Serum Beta-2 Microglobulin Predicts the Survival Outcome after Autologous Stem Cell Transplantation in Relapse or Refractory Diffuse Large B Cell Lymphoma
Authors: Im Hyeun-Su , Hong Jung Yong , Yoon Dok Hyun , Kim Shin , Park Jung Sun , Lee Sang Wook , Park Chan-Sik , Ryu Jin-Sook , Huh Jooryung , Suh Cheolwon 
Published: October 2019

Abstract
Background:
Treatment outcomes for diffuse large B-cell lymphoma (DLBCL) have improved with the addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, up to 40% of patients with DLBCL do not achieve durable remission and develop relapsed or refractory disease. The standard treatment for relapsed or refractory patients is salvage chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT). But long-term survival outcome is still unsatisfactory. So, we investigated survival outcome and prognostic factors for patients with relapsed or refractory DLBCL who received salvage chemotherapy followed by ASCT.
Methods:
We retrospectively identified 117 patients with relapsed or refractory DLBCL who received salvage chemotherapy and ASCT at Asan Medical Center between January 2008 and December 2017. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards regression was used to analyses prognostic factor for survival outcomes.
Results:
The median age at ASCT was 52 years (range, 17 to 69 years) with the study group comprised of 47 women (40.2%) and 70 men (59.8%). Sixty-one patients (52.1%) received etoposide, cytarabine, cisplatin, and methylprednisolone (ESHAP) salvage chemotherapy; 12 (10.3%) vincristine, methotrexate, ifosfamide, etoposide, cytarabine, cyclophosphamide, doxorubicin, and dexamethasone (BNHL); 11 (9.4%) ifosfamide, carboplatin, etoposide, and dexamethasone (ICE-D); and the remaining 33 (28.2%) other regimens. The ASCT conditioning regimens were thiotepa, busulfan, and cyclophosphamide (TBC) in 27 patients (23.1%), busulfan, etoposide, and cyclophosphamide (BuCyE) in 68 (58.1%), and other regimes in 22 (18.8%). After receiving ASCT, 86 patients (73.5%) achieved complete response; 17 (14.5%) partial response; and 13 (11.1%) stable disease or progressive disease. At a median follow-up of 14.1 months (range, 0.2 to 117.6 months), 81 patients had an event and 64 patients had died.
The two-year progression-free survival (PFS) and overall survival (OS) for all study patients were 30.3% and 48.2%, respectively. A univariate analysis showed the performance status at ASCT (HR 1.7, 95%CI 1.0 to 2.8, p=0.04), stage at ASCT (HR 2.7, 95%CI 1.5 to 4.9, p<0.01), beta-2 microglobulin (B2MG) at ASCT (HR 2.0, 95%CI 1.2 to 3.3, p<0.01), age-adjusted International Prognostic Index (AA-IPI) at ASCT (HR 2.8, 95%CI 1.6-5.0, p<0.01), number of previous chemotherapy (HR 2.4, 95%CI 1.3 to 4.3, p<0.01), and achievement of complete response after salvage chemotherapy (HR 1.8, 95%CI 1.1 to 3.1, p=0.02) as significant prognostic factors for ASCT. When B2MG at ASCT was divided into high and low group base on 2.4 ug/mL, two-year PFS was 36.7% and 19.9% (HR 1.8, 95%CI 1.1 to 2.8, p=0.01), respectively, two-year OS was 57.7% and 31.2% (HR 2.0, 95%CI 1.2 to 3.4, p<0.01), respectively. Kaplan Meier survival analysis was shown in figure 1. A multivariate analysis revealed B2MG at ASCT (HR 1.9, 95%CI 1.1 to 3.2, p=0.02), AA-IPI at ASCT (HR 2.7, 95%CI 1.4 to 5.2, p<0.01), and number of previous chemotherapy (HR 2.2, 95%CI 1.2 to 4.0, p=0.01) as significant factors for the OS.
Conclusions:
In this study, B2MG at ASCT, AA-IPI at ASCT, and number of previous chemotherapy were independent predictors of overall survival in relapsed or refractory DLBCL undergoing salvage chemotherapy followed by ASCT. To our knowledge, this is the first report showing that B2MG at ASCT is an independent prognostic factor for overall survival after ASCT and we suggest that further studies are needed.

Disclosures
No relevant conflicts of interest to declare.