Successful Treatment of Lung Aspergillus terreus Infection After a Second Hematopoietic Stem Cell Transplant in a Patient With Myelodysplastic Syndrome

Abstract

A 24-year-old man was diagnosed with myelodysplastic syndrome and received a haploidentical hematopoietic stem cell transplant. The patient experienced graft failure posttransplant. Analysis of specific antibodies revealed that the patient had strongly positive donor-specific antibodies; therefore, we changed the donor to the patient's mother and added a single unit of cord blood to perform the second transplant. Corresponding treatments targeting donor-specific antibodies were administered to reverse the graft rejection and to reduce the antibody load. The grafts were implanted successfully, but the patient developed an invasive fungal infection. A lung biopsy was performed, and the pathogen was confirmed to be Aspergillus terreus via gene sequencing and analysis. The combined treatment of micafungin and posaconazole had good efficacy in this case, and this patient now receives close follow-up and receives oral posaconazole for antifungal maintenance treatment. Key words: Donor-specific antibodies, Fungal infection, Graft failure Case ReportA 24-year-old man was diagnosed with myelodysplastic syndrome (MDS, RAEB-II) in May 2015. He had an intermediate karyotype (+8) and pancytopenia. The bone marrow showed 14% blast cells, which was categorized as very high risk (6.5 points) according to the Revised International Prognostic Scoring System. 1 The patient needed a transplant; however, no human leukocyte antigen (HLA)-identical sibling or unrelated donor was available. The patient's father, who was HLA halfmatched, agreed to donate stem cells. The treatment approach before transplant consisted of omacetaxine mepesuccinate (2 mg intravenously [IV], once daily from day 1 to day 7), cytarabine (25 mg subcutaneously, twice daily from day 1 to day 7), and aclarubicin (20 mg IV, once daily on days 1, 3, and 5) every 28 days for 1 course and 25 mg/m 2 IV decitabine once daily for 5 days every 28 days for 2 courses.In August 2015, the patient received a haploidentical hematopoietic stem cell transplant (HSCT; peripheral blood + bone marrow) with a myeloablative conditioning regimen based on cytarabine (4 g/m 2 /d IV for 2 days), busulfan (3.2 mg/kg/d IV for 3 days), cyclophosphamide (3.6 g/m 2 /d IV for 2 days), and antilymphocyte globulin (10 mg/kg/d IV for 4 days). Graft-versus-host disease prophylaxis consisted of mycophenolate mofetil, cyclosporine, and short-term methotrexate. The patient received 8.46 × 10 6 CD34-positive cells/kg. On day 21 after transplant, granulocytes and platelets were not engrafted into the patient. The bone marrow puncture report suggested extremely low bone marrow proliferation. Primary engraftment failure was considered, possibly associated with donor-specific antibodies (DSAs).Peripheral blood specimens from both the patient and the parents were sent for DSA detection. The results suggested that there were strongly positive anti-HLA-I antibodies in the patient's body. Analysis of specific sites (detection performed using HLA-I, HLA-II, and major histocompatibility complex class I p...