Poor Treatment Compliance in Children With Down Syndrome and Acute Lymphoblastic Leukemia

Bohnstedt, Catherine; Taskinen, Mervi; Zeller, Bernward; Björgvinsdóttir, Helga; Hafsteinsdóttir, Solveig; Schmiegelow, Kjeld

doi:10.1097/mph.0b013e31818b37a9

Cited by 7 publications

(10 citation statements)

References 16 publications

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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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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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“…Several distinct clinical and biological features have been reported to be associated with DS-ALL: lack of infantile ALL, low frequency of a T cell phenotype [5][6][7][8][9][10], frequent chromosomal abnormalities with ?X, t(8;14), or del(9q), and rare occurrence of poor prognostic cytogenesis such as t(9;22) or 11q23 translocations [13,14]. In agreement with these features reported in the literature, all of our study patients had a BCP phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…3 in this report, dose reduction of chemotherapy was defined as a reduction in the dose of at least 3 drugs by at least 30%. According to this definition, the dose of chemotherapy was reduced in 4 patients ( UPN 5,8,9,and 10). Among the 6 patients with congenital abnormalities, chemotherapy was reduced in 2 patients (33.3%), whereas the dose of chemotherapy was reduced in 2 out of 7 patients (28.6%) who did not have congenital abnormalities (P = 0.68).…”

Section: Toxicities and Protocol Compliancementioning

confidence: 96%

“…In contrast to AML in DS, several groups have reported that the treatment outcome of DS-ALL was inferior to that of NDS-ALL. The high incidence of therapy toxicities [5,6], administration of sub-optimal doses of anti-leukemia drugs [7,8], or the unique biological characteristics of ALL blasts, such as a reduced occurrence of favorable cytogenesis [9,10] has been suggested to be associated with treatment failure in DS-ALL. To improve the therapeutic outcome of DS-ALL, it is important to accumulate data on outcomes of diverse therapeutic regimens performed in different groups.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2011

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The Tokyo Children's Cancer Study Group (TCCSG) and the Kyushu Yamaguchi Children's Cancer Study Group (KYCCSG) performed a collaborative analysis of data on children with Down syndrome and acute lymphoblastic leukemia (DS-ALL). Among the 1,139 patients who were enrolled in the TCCSG L99-15, L99-1502, or the KYCCSG ALL 96 study, 13 patients with newly diagnosed ALL had DS. In the DS patients, a significantly higher proportion of patients developed ALL at age 5 years or older compared with the non-DS ALL patients (P < 0.001). The 5-year relapse-free or overall survival of DS-ALL patients was 50.0 or 61.5%, respectively. Relapse accounted for all causes of death. In the TCCSG L99-15 cohort, the overall survival of DS-ALL patients was 42.9%, which was significantly worse compared with 87.9% in the non-DS population (P < 0.001). The survival of patients who received reduced-dose chemotherapy was significantly worse than those who received full-dose chemotherapy (P < 0.001). However, a higher dose of methotrexate was not associated with a better outcome. Results of our preliminary study suggest that the survival of DS-ALL patients could be improved by treatment without dose reduction if possible, although the appropriate dose of methotrexate for DS-ALL needs to be determined.

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“…Furthermore, lack of physician compliance to dose titration has been associated with an increased risk of treatment failure. 31,[34][35][36] This study emphasizes the association between the degree of myelosuppression and the chance of cure, and indicates that this is especially pronounced for adolescents. Furthermore, the lack of correlation between the age and mWBC for the patients that relapsed could indicate that the risk of relapse is related to the absolute mWBC levels rather than to the relative degree of myelosuppression with respect to the patients normal WBC levels.…”

Section: Discussionmentioning

confidence: 99%

The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse

et al. 2010

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Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (X10 years) and 176 non-adolescents (o10 years) with B-cell precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC) o50 Â 10 9 /l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS 12y :0.71 vs 0.83, P ¼ 0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (r S ¼ 0.36, P ¼ 0.02), which became nonsignificant for those who relapsed (r S ¼ 0.05, P ¼ 0.9). The best-fit multivariate Cox regression model to predict risk of relapse included mWBC and thiopurine methyltransferase activity, which methylates mercaptopurine and reduces the intracellular availability of cytotoxic 6-thioguanine nucleotides (coefficient: 0.11, P ¼ 0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient ¼ 0.65, P ¼ 0.003) than for non-adolescents (coefficient ¼ 0.42, P ¼ 0.04). Adolescents had higher mean neutrophil counts (P ¼ 0.002) than nonadolescents, but received nonsignificantly lower mercaptopurine and MTX doses during maintenance therapy. Red blood cell MTX levels were significantly related to the dose of MTX among adolescents who stayed in remission (r S ¼ 0.38, P ¼ 0.02), which was not the case for those who developed a relapse (r S ¼ 0.15, P ¼ 0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL.

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Poor Treatment Compliance in Children With Down Syndrome and Acute Lymphoblastic Leukemia

Cited by 7 publications

References 16 publications

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

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

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

The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse

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