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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None of the 5 patients with t 9;22 were treated with tyrosine kinase inhibitors.

Another impediment in comparing reports is the more favourable outcomes of non-sibling donors SCT over the years. Transplant related mortality could be effectively reduced by improved T cell rex and close monitoring of viral loads followed by preemptive therapy[ 71 ]. Understanding the biological factors contributing to relapse will probably contribute to identify new agents able to increase the chances of a sustained second remission and cure.

No difference in outcome between children and adolescents transplanted for acute lymphoblastic leukemia in second remission. Unrelated donor stem cell transplantation compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission: Complete remission after blinatumomab-induced donor T-cell tez in three pediatric patients with post-transplant relapsed acute lymphoblastic leukemia.

It has been debated whether the intensity of frontline treatment affects the outcome of patients after relapse[ 29 ]. Minimal residual disease MRD status prior to allogeneic stem cell transplantation is a powerful predictor for post-transplant outcome in children with ALL.

Relatively few studies of the long-term outcome after relapsed childhood ALL have been published. Epratuzumab is a humanized monoclonal antibody that binds to the third extracellular domain of CD Rdz the end of intensive systemic chemotherapy, local radiotherapy is applied as indicated followed by conventional maintenance therapy up to 2 years[ 42 ].

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

June 18, Published online: 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 erz co-variates in the models. The optimal post-remission therapy for children with late B-cell precursor BM relapse either isolated or combined is controversial[ 20 ].


Although the majority of these patients died from a relapse of leukaemia, the benefits of the conditioning and the possible graft- vs -leukemia effect after SCT did not outweigh the benefit of the prolonged chemotherapy[ 38 ]. Chemoimmunotherapy reinduction with epratuzumab in bbfm with acute lymphoblastic leukemia in marrow relapse: This study was approved by the Ethical Review Board in Stockholm and was conducted in accordance with the Declaration of Helsinski.

Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. Relapsed ALL remains a significant challenge for pediatric 20002. Corresponding Author of This Article. Allogeneic SCT is a curative option for several hematologic malignancies and the current availability of several different stem cell sources has expanded this option for many children.

In a recent analysis of patients aged years registered in four consecutive Austrian ALL-BFM trials, prognosis of relapsed leukaemia was significantly better for younger patients patients aged years at primary diagnosis than for adolescent i. To this regard, even when a clear superiority from one arm to the other was obtained regarding the primary outcome i. Therapeutic irradiation of manifest extramedullary leukemia in addition to systemic chemotherapy for patients experiencing CNS recurrence can be regarded as standard of care, since the disease is protected from chemotherapy by biological blood 22002 in extramedullary sanctuary sites such as the CNS and the testes[ 18 ].

Ko and coworkers[ 19 ] found increased survival for patients undergoing SCT, regardless of time to relapse or the number of prior relapses. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia ALL R3: Allogeneic hematopoietic cell transplantation in children with relapsed acute lymphoblastic leukemia isolated to the central nervous system.

Patients who relapse after allogeneic SCT often have refractory disease and are particularly susceptible to chemotherapy-related toxicity[ 79 ]. Altogether, of patients An objective of this study was to improve the depth of CR2 using three intensive non-overlapping blocks of chemotherapy derived from combinations that were previously shown to be effective in the management of recurrent ALL.


Reez minimal residual disease before hematopoietic cell transplantation is prognostic but does not preclude cure for children with very-high-risk leukemia. MRD-negative early relapse patients and MRD-positive late relapse patients appeared to form an intermediate group.

Immunophenotype is commonly used in the risk assessment at relapse, but although rrez was a risk factor in the univariate analysis, it was not in the multivariate analysis.

Blinatumumab is an attractive drug to be explored in the near future for children with second or greater relapsed or refractory ALL[ 78 ]. Thus, the use of clofarabine-based regimens should be considered in children with either resistant or second or subsequent BM relapse[ 18 ].

Current approach to relapsed acute lymphoblastic leukemia in children

A variety of other extramedullary sites may be involved in ALL relapse. All tests were two-sided. Donor- vs -recipient NK alloreactivity has emerged as a crucial factor for the outcome of haplo-SCT[ 7273 ].

Although the pattern of relapse and outcome after relapse was very similar between the two NOPHO protocols, we observed a significant improvement in outcome for relapses occurring between and compared to —, as well as a lower proportion of relapses generally associated with worse outcome very early and early relapses in the later period. January 29, Revised: Reported outcomes of trials and cohorts bf, relapsed childhood acute lymphoblastic leukemia.

Tailored risk-adapted treatment is the cornerstone of modern relapse therapy, but there is an urgent need for the development of new drugs and targeted therapies.