5 research outputs found
A single high dose of idarubicin combined with high dose ARA-C for the treatment of first recurrence childhood “high risk” acute lymphoblastic leukemia (ALL).
Multidimensional approach for the proper management of a complex chronic patient with chronic obstructive pulmonary disease
A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood 'high-risk' acute lymphoblastic leukaemia: a study of the AIEOP group.
The outcome of children with acute lymphoblastic leukaemia (ALL) and early
relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana
di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL
in first isolated or combined bone marrow relapse defined at high risk according
to the length of first remission and the immunophenotype. The treatment plan
included the combination of a single high-dose idarubicin and high-dose
cytarabine as induction therapy followed by an intensive consolidation and stem
cell transplant (SCT). In total, 100 children from 16 Italian centres were
enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete
remission; eight (8%) died during induction and 11 (11%) failed to respond. A
total of 42 out of the 80 responders (52.5%) received a SCT: 19 from an identical
sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood
cells. The estimated 4-year overall survival and event-free survival were 25% and
21% respectively. Disease-free survival at 4 years was 25.8% for the 80
responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free
of leukaemia. This induction therapy has shown antileukaemic efficacy with
acceptable toxicity; moreover, all responders proved eligible for intensive
consolidation
CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia
Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL. We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers. Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated. Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib. In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway