Background
Reference, year, ref, and median age | Patients (No.) | Diagnosis | Graft | ANC median (range) | PLT median (range) | GVHD | TRM | Relapse | LFS | OS | |
---|---|---|---|---|---|---|---|---|---|---|---|
Acute II–IV | Chronic | ||||||||||
Unmanipulated haplo-SCT with ATG | |||||||||||
Di Bartolomeo P, et al. [57] (37) | 80 | HM | G-BM | 21 (12–38) | 28 (14–185) | 24 % | 17 % at 2 yr | 36 % at 3 yr | 21 % at 1 yr | 38 % at 3 yr | 45 % at 3 yr |
Wang Y, et al. [10] (25) | 1210 | HM | G-BM + G-PB | 13 (8–49) | 16 (5–100) | 40 % | 50 % | 17 % at 3 yr | 17 % at 3 yr | 67 % at 3 yr | 70 % at 3 yr |
Luo Y, et al. [14] (25) | 99 | HM | G-PB | 12 (8–24) | 15 (6–53) | 42.4 % | 41.4 % at 2 yr | 30.5 % at 5 yr | 14.2 % at 5 yr | 58.3 % at 5 yr | 60.8 % at 5 yr |
Gao L, et al. [66] (25.4) | 26 | SAA | G-PB + G-BM | 13 (11–19) | 13 (10–21) | 8.0 % | 40 % | 15.4 % at 2 yr | NA | NA | 84.6 % at 2 yr |
Peccatori J, et al. [19] (48) | 121 | HM | G-PB | 17 (11–61) | 19 (7–154) | 35 % | 47 % at 2 yr | 31 % at 3 yr | 48 % at 3 yr | 20 % at 3 yr | 25 % at 3 yr |
Shin SH, et al. [29] (48) | 60 | MDS | G-PB | 12 (8–23) | 15 (6–132) | 36.7 % | 48.3 % | 23.3 % at 2 yr | 34.8 % at 2 yr | 41.9 % at 2 yr | 46.6 % at 2 yr |
Yahng SA, et al. [120] (41) | 80 | AML | G-PB | 11 | 10 | 47.5 % | 45 % | 12.2 % at 2 yr | 26.6 % at 2 yr | 61.1 % at 2 yr | 66 % at 2 yr |
Lin X, et al. [78] (23) | 105 | HM | G-PB | 14 (10–25) | 16 (9–38) | 21.9 % | 24.1 % at 2 yr | 30.5 % at 3 yr | 21.9 % at 3 yr | 41.1 % at 3 yr | 50.6 % at 3 yr |
TCR haplo-SCT with PT/Cy | |||||||||||
Raiola AM, et al. [38] (45) | 92 | HM | SS-BM (92) | 18 (11–32) | 32 (5–83) | 14 % | 15 % | 18 % at 1000 days | 35 % | 43 % at 4 yr | 52 % at 4 yr |
McCurdy SR, et al. [36] (55) | 372 | HM | SS-BM | 90 %a
| 88 %b
| 32 % at 6 m | 13 % at 2 yr | 11 % at 1 yr | 46 % at 3 yr | 40 % at 3 yr | 50 % at 3 yr |
Bacigalupo A, et al. [37] (47) | 148 | HM | SS-BM | 17 (13–32) | NA | 18 % | 20 % at 2 yr | 14 % at 4 yr | 27 % at 4 yr | NA | 77 % for CR1 49 % for CR2 38 % for AD |
Solomon SR, et al. [61] (46) | 30 | HM | G-PB | 16 (NA) | 25 (NA) | 43 % | 56 % | 3 % at 2 yr | 24 % at 2 yr | 73 % at 2 yr | 78 % at 2 yr |
Cieri N, et al. [64] (55) | 40 | HM | G-PB | 18 (13–45) | 16 (9–100) | 15 % | 20 % at 1 yr | 17 % at 1 yr | 35 % at 1 yr | 48 % at 1 yr | 56 % at 1 yr |
Esteves I, et al. [65] (17) | 16 | SAA | SS-BM (13) G-PB (3) | 19 (16–29) | 21 (20–29) | 13 % | 20 % | 32.9 % at 1 yr | NA | NA | 67.1 % at 1 yr |
Ciurea SO, et al. [62] (NA) | 104c
| AML | SS-BM (85) G-PB (19) | 90 % | 88 % | 16 % | 30 % at 3 yr | 14 % at 3 yr | 44 % at 3 yr | NA | 45 % at 3 yr |
88d
| AML | SS-BM (77) G-PB (11) | 93 % | 88 % | 19 % | 34 % at 3 yr | 9 % at 3 yr | 58 % at 3 yr | NA | 46 % at 3 yr | |
Kasamon YL, et al. [59] (61) | 271 | HM | SS-BM | 88–93 % | 84–89 % | 33 % at 6 m | 12 % at 1 yr | 10 % at 1 yr | 46 % at 3 yr | 37 % at 3 yr | 46 % at 3 yr |
Effects of the locus of HLA-mismatch on haplo-SCT outcomes
Donor selection based on non-HLA variables
Variables | Unmanipulated haplo-SCT with ATG | Ref | TCR haplo-SCT with PT/Cy | Ref | |
---|---|---|---|---|---|
DSA | DSA was associated with primary graft failure, including GR and PGF. | [12] | DSA was associated with an increased risk of graft failure. | [93] | |
Donor age | Young donor age (<30) was associated with decreased 2–4 acute GVHD, NRM, and superior survival. | [10] | No effect of donor age on clinical outcomes was found. | [59] | |
Donor gender | F-M (versus others) correlated with higher incidence of 2–4 acute GVHD. | Male donors were associated with less NRM and better survival. | |||
NK alloreactivity | KIR-ligand mismatch was associated with inferior survival. | [23] | A survival benefit associated with donor-recipient mismatches of inhibitory KIR and KIR haplotype B donors. | [59] | |
NIMA mismatch | NIMA-mismatched was associated with a lower incidence of acute GVHD in unmanipulated haplo-SCT. | [10] | – | ||
Type of donor | Children | Children donors were associated with less acute GVHD than sibling donors. | [10] | – | |
Mather | Maternal donors were associated with more acute GVHD, chronic GVHD, and NRM. | – | |||
Older sister | Older sister donors were inferior to father donors in NRM and survival. | – | |||
Father | Father donors were associated with less acute GVHD, less NRM, and better survival than mother donors. | – |
DSA
Donor age
Donor gender
ABO compatibility
Killer immunoglobulin-like receptor mismatches and NK cell alloreactivity
Biology of NK cells
Role of NK cell alloreactivity in haplo-SCT
NIMA mismatching
Family relationship or type of donor
Donor and recipient serum CMV status
Recommendations
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HLA matching: The effects of HLA disparity on transplantation outcomes has vanished, due to the improved approaches of unmanipulated haplo-SCT with ATG and haplo-SCT with PT/Cy.
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Donor-specific antibodies: DSA must be incorporated in the algorithm for haploidentical donor selection, both in unmanipulated haplo-SCT with ATG and in haplo-SCT with PT/Cy. Procedures to reduce DSA prior to transplantation should be considered for patients that have DSA against potential haploidentical donors.
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ABO compatibility: ABO compatibility should be considered in both unmanipulated haplo-SCT with ATG and haplo-SCT with PT/Cy.
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Serum CMV status: Among haploidentical donors, donor and recipient CMV serostatus should be considered, in both unmanipulated haplo-SCT with ATG and haplo-SCT with PT/Cy.
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Donor age: Among haploidentical donors, young males should be considered optimal, in both unmanipulated haplo-SCT with ATG and haplo-SCT with PT/Cy.
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Family relationship: Family relationships should be considered in unmanipulated haplo-SCT with ATG-based conditioning, with the following order of donor preference: child, younger brother, older sister or father, older sibling, mother, and collateral relatives.
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NIMA mismatches: NIMA mismatching should be incorporated into the algorithm for donor selection in unmanipulated haplo-SCT with the ATG protocol. The order of donor eligibility should be NIMA mismatches, followed by NIPA mismatches.
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NK cell alloreactivity: NK cell alloreactivity should be considered in choosing a donor for both unmanipulated haplo-SCT with ATG and haplo-SCT with PT/Cy.