Engraftment Syndrome Following Unrelated Cord Blood Transplant in Pediatric Patients.

Abstract

Engraftment syndrome or hyper-acute graft versus host disease like syndrome describes a constellation of symptoms that occur prior or during neutrophil recovery after both allogeneic and autologous stem cell transplant. The usual symptoms are high grade fever and diffuse erythematous rash. There are no prior published reports describing the incidence and clinical implications of engraftment syndrome in recipients of unrelated cord blood transplant. There were 326 patients ≤ 18 years of age with malignant (N=229) or non-malignant (N=97) diseases enrolled on a prospective National Heart Lung Blood Institute (NHLBI) sponsored cord blood transplant study between 1999 and 2003. Dataset was abstained after signed agreement with the NHLBI and local IRB approval. All patients received myeloablative preparative regimen with either total body irradiation or busulfan based regimens with cyclosporine and prednisone GVHD prophylaxis. All patients received anti-thymocyte globulin as part of their conditioning regimen. ES was defined as high grade fever and diffuse erythematous rash without documented infections. The median age was 4.65 years (range 0.04 – 17.90) with 127 (60%) male, 264 (81%) had a performance status of ≥ 90. Two hundred twenty eight (70%) of the patients had malignant diseases and 179 (55%) received a cord blood unit matched at 3/6 or 4/6 HLA antigens and 147 (45%) received a cord blood unit matched at 5/6 or 6/6 HLA antigens. The median total nucleated cell dose per kg infuses was 6.94 x 107/kg (range 0.08–809.4 x 107/kg). Sixty-four patients (20%) developed engraftment syndrome at a median of 10 days (range 5–24) post transplant. All patients developed engraftment syndrome prior to engraftment and were treated with high dose steroids. Patients who developed engraftment syndrome had a median age of 2.47vs. 5.57 years, 48% had nonmalignant disease versus 25%, compared to those who did not develop engraftment syndrome respectively. The median pre-cyopreserved total nucleated cells infused was 8.58x107/kg (range 1.54x107 to 27.49 x107) in those who developed engraftment syndrome compared to 6.68x107/kg (range 0.08 x107 to 80.91x107) to those who did not. A multivariable analysis using Cox regression analysis using engraftment syndrome as a time dependent co-variable was performed including patients age, sex, performance status (<90 versus ≥ 90), disease (malignant versus non malignant), HLA match (3–4/6 versus 5–6/6 HLA match), and total nucleated cell count per kg infused. Overall survival was significantly worse in female recipients (HR 1.78, CI 1.31–2.41, p=0.0002), those with malignant diseases (HR 1.75, CI 1.15–2.66, p=0.009), patients with performance status <90 (HR 1.66, CI 1.15–2.40, p=0.007) and those who developed engraftment syndrome (HR 1.61, CI 1.15–2.28, p=0.006). Engraftment syndrome is a common complication following unrelated cord blood transplant in pediatric patients that increases the risk of overall mortality.