyelocytic Leukemia ◽

Oncology Group ◽

Children With Down Syndrome ◽

Pediatric Oncology Group ◽

Acute Myeloid

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Tandem Duplications of the FLT3 and MLL Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia. AML99 Study in Japan.

Blood ◽

10.1182/blood.v106.11.2779.2779 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2779-2779 ◽

Cited By ~ 2

Author(s):

Akira Shimada ◽

Tomohiko Taki ◽

Ken Tabuchi ◽

Takeshi Taketani ◽

Ryoji Hanada ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Down Syndrome ◽

Prognostic Factors ◽

Myeloid Leukemia ◽

Tandem Duplication ◽

Treatment Protocol ◽

Disease Free Survival ◽

Normal Karyotype ◽

Pediatric Acute Myeloid Leukemia ◽

Acute Myeloid

Abstract To find poor prognostic factors other than karyotypes is desired to improve the treatment outcome in pediatric acute myeloid leukemia (AML). Total three hundread and eighteen patients were enrolled in Japanese Childhood AML Cooperative Treatment Protocol, AML99, from January 2000 to December 2002. We performed the mutation analysis of FLT3 and MLL in 158 patients (13 of 29 with FAB-M3, 10 of 49 with Down syndrome, 135 of 240 with other type of AML) Patients with FAB-M3 and patients with Down syndrome were treated on different protocol. Seventeen (12.6%) of 135 patients had FLT3-internal tandem duplication (ITD). The differences between AML patients with or without FLT3-ITD were significant in 4-year overall survival (OS) (35.3% vs. 86.1%, p<0.00001), disease free survival (DFS) (38.5% vs. 68.1%, p=0.0013), and relapse rate (RR) (53.8% vs. 28.5%, p=0.0029). Furthermore, MLL-partial tandem duplication (PTD) was found in 21 (15.6%) of 135 patients. The differences between patients with or without MLL-PTD were significant in 4y-OS (56.3% vs. 81.4%, p=0.013), DFS (41.7% vs. 68.3%, p=0.017), and RR (53.9% vs. 27.5%, p=0.0078). Out of 18 patients with MLL-PTD who received allo-SCT, 9 patients survived (6 of 8 in 1st CR, 3 of 4 in 2nd CR, 0 of 6 in non CR). Out of 12 patients with FLT3-ITD who received allo-SCT, 4 patients survived (4 of 6 in 1st CR, 0 of 6 in non CR). Allo-SCT is considered to be effective for the patients with TD of both genes. Coduplication of both genes was observed in 3 patients. FLT3 kinase domain mutation was found in 7.0% and MLL translocations were found in 11.4% of the patients, but both aberrations did not show poor outcome in this study. FLT3-ITD and MLL-PTD were found in 9 (25.7%) and 8 (22.9%) of 35 patients with normal karyotype. FLT3-ITD and MLL-PTD are considered to be independent poor prognostic factors of pediatric AML patients, especially in patients with normal karyotype. The different therapeutic approach including allo-SCT will be needed for these patients.

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Post-Induction Minimal Residual Disease Measured By Flow Cytometry and Deep Sequencing of Mutant GATA1 Are Both Significant Prognostic Factors for Children with Myeloid Leukemia and Down Syndrome: A Nationwide Prospective Study of the Japanese Pediatric Leukemia/Lymphoma Study Group

Blood ◽

10.1182/blood-2019-123302 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3848-3848 ◽

Cited By ~ 1

Author(s):

Takashi Taga ◽

Shiro Tanaka ◽

Kiminori Terui ◽

Shotaro Iwamoto ◽

Hidefumi Hiramatsu ◽

...

Keyword(s):

Down Syndrome ◽

Prognostic Factors ◽

Deep Sequencing ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Residual Disease ◽

Study Group ◽

Pediatric Leukemia ◽

Lymphoma Study Group ◽

Minimal Residual

Background: Myeloid leukemia in Down syndrome (ML-DS) is associated with good response to chemotherapy thus results in a favorable outcome. However, relapsed and refractory cases are rarely salvageable, regardless of receiving hematopoietic stem cell transplantation. Several factors such as certain chromosomal abnormalities and age at diagnosis are somewhat prognostic, but no universal prognostic factor has been found to date. In order to identify a subgroup with high risk of treatment failure, the role of minimal residual disease (MRD) with three methods were explored in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) trial AML-D11. Procedure: AML-D11 is a nationwide single-arm clinical trial for children (4 months to 17 years old) with ML-DS. All patients received an identical chemotherapy to the previous AML-D05 study (Taga T. Pediatr Blood Cancer 2016). MRD was evaluated at two time points, one after the induction therapy and another at the end of whole chemotherapy, using 3 different methods; flow cytometric MRD (FCM-MRD), deep sequencing MRD of mutant GATA1 (GATA1-MRD) and PCR MRD of WT1 mRNA expression (WT1-MRD). WT1-MRD was measured in both bone marrow (BM) and peripheral blood (PB) samples, while FCM- and GATA1-MRD were measured only in BM samples. Results: A total of 78 patients were eligible and followed-up with a median of 47.6 months (range, 8 to 68.8 months). Seventy-six patients were stratified to the standard risk (SR) and one patient to the high risk (HR) group by morphological response. One patient died of sepsis during initial induction therapy. Three-year event-free survival (EFS) and overall survival (OS) rates were 87.2% (95%CI, 77.5 to 92.9%) and 89.7% (95%CI, 80.5 to 94.7%), respectively. FCM-MRD and GATA1-MRD after initial induction therapy were positive in 5/65 and 7/59 patients, respectively, which were both significantly prognostic (Fig.1). Prognostic significance of WT1-MRD could not be evaluated due to a limited number of collected samples. Conclusions: MRD detections by FCM and targeted deep sequencing of GATA1 after initial induction therapy are both significant prognostic factors for predicting relapse. Risk stratification using FCM-MRD is currently incorporated in the on-going Japan Children's Cancer Group ML-DS trial (AML-D16; jrct.niph.go.jp, jRCTs041190047). Figure 1 Disclosures No relevant conflicts of interest to declare.

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