What's up with down syndrome and leukemia‐A lot!

Taub, Jeffrey W.; Ravindranath, Yaddanapudi

doi:10.1002/pbc.23033

Cited by 6 publications

(10 citation statements)

References 37 publications

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“…[1] Although children with Down syndrome comprise approximately 3% of children with acute lymphoblastic leukemia, up to 15% of children suffering from acute myeloid leukemia (AML) are children with Down syndrome, in whom the disease typically occurs before the age of 4 years. [2][3][4] In contrast to transient myeloproliferative disorder, which occurs in 5% of newborns with Down syndrome and disappears spontaneously in most patients, older children without treatment have a poor prognosis. [5] It has been shown that very intensive treatment, as needed in children with AML, is associated with significant treatment-related toxicity in children with AML and Down syndrome.…”

Section: Introductionmentioning

confidence: 99%

Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML‐BFM 2004

Hassler

Bochennek

Gilfert

et al. 2016

Pediatric Blood & Cancer

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Section: Introductionmentioning

confidence: 99%

Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML‐BFM 2004

Hassler

Bochennek

Gilfert

et al. 2016

Pediatric Blood & Cancer

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“…Of note, pediatric cancer patients with Down syndrome (DS, trisomy 21) constitute a population at particularly greater risk for anthracycline-related cardiotoxicity, and a safe dose of anthracyclines for cancer patients with- DS remains to be defined (6, 7). For example, children with- DS represent 15% of pediatric acute myeloid leukemia (AML) cases, and a report from the Children’s Oncology group has documented clinically symptomatic cardiomyopathy in 17.5% of DS-AML patients treated with an anthracycline-containing regimen (7, 8). …”

Section: Introductionmentioning

confidence: 99%

Interindividual Variability in the Cardiac Expression of Anthracycline Reductases in Donors With and Without Down Syndrome

et al. 2014

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Purpose The intracardiac synthesis of anthracycline alcohol metabolites (e.g., daunorubicinol) contributes to the pathogenesis of anthracycline-related cardiotoxicity. Cancer patients with Down syndrome (DS) are at increased risk for anthracycline-related cardiotoxicity. We profiled the expression of anthracycline metabolizing enzymes in hearts from donors with- and without- DS. Methods Cardiac expression of CBR1, CBR3, AKR1A1, AKR1C3 and AKR7A2 was examined by quantitative real time PCR, quantitative immunoblotting, and enzyme activity assays using daunorubicin. The CBR1 polymorphism rs9024 was investigated by allelic discrimination with fluorescent probes. The contribution of CBRs/AKRs proteins to daunorubicin reductase activity was examined by multiple linear regression. Results CBR1 was the most abundant transcript (average relative expression; DS: 81%, non-DS: 58%), and AKR7A2 was the most abundant protein (average relative expression; DS: 38%, non-DS: 35%). Positive associations between cardiac CBR1 protein levels and daunorubicin reductase activity were found for samples from donors with- and without- DS. Regression analysis suggests that sex, CBR1, AKR1A1, and AKR7A2 protein levels were significant contributors to cardiac daunorubicin reductase activity. CBR1 rs9024 genotype status impacts on cardiac CBR1 expression in non-DS hearts. Conclusions CBR1, AKR1A1, and AKR7A2 protein levels point to be important determinants for predicting the synthesis of cardiotoxic daunorubicinol in heart.

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“…Consequently, children with DS comprise approximately 3% of pediatric acute lymphoblastic leukemia (ALL) [3] and up to 15% of pediatric acute myeloid leukemia (AML) cases enrolled in clinical trials [4]. Recent studies have provided new insights into the unique epidemiology, pathogenesis and treatment response of ALL and AML in children with DS [2].…”

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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What's up with down syndrome and leukemia‐A lot!

Cited by 6 publications

References 37 publications

Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML‐BFM 2004

Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML‐BFM 2004

Interindividual Variability in the Cardiac Expression of Anthracycline Reductases in Donors With and Without Down Syndrome

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

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