ABSTRACT
Objective:To evaluate the efficacy of allogeneic hematopoietic cell transplantation(allo-HSCT) using unrelated cord blood or haploidentical donors in the treatment of children with primary immunodeficiency diseases (PID).Methods:The clinical data of 60 children with PID admitted to Chinese People′s Liberation Army General Hospital-Sixth Medical Center from April 2014 to October 2019 were retrospectively analyzed, including 56 cases of chronic granulomatous disease, 2 cases of severe combined immunodeficiency disease, 1 case of high-IgM syndrome and 1 case of severe congenital neutropenia.All patients underwent allo-HSCT, including 12 cases receiving the transplantation from unrelated cord blood (UCB group) and 48 cases from haploidentical donors combined with a third party unrelated cord blood (haploid group). Among these patients, there were 59 males and 1 female, with a median age of 3.4 years.All patients received a myeloablative conditioning regimen based on Busulfan.The prophylaxis of acute graft versus host disease (aGVHD) was performed based on Cyclosporine.In the UCB group, the median dose of mononuclear cells and CD 34+ cells was 0.67×10 8/kg and 0.51×10 6/kg recipient body weight, respectively; In the haploid group, bone marrow and peripheral stem cells from haploid donors were infused on day 01 and day 02, respectively.The third party cord blood was infused 4 hours before bone marrow infusion.The median dose of mononuclear cells and CD 34+ cells of bone marrow and peripheral stem cells from haploid donors was 9.97×10 8/kg and 5.12×10 6/kg recipient body weight, respectively.Kaplan-Meier method was used to analyze the overall survival rate. Results:The median day to neutrophil and platelet engraftment was 13.0 days and 23.5 days, respectively.The rate of complete donor chime-rism was shown 30.0 days after transplantation.There was no case with primary engraftment failure, and 1 case with secondary engraftment failure.The incidence of grade Ⅰ-Ⅱ and grade Ⅲ-Ⅳ aGVHD was 43.3% and 15.5%, respectively.The incidence of chronic graft versus host disease with limited skin type was 6.7%, while that with extensive type was 1.1%.The median follow-up period was 818 days.There were 6 death cases, among which, 5 cases died from infection and 1 case died from heart failure.The total mortality related to transplantation was 11.9%.A total of 53 cases survived without diseases.The estimated 5-year failure free survival and overall survival rate was 83.9% and 88.1%, respectively.Conclusion:The efficacy of allo-HSCT in the treatment of children with PID using unrelated cord blood and haploidentical donors is favorable.
ABSTRACT
BACKGROUND: Allogeneic hematopoietic stem cell transplantation is still the only cure method for acquired severe aplastic anemia. How to select patients for treatment has become a research hotspot in recent years. OBJECTIVE: To review the progress of allogeneic hematopoietic stem cell transplantation from three aspects: HLA full-phase matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT), unrelated cord blood transplantation (UCBT) and haploidentical hematopoietic stem cell transplantation (HID-HSCT). METHODS: Literatures on allogeneic hematopoietic stem cell transplantation for severe aplastic anemia collected in PubMed, CNKI full-text database and WanFang database from 2000 to 2018 were retrieved with the keywords “unrelated donor; haploidentical; unrelated cord blood; severe aplastic anemia” in Chinese and English. RESULTS AND CONCLUSION: MSD-HSCT is the first-line treatment for severe aplastic anemia, but in view of China’s special national conditions, HLA matched donor is not easy to find. As an important alternative treatment, MUD-HSCT is close to MSD-HSCT. However, the incidence of graft versus host disease and severe infection after MUD-HSCT is still higher than that after MSD-HSCT. It is still necessary to consider multiple factors when choosing MUD-HSCT treatment. Umbilical cord blood hematopoietic stem cells are widely used because of their abundant sources and high match success rate. The probability of UCBT is very high when the amount of pre-frozen total nucleated cells is more than 3.9×107/kg. However, in view of the delay of UCBT and immune function reconstruction, unless other transplantation methods are not feasible in clinical treatment of severe aplastic anemia and immunosuppressive therapy fails in the first course of treatment, UCBT should not be considered. HID-HSCT has the advantages of easy access and good compliance of donors and is close to full-matched transplantation. It has become an important alternative to transplantation. The use of baliximab and/or antithymocyte globulin is expected to reduce the incidence of graft versus host disease and expand the clinical application of HID-HSCT.
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Objective To investigate the effect of unrelated cord blood transplantation (UCBT)on the treatment of high-risk childhood and adult acute leukemia.Methods Ten patients with high-risk acute leukemia underwent UCBT.Among the 1 0 patients,3 were children and 7 were adults with the median age of 29 years old (1 1 -41 years old).Six patients underwent one-unit cord blood transplantation and four patients underwent two-unit cord blood transplantation.The myeloablative conditioning regimen without antithymocyte globulin (ATG)was adopted.Cytarabine (Ara-C),fludarabine (Flu)or total body irradiation (TBI)was added on the basis of busulfan (Bu)and cyclophosphamide (Cy).Ciclosporin and mycophenolate mofetil were used to prevent graft-versus-host disease (GVHD).Results The transplantation was successful in 8 (80%) patients.The median implant-time of leukocytes was 1 9 d(1 4-25 d)and that of platelets was 40 d(33-60 d).Three patients developed acute GVHD and no patient developed chronic GVHD.The median follow-up time was 24 months (1 -29 months).Seven patients remained in disease-free survival.Both the 2-year overall survival and disease-free survival rates were 66.7%.Conclusions UCBT is feasible in the treatment of high-risk acute leukemia.UCBT is the preferred option for the high-risk patients without HLA-identical sibling donors,which is characterized by low incidence of GVHD and low recurrence rate.It may make patients with acute leukemia remain long-term survival.
ABSTRACT
We present two cases of Wiskott-Aldrich syndrome (WAS), in which nonsense mutations in the WASP gene were corrected phenotypically as well as genotypically by unrelated cord blood stem cell transplantation (CBSCT). Two male patients were diagnosed with WAS at the age of 5-month and 3-month and each received unrelated CBSCT at 16-month and 20-month of age, respectively. The infused cord blood (CB) units had 4/6 and 5/6 HLA matches and the infusion doses of total nucleated cells (TNC) and CD34+ cells were 6.24x10(7)/kg and 5.08x10(7)/kg for TNC and 1.33x10(5)/kg and 4.8x10(5)/kg for CD34+ cells, for UPN1 and UPN2, respectively. Complete donor cell chimerism was documented by variable number tandem repeat (VNTR) with neutrophil engraftment on days 31 and 13 and platelets on days 58 and 50, respectively. Immunologic reconstitution demonstrated that CBSCT resulted in consistent and stable T-, B-, and NK-cell development. Flow cytometric analysis for immunologic markers and sequence analysis of the WASP gene mutation revealed a normal pattern after CBSCT. These cases demonstrate that CBs can be an important source of stem cells for the phenotypical and genotypical correction of genetic diseases such as WAS.