The aim of the present study was to determine the frequency and clinical relevance of the most common secondary karyotype abnormalities in TEL/AML1 þ B-cell precursor acute lymphoblastic leukemia (ALL) as assessed with fluorescence in situ hybridization (FISH) analyses. Screening of 372 patients who were enrolled in two consecutive Austrian childhood ALL multicenter trials identified 94 (25%) TEL/AML1 þ cases. TEL deletions, trisomy 21 and an additional der(21)t(12;21) were detected in 52 (55%), 13 (14%) and 14 (15%) TEL/AML1 þ patients, respectively. The 12p aberrations (P ¼ 0.001) and near tetraploidy (P ¼ 0.045) were more common in TEL/AML1 þ patients, whereas the incidence of diploidy, pseudodiploidy, hypodiploidy, low hyperdiploidy, near triploidy, del(6q), chromosome 9 and 11q23 abnormalities was similar among TEL/ AML1 þ and TEL/AML1À patients. None of the TEL/AML1 þ patients had a high hyperdiploid karyotype. Univariate analysis indicated that among TEL/AML1 þ patients those with a deletion of the nontranslocated TEL allele had a worse prognosis than those without this abnormality (P ¼ 0.034). We concluded that the type and incidence of the most common secondary aberrations in TEL/AML1 þ ALL can be conveniently identified with little additional effort during interphase screening with appropriate TEL and AML1 FISH probes. We also provided preliminary evidence that the deletion of the nontranslocated TEL allele may adversely influence the clinical course of TEL/AML1 þ ALL.
Post-relapse therapy remains critical for survival in children with acute myeloid leukemia (AML). We evaluated survival, response and prognostic variables following relapse in independent cooperative group studies conducted by COG and the population-based AML-BFM study group. BFM included 197 patients who relapsed after closure of the last I-BFM relapse trial until 2017, while COG included 852 patients who relapsed on the last Phase 3 trials (AAML0531, AAML1031). Overall survival at 5 years (OS) was 42 ± 4% (BFM) and 35 ± 2% (COG). Initial high-risk features (BFM 32 ± 6%, COG 26 ± 4%) and short time to relapse (BFM 29 ± 4%, COG 25 ± 2%) predicted diminished survival. In the BFM dataset, there was no difference in OS for patients who had a complete remission with full hematopoietic recovery (CR) following post-relapse re-induction compared to those with partial neutrophil and platelet recovery (CRp and CRi) only (52 ± 7% vs. 63 ± 10%, p = 0.39). Among 90 patients alive at last follow-up, 87 had received a post-relapse hematopoietic stem cell transplant (HSCT). OS for patients with post-relapse HSCT was 54 ± 4%. In conclusion, initial high-risk features and early relapse remain prognostic. Response assessment with full hematopoietic recovery following initial relapse therapy does not predict survival. These data indicate the need for post-relapse risk stratification in future studies of relapse therapies.
Intensive chemotherapy directed against acute myeloid leukemia of
childhood is followed by profound neutropenia and high risk for bacterial and fungal
infections, including viridans group streptococci as a common cause for
gram-positive septicemia. Few retrospective studies have shown the efficacy of
various antibiotic prophylactic regimens in children. We retrospectively studied 50
pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St.
Anna Children’s Hospital and assessed the effect of antibiotic prophylaxis on the
frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric patients
underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred after none of
98 cycles with prophylactic administration of teicoplanin/vancomycin in comparison
to 12 cases of viridans sepsis among 79 cycles without systemic antibacterial
prophylaxis (0 vs. 15 %, p < 0.0001). In
addition, there were significantly fewer episodes of febrile neutropenia in the
teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p < 0.0001). Severity of infection seemed to be worse when no
antibiotic prophylaxis had been administered with a higher rate of intensive care
unit treatment (0/98, 0 %, vs. 4/79, 5 %, p = 0.038). So far, no increase of vancomycin-resistant enterococcus
isolates in surveillance cultures was noticed. Antibiotic prophylaxis with
teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication of
viridans sepsis and decreased incidence of febrile neutropenia in pediatric AML
patients. The possibility to administer teicoplanin on alternate days on an
outpatient basis or at home could contribute to patient’s quality of life and
decrease health care costs.Electronic supplementary materialThe online version of this article (doi:10.1007/s00277-016-2833-5) contains supplementary material, which is available to authorized
users.
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