Table 3 Clinical trials of MSCs to promote engraftment

Adult breast cancer, n = 28

Autologous PB

Cy/Thio/Carbo; n/a

Autologous BM

Day 0 − +1: ≥ 1 × 10⁶/kg

FBS; Fresh or cryopreserved (n = 8); Passages NR

Engraftment of neutrophils 8 d & platelets 8.5 d; No difference compared to historical control group

29

Pediatric HR acute leukemia, n = 8

UCB

Cy/TBI or Bu/Mel (age <1 yr) & eATG/MP; CSA & MP

Haplo BM (parent)

Day 0: 2.1 × 10⁶/kg; Day 21: 1 × 10⁶/kg, n = 3

PlasmaLyte A, 5 % HSA; Cryopreserved; P1-P4

100 % donor chimerism (d 21), engraftment of neutrophils 19 d & platelets 53 d; 14 % gr II-IV aGVHD, no cGVHD; No difference compared to historical control group

30

Pediatric leukemia or HLH, n = 13

UCB

TBI or chemotherapy-based; CSA +/− steroids

Haplo BM (parent)

Day 0: 1.9 × 10⁶/kg

FBS; Fresh or cryopreserved; P2-P3

85 % donor engraftment, engraftment of neutrophils 30 d & platelets 32 d; 31 % gr II-IV aGVHD (0 % gr III-IV), 0 % cGVHD; ↓ gr III-IV aGVHD (p = 0.05), otherwise no difference compared to historical control group

31

Pediatric hemoglobinopathy, SCD (n = 4) or thalassemia major (n = 2)

UCB (1 single, 3 double) or UD BM (2)

Flu/Mel/alemtuzumab; CSA & MMF

Haplo (1) or third-party (5) BM

Day 0: 2 × 10⁶/kg; Day 2: 2 × 10⁶/kg

FBS; Cryopreserved; Passages NR

2 with primary graft failure & 2 with secondary graft failure, 4 deaths; Study prematurely terminated

32

Adult HR hematologic neoplasms, n = 9

UCB + third-party TCD PB HSC

Myeloablative; CSA & MP

Third-party BM (same as HSC; n = 7 haplo)

Day 0: 1.2 × 10⁶/kg

FBS; Cryopreserved; P1-P3

100 % donor engraftment (51 d), engraftment of neutrophils 12 d & platelets 44 d; 44 % gr II-IV aGVHD (0 % gr III-IV), 13 % cGVHD; No difference compared to concurrent control group

33

Pediatric & adult patients, leukemia (n = 3) or NMD (n = 4), indication graft failure in 3

MSD BM (1) or PB (2); UD BM (1), PB (2), or UCB (1)

Myeloablative (3) or RI (4) +/− ATG (6); CSA +/− MTX (4)

Haplo (4) or MSD (3) BM

Day 0: 1 × 10⁶/kg

FBS; Fresh vs cryopreserved NR; P2-P3

100 % donor engraftment, engraftment of neutrophils 12 d & platelets 12 d; 29 % gr II-IV aGVHD (0 % gr III-IV), 14 % cGVHD; No comparison group

34

Adult hematologic malignancy, n = 46

MSD BM or PB

Myeloablative; CSA & MTX

MSD BM

Day 0: 1, 2.5, or 5 × 10⁶/kg (actual dose)

FBS; Cryopreserved; Passages NR

Engraftment of neutrophils 14 d & platelets 20 d; 28 % gr II-IV aGVHD, 61 % cGVHD; No comparison group

35

Adult hematologic neoplasm, poor hematological recovery post-HCT, n = 6

Haplo TCD or MSD PB

TBI or chemotherapy-based +/− ATG (haplo); CSA +/− MTX (MSD)

Haplo or MSD BM (same as HSC)

1 × 10⁶/kg, day +159.5 (median)

Ultroser G serum substitute; Fresh vs cryopreserved NR; P2-P3

No response in 4 patients; 2 patients in CR1 with prompt neutrophil recovery (d 5 & 15) and platelet recovery (d 12 & 21); No comparison group

36

Pediatric patients, Hematologic malignancy (n = 11) or NMD (n = 3)

Haplo TCD PB CD34⁺

TBI or chemotherapy-based (64 %); NR

Haplo BM (same as HSC)

Day 0: 1.6 ×10⁶/kg (mean)

FBS; Fresh or cryopreserved; P1-P3

100 % donor engraftment, engraftment of neutrophils 12 d & platelets 10 d (mean); 38 % gr II-IV aGVHD (0 % gr III-IV), 7 % cGVHD; Faster reticulocyte (p = 0.03) & leukocyte recovery (p = 0.009), otherwise no difference compared to historical control group

37

Adult & young adult patients, hematologic malignancy, n = 30

MSD PB or BM

Cy/TBI or Bu/Cy; CSA & MTX; open-label randomization to control or MSC group, n = 15 per group

MSD BM

Day 0: 3.3 × 10⁵/kg

FBS; Fresh vs cryopreserved NR; Passages NR

5 patients in MSC group did not receive MSCs due to failed expansion; No difference in time to neutrophil & platelet engraftment; decreased incidence aGVHD (11.1 vs 53.3 %) & cGVHD (14.3 vs 28.6 %); comparable rates of infection; increased relapse (60 vs 20 %) and decreased DFS (30 vs 66.7 %) and OS (40 vs 66.7 %), no p-values reported

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