CD34 selected stem cell boost provides robust outcomes in patients with poor graft function

Abstract

Abstract Background: Allogenic stem cell transplantation (SCT) is a curative option in several hematological malignancies. However, patients that have poor graft function (PGF) have increased non-relapse mortality as therapeutic options for PGF are currently limited. Larocca et al had first reported the use of CD34 selected stem cells for treatment of PGF[1]. They found outcomes in PGF patients were significantly better in the CD34 selected boost group compared to patients who were untreated or patients who got unselected stem cell infusions. As such, CD34 selected stem cell boost can be a potential option to mitigate PGF and address the high morbidity and mortality associated with it. However, CD34 selected stem cell boost is still a relatively new strategy and treatment outcomes across institutions and factors that affect it are largely unknown. Methods We reviewed the outcomes of CD34+ selected stem cell boost in two institutions, Case Western Reserve University (Cohort 1; n=15) and The Ohio State University (Cohort 2; n=13). Source of CD34+ stem cells was fresh granulocyte-colony stimulating factor (G-CSF) mobilized apheresis-products. Manufacturing was 100% successful in Cohort 1 and 93 %. successful in Cohort 2. CD34 enrichment was performed on the CliniMACS® CD34 Reagent System (Miltenyi Biotech, Germany) using established GLP protocols[2, 3]. Results: The median CD34 recovery percentage was 58 % for Cohort 1 and 68% at Cohort 2. Post enrichment the median CD3 cell count for Cohort 1 was 1.297 x10e5/kg and 1.13 x10e5/kg in cohort 2. Median CD3 cell log depletion was similar in the two cohorts. Median time to CD34+ boost was 127 days (range 69-839 days) for Cohort 1 and 134 days (range 41-1856 days) for Cohort 2. Our results showed that overall hematological response rate to the boost was 68% with a complete hematological response seen in 32% of patients. There was no difference in boost efficacy for infused cell doses below and above 5x10e6 CD34 cells/kg. There were significant differences in outcomes when comparing patients who received boost within 120 days of transplant and those after 480 days of transplant with earlier boost more effective (p=0.016). Furthermore, patients with Peripheral Blood derived allografts responded better to boost than those with bone marrow derived grafts (p=0.0297). Two patients developed new acute Graft-versus-host disease (GVHD) post boost and four had acute GVHD flare post boost. At 90 days post boost, 61% and 68% achieved packed red blood cell and platelet transfusion independence respectively. The one-year overall survival and median relapse-free survival were 45% and 0.47 years respectively. Conclusion: Our data shows that CD34+ stem cell selection products are comparable between institutions and CD34+ selected stem cell boost is an effective treatment for PGF after allogeneic SCT across institutions References Larocca, A., et al., Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. haematologica, 2006. 91(7): p. 935-940. Luznik, L., et al., Randomized phase III BMT CTN trial of calcineurin inhibitor–free chronic graft-versus-host disease interventions in myeloablative hematopoietic cell transplantation for hematologic malignancies. Journal of Clinical Oncology, 2022. 40(4): p. 356-368. Askaa, B., et al., Treatment of poor graft function after allogeneic hematopoietic cell transplantation with a booster of CD34-selected cells infused without conditioning. Bone marrow transplantation, 2014. 49(5): p. 720-721.