Haploidentical haematopoietic stem cell transplantation for malignant infantile osteopetrosis and intermediate osteopetrosis: a retrospective analysis of a single centre

Abstract

Objective To evaluate the clinical efficacy of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) for the treatment of malignant infantile osteopetrosis (MIOP) and intermediate osteopetrosis. Methods Children with MIOP and IOP who underwent haplo-HSCT in Beijing Children’s Hospital, Capital Medical University, from January 2010 to May 2018 were retrospectively analysed. Data relating to the clinical manifestations, engraftment, and prognosis of the children were extracted from medical records. Results Twenty-seven patients, including 18 males and 9 females, with an onset age of 12 (0.04–72) months were enrolled in this study. The median time from diagnosis to transplantation was 4 (1–23) months. All patients received haplo-HSCT with a myeloablative conditioning regimen (including fludarabine, busulfan, and cyclophosphamide). Graft versus host disease (GVHD) prophylaxis was based on anti-human T lymphocyte porcine immunoglobulin/anti-human thymus globulin, methotrexate, and mycophenolate mofetil. The median observation time was 55.2 (0.3–126.2) months. By the end of follow-up, twenty patients survived and seven patients died. The 5 year overall survival rate was 73.9%. Stage I-II acute GVHD was observed in 20 patients, stage III GVHD in 1 patient and no patients had stage IV disease. Chronic GVHD was observed in 11 patients (40.7%) and was controlled by anti-GVHD therapy. Conclusions Haplo-HSCT was an effective treatment for MIOP and IOP, with a high survival rate and significantly improved clinical symptoms. For patients with a vision impairment before HSCT, the improvement was slow after transplantation. The incidence of GVHD was high but mild and was effectively controlled by appropriate treatment. These data indicated that haplo-HSCT was a feasible treatment for MIOP and IOP.

Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation

“…The optimal balance between treatment benefits (immunological and kidney protective) and risks (infections) of the typical lymphocyte-depleting antibody rATG still remains to be properly elucidated. pALG has been already used in the hematology and transplantation fields ( 20 , 23 ), and offers an appropriate option to build an individualized induction therapy based on relevant immunological characteristics.…”

“…pALG has been successfully used as first-line treatment in acquired severe aplastic anemia ( 20 – 22 ). It has also been employed for other hematological indications such as graft versus host disease prophylaxis ( 23 ). Meanwhile, pALG has been used in transplantation including hematopoietic stem cell transplantation ( 19 , 24 , 25 ) and kidney transplantation ( 26 ).…”

Bone marrow transplantation as a therapy for autosomal dominant osteopetrosis type 2 in mice

“…Importantly, due to recent developments in the transplantation schemes, the survival rate of patients who undergo BMT therapy improved significantly as high as 75%-100% depending on the age of the recipient, use of the conditioning regimens, the degree and identity of the donor and transplantation centers where this procedure was performed. [23][24][25][26] As the patients usually suffer from related complications of hematopoietic cell transplants, 15,16 this still remains a critical issue for the overall outcome of the transplantation. However, ADO2 patients who might be candidates for this risky procedure are those who are transfusion dependent or suffer from complications of multiple progressive pathological fractures, and severe osteomyelitis and, therefore, the quality of life is severely compromised.…”

“…Ultimately, if this approach works, the functioning osteoclasts and normal hematopoiesis will assist in the resolution of the abnormal bone phenotype or at least decrease the disease severity of ADO2. Importantly, due to recent developments in the transplantation schemes, the survival rate of patients who undergo BMT therapy improved significantly as high as 75%–100% depending on the age of the recipient, use of the conditioning regimens, the degree and identity of the donor and transplantation centers where this procedure was performed 23–26 . As the patients usually suffer from related complications of hematopoietic cell transplants, 15,16 this still remains a critical issue for the overall outcome of the transplantation.…”

Assessing the Efficacy of Alkylating Agent Regimens in the Treatment of Infantile Malignant Osteopetrosis: Cyclophosphamide, Busulfan, or Thiotepa

“…With a weak immune system, patients are more susceptible to infections, diseases, and cancer. Another danger that claims the lives of over 10% of HCT patients is graft vs host disease (GVHD), a reaction between residual host cells and transplanted cells [5,6]. There are many factors that must be considered for this treatment plan to be successful and to cure infants from IMO.…”