Graft-Versus Host Disease (GVHD) and Infectious Complications Following Reduced Intensity Conditioning (RIC) Umbilical Cord Blood Transplantation (UCBT) in Adults.
Authors: Furst Sabine , Mohty Mohamad , Faucher Catherine , El-Cheikh Jean , Ladaique Patrick , Lemarie Claude , Vey Norbert , Bouabdallah Reda , Stoppa Anne-Marie , Marchetti Nicolas , Chabannon Christian , Blaise Didier 
Published: October 2019

Abstract
UCBT in adults with hematological malignancies has significantly increased over the last 5 years. In addition, the introduction of RIC regimens can allow a decreased incidence of TRM. Thus, the use of UCBT after a RIC regimen is an attractive modality for those high risk patients lacking a suitable HLA-matched donor. The aim of this analysis was to assess the outcome of 27 patients who received RIC UCBT in a single centre between 2005 and 2007, with a focus on GVHD and infectious complications. All 27 patients had high risk hematological malignancies (AML, n=15; ALL, n=7; NHL, n=3; CML, n=1; and Hodgkin disease, n=1). 23 patients (85%) were in CR (CR1, n=17; CR2, n=5; CR3, n=1), whereas 4 had a more advanced disease at time of UCBT. Of note, 9 patients (33%) have already received and failed prior autologous transplantation. The median age and weight was 43 (range, 17–59) years and 62 (range, 47–125) kg respectively. The RIC regimen included fludarabine 200 mg/m2, cyclophosphamide 50 mg/kg and low dose TBI (2 Gy). All patients received CSA and MMF for GVHD prophylaxis. 11 patients (41%) received a single CB unit, whereas 16 (59%) received 2 CB units in order to achieve a minimum cryopreserved cell dose of 3.0 × 10e7 TNC/kg (as required per protocol). For the entire group, the median cryopreserved and infused cell doses were 4.9 × 10e7 TNC/Kg (range, 3.3–7.0) and 3.7 × 10e7/Kg (range, 1.9–5.5) respectively. Neutrophil engraftment (ANC>500/μL) occurred in 26 patients (96%) at a median of 19 (range, 6–45) days after UCBT. A sustained platelets recovery (>50000/μL) was observed in 19 patients (70%) at a median of 48 (range, 29–131) days after UCBT. Hematological recovery was comparable between single and double CB unit recipients. Primary and secondary graft failure occurred in 3 and 1 patients respectively. 2 out of these 4 patients underwent and failed a second UCBT. The overall incidence of grade II–IV acute GVHD was 58% (95%CI, 39–77%; 5 grade II, 9 grade III and 1 grade IV). 16 patients were evaluable for chronic GVHD for an overall incidence of 41% (7 limited and 4 extensive). 16 patients (59%; 95%CI, 40–77%) experienced at least one episode of a “serious” or “life-threatening” infectious complication (virus other than CMV reactivation, n=8; bacteria, n=8; fungal, n=4), requiring long-term hospitalization, and of whom 7 patients were in grade III–IV acute GVHD. 6 patients (22%) experienced severe interstitial pneumonia, with 4 patients (15%) developing ARDS. Most importantly, 5 patients (19%) also required transfer to ICU. With a median follow-up of 385 (range, 111–903) days, 5 patients (18%) had relapsed with this being significantly lower in those patients transplanted in CR (P=0.01), but without a significant difference between single and double CB recipients. 8 patients have died (infection, n=4; GVHD, n=2; relapse, n=2; TRM=22%). The KM estimate of OS and EFS was 73% and 58% at 2 years respectively with no significant differences between single and double CBT recipients. However, there was a trend towards an improved OS and less grade II–IV acute GVHD in patients without HLA-DRB1 antigen mismatch (P=0.05 and P=0.08 respectively). We conclude that RIC UCBT is an efficient therapy for high risk hematological malignancies. However, GVHD and serious infections are still a matter of concern warranting prospective efforts to define optimal prophylactic approaches.