A systematic review of clinical effectiveness and safety for historical and current treatment options for metachromatic leukodystrophy in children, including atidarsagene autotemcel

Table 11 Number of patients experiencing fatal AE after HSCT

Treatment	MLD type	Symptom status	Timepoint after treatment	n/N (%)	Source—design
HSCT	J	Mixed	NR	13/27 (48.1%)^a	Boucher [21]—R
	J	Mixed	NR	0/8 (0%)	Bohringer [19]—NR*
	LI	Mixed	NR	2/4 (50%)^b	Boucher [21]—R
	J	Mixed	Within wks of HSCT (exact time NR)—TRAE	4/24 (16.7%)^c	Groeschel [16]—R*
	LI to LJ**	Mixed	Median 5.1 years (range 2.4–14.7 years)	7/27 (25.9%)^d	Martin [23]—R

Mixed refers to populations with a mixture of pre-symptomatic and symptomatic patients
EJ early juvenile, HSCT haematopoietic stem cell transplant, LI late infantile, n number with outcome, N total number assessed, NR not reported, Pre-symp pre-symptomatic, R retrospective study, TRAE treatment related adverse event, yr year
*Indicates that there is a possibility of overlap with populations reported in other studies based in German study centres and/or using the LEUKONET database
**LJ disease is no longer relevant to the indication for Atidarsagene treatment
^aCause of death: hepatic veno-occlusive disease (VOD) n = 1, cGVHD n = 2, aGVHD n = 1, sepsis n = 5, MLD n = 2, multi-system organ failure (MSOF) n = 1, thrombotic thrombocytopenic purpura (TTP) n = 1
^bCause of death: unknown n = 1, hepatic veno-occlusive disease (VOD) n = 1
^cTransplantation-related mortality occurred in 4 children (17%), all of whom died of infections associated in part with graft rejection
^dIncludes: multiple organ failure n = 1; Respiratory failure (after chronic lung disease) n = 2; Viral infections/malignancy n = 3 (includes one EBV PTLD); Disease progression and infection n = 1

ISSN: 1750-1172