Table 1.
Selected studies of three haploBMT approaches for treating haematological malignancies
| Period of study, median follow-up (y), n, median age (y) |
Diseases | Graft failure |
GVHD | NRM (due to Infection) |
Relapse | PFS/ DFS |
OS | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AML or MDS |
ALL | Lymph | Other | Acute II–IV |
Acute III–IV |
Chronic | ||||||
| T-cell depletion with ‘megadose’ CD34+ cells | ||||||||||||
| 1993–199448 0.6, n = 17, 23 | 5 | 9 | 0 | 3 | 6% | 6% | 6% | NR | 53 (35)% | 12% | 35% | 35% |
| 1995–199749 1.5, n = 43, 22 | 20 | 23 | 0 | 0 | 5% | 0% | 0% | 0% | 40 (26)% | 30% | 28% | NR |
| 1995–200352 4.1, n = 63, 9 | 12 | 32 | 4 | 15 | 17% | 7% | 0% | 13% | 29 (17)% | ∼40% | 41% | ∼50% |
| 1999–200450 1.8, n = 104, 33 | 67 | 37 | 0 | 0 | 9% | 8% | 2% | 5% | 37 (26)% | 25% | 39% | 40% |
| 1995–200451 3.9 (AML) and 2.4 (ALL), n = 147, 37 (AML) and 21 (ALL) |
86 0 |
0 61 |
0 0 |
0 0 |
9%* | 5% 18% |
2% 11% |
10% 19% |
52 (30)% 48 (30)% |
21% 27% |
29% 23% |
NR NR |
| 1995–200453 NR, n = 102, 9 | 0 | 102 | 0 | 0 | 13% | 22% | 9% | 17% | 37 (22)% | 36% | 27% | 29% |
| 2003–200758 0.7, n = 29, 42 | 16 | 7 | 3 | 3 | 3% | 48% | 14% | 10% | 28 (24)% | NR | 35% | 35% |
| 2004–201259 4.3, n = 46, 11 | 20 | 26 | 0 | 0 | 13% | 27% | 7% | 21% | 20 (2)% | 63% | 25% | 37% |
| 2008–201271‡ 3.8, n = 43, 40 | 33 | 10 | 0 | 0 | 5% | 15% | NR | 2% | 40 (20)% | 5% | 56% | NR |
| GIAC protocol | ||||||||||||
| 1999–200086§ 1.8, n = 15, 15 | 2 | 10 | 0 | 3 | 0% | 33% | 20% | 100% | 33 (13)% | 7% | 60% | 60% |
| 2000–200291|| 2.6, n = 38, 18 | 10 | 16 | 0 | 12 | 0% | 11% | NR | 89% | 32 (18)% | NR | NR | 53% |
| 2000–200587¶ 1.9, n = 171, 23 | 58 | 66 | 0 | 47 | 0% | 55% | 23% | 74% | 23 (12)% | 19% | 65% | 65% |
| 2002–200688 3.0, n = 42, 10–14 | 12 | 24 | 0 | 6 | 0% | 57% | 14% | 57% | 20 (10)% | ∼20% SR, 37% HR |
57% | 64% |
| 2003–200520 NR, n = 56, 28 | 14 | 19 | 0 | 23 | 4% | 27% | NR | 23% | 13 (5)% | 22% | 68% | 70% |
| 2001–200796# 3.0, n = 250, 25 | 108 | 142 | 0 | 0 | 0% | 46% | 13% | 54% | 26 (17)% | 18% | 56% | 59% |
| 2004–200989** 2.2, n = 83, 40 | 67 | 16 | 0 | 0 | 0% | 20% | 7% | 34% | 18 (6)% | ∼30% CR, 79% AD |
∼55% CR, 9% AD |
∼50% CR, 9% AD |
| 2005–201092|| 1.5, n = 80, 37 | 48 | 15 | 7 | 10 | 7% | 24% | 5% | 17% | 36 (20)% | 28% | 38% | 45% |
| 2008–201393‡‡ 2.2, n = 99, 25 | 39 | 50 | 3 | 7 | 0% | 42% | 17% | 41% | 30 (16)% | 14% | 58% | 61% |
| 2010–201394 2.6, n = 231, 28 | 231 | 0 | 0 | 0 | 0% | 36% | 10% | 42% | 13 (NR)% | 15% | 74% | 79% |
| Post-transplantation cyclophosphamide§§ | ||||||||||||
| 2002–2012127|||| 4.1, n = 372, 55 | 107 | 24 | 212 | 29 | 8% | 32% | 4% | 13% | 14 (8)% | 46% | 40% | 50% |
| 2005–201021 3.0, n = 53, 46 | 21 | 10 | 18 | 4 | 2% | 30% | 11% | 38% | 7 (NR)% | 33% | 60% | 64% |
| 2006–2009131¶¶ 3.3, n = 27, 52 | 18 | 4 | 3 | 2 | 8% | 59% | 7% | 16% | 22 (11)% | 32% | NR | 48% |
| 2006–201222 1.6, n = 92, 45 | 49## | 25 | 18 | NR | 14% | 4% | 15% | 18 (10)% | 35% | 43% | 52% | |
| 2008–2010151 1.0, n = 50, 48 | 22 | 6 | 19 | 3 | 2% | 32% | 0% | 13% | 7 (5)% | 45% | 48% | 62% |
| 2009–2011150 0.9, n = 32, 45 | 16 | 4 | 5 | 7 | 6% | 20% | 5% | 7% | 16 (9)% | 34% | 50% | 64% |
| 2009–2012149 1.7, n = 49, 45 | 0 | 0 | 49 | 0 | 4% | 26% | NR | 5% | 16 (14)% | 19% | 63% | 71% |
| 2009–2013133 1.4, n = 55, 49 | 21 | 2 | 25 | 7 | 4% | 53% | 8% | 18% | 23 (19)% | 28% | 48% | 51% |
| NR132¶¶ 2.6, n = 28, 47 | 16 | 10 | 2 | 0 | 0% | 39% | 4% | 22% | 4 (0)% | 21% | 74% | 77% |
| 2012–2014130 2.0, n = 30, 46 | 17 | 6 | 2 | 5 | 0% | 43% | 23% | 56% | 3 (0)% | 24% | 73% | 78% |
Where an explicit cumulative incidence or survival probability by competing risk analysis was not provided in a manuscript, a simple percentage was substituted where possible. Where an explicit percentage was not reported but was shown in a figure, then an approximate percentage is reported.
Engraftment was reported for both cohorts (patients with AML and patients with ALL) together.
Infusions of regulatory and conventional T cells were added to the TCD-haploBMT platform.
This initial pilot study used an approach similar to the GIAC protocol except that the conditioning was different and it used only BM allografts. This study was used as a comparator group in reference 91.
Differs from the GIAC protocol in terms of the conditioning, the use of only BM allografts, and the addition of basiliximab.
Includes an expanded cohort of reference 19, so is listed instead of reference 19.
117 patients were also reported in reference 87, but had longer follow-up in this study.
GIAC protocol was modified in terms of RIC, the use of PBSC allografts only, and the omission of MMF.
GIAC protocol was modified in terms of the use of only PBSC allografts and longer durations of MMF (100 days) and CsA (9 months).
PTCy studies all have in common the use of PTCy for GVHD prophylaxis after haploBMT. The conditioning used and the source of stem cells (peripheral blood versus bone marrow) vary between (and sometimes within) studies.
Includes an expanded cohort of patients reported in reference 124, so is listed instead of reference 124. Infectious deaths were not reported in this manuscript but had been reported for a slightly smaller cohort of 210 patients (reference 126). Consequently, the percentage from reference 126 is substituted here.
Involves a ‘two-step’ approach to PTCy–haploBMT in which, after conditioning, a fixed-dose of peripheral blood T-cells is given, then PTCy is administered 3 and 4 days later, and finally a CD34+-selected PBSC allograft is given.
Indicates patients had either AML, MDS or ALL.
Abbreviations: AD, active disease at haploBMT; AML, acute myeloid leukaemia; ALL, acute lymphoblastic leukaemia; BM, bone-marrow; CsA, ciclosporin-A; CR, complete remission at haploBMT; DFS, disease-free survival; GVHD, graft-versus-host disease; haploBMT, human leukocyte antigen-haploidentical allogeneic blood or bone-marrow transplantation; HR, high-risk disease; Lymph, lymphoma; MDS, myelodysplastic syndrome; MMF, mycophenolate mofetil; n, number of patients transplanted; NR, not reported; NRM, nonrelapse mortality; PBSC, peripheral blood stem cells; PFS, progression-free survival; PTCy, post-transplantation cyclophosphamide; RIC, reduced-intensity conditioning; SR, standard-risk disease; TCD, T-cell depletion; y, years.