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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There have been few reports on randomized controlled trials in patients with relapsed childhood ALL, and with the numbers of relapse patients decreasing, an international collaboration is very important to serve as a platform for progress to be made in the treatment of relapsed childhood ALL.

The authors concluded that extending the duration of re-induction to three blocks appears to be beneficial for the group of patients with initial favourable morphologic responses and were MRD-negative at the end of the first month of treatment[ 28 ]. In a report by investigators at St. Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia ALL: Relapsed ALL remains a significant challenge for pediatric oncologists.

Successful rdz allogeneic stem cell transplantation in second remission induced by dasatinib in a child with Philadelphia chromosome positive acute lymphoblastic leukemia. These factors rrz their relevance in patients undergoing SCT, and MRD remained the only independent prognostic variable in this setting[ 42 ]. These results suggest that age at initial diagnosis is a prognostic factor in relapsed ALL, just as it is for newly diagnosed disease[ 29 ].

Biol Blood Marrow Transplant. Today, relapses have become relatively rare events in ALL although, because of the frequency of ALL, they are still a significant cause of death in children and adolescents.

Long-term results of the pediatric oncology group studies for childhood acute lymphoblastic leukemia Immunophenotype is commonly used in the risk assessment at relapse, but although immunophenotype was a risk factor in the univariate analysis, it was not in the multivariate analysis.

Most treatment failures after the CR2 are related to subsequent relapses[ 21 ]. Second complete remission; HR: At present, patients with relapsed ALL are allocated bfmm different risk groups based on the immunophenotype, the time from primary diagnosis to relapse and the anatomic site of relapse.


In extramedullary relapses, a clear distinction also has to be made for early relapses vs late relapses. For the standard-risk group, age ten years or over HR 1. Immune cells are genetically modified to express chimeric antigen receptors CAR that contain a target recognition domain linked to an intracellular component that activate a signalling cascade[ 80 ].

In addition, cranial or cranio-spinal radiation was delivered in an age-dependent manner to all patients[ 222426 ]. Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: Patients failing to achieve a CR2 after reinduction chemotherapy have a dismal prognosis[ 252867 ]. This approach can reduce the risk of graft failure retaining CDnegative stem cells and most other immune cells, thus allowing expedite immune reconstitution during the early post-transplant period.

The combination of timing of relapse and MRD appeared to identify three groups of patients. Lethal bacterial sepsis was the principal toxicity[ 87 ]. SCT vs continuation of chemotherapy. White blood cell count.

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Central nervous system; COG: Furthermore, the overall outcome of the SCT-group improved in the second time-period, when MRD was presumably available speaking against this type of negative selection data not shown.

Adjusting for other non-stratifying base-line variables neither changed the HRs significantly 2. In another study, classical risk factors such as immunophenotype, site of relapse, time to relapse, and others were only significant in patients who receive chemotherapy in CR2.

Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies, and on childhood acute lymphoblastic leukemia. Bhojwani et al [ 48 ], Yang et al [ 45 ], Mullighan et al [ 46 ], Hogan et al [ 49 ], Early relapse patients who were MRD positive had a dismal outcome, while late relapse patients who were MRD negative had an excellent outcome, approaching that seen in newly diagnosed patients.

Prognosis seems to be particularly poor for those patients relapsing after SCT[ 22 ]. Current treatment approaches for relapsed ALL begin with reinduction therapy in an attempt to induce a CR2.

Genome-wide expression analysis of paired diagnosis-relapse samples in ALL indicates involvement of pathways related to DNA replication, cell cycle and DNA repair, independent of immune phenotype. It remains unclear as to what will be the most effective approach for HR patients who continue to have high levels of disease before or after transplantation, as this is associated with a high incidence of relapse post-allogenic SCT[ 20 ].


After reinduction chemotherapy, high risk HR patients are clear candidates for allogeneic stem cell transplantation SCT while standard risk patients do better with conventional chemotherapy and local therapy. Early-relapse mechanisms appear to be more homogeneous and are suggestive of the selection of a resistant, more proliferative clone Table 3 [ 48 ].

HR for death was 0. All tests were two-sided. This article has been cited by other articles in PMC.

Children Oncology Group; CR: According to the site of relapse, patients are commonly classified as isolated marrow, concurrent marrow, isolated central nervous system CNSisolated testicular and other extramedullary relapses vfm or without CNS involvement Table 2 [ 16 ].

Risk stratification according to bffm BFM Group classification[ 42 ]. 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 ]. The optimal post-remission therapy for children with late B-cell precursor BM relapse either isolated or combined is controversial[ 20 ].

Log rank test was used for comparing survival across groups.

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

In contrast, for those with a late first relapse and second relapse, leukemia-free and Alk rates were similar after chemotherapy alone and transplantation[ 57 ]. Minimal residual disease status before allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukemia.

Since we were studying a large cohort, we were able to include a number of variables in the regression analysis.

Early relapse Patients failing to achieve CR2 with the same agents used at primary diagnosis usually bfmm not respond to different drug combinations Intrinsic drug resistance: Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: Prognostic impact of karyotypic findings in childhood acute lymphoblastic leukaemia: Rapid immune reconstitution after a reduced-intensity conditioning regimen and a CD3-depleted haploidentical stem cell graft for paediatric refractory haematological malignancies.

May 31, Accepted: C Cumulative incidence of second relapse using competing risks.