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Peripheral Blood or Bone Marrow Grafts for Mismatched Unrelated Donors with Post-Transplantation
Leonardo Javier Arcuri1, Victor Hugo Glasser Natal2, Mariana Nassif Kerbauy3
1Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
Peripheral blood stem cell (PBSC) grafts generally are considered a risk factor for graft-versus-host disease (GVHD) compared to bone marrow (BM) in hematopoietic cell transplantation (HCT). High-dose post-transplantation cyclophosphamide (PTCy), originally introduced for T cell-replete haploidentical transplantation, has become more widely used in matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT with PBSCs and has been shown to reduce the difference between MUDs and MMUDs. Despite this progress, the comparative impact of PBSC grafts versus BM grafts in this specific setting remains unclear. Using data collected by the Cetner for International Blood and Marrow Transplant Research, we aimed to compare outcomes between PBSCs and BM as graft sources in patients undergoing HCT with an HLA 7/8 MMUD receiving PTCy-based prophylaxis. The primary outcomes were overall survival (OS) and systemic immunosuppressive therapy-requiring chronic GVHD (IST-R cGVHD). With a median follow-up of 36 months, 709 patients received PBSC grafts and 171 received BM grafts from an MMUD. The 2 groups were closely comparable. In univariable analyses, 3-year OS was similar in the PBSC group (57%; 95% CI [confidence interval], 53% to 61%) and the BM group (58%; 95% CI, 51% to 66%) (P = 0.63), as was the rate of IST-R cGVHD (30% [95% CI, 26% to 33%] versus 25% [95% CI, 19% to 32%]; P = .25). Other secondary outcomes showed no statistically significant difference between the 2 groups. In multivariable analyses, the use of PBSC grafts was not associated with different OS (HR, 0.96; 95% CI, 0.74 to 1.25; P = .78) or IST-R cGVHD (HR, 1.40; 95% CI, 0.99 to 1.98; P = .054). However, all grades of cGVHD were significantly higher with PBSC grafts (HR, 1.46; 95% CI, 1.06 to 2.00; P = .019). Other outcomes did not differ statistically in the multivariable analysis. Our results indicate no significant difference in the primary outcomes between bone marrow and peripheral blood in HLA 7/8 MMUD transplants with PT-Cy-based GVHD prophylaxis. This challenges the historical belief that BM transplantation leads to better outcomes in unrelated donor settings compared with PBSC transplantation. Until randomized studies indicate otherwise, choosing graft sources can reasonably focus on donor convenience and logistic feasibility.
Peripheral blood stem cell (PBSC) grafts generally are considered a risk factor for graft-versus-host disease (GVHD) compared to bone marrow (BM) in hematopoietic cell transplantation (HCT). High-dose post-transplantation cyclophosphamide (PTCy), originally introduced for T cell-replete haploidentical transplantation, has become more widely used in matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT with PBSCs and has been shown to reduce the difference between MUDs and MMUDs. Despite this progress, the comparative impact of PBSC grafts versus BM grafts in this specific setting remains unclear. Using data collected by the Cetner for International Blood and Marrow Transplant Research, we aimed to compare outcomes between PBSCs and BM as graft sources in patients undergoing HCT with an HLA 7/8 MMUD receiving PTCy-based prophylaxis. The primary outcomes were overall survival (OS) and systemic immunosuppressive therapy-requiring chronic GVHD (IST-R cGVHD). With a median follow-up of 36 months, 709 patients received PBSC grafts and 171 received BM grafts from an MMUD. The 2 groups were closely comparable. In univariable analyses, 3-year OS was similar in the PBSC group (57%; 95% CI [confidence interval], 53% to 61%) and the BM group (58%; 95% CI, 51% to 66%) (P = 0.63), as was the rate of IST-R cGVHD (30% [95% CI, 26% to 33%] versus 25% [95% CI, 19% to 32%]; P = .25). Other secondary outcomes showed no statistically significant difference between the 2 groups. In multivariable analyses, the use of PBSC grafts was not associated with different OS (HR, 0.96; 95% CI, 0.74 to 1.25; P = .78) or IST-R cGVHD (HR, 1.40; 95% CI, 0.99 to 1.98; P = .054). However, all grades of cGVHD were significantly higher with PBSC grafts (HR, 1.46; 95% CI, 1.06 to 2.00; P = .019). Other outcomes did not differ statistically in the multivariable analysis. Our results indicate no significant difference in the primary outcomes between bone marrow and peripheral blood in HLA 7/8 MMUD transplants with PT-Cy-based GVHD prophylaxis. This challenges the historical belief that BM transplantation leads to better outcomes in unrelated donor settings compared with PBSC transplantation. Until randomized studies indicate otherwise, choosing graft sources can reasonably focus on donor convenience and logistic feasibility.
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