Acute lymphoblastic leukemia and Down syndrome

Aricò, Maurizio; Ziino, Ottavio; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Baronci, Carlo; Messina, Chiara; Pession, Andrea; Santoro, Nicola; Basso, Giuseppe; Conter, Valentino

doi:10.1002/cncr.23587

Cited by 50 publications

(21 citation statements)

References 24 publications

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“…These deaths have primarily been attributed to infection after chemotherapy-induced myelosuppression during induction as well as post-remission therapy [9-12]. These observations have led to treatment modifications specifically for DS-ALL.…”

Section: Introductionmentioning

confidence: 99%

Infections in children with down syndrome and acute myeloid leukemia: a report from the Canadian infections in AML research group

Tran

Mitchell

Dix

et al. 2013

Infect Agents Cancer

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BackgroundChildren with Down syndrome (DS) are at high risk of infectious toxicity when treated with acute lymphoblastic leukemia chemotherapy protocols optimized in children without DS. Our objective was to determine if children with DS and acute myeloid leukemia (AML) have a different risk of infection when treated with chemotherapy protocols developed for children with DS compared to AML treatment protocols developed for children without DS.MethodsWe conducted a retrospective, population-based cohort study that included DS children ≤ 18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, and treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease or death (whichever occurred first). Trained research associates abstracted all information from each site.ResultsThere were 31 children with DS included; median age was 1.7 (range 0.1-11.1) years. Eleven were treated according to a DS-specific protocol while 20 were treated with non-DS specific protocols. A total of 157 courses of chemotherapy were delivered. Microbiologically documented sterile site infection occurred in 11.9% and 14.3% of DS-specific and non-DS specific AML treatment courses respectively. Sepsis was rare and there were no infection-related deaths. In multiple regression, treatment with a DS-specific protocol was independently associated with a reduction in microbiologically documented sterile site infection (adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42-0.99; P = 0.044), and clinically documented infection (adjusted OR 0.36, 95% CI 0.14-0.91; P = 0.031) but not bacteremia (adjusted OR 0.73, 95% CI 0.44-1.22; P = 0.231).ConclusionsOur study suggests that children with DS do not experience excessive infectious toxicity during treatment for AML compared to children without DS. Incorporation of DS-specific AML treatment protocols is associated with a more favorable infection profile for children with DS-AML.

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Section: Introductionmentioning

confidence: 99%

Infections in children with down syndrome and acute myeloid leukemia: a report from the Canadian infections in AML research group

Tran

Mitchell

Dix

et al. 2013

Infect Agents Cancer

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“…The fact that induction failure was more common in the former group was not surprising; this has been repeatedly observed [4,11,41]. However, the lack of secondary malignant neoplasms (SMN) after treatment for DS-ALL is noteworthy – none of the 128 DS-ALL patients in the Nordic countries has developed SMN.…”

Section: Discussionmentioning

confidence: 92%

“…However, the lack of secondary malignant neoplasms (SMN) after treatment for DS-ALL is noteworthy – none of the 128 DS-ALL patients in the Nordic countries has developed SMN. Although not stressed in previous studies, this seems to be the case also in several other treatment trials, such as those from the Berlin-Frankfurt-Münster (BFM), Children's Cancer Group (CCG), and Italian Association of Pediatric Hematology and Oncology (AIEOP) groups [10,11,41,42]. It is well known that individuals with DS in general have a lower incidence of solid tumors than non-DS-individuals [2], with possible explanations including gains of tumor suppressor genes on chromosome 21, impaired angiogenesis, and accelerated cell ageing [43].…”

Section: Discussionmentioning

confidence: 95%

“…Data on improved outcome for DS-ALL have emerged during the last few years from some treatment trials [41,42,44], suggesting that induction and/or maintenance therapy has improved for this patient cohort. However, in the present study, both EFS and OS were still inferior for the DS-ALL cohort in the combined ALL-1992/2000 protocols (Figure 4; Table 5).…”

Section: Discussionmentioning

confidence: 99%

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Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries

et al. 2014

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BackgroundChildren with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL.MethodsTo address clinical and genetic differences between DS-ALL and non-DS-ALL and to identify prognostic factors in DS-ALL, we ascertained and reviewed all 128 pediatric DS-ALL diagnosed in the Nordic countries between 1981 and 2010. Their clinical and genetic features were compared with those of the 4,647 B-cell precursor (BCP) ALL cases diagnosed during the same time period.ResultsAll 128 DS-ALL were BCP ALL, comprising 2.7% of all such cases. The 5-year event-free survival (EFS) and overall survival (OS) were significantly (P = 0.026 and P = 0.003, respectively) worse for DS-ALL patients with white blood cell counts ≥50 × 109/l. The age distributions varied between the DS and non-DS cases, with age peaks at 2 and 3 years, respectively; none of the DS patients had infant ALL (P = 0.029). The platelet counts were lower in the DS-ALL group (P = 0.005). Abnormal karyotypes were more common in non-DS-ALL (P < 0.0001), and there was a significant difference in the modal number distribution, with only 2% high hyperdiploid DS-ALL cases (P < 0.0001). The 5-year EFS and 5-year OS were significantly worse for DS-ALL (0.574 and 0.691, respectively) compared with non-DS-ALL (0.783 and 0.894, respectively) in the NOPHO ALL-1992/2000 protocols (P < 0.001).ConclusionsThe present study adds further support for genetic and clinical differences between DS-ALL and non-DS-ALL.

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“…Approximately 2% to 3% of childhood ALL cases are associated with DS [100][101][102]. In childhood ALL with DS, CRLF2 is highly expressed in about 50% to 60% of cases [80,86,103].…”

Section: Down Syndromementioning

confidence: 99%