Evolution of Peripheral Blood Stem Cell Transplantation.

Blood-derived progenitors have become the predominant source of hematopoietic stem cells for clinical transplantation. The main advantages compared to the bone marrow are as follows: harvesting blood stem cells is less painful for the donor, utilizes much less resources such as operating theater time and general anesthesia, and, above all, is associated with significantly accelerated reconstitution. The latter has ultimately improved patient safety as a consequence of significantly shortened aplastic phase and hence reduced morbidity and mortality after transplantation. Basic and translational research efforts in the 1960s to the mid-1980s have made the first blood stem cell transplantation in Heidelberg in 1985 possible. Diverse groups around the world have contributed to incremental knowledge that culminated in the first successful attempts in blood stem cell transplantation. These efforts have spawned modern research into stem cell biology and the immune modulatory effects of allogeneic transplantations.

[Introduction and the current status of unrelated peripheral blood stem cells transplantation in Japan].

In other countries, unrelated donor peripheral blood stem cell transplantation (PBSCT) is more prevalent than bone marrow transplantation; however, in Japan, it was introduced in 2010 after confirming the safety of donors. PBSCT does not require blood donation, general anesthesia, or frequent bone marrow aspiration of the donor. After PBSCT, numerous hematopoietic cells can prompt blood recovery and engraftment, which has enabled reduced intensity transplantation in elderly patients and patients with concurrent diseases, such as infection. In addition, GVL effect by a large number of donor lymphocytes is expected, however, chronic GVHD is a major concern. When introducing PBSCT in Japan, manuals were drafted considering the short-term safety of donors, and data were collected on the occurrence of long- and short-term adverse events. A randomized trial reported no difference in the survival rate between bone marrow transplantation and PBSCT at 5 years; however, it revealed that QOL was better in the former. PB is a essential transplant source option, and attempts are being made to overcome chronic GVHD. PBSC contains abundant stem cells, progenitor cells, and immunocompetent cells and is indispensable for the development of cell therapy for blood diseases in the future.

Rescue haploidentical peripheral blood stem cell transplantation for engraftment failure: a single-centre case series.

Graft failure affects approximately 5% of allogeneic stem cell transplants, with a poor prognosis. Salvage second allogeneic stem cell transplantation (alloSCT2) is limited by high rates of transplant-related mortality from infection and graft-versus-host disease. We report on five adult patients receiving rescue alloSCT2 using haploidentical peripheral blood stem cells. All patients achieved neutrophil engraftment, two subsequently died from sepsis and disease relapse, respectively. Three patients remain alive up to 2 years post-transplant. We suggest consideration of haploidentical alloSCT2 for patients with graft failure.

[Therapeutic cellular angiogenesis in treatment of peripheral artery diseases].

High incidence of peripheral artery disease and limited possibilities of either open or endovascular methods of treatment, as well as low efficacy of medicamentous treatment of this pathology compel the professionals concerned to search for new methods of treatment aimed at improving the condition of the distal arterial bed, decreasing peripheral resistance and stimulating the development of the capillary network. One of the possible ways to solve this problem is the use of cellular technologies for stimulating angiogenesis. This novel and rather promising method consists in using autologous cell therapy in treatment of peripheral arterial diseases.

Twenty-five years of peripheral blood stem cell transplantation.

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.

Haematopoietic stem cell transplantation in Hong Kong.

The first case of haematopoietic stem cell transplant (HSCT) was performed at the Bone Marrow Transplant Center, Queen Mary Hospital (QMH) in 1990. Since then three more transplant centres have been established: Prince of Wales Hospital (1991) mainly in paediatric transplant, Queen Elizabeth Hospital (1995) and Tuen Mun Hospital (2006) in adult autologous transplant. Up to the end of 2008, a little over 2000 transplants have been performed in Hong Kong, and QMH takes up about 85% of the total number of cases. A unified HSCT registry in Hong Kong is desirable and is yet to be established. At QMH, by the end of 2008, a total of 1708 transplant procedures have been performed with 83% (1417) being first-time transplants and the rest (291, 17%) are repeat transplants mostly for relapsed patients. The numbers of male and female patients are 955 and 753, respectively. The median age is 35.4 years (range, 3 months to 67 years) with 85.8% of the transplants performed in adults (> 18 years). The type of donor includes 34% autologous, 1% syngeneic, 38% related allogeneic and 27% unrelated allogeneic. The top five indications of the first-time transplants are acute myeloid leukaemia (25.8%), chronic myeloid leukaemia (15.9%), lymphoma (14.6%), acute lymphoblastic leukaemia (14.5%), and myeloma (8.6%). With the development of peripheral blood stem cell collection, in recent years it is performed in 50% of the allogeneic and 80% of the autologous cases. Bone marrow harvest in autologous cases is only for patients who fail peripheral blood stem cell mobilisation. Transplant outcomes are reported to the Center for International Blood and Marrow Transplant Research and long-term survivals are in general comparable to international standard.

The history and future prospective of haplo-identical stem cell transplantation.

Initial attempts at haplo-identical transplantation with T-cell replete bone marrow (BM) were associated with a high transplant-related mortality (TRM), mainly caused by severe graft-versus-host disease (GvHD), and previous efforts to prevent GvHD by ex vivo T-cell depletion of haplo-identical BM were associated with a high risk of graft failure and other complications. Improvements in large-scale T-cell depletion techniques of haplo-identical peripheral mobilized stem cells (PBSC) have overcome the human leukocyte antigen (HLA) barrier by using megadose numbers of stem cells obtained by either highly purified CD34(+) selection or negative depletion of T cells. In addition, recent insights into the role of graft-facilitating and anti-leukemic alloreactive natural killer (NK) cells, the permanent availability of the haplo-identical donor post-transplant and continuous improvements in graft-engineering techniques for the generation of effector cells for post-transplant adoptive transfer, have facilitated the development of strategies to decrease regimen-related toxicity through the use of less intensive preparative regimens, prevent severe infections by rebuilding the immune system and decrease the risk of relapse by exploiting the alloreactivity of donor NK cells and other donor-derived effector cells.

Peripheral blood as a source of stem cells for regenerative medicine.

Converging evidence indicates that peripheral blood (PB) contains stem cells (SCs) with multidifferentiation potential, thus representing a potential source for regenerative medicine in several human disorders, as has also been confirmed by promising results obtained in several preliminary clinical trials. In addition to the classic haematopoietic SCs, PB also harbours endothelial progenitor cells, mesenchymal SCs, tissue-committed SCs and monocyte-like SCs. In spite of a series of different names and/or definitions, a large overlap seems to exist among surface markers, functions and origin of these different SC types. This review analyses the different subsets of SCs described in PB, the different hypotheses suggested to explain their origin, and the possible mechanisms that provide the basis for their biological potential.