Twenty-five years of peripheral blood stem cell transplantation

Abstract Peripheral blood stem cell transplantation (PBSCT) is the most common transplantation procedure performed in medicine. Its clinical introduction in 1986 replaced BM as a stem-cell source to approximately 100% in the autologous and to approximately 75% in the allogeneic transplantation setting. This historical overview provides a brief insight into the discovery of circulating hematopoietic stem cells in the early 1960s, the development of apheresis technology, the discovery of hematopoietic growth factors and small molecule CXCR4 antagonist for stem- cell mobilization, and in vivo experimental transplantation studies that eventually led to clinical PBSCT. Also mentioned are the controversies surrounding the engraftment potential of circulating stem cells before acceptance as a clinical modality. Clinical trials comparing the outcome of PBSCT with BM transplantation, registry data analyses, and the role of the National Marrow Donor Program (NMDP) in promoting unrelated blood stem-cell donation are addressed.

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A novel conditioning regimen improves outcomes in β-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation

Blood ◽

10.1182/blood-2012-03-417998 ◽

2012 ◽

Vol 120 (19) ◽

pp. 3875-3881 ◽

Cited By ~ 49

Author(s):

Chunfu Li ◽

Xuedong Wu ◽

Xiaoqing Feng ◽

Yuelin He ◽

Huaying Liu ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Thalassemia Major ◽

Blood Stem Cell ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Blood Stem Cell Transplantation

Abstract We used a novel NF-08-TM transplant protocol based on intravenous busulfan, cyclophosphamide, fludarabine, and thiotepa in 82 consecutive patients with β-thalassemia major (TM), including 52 with allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors (UDs) with well-matched human leukocyte antigens and 30 with hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs). The median age at transplantation was 6.0 years (range, 0.6-15.0 years), and the ratio of male-to-female patients was 56:26. The median follow-up time was 24 months (range, 12-39 months). The estimated 3-year overall survival and TM-free survival were 92.3% and 90.4% in the UD-PBSCT group and 90.0% and 83.3% in the MSD-HSCT group. The cumulative incidences of graft rejection and grades III-IV acute graft-versus-host disease were 1.9% and 9.6%, respectively, in the UD-PBSCT group and 6.9% and 3.6%, respectively, in the MSD-HSCT group. The cumulative incidence of transplant-related mortality was 7.7% in the UD-PBSCT group and 10.0% in the MSD-HSCT group. In conclusion, UD-PBSCTs using the well-tolerated NF-08-TM protocol show similar results to MSD-HSCTs and can be used to treat β-thalassemia patients in the absence of MSDs.

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A Novel Conditioning Regimen Improves Outcomes in b-Thalassemia Major Patients Using Unrelated Donor Peripheral Blood Stem Cell Transplantation

Blood ◽

10.1182/blood.v120.21.4514.4514 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4514-4514

Author(s):

Li Chunfu ◽

Liu Huayin ◽

Qifa Liu

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Thalassemia Major ◽

Blood Stem Cell ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Blood Stem Cell Transplantation

Abstract Abstract 4514 We used a novel NF-08-TM transplant protocol in 100 consecutive patients with β-thalassemia major (TM), including 66 with allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors (UD) with well-matched human leukocyte antigens (HLAs) and 34 with hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSD). The median age at transplantation was 6.5 yo (range: 0.6–15 yo), and the ratio of male to female patients was 68:32. The median follow-up time was 24 months (range: 12–39 months). The 3-year overall survival (OS) and TM-free survival (TFS) were 92.4% and 90.9% in the UD-PBSCT group and 88.2% and 82.4% in the MSD-HSCT group. The cumulative incidences of graft rejection (GR) and grade II–IV acute graft-versus-host disease (aGVHD) were 1.5% and 10.6%, respectively, in the UD-PBSCT group and 6.1% and 5.9%, respectively, in the MSD-HSCT group. The cumulative incidence of transplant-related mortality (TRM) was 7.6% in the UD-PBSCT group and 11.8% in the MSD-HSCT group. In conclusion, UD-PBSCTs using the well-tolerated NF-08-TM protocol show similar results to MSD-HSCTs and can be used to treat b thalassemia patients in the absence of MSD. Disclosures: No relevant conflicts of interest to declare.

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Homeostasis of telomere length rather than telomere shortening after allogeneic peripheral blood stem cell transplantation

Blood ◽

10.1182/blood-2002-06-1832 ◽

2003 ◽

Vol 101 (1) ◽

pp. 358-362 ◽

Cited By ~ 31

Author(s):

Helene Roelofs ◽

Elmar S. D. de Pauw ◽

Aeilko H. Zwinderman ◽

Sonja M. Opdam ◽

Roel Willemze ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Telomere Length ◽

Cell Transplantation ◽

Peripheral Blood ◽

Blood Stem Cell ◽

Telomere Shortening ◽

Hematopoietic Stem ◽

Blood Stem Cell Transplantation

Abstract Hematopoietic reconstitution after stem cell transplantation requires excessive replicative activity because of the limited number of stem cells that are used for transplantation. Telomere shortening has been detected in hematopoietic cells after bone marrow transplantation. This has been thought to result from excessive replication of the stem cells, with putative concomitant reduction of their replicative potential. Hematopoietic stem cells from cytokine-mobilized peripheral blood are increasingly used for stem cell transplantation. These grafts contain higher numbers of hematopoietic stem cells, resulting in a faster hematopoietic reconstitution. We have performed a combined prospective and cross-sectional study of hematologic recovery and telomere length dynamics in the immediate reconstitution period after allogeneic T-cell–depleted blood stem cell transplantation. We analyzed hematologic recovery and telomere length of granulocytes, monocytes, B cells, and T-cell subsets in 30 donor/recipient combinations. We found fast recovery in combination with transient telomere shortening in the myeloid lineages. This initial reduction of telomere length was followed by an increase in telomere length to such an extent that 1 year after transplantation the telomere length in recipient cells was similar to the telomere length in donor-derived cells. Therefore, our data indicate telomere length homeostasis after peripheral blood stem cell transplantation, implying no loss of replicative capacity of the stem cells. Our data indicate that fast expansion is accompanied by a reduction of telomere length and that telomere length homeostasis is achieved by de novo generation of hematopoietic cells from stem cells without transplantation-related telomere loss.

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