HR-03. Application of selected CD34+ cells for the treatment of poor graft function after allogeneic stem cell transplantation
Ulyana V. Maslikova, Mikhail Yu. Drokov, Denis V. Kamelskikh, Maxim A. Telyashov, Ekaterina D. Mikhaltsova, Natalia N. Popova, Daria S. Dubniak, Anna A. Dmitrova, Olga M. Koroleva, Zoya V. Konova, Mobil I. Akhmedov, Maria V. Dovydenko, Olga S. Starikova, Feruza A. Omarova, Elmira I. Kolgaeva, Vera A. Vasilieva, Larisa A. Kuzmina, Elena N. Parovichnikova
National Research Center for Hematology, Moscow, Russian Federation
Contact: Dr. Mikhail Yu. Drokov, e-mail: mdrokov@gmail.com
Summary
Introduction
Poor graft function is a complication of the allogeneic bone marrow transplant, characterized by the presence of 2 or 3-lineage cytopenia within 14 days of confirmed engraftment, with complete or mixed chimerism, in which donor hemopoiesis comprises more than 95%. According to the National Research Center for Hematology, the frequency of poor graft function ranges from 5.3 to 25%, depending on the source of hematopoietic stem cells (HSC), and the type of transplantation. Poor graft function is associated with high risks of infectious and hemorrhagic complications, and transplant-associated mortality. There is currently no uniform approach to the treatment of poor graft function among transplantation centers, but we believe that application of selected CD34+ donor cells may be one of effective and safe therapies. The aim of the work was to assess the effectiveness and safety of the use of selected CD34+ cells in the treatment of poor graft function after allogenic stem cell transplantation.
Materials and methods
The study included five patients who received CD34+ selective cell infusions at the National Research Center for Hematology between 2018 and 2020. The group included two patients after transplantation from related HLA-identity donor, two patients from a non-related partially compatible donor, one patient from a related haploid donor with TCRab/CD19-depletion. The median age was 35 years (21-48 l). The group of patients included two patients with acute leukemia and three patients with non-tumor blood diseases (MDS, AA, PMF). All patients had 100% donor hematopoiesis upon infusion of selected cells, according to bone marrow puncture data. Three patients had 3-lineage cytopenia (granulocytopenia <0.5*109/l, thrombocytopenia <20*109/l, hemoglobin <70 g/l after confirmation of engraftment), one had 2-lineage of cytopenia and one had partial red cell aplasia (PRCA), which could not be treated by conventional approaches (plasmapheresis, rituximab, plasmosorption). In 80% of cases, graft hypofunction developed against the background of infectious complications. The median for the procedure was 130 days after allo-HSCT (102-410d). The CD34+ cells were prepared using standard mobilization protocols (G-CSF 10 µg/kg) and apheresis from the same donor as the “main” transplant. Thereafter, products with a median CD34+ cell concentration of 98.83% (97.64-99.48%) were selected by immunomagnetic separation. The median for transfused CD34+ cells was 4.2 (3.16-6.8*106/kg).
Results
A complete response (restoration of all hematopoietic lineages, no transfusions requirements) was achieved in 4 patients. Median time for a complete response to the therapy was 14 (13-30) days. In one patient, a partial response was achieved, i.e., restoration of granulocytic lineage, reduced needs for RBC transfusions, however, retained dependence on platelet transfusions. No cases of GVHD have been reported in the patients since recovery.
Conclusion
Despite the small sample of patients, one may argue that the introduction of selected CD 34+ cells may be a sufficiently safe and effective method of treating poor graft function. A need for repeated HSCs donations from the donor is a sufficient disadvantage of this method.
Keywords
Allogeneic hematopoietic stem cell transplantation, poor graft function, CD34+ cells, selection.
