Table 1.

Knowns and unknowns with regard to various alternatives to traditional cytotoxic chemotherapy before or after HSCT for paediatric BCP-ALL.

	Knowns	Unknowns	Ongoing trials
Specific agents
Blinatumomab	First relapse: improved outcome, decreased toxicity	Specific effects on HSCT outcome
		Should it be integrated first-line in specific disease subsets?	Interfant—pilot and future protocols AALL1731, various populations, including standard risk patients with Trisomy 21 (NCT03914625) NCT04604691 ALL Together 1, patients with Trisomy 21
		Comprehensive safety/efficacy in infants	Trial NL5993 NCT05029531
Inotuzumab Ozogamicin	Activity in paediatric patients with r/r CD22+ ALL Increased VOD/SOS in adults	Increased VOD/SOS affecting HSCT outcome in children	ITCC-059 (EudraCT Number 2016-000227-71)
General unanswered questions (unknowns)
Use of these therapies in the post-HSCT setting	use as maintenance in HR populations?		Blinatumomab NCT04785547
	impact on GVHD and other HSCT-specific morbidities (e.g., VOD/SOS)?		NCT04044560 NCT047462069
	effect of incomplete immune reconstitution on the efficacy of these therapies?		NCT02807883 NCT03982992 NCT03849651 NCT03849651 InO NCT03913559 NCT03104491 NCT03856216