Low Dose Splenic Irradiation as Adjunct Therapy for Patients With High Level of Anti-Human Leukocyte Antigen Donor-Specific Antibodies (Anti-HLA DSAs) Prior to Haploidentical Hematopoietic Stem Cell Transplantation (Haplo-HSCT)

Abstract

With the increasing numbers of haploidentical hematopoietic stem cell transplants (Haplo-HSCT), the roles affecting transplant outcomes of anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) are currently being evaluated. Patients with high levels of DSAs were desensitized with plasmapheresis, immunoglobulin and rituximab prior to transplantation. However, the therapies were not very effective, probably because the source of DSA production was not controlled effectively. Rescue splenectomy has been used with short-term success by establishing source control for the DSA-producing plasmablasts in renal transplantation patients. Splenic irradiation was also proved to be effective in these patients. Herein, we describe the first reported use of splenic irradiation as adjunct therapy for patients with high level of DSAs prior to haplo-HSCT.14 haplo-HSCT patients were involved, including 3 males and 11 females. The median age was 45 years (26-55). Before transplantation, 9 patients were tested positive of HLA-I DSA, and 6 patients were positive of HLA-II DSA, including 1 patient which was tested positive for both HLA-I and II. 12 patients were diagnosed with acute patients and were in complete remission before transplantation, and the other 2 patients with myelodysplastic syndrome received no treatment before transplantation. Modified busulfan/ cyclophosphamide (BU/CY) protocol was processed in all 14 patients. All patients received DSA desensitization treatments as below: spleen irradiation (before transplant, 200cGY in total, 50cGY/d × 4 days), plasmapheresis (before transplant, 40ml/kg × 2 doses), rituximab (before transplant, 375mg/m2 × 1 dose), immunoglobulin (before transplant, transplant day, 0.4g/kg).The average of median fluorescence intensity (MFI) were tested significantly decreased after transplantation (15628 vs 6889, P < 0.05). During the median follow-up of 132 days (42-243), 14 patients (100.0%) achieved HSCT successfully and 13 patients (92.9%) were alive with disease remission, except one death because of transplantation associated thrombotic microangiopathy on +200 days after transplant. The average engraftment time of neutrophils and platelet was 13 days (10-22) and 23 days (10-76), respectively. 4 patients (28.6%) developed acute GVHD (skin, digestive tract), and all improved after treatment. 7 patients (50.0%) developed cytomegaloviremia, all of which was controlled after treatment. 4 cases (28.6%) developed chronic GVHD (skin and liver), which were stable after treatment.Spleen irradiation combined with plasmapheresis, rituximab and immunoglobulin therapy can reduce the levels of anti-HLA DSAs, improving engraftment and survival after haplo-HSCT. No excess toxicity is observed. This protocol can help to improve the prognosis of DSA-positive haplo-HSCT patients, but further study proving the efficacy is still needed.