Reduced-Intensity Conditioning of Allogeneic Transplantation for Nodal Peripheral T-Cell Lymphomas
Authors: Aoki Kazunari , Suzuki Ritsuro , Chihara Dai , Suzuki Tatsuya , Kim Sung-Won , Fukuda Takahiro , Uchida Naoyuki , Tsudo Mitsuru , Matsuoka Ken-ichi , Ago Hiroatsu , Nagamura-Inoue Tokiko , Morishima Yasuo , Sakamaki Hisashi , Atsuta Yoshiko , Suzumiya Junji 
Published: November 2019

Abstract
Introduction
The outcome and the role of allogeneic hematopoietic cell transplantation (Allo-HCT) with reduced-intensity conditioning (RIC) in patients with nodal peripheral T-cell lymphomas (PTCLs) remain unclear.
Patients and Methods
To address this issue, we retrospectively analyzed the outcome of Allo-HCT for patients with nodal PTCLs using the transplant registry data from the Japan Society for Hematopoietic Cell Transplantation (JSHCT).
Patients who fulfilled the following criteria were included in this study: aged 16-69 years, diagnosed with PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), or anaplastic large cell lymphoma (ALCL), and received the first Allo-HCT in Japan between January 1, 2001 and December 31, 2011.
In this analysis, conditioning regimen intensity was the main variable of interest. The conditioning regimen was classified as myeloablative conditioning (MAC) if it included total body irradiation (TBI) > 8 Gy, oral busulfan (BU) ≥ 9 mg/kg, intravenous BU ≥ 7.2 mg/kg, or melphalan (MEL) > 140 mg/m2. Otherwise, it was classified as RIC.
Results
A total of 354 patients (200 PTCL-NOS, 77 AITL, and 77 ALCL) were analyzed. Median follow-up duration of surviving patients was 3.8 years. Donor sources consisted of 122 human-leukocyte-antigen (HLA)-matched bone marrow (BM)/peripheral blood (PB), 122 HLA-mismatched BM/PB, and 110 cord blood.
Of the 354 patients, 146 (41.2%) received MAC, which consisted of cyclophosphamide (CY)-TBI-based (n = 84), other TBI-based (n = 24), BU-CY-based (n = 11), fludarabine (FLU)-BU-based (n = 10), FLU-MEL-based (n = 15), and other (n = 2) MAC. The remaining 208 (58.8%) patients received RIC, which consisted of FLU-BU-based (n = 62), FLU-MEL-based (n = 108), and other (n = 38) RIC.
Comparison of the patients who received MAC and RIC revealed that the RIC patients were significantly older (median age: 40.5 years vs. 50.3 years; P < 0.001) and more likely to have received autologous-HCT prior to Allo-HCT (15.1% vs. 29.3%; P = 0.002).
The unadjusted 3-year cumulative incidence of non-relapse mortality were following: younger patients receiving MAC, 22%; younger patients receiving RIC, 14%; elderly patients receiving MAC, 50%; elderly patients receiving RIC, 30% (P < 0.001; Figure 1). The multivariate analysis showed that patients receiving RIC had a significantly lower non-relapse mortality than patents receiving MAC (HR, 0.51; 95% CI, 0.32-0.80; P = 0.004).
Figure 1. Unadjusted non-relapse mortality. Figure 1. Unadjusted non-relapse mortality.
The unadjusted 3-year cumulative incidence of relapse mortality were following: younger patients receiving MAC, 35%; younger patients receiving RIC, 30%; elderly patients receiving MAC, 32%; elderly patients receiving RIC, 35% (P = 0.692; Figure 2). The multivariate analysis showed that patients receiving MAC and RIC had a comparable relapse mortality (HR, 1.08; 95% CI, 0.73-1.58; P = 0.711).
Figure 2. Unadjusted relapse mortality Figure 2. Unadjusted relapse mortality
The unadjusted 3-year overall survival rates were following: MAC for younger patients (aged 16-49 years), 43%; RIC for younger patients, 56%; MAC for elderly patients (aged 50-69 years), 18%; RIC for elderly patients, 35% (P < 0.001; Figure 3). The multivariate analysis showed that patients receiving RIC had a significantly superior overall survival than patients receiving MAC (HR, 0.74; 95% CI, 0.54-1.00; P = 0.047; Table I).
Figure 3. Unadjusted overall survival Figure 3. Unadjusted overall survival
Table I. Multivariate analysis for overall survival Overall Survival HR (95% CI) P value Conditioning Regimen myeloablative 1.00 - reduced-intensity 0.74 (0.54-1.00) 0.047 Patient Age 16 to 34 1.00 - 35 to 49 1.26 (0.83-1.91) 0.270 50 to 59 2.17 (1.46-3.23) < 0.001 60 to 69 2.24 (1.40-3.59) 0.001 Karnofsly Performance Status 90 to 100 1.00 - 10 to 80 2.02 (1.41-2.91) <0.001 missing 1.50 (1.07-2.10) 0.017 Disease Status complete remission 1.00 - partial remission 1.13 (0.71-1.82) 0.607 resistant relapse 2.02 (1.27-3.21) 0.003 primary induction failure 2.09 (1.33-3.27) 0.001
Conclusion
We showed a favorable outcome of Allo-HCT with RIC in patients with nodal PTCLs. The efficacy of RIC Allo-HCT for nodal PTCLs needs to be explored in prospective study.

Disclosures
No relevant conflicts of interest to declare.