Graft Failure Incidence, Risk Factors, and Outcomes in Patients Undergoing Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.

BACKGROUND: Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) that results in significant morbidity and mortality. Post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has emerged as an effective regimen across the spectrum of donor-match settings, but few studies have investigated the characteristics of GF in the setting of PTCy-based GVHD prophylaxis.

OBJECTIVES: The objective was to detail the incidence, clinical features, risk factors, and outcomes for patients with primary graft failure (PGF) and secondary graft failure (SGF).

STUDY DESIGN: In this retrospective study at a single institution, 958 consecutive patients undergoing first non-myeloablative (NMA) alloHCT with PTCy-based GVHD prophylaxis were analyzed. PGF was defined as a failure to achieve an ANC ≥ 500 cells/m3 by day 30 of transplant in the absence of residual disease. SGF was defined as complete loss of donor chimerism after initial engraftment.

RESULTS: The incidences of PGF and SGF were 3.8% (n=37) and 1.8% (n = 17), respectively. Neither PGF nor SGF were associated with HLA disparity. In a multivariate analysis, risk factors for PGF in this cohort included age ≥ 65 (OR 2.4, 95% CI 1.2-4.8, P=0.012), an underlying diagnosis of MDS, MPN, or MDS/MPN overlap (OR 2.8, 95% CI 1.4-5.7, P=0.005), post-transplant viremia with HHV-6 (OR 2.9, 95% CI 1.5-5.7, P=0.003), and low CD34+ dose (OR 0.7, 95% CI 0.5-0.9, P=0.008). Patients with PGF had poor overall survival, driven primarily by a high rate of non-relapse mortality (59% at 36 months). SGF was associated with use of a bone marrow graft source and a diagnosis of Hodgkin lymphoma. Patients with SGF had excellent clinical outcomes with only one of seventeen patients experiencing relapse and relapse-related mortality.

CONCLUSIONS: The incidence of PGF and SGF in patients receiving NMA conditioning and PTCy is low and is not impacted by HLA disparities between donors and recipients. PGF is more common in recipients with age ≥ 65, a diagnosis of MDS, MPN, or MDS/MPN-overlap, post-transplant HHV-6 viremia, and low CD34+ cell dose. Low total nucleated cell dose is also a risk factor for PGF in patients receiving a bone marrow graft source. Patients who experience PGF have poor outcomes due to high rates of non-relapse mortality, whereas patients who experience SGF have excellent long-term outcomes.