1.Transplantation of peripheral blood stem cells mobilized by intensified consolidation and granulocyte colony-stimulating factor in acute leukemia.
Yoo Hong MIN ; Seung Tae LEE ; Jin Seok KIM ; Joon Ho JANG ; Hyung Chan SUH ; Hyun Ok KIM ; Jae Sook HAHN ; Yun Woong KO
Yonsei Medical Journal 2001;42(1):65-73
The purpose of this study was to evaluate the feasibility and efficacy of autologous transplantation of peripheral blood stem cells (PBSC) mobilized with high-dose consolidation chemotherapy and granulocyte colony-stimulating factor in patients with acute myelogenous leukemia (AML). Twenty patients received myeloablative chemotherapy or chemo-radiotherapy including total body irradiation followed by the infusion of PBSC. PBSC were collected by large-volume leukaphereses. The mean number of mononuclear cells and CD34-positive cells infused were 7.2 x 10(8)/kg (range, 2.2-16.6), and 6.6 x 106/kg (range, 2.1-27.7), respectively. Engraftment failure was not seen in the enrolled patients. The median time to neutrophil (> or = 500/microL) and platelet recovery (> or = 50,000/microL) from the transplant was 12 days (range, 8-20) and 28 days (range, 10-600), respectively. The 2-year probability of disease-free survival (DFS) and relapse were 43% and 57% for patients with AML transplanted in first complete remission (CR1). The outcome of the patients transplanted in the advanced status was significantly worse than the patients transplanted in CR1 (P=0.04). Most relapses occurred within 1 year after transplantation. Fatal hepatic veno-occlusive disease was observed in one case. Other transplantation-related toxicities were mild. Our results demonstrated that autologous transplantation of high-dose consolidation chemotherapy-mobilized peripheral blood progenitor cells is feasible in the patients with AML in CR1. To further reduce the risk of leukemia relapse, much effort should be contributed to the field of ex vivo purging and post-transplant immunotherapy.
Adult
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Female
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Hematopoiesis
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Hematopoietic Stem Cell Mobilization*
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Hematopoietic Stem Cell Transplantation*/adverse effects
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Human
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Leukemia, Myelocytic, Acute/therapy*
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Leukemia, Myelocytic, Acute/mortality
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Male
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Middle Age
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Transplantation, Autologous
2.Retrospective Analysis of Peripheral Blood Stem Cell Transplantation for the Treatment of High-Risk Neuroblastoma.
Eun Kyung KIM ; Hyoung Jin KANG ; Jeong Ah PARK ; Hyoung Soo CHOI ; Hee Young SHIN ; Hyo Seop AHN
Journal of Korean Medical Science 2007;22(Suppl):S66-S72
Disease relapse after autologous peripheral blood stem cell transplantation (APBSCT) is the main cause of treatment failure in high-risk neuroblastoma (NBL). To reduce relapse, various efforts have been made such as CD34+ selection and double APBSCT. Here the authors reviewed the clinical features and outcomes of highrisk NBL patients and analyzed their survival. The medical records of 36 patients with stage III or IV NBL who underwent APBSCT at Seoul National University Children's Hospital between May 1996 and May 2004 were reviewed. Total 46 APBSCTs were performed in 36 patients. Disease free survival (DFS) and overall survival of all patients were 47.7% and 68.8%, respectively. The patients were allocated to three groups according to the APBSCT type. The DFS of CD34+ non-selected single APBSCT patients (N=13), CD34+ selected single APBSCT patients (N=14), and CD34+ selected double APBSCT patients (N=9) were 55.6%, 40.6%, and 50.0%, respectively, which were not significantly different. Thus the survival was not found to be affected by CD34+ selection or transplantation number. To improve long-term survival, various efforts should be made such as chemotherapy dose intensification, more effective tumor purging, and control of minimal residual disease via the use of differentiating and immune-modulating agents.
Antigens, CD34/metabolism
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Child
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Child, Preschool
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Disease-Free Survival
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Female
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Hematopoietic Stem Cell Mobilization
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Humans
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Infant
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Korea/epidemiology
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Male
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Neuroblastoma/mortality/*therapy
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Peripheral Blood Stem Cell Transplantation/adverse effects/mortality
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Prognosis
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Retrospective Studies
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Survival Rate
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Transplantation Conditioning
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Transplantation, Autologous
3.Recent advances in treatment of aplastic anemia.
Seung Hwan SHIN ; Sung Eun LEE ; Jong Wook LEE
The Korean Journal of Internal Medicine 2014;29(6):713-726
Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.
Anemia, Aplastic/blood/diagnosis/mortality/*therapy
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Humans
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Immunosuppressive Agents/adverse effects/*therapeutic use
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Iron Chelating Agents/adverse effects/*therapeutic use
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Risk Factors
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*Stem Cell Transplantation/adverse effects/mortality
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Survival Analysis
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Time Factors
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Treatment Outcome
4.Selected CD34+ cell autologous transplantation for advanced malignant tumors.
Lu-jia DONG ; Hu CHEN ; Min JIANG ; Liang-ding HU ; Mao-quan QIN ; Wei-jing ZHANG ; Zhi-yong YU ; Shi-kai WU ; Xi-lin CHEN ; Yun-hua BAO ; San-tai SONG ; Duan-qi LIU
Chinese Journal of Oncology 2003;25(2):183-185
OBJECTIVETo determine the clinical results of selected CD34(+) cell autologous transplantation in advanced malignant tumors.
METHODSAfter pretreatment, fifteen patients aged 12 - 70 (49.5) years with various Stage III or IV malignant tumors were given the sorted CD34(+) cells collected by magnetic-activated cell sorting (Clini MACS, Milteny Biotech, Germany).
RESULTSPeripheral blood progenitor cells (PBPC) from the patients were mobilized by chemotherapy and G-CSF 5 micro g/kg per day. CD34(+) cells gave 2.0 - 5 log depletion after cell sorting, with a median yield of CD34(+) selected cells of 2.4 (0.15 - 12.03) x 10(6)/kg. It gave a median recovery of 64 (52 - 81.4)% and median purity of 98.2 (83.2 - 99.7)%. The median time of neutrophil recovery > 1.0 x 10(9)/L and platelet recovery > 20 x 10(9)/L post-transplantation were 14 (8 - 26) days and 13 (11 - 35) days, respectively. On follow-up of 2 - 33 (11) months, the event-free survival rate was 53.3% (8/15) and the overall survival rate was 66.7% (10/15).
CONCLUSIONTransplantation of autologous selected PBPC CD34(+) cells gives prompt and stable engraftment. Selected CD34(+) cell transplantation, being a safe approach, may improve the clinical outcome even in patients with advanced malignant tumors.
Adolescent ; Adult ; Aged ; Antigens, CD34 ; analysis ; Child ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Neoplasms ; mortality ; therapy ; Survival Rate ; Transplantation, Autologous
5.Hematopoietic Stem Cell Transplantation in Children with Leukemia: A Single Institution Experience with Respect to Donors.
Hee Jo BAEK ; Hoon KOOK ; Dong Kyun HAN ; Tai Ju HWANG
Journal of Korean Medical Science 2011;26(12):1548-1555
Aim of this study was to compare the outcomes of transplantation by donor source and to help select the best alternative donor in children with leukemia. Donor sources included matched related donor (MRD, n = 35), allele-matched unrelated donor (M-UD, n = 10) or -mismatched (MM)-UD (n = 13) or unrelated umbilical cord blood (UCB, n = 11). UCB group had a significantly higher incidence of grade II-IV acute graft versus host disease (MRD, 11.8%; M-UD, 30.0%; MM-UD, 15.4%, UCB, 54.4%, P = 0.004) but there was no difference in incidence of chronic graft versus host disease between 4 groups. The 5-yr leukemia-free survival (LFS) was 76.7%, 60.0%, 69.2%, and 45.5%, respectively (P = 0.128). MRD group showed higher LFS rate than UCB group (P = 0.022). However, LFS of M-UD and MM-UD together (65.2%) was not different from that of MRD group (76.7%, P = 0.325), or from that of UCB (45.5%, P = 0.190). The relapse incidence at 5 yr was 17.1%, 20.0%, 15.4%, and 0%, respectively (P = 0.460). The 100-day treatment-related mortality was 2.9%, 20.0%, 7.7%, and 36.4%, respectively (P = 0.011). Despite the limitations of small number of patients, unrelated donor transplants including even allele-mismatched ones, seem to be as effective in children with leukemia lacking suitable relative donors. Also, UCB transplant may serve as another possible option in urgent transplants.
Adolescent
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Child
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Child, Preschool
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*Cord Blood Stem Cell Transplantation/adverse effects/methods
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Disease-Free Survival
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Female
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Fetal Blood/transplantation
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Graft vs Leukemia Effect
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*Hematopoietic Stem Cell Transplantation/adverse effects/methods/mortality
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Histocompatibility Testing
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Humans
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Infant
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Leukemia/mortality/*therapy
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Male
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Transplantation, Homologous
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Treatment Outcome
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Unrelated Donors
6.A novel approach to human leukocyte antigen-mismatched transplantation in patients with malignant hematological disease.
Xiao-jun HUANG ; Wei HAN ; Lan-ping XU ; Yu-hong CHEN ; Dai-hong LIU ; Jin LU ; Huan CHEN ; Yao-chen ZHANG ; Qian JIANG ; Kai-yan LIU ; Dao-pei LU
Chinese Medical Journal 2004;117(12):1778-1785
BACKGROUNDMany patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) do not have an human leukocyte antigen (HLA)-matched donor. Alternative donors, such as HLA mismatched family donors, are associated with higher rates of graft rejection and acute graft versus host disease (aGVHD) if T cells are not first depleted. We developed a new technique for HLA mismatched allogeneic HSCT using G-CSF primed bone marrow plus G-CSF-mobilized peripheral blood stem cells without ex vivo T cell depletion.
METHODSIn this study, 58 patients, including 33 with high-risk or advanced leukemia, were transplanted with cells from an HLA-haploidentical family donor with 1 - 3 mismatched loci. After conditioning, patients received G-CSF-primed bone marrow grafts that had not been depleted ex vivo of T cells, in combination with G-CSF-mobilized peripheral blood stem cells, as well as GVHD prophylaxis.
RESULTAll patients achieved sustained, full donor-type engraftment. The incidence of grade II-IV aGVHD was 37.9%, including 3 patients with grade III-IV aGVHD. The development of aGVHD was not associated with the extent of HLA disparity. Chronic GVHD was observed in 30 of 51 evaluable patients (65.4%). Fourteen patients died among whom 7 died of recurrent disease and 7 of transplant-related complications. Forty-four of the 58 patients survived, and 42 remained disease free at the time of a median follow-up of 12 months (3.5 to 39.5 months). The 2-year probabilities of disease-free survival were 74.8% and 69.3% for standard- and high-risk patients, respectively.
CONCLUSIONWe developed a new method to use bone marrow from haploidentical family donors without ex vivo T cell depletion, in combination with G-PBSCs, as a source of stem cells even in cases of HLA mismatched transplantation.
Adolescent ; Adult ; Child ; Female ; Graft vs Host Disease ; etiology ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematologic Neoplasms ; mortality ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; mortality ; Histocompatibility Testing ; Humans ; Male ; Middle Aged ; Recurrence ; Transplantation Conditioning ; Transplantation, Homologous
7.A preliminary study on the treatment of severe autoimmune disease by autologous peripheral CD(34)(+) cell transplantation.
Dao-bin ZHOU ; Yan ZHAO ; Shu-jie WANG ; Tai-sheng LI ; Jie-ping ZHANG ; Yong-qiang ZHAO ; Yun DUAN ; Feng-chun ZHANG ; Fu-lin TANG ; Lian-jun BAI ; Wei CUI ; Pei WU ; Fu-quan ZHANG ; Ti SHEN
Chinese Journal of Hematology 2003;24(9):460-463
OBJECTIVETo evaluate the feasibility of autologous peripheral CD(34)(+) cell transplantation for the treatment of severe autoimmune disease.
METHODSTen patients received mobilized and purified CD(34)(+) cells transplantation. The mobilization regimen was CTX plus rhG-CSF and the CD(34)(+) cells were selected by CliniMACS. (1.98 +/- 0.95) x 10(8) CD(34)(+) cells were obtained. The purity of CD(34)(+) cells was (91.4 +/- 10.6)% and the recovering rate was (60.5 +/- 19.8)%. The conditioning regimens were CTX (200 mg/kg) plus ATG (90 mg/kg) or CTX (150 mg/kg) plus TBI (4 - 6 Gy). (2.14 +/- 1.05) x 10(6)/kg CD(34)(+) cells were infused. The time of ANC >or= 0.5 x 10(9)/L was 8.6 +/- 2.5 days, and platelet >or= 20 x 10(9)/L was 9.0 +/- 5.2 days. After the hematopoietic recovery, the levels of CD(3)(+) T cell, CD(19)(+) B cells and CD(16)(+)CD(56)(+) NK cells were all below that of pre-transplantation. The main transplant-related complication was CMV infection. The transplant-related mortality was 2/10. All patients who survived showed improvement of the disease with DAI score decreasing from 17 to 4 in systemic lupus erythematosus patients, DAS 28 score from 6.4 to 1.8 in rheumatoid arthritis patients.
CONCLUSIONThe result suggests that autologous peripheral CD(34)(+) cell transplantation is an alternative choice for the treatment of severe autoimmune disease. The short-term outcome is satisfying.
Adolescent ; Adult ; Antigens, CD34 ; analysis ; Autoimmune Diseases ; immunology ; therapy ; Female ; Hematopoiesis ; Hematopoietic Stem Cell Mobilization ; Humans ; Immune Tolerance ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; adverse effects ; mortality ; Transplantation, Autologous
8.Clinical effect of umbilical cord blood transplantation in 37 pediatric patients with hematologic malignancies: a single-center experience.
Zuo LUAN ; Xiang-Feng TANG ; Nan-Hai WU ; Shi-Xia XU ; Bo ZHANG ; Kai WANG ; Hong DU
Chinese Journal of Contemporary Pediatrics 2014;16(7):714-719
OBJECTIVETo evaluate the clinical effect of umbilical cord blood transplantation (UCBT) in children with hematologic malignancies.
METHODSA retrospective analysis was performed on the clinical data of 37 pediatric patients with hematologic malignancies that consisted of 14 cases of acute lymphocyte leukemia, 9 cases of acute myeloid leukemia, 5 cases of juvenile myelomonocytic leukemia, 3 cases of chronic myeloid leukemia, 2 cases of acute mixed leukemia, 3 cases of myelodysplastic syndrome, and 1 case of lymphosarcomatous leukemia. Thirty-seven children with hematologic malignancies received UCBT from unrelated donors (34 cases) and related donors (3 cases). Grafts were 6/6 HLA-matched in 5 cases, 5/6 HLA-matched in 12 cases, 4/6 HLA-matched in 11 cases, and 3/6 HLA-matched in 9 cases. Before transplantation, these patients received rabbit antithymocyte globulin-containing conditioning regimen. The myeloablative conditioning regimen was given in 36 cases and the reduced-intensity conditioning regimen in one case. The median age of transplantation was 5.7 years, and the median weight was 20 kg. The grafts that contained a median of 6.2×10(7) total nucleated cells (TNC)/kg and 2.7×10(5) CD34(+) cells/kg were infused.
RESULTSThe median times to neutrophil engraftment and platelet engraftment were 12 days and 25 days, respectively, and the rates of neutrophil engraftment and platelet engraftment were 95% and 78%, respectively. The rate of neutrophil engraftment was positively correlated with the number of CD34(+) cells (P=0.011), while the rate of platelet engraftment was correlated with the numbers of CD34(+) cells and TNC (P=0.001; P=0.014). The incidence rates of acute and chronic graft-versus-host disease were 49% and 11%, respectively. The median follow-up was 54 months. The 5-year transplant-related mortality, overall survival, and disease-free survival were 27%, 57.4% and 41%, respectively.
CONCLUSIONSUCBT is an alternative source of hematopoietic stem cells for patients with hematologic malignancies.
Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; adverse effects ; Female ; Follow-Up Studies ; Graft vs Host Disease ; epidemiology ; Hematologic Neoplasms ; mortality ; therapy ; Humans ; Infant ; Male ; Retrospective Studies
10.Umbilical cord blood transplantation for patients with beta-thalassemia major.
Xin SUN ; Sha LIU ; Wen-ge HAO ; Zhan-xi CHEN ; Nai-lan GUO
Chinese Journal of Pediatrics 2005;43(3):178-182
OBJECTIVEThe beta-thalassemia major is a common hereditary hematology disease in southern China. The combination of blood transfusion and iron chelation is now the reference treatment. The allogeneic hematopoietic stem cell transplantation is the only curative therapy for beta-thalassemia major. In this study the investigators observed and evaluated the effects of umbilical cord blood transplantation (UCBT) for patients with beta-thalassemia major.
METHODSTwelve cases of beta-thalassemia major aged from 1.3 to 8.3 years (8 male and 4 female) received UCBT. Eleven of the twelve donors were siblings and one was unrelative. Eight patients received no antigen and four patients received two antigen disparate grafts. According to the Pesaro's classification for thalassemia, 10 patients were at grade I or II, and 2 were at grade III. The HLA-identical patients accepted the conditioning regimen consisting of busulfan, cyclophosphamide and antithymocyteglobulin. The HLA-mismatched patients accepted the conditioning regimen consisting of hypertransfusions, continuous iv desferrioxamine, hydroxyurea, fludarabine, busulfan, cyclophosphamide and antithymocyteglobulin. The harvest stem cells contained 3.63 - 16.0 x 10(7)/kg of nucleated cells, 0.11 - 1.03 x 10(6)/kg of CD(34)(+) cells and 0.17 - 1.18 x 10(5)/kg of colony-forming-unit-granulocyte macrophages. Cyclosporine alone or in combination with mycophenolate mofetil (MMF) was given for acute graft-versus-host disease (aGVHD) prophylaxis.
RESULTSOf the 12 patients, 10 were engrafted. Ten patients had neutrophil recovery (> 0.5 x 10(9)/L) and seven patients had platelet recovery (> 50 x 10(9)/L). The median time was 18.1 and 57.3 days, respectively. Seven patients had disease-free survival (DFS) at a median follow up of 23 months (range 4 - 63 months). Three patients had rejection and autologous hematopoitic reconstitution. Two patients were not engrafted. One patient acquired severe aplastic anemia, another patient died of severe infection. The incidences of grade I and grade II aGVHD were 60% (6/10) and 40% (4/10), respectively. There were no long-term complications in the disease free survivors.
CONCLUSIONSGrade I-II beta-thalassemia major patients receiving sibling UCBT had high DFS. UCBT is an effective way to treat beta-thalassemia major.
Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; adverse effects ; Female ; Graft vs Host Disease ; epidemiology ; Hematopoiesis ; Humans ; Infant ; Male ; beta-Thalassemia ; mortality ; therapy