Association of CD34 Cell Dose with 5-Year Overall Survival after Peripheral Blood Allogeneic Hematopoietic Cell Transplantation in Adults with Hematologic Malignancies.

Higher CD34 cell dose is associated with improved engraftment after peripheral blood allogeneic hematopoietic stem cell transplantation (alloHCT) but also may increase the risk of long-term complications, such as graft-versus-host disease (GVHD). Prior studies examining the relationship between CD34 cell dose and long-term survival outcomes have yielded conflicting results. In this study, we sought to clarify the prognostic impact of CD34 cell dose by examining a large contemporary cohort of patients undergoing alloHCT with a matched sibling peripheral blood stem cell (PBSC) donor. We retrospectively examined the impact of CD34 cell dose on overall survival (OS), neutrophil engraftment, platelet engraftment, treatment-related mortality, relapse, acute GVHD grade II-IV and III-IV, and chronic GVHD in 377 consecutive patients undergoing alloHCT with a PBSC graft source from a matched sibling donor at the University of Minnesota between 2002 and 2015. The patients were classified into 3 groups based on the tertile (T) of CD34 cell dose received: T1, <5 × 106 cells/kg; T2, 5 to 7.5 × 106 cells/kg; and T3, ≥7.5 × 106 cells/kg. Multivariable analysis demonstrated that high CD34 cell dose was associated with superior 5-year OS (hazard ratio [HR], 0.57; P = .01) and more rapid platelet engraftment (HR, 1.70; P < .01). Higher CD34 cell dose also was associated with improved absolute neutrophil count engraftment (T2: HR, 1.54; T3: HR, 1.52; P < .01). There was no association between CD34 cell dose and TRM or relapse at 5 years. Although higher CD34 cell dose was not associated with acute GVHD grade II-IV, it was associated with chronic GVHD (T2: HR, 1.68; T3: HR, 1.50; P = .04). Our data indicate that higher CD34 cell dose (>7.5 × 106/kg) is associated with superior OS at 5 years and improved engraftment but carries an increased risk of chronic GVHD. These data support a target CD34 cell dose goal of 7.5 × 106/kg for sibling PBSC graft donors.

Biomarkers in Graft-Versus-Host Disease: from Prediction and Diagnosis to Insights into Complex Graft/Host Interactions.

PURPOSE OF REVIEW: Acute graft versus host disease (aGVHD) is a frequent cause of treatment-related mortality after allogeneic hematopoietic stem cell transplantation (alloHCT), with few effective treatment options beyond systemic steroids. Discovery of biomarkers for aGVHD may provide insight into the pathophysiology of aGVHD and suggest novel mechanisms for treatment. RECENT FINDINGS: We highlight biomarkers within innate immune activation, T-cell-mediated tissue damage, endothelial damage, dysbiosis, and poor wound healing that can be obtained prior to transplant, in the early transplant period, or at the onset of aGVHD. aGVHD biomarkers have predictive and prognostic utility but also suggest novel mechanisms of recipient tissue damage and impaired regenerative capacity. These mechanisms should be further studied and tested in therapeutic clinical trials to improve outcomes post-alloHCT.