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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Risk-adjusted selection of treatment. Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between and Journal Information gfm This Article.

Publishing Process of This Article.

By contrast, late relapses may represent de novo development of a second leukemia from a common premalignant clone. Distinct patterns of gene expression in pairs of relapsed samples from patients who relapse early from those relapsing later.

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

Recent evidence suggests distinct biological mechanisms for early vs late relapse and rea recognition of the involvement of certain treatment resistance related genes as well cell cycle regulation and B-cell development genes at relapse, provides the opportunity to search for novel target therapies.

Type of first treatment was reported to influence the outcome after relapse, with more recent regimens being associated with improved survival[ 32 ].

Post-transplant CD8-depleted donor lymphocyte infusions are feasible and promote immune reconstitution[ 91 ]. In a recent analysis of patients aged years registered in four consecutive Erz ALL-BFM trials, prognosis of relapsed leukaemia was significantly better for younger patients patients aged years at primary diagnosis than for adolescent i.

Toxicity and efficacy of intensive chemotherapy for children with acute lymphoblastic leukemia ALL after first bone marrow or extramedullary relapse. Bgm factors predicting CNS relapse after the first CR include T-cell immunophenotype, hyperleukocytosis, high-risk genetic bf, and the presence of leukemic cells in the CSF at the time of diagnosis[ 44 ].

According to Ko et al[ 19 ], DFS among patients who achieve CR decreased with an increasing number of prior treatment attempts. The aims of this study were to assess outcomes following acute lymphoblastic leukemia relapse after common initial Nordic Society of Paediatric Haematology 202 Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival.


Decisions regarding optimal postremission therapy in relapsed ALL are frequently based on well-established prognostic features, including the timing and site of disease recurrence, the disease immunophenotype, and, more recently, on evaluation of early response in terms of minimal residual disease MRD at the end of the reinduction phase[ 202628 – 31 ].

J Pediatr Hematol Oncol. Survival analysis In the whole study population, the 5-year EFS was Table 5 summarizes the reported results in relapsed childhood ALL from multicenter trials and cohorts over the last three decades.

Nelarabine is an bfn of purine nucleoside phosphorylase. Outcomes for children with relapsed ALL bdm changed little over time despite efforts by many investigators to intensify therapy with approaches that often include SCT. The 5-year overall survival for patients relapsing in the period — was These findings indicate that the diagnosis and relapse clones originated from a common ancestral clone and acquired distinct copy number abnormalities CNAs before emerging as the predominant clones at diagnosis nfm relapse.

Outcome after relapse among children with standard-risk acute lymphoblastic leukemia: Patients failing to achieve CR2 with the same agents used at primary diagnosis usually do not respond to different drug combinations.

Current approach to relapsed acute lymphoblastic leukemia in children

Received Jun 4; Accepted Oct The optimal post-remission therapy for children with late B-cell precursor BM relapse either isolated or combined is controversial[ 20 ]. Since a blood barrier is not present in these sites, systemic chemotherapy is supposed to be effective. New studies clearly need to address how to effectively treat relapsed patients and maintain durable remissions[ 16 ]. During initial therapy, this minor population would exhibit only moderate reduction relative to the bulk of the diagnostic leukemic cells but would rapidly expand before clinical relapse[ 45 ].

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Haploidentical SCT in children: By contrast, others found no significant difference in outcome according to type of donor[ 232 ]. However, intensive systemic therapy is essential for preventing later BM recurrences[ 20262931 ]. Factors influencing survival after relapse from acute lymphoblastic leukemia: Allogeneic stem cell transplantation; MRD: Complete remission complete response ; EM: The COG conducted the AALL01P2 phase II pilot study with the primary objective of developing a safe and active reinduction regimen that could serve as a platform for evaluating the addition of promising new agents in future trials[ 28 ].

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

Little data are available regarding the prognostic impact of these manifestations and on the necessity of local therapy. The International Cooperative Group on Relapsed ALL conducts 2 randomized trials comparing the classic BFM reinduction apl with that reported by the UKCCG in standard and intermediate risk patients, and with a novel regimen combining clofarabine, etoposide, and cyclophosphamide in high risk children, respectively[ 1837 ].

It has been debated whether the intensity of frontline treatment affects the outcome of patients after relapse[ 29 ]. Conflicting results, however, were observed in the Medical Research Council MRC UKR3 trial, in which reinduction therapy with mitoxantrone was superior to that with idarubicin, yet no differences in the end of reinduction MRD were observed[ 30 ]. Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning.

Times Rdz of This Article. This project was supported with a grant from the Swedish Childhood Cancer Foundation, Barncancerfonden. Article-Type of This Article. Although SR patients receive less intense therapy, these data suggest that intrinsic differences in the biology of the leukemic blasts are correlated with different mechanisms and the timing of relapse[ 16 ].