BACKGROUND: The impact of early peripheral blood chimerism on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We aimed to determine whether day 14 peripheral blood chimerism after allo-HSCT predicts outcomes in patients with non-malignant diseases. METHODS: Data from 56 patients who received allo-HSCT between April 2007 and March 2016 were retrospectively analyzed. Chimerism was evaluated using short-tandem repeat polymerase chain reaction, with mixed chimerism (MC) defined as greater than 1% recipient cells which was further categorized into low-level MC (> 1% and < 15% of recipient-derived cells) and high-level MC (≥ 15% of the recipient-derived cells). RESULTS: Thirty-six patients showed complete donor chimerism (CC), 14 low-level MC, and 6 high-level MC at day 14 post-transplant. The estimated 5-year event-free survival (EFS) was higher in the CC or low-level MC groups than in the high-level MC group (86.1% vs. 71.4% vs. 33.3%; P = 0.001). In BM or peripheral blood stem cell (BM/PBSC) transplants, the 5-year EFS was higher in the CC or low-level MC group than in the high-level MC group (93.1% vs. 66.7% vs. 0%; P < 0.001). However, in cord blood transplants, the 5-year OS and EFS according to the day 14 peripheral blood chimerism did not reach statistical significance. CONCLUSION: Although CC is not always necessary after allo-HSCT for non-malignant diseases, our data suggest that day 14 peripheral blood chimerism may predict outcomes in patients with non-malignant diseases who underwent BM/PBSC transplants.
Bone Transplantation ; Chimerism ; Disease-Free Survival ; Fetal Blood ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Polymerase Chain Reaction ; Retrospective Studies ; Stem Cells ; Tissue Donors ; Treatment Outcome

The dose of CD34+ cells is known to influence the outcome of allogeneic peripheral blood stem cell (PBSC) and/or T-cell-depleted transplantation. A previous study proposed that 2×10⁶ CD34+ cells/kg is the ideal minimum dose for allogeneic transplantation, although lower doses did not preclude successful therapy. In the case we present here, CD34+ cells were collected from a matched sibling donor on the day of allogeneic hematopoietic stem cell transplantation; however, the number of cells was not sufficient for transplantation. Consequently, PBSCs were collected three additional times and were infused along with cord blood cells from the donor that were cryopreserved at birth. The cumulative dose of total nuclear cells and CD34+ cells was 15.9×10⁸ cells/kg and 0.95×10⁶ cells/kg, respectively. White blood cells from this patient were engrafted on day 12. In summary, we report successful engraftment after infusion of multiple low doses of CD34+ cells in a patient with severe aplastic anemia.
Anemia, Aplastic ; Cord Blood Stem Cell Transplantation ; Fetal Blood ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukocytes ; Parturition ; Peripheral Blood Stem Cell Transplantation ; Siblings ; Stem Cells ; Tissue Donors ; Transplantation, Homologous

Cord blood (CB) has been used as an important source for hematopoietic stem cell transplantation and has been stored in public CB banks (CBBs) worldwide since the mid-1990s. Recently, the application of cell-based therapy using CB has expanded its clinical utility for various refractory diseases and immunologic diseases through the manufacture of mesenchymal stem cells or induced pluripotent stem cells and the isolation of mononuclear cells from CB. In this review, I briefly summarize the biologic characteristics and banking process of CB, as well as the current status of public and private CBBs. I also review the current status of stem cell transplantation and cell-based therapy using CBs. Finally, I suggest strategies of banking CBs in anticipation of future medical advances.
Cell- and Tissue-Based Therapy ; Cryopreservation ; Fetal Blood ; Hematopoietic Stem Cell Transplantation ; Immune System Diseases ; Induced Pluripotent Stem Cells ; Mesenchymal Stromal Cells ; Population Characteristics ; Stem Cell Transplantation ; Transplantation

Stem cells are primitive self renewing undifferentiated cell that can be differentiated into various types of specialized cells like nerve cell, skin cells, muscle cells, intestinal tissue, and blood cells. Stem cells live in bone marrow where they divide to make new blood cells and produces peripheral stem cells in circulation. Under proper environment and in presence of signaling molecules stem cells begin to develop into specialized tissues and organs. These unique characteristics make them very promising entities for regeneration of damaged tissue. Day by day increase in incidence of heart diseases including left ventricular dysfunction, ischemic heart disease (IHD), congestive heart failure (CHF) are the major cause of morbidity and mortality. However infracted tissue cannot regenerate into healthy tissue. Heart transplantation is only the treatment for such patient. Due to limitation of availability of donor for organ transplantation, a focus is made for alternative and effective therapy to treat such condition. In this review we have discussed the new advances in stem cells such as use of cord stem cells and iPSC technology in cardiac repair. Future approach of CB cells was found to be used in tissue repair which is specifically observed for improvement of left ventricular function and myocardial infarction. Here we have also focused on how iPSC technology is used for regeneration of cardiomyocytes and intiating neovascularization in myocardial infarction and also for study of pathophysiology of various degenerative diseases and genetic disease in research field.
Blood Cells ; Bone Marrow ; Fetal Blood* ; Heart Diseases ; Heart Failure ; Heart Transplantation ; Humans ; Incidence ; Mortality ; Muscle Cells ; Myocardial Infarction ; Myocardial Ischemia ; Myocytes, Cardiac ; Neurons ; Organ Transplantation ; Pluripotent Stem Cells* ; Regeneration ; Skin ; Stem Cells* ; Tissue Donors ; Transplants ; Ventricular Dysfunction, Left ; Ventricular Function, Left

BACKGROUND: The aim of this study was to compare the outcomes of children with acute myeloid leukemia (AML) who received stem cell transplantation from different donor groups.METHODS: This study included 37 pediatric AML patients who received allogeneic stem cell transplantation from March 1996 to December 2012 at Chonnam National University Hospital and Chonnam National University Hwasun Hospital. The overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of graft versus host disease (GvHD), relapse and transplant-related mortality (TRM) were compared between different donor groups.RESULTS: Transplant donor groups included matched sibling donor (MSD, n=15), unrelated donor (URD=13), unrelated umbilical cord blood (UCB, n=7), or haploidentical donor (HD, n=2). Twenty-six patients survived with a median follow-up of 7.3 years. The 7-year EFS rates were 80.0±10.3% in MSD, 69.2±12.8% in URD and 57.1±18.7% in UCB, and 0% in HD, respectively (P=0.019). The CI of relapse at 5 years was 20.0%, 15.4%, 33.3%, 50%, respectively (P=0.721). The CI of TRM at 2 years was 0%, 15.4%, 16.7%, 50.0%, respectively in each donor group (P=0.017). The CI of grade II-IV acute and extensive chronic GvHD were higher in UCB (P=0.003, P=0.020, respectively). There were no significant differences in OS, EFS, and CI of TRM and relapse between allele-mismatched URD and UCB.CONCLUSION: Despite the limitation of small number of patients, the comparable outcome of pediatric AML patients transplanted from alternative donor with those transplanted from MSD are encouraging. Especially, if a matched donor is not available, allele-mismatched URD or UCB transplant may offer the advantage of prompt availability for patients who urgently require transplantation.
Child ; Disease-Free Survival ; Fetal Blood ; Follow-Up Studies ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Incidence ; Jeollanam-do ; Leukemia, Myeloid, Acute ; Mortality ; Recurrence ; Siblings ; Stem Cell Transplantation ; Tissue Donors ; Unrelated Donors

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has been established as an important curative method in genetic rare diseases in children. However, adverse effects have been obstacles for successful outcomes. This study aims to review the transplant outcomes of genetic rare diseases over the last 2 decades, to analyze the prognostic factors that may affect outcome, and to suggest future perspective of HSCT in these diseases.METHODS: Seventeen patients younger than 18 years who were transplanted at Department of Pediatrics, Chonnam National University Hospital and Chonnam National University Hwasun Hospital from 1996 to 2015 were retrospectively reviewed. Outcomes were analyzed by donor source, intensity of conditioning [myeloablative conditioning (MAC) vs. reduced-intensity conditioning (RIC)], and disease type.RESULTS: The 5-year Kaplan-Meier overall survival (OS), and event-free survival (EFS) was 64.7±14.3% and 52.9±12.9%, respectively. Among subgroups, the 5-year OS was 61.5±15.8% after RIC as compared to 28.6±17.1% after MAC (P=0.27). The 5-year EFS was 60.0±25.0% after matched sibling donor transplants, 62.5±20.4% after mismatched related/unrelated bone marrow/peripheral blood stem cell transplants, and 28.6±17.1% after unrelated umbilical cord blood transplants, respectively. The 5-year OS according to disease type was as follows: 60.0±21.9% for Fanconi anemia, 50.0±25.0% for familial hemophagocytic lymphohisticytosis. All patients with primary immunodeficiency survived, but none with adrenoleukodystrophy.CONCLUSION: Although definitive conclusions cannot be drawn due to the limited number of cases, RIC may be preferred in select, genetic rare diseases. Better strategies are required to improve outcomes after cord blood transplantation. Moreover, special attention should be given to minimize late complications in children.
Adrenoleukodystrophy ; Child ; Disease-Free Survival ; Fanconi Anemia ; Fetal Blood ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Jeollanam-do ; Methods ; Pediatrics ; Rare Diseases ; Retrospective Studies ; Siblings ; Stem Cells ; Tissue Donors

The prevalence of renal disease continues to increase worldwide. When normal kidney is injured, the damaged renal tissue undergoes pathological and physiological events that lead to acute and chronic kidney diseases, which frequently progress to end stage renal failure. Current treatment of these renal pathologies includes dialysis, which is incapable of restoring full renal function. To address this issue, cell-based therapy has become a potential therapeutic option to treat renal pathologies. Recent development in cell therapy has demonstrated promising therapeutic outcomes, in terms of restoration of renal structure and function impaired by renal disease. This review focuses on the cell therapy approaches for the treatment of kidney diseases, including various cell sources used, as well recent advances made in preclinical and clinical studies.
Cell- and Tissue-Based Therapy/*methods ; Fetal Stem Cells/transplantation ; Humans ; Kidney/cytology ; Kidney Diseases/*therapy ; Pluripotent Stem Cells/transplantation ; Stem Cell Transplantation/methods

Bronchopulmonary dysplasia (BPD), a chronic lung disease affecting very premature infants, is a major cause of mortality and long-term morbidities despite of current progress in neonatal intensive care medicine. Though there has not been any effective treatment or preventive strategy for BPD, recent stem cell research seems to support the assumption that stem cell therapy could be a promising and novel therapeutic modality for attenuating BPD severity. This review summarizes the recent advances in stem cell research for treating BPD. In particular, we focused on the preclinical data about stem cell transplantation to improve the lung injury using animal models of neonatal BPD. These translational research provided the data related with the safety issue, optimal type of stem cells, optimal timing, route, and dose of cell transplantation, and potency marker of cells as a therapeutic agent. Those are essential subjects for the approval and clinical translation. In addition, the successful phase I clinical trial results of stem cell therapies for BPD are also discussed.
Bronchopulmonary Dysplasia/*therapy ; Cell- and Tissue-Based Therapy ; Clinical Trials as Topic ; Fetal Blood/cytology/transplantation ; Humans ; Infant, Newborn ; Infant, Premature ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology

BACKGROUND: Currently, data on the role of tacrolimus and mini-dose methotrexate (MTX) in pediatric unrelated hematopoietic stem cell transplantation (HSCT) is limited. We report the outcomes of unrelated hematopoietic stem cell recipients, evaluating engraftment status, incidence of acute and chronic graft-versus-host disease (GVHD) and toxicities after use of tacrolimus and mini-dose MTX for GVHD prophylaxis.METHODS: Thirty-five children who received tacrolimus and mini-dose MTX as prophylaxis from January 2004 to December 2013 were reviewed. All patients received tacrolimus beginning the day prior to transplant at a dose of 0.03 mg/kg/day by continuous intravenous infusion. MTX was administered at a dose of 5 mg/m2 IV on days 1, 3, 6 and 11.RESULTS: Median age at transplantation was 8.42 years (range 0.75-18.9 years). Seventeen patients received human leukocyte antigen (HLA) fully matched donor transplants and 18 received partially mismatched transplants. All but two patients who received unrelated cord blood transplants showed successful engraftment. The median time to ANC recovery was 12 days. The incidence of acute GVHD was 33.3% including 15.1% grade III-IV GVHD. Localized chronic GVHD developed in only 2 of 27 (7.4%) evaluable patients. Lower tacrolimus levels during days 1-21 were associated with a higher incidence of acute GVHD (P=0.033). The estimated 4-year event free survival and overall survival of the patients were 71.2% and 80.0%.CONCLUSION: Overall, the combination of tacrolimus and mini-dose MTX could be effectively administered in the setting of pediatric unrelated HSCT.
Child ; Disease-Free Survival ; Fetal Blood ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Incidence ; Infusions, Intravenous ; Korea ; Leukocytes ; Methotrexate ; Tacrolimus ; Tissue Donors

Umbilical cord blood (CB) has been an alternative hematopoietic stem cell source especially for patients without an appropriate marrow or mobilized peripheral blood donor. Although many studies have shown similar overall survival rates after CB transplantation compared with other donor sources, higher rate of non-relapse mortality is a major obstacle for a successful CB transplantation. Thus, selecting a best appropriate unit is very important to improve the outcome of CB transplantation. Adequate cell dose and better HLA matching (antigen-level for -A, -B, and allele-level for -DRB1) have been considered most important criteria of donor choice for CB transplantation. In recent, other criteria including non-inherited maternal antigens, HLA-C matching, allele-level matching at 8 loci (-A, -B, -C, -DRB1), and anti-HLA antibodies are also suggested as factors that might affect the outcome of CB transplantation. This review will highlight current issues regarding criteria of donor choice for CB transplantation. Finally, I will introduce the algorithm and detailed guideline for CB selection recently developed in Korea, which may help physicians to choose best unit available.
Antibodies ; Blood Donors ; Bone Marrow ; Fetal Blood* ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; HLA-C Antigens ; Humans ; Korea ; Mortality ; Survival Rate ; Tissue Donors