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Progressive improvement in pEFS and pOS was observed over time (Table 1, Fig. 1A and Bafilomycin A1 solubility dmso B). The 5-year pEFS improved from 50%?��?4% in 1992�C1996 to 71%?��?4% in 2003�C2008 (pooled P?<?0.001), and the 5-year pOS improved from 57%?��?4% to 78%?��?4%, respectively (pooled P?<?0.001). There was a trend for further survival improvement in 2009�C2012, however, follow-up time for these patients was relatively short ( Table 1, Fig. 1A and B). Advance was more prominent with a borderline significance for BCP patients with 5-year pEFS increasing from 68%?��?6% in 1997�C2002 to 77%?��?4.5% in 2003�C2008 (P?=?0.065), with a trend for further improvement in 2009�C2012 (pooled P?=?0.043) ( Fig. 2A). In contrast, survival rates were less prominent for T-ALL ( Fig. 2B). However, number of T-ALL patients was small (N?=?17, 20 and 15 in 1997�C2002, 2003�C2008 and 2009�C2012, respectively). Out of four events for T-ALL patients in the recent period, two deaths appeared for HR patients due to septic complications during block therapy induced myelosuppression (N?=?1) or cytomegalovirus pneumonia during maintenance (N?=?1). <a href="https://en.wikipedia.org/wiki/Phosphoprotein_phosphatase">Phosphoprotein phosphatase The rest two events were relapses which are described below. Five-year cumulative incidence of relapses reduced from 27%?��?4.5% in 1992�C1996 to 14%?��?3.6% in 2003�C2008 (P?=?0.042) ( Fig. 1A). In 2009�C2012, of the 82 patients, four developed early relapses so far (5%) after 0.6�C1.4 years from diagnosis. One of them (IR, BCP) developed an isolated bone marrow relapse after parents abandoned the treatment. Another patient (IR, T-ALL) developed an isolated CNS relapse. The remaining two isolated bone marrow relapses occurred for HR Ponatinib manufacturer ALL patients (T-ALL with hyperleukocytosis and BCP with MLL? rearrangement). Incidence of CNS disease at diagnosis remained stable during the study period (Table 1), while the 5-year cumulative incidence of CNS involving relapses decreased from 17%?��?3.9% in 1992�C1996 to 9%?��?2.9% in 1997�C2002 (P?=?0.077), and after high dose MTX of 5?g/m2 was introduced in 2003�C2008, it decreased further down to 1%?��?1.0% (P?<?0.001) ( Fig. 1B). Importantly, cumulative incidence of CNS involving relapses did not increase in 2009�C2012 period (3-year cumulative incidence 2%) after cranial irradiation was omitted for all patients. However, follow-up is short for the recent period. In contrast, cumulative incidence of induction failure and DCR1 remained high, albeit decreasing, all over the study period (Table 1). Induction failure was considered as death during induction (N?=?30) or later if remission was not achieved (N?=?1) or remission status in bone marrow was not evaluated (N?=?3).</div>
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