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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But unlike the risk stratification at primary diagnosis, cytogenetics are not used to individualize the treatment intensity. Acute lymphoblastic leukemia in children with Down syndrome: In general, a higher dose intensity is used than in first-line treatment but published data do not show one chemotherapy combination to be better than others[ 47 ].

An unmanipulated HLA-haploidentical SCT has been proposed for those few patients who are unable to locate an HLA-compatible donor, a suitable umbilical cord blood unit, or an NK-alloreactive bdm 18 ].

Donor lymphocyte infusions have been advocated to convert stable mixed chimerism into full chimerism and have been used successfully in patients with persistent, relapsed, or progressive disease both after conventional and nonmyeloablative SCT to exert graft- vs 20002 effects, most notably in patients with chronic myeloid leukemia[ 9293 ]. Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from to Outcomes for children and adolescents with cancer: Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: Today, most patients achieve a second remission.

Current approach to relapsed acute lymphoblastic leukemia in children

Biology, risk stratification, and therapy of pediatric acute leukemias: Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies. 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.


Intrathecal lyposomal cytarabine may have a role in relapsed ALL with CNS involvement and resistance to conventional therapy[ 18 ].

Donor- vs -recipient NK alloreactivity has emerged as a crucial factor for the outcome of haplo-SCT[ 7273 ]. Clofarabine was safe and effective when used in combination with cyclophosphamide and etoposide aol a high risk of severe infection was noted, including fungal and viral infection.

New studies clearly need to address how to effectively treat relapsed patients and maintain durable remissions[ 16 ].

Within the BFM studies, orchidectomy has been the treatment of choice for the involved testicle in the case of testicular relapse. The role of Sll for patients with a second or third relapse has been debated.

For early BM relapse they also found no difference in treatment modality; the 2-year estimated EFS was Outcome after first relapse in childhood acute lymphoblastic leukaemia – lessons from the United Kingdom R2 trial.

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

The distribution of patients experiencing early and late relapses were highly skewed towards NCI HR in the former group and NCI standard risk in the latter.

Detectable minimal residual disease before hematopoietic cell transplantation is prognostic but does not preclude cure for children with very-high-risk leukemia.

All deaths occured aol second relapse. Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: Therefore, better consolidation methods are needed without increasing the burden of treatment toxicities.

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

However, this may reflect the fact that those patients selected for HSCT had a higher risk based on the MRD response after re-induction. Our results indicate that the risk classification used in IntReALL is a reasonable approach, but we question whether early combined pre-B relapses should be classified as standard-risk instead of high-risk, since the 5-year overall survival for this subgroup was only Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from to Complete remission complete response ; EM: According to these findings, patients classified as being intermediate risk with conventional clinical parameters could be further classified into a very HR subgroup if MRD proves to persist at a high level until transplantation[ 61 ].


Rapid molecular response during early induction chemotherapy predicts a good outcome in childhood acute lymphoblastic leukemia. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse. By contrast, some of the genes down-regulated at relapse compared with initial diagnosis included proapoptotic genes, antiproliferative genes and a putative tumor suppressor gene[ 48 ].

Epratuzumab is a humanized monoclonal antibody that binds to the third extracellular domain of CD After remission reinduction, recommendations for continuation therapy include ongoing intensive chemotherapy with or without radiation therapy or SCT. Comparison of relapse periods — and — Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between and To validate the commonly used risk classification systems, we retrospectively assigned relapse risk groups according to the criteria in the new IntReALL trial and compared the overall survival between the groups Table 1.

Outcome and toxicity of chemotherapy wll acute lymphoblastic leukemia in children with Down syndrome. Several published retrospective studies suggest some benefit for SCT, particularly for patients with early BM relapse[ 19224257 ]. Epratuzumab administration was tolerated with acceptable toxicity, both as a single agent and when combined with chemotherapy.

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Since there were only 3 patients with T-cell immunophenotype plus hyperleukocytosis in the standard-risk group, this variable was not included in the model as a single co-variate. Our study cohort is population-based and includes over patients treated according to common up-front protocols, making it, to our best knowledge, the largest of its kind.

Thus, apart from the fact that T-cell recurrences tend to occur early, T-cell immunophenotype itself is associated with a very poor outcome after relapse regardless of site and time to relapse[ 1620 – 2224 – 262832 ].

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