Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome

Abstract

R elapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5±3.4%, but 44.7±3.2% (P<0.001) if relapse occurred in the period 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ten years or over, unfavorable cytogenetics, and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless in combination with hyperleukocytosis at diagnosis. The outcome for early combined pre-B relapses was unexpectedly poor (5-year overall survival 38.0±10.6%), which supports the notion that these patients need further risk adjustment. Although survival outcomes have improved over time, the development of novel approaches is urgently needed to increase survival in relapsed childhood acute lymphoblastic leukemia. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome

Treatment‐related mortality in relapsed childhood acute lymphoblastic leukemia

“…Despite attempts to improve cytotoxic chemotherapy regimens for ALL relapse, the rate of second relapses is high and the overall survival is still relatively poor. In our previous study, we observed an improvement in survival between the relapse periods 1992–2001 and 2002–2011 . This was mainly caused by a decrease in the frequency of second relapses but in this study we did not observe a difference in TRM between the relapse periods.…”

“…Surprisingly none of the patients with DS died of treatment‐related causes. In our previous study, patients with ALL relapse and DS had a poor overall survival caused by the high occurrence of second relapses . This is in contrast to previous findings where patients with DS‐ALL had worse outcome mainly because of the high incidence of TRM .…”

“…A description of the risk groups and treatment used in the NOPHO ALL‐92 and ALL‐2000 trials as well as the long‐term results were published in Leukemia 2010 . Furthermore, a detailed description of the prognostic factors, treatment, and outcome for relapsed ALL in the same initial cohort was recently published in Haematologica …”

“…These results are mostly due to the intensification of chemotherapy, better supportive care, and advances in allogeneic hematopoietic stem cell transplantation (HSCT). Nevertheless, relapse remains a challenge since it occurs in 8–20% of patients in first remission and only half is expected to survive long term . For each patient with ALL, the road to long‐term survivorship is long and is often complicated with serious side effects of the treatment.…”

Use of inotuzumab‐ozogamicin in a child with Down syndrome and refractory B‐cell precursor acute lymphoblastic leukemia

“…It has been suggested that a higher incidence of treatment‐related toxicity could result in dose reduction of some drugs, such as methotrexate. Treatment of relapsed/refractory ALL remains an important challenge in patients with DS because of increased TRM and the high rate of relapse . In this context, enrolling patients with DS‐ALL in clinical trials with immunotherapy is crucial, because the potentially less severe myelosuppression in these therapies could result in less toxicity …”