Table 2.

Studies on second HSCT. Abbreviations: HSCT: hematopoietic stem cell transplantation, CR: complete remission, PR: partial remission, CRi: complete remission with incomplete hematologic recovery, MLFR: myeloid leukemia free state, no resp: no response, SD: stable disease, CIR: cumulative incidence of relapse, ORR: overall response rate, OS: overall survival, RFS: relapse-free survival, EFES: event-free survival, DFS: disease-free survival, AML: acute myeloid leukemia, MDS: myelodysplastic syndrome, ALL: acute lymphoblastic leukemia, mts: months, DLI: donor lymphocyte infusion, MRD: matched-related donor, UD: unrelated donor, MMRD: mismatched-related donor, MMUD: mismatched unrelated donor, Haplo: haploidentical, EBMT: European bone marrow transplantation, CIBMTR: Center International for Blood and Marrow Transplantation Research, MDACC: MD Anderson Cancer Center, GETH: Group Espanol de Transplante Hematopoyetico.

Authors	Register/ Institute	N Pts	Period	Donor Type (MRD, MMRD, UD, MMUD, HAPLO)	Outcome (OS, LFS)	Risk Factors (p-Value)
Christopeit M. et al., 2013 [91]	EBMT	179 (132 AML, 46 ALL, 1 unclassifiable leukemia)	1998–2009	Previous MRD: Same MRD: 51% Different MRD: 11% UD: 38% Previous UD: Same UD (42%) Different UD (58%)	2-year LFS: 21% 2-year OS: 25%	OS advantage: -Previous CR longer than 6 mts (p < 0.001) -CR at 2nd HSCT (p = 0.006) -1st HSCT from MRD than UD (p = 0.042)
Orti G. et al., 2016 [92]	GETH	116 (88 AML, 25 MDS, 3 MPN)	1979–2011	MRD: 83% UD: 11% MMRD: 4% Syngenic: 2%	5-year DFS: 30% 5-year CIR: 37.8% 5-year OS: 32%	Shorter OS: -active disease (p < 0.001.) -time between 1st and 2nd HSCT <430 days (p < 0.001). -2nd HSCT from a donor different from MRD. (p = 0.03)
Shimoni A. et al., 2019 [96]	EBMT	556 AML	2006–2016	3 groups: 1- From 1st MRD or UD to 2nd same donor group 2- From 1st MRD or UD to 2nd different MRD or UD 3- From 1st MRD or UD to 2nd HAPLO	2-year LFS: 23.5% vs. 23.7% vs. 21.6% (p = 0.3) 2-year CIR: 51% vs. 49% vs. 44% (p = 0.9) 2-year OS: 36.4% vs. 28.7% vs. 23.3% (p = 0.21)	Shorter LFS and OS: -relapse <6 mo after 1st HSCT (p = 0.01) -advanced age (p = 0.07). -2nd HAPLO donor (p = 0.07). Better LFS and OS: -CR at 2nd HSCT (p = 0.002)
Kharfan-Dabaja M. et al. [97] 2021	EBMT	455 AML	2006–2019	2nd HSCT from UD (320 pts) vs. Haplo (135 pts)	2-year LFS: 25% vs. 29% (p = 0.73) 2-year OS: 31% vs. 29% (p = 0.57)	OS advantage: -Relapse > 1 year after 1st HSCT (p < 0.0001) -CR at 2nd HSCT (p = 0.02)
Rank A. et al., 2021 [98]	EBMT	45 (34 AML, 11 ALL)	2001–2018	3rd HSCT: 25 pts different donor from 2nd HSCT; 30% of pts had at least 2 donors	1-year PFS: 11% 1-year OS: 20%	OS/PFS advantage: -Change donor at least one time (p = 0.009/p = 0.007) -KS > 80% (p = 0.083/p = 0.046) -3rd HSCT from UD (p = 0.014/p = 0.012) -3rd HSCT after 2010 (p = 0.011/p = 0.012)
Kharfan-Dabaja M. et al. [99] 2018	EBMT	418 AML	1992–2015	Retrospective comparison 2nd HSCT vs. DLIs2 groups: 2nd HSCT (MRD 56%, UD 43%) vs. DLIs (MRD 54%, UD 46%)	2-year OS in pts relapsing <6 mo: 11% vs. 9% (p = 0.86) 2-year OS in pts relapsing >6 mo: 36% vs. 37% (p = 0.53) 2-year OS in pts in CR at intervention: 35% vs. 51% (p = 0.22) 2-year OS in pts not in CR at intervention: 20% vs. 19% (p = 0.59)	OS advantage: -Relapse > 6 months after 1st HSCT (p < 0.001) -CR at 2nd HSCT (p = 0.001) -prior cGVHD (p = 0.02)
Yalniz et al., 2021 [94]	MDACC	91 AML	2000–2019	MRD: 41% UD: 37% HAPLO: 21% Cord Blood: 1%	2-year PFS: 27% 2-year OS: 36%	Shorter OS: -cGVHD after 1st HSCT (p = 0.001) -HCT-CI ≥2 at 2nd HSCT (p < 0.003). -Relapse < 6 months after 1st HSCT (p < 0.02) -2nd HSCT before 2011 (p = 0.02) Shorter PFS: -cGVHD after 1st HSCT (p = 0.001) -HCT-CI ≥2 at 2nd HSCT (p = 0.01)
Duncan CN et al., 2015 [93]	CIBMTR	146 Children (64 AML, 66 ALL, 12 MDS, 4 JMMS) 179 Adults (111 AML, 54 ALL, 14 MDS)	1980–2009	Children: MRD: 53% UD: 41% Other Related: 5% Adults: MRD: 55% UD: 40% Other Related: 4%	2-year OS: Children: 83% Adults: 75% 6-year OS: Children: 64% Adults: 51% 10-year OS: Children: 55% Adults: 39%	Shorter OS: -Disease not in CR before 2nd HSCT (<0.01)