Table 1.

Survival outcomes and targeted therapies for patients with high-risk acute lymphoblastic leukemia.

ALL Type	5-Year EFS Rate	5-Year OS Rate	Targeted Therapies
Ph+	58 ± 6% (children and adolescents 1–21 years) [13]	70 ± 6% (children and adolescents 1–21 years) [13]	TKIs (imatinib, dasatinib) [13]
Ph-like	58.2 ± 5.3% (children 1–15 years), 41.0 ± 7.4% (adolescents 16–20 years), and 24.1 ± 10.5% (young adults 21–39 years) [14]	72.8 ± 4.8% (children 1–15 years), 65.8 ± 7.1% (adolescents 16–20 years), and 25.8 ± 9.9% (young adults 21–39 years) [14]	TKIs, JAK inhibitors (ruxolitinib) [15,16]
KMT2A rearranged	6-year EFS 73.9% (infants) [17]	6-year OS 87.2% (infants) [17]	Blinatumomab, CAR T-cells [18], menin inhibitors [19]
MEF2D rearranged	74% (63–82%) (children and adolescents 1–18 years) [20]	81% (71–88%) (children and adolescents 1–18 years) [20]	HDAC inhibitors [21], proteasome inhibitors [22]
TCF3::HLF fusion	25 ± 21.7% (infants, children, and adolescents 0–18 years) [23]	37.5 ± 28.6% (infants, children, and adolescents 0–18 years) [23]	BCL2 inhibitors [24], PARP inhibitors [25], blinatumomab followed by HSCT [26]
Hypodiploid	55.1% (95% CI, 49.3–61.5%) (infants, children, and adolescents up to 21 years) [27]	61.2% (95 CI, 55.5–67.4%) (infants, children, and adolescents up to 21 years [27]	BCL2 inhibitors, PI3K inhibitors, immunotherapy, CAR T-cells [22,28,29,30]
iAMP21	4-year EFS 72.7 ± 5.8% (children, adolescents, and young adults 1–30 years) [31]	4-year OS 87.6 ± 4.4% (children, adolescents, and young adults 1–30 years) [31]	Trials of target therapies are needed
ETP-ALL	87.0% (children, adolescents, and young adults 1–31 years) [32]	93.0% (children, adolescents, and young adults 1–31 years) [32]	Trials of target therapies are needed
MPAL	72 ± 8% (entire cohort 1–30 years), 75 ± 13% (patients on ALL regimen), 62 ± 14% (patients on AML regimen) [33]	77 ± 7% (entire cohort 1–30 years), 84 ± 9% (patients on ALL regimen), 69 ± 14% (patients on AML regimen) [33]	CD19 bispecific T-cell engagers and CAR T cells [34,35], immunotherapy with blinatumomab bridge to HSCT [36,37]

Abbreviations: EFS, event-free survival; OS, overall survival; Ph+ ALL, Philadelphia chromosome-positive ALL; TKI: tyrosine kinase inhibitor; Ph-like ALL, Philadelphia chromosome-like ALL; CAR, chimeric antigen receptor; HDAC, histone deacetylase; BCL2, B-cell lymphoma 2; PARP, poly(ADP-ribose) polymerase; CI, confidence interval; PI3K, phosphoinositide 3-kinase; iAMP21, intrachromosomal amplification of chromosome 21; ETP-ALL, early T-cell precursor ALL; MPAL, mixed-phenotype acute leukemia; HSCT, hematopoietic stem cell transplantation.