Umbilical Cord Blood Transplantation with Non-TBI Regimens for Advanced Hematological Malignant Diseases
Authors: Nakano Nobuaki , Takatsuka Yoshifusa , Kubota Ayumu , Tokunaga Masahito , Tokunaga Mayumi , Makino Torahiko , Takeuchi Shogo , Utsunomiya Atae 
Published: October 2019

Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) for advanced hematological diseases dose not reach a satisfactory result so far. Recently, umbilical cord blood transplantation (UCBT) is widely practiced for advanced hematological diseases by its tolerance of HLA matching. However, high incidence of transplant related complications such as engraftment failure, infections, pre-engraftment immune reaction (PIR) etc. are still issues to resolve. Although non-TBI regimens are easy to prepare, few reports investigated non-TBI regimens for UCBT. With respect to UCBT with non-TBI conditioning regimens, we examined efficacy and feasibility of them for high-risk hematological diseases.
Non-CR hematological malignancies, and int-2/high risk MDS categorized by IPSS were defined as advanced hematological disease. From June 2011 to January 2015, 47 patients consecutively underwent UCBT at our center. Thirty-five of 47 patients (23 male, 12 female), who were suffered from advanced hematological diseases were undergone first-time UCBT with non-TBI conditioning regimens. There were five non-TBI regimens such as fludarabine (Flu) 180mg/m2 + intravenous buslufan (Bu) 12.8mg/kg + melpharan (Mel) 80mg/m2 (FB4M) and Flu 125mg/m2 + Mel 200 mg/m2 (FM200) as the myeloablative conditioning regimens (MAC) and Flu 125mg/m2 + Mel 140mg/m2 (FM140), Flu 180mg/m2 + Bu 6.4mg/kg + Mel 140mg/m2 (FB2M140) and Flu125mg/m2 + cyclophosphamide (Cy) 120mg/kg + ATG 2.5mg/m2(FCyATG) as the reduced intensity conditioning regimens (RIC) has been used at our center. We investigated patients' characteristics, engraftment, overall survival (OS), incidence of transplant related mortality (TRM) and disease related death (DRD). OS was calculated with Kaplan-Meier method and the cumulative incidence of neutrophil engraftment, TRM and DRD was calculated with Gray′s method. Statistical significance was regarded as less than 0.05 of p-value. Statistical analyses were carried out using EZR (Kanda Y. BMT 2013).
Median age at UCBT was 57 years (21-70). Fourteen patients with myeloid diseases (11 AML, 3 MDS) and 21 lymphoid diseases (17 ATLL, 1 ALL, 3 NHL) were included. 25 patients used MAC, 21 patients received FB4M, 4 FM200 followed by UCBT. On the other hand, 10 patients recieved RIC, 8 patients with FM140 and 1 each FB2M140, and FCyATG. Median time to neutrophil engraftment was 23 days (14-58) and cumulative incidence of neutrophil engraftment at day100 with the competing risk as early death (14.3%; 95%CI: 0.51-28.0) was 82.9% (95%CI: 64.1-92.4). Cumulative incidence of TRM at day 100 after UCBT was 37.4% (95%CI: 21.5-53.3). Also cumulative incidence of DAD at 3 month after UCBT was 14.9% (95%CI: 5.3-29.2). These results suggested that additional use of melpharan will be contributed to high incidence of engraftment and low incidence of relapse. In patients with myeloid diseases, cumulative incidence of DAD at 6 months after UCBT was 7.9% (95%CI: 0.4-31.3). However, in the patients of lymphoid diseases, cumulative incidence of DAD at 6 months was relatively high (37.1%; 95%CI: 12.4-62.5). There was no statistical difference between myeloid diseases and lymphoid disease about the incidence of TRM at day100 after UCBT.
Although a lot of problems to solve were still remained in lymphoid diseases (OS at 1 year: 21.4%; 95%CI: 9.3-66.8), UCBT with non-TBI regimens would be feasible in the aspect of neutrophil engraftment and can be a promising treatment strategy for patients who suffered from advanced myeloid diseases (OS at 1 year: 55%; 95%CI: 25.8-76.8).

Disclosures
No relevant conflicts of interest to declare.