We categorized the relapse treatment into four groups: ALL-REZ BFM protocols ( 90, 95/96 and ), NOPHO ALL and ALL HR arms. In a prospective and blinded study, the ALL-REZ BFM Study Group .. In the subsequent trial ALL-REZ BFM , this level of MRD after. n = 46; ALL-REZ BFM 95/96, n = 46; ALL-REZ BFM , n = 9). Six/ (3%) cases received palliative treatment for first relapse, and 71/

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However, data from relapsed patients after primary therapy within the COG CCG Study, demonstrated that there was 20002 difference in 3-year 202 survival between two alo of patients having primarily received augmented vs standard intensity post-induction intensification. As in newly diagnosed patients, treatment must be tailored after relapse of ALL, since outcome will be influenced by several risk factors.

A risk-adapted intensification of treatment by prolonging the intensive treatment phase in an ALL-REZ BFM Study could not prevent a high relapse rate in the high-risk group early isolated or combined bone marrow relapse [ 24 ]. Treatment failures, the development of a second malignant neoplasm, or death from any cause are generally considered events for DFS analysis[ 19 ]. Long-term results of Taiwan Pediatric Oncology Group studies and for childhood acute lymphoblastic leukemia.

Childhood acute lymphoblastic leukaemia and relapse.

ALL-REZ BFM–the consecutive trials for children with relapsed acute lymphoblastic leukemia.

Bortezomib is a proteasome inhibitor, which renders leukemic cells more sensitive to the apoptotic effects of chemotherapy. These outcomes have been remarkably consistent over recent decades, irrespective of differences in the components of salvage regimens[ 212428 ].

Altogether, of patients Chessells et al [ 32 ], Slow early response was also associated with a higher risk of relapse.

The standard risk group includes patients with: Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia: Some studies require the demonstration of the presence of leukemic cells in the cerebrospinal fluid CSF in two consecutive CSF samples taken with an interval of at least 24 h[ 3840 ].


Adding up-front or relapse protocol to the adjusted model did not generate significant HRs or result in any notable change in the HRs of the other co-variates in the models. Resistant leukemia subclones are probably present at primary diagnosis in those patients destined for early relapse. Most children with extramedullary and late bone marrow BM relapses achieve a second CR; remission rates in patients with high-risk features, however, remain still unsatisfactory.

This study was approved by the Ethical Review Board in Stockholm and was conducted in accordance with the Declaration of Helsinski. Little data are available regarding the prognostic impact of these manifestations and on the necessity of local therapy.

With improved techniques allogeneic hematopoietic stem cell transplant HSCT has become a relatively safe treatment but is not necessary for all patients as postremission therapy. The Annals of Statistics. This article has been cited by other articles in PMC.

ALL-REZ BFM–the consecutive trials for children with relapsed acute lymphoblastic leukemia.

Some late relapses are thought to arise from a common precursor that retains the chemosensitivity of the original clone, which could explain the high cure rates achieved with chemotherapy alone in late relapses[ 30 ]. Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Risk-adjusted selection of treatment. A cut-off point MRD after reinduction of 10 -3 quantified by PCR was recently proposed by Eckert et al[ 31 ] to discriminate between patients with a good or a poor prognosis.

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Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: Early-relapse mechanisms appear to be more homogeneous and are suggestive of the selection of a resistant, more proliferative clone Table 3 [ 48 ].

In this scenario, donor- vs -recipient NK alloreactivity has emerged as a crucial factor for the outcome of haplo-SCT. Type of first treatment was reported to influence the outcome after relapse, with more recent regimens being associated with improved survival[ 32 ].

Intraventricular therapy has several theoretical advantages: Prognostic factors Since we were studying a large cohort, we were able to include a number of variables in the regression analysis. White blood cell count. The equivalent post-relapse survival for patients undergoing different intensity regimens as first line therapy, suggests that the malignant cells responsible for relapse are present at diagnosis and mutate to a resistant phenotype through the acquisition of spontaneous mutations that are dependent on intrinsic genomic instability rather than treatment exposures[ 17 ].


Outcome after first relapse in children with acute lymphoblastic leukemia: Ko and coworkers[ 19 ] found increased survival for patients undergoing SCT, regardless of time to relapse or the number of prior relapses. Five-year survival rates for isolated CNS 20002 between Early MRD response assessment is currently applied to identify those patients within the more heterogeneous intermediate risk group who should undergo SCT as consolidation therapy.

A Overall survival after relapse. Allogeneic SCT with a matched donor is currently the preferred therapeutic option for these children after the CR2[ 20262933384269 ].

With improved supportive care and better donor selection, the outcome bffm unrelated donor and 2020 sibling SCT for relapsed ALL has become more equal[ 68 ]. Lesion specific backtracking studies revealed that in most cases the relapse clone existed as a minor sub-clone within the diagnostic sample prior to the initiation of therapy suggesting that the relapse clone was selected for during treatment.

Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic 202 and delayed CNS radiation: Complete remission after blinatumomab-induced donor T-cell activation in three pediatric patients with post-transplant relapsed acute lymphoblastic leukemia. Looking for a possible explanation for these differences, we compared the pattern of relapse between the two time periods and observed a difference in the time distribution of relapses Online Supplementary S3. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.