Treating Childhood Acute Lymphoblastic Leukemia without Cranial Irradiation

Abstract

Background We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted in all children with newly diagnosed acute lymphoblastic leukemia. Methods A total of 498 evaluable patients were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission induction treatment. Continuous complete remission was compared between the 71 patients who previously would have received prophylactic cranial irradiation and the 56 historical controls who received it. Results The 5-year event-free and overall survival probabilities (95% confidence interval) for all 498 patients were 85.6% (79.9% to 91.3%) and 93.5% (89.8% to 97.2%), respectively. The 5-year cumulative risk of isolated central-nervous-system (CNS) relapse was 2.7% (1.1% to 4.2%), and that of any CNS relapse (isolated plus combined) was 3.9% (1.9% to 5.9%). The 71 patients had significantly better continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remain in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blasts at diagnosis and a high level of minimal residual disease (≥ 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the presence of the t(1;19)[TCF3-PBX1], any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to L-asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. Conclusions With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted in the treatment of childhood acute lymphoblastic leukemia.

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

“…Patients with T-cell ALL have a higher incidence of induction failure and CNS relapse [15,38]. Compared with precursor B-cell ALL, the prognostic markers for T-cell ALL are relatively inadequate for treatment planning.…”

“…Although the use of intensive chemotherapy has enabled patients with T-cell ALL to fare as well as patients with B-cell precursor ALL in some studies, the outcomes are significantly worse for the patients with T-cell ALL in most treatment protocols [3][4][5][6][7][8][9][10][11][12][13][14][15]. Chromosomal alterations, including numbers and translocations, have helped to classify pediatric patients with B-cell precursor ALL and improve treatment outcomes in the past three decades [16].…”

Implementation of an intensive risk‐stratified treatment protocol for children and adolescents with acute lymphoblastic leukemia in Lebanon

“…As intensive risk-directed multi-agent chemotherapy protocols have shown excellent results, a risk-stratified protocol was implemented at Children's Cancer Center of Lebanon (CCCL). The protocol was adapted from the Total XV Therapy Study [14] of St. Jude Children's Research Hospital with the aim to improve survival in Lebanese children with ALL. In this manuscript, we describe our experience in characterizing and treating pediatric ALL patients using our adapted protocol at a major tertiary referral center in Lebanon.…”

The utility of performing the initial lumbar puncture on day 8 in remission induction therapy for childhood acute lymphoblastic leukemia: TCCSG L99‐15 study

“…The prognostic significance of the presence of leukemic blasts in the cerebrospinal fluid (CSF) without pleocytosis, referred to as CNS-2, has varied in clinical trials and is heavily dependent on the effectiveness of systemic and CNS-directed therapy [8][9][10][11]. By contrast, traumatic lumbar puncture with leukemic blasts (TLPþ) adversely affects the outcome of patients with ALL as well as overt CNS leukemia [2,[9][10][11]. Though controversy over whether TLPþ is an iatrogenic event or intrinsically inevitable status still exists, clinicians should pay attention to keep the rate of TLPþ to a minimum.…”

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INTRODUCTIONThe long-term cure rate in childhood acute lymphoblastic leukemia (ALL) is as high as 80% [1,2], and this is largely attributable to sufficient central nervous system (CNS)-directed therapy, such as prophylactic cranial irradiation (pCRT) and intrathecal chemotherapy (IT) [3]. However, administering CNS-directed therapy always results in a dilemma between sufficient intensity and treatmentrelated toxicity.

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