Table 1.
Study | Patients | Donor | Intervention | Numbers (n) | Acute GVHD | Chronic GVHD | EFS/OS | CRFS | Relapse | NRM | CMV | EBV | BK | Adeno |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ATG | ||||||||||||||
Chang et at14 | Adult hematological malignancies | MRD; PBSC/BM | ATG-T 1.5 mg/kg on day –3 to –1 | 263 | II–IV: 13.7% | 2 y 27.9% (ext 8.5%) | 3 y OS 69% | 3 y 38.7% | 3 y 20.8% | 3 y 9.9% | Day 100: 22.7% | Day 180: 7.8% | NA | NA |
III–IV: 8.4% | LFS 65.7% | |||||||||||||
Walker et al15 | Adult hematological malignancies | MUD/MMUD; PBSC/BM | ATG-T 5 mg/kg on day –2, and 2 mg/kg on days –1 and +1 | 101 | NA | 2 y 26.3% | 2 y OS 70.6% | 1 y 57.6% | 2 y 16.7% | 2 y 21.2% | NA | 20% DNAemia requiring therapy | NA | NA |
Socié et al16 | Adult hematological malignancies | MUD; BM/PBSC | ATG-F 20 mg/kg day –3 to –1 | 103 | NA | 3 y 12.2% | 3 y OS 55% | NA | 3 y 33% | 3 y 19% | NA | NA | NA | NA |
Baron et al17 | Adult AML | MRD/MUD; PBSC | ATG-F 30 mg/kg or ATG-T 5 mg/kg; days not known | 569 ATG-fresenius; 249 ATG-thymoglobulin | II–IV: 18%–24% | 2 y 30% | 2 y | 2 y 50%–52% | 2 y 24%–28% | 2 y | NA | NA | NA | NA |
III–IV: 6%–7%; | OS 67%–68% | 11.5%–16% | ||||||||||||
LFS 60%–61% | ||||||||||||||
Finke et al18 | Adult hematological malignancies | MRD/MUD; PBSC/BM | ATG-F 20 mg/kg on day –3 to –1 | 103 | I–IV: 56.3% | 2 y 30.8% (ext 12.2%) | 2 y | NA | 2 y 28.9% | 2 y 19.6% | 53.8% DNAemia; 5.7% CMV disease | 5% PTLD | NA | NA |
II–IV: 33% | OS 59.2% | |||||||||||||
III–IV: 11.7% | EFS 51.6% | |||||||||||||
Soiffer et al19 | Adult AML, MDS, ALL | MUD; PBSC/BM | ATG-F 20 mg/kg –3 to –1 | 126 | II–IV: 23% | 2 y 16% | 2 y | 2 y 38% | 2 y 32% | 2 y 21% | 62% (R+) DNAemia | 1.6% PTLD | NA | NA |
III–IV: 4.3% | Moderate-severe 12% | OS 59% | ||||||||||||
PFS 47% | ||||||||||||||
Alemtuzumab | ||||||||||||||
Green et al20 | Adult hematological malignancies | Matched/mismatched; PBSC/BM | Alemtuzumab dose 50–100 m | 313 | II–IV: 32%–40% | 2 y 32%–41% | NA | NA | 2 y 24%–36% | 2 y 16%–24% | >80% (R+) DNAemia | NA | NA | NA |
III–IV: 2%–15% | ||||||||||||||
van Besien et al21 | Adult AML/MDS | MRD/MUD/MMUD PBSC/BM | Alemtuzumab | 95 | II–IV: 23.3% | 2 y 16% | 2 y | NA | 1 y 23.7% | 1 y 24.6% | NA | NA | NA | NA |
OS 40.5% | ||||||||||||||
III–IV: 8.6% | PFS 33% | |||||||||||||
Carpenter et al22 | Adult hematological malignancies | MRD/MMRD/MUD/MMUD; PBSC/BM | Alemtuzumab (75 in vivo, 36 ex vivo) | 111 | NA | NA | NA | NA | NA | NA | NA | 2 y | NA | NA |
40.3% DNAemia; 1% PTLD | ||||||||||||||
PTCy | ||||||||||||||
Kanakry et al23 | Adult leukemia/MDS | MRD/MUD; BM | PTCy | 209 | II–IV: 45% | 3 y 13% | 3 y OS 58% | 3 y 39% | 3 y 36% | 3 y 17% | NA | NA | NA | NA |
III–IV: 11% | EFS 46% | |||||||||||||
Cieri et al24 | Adult high-risk hematological malignancy | Haplo; PBSC | PTCy | 40 | II–IV: 15% | 1 y 20%; severe 5.1% | 1 y OS 56% | NA | 1 y 35% | 1 y 17% | 63% DNAemia | 15% DNAemia (66% of these pts treated). No PTLD | 18% | NA |
III–IV: 7.5% | EFS 48% | 17% CMV disease | ||||||||||||
Berger et al25 | Pediatric; high-risk hematological malignancy | Haplo; BM/PBSC | PTCy | 33 | II–IV: 22% | 1 y 4% | 1 y OS 72% | NA | 1 y 24% | 1 y 9% | 36% DNAemia | 3% DNAemia | 17% | 3% DNAemia; not symptomatic |
III–IV: 3% | EFS 61% | No CMV disease | No PTLD | |||||||||||
Devillier et al26 | AML/high-risk MDS | Haplo; BM/PBSC | PTCy | 60 | II–IV: 18% | 2 y 14%; severe 4% | 1 y | 1 y 37% | 1 y 34% | 1 y 27% | NA | NA | NA | NA |
OS 50% | ||||||||||||||
III–IV: 2% | EFS 39% | |||||||||||||
Mehta et al27 | Adult hematological malignancies | MMUD; BM/PBSC | PTCy | 41 | II–IV: 37% | 2 y 30% | 2 y OS 52% | NA | 2 y 20% | 2 y 35% | NA | NA | NA | NA |
III–IV: 17% | EFS 42% | |||||||||||||
Mielcarek et al28 | Adult hematological malignancies | MRD/MUD/MMUD; PBSC | PTCy | 43 | II–IV: 77% | 1 y 16% requiring IS; ext 30% | 2 y OS 70% | 2 y 50% | 2 y 17% | 2 y 14% | NA | NA | NA | NA |
III–IV: 0% | 2 y EFS 69% | |||||||||||||
PTCy vs ATG | ||||||||||||||
Battipaglia et al29 | Adult AML | MMUD; BM/PBSC | PTCy vs ATG-F/ATG-T | 93 PTCY, 179 ATG | PTCY | PTCY | PTCY | PTCY: | PTCY: | PTCY: | NA | NA | NA | NA |
II–IV: 30% | Any: 39% | 2 y OS: 56% | 2 y 37% | 2 y 29% | 2 y 16% | |||||||||
III–IV: 9% | Ext: 17% | 2 y EFS: 55% | ATG: | ATG: | ATG: | |||||||||
ATG: | ATG | ATG | 2 y 28% | 2 y 37% | 2 y 29% | |||||||||
II–IV: 32% | Any: 36% | 2 y OS: 38% | ||||||||||||
III–IV: 19% | Ext: 20% | 2 y EFS: 34% | ||||||||||||
Battipaglia et al30 | Adult AML | MRD; BM/PBSC | PTCy vs ATG-F (26%)/ATG-T (74%) | 197 PTCY, 1913 ATG | PTCY | PTCY | PTCY | PTCY: | PTCY: | PTCY: | NA | NA | NA | NA |
II–IV: 19% | Any: 37% | 2 y OS: 64% | 2 y 44% | 2 y 36% | 2 y 8% | |||||||||
III–IV: 6% | Ext: 16% | 2 y PFS: 55% | ATG: | ATG: | ATG: | |||||||||
ATG: | ATG | ATG | 2 y 49% | 2 y 32% | 2 y 10% | |||||||||
II–IV: 17% | Any: 30% | 2 y OS: 65% | ||||||||||||
III–IV: 6% | Ext: 12% | 2 y PFS: 58% | ||||||||||||
Brissot et al31 | Adult AML | MUD; BM/PBSC | PTCy vs ATG-T 5 mg/kg | 174 PTCY, 1452 ATG | PTCY | PTCY | PTCY | PTCY: | PTCY: | PTCY: | NA | NA | NA | NA |
II–IV: 28.8% | Any: 31.4% | 2 y OS: 62.7% | 2 y 41.6% | 2 y 25.2% | 2 y 15.2% | |||||||||
III–IV: 8.8%; | Ext: 18.5% | 2 y PFS: 59.7% | ATG: | ATG: | ATG: | |||||||||
ATG: | ATG | ATG | 2 y 49.3% | 2 y 23.7% | 2 y 16.7% | |||||||||
II–IV: 29.2% | Any: 33.6% | 2 y OS: 64.8% | ||||||||||||
III–IV: 9% | Ext: 13.1% | 2 y PFS: 59.6% | ||||||||||||
Ruggeri et al32 | Adult AML | MUD; BM/PBSC | PTCy vs ATG-F/ATG-T | 193 PTCY, 115 ATG | PTCY | PTCY | PTCY | PTCY: | PTCY: | PTCY: | NA | NA | NA | NA |
III–IV: 4.7% | Any: 33.7% | 2 y OS: 58% | 2 y 50.9% | 2 y 21.6% | 2 y 22.4% | |||||||||
ATG: | Ext: 8.6% | 2 y PFS: 56% | ATG: | ATG: | ATG: | |||||||||
III–IV: 12.5% | ATG | ATG | 2 y 38.9% | 2 y 22.3% | 2 y 30.5% | |||||||||
Any: 28.3% | 2 y OS: 54.2% | |||||||||||||
Ext: 12.6% | 2 y PFS: 47.2% | |||||||||||||
Retière et al33 | Adult hematological malignancies | MRD/MUD/MMUD/haplo; BM/PBSC | PTCy vs ATG-T 2.5 mg/kg on day –1 or days –2 and –1 | 30 PTCY, 15 ATG | PTCY | NA | PTCY | NA | PTCY: | NA | DNAemia | DNAemia requiring treatment | PTCY 3% | PTCY 15% |
II–IV: 47% | 2 y OS: 79% | 2 y 17% | PTCY 27% | PTCY 0% | ATG 0% | ATG 20% | ||||||||
III–IV: 10% | 2 y PFS: 63% | ATG: | ATG 40% | ATG 33% | ||||||||||
ATG: | ATG | 2 y 33% | ||||||||||||
II–IV: 47% | 2 y OS: 73% | |||||||||||||
III–IV: 20% | 2 y PFS: 60% | |||||||||||||
Ex vivo graft engineering | ||||||||||||||
Pasquini et al34 | Adult AML | MRD; PBSC | CD34+ T cell depletion | 44 | II–IV: 23% | 2 y 19% | 2 y OS 59% | 2 y 42% | 2 y 24% | 2 y 21% | NA | NA | NA | NA |
III–IV: 4.5% | EFS 55% | |||||||||||||
Barba et al35 | Adult leukemia | MRD/MUD/MMUD; PBSC | CD34+ T cell depletion | 241 | II–IV: 16% | 3 y 5% | 3 y OS 57% | 1 y 65% | 3 y 22% | 3 y 24% | NA | NA | NA | NA |
III–IV: 5% | EFS 54% | 3 y 52% | ||||||||||||
Bayraktar et al36 | Adult AML | MRD/MUD/MMUD; PBSC/BM | CD34+ T cell depletion | 115 | II–IV: 5% | 3 y 13% | 1 y OS 68% | NA | 1 y 17% | 1 y 18% | NA | NA | NA | NA |
III–IV: 1% | EFS 62% | 3 y 18% | 3 y 24% | |||||||||||
3 y OS 57% | ||||||||||||||
EFS 58% | ||||||||||||||
van Esser et al37 | Adult hematological malignancies | SIB/MUD; BM/PBSC | CD34+ T cell depletion or sheep erythrocyte rosetting | 85 | II–IV: 57% | 1 y 38% | NA | NA | NA | 1 y 29% | NA | 54% (R+) DNAemia | NA | NA |
12% PTLD | ||||||||||||||
de Witte et al38 | Adult hematological malignancies | MRD/MUD/MMUD; PBSC | αβT cell depletion | 35 | II–IV: 37% | 2 y | 2 y | NA | 2 y 29% | 2 y 32% | 64% (R+) DNAemia, CMV disease 6% | 44% | NA | NA |
III–IV: 17% | 23% | OS 52% | ||||||||||||
Moderate: 17% | EFS 40% | |||||||||||||
Locatelli et al39 | Pediatric AML/ALL | Haplo; PBSC | αβT cell/CD19 depletion | 80 | I–II skin only: 30% | 0% | 5 y: | NA | 5 y 24% | 5 y 5% | NA | NA | NA | NA |
>II or visceral: 0% | OS 72% | |||||||||||||
LFS 71% | ||||||||||||||
Laberko et al40 | pediatric malignant (114) + nonmalignant (68) | MUD/haplo; PBSC | αβT cell/CD19 depletion | 182 | Malignant: II–IV: 40% | NA | 2 y OS 68% | NA | 2 y 37% | 2 y 13% | 51% | 33% | NA | NA |
Nonmalignant II–IV: 27% | 2 y malignant 58% | |||||||||||||
2 y nonmalignant 78% | ||||||||||||||
Lang et al41 | Pediatric AML/MDS/nonmalignant | Haplo; PBSC | αβT cell/CD19 depletion | 41 | II: 10% | 1.6 y average FU: 18% limited; 9% ext | 1.6 y average FU: OS 52%; EFS NA | NA | 1.6 y average FU: 42% | 1.6 y average FU: 7% | NA | NA | NA | NA |
III–IV: 15% | ||||||||||||||
Maschan et al42 | Pediatric high-risk AML | MUD/MMUD/haplo; PBSC | αβT cell/CD19 depletion | 33 | II: 23% | 2 y 30% | 2 y | NA | 2 y 31% | 2 y 10% | 52% DNAemia; 6% CMV disease | 50% DNAemia; 6% rituximab | NA | NA |
III: 16% | OS 67% | |||||||||||||
IV: 0% | EFS 60% | |||||||||||||
Bertaina et al43 | Pediatric nonmalignant | Haplo; PBSC | αβT cell/CD19 depletion | 23 | I–II: 13.1% | 0% | 2 y | NA | NA | 9.3% | 38% DNAemia CMV/adeno | 50% DNAemia; 6% rituximab | NA | 38% DNAemia CMV/adeno |
III–IV: 0% | OS 91% | |||||||||||||
EFS 74% | ||||||||||||||
Balashov et al44 | Pediatric nonmalignant | MUD/MMRD/haplo; PBSC | αβT cell/CD19 depletion | 37 | II: 21.5% | Any 3% | 2 y | NA | NA | NA | NA | NA | NA | NA |
IV: 2.8% | Ext 3% | OS 96.7% | ||||||||||||
EFS 67.7% |
Depicted is a selection of studies.
Adeno = adenovirus; ALL = acute lymphoblastic leukemia; AML = acute myeloid leukemia; ATG = anti-thymocyte globulin; ATG-F = anti-thymocyte globulin-fresenius; ATG-T = anti-thymocyte globulin-thymoglobulin; BK = BK virus; BM = bone marrow; CMV = cytomegalovirus; CRFS = cGVHD-free relapse-free survival; cGVHD = chronic graft vs host disease; EBV = Epstein-Barr virus; EFS = event-free survival; ext = extensive; FU = follow up; GVHD = graft vs host disease; haplo = haploidentical donor; IS = immune suppression; LFS = leukemia-free survival; MDS = myelodysplastic syndrome; MMRD = mismatched related donor; MMUD = mismatched unrelated donor; MRD = matched related donor; MUD = matched unrelated donor; NA = not available; NRM = nonrelapse mortality; OS = overall survival; PBSC = peripheral blood stem cell; PFS = progression-free survival; PTCY = post-transplantation cyclophosphamide; PTLD = posttransplant lymphoproliferative disease; pts = patients; R+ = cytomegalovirus positive recipient; SIB = sibling; y = year.