To Augment or Not to Augment Consolidation Therapy for High-Risk Childhood Acute Lymphoblastic Leukemia

Nachman et al in the year 1998 published results of Children's Cancer Group (CCG)-1882 study which they explored role augmented intensive postinduction therapy among children with high-risk acute lymphoblastic leukemia (ALL).[1] Following this study, Berlin-Frankfurt-Munster (BFM) consolidation consists additional vincristine and asparaginase during periods myelosuppression standard IB phase became preferred for ALL across several cooperative groups. Nearly 25 years later, intercontinental BFM group have BFM-2009 aimed to address a similar question.[2] In patients belonging intermediate-/high-risk were randomized following induction either or phase. The showed no difference relapse incidence (19.1% vs. 20.5%; p = 0.55) overall survival (OS) (81.9% 80.3%; 0.46) between phases, respectively. Further, subgroup analysis failed demonstrate an impact regimen on risk (intermediate-risk high-risk) immunophenotype (B-ALL T-ALL). addition, allergic reactions asparaginase, infections, pancreatitis higher arm. contrast CCG-1882 significant improvement augmentation therapy.[1] So, what accounted disparity two studies? First, included National Institute (NCI) (age ≥ 10 total leukocyte count [TLC] 50 × 109 /L) poor early response defined as > 25% marrow blasts day 7, whereas employed different age (6 years) TLC cutoff (≥ 20 109/L) addition 15 measurable residual disease (MRD) adverse cytogenetics define groups eligible randomization. Moreover, extended intensification not only but also interim maintenance delayed while limited A was observed central nervous system (CNS) prophylaxis studies. restricted cranial radiotherapy (CRT) exclusively CNS-3 offered high-dose methotrexate (HDMTX) all patients, Capizzi I escalating intravenous MTX without leucovorin rescue plus prophylactic CRT patients. promising led (CCG-1961) NCI rapid (< 7), again concluded favor regimen.[3] More recently, Medical Research Council their UKALL-2003 trial studied manner patients.[4] intermediate-risk based 8 response, receive risk-specific if had MRD more than 0.01% 29 induction. Augmented context consisted eight doses pegylated extra 18 along MTX. study's findings indicated superior event-free (89.6% 82.8%, 0.04) OS (92.9% 88%, 0.16) receiving therapy. While highlights importance augmenting persistent at end induction, it does definitely establish benefit consolidation.[4] Several previous studies shown achieving clearance by 78 (end consolidation), both B- T-cell ALL.[5] [6] [7] [8] COG AALL0232 B-ALL received four-drug followed consolidation.[6] Among 2,473 evaluated 685 positive 0.01%) small proportion (n 45) remained This suggests that employing might be justified subset MRD, has potential effective MRD. limitation lack details, could shed light backbone chemotherapy. It is important note HDMTX effect HDTMX (compared MTX) pronounced who positive. Based data from ALL0232 recent UKALL-2011 may mitigating bone its sanctuary sites.[9]