Impact of Human Leukocyte Antigen Compatibility on Engraftment in Adult Patients Receiving Reduced-Intensity Umbilical Cord Blood Transplantation Using Calcineurin Inhibitor Alone for GVHD Prophylaxis.
Authors: Matsuno Naofumi , Wake Atsushi , Uchida Naoyuki , Takagi Shinsuke , Kato Daisuke , Matsuhashi Yoshiko , Seo Sachiko , Masuoka Kazuhiro , Miyakoshi Shigesaburo , Matsuzaki Michio , Yoneyama Akiko , Taniguchi Shuichi 
Published: October 2019

Abstract
Despite the fact that the majority of cord blood grafts were human leukocyte antigen (HLA) disparate at one to two antigens, acute graft-versus-host disease (GVHD) was less severe after cord blood transplantation (CBT) compared to unrelated bone marrow transplantation. On the other hand, engraftment failure is a serious problem after CBT. We retrospectively analyzed the influence of HLA compatibility on engraftment after reduced-intensity umbilical cord blood transplantation (RI-CBT). We analyzed the clinical outcome of patients who underwent first RI-CBT at Toranomon hospital between January 2002 and December 2005. Those who had died within 28 days from the day of transplant were excluded from these analyses. All 156 patients had hematological malignancies including 41 with AML, 21 with ALL, 6 with CML, 19 with MDS, 31 with malignant lymphoma, 14 with adult T-cell leukemia/lymphoma, 6 with other diseases. Median age was 54 years (range, 17–79 years). All of them were considered to be inappropriate for conventional stem cell transplantation due to the lack of an HLA-identical related donor, age >50 years old and/or organ dysfunction. The preparative regimens were mainly composed of fludarabine 125 mg/m2, melphalan 80 mg/m2, and 4 Gy total body irradiation. GVHD prophylaxis was composed of cyclosporine or tacrolimus alone. Eight, 46, 98 and 4 patients received 6 of 6, 5 of 6, 4 of 6 and 3 of 6 HLA antigen matched cord blood in graft-versus-host (GVH) direction. Primary engraftment failure was diagnosed in 18 patients (11.5%). Median time to engraftment was 19 days (range, 11–55 days) for the total patient group. In GVH direction, the cumulative incidence of engraftment at day 100 were 94.4% in 5 to 6 of 6 antigen matched cord blood and 85.3% in 3 to 4 of 6 antigen matched cord blood (p=0.001). Median time to engraftment was 17 days (range, 11–36 days) in 5 to 6 antigen matched cord blood and 20 days (range, 11–55 days) in 3 to 4 antigen matched cord blood. In host-versus-graft direction, the cumulative incidence of engraftment at day 100 were 90.9% in 5 to 6 antigen matched cord blood and 87.5% in 3 to 4 antigen matched cord blood (p=0.5895). Median time to engraftment was 18.5 days (range, 11–55 days) in 5 to 6 antigen matched cord blood and 19 days (range, 11–49 days) in 3 to 4 antigen matched cord blood. In univariate analysis, both total cell dose (>3 x 107/kg) and CD34 positive cell dose (>1 x105/kg) were significantly associated with the engraftment (p=0.0009 and p=0.0005). Age, gender, risk, GVHD prophylaxis, blood type mismatch and early immune reaction were not associated with the engraftment kinetics. Multivariate analysis revealed 5 to 6 antigen mismatch in GVH direction was a significant independent factor for engraftment (p=0.0073), as well as CD34 positive cell dose. In conclusion, HLA disparities in GVH direction are associated with engraftment in adult patients receiving reduced-intensity umbilical cord blood transplantation using calcineurin inhibitor alone for GVHD prophylaxis.