关键词: 干细胞, 移植, 造血干细胞, 脐带间充质干细胞, 再生障碍性贫血, 单倍体相合移植, 非血缘

Abstract:

BACKGROUND: It is fatal for children with acute severe aplastic anemia undergoing failed first allogeneic. If there are secondary lymphoma and other complications, treatment is more difficult. Up to now, there is yet no feasible treatment.
OBJECTIVE: To investigate the possibility and safety of second haploidentical hematopoietic stem cell transplantation because of the failure in the first unrelated blood transplantation and secondary lymphoma.
METHODS: A 3-year-old boy with severe aplastic anemia underwent HLA 8/10 matched unrelated peripheral blood stem cell transplantation on November 25, 2011. There was a major ABO mismatch. The time of neutrophil exceeding 0.5×109/L and platelets recovery exceeding 20×109/L were 11 and 14 days, respectively after transplantation. Bone marrow aspiration showed normal while full donor engraftment was found by chromosomal analyses on day 30. Grade I graft-versus-host disease occurred after 35 days. Autoimmune hemolytic anemia and pure red cell aplasia were also diagnosed on day +54. He was given high-dose gamma globulin, erythropoietin and glucocorticoids, and autoimmune hemolytic anemia and pure red cell aplasia were controlled. Unfortunately, on day +90, the boy suffered from fever and superficial lymph nodes of the bilateral neck. B ultrasound-guided needle biopsy was done on the right cervical lymph nodes, and post transplant lymphoproliferative disorder was considered. Pathological examination showed diffuse large B-cell lymphoma. Managements for patients consisted of withdrawal of immunosuppressive treatment and application of rituximab plus chemotherapy. After treatment, the lymph node shrank, Epstein-Barr virus copy number was decreased, and the body temperature recovered. However, on day +150, blood routine examination and bone marrow aspiration showed transplant failure. Then, the boy received the second haploidentical stem cell transplantation on May 15, 2012. The donor was his father. A myloablative condition regimen was selected: high-dose fludarabine+cyclosphosphamide+ busulfan+mitoxantrone+anti-CD52 monoclonal antibody. Hematopoietic stem cells and mesenchymal stem cells were re-infused simultaneously. Prophylaxis strategy for graft-versus-host disease consisted of cyclosporine A +short-term methotrexate+CD25 monoclonal antibody combined with mycophenolate mofetil. Nucleated cells and CD34+ cells were re-infused at a dose of 13.52×108/kg and 2.45×106/kg, respectively. The follow-up time was 24 months after transplantation.
RESULTS AND CONCLUSION: After second implantation, the time of neutrophil exceeding 0.5×109/L and platelets recovery exceeding 20×109/L was 14 and 30 days, respectively. DNA test showed full donor engraftment was found. The swollen lymph nodes shrank after pretreatment, but tended to be enlarged at 2 months after surgery. After withdrawal of immunosuppressor and local radiotherapy, the lymph node shrank stably. PET showed no obvious area with presence of metabolic abnormalities. Regular follow-up every 6 months after transplantation has showed that the body has normal life and goes to school. Results suggest that the co-transplantation of haploidentical hematopoietic stem cells and mesenchymal stem cells is safe and effective for treatment of severe aplastic anemia following the failure of first transplantation. Pretreatments can faster hematopoietic recovery and control graft-versus-host disease, which is worth further clinical research.

Key words: hematopoietic stem cell transplantation, umbilical cord, mesenchymal stem cell transplantation, anemia, aplastic