Cyclosporine combined with eltrombopag for treatment of secondary graft failure after autologous hematopoietic stem cell transplantation

Abstract

Graft failure (GF) is an extremely rare complication of autologous hematopoietic stem cell transplantation (auto-HSCT) with a frequency not exceeding 3–5 % of all cases of this technology. Primary graft failure is distinguished when restoration of hematopoiesis has not occurred by day +28 after hematopoietic stem cell transfusion, and secondary GF, implying the occurrence of neutropenia <0.5 × 109 /L after successful initial engraftment, which cannot be explained by tumor relapse, infections or chemotherapy toxicity.In this report, we present a clinical case of a 57-year-old woman with newly diagnosed diffuse large B-cell lymphoma with multiple lesions of the skeletal bones and lymph node involvement on both sides of the diaphragm. A feature of this case of diffuse large B-cell lymphoma was the secretion of monoclonal IgGκ and plasmacytoid differentiation of tumor cells. Firstline therapy with 6 cycles of R-CHOP was unsuccessful. A complete metabolic response according to positron emission tomography combined with computed tomography (PET/CT) was obtained after 2 cycles of second-line R-DHAP therapy, followed by myeloablative consolidation and transfusion of 16.9 × 106/kg CD34+ autologous hematopoietic stem cells. The patient was discharged from the hospital on day +15 with stable restoration of hematopoiesis. The pancytopenia and aplasia of bone marrow hematopoiesis developed across 3 months after auto-HSCT. For secondary GF, the patient received G-CSF, transfusions of blood components, and treatment similar to that for aplastic anemia (cyclosporine 5 mg/kg plus eltrombopag). A partial hematological response was obtained within 9 months, and a complete response by 24 months of therapy. According to PET/CT data 36 months after auto-HSCT, the patient had a local increase in the level of 18F-fluorodeoxyglucose fixation (maximum standardized uptake value 3.33), possibly of an inflammatory nature, in the body of the L4 vertebra on the background of bone cement after vertebroplasty performed at the onset of the disease. In addition, monoclonal secretion of IgGκ persists in the absence of immunomorphological evidence of bone marrow involvement.In conclusion, the article discusses the possible causes of the monotonous monoclonal IgGκ secretion and presents a literature review of known GF treating methods.