. 2021 Aug 3;12:695051. doi: 10.3389/fimmu.2021.695051

Table 2.

Selected published strategies of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia (HR-AML).

Allo-HSCT strategy	Study design	AML patient cohort in the study	Conditioning regimen	Graft-versus-Host Disease (GvHD) prophylaxis	Outcomes	Ref.
HLA-matched allo-HSCT	Retrospective multicenter study of URD^a and MSD^b allo-HSCT in patients (pts) with high-risk acute myeloid leukemia (HR-AML) in CR1^c.	584 adult HR-AML pts:	MAC^e:	ATG^g:	3-year OS°:	(66)
		- CK^d: 32%	- MSD^b: n=183	- MSD^b: n=18	- MSD^b=45%
		- -7/del(7q): 25%	- URD^a: n=252	- URD^a: n=96	- HLA-well-matched URD^a= 37%
		- Others: 43%	RIC^f:	CsA^h:	- Partially-matched URD^a=31%
			- MSD^b: n=252	- MSD^b: n=155	Median follow-up:
			- URD^a: n=106	- URD^a: n=137	- MSD^b: 61 months
				Tacrolimus:	- URD^a: 35 months
				- MSD^b: n=40	3-year TRMⁱ:
				- URD^a: n=191	- MSD^b=21%
				T-cell depletion:	- HLA-well-matched URD^a=26%
				- MSD^b: n=20	- Partially-matched URD^a=47%
				- URD^a: n=29
				Others/missing:
				- MSD^b n=11
				- URD^a: n=
	Retrospective multicenter study of MSD^b, MUD^p, and MMUD^q allo-HSCT in CK^d AML pts.	1,342 adult CK^d AML pts:	MAC^e: n=739	T-cell depletion: n=665	2-year OS^m = 36.8%	(14)
		- 357 with -7/del(7q)	RIC^f: n=603		2-year NRM° = 17.6%
		- 259 with -5/del(5q)	RIC^f: n=603		2-year NRM° = 17.6%
HLA-haploidentical allo-HSCT	Prospective multicenter trial of G-CSF-primed grafts for haploidentical allo-HSCT in pts with blood neoplasms.	45 adult AML pts:	MAC^e: n=64	ATG^g	18-month LFS^x = 44%	(67)
(Haplo-HSCT)		- 34 standard-risk AML	RIC^f: n=16	CsA^h
		- 11 HR-AML		Methotrexate
		In HR-AML group:		Mycophenolate
		- 2 pts in CR3ⁿ		Basiliximab
		- 9 pts with active disease		Basiliximab
	Retrospective multicenter study of unmanipulated haploidentical allo-HSCT in patients with AML.	Within the entire AML cohort:	MAC^e	CsA^h	4-year OS^h = 57%	(68)
		- 99 pts in CR^l		Mycophenolate
		- 51 pts with active disease150 adult AML pts:
		- 95 HR-AML
	Retrospective single-center analysis of MSD^b vs URD^a vs HRD^r allo-HSCT for pts >60 years with AML.	94 adult AML pts:	In HRD^r allo-HSCT:	In HRD^r allo-HSCT:	4-year TRMⁱ = 20%	(69)
		- 28 HR-AML	MAC^e: n=0	Post-transplant cyclophosphamide	2-year OS^h = 55%
		Within the entire AML cohort:	Non-MAC^e: n=9	CsA^h	2-year TRM^d = 24%
		- 80 pts in CR^l	RIC^f: n=24	Mycophenolate	2-year GRFS^e = 32%
		- 14 with active disease	RIC^f: n=24	Mycophenolate	2-year GRFS^e = 32%
	Prospective trial of TCR^s HRD^r allo-HSCT in pts with blood neoplasms, compared with a retrospective cohort of pts treated with TCD^t haplo-HSCT.	65 pts:	TCR^s group (n=32):	In TCR:	1-year OS^m:	(70)
		- 42 AML/MDS	- MAC^e: n=26	Post-transplant cyclophosphamide, Tacrolimus,	- TCR^s = 64%
			- RIC^f: n=6	Mycophenolate	- TCD^t= 30%
			TCD^t group (n=33):	In TCD:	1-year TRMⁱ:
			- MAC^e	ATG^g	- TCR^s = 16%
			- MAC^e	ATG^g	- TCD^t = 42%
	Prospective trial of α/β TCD^t HRD^r allo-HSCT without ATG in children with chemorefractory AML.	22 AML:	MAC^e	Bortezomib and tocilizumab +/− abatacept	2-year OS^m = 53%	(71)
		- 9 HR-AML			2-year EFS^v for HR-AML = 44%
		- 10 primary refractory			TRMⁱ = 9%
		- 12 R/R^u AML with active disease			TRMⁱ = 9%
	Retrospective analysis in children with HR-AML in CR^l receiving α/β TCD^t HRD^r allo-HSCT or MUD^p.	73 HR-AML:	MAC^e	36 pts ATG^g, tacrolimus and methotrexate	3-year OS^m: 74%	(72)
		- 59 pts in CR1^c		47 pts ATG^g, Bortezomib and rituximab	OS^m:
		- 14 pts ≥ CR2^w			- MUD^p = 64%
					- haplo-HSCT = 86%
					GRFS^z:
					- MUD^p = 49%
					- haplo-HSCT = 70%
					TRMⁱ:
					- MUD^p = 14%
					- haplo-HSCT = 5%
	Prospective trial of α/β TCD^t and B cell-depleted HRD^r allo-HSCT in children with AL.	80 AL:	MAC^e	ATG^g	For entire cohort:	(73)
		- 24 CRⁱ (CR1^c=16, CR2^w=8)			5-year OS^m = 72%
		- 4 HR-AML			5-year CRFS^y = 71%
					5-year TRMⁱ = 5%
					For AML sub-cohort:
					5-year LFS^x = 68%
	Retrospective multicenter comparative analysis of URD^a- or α/β TCD^t HRD^r allo-HSCT in children with AL.	342 AL:	MAC^e	In HRD^r allo-HSCT:	For α/β TCD^t haplo-HSCT AL cohort:	(74)
		- MUD^p: 127		α/β⁺ and CD19⁺ negative selection + ATG^g	5-year probability of OS^m = 68%
		- MMUD^q: 118			5-year LFS^x = 62%
		- HRD^r: 98			5-year CRFS^y = 59%
		105 CR^l AML:			TRMⁱ = 9%
		- MUD^p: 43			Cumulative incidence of relapse for AML sub-cohort = 21%
		- MMUD^q: 32
		- haplo-HSCT: 30
	Prospective single-arm clinical trial of naïve TCD^t peripheral blood stem cells grafts for adult pts with high-risk leukemia.	35 Adult high-risk leukemia:	MAC^e	Tacrolimus	2-year OS^m = 78%	(75)
		- 10 AML	MAC^e	Tacrolimus	2-year OS^m = 78%	(75)
	Prospective single-center trial of adult AML pts undergoing HRD^r allo-HSCT combined with regulatory and conventional T cells adoptive immunotherapy	50 adult AML pts:	Age-adapted MAC^e	None	29-month OS^m = 77%	(76)
		- 20 HR-AML			CRFS^y = 75%
		- 42 CRⁱ			CRFS^y (for HR-AML) = 72%
		- 8 with active disease			TRMⁱ = 21%
	Cumulative Incidence of relapse: 4%	- 8 with active disease

URD, unrelated donor; ^bMSD, matched sibling donor; ^cCR1, first complete remission; ^dCK, complex karyotype; ^eMAC, Myeloablative conditioning regimen; ^fRIC, Reduced-intensity conditioning regimen; ^gATG, anti-thymocyte immunoglobulin; ^hCsA, cyclosporin; ⁱTRM, transplant-related mortality; ^lCR, complete remission; ^mOS, overall survival; ⁿCR3, third complete remission; ^oNRM, non-relapse mortality; ^pMUD, matched unrelated donors; ^qMMUD, mismatched unrelated donors; ^rHRD, haploidentical related donor; ^sTCR, T-cell replete; ^tTCD, T-cell deplete; ^uR/R, relapsed/refractory; ^vEFS, event-free survival; ^zGRFS, GvHD-free, relapse-free survival; ^wCR2, second complete remission; ^XLFS, leukemia-free survival; ^yCRFS, chronic GvHD-free, relapse-free survival.