Single Institute Analysis of Reduced Intensity Cord Blood Transplantation from Unrelated Donors for Adults with Advanced Lymphoid Malignancies.
Authors: Wake Atsushi , Uchida Naoyuki , Ishiwata Kazuya , Takagi Shinsuke , Tsuji Masanori , Yamamoto Hisashi , Yoshimi Mayumi , Narita Madoka , Sagawa Kimiko , Araoka Hideki , Kato Daisuke , Matsuno Naofumi , Masuoka Kazuhiro , Yoneyama Akiko , Makino Shigeyoshi , Taniguchi Shuichi 
Published: April 2020

Umbilical cord blood transplantation with reduced-intensity conditioning (RICBT) has been widely applied to various diseases. However, little information on long-term outcome of RICBT in advanced mature or immature lymphoid malignancies has been available so far. We retrospectively reviewed patients who had lymphoid malignancies and underwent RICBT as the first allogeneic transplant at our institute from Jan. 2002 to Apr. 2008 consecutively, excluding those who had active infection before RICBT. This study includes 110 CB recipients who diagnosed as lymphoblastic lymphoma (LBL)/acute lymphoblastic leukemia (ALL) (n=26, including 12 Ph positive) and mature lymphoid malignancies (n=84, 29 DLBCL, 6 FL/CLL, 16 peripheral T-cell lymphoma, 5 HL, 6 MM, and 22 adult T-cell leukemia (ATL)). Median age was 53 (range 26–79). The numbers of HLA-A, B and DR antigen mismatches were 0 (1.8%), 1 (8.1%) and 2 (89.1%). Median number of total nucleated cells (TNC) and CD34 positive cells infused were 2.68 x 107/kg and 0.87 x 105/kg, respectively. Majority (81.8%) had advanced disease (relapse or refractory disease), 36 cases (32.7%) had poor performance status (ECOG PS≥ 3), and 27 cases (24.5%) had prior autologous transplant. Conditioning regimen consisted mainly of fludarabine 125mg/m2, melphalan 80–140 mg/m2, and 0–8 Gy TBI. Cyclosporine A or taclolimus±mycophenolate mofetil were used as GVHD prophylaxis. Eighty five percent of the cases who survived longer than 28 days showed neutrophil recovery (median 19 days (11–44)). The incidence of grades II–IV acute GVHD and chronic GVHD among evaluable patients were 42.3% and 37.6%, respectively. Median follow-up time of survivors was 1422 days (109–1896). Overall survival (OS) and progression-free survival (PFS) were 36.9%(27.8–46.0) and 30.6%(22.0–39.3) at 1 year, and 25.3%(17.0–33.6) and 22.8%(14.9–30.8) at 3years, respectively. Treatment related mortality (TRM) and relapse mortality (RM) at 500days were 41.9% and 28.6%, respectively. The diagnosis-based PFS at 3 years were 33.8% for ALL, 20.7% for DLBCL, 33.3% for FL/CLL, 25.5% for PTCL, 40.0% for HL, 20.0% for MM, and 9.1% for ATL. In univariate analyses, factors significantly associated poor PFS were the diagnosis of ATL, high disease risk, poor PS (≥ 2), high HCT-CI (≥ score 2), and high LDH level (high tumor burden). Factors associated higher TRM were poor PS (≥ 2) and lower TNC infused (&lt;2.5 x 107 TNC/kg). Higher age (≥ 55years) did not reach statistical significance. RM was significantly higher in ATL patients. In ALL patients, OS and PFS were significantly higher for patients who received higher dose of TBI (8&gt;4Gy), although Ph chromosome was not associated with OS or PFS. In multivariate analyses of all patients, poor PS (≥ 2) was the only significant factor associated with lower OS (RR 2.63, p=0.0093), PFS (RR2.13, p=0.0338) and not only higher TRM (RR 2.30, p=0.0148),but higher RM (RR 2.94, p=0.0081), suggesting poor PS group have highly advanced disease. Interstingly, higher LDH level, not poor PS, was found to be the only significant factor associated with lower OS and PFS in multivariate analysis of mature lymphoid malignancies. Although the high TRM should be improved, these data indicate RICBT to have sufficient potential to achieve long-term durable remission for both immature and mature lymphoid malignancies except ATL in advanced status. Lower tumor burden (low LDH level) in mature lymphoid malignancies and higher dose of TBI in ALL may be the keys to further improve long-term outcome.