B-Cell Lymphoma Unclassified, Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma: A Single Center Experience of Intensive Chemotherapy with and without Auto-SCT
Authors: Lukina Anna E. , Baryakh Elena A. , Kovrigina Alla M. , Gemdzhian Eduard G. , Misyurin Vsevolod A. , Kravchenko Sergey K. , Vorobyev Vladimir I. , Mangasarova Jana K. , Magomedova Aminat U. , Polyakov Yuri U. , Obukhova Tatiana N. , Zvonkov Eugene E. , Morozova Anna K. , Savchenko Valeri G. 
Published: October 2019

Abstract
Background: According to current data B-cell lymphoma unclassified (BCLU), intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma represents a highly aggressive type of lymphoma with dramatically bad response for chemotherapy. Cases with translocation of two genes (MYC and BCL2 or BCL6) are divided into double-hit lymphomas (DHL). We need to estimate risk factors to intensify treatment and manage indications for autologous stem cell transplantation (auto-SCT) according to individual characteristics.
Aim: To evaluate results of BCLU treatment according to LB-M-04±R protocol in adults younger than 60 years old and CHOP-like regimens in elderly patients (≥60 years old) with auto-SCT in high risk patients group.
Patients and Methods: 21 pts observed in National Research Center for Hematology (Moscow) between 2004 and 2014 years were included in a current study. All of them were convenient to BCLU diagnosis criteria according to WHO classification of hematological malignancies (2008). Genetic analysis included: standard karyotyping in 7 pts (6 – lymph nodes samples, 1 sample of cerebrospinal fluid). FISH analysis was performed in 21 pts (in 7 cases on tumor cells; on imprints of tumor in 4 cases, on histologic slides from paraffin blocks - in 10 cases). Taking into account heterogeneity of a common group we divided all pts into 2 subgroups: DHL and non-DHL cases (7 vs. 14 respectively).
Pts younger than 60 years old (17 pts) were treated according to LB-M-04±R protocol which included A-C-A-C courses. Course A consisted from dexamethasone 10 mg/m2 i.v. 1-5 ds, methotrexate 1500 mg/m2 12-hours infusion 1st d, ifosfamide 800 mg/m2 1-5 ds, vincristine 1 mg/m2 1st d, doxorubicine 50 mg/m2 3rd d, cytarabine 150 mg/m2 4-5 ds, etoposide 100 mg/m2 4-5 ds; course C included dexamethasone 10 mg/m2 i.v. 1-5 ds, methotrexate 1500 mg/m2 12-hours infusion 1st d, vinblastine 5 mg/m2 1st d, cytarabine 2000 mg/m2 twice a day 2-3 ds, etoposide 150 mg/m2 3-5 ds. Rituximab were indicated before chemotherapy in dosage 375 mg/m2. CNS prophylaxis was made by intrathecal administration of prednisolone 30 mg, cytarabine 30 mg, methotrexate 15 mg in 1st day of each course. When complete remission (CR) was achieved after 2 courses, treatment lasted 4 courses. When tumor regression was diagnosed after 4 courses, treatment continued till 6 courses. 4 pts ˃60 years were managed by CHOP-like regimens ±R. We performed auto-SCT in non-DHL group with signs of poor prognosis (bone marrow involvement, multiple extranodal sites, CR after 6 courses) and in DHL when CR had been achieved after 4 courses. Pts with DHL after auto-SCT received 2 R-EPOCH courses more. As a conditional regimen BEAM was used. An overall survival (OS) as a primary endpoint and event-free survival (EFS) were assessed with using the Kaplan-Meier method (with log-rank test) to estimate an efficacy of treatment. Statistical analysis was performed with SAS 9.3 (SAS Institute Inc. Cary, NC).
Results: Studying group included 9 males and 12 females. Comparing pts according DH and non-DH status, DHL group (n=7) consisted of 2 males and 5 females, median age 48 years (30-74), ECOG status was 2.6 (95%CI 1.3-3.9) and non-DH group consisted of 7 male and 7 female, median age was 46 (23-76), ECOG status was 2.4 (95%CI 1.8-3.1). DHL pts had stage II of lymphoma according to Ann-Arbor classification in 1 case, III in 1 case, IV in 5 cases. Non-DHL pts had stage II of lymphoma in 2 cases and IV in 12 cases. Bone marrow involvement was revealed in 2 cases in DHL group and in 5 cases in non-DHL group. More than 1 extranodal site took place in 3 cases of DHL and 8 cases of non-DHL. Survival rates of groups were comparable because they were not significantly different of these characteristics. The 2-year OS and EFS rates were less for DHL pts compared with non-DHL pts: OS: 43 vs. 75%, P=0.24 and EFS: 29 vs. 66%, P=0.09 respectively (Figures 1and 2). Auto-SCT was performed in 2 pts with DHL treated by LB-M-04±R protocol (both pts still be alive) and in 3 pts with non-DHL (1 pt treated by LB-M-04±R and 1 treated by CHOP-like regimen+R are alive in CR and 1 pt treated by LB-M-04±R protocol developed a relapse).
Conclusions: Low OS and EFS in BCLU group are caused particularly by DHL cases. We need to enlarge an observation group to confirm benefits of auto-SCT in BCLU pts with signs of poor prognosis.
Figure 1 Figure 1. Figure 2 Figure 2.

Disclosures
No relevant conflicts of interest to declare.