Table 1. Principal studies reporting patients receiving a CBT for BMF.
| Author; type of study | Patients, n | Type of BMF |
Median age, years (range) | Graft source (-/6 HLA) | Conditioning regimen | Survival | CIF PNN engraftment | CIF acute and chronic GVHD |
|---|---|---|---|---|---|---|---|---|
| Gluckman et al. NEJM 1997; retrospective (25) | N=147 all hematological diseases; N=26 BMF |
N=7 SAA; N=16 FA; N=1 DC; N=2 BDA |
6 (0.2–45) |
All diseases: N=65 UCBT/N=78 rCBT; BMF: N=9 UCBT/N=17 rCBT |
Heterogeneous | 1-year OS rCBT: 63% (all diseases); 1-year OS UCBT: 29% (all diseases) |
At 60 days: rCBT: 79%; UCBT: 87% | 9% rCBT, 50% UCBT aGVHD |
| Lau et al. JHSCR 2001; retrospective (36) |
2 | SAA | 17, 18 | UCBT (4/6 HLA) | (I) Cy 50 mg/kg/d (day −1); ATG: 5 mg/kg (day −5 to −1); (II) Flu 1 mg/kg/d (day −5 to −1); ATG 5 mg/kg (day−5 to −1) |
Both patients alive (fup 6 months) | Day 44 and day 37 | No GVHD events |
| Mao et al. EJH 2005; retrospective (37) | 9 | SAA | 24 [15–37] |
Single and double UCBT (4/6, 5/6 or 6/6) | Cy 20 mg/kg/d day −6 to −4; ALG 40 mg/kg/d day −3 to −1 |
2-year OS 77% (7/9 patient alive, median fup 32 months) | 88% at day 15 | 22% cGVHD. No aGVHD |
| Yoshimi et al. BBMT 2008; retrospective (39) | 31 | SAA | 28 (0.9–72.3) |
Single and double UCBT (4/6, 5/6 or 6/6) | Heterogeneous | 2-year OS 41% | 55% at day 30 | 17% grade II–IV aGVHD; 20% cGVHD |
| Gluckman et al. BBMT 2007; retrospective (14) | 93 | FA | 8.6 [1–45] |
Single and double UCBT (3/6, 4/6, 5/6 or 6/6) | Heterogeneous (61% Flu based) | 2-year OS 40% | 60% at day 60 | 32% grade II–IV aGVHD; 16% cGVHD |
| Peffault de Latour et al. BBMT 2011; retrospective (40) | 71 | SAA (N=61), PNH (N=9) |
13 [2–68] |
Single and double UCBT (3/6, 4/6, 5/6 or 6/6) | Heterogeneous | 3-year OS 38% | 51% at day 60 | 20% grade II–IV aGVHD; 18% cGVHD |
| Ayas et al. BBMT 2012; retrospective (53) | 26 (N=19 UBMT and N=7 UCBT) |
FA | 7.8 (1.4–12.9) |
Single and double UCBT (4/6, 5/6 or 6/6) | Cy 5 mg/kg/d (day −5 to −2); Flu 30 mg/m2/d (day −6 to −2); rATG 5 mg/kg/d (day −5 to −2) |
2/7 patients alive at 19 months | 3/7 engrafted at day 30 | 1/7 grade II aGVHD, 1/7 cGVHD |
| Jaing et al. JPHO 2014; retrospective (54) | 3 | FA | 2 (0.8–4.3) |
Single UCBT (5/6 or 6/6) | Flu 30 mg/m2/d (day −10 to −5); Cy 60 mg/kg/d (day −6 to −5); rATG 2.5 mg/kg/d (day −4 to −1) |
5-year OS 100% (median fup 64 months) | 100% at day 30 | 3/3 grade II aGVHD; 2/3 limited cGVHD |
| MacMillan et al. Blood 2015; prospective (55) | 130 (N=99 UBMT and N=31 UCBT) |
FA | 9 [1–48] |
Single and double UCBT (4/6, 5/6 or 6/6) | Cy 10 mg/kg/d (day −6 to −3); hATG 30 mg/kg/d (day −6 to −1); TBI (3, 4.5 or 6 Gy in 1 day) + Flu 35 mg/m2/d (day −6 to −2) in 107 patients |
1-year OS 63% (entire cohort) | 90% at day 40 (entire cohort) | 20% grade II–IV aGVHD; 10% cGVHD (entire cohort) |
| Kuwatsuka et al. BBMT 2016; retrospective (41) | 272 (203 UBMT and 69 UCBT) |
SAA | 49 for UCBT | 203 UBMT; 69 single UCBT (4/6, 5/6 or 6/6) | Heterogeneous (mainly Flu/Mel or Flu/Cy based) rATG only in 3 patients | 3-year OS for UCBT 69% | 68% at day 28 | 32% grade II–IV aGVHD; 21% cGVHD |
| Peffault de Latour et al. Blood 2018; prospective (42) | 26 | SAA | 16 (9.3–23.4) |
Single and double UCBT (4/6, 5/6 or 6/6) | Flu 30 mg/m2/d (day −6 to −3); Cy 30 mg/kg/d (day −6 to −3); rATG 2.5 mg/kg/d day −3, −2; TBI (2 Gy day −2) |
1-year OS 88.5% | 88% at day 60 | 1/26 aGVHD; 1/26 cGVHD |
| Bizzetto et al. Hematologica 2011; retrospective (59) | 64 | Inherited BMF non FA (N=21 DBA, N=16 CAT, N=8 DC, N=2 SDS, N=16 CN, N=1 unclassified) | 5 (0.3–26) |
N=20 rCBT; N=44 UCBT | Heterogeneous | 3-year OS rCBT: 95% UCBT: 61% | At day 60: rCBT: 95%; UCBT: 55% | rCBT: 10% II–IV aGVHD and 11 cGVHD UCBT: 24% II–IV aGVHD; 53% cGVHD |
| Pagliuca et al. BBMT 2017; retrospective (60) | 117 (inherited and acquired BMF, related HLA identical CBT) |
N= 20 SAA; N=48 FA; N=2 SDS; N=3 DC; N=5 CAT; N=27 DBA; N=4 CN; N=8 unclassified |
6.7 [1–16] |
N=82 single rCBT; N=35 rCBT + rBMT | Heterogeneous | 7-year OS: 87.9% | 84.2% at day 60 | 14%: II–IV aGVHD; 14.5% cGVHD |
| Ochi et al. BBMT 2019; retrospective (38) | 6 | SAA | 38.5 [32–45] |
Single and double UCBT (4/6, 5/6 or 6/6) | Flu 30 mg/m2 day −6 to −2; Cy 60 mg/kg day −6 to −5; TBI 4 Gy day −1 |
1-OS 100% | 100% at day 40 | 3/6 grade II aGVHD (no III–IV grade); 2/6 cGVHD |
CIF, cumulative incidence function; BMF, bone marrow failure; UCBT, unrelated cord blood transplantation; rCBT, related cord blood transplantation; rBMT, related bone marrow transplantation; OS, overall survival; aGVHD, acute graft versus host disease; cGVHD, chronic graft versus host disease; PNN, neutrophil; CB, cord blood; BM, bone marrow; UBMT, unrelated bone marrow transplantation; Cy, cyclophosphamide, Flu, fludarabine, Mel, melphalan; TBI, total body irradiation; rATG, rabbit anti-thymoglobulin, hATG, horse anti-thymoglobulin; FA, Fanconi anemia, DC, Dyskeratosis congenita, DBA, Diamond Blackfan anemia, CN, congenital neutropenia; SAA, severe aplastic anemia; PNH, paroxysmal nocturnal hemoglobinuria; fup, follow-up; CAT, congenital amegakaryocytic thrombocytopenia.