Skip to main content

Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Table 3 Clinical trials of MSCs to promote engraftment

From: Mesenchymal stromal cells to modulate immune reconstitution early post-hematopoietic cell transplantation

Patient population HSC source Conditioning; Immune suppression MSC source MSC dose MSC culture conditions Outcome Ref
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 38
  1. MSCs indicates mesenchymal stromal cells, HSC hematopoietic stem cell, PB peripheral blood, Cy cytoxan, Thio thiotepa, Carbo carboplatin, n/a not applicable, BM bone marrow, FBS fetal bovine serum, NR not reported, d days, MSD matched sibling donor, CSA cyclosporine, MTX methotrexate, aGVHD acute graft-versus-host disease, cGVHD chronic graft-versus-host disease, NMD non-malignant disease, haplo haploidentical, TCD T cell depleted, TBI total body irradiation, DFS disease-free survival, OS overall survival, HR high-risk, UCB umbilical cord blood, eATG equine anti-thymocyte globulin, MP methylprednisone, HSA human serum albumin, CR1 complete remission 1, HLH hemophagocytic lymphohistiocytosis, SCD sickle cell disease, UD unrelated donor, Flu fludarabine, Mel melphalan