Extremely Higher Incidence of CMV-pp65 Antigenemia After Allogeneic Hematopoietic Stem Cell Transplantation in Adult T-Cell Leukemia/Lymphoma (ATL) Compared with Other Hematological Diseases
Authors: Nakano Nobuaki , Takatsuka Yoshifusa , Takeuchi Shogo , Tokunaga Masahito , Kubota Ayumu , Tokunaga Mayumi , Makino Torahiko , Utsunomiya Atae 
Published: October 2019

Abstract
Abstract 4477
Cytomegalovirus (CMV) infection is one of significant factors contribute to morbidity and mortality in recipients of allogeneic hematopoietic stem cell transplantation (SCT). Prevention and treatment of active CMV infection based on monitoring CMV-pp65 antigenemia test or CMV-DNA PCR assay have been done in this field. As the limitation of insurance, only CMV-pp65 antigenemia test can be clinically carried out in Japan. Adult T-cell leukemia/lymphoma (ATL), HTLV-1 related hematological malignancy, is known as poor prognostic disease and only allogeneic SCT had been prolonged survival outcomes. ATL cells are morphologically characterized as having complicated nuclei and their surface markers are usually shown as CD3+CD4+CD25+. Some reports suggested that ATL patients have tendency to be in immune compromised status. However, in our knowledge, there was no report about incidence of CMV-replication in ATL patients following allgeneic SCT so far. Here we analyze the incidence of CMV-pp65 antigenemia and related clinical issues in 85 allogeneic SCT recipients of single center located in HTLV-1 endemic area. There were consecutively 97 patients (106 times) undergone allogeneic SCT from November 2006 to May 2012 in Imamura Bun-in Hospital, Kagoshima, Japan. Totally, 12 patients (21 times), 9 times of deaths earlier than 30 days after SCT, 3 times of deaths earlier than engraftment, 9 times of second or more chances of SCTs, were excluded from this study. Rest of 85 (male: 52, female: 33) patients (85 times) were analyzed. We have first picked up patients' clinical data from medical charts including result of CMV-pp65 antigenemia tests and related data. Statistical analysis had carried out using SPSS 11.0J (SPSS Japan Inc., Japan). Cumulative incidences of CMV-pp65 antigenemia were analyzed by Kaplan-Meir method in total 85 patients. Statistical significance defined P<=0.05 in Log-Rank test. Cox regression analysis about incidence of CMV-pp65 antigenemia were also done in 68 patients who had available data including positivity of CMV-IgG before SCT. Median age was 52 (range 19–69) yrs. Thirty-seven ATL patients and 48 non-ATL (AML 21, MDS 14, NHL 7, ALL 3, AA 2, MM 1) patients were included. In disease status, 49 patients were categorized as high risk and 36 standard risk. Donor sources were 19 of related donors (BM 7, PB 12), 66 unrelated (UBM 56, UCB 10) respectively. Sixty four patients carried out SCT with myeloablative conditioning regimens (MAC) and 21 reduced intensive conditioning regimens (RIC). Sixty-eight recipients (ATL: 27, non-ATL: 41) had available data of their CMV-IgG antibody before SCT and 79.4% (ATL/non-ATL: 96.3%/70.7%, P<0.001) of them were shown antibody positive. Although there were no significant differences about positivity of CMV-IgG antibody before SCT between age >=50 and <50 in ATL patients, there was significant difference between age >=50 and <50 in non-ATL patients. There were no significant differences about positivity of donors' CMV-IgG antibody before SCT between ATL and non-ATL. Among patients shown CMV-pp65 antigenemia, 45/68 patients had administrated iv steroids before or after CMV-pp65 antigenemia. Twenty-four out of 45 were administrated iv steroids as treatment of GVHD or engraftment syndrome, on the other hand, 21 as premedication of blood transfusion. Absolute WBC counts, lymphocyte counts and CMV-pp65 antigen positive WBCs counts at the incidence of CMV antigenemia, duration from SCT to CMV-pp65 antigenemia and duration of treatments with anti-viral agents didn't have statistically significant differences between ATL and non-ATL respectively. CMV disease occurred in 7 (ATL 4, non-ATL 3) patients, however, there was also no significant difference between ATL and non-ATL. The cumulative incidence of CMV-pp65 antigenemia in ATL and non-ATL patients were 91.9% and 60.4% respectively (P<0.001). Interestingly, recipients whose ages were >=50 showed significantly high incidence of incidence of CMV-pp65 antigenemia compared with <50 (P=0.002). However, there were no difference between age >=50 and <50 (92% vs 91.7%) in ATL recipients. In multivariate analysis, ATL (HR: 2.625, P=0.008) and MAC (HR: 2.532, P=0.014) were positively contributed to incidence of CMV antigenemia by Cox regression analyses. Our study suggests that ATL could be one of independent risk factors of CMV replication after allogeneic hematopoietic stem cell transplantation.

Disclosures:
No relevant conflicts of interest to declare.