Acute lymphoblastic leukemia and Down syndrome: the collaborative study of the Tokyo Children’s Cancer Study Group and the Kyushu Yamaguchi Children’s Cancer Study Group

Goto, Hiroaki; Inukai, Takeshi; Inoue, H.; Ogawa, Chitose; Fukushima, Takashi; Yabe, Miharu; Kikuchi, Akira; Koike, Kenichi; Fukushima, Keitaro; Isoyama, Keiichi; Saito, Tomohiro; Ohara, Akira; Hanada, Ryoji; Iwamoto, Jiro; Hotta, Norifumi; Nagatoshi, Yoshihisa; Okamura, Jun; Tsuchida, Masahiro

doi:10.1007/s12185-011-0765-3

Cited by 21 publications

(28 citation statements)

References 29 publications

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“…5,10,47 Despite a high rate of TRM, and different from what is often suggested, relapse remained the main cause of treatment failure in DS patients. Interestingly, the relapses tend to occur later in DS.…”

Section: Discussionmentioning

confidence: 95%

“…48 This finding suggests that the currently accepted strategy of treatment reduction in DS-AML, which is characterized by a chemotherapy-sensitive phenotype, 49 is not applicable to DS-ALL. 47 The only exception may be DS-ALL patients with ETV6-RUNX1 or HeH, in which TRM outweighed the risk of relapse, for whom a 3-drug induction and a limited reinduction might be adequate. Interestingly, and in accordance with previous results, the incidence of secondary malignancies was significantly lower in DS patients as compared with non-DS-ALL patients.…”

Section: Discussionmentioning

confidence: 99%

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Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group

Buitenkamp

Izraeli

Zimmermann³

et al. 2014

Blood

205

292

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Key Points• Although the risk of ALL relapse is significantly higher in children with DS, goodprognosis subgroups have been identified. • Patients with DS-ALL have higher treatment-related mortality throughout the treatment period independent of the therapeutic regimen.Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt-Münster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% 6 2% vs 15% 6 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% 6 1% vs 2.0% 6 <1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% 6 2% vs 81% 6 2%, P < .0001) and overall survival (74% 6 2% vs 89% 6 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] 5 0.58, P 5 .002), white blood cell (WBC) count <10 3 10 9 /L (HR 5 0.60, P 5 .005), and ETV6-RUNX1 (HR 5 0.14, P 5 .006) for EFS and age (HR 5 0.48, P < .001), ETV6-RUNX1 (HR 5 0.1, P 5 .016) and high hyperdiploidy (HeH) (HR 5 0.29, P 5 .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DSALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups. (Blood. 2014; 123(1):70-77)

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group

Buitenkamp

Izraeli

Zimmermann³

et al. 2014

Blood

205

292

View full text Add to dashboard Cite

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“…7,[20][21][22][23][24][25][26][27] The 10-year survival of 653 DS-ALL patients enrolled in 16 international prospective therapeutic studies between 1995 and 2005 analyzed in the PdL study was 70% compared with 88% in children without DS. 7 This poor outcome is related to increased relapse risk coupled with increased TRM.…”

Section: Clinical Course Relapse Riskmentioning

confidence: 99%

How I treat ALL in Down's syndrome: pathobiology and management

Izraeli

Vora

Zwaan

et al. 2014

Blood

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Children with Down syndrome are at high risk for developing B-cell precursor acute lymphoblastic leukemia (DS-ALL) associated with poor outcome due to both a high relapse rate and increased treatment-related mortality (TRM) from infections. Biologically, these heterogeneous leukemias are characterized by under-representation of the common cytogenetic subgroups of childhood ALL and overrepresentation of CRLF2-IL7R-JAK-STAT activating genetic aberrations. Although relapse is the major determinant of poor outcomes in this population, de-escalation of chemotherapy intensity might be feasible in the 10% to 15% DS-ALL patients with ETV6-RUNX1 or high hyperdipoidy in whom TRM is the major limiting event. As infection-associated TRM occurs during all treatment phases, including the maintenance period, increased surveillance and supportive care is required throughout therapy. Improvement in outcome will require better understanding of the causes of treatment failure and TRM, incorporation of new therapies targeting the unique biological properties of DS-ALL, and enhanced supportive care measures to reduce the risk of infection-related TRM. To facilitate these goals, an international collaboration plans to establish a prospective DS-ALL registry and develop specific supportive care recommendations for this at-risk population.

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“…They are also at higher risk for infection-related mortality throughout all treatment phases [5]. Patients with DS-ALL tend to have poorer outcomes than those with No DS-ALL .One reason for previous treatment failures in children with DS-ALL is that these patients tend to develop toxic reactions to therapies In particular, a severe toxicity to methotrexate has been noted [6]. Methotrexate pharmacokinetics were analyzed retrospectively in children with ALL, comparing 44 with Down syndrome and 87 without the syndrome.…”

Section: Discussionmentioning

confidence: 99%