Graft-Versus-Host Disease (GVHD) in Cord Blood Transplantation (CBT): Risk Factors, Clinical Manifestations and Outcomes.
Authors: Couriel Daniel , Patah Poliana , Saliba Rima , Cooper Lawrence , Worth Laura , Petropoulos Dimitrios , Depadua Leandro , Zhang Weiqing , Giralt Sergio , Champlin Richard , Shpall Elizabeth J. , de Lima Marcos 
Published: October 2019

Abstract
Introduction: Umbilical CBT from mismatched donors can restore hematopoiesis both in children and adults with acceptable rates of severe acute (aGVHD) and chronic GVHD (cGVHD). Acute and chronic GVHD, including risk factors, clinical manifestations and its specific impact on outcomes has not been systematically evaluated in this particular patient population.
Objective: To analyze the manifestations of GVHD in CBT, with emphasis on risk factors and impact on overall survival.
Methods: Prospective evaluation of aGVHD and cGVHD in 138 adult and pediatric patients undergoing single or double CBT for hematological disorders and solid tumors from 3/96 and 6/07. cord blood units were selected on the basis of a maximum of 2 MM (HLA-A, B, DRB1) and the minimum of 1x107TNC/Kg. Risk factors for aGVHD after CBT were assessed using the Cox proportional hazards method. The estimates of aGVHD and cGVHD were performed accounting for competing risks such as death and engraftment using the cumulative incidence (CI) method.
Results: A total of 138 adult (n=78) and pediatric (n=60) CBT were performed in the time period. Median age was 21 (1-64), 58 females and 80 males. The majority received a transplant for hematological malignancies (n= 132), mostly MDS/AML and ALL (n= 98, 71%). The remainder had AA (n= 3) and one a solid tumor (n=1). Seventy-seven patients (56%) were in remission of their disease at the time of transplant. Most patients received a myeloablative regimen (n= 125, 91%), and single cord grafts (n= 81, 59%). Of 100 CBT where HLA typing is available, 39%, 45 and 9% have 1, 2 and 3 mismatched loci respectively. Twenty-four patients (17%) did not engraft. At 3 months post transplant, the CI of grade II-IV aGVHD was 36% (adult 38%, pediatric 34%, p= 0.9), and that of grade III-IV was 12% (adult 14%, pediatric 10%, p= 0.9). Skin was the organ most often involved (84%, adult 71%, pediatric 100%, p= 0.017). In adults skin was the only organ involved in 80% of patients with skin GVHD. Lower GI, upper GI and liver involvement were observed in 24, 18, and 21% of patients respectively, without significant difference between adults and children. The total nucleated cell count (TNC) of the graft was the strongest predictor of aGVHD. In children, active disease at the time of transplant was also significantly associated with higher incidence aGVHD. Other factors analyzed, including number and type of mismatched HLA loci were not significant risk factors for aGVHD. CI of cGVHD was 20%, and significantly lower in children compared to adults (8 vs 31%, p= 0.002). Nonrelapse mortality (NRM) at 2 years was 30%, and significantly lower in children (18 vs 41%, p= 0.007). Only 7/43 (16%) deaths were attributed to aGVHD or cGVHD.
Conclusions: CBT can be performed in children and adults with acceptable rates of GVHD, even in the presence of multiple HLA mismatched loci. Most cases of acute GVHD involved the skin, often as the only organ. Chronic GVHD and NRM are significantly higher in adults. GVHD accounts for a relatively small proportion of nonrelapse deaths.