Table 3.

Clinical Research Findings from Selected Collaborative Studies (I will revise this table)

Subgroup of ALL	Years of Study	No. of Study groups	No. of Patients	Major Findings	References
Infant ALL	1995–2005	17	482	Hybrid treatment regimen with drugs against both ALL and acute myeloid leukemia improved outcome. Transplantation benefited high-risk subgroup with MLL rearrangement, age < 6 months, and poor early steroid response or hyperleukocytosis.	Pieters et al21 Mann et al.22
Down syndrome	1995–2004	16	653	These patients have increased risk of relapse and treatment-related mortality. More than half of the cases are characterized by aberrant expression of CRLF2, often associated with JAK-STAT activation.	Buitenkamp et al.23,25 Mullighan et al.24
Induction failure	1985–2000	14	1041	Treatment outcome for patients with induction failure was highly heterogeneous. Only patients >6 years with B-ALL and those with T-cell ALL appeared to benefit from allogeneic transplantation.	Schrappe et al.26
Early T-cell precursor	1992–2006	2	30	These patients have distinctive immunophenotype (CD1a−, CD8−, CD5weak with stem-cell or myeloid markers) and high levels of minimal residual disease after remission induction.	Coustan-Smith et al.28
Philadelphia chromosome-positive	1986–1996	10	326	Older age, high presenting leukocyte count, and poor steroid response adversely affected treatment outcome.	Arico et al.31
	1995–2005	10	610	Both matched-related and matched-unrelated transplantation improved treatment outcome.	Arico et al.32
	2004–2009	10	178	Imatinib combined with intensive chemotherapy was well tolerated and might improve outcome.	Biondi et al.33
Philadelphia chromosome-like	2008–2009	2	221	Genetic alteration of IKZF1 was associated with high levels of minimal residual disease and a poor prognosis.	Mullighan et al.45
	2008–2009	2	297	These cases had frequent deletions of genes involved in B-cell development, resistance to asparaginase and daunorubicin, and poor outcome.	Den Boer et al.46
	2014	5	264	Over 90% of the cases have kinase activating alterations, some amenable to inhibition with tyrosine kinase inhibitors.	Roberts et al.48,49
MLL-rearranged	1983–1995	11	497	Prognosis varied according to the age of presentation, type of MLL rearrangement and early steroid treatment response; allogeneic transplantation in general did not improve outcome.	Pui et al.38,39
	1983–1995	12	450	Secondary chromosomal abnormalities have no prognostic significance in patients with 11q23 rearrangements.	Moorman et al.40
Hypodiploid<44 chromosomes	1986–1996	11	139	Prognosis was poor, especially among patients with near-haploid or low-hypodiploid ALL.	Nachman et al.41
	2008–2013	2	126	Near-haploid cases have genetic alterations targeting receptor tyrosine kinase and Ras pathway and IKZF3 mutations, and low-hypodiploid cases are characterized by IKZF2 alterations and TP53 mutations, half of which are inherited.	Holmfeldt et al.42