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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Journal List Haematologica v. J Pediat Hematol Oncol.

Primary risk groups were not included in the adjusted models since we adjusted for base-line characteristics at diagnosis. Survival analysis In the whole study population, the 5-year EFS was Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between and There was no significante difference in CR2 rate between the two primary protocols, relapse periods or specific relapse protocols.

Treatment for second and subsequent relapses. 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 ]. Minimal residual disease; PPR: Rapid molecular response during early induction chemotherapy predicts a good outcome in childhood acute lymphoblastic leukemia. Transplantation with a TBI-containing regimen resulted in significantly lower risks of relapse, treatment failure, and overall mortality compared to non-TBI regimens and this was independent of the duration of the first remission[ 57 ].

Moreover, DFS estimates are not appreciably improved by aggressive chemo-radiotherapy, as recurrent or refractory malignancies have usually become resistant to chemotherapy.

Current approach to relapsed acute lymphoblastic leukemia in children

Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from tez J Pediatr Hematol Oncol. N Engl J Med. Local therapy for extramedullary ALL.

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 ].


Received Jun 4; Accepted Oct The role of SCT for patients with a second or third relapse has been debated. Such conditioning regimens reduce graft rejection but they can cause considerable mortality due to severe toxicity, delayed immune restoration and severe infection, especially in heavily pre-treated patients. In all survival analyses, the time-scale was defined by the time of diagnosis of relapse. HR for death was 0. Many factors complicate the analysis of published results comparing outcomes after SCT vs chemotherapy only, including intrinsic selection biases, different lengths of the interval between diagnosis of relapse and transplantation as bvm as disparate conditioning regimens, bffm strategies and stem cell sources[ 2134 ].

There were wll statistically significant differences in outcome between the btm protocols or between the relapse protocols used, but an improvement over time was observed. However, this risk factor may be of limited additional value since with the current risk stratification, the majority of these patients are categorized as high-risk at relapse.

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

In the univariate analyses, age ten years or over at primary diagnosis, T-cell immunophenotype, short time in CR1, hyperleukocytosis at primary diagnosis, isolated bone marrow relapse, and unfavorable cytogenetics were adverse prognostic factors. Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: In a prospective randomized trial, Gaynon et al[ 21 ] found poor protocol adherence with small numbers of patients recruited to the chemotherapy arm.

Although we adjusted for base-line variables such as age, WBC at diagnosis and cytogenetics, this survival difference remained clearly significant. Age at primary diagnosis might influence outcome after relapse.

This study was approved by the Ethical Review Board in Stockholm and was conducted in accordance with the Declaration of Helsinski. B Event-free survival after relapse.

We analyzed separately the standard-risk group and adjusted for sex, age, Down syndrome and cytogenetics data not shown. A variety of other extramedullary sites may be involved in ALL relapse.


The study reached its predefined early stopping rule for efficacy when 14 complete responses were observed among the first 22 patients enrolled. Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Risk allocation is based on immunophenotype, time and site of relapse see Table 5. T-cell immunophenotype was not an independent prognostic factor unless in combination with hyperleukocytosis at diagnosis.

High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia: Given the rarity of the disease, prospective clinical trials need to be coordinated within international cooperative groups.

Since patients that relapse after HSCT in CR1 differ substantially from patients treated with chemotherapy only, in baseline characteristics, treatment and outcome, they were excluded from all outcome analysis. Very often, reported trials assigned HR with matched family donors to allogeneic transplantation and those without donors to chemotherapy or autologous transplantation[ 47 ]. Clofarabine was safe and effective when used in combination with cyclophosphamide and etoposide although a high risk of severe infection was noted, including fungal and viral infection.

Though slightly different variables were measured, results from different study groups showed similar poor outcomes for patients in second complete remission CR2 [ 1620 – 22242532 – 34 ]. There was no difference in the median time-to-death post-relapse according to initial regimen, Late recurrence of childhood T-cell acute lymphoblastic leukemia frequently represents a second leukemia rather than a relapse: 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.

For patients with late isolated CNS relapse not allocated to SCTcranio-spinal irradiation is generally postponed until the end of intensive chemotherapy or even after the end of maintenance treatment, in order to avoid intolerability for chemotherapy[ 38 ].