Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia

Abstract

BackgroundIn the ALL-BFM 95 trial for treatment of acute lymphoblastic leukemia, response to a prednisone pre-phase (prednisone response) was used for risk stratification in combination with age and white blood cell count at diagnosis, response to induction therapy and specific genetic high-risk features. Design and MethodsCytomorphological marrow response was prospectively assessed on Day 15 during induction, and its prognostic value was analyzed in 1,431 patients treated on ALL-BFM 95. ResultsThe 8-year probabilities of event-free survival were 86.1%, 74.5%, and 46.4% for patients with M1, M2, and M3 Day 15 marrows, respectively. Compared to prednisone response, Day 15 marrow response was superior in outcome prediction in precursor B-cell and T-cell leukemia with, however, a differential effect depending on blast lineage. Outcome was poor in T-cell leukemia patients with prednisone poor-response independent of Day 15 marrow response, whereas among patients with prednisone good-response different risk groups could be identified by Day 15 marrow response. In contrast, prednisone response lost prognostic significance in precursor B-cell leukemia when stratified by Day 15 marrow response. Age and white blood cell count retained their independent prognostic effect. ConclusionsSelective addition of Day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95 (currently in use in several countries as regular chemotherapy protocol for childhood acute lymphoblastic leukemia) may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries that lack the technical and/or financial resources associated with the application of minimal residual disease analysis.Key words: pediatric acute lymphoblastic leukemia, early treatment response, clinical trial. -cell and T-cell leukemia. Haematologica 2012;97(7):1048-1056. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Lauten M, Möricke A, Beier R, Zimmermann M, Stanulla M, Meissner B, Odenwald E, Attarbaschi A, Niemeyer C, Niggli F, Riehm H, and Schrappe M. Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor BPrediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia © F e r r a t a S t o r t i F o u n d a t i o n

Improvements in the survival of children and adolescents with acute lymphoblastic leukemia

“…This study confirms that T-cell ALL remains a more aggressive disease than B-cell ALL and that additional treatment options need to be explored for T-ALL. 1,4 Recent studies have identified new targets for therapy in T-ALL, 5 although trials to investigate the importance of new targeted drugs will be difficult due to the relatively low number of T-ALL patients (about 10% of ALL cases). 1 Similarly, patients in the NCI (National Cancer Institute) high-risk group had only 82.9% 5-year overall survival, while patients from the standard risk group had 95% 5-year overall survival.…”

Effect of Prechemotherapy Steroid on Initial Tumor Load: An Outcome Indicator of Induction of Remission in Childhood Acute Lymphoblastic Leukemia (ALL)

“…Response of leukemic tumor burden to glucocorticoids is said to be the strongest predictor of outcome of the treatment of ALL. 7,8 Most of the studies were carried out using prednisolone. Therefore, this study was designed to see the effect of dexamethasone on tumor load and their relationship with response to induction chemotherapy.…”

Detection and management of minimal residual disease in acute lymphoblastic leukemia

“…1,4,[31][32][33] The general message for the individual patient is simple: the fast reduction or even elimination of the leukemia (or its predominant clone) is highly predictive of superior relapse-free survival. 8,34 Borowitz et al clearly demonstrated that distinct levels of MRD (by FCM) in the peripheral blood at day 8 of induction therapy in a large set of precursor B-cell (pcB) ALL patients (n ϭ 2143) were associated with the probability of EFS (pEFS).…”

“…3 Despite the clear separation of risk groups by BM cytology, 2/3 of the relapses occur in patients with M1 or M2 BM on day 15 of induction. 4 Therefore, advanced and highly sensitive methods for response assessment were needed and developed to detect minimal residual disease (MRD). The choice of technique for MRD detection mainly depends on the aims of the clinical trial and on the availability of resources.…”