Table 1.
Selected reports on CMV infection after haploidentical stem cell transplantation.
| Group | Year | Country | haploSCT Sample size | Primary Disease (n) | Stem cell source (n) | Graft manipulation | Dose of ATG | Conditioning (n) | GVHD prophylaxis | Assays measuring CMV DNAemia | Cutoff values for CMV reactivation or reactivation needing PET | CMV reactivation | CMV disease | Clinical outcome/Comments | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y Wang et al. | 2013 | China | 756 | AML (321); ALL (299); CML (136) | BM+PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | Modified BUCY | CsA+MMF+short-term MTX | Real-time PCR or with a CMV pp65 antigenemia test | NR | 100-day 64% | 4% | 2-year relapse (18%); 3-year OS (67%), LFS (63%), NRM (18%). More CMV-seropositive patients became antigenemia-positive than CMV-seronegative patients. | (4) |
| Y Chen et al. | 2016 | China | 248 | AL (201); CML (32); Others (15) | BM+PBSC | in vivo TCD-haploSCT | r-ATG 2.5 or 1.5mg/kg×4d | Modified BUCY (241); TBI+CY+Me-CCNU (7) | CsA+MMF+short-term MTX | Real-time PCR (RT-PCR) | A viral load of >500 copies/ml for two consecutive readings 5 days apart | 59.50% | 6.85% | CMV DNAemia was found to be a poor prognostic factor in terms of NRM and OS. HBsAg seropositivity was associated with an increased risk of cytomegalovirus DNAemia. | (5) |
| CH Yan et al. | 2020 | China | 1466 | AML (801); ALL (490); MDS (175) | BM+PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | Modified BUCY (1416); TBI+CY+Me-CCNU (50) | CsA+MMF+short-term MTX | Automated, real-time, quantitative PCR assay | A detection threshold of >1000 copies/ml was defined as positive | 64.80% | 1-year CMVR 2.3% | CMVR was a rare complication after haploidentical HSCT but that the risk was greater in patients with multiple risk factors. | (6) |
| XY Meng el al. | 2020 | China | 3862 | AML (36); ALL (51); MDS (14); CML (4); SAA (2); Others (6) | BM+PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | Modified BUCY or TBI+CY+Me-CCNU BUCY (SAA) |
CsA+MMF+short-term MTX | Real-time PCR | A limit of detection of 509 IU/mL | NR | 2.92% | 1 year NRM 34.9% in patients with CMV diseases | (7) |
| LP Xu et al. | 2016 | China | 101 | SAA | BM+PBSC (100); BM (1) | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | BUCY | CsA+MMF+short-term MTX | NR | NR | 68.30% | 1% | 3-year OS (89.0%); FFS (86.8%) | (9) |
| LP Xu et al. | 2017 | China | 89 | SAA (69); VSAA (20) | BM+PBSC (78); BM (9); PBSC (2) | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | BUCY | CsA+MMF+short-term MTX | NR | NR | 51.70% | 1.12% | 3-year OS (86.1 ± 3.7%); FFS (85.0 ± 3.9%) | (10) |
| LP Xu et al. | 2018 | China | 51 | SAA | BM+PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | BUCY | CsA+MMF+short-term MTX | NR | NR | 84.00 ± 0.29% | 1.96% | 1- and 3-year OS 83.5 ± 5.4% (the probabilities of FFS were equal to the OS) | (11) |
| LP Xu et al. | 2017 | China | 52 pediatric patients | SAA (32); VSAA (20) | BM+PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | BUCY | CsA+MMF+short-term MTX | NR | NR | 69.20% | NR | 3-year OS (84.5 ± 5.0%); FFS (82.7 ± 5.2%) | (12) |
| Y Lu et al. | 2018 | China | 41 | SAA | BM+PBSC | in vivo TCD-haploSCT | r-ATG 7.5 mg/kg (total dose) ATG-F 20mg/kg (total dose) | BUCY | Tacro+MMF+short-term MTX | PCR | Higher than 500 copies/mL | 65.90% | 4.88% | 3-year OS (80.3 ± 5.1%); FFS (76.4 ± 5.1%); GFFS (79.0 ± 8.6%) | (13) |
| L Liu et al. | 2020 | China | 146 | SAA (75); VSAA (71); SAA with PNH clone (15) | BM (15); PBSC (4); BM + PBSC (127) | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | BUCY | CsA+MMF+short-term MTX | Real-time PCR | NR | 42.47% | 2.05% | 4-year OS (81.4 ± 3.3%); GFFS (69.2 ± 3.9%) | (24) |
| Z Liu et al. | 2017 | China | 44 | SAA (31); VSAA (13) | BM+PBSC+MSCs | in vivo TCD-haploSCT | r-ATG 3.125 mg/kg×4d | BUCY | CsA+MMF+short-term MTX | NR | NR | 65.90% | 0 | 2-year OS 77.3% | (27) |
| Z Wang et al. | 2014 | China | 17 children and adolescents | SAA (11); VSAA (5); 2nd HSCT (1) | BM+PBSC+MSC | in vivo TCD-haploSCT | r-ATG 5mg/kg×4d (-4 to -1); ALG 20mg/kg/day d-4 to -1 | Flu+BUCY | CsA+MMF+short-term MTX+basiliximab | Real-time PCR | NR | 82.30% | 0 | 1-year OS 71.60 ± 17.00% | (14) |
| L Gao et al. | 2014 | China | 26 | SAA (16); VSAA (10) | BM+PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | Flu+CY | CsA+MMF+short-term MTX | PCR | NR | 23.08% | 3.85% | TRM 3.8% (100-day), 11.5% (1-year), 15.4% (2-year); OS 84.6% (follow-up of 1313.2 days) | (15) |
| Y Lu et al. | 2021 | China | 377 | AML | BM+PBSC | in vivo TCD-haploSCT | r-ATG 7.5-10mg/kg; ATG-F 20mg/kg | Modified BUCY, n=118; Intensified BU-based MAC, n=259 | CsA+MMF+short-term MTX | Real-time quantitative PCR | NR | 67.4 ± 5.1% | 1.06% | 3-year OS 74.9 ± 2.4%; LFS 73.8 ± 4.8%; relapse rates 14.3 ± 4.0%; NRM 12.3 ± 3.5% | (16) |
| Jiafu Huang et al. | 2020 | China | 75 patients aged over 50 years | AML (60); MDS (15) | BM+PBSC | in vivo TCD-haploSCT | r-ATG 7.5-10mg/kg | BUCY or BF or TBI+CY | CsA+MMF+short-term MTX | PCR | NR | 64.00% | 4.00% | 2-year relapse 27.0% ± 5.6%; PFS 59.3% ± 5.8%; OS 63.0% ± 5.8%; GRFS 42.6% ± 5.9% | (17) |
| P Suo et al. | 2020 | China | 27 | MDS | BM+PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | Modified BUCY | CsA+MMF+short-term MTX | Quantitative PCR | PET was given when a single CMV DNA > 1000 copies/mL or 600 copies/mL were observed twice. | 59.30% | 0 | 3-year DFS and 3-year OS 81.9% | (20) |
| P Ke et al. | 2018 | China | 48 | MDS | BM (9); PBSC (1); BM+PBSC (38); coinfusion of the cord blood | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | Modified BUCY | CsA+MMF+short-term MTX | NR | NR | 42% | 0 | 2-year OS 64%; RFS 56%; relapse 12%; NRM 33% | (19) |
| L Gao et al. | 2015 | China | 47 | Ph+ ALL | BM+PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | TBI+Ara-C+CY | CsA+MMF+short-term MTX | NR | NR | 38.30% | 8.51% | 2-year OS 63.8%; LFS 59.5% | (18) |
| H Zhao et al. | 2020 | China | 55 | ALL | BM+PBSC or PBSC | in vivo TCD-haploSCT | NR | BUCY+TBI or nonmyeloablative regimens | NR | NR | NR | 56.10% | NR | 2-year LFS 65.6%; OS 77.0% | (21) |
| L Gao et al. | 2017 | China | 174 | AML (73); ALL (61); CML (22); MDS (18) | BM+PBSC | in vivo TCD-haploSCT | ATG-F 5mg/kg×4d | CCNU+BU+CY+Ara-C (AML,CML and MDS) CY+TBI+Ara-C (ALL) |
CsA/Tacro+MMF+short-term MTX | PCR | NR | 39.5% (Short-term Tacro); 37.5% (CsA) | NR | 2-year OS 59.3% (Short-term Tacro), 55.7% (CsA); 2-year DFS 65.1% (Short-term Tacro), 61.4% (CsA) | (37) |
| Y Wang et al. | 2014 | China | 224 | AML (106); ALL (91); CML (14); MDS (13) | BM+PBSC | in vivo TCD-haploSCT | r-ATG 1.5 mg/kg×4d, n=112; r-ATG 2.5 mg/kg×4d, n=112 | Modified BUCY, n=218; TBI based regimen, n=6 | CsA+MMF+short-term MTX | Real-time Taqman CMV DNA PCR | >600 copies/mL | 1-year 75.0% (ATG-6) and 78.6% (ATG-10) | 0.89% (ATG-6) and 5.36% (ATG-10) | 1-year relapse 7.6% (ATG-6), 4.6% (ATG-10); NRM 8.1% (ATG-6), 10.3% (ATG-10); OS 88.4% (ATG-6), 87.0% (ATG-10); DFS 84.3% (ATG-6); 86.0% (ATG-10) | (31) |
| S Kako et al. | 2017 | Japan | 12 | AML (5); ALL (1); CMML (1); Ph+ ALL (2); NHL (1); LCS (1); PMF (1) | PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×2d (-4 to -3) | BU+Mel, n=2; CY+TBI, n=6; Flu+Mel+TBI, n=3; Flu+BU+TBI, n=1 | CsA+short-term MTX | NR | NR | 41.67% | 0 | 1-year OS 33.3%, PFS 24.3%, RR 59.0%, and NRM 16.7% | (34) |
| GJ Min et al. | 2020 | Korea | 186 | AML | BM or PBSC | in vivo TCD-haploSCT | r-ATG 1.25 mg/kg×4d | Flu+BU+TBI | CsA+short-term MTX | Real-time quantitative-PCR | NR | 72.70% | 19.40% | OS 52.3% (mismatched) and 55.3% (matched); GRFS 40.6% (mismatched) and 42.2% (matched); Relapse 22.5% (mismatched) and 8.6% (matched); NRM 28.9% (mismatched) and 27.1% (matched) | (35) |
| L Zhu et al. | 2015 | China | 25 | AML (7); ALL (17); Bi-lineage AL (1) | BM+PBSC+MSC (21) or BM+MSC (4) | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d (-4 to -1) | BU+Ara-C+CY | CsA+MMF+short-term MTX | NR | NR | 92% | NR | 14-month OS 53.28% | (28) |
| J Xu et al. | 2020 | China | 72 | T-ALL | BM or PBSC or BM+PBSC combined with CB | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d (-4 to -1) | Modified BUCY | CsA+MMF+short-term MTX | PCR | NR | 19.40% | NR | 3-year OS (66.6 ± 6.2)%; RFS (62.0 ± 6.5)%; relapse (24.2 ± 6.4)%; NRM (16.9 ± 5.1)% | (25) |
| J Wang et al. | 2019 | China | 139 | AML (100); ALL (39) | BM+PBSC or BM+PBSC+UCB | in vivo TCD-haploSCT | ATG-F 5 mg/kg×4d | BUCY+Me-CCNU+FLAG/CLAG, n=96; TBI+CY+Me-CCNU+FLAG/CLAG, n=43 | CsA+MMF+short-term MTX | Real-time PCR | NR | 100-day 59.8% (Cord-HaploSCT) and 47.6% (HaploSCT) | 2.88% | 2-year relapse 25.9% (Cord-HaploSCT) and 53.2% (HaploSCT); NRM 38.8% (Cord-HaploSCT) and 24.6% (HaploSCT); OS 35.5% (Cord-HaploSCT) and 22.7% (HaploSCT); PFS 35.5% (Cord-HaploSCT) and 17.9% (HaploSCT) | (26) |
| XN Gao et al. | 2020 | China | 110 | AML (58); MDS (6); CML (4); MDS/MPN (1); ALL (38), NHL (3), PCL (1) | PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | Modified BUCY, n=95; TBI+CY, n=3; Flu+BU, n=4; BU+FLAG, n=8 | CsA+MMF+short-term MTX | Real-time quantitative PCR | CMV DNA loads exceeded 1000 copies/mL | 1-year 55.0% | 1-year 7.9% | 3-year NRM 30.5% (CMV DNAemia+) and 13.7% (CMV DNAemia-); 3-year OS 55.0% (CMV DNAemia+) and 60.4% (CMV DNAemia-) | (29) |
| HH Li et al. | 2017 | China | 94 | AML (46); Therapy-related AML (6); MDS transformed AML (5); MDS-refractory anemia with excess blast (1); ALL (26); CML (5); Lymphoma (5) | PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg×4d | Modified BUCY, n=60; TBI+CY, n=28; BF, n=6 | CsA+MMF+short-term MTX | NR | NR | 1-year 62.1% | 1-year 8.1% | 3-year NRM 24.0% (HaploSCT) and 10.2% (MSD); relapse 39.0% (HaploSCT) and 22.6% (MSD); DFS 45.7% (HaploSCT) and 78.9% (MSD) | (30) |
| E Shmueli et al. | 2014 | Israel | 102 | Congenital disease; SAA; hematological malignancy; solid tumor | NR | in vivo TCD-haploSCT | ATG* | Flu+TT+TBI | NR | Real-time PCR | Higher than 50 copies/mL | 66.70% | 11.6% | The high rate of drug resistance as interlinked with severe disease in haplo-HSCT recipients. | (8) |
| SS Park et al. | 2021 | Korea | 46 | SAA | PBSC | in vivo TCD-haploSCT | r-ATG 5-10 mg/kg | TBI+Flu | Tacro+short-term course MTX | NR | NR | 45.70% | NR | 3-year OS 84.4%; 3-year TRM 11.2% | (36) |
| A Bertaina et al. | 2014 | Italy | 23 | SCID (8); SAA (4); FA (4); IPEX (1); CAMT (1); SDS (1); UNC13D-mutated HLH (1); DOCK-8-mutated HIEs (1); Osteopetrosis (1); Thalassemia (1) | PBSC | ex vivo TCD-haploSCT (αβ+ T and CD19+ B cells depletion) | r-ATG 4 mg/Kg×3d (-5 to -3) | BU+TT+Flu, n=3; Treo+TT+Flu, n=4; Treo+Flu, n=8; Flu+CY ± TBI, n=8 | No posttransplantation pharmacologic GVHD prophylaxis | NR | NR | 38% (CMV and adenovirus) | 4.35% | The 2-year probability of both OS and DFS was 91.1% | (42) |
| AE Hammerstrom et al. | 2018 | USA | 86 | Leukemia (75); Lymphoma (8); MM (1); AA (2) | BM (83); PBSC (3) | PTCy-haploSCT | No | Mel+TT+Flu | MMF+Tacro | pp65 CMV antigenemia assay or PCR. | CMV antigenemia with ≥1 cell/million or detectable CMV DNA | Traditional 81%; Hybrid 53%; Intermediatedose 71% | 8% (Traditional), 0% (Hybrid), and 0% (Intermediate dose) | 100-day NRM 0 (Traditional), 13% (Hybrid), and 13% (Intermediate dose); 100-day OS 100% (Traditional), 80% (Hybrid), and 87% (Intermediate dose) | (60) |
| R Mitchell et al. | 2019 | Australia | 19 | Primary immunodeficiency disease; HLH; FA; AML; ALL | PBSC; BM | ex vivo TCD-haploSCT (αβ+ T and CD19+ B cells depletion) | ATG* | Treo+Flu+TT; Bu+Flu+TT; Treo+Flu; Bu+CY+Flu; Flu+CY; Flu+Mel+TT; TBI+Flu+Mel+TT | MMF (n=11) or CsA (=3) or combination CsA/MMF (n=5), or no prophylaxis (n=1) | CMV PCR screening | NR | 50.00% | 5.26% | 100-day TRM 0% and 1-year TRM 15%; 5-years OS 80% | (43) |
| SH Kang et al. | 2021 | Korea | 81 | Malignant disease (45); Nonmalignant disease (36) | PBSC | ex vivo TCD-haploSCT (αβ T lymphocyte depletion) | Malignant disease r-ATG (2 mg/kg at -8d and 1 mg/kg at -7d); Nonmalignant disease r-ATG (2.5 mg/kg/day, -8d to -6d) | Flu+CY+TBI | NR | Quantitative real-time PCR | >2.49 log copies/mL | 50.8% (GCV/FCV 44.4% vs GCV 62.6%) | 15.4%; no significant difference in the incidence of CMV disease according to prophylaxis method | Interim-FCV prophylaxis effectively prevented CMV reactivation in those undergoing αβ T cell-depleted haploSCT. | (41) |
| I Airoldi et al. | 2015 | USA | 27 | ALL (9); AML (6); SCID (4); FA (3); Hyper-IgE syndrome (1); Refractory cytopenia of childhood (2); Kostmann syndrome (1); Osteopetrosis (1); SDS (1) | PBSC | ex vivo TCD-haploSCT (TCR-αβ+/CD19+ lymphocytes depletion) | No | TBI+TT+Mel; TBI+TT+CY; TBI+TT+Flu; Treo+TT+Mel; BU+TT+Flu; BU+CY+Mel; Treo+TT+Flu; Treo+Flu; TBI+CY+Flu; BU+Flu | No posttransplantation pharmacologic GVHD prophylaxis | NR | NR | 55.50% | NR | 81.5% survived at last follow-up | (44) |
| L Kaynar et al. | 2017 | Turkey | 34 | AML (24); ALL (10) | PBSC | ex vivo TCD-haploSCT (TcRαβ-depletion) | ATG-F 30 mg/kg (-12 to -9) | Flu+TT+Mel | MMF | PCR | NR | 73.5% (AML 66.7%; ALL 90.0%) | 0 | 1-year DFS 42%; OS 54% | (39) |
| HF Nazir et al. | 2020 | Oman | 12 | FHLH | PBSC | ex vivo TCD-haploSCT (CD3/CD19 depletion) | ATG-F 10 mg/kg (-6 to -3) | Treo+TT+Flu+Rituximab | CsA or Tacro or No pharmcologic prophylaxis | PCR | CMV viral load exceeded 500 copies/mL | 75.00% | 16.67% | 3-year DFS 58.3% | (45) |
| F Erbey et al. | 2018 | Turkey | 21 | ALL (14); AML (7) | PBSC | ex vivo TCD-haploSCT (TcRαβ-depletion) | r-ATG 20mg/kg (-13 to -9) | Flu+TT+Mel | MMF with or without CsA | PCR screening | NR | 81.00% | NR | 5-year OS 71.1%; RFS 86.9%; TRM 16.3% | (40) |
| S Gaballa et al. | 2016 | USA | 50 | AML (27); MDS or MPD (3); ALL (14); NHL (5); AA (1) | DLI + CD34-selected stem cell | PTCy-haploSCT | No | TBI (12 Gy over 4 day) | Tacro+MMF | PCR | NR | 100-day 67% | 0 | 3-year OS 70%; PFS 68%; NRM 10% | (38) |
| R Crocchiolo et al. | 2015 | Italy | 70 | HL (35); NHL (20); MM (2); AL (11); CLL (2) | BM (66); PBSC (4) | PTCy-haploSCT | No | NMA, n=48; RIC, n=16; MAC, n=6 | Tacro/CsA+MMF | PCR | Threshold of CMV viremia for PET was 3300 copies/mL | 54.00% | 4.29% | 2-year OS 48%, TRM 26% | (53) |
| J Gaziev et al. | 2018 | USA | 54 | Thalassemia (45); Sickle cell anemia (7); HbS-b thalassemia (2) | PBSC and/or BM | ex vivo TCD-haploSCT (CD34 selection of PBSCs and BM, n=32; CD34 selection of PBSCs and CD3/CD19 depletion of BM, n = 8; TCRαβ/CD19 depletion of PBSCs, n = 14) | r-ATG 12.5 mg/kg over 4 days, n=6; ATG-F 50 to 25 mg/kg over 5 days, n=48 | BUTT10CY200 preceded by HuAzFlu or BUTT10CY200 preceded by Flu with/without Rituximab prophylaxis | CsA +methylprednisolone or CsA+MMF | reverse-transcription PCR | NR | 64.00% | 0 | OS 78% (TCR group) and 84% (CD34 group); DFS 69% (TCR group) and 39% (CD34 group) | (47) |
| L Prezioso et al. | 2019 | Italy | 59 | AML (32); ALL (6); NHL (6); HL (8); MF (4); MDS (2); MM (1); PCL (1) | PBSC (24); CD34+ (35) | ex vivo TCD-haploSCT (αβTCR/CD19+ depletion or selection of the CD34+ cells) | r-ATG 1.5 mg/kg ×4d (-9 to -6) | Flu+TT | No posttransplantation pharmacologic GVHD prophylaxis | PCR | NR | 7.27% | 1.69% | 2-year OS 50.8% | (46) |
| D Huntley et al. | 2020 | Spain | 118 | AL (43); CL (9); Lymphoma (26) MDS/MM/Myelofibrosis (25); Other (15) |
PBSC (110); BM (8) | PTCy-haploSCT | Only one patient received ATG | MAC,n=35; RIC,n=83 | CsA or Tacro | RealTime CMV PCR | 31 IU/ml or 137 IU/ml at different centers | 63.90% | 4.50% | 1-year OS 70.3% | (55) |
| LJ Arcuri et al. | 2020 | USA | 87 | SAA | BM (81); PBSC (3); BM+PBSC (3) | PTCy-haploSCT | 12 patients received r-ATG | Flu+CY+TBI | CsA+MMF or Tacro+MMF | Positive antigenemia or PCR | NR | 100-day 61%, 1-year 62%, 2-year 62% | NR | 2-year OS 79%; 2-year EFS 70% | (62) |
| M Slade et al. | 2017 | USA | 104 | AML (70); ALL (11); MDS (11); Other (12) | PBSC | PTCy-haploSCT | NR | MAC, n=43; NMA, n=61 | CsA+MMF or Tacro+MMF | PCR | >40 000 IU/mL | 55.00% | 15% | 51% survived at last follow-up | (69) |
| E Katsanis et al. | 2020 | USA | 17 | AL,CML, NHL | BM | PTCy/BEN-haploSCT (9); PTCy-haploSCT (8) | No | TBI+Flu or BU+Flu+Mel | MMF+Tacro | PCR | NR | 12.5% in PTCy-BEN with 71.4% in PTCy | NR | 2-year OS 83.3% in PTCy-BEN with 58.3% in PTCy | (64) |
| GC Irene et al. | 2021 | Spain | 40 | AL/MDS (28); MPN (1); Lymphoid malignancies (9); Others (2) | PBSC or BM | PTCy-haploSCT | No | RIC,n=1;MAC,n=39; | Tacro | Quantitative PCR | PET: a level of DNAemia of >1000 IU/ml in one blood sample or two consecutive samples with a level of >500 IU/mL | 18-month 61% | 2.50% | 18-month OS 71.3%; PFS 67.4% with no differences by donor type | (59) |
| RV Raj et al. | 2016 | USA | 43 | AML/MDS (27); ALL (5); Myeloma (4); NHL/HL (4); Others (3) | BM (22); PBSC (21) | PTCy-haploSCT | No | Flu+CY+TBI, n=23; Flu+Bu+CY, n=15; Flu+Mel+TBI, n=5 | Tacro+MMF | Quantitative nucleic acid amplified tests (NAAT) | NR | RIC with 40% in MAC | 0 (RIC) and 7% (MAC) | NR | (63) |
| SR Goldsmith et al. | 2016 | USA | 138 | AML (93); MDS (15); Other (30) | PBSC | PTCy-haploSCT | No | MAC, n=58; RIC, n=80 | Tacro+MMF or other | Real-time qPCR | NR | 58.00% | 16.67% | Post-transplant CMV viremia was not associated with a statistical difference in overall survival | (65) |
| J Montoro et al. | 2020 | Spain | 42 | AL (15); MM (5); Lymphoproliferative disorders (13); MDS (5); MPD (4) | BM (5); PBSC (37) | PTCy-haploSCT | No | TBF-MAC, n=9; TBF-RIC, n=2; BU+Flu+CY, n=11 | MMF+Sirolimus | Quantitative real-time PCR assays | NR | 52.00% | 2.38% | 1-year NRM 14%; EFS 75%; OS 82%; GRFS 47%. A higher cumulative incidence of CMV DNAemia requiring pre-emptive antiviral therapy in the haploidentical cohort. | (70) |
| N Cieri et al. | 2015 | Italy | 40 | AML (22); ALL (5); MDS (1); CML (1); HL (6); NHL (5) | PBSC | PTCy-haploSCT | No | Flu+Treo+Mel | MMF+Sirolimus | Quantitative PCR | PET was started when CMV DNA copy number was more than 1000 copies/mL or increased more than.5 log in peripheral blood plasma. | 63.00% | 15% | 1-year OS 56%; DFS 48% | (71) |
| N Stocker et al. | 2020 | France | 19 | AML (10); MPN (1); MDS (1); ALL (4); NHL (3) | PBSC | PTCy-haploSCT | 2.5 mg/kg, n=3; 5 mg/kg, n=16 | RTC, n=13; TT+etoposide+CY+RIC, n=6 | CsA+MMF | Quantitative PCR | PET was initiated when CMV was above 1000 IU/mL | 46.00% | NR | 2-year Relapse 19% (Control group) and 19% (PTCy group); PFS 73% (Control group) and 70% (PTCy group); OS 78% (Control group) and 79% (PTCy group) | (67) |
| Crocchiolo R et al. | 2016 | Italy and France | 207 | AL (44); HL (54); NHL (61); MM (13); MDS/MPS (25); Drepanocytosis (1) | PBSC (111); BM (96) | PTCy-haploSCT | NR | NMA/RIC, n=181; MAC, n=26 | NR | NR | NR | 42.00% | 1.45% | Two-year OS 62% (Cohort 1); 65% (Cohort 2); 50% (Cohort 3); 42% (Cohort 4) | (56) |
| SR Goldsmith et al. | 2021 | USA | 757 | AML/ALL/MDS | BM or PBSC | PTCy-haploSCT | No | MAC or RIC/NMA | Tacro or CsA | PCR | NR | 180-day 42% | 100-day 2.8% | 2-year mortaligy 49.5% | (51) |
| Y Lu et al. | 2018 | China | 41 | SAA (28)/VSAA (13) | BM+PBSC | in vivo TCD-haploSCT | ATG-r 7.5 mg/kg, n=42; ATG-F 20 mg/kg, n=47 | BU+Flu+CY | Tacro+MMF+short-term MTX | PCR | Higher than 500 copies/mL in plasma | 65.90% | 4.88% | 3-year OS 80.3% ± 5.1%; 3-year FFS 76.4% ± 5.1% | (13) |
| W-R Huang et al. | 2016 | China | 130 | AML; ALL; CML; Lymphoma | PBSC | in vivo TCD-haploSCT | r-ATG 2.5 mg/kg/day -5d to -2d | Modified BUCY, n=90; Modified BF, n=32; TBI+CY, n=8 | CsA+MMF+short-term MTX | PCR | NR | 1-year 61.0 ± 5.3% | 1-year 8.0% ± 2.9% | 3-year OS 45.6% ± 5.6%; LFS 44.2% ± 5.9% | (23) |
| BM Triplett et al. | 2015 | USA | 17 | ALL (6); AML (9); MLL (1); MDS (1) | PBSC | ex vivo T-cell depletion (CD45RA-depletion) | No | TLI+Flu+CY+TT+Mel | Sirolimus or MMF | PCR | NR | 17.65% | 0 | 76.5% survived at a median of 223 days | (49) |
| BM Triplett et al. | 2018 | USA | 67 | ALL (28); AML (22); MLL (4); MDS (8); Lymphoma (3); CML (2) | PBSC | ex vivo T-cell depletion (CD3-depletion,n=41; CD45RA-depletion,n=26) | No | CD3-depleted: Flu+TT+Mel+OKT3 (n = 21) or alemtuzumab (n=20)+Rituximab CD45RA-depleted: Flu+TT+Mel+lymphoid irradiation+CY |
a short (<60 days) course of MMF | Quantitative PCR | NR | CD3-depleted 56%, CD45RA-depleted 19% | NR | 180-day mortality CD3dep recipients 22% vs CD45RAdep recipients 15.4% | (50) |
| A Fayard et al. | 2019 | France | 381 | AL/MDS (208); HL/NHL (115); MPN (31); MM/solitary plasmacytoma (15); chronic leukemia (10); bone marrow failure syndrome (2) | BM (103); PBSC (278) | PTCy-haploSCT | No | RIC, n=307; MAC, n=73 | an anticalcineurin +MMF | A single pp65 antigen-positive leukocyte or a positive viremia in peripheral blood | NR | 48.80% | 4.50% | Median of PFS 19.9 months; Median of OS 33.5 months | (52) |
| A Esquirol et al. | 2021 | Spain | 236 | AML (76); MDS (39); ALL (22); NHL (39); HL (31); CLL (8); CML/MPN (12); MM (5); biphenotypic acute leukemia (2); aplasia (1); prolymphocytic leukemia (1) | BM (45); PBSC (191) | PTCy-haploSCT | NR | Flu+BU; Flu+Bu+CY; TBF; Other | CsA+MMF or Tacro alone | PCR | >1000 IU/mL | 69.00% | 2.12% | 12-month OS 64%; 12-month PFS 57% | (54) |
| Monzr M. Al Malki et al. | 2017 | USA | 119 | Acute leukemia (80); bone marrow failure (15); lymphoma (11); chronic leukemia (6); hemoglobinopathies (5); MM (2) | PBSC (81); BM (38) | PTCy-haploSCT | NR | MAC, n=46; RIC/NMA, n=73 | Tacro/MMF | PCR | NR | 100-day 69.2% | 0 | CMV reactivation was not associated with OS, RFS, relapse incidence, or NRM. | (57) |
| D Huntley et al. | 2020 | Spain | 71 | Acute leukemia (24); Chronic leukemia (6); Lymphoma (15); Myelofibrosis/MDS (18); Other (5) | PBSC (65); BM (6) | PTCy-haploSCT | No | MAC, n=17; RIC, n=54 | Tacro-based, n=41; MMF-based, n=15 | Real-time PCR | Higher than 600 IU/ml or higher than IU/ml at different centers | 59.70% | 4.23% | PTCy-haploSCT recipients may reconstitute CMV-specific T-cell immunity to the same extent as patients undergoing HLA-matched allo-HSCT | (58) |
| R Uppuluri et al. | 2019 | India | 16 | Primary immune deficiency disorder | BM (6); PBSC (10) | PTCy-haploSCT | NR | Flu+Mel, n=5; Flu+Treo, n=3; Treo+Flu+TBI, n=3; Treo+Flu, n=1; Flu+Treo+TBI, n=4 | NR | NR | NR | 43.70% | 6.25% | Overall mortality 37.5%; OS 62.5%; Cytokine release syndrome (CRS) 75% | (61) |
| SR Solomon et al. | 2015 | USA | 30 | AML (16); ALL (6); CML (5); MDS (1); NHL (2) | PBSC | PTCy-haploSCT | No | Flu+TBI | Tacro+MMF | Quantitative CMV PCR | PET was initiated if viral reactivation was detected (higher than 400 copies/mL) | 58.00% | 0 | 2-year OS 78%; 2-year DFS 73% | (66) |
| C Oltolini et al. | 2020 | Italy | 145 | Myeloid disorders (106); Lymphoid disorders (39) | PBSC | PTCy-haploSCT | No | MAC, n=110; RIC, n=35 | sirolimus+MMF, n=141; CsA+MMF, n=3 | PCR | PET was started when plasmatic CMVDNA higher than 1000 copies/mL or increased >0.5 log. | 61% (68%, haploSCT) | 13.79% | Relapse 44% | (68) |
| AD Law et al. | 2018 | Canada | 50 | AML (28); MDS (8); MPN (6); ALL (2); Lymphoma (5); BPDCN (1) | PBSC | PTCy-haploSCT | r-ATG 4.5 mg/kg | Flu+BU+TBI | CsA | NR | NR | 74% | 8% | 1-year OS 48.1%; NRM 38.2% | (72) |
| MQ Salas et al. | 2020 | Canada | 52 | AML (29); MDS (8); MPN (5); ALL (3); Lymphoproliferative disease (6); BPDCN (1) | PBSC | PTCy-haploSCT | r-ATG 4.5 mg/kg | Flu+BU+TBI | CsA | Quantitative PCR | >200 copies/ml | 58% | 4% | 1-year OS 58.8 (44–70.9)%; 1-year RFS 53.3 (38.8–65.8)% | (73) |
| J Tischer et al. | 2015 | Germany | 55 | AML (33); CML (2); ALL (7); SAA (1); NHL (14); CLL (2) | BM+PBSC | ex vivo T-cell depletion (cTCR/TCD: CD6-depleted G-CSF-mobilized peripheral blood stem cells); PTCy-haploSCT | cTCR/TCD: r-ATG 20 mg/kg for 5 days; TCR/PTCY: No ATG | RIC or MAC | CsA+MTX or Tacro+MMF or MMF | Quantitative real-time PCR | NR | cTCR/TCD 42.9%; TCR/PTCy 14.8% | 7.14% (cTCR/TCD) and 0 (TCR/PTCy) | cTCR/TCD: 1-year OS 39%, RFS 38%; TCR/PTCY: 1-year OS 59%; RFS 55% | (78) |
HaploSCT, haploidentical stem cell transplantation; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; CML, chronic myeloid leukemia; AL, acute leukemia; MDS, myelodysplastic syndromes; AA, aplastic anemia; SAA, severe aplastic anemia; VSAA, very severe aplastic anemia; Ph+, Philadelphia chromosome-positive; PNH, paroxysmal nocturnal hemoglobinuria; CMML, chronic myelomonocytic leukemia; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; PCR, polymerase chain reaction; PET, preemptive therapy; LCS, Langerhans cell sarcoma; PMF, primary myelofibrosis; BPDCN, blastic plasmacytoid dendritic cell neoplasm; PCL, plasma cell leukemia; SCID, severe combined immunodeficiency; FA, Fanconi anemia; IPEX, immunodeficiency with polyendocrinopathy and enteropathy X-linked; CAMT, congenital amegakaryocytic thrombocytopenia; SDS, Shwachmann-Diamond syndrome; HLH, hemophagocytic lymphohistiocytosis; UNC13D-mutated HLH, UNC13D-mutated hemophagocytic lymphohistiocytosis; DOCK-8-mutated HIEs, DOCK-8–mutated hyper-IgE syndrome; FHLH, familial hemophagocytic lymphohistiocytosis; MPD, myeloproliferative disease; HL, Hodgkin lymphoma; CLL, chronic lymphocytic leukemia; CL, chronic leukemia; MPN, myeloproliferative neoplasm; MPS, myeloproliferative syndrome; MLL, mixed lineage leukemia; BM, bone marrow; PBSC, peripheral blood stem cells; HSCT, hematopoietic stem cell transplant; MSC, mesenchymal stem cell; CB, cord blood; UCB, umbilical cord blood; DLI, donor lymphocyte infusion; TCD, T-cell depletion; PTCy, posttransplant cyclophosphamide; ATG, anti-thymocyte globulin; ATG-F, ATG-Fresenius; r-ATG, ATG-Genzyme; BU, busulfan; CY, cyclophosphamide; BUCY, busulfan cyclophosphamide regimen; CCNU, lomustine; Me-CCNU, simustine; Ara-c, cytosine arabinoside; BF, busulfan fludarabine regimen; FLAG, fludarabine+ cytarabine + granulocyte colony-stimulating factor; CLAG, cladribine + cytarabine + granulocyte colony-stimulating factor; Flu, fludarabine; TT, thiotepa; Treo, treosulfan; Mel, melphalan; Az, azathioprine; Hu, hydroxyurea; TBI, total body irradiation; TBF, thiotepa busulfan fludarabine; MAC, myeloablative conditioning, NMA, non-myeloablative; RIC, reduced-intensity conditioning; RTC, reduced toxicity conditioning; TLI, total lymphoid irradiation; CMV, cytomegalovirus; CsA, cyclosporine A; Tacro, tacrolimus; MMF, mycophenolate mofetil; MTX, methotrexate; GCV, ganciclovir; FCV, foscarnet; TCR, T-cell-replete; HLA, human leukocyte antigen; CMVR, cytomegalovirus retinitis; RRM, relapse-related mortality; OS, overall survival; LFS, leukemia-free survival; NRM, non-relapse mortality; TRM, transplant-related mortality; GVHD, graft-versus-host disease; aGVHD, acute graft-versus-host disease; FFS, failure-free survival; GFFS, GVHD-free and relapse-free survival; GRFS, GVHD-free relapse-free survival; PFS, progression-free survival; EFS, event-free survival; DFS, disease-free survival; RFS, relapse-free survival; RR, relapse rate; MSD, matched sibling donor; NR, not reported.
*The dose of ATG is not mentioned in the paper.