BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Humans ; Fetal Blood ; Hematopoietic Stem Cell Transplantation ; Transplantation, Homologous ; Anemia ; Cord Blood Stem Cell Transplantation/methods* ; Graft vs Host Disease

Objective: To investigate the risk factors and outcomes of cytomegalovirus (CMV) infection post umbilical cord blood stem cell transplantation (UCBT) in children with primary immunodeficiency diseases (PID). Methods: Clinical data of 143 PID children who received UCBT in the Children's Hospital of Fudan University from January 2015 to June 2020 were collected retrospectively. CMV-DNA in the plasma was surveilled once or twice a week within 100 days post-UCBT. According to the CMV-DNA test results, children were divided into the CMV-infected group and the CMV-uninfected group. The incidence and risk factors of CMV infection were analyzed. At 1-month post-UCBT, the absolute lymphocyte count, ratio of lymphocyte subsets and immunoglobulin levels were compared between those whose CMV infection developed 1-month later post-UCBT and those not. Mann-Whitney U test and chi-squared test were used for comparision between groups. Kaplan-Meier survival analysis was used to analyze the impact of CMV infection on survival. Results: Among 143 patients, there were 113 males and 30 females, with a age of 14 (8, 27) months at UCBT. Chronic granulomatosis disease (n=49), very-early-onset inflammatory bowel disease (n=43) and severe combined immunodefiency (n=29) were the three main kinds of PID. The rate of CMV infection was 21.7% (31/143), and the time of infection occurring was 44 (31, 49) days post-UCBT. The incidence of recurrent CMV infection was 4.2% (6/143) and refractory CMV infection was 4.9% (7/143).There was no significant difference in the first time CMV-DNA copy and peak CMV-DNA copy during treatment between the recurrent CMV infection group and the non-recurrent CMV infection group (32.8 (18.3, 63.1)×10⁶ vs. 22.5 (13.2, 31.9)×10⁶ copies/L, Z=-0.95, P=0.340;35.2 (20.2, 54.6)×10⁶ vs. 28.4 (24.1, 53.5)×10⁶copies/L, Z=-0.10, P=0.920), so were those between the refractory CMV infection group and non-refractory CMV infection group (21.8 (13.1, 32.2)×10⁶ vs. 25.9 (14.2, 12.2)×10⁶copies/L, Z=-1.04, P=0.299; 47.7 (27.9, 77.6)×10⁶ vs. 27.7 (19.7,51.8)×10⁶copies/L, Z=-1.49, P =0.137). The CMV-infected group accepted more reduced-intensity conditioning (RIC) regimen than the CMV-uninfected group (45.2% (14/31) vs. 25.0% (28/112), χ²=4.76, P<0.05). The rate of CMV-seropositive recipients and Ⅱ-Ⅳ acute graft versus host diseases (aGVHD) are significantly higher in the CMV-infected group than the CMV-uninfected group (100% (31/31) vs. 78.6% (88/112), 64.5% (20/31) vs. 26.8% (30/112), χ²=7.98,15.20, both P<0.05). The follow-up time was 31.6 (13.2, 45.9) months, CMV infection had no effect on overall survival (OS) rate (χ²=0.02, P=0.843). There was significant difference in the survival rate among three groups of refractory CMV infection, non-refractory CMV infection and the CMV-uninfected (4/7 vs.95.8% (23/24) vs. 86.6% (97/112), χ²=5.91, P=0.037), while there was no significant difference in the survival rate among three groups of recurrent CMV infection, non-recurrent CMV infection and the CMV-uninfected (5/6 vs. 88.0% (22/25) vs. 86.6% (97/112), χ²=0.43, P=0.896). Children who developed CMV infection after 30 days post-UCBT had lower absolute count and rate of CD4⁺ T cells and immunoglobulin G (IgG) level than those in the CMV-uninfected group (124.1 (81.5, 167.6) ×10⁶ vs. 175.5 (108.3, 257.2) ×10⁶/L, 0.240 (0.164, 0.404) vs. 0.376 (0.222, 0.469), 9.3 (6.2, 14.7) vs. 13.6 (10.7, 16.4) g/L, Z=-2.48, -2.12,-2.47, all P<0.05), but have higher rate of CD8⁺T cells than those in CMV-uninfected group (0.418 (0.281, 0.624) vs. 0.249 (0.154, 0.434), Z=-2.56, P=0.010). Conclusions: RIC regimen, grade Ⅱ-Ⅳ aGVHD and CMV-seropositive recipients are the main risk factors associated with CMV infection in PID patients post-UCBT. Survival rate of children with refractory CMV infection after UCBT is reduced. Immune reconstitution in children after UCBT should be regularly monitored, and frequency of CMV-DNA monitoring should be increased for children with delayed immune reconstitution.
Child ; Cord Blood Stem Cell Transplantation/adverse effects* ; Cytomegalovirus ; Cytomegalovirus Infections/etiology* ; DNA ; Female ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Immunoglobulin G ; Infant ; Male ; Primary Immunodeficiency Diseases ; Prognosis ; Retrospective Studies ; Risk Factors

Child ; Cord Blood Stem Cell Transplantation ; Hematopoietic Stem Cell Transplantation ; Humans ; Primary Myelofibrosis/therapy* ; Thiotepa ; Transplantation Conditioning

OBJECTIVE: To study the association of different maternal and infant factors with the number of total nucleated cells and CD34 METHODS: A prospective study was performed for the umbilical cord blood samples of 130 neonates who were born in Dalian Women and Children's Medical Center from June 2019 to January 2020, with a male/female ratio of 1:1. Related perinatal information was collected, including maternal age and blood type, presence or absence of gestational diabetes or gestational hypertension, pregnancy method, mode of delivery, singleton pregnancy/twin pregnancy, body weight and sex of neonates, Apgar score after birth, and the conditions of placenta, amniotic fluid, and umbilical cord. RESULTS: The neonates were grouped according to maternal blood type, gestational diabetes, gestational hypertension, pregnancy method, mode of delivery, singleton pregnancy/ twin pregnancy, sex of neonates, Apgar score after birth, placental morphology, meconium staining of amniotic fluid, and umbilical cord around the neck. The comparison between groups showed no significant differences in the numbers of total nucleated cells and CD34 CONCLUSIONS The number of CD34
Antigens, CD34 ; Female ; Fetal Blood ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Infant ; Infant, Newborn ; Male ; Pregnancy ; Prospective Studies ; Umbilical Cord

OBJECTIVE: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Juvenile myelomonocytic leukemia (JMML). METHODS: The clinical data of 5 children with JMML who were treated with unrelated UCBT from October 2011 to July 2019 were retrospectively analyzed. The age of onset for the five children (male) ranged from 0.4 to 5.0 years old, with a median age of 1.5 years old. All the patients received myeloablative conditioning regimen without ATG to whom cyclosporine A (CsA) with short-term mycophenolate mofetil (MMF) was given for GVHD prophylaxis. RESULTS: Four children acquired engraftment. One patient received secondary haploidentical hematopoietic stem cell transplantation because of the failure in the first unrelated UCBT. Grade Ⅲ to Ⅳ aGVHD occurred in 2 cases and was controlled, and none of the patients developed cGVHD. Three cases achieved long-time disease free survival，and no patient relapsed. CONCLUSION UCBT is an effective treatment for children with JMML.
Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Leukemia, Myelomonocytic, Juvenile ; Male ; Retrospective Studies ; Transplantation Conditioning

Abstract　　Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells (HSCs) for patients who were lack of HLA match related or unrelated donors. Compared with bone marrow and mobilized peripheral blood, UCB has the advantages of easy availability, safety for donors, and low requirement for HLA match between donors and recipients. However, the cell amount in UCB is relatively less, which was associated with increased graft failure, delayed hematologic recovery, immune reconstitution, and higher transplant related mortality after UCB transplantation (UCBT). Double-unit UCB is a straightforward method to augment cell amount in UCB. Compared with single-unit UCBT, double-unit CBT associated with less risk of primary disease relapse and increased incidence rate of graft-versus-host disease (GVHD), but the hematologic recovery and overall survival of recipients were no significantly difference between single and double-unit UCBT. Novel strategies for UCB expansion significantly increased the cell amount in UCB, single-unit expanded UCBT not only increased the sources of UCB, but also decreased the high cost of double-unit UCB. ATG can decrease the risk of graft failure and GVHD rate, but the role of ATG in UCBT is still controversial. Herein, the recent clinical advances on UCBT in the treatment of hematologic diseases are systematically reviewed.
Cord Blood Stem Cell Transplantation ; Graft vs Host Disease ; Hematologic Diseases ; Hematopoietic Stem Cell Transplantation ; Humans ; Unrelated Donors

Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.
Adolescent ; Adult ; Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; Female ; Graft vs Host Disease ; HLA Antigens ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Receptors, KIR ; Retrospective Studies ; Young Adult

OBJECTIVE: To investigate the clinical efficacy of haploid hematopoietic stem cells (haplo-HSC) combined with third-party umbilical cord blood (tpCB) transplantation in the treatment of X-linked chronic granulomatous disease (X-CGD). METHODS: The clinical data of 26 boys with X-CGD were retrospectively analyzed who were admitted to the Sixth Medical Center of PLA General Hospital between April 2014 and March 2018. All the patients were treated with haplo-HSC combined with tpCB transplantation. The median age of the patients was 3.5 years. The donor was the father in 25 cases and an aunt in 1 case. Transplantation was 5/6 HLA-matched in 9 cases, 4/6 in 12 cases, and 3/6 in 5 cases. The patients received busulfan, cyclophosphamide, fludarabine, or anti-thymocyte globulin for myeloablative preconditioning. Cyclosporine A and mycophenolate mofetil were used for prevention of acute graft-versus-host disease (aGVHD). Then the patients were treated with haploid bone marrow hematopoietic stem cells combined with tpCB transplantation on day 1 and haploid peripheral hematopoietic stem cells on day 2. The counts of median donor total nucleated cells, CD34 cells, and CD3 cells were 14.6×10/kg, 5.86×10/kg, and 2.13×10/kg respectively. RESULTS: The median time to neutrophil and platelet engraftment was 12 and 23 days after transplantation respectively. Full donor hematopoietic chimerism was observed on day 30. Twenty-five cases were from haplo-HSC and 1 was from cord blood. No primary implant failure and implant dysfunction occurred, and secondary implant failure occurred in one case. The NADPH oxidase activity returned to normal one month after transplantation. The incidence of grade I-II aGVHD and grade III-IV aGVHD was 35% and 15% respectively. Chronic GVHD (cGVHD) of the skin occurred in one case, and no progression was observed after steroid administration. During the follow-up period of 6-51 months, 25 patients survived, of whom 24 were disease-free (23 patients without cGVHD and 1 with cGVHD of the skin) and NADPH oxidase activity returned to normal; one patient developed secondary implant failure but survived; one patient died of viral interstitial pneumonia 16 months after transplantation. The 5-year event-free survival rate and overall survival rate were 81%±12% and 89%±10% respectively. CONCLUSIONS Haplo-HSC combined with tpCB transplantation is one of the effective methods for the treatment of X-CGD in children.
Child, Preschool ; Cord Blood Stem Cell Transplantation ; Graft vs Host Disease ; Granulomatous Disease, Chronic ; Haploidy ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Male ; Retrospective Studies ; Transplantation Conditioning

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