Treatment of Primary Bone Lymphoma with Intensive Chemotherapy
Authors: Morozova Anna , Zvonkov Eugene , Mamonov Vasilii , Kovrigina Alla M. , Kravchenko Sergei , Lorie Yuri , Vorobyev Vladimir I. , Penskaya Ekaterina , Gemdjian Eduard , Savchenko Valeriy G 
Published: October 2019

Abstract
Abstract 4874

Background
Primary bone lymphoma (PBL) is a rare extranodal type of tumor. A diagnosis of diffuse large B-cell lymphoma (DLBCL) is made in 90% of all cases. The treatment standard for PBL is ÑÍÎ−D chemotherapy (CT) combined with radiation therapy. In the group of PBL patients with a local (IE) stage and without any unfavourable prognostic factors (elevated lactate dehydrogenase (LDH) concentrations, Â-symptoms, tumor size ≥10 cm) treated with standard chemotherapy and radiation, the relapse-free 5-year survival rate is as high as 80% to 100%. In advanced disease stages (stage II, IVE and any unfavourable prognostic factor) this treatment strategy leads to a remission in just 20% of patients (Ramadan KM, Shenkier T et al. Ann Oncol 18:129–135, 2007). Therefore, the results achieved with the ÑÍÎ−D regimen and radiation therapy in the treatment of adult patients with advanced PBL are unsatisfactory. Further research is thus needed to boost treatment efficacy for patients with advanced PBL. One of the ways to overcome the chemotherapy resistance of the tumor is primary intensification of CT. For instance, according to Children's Cancer Group data, high-dose CT was effective in children suffering from advanced PBL (Lones MA, Perkins SL et al. Clin Oncol 20:2293–2301, 2002). Intensive CT has not been used previously in adult patients with PBL.

Purpose
To evaluate the efficacy of intensive CT according to the mNHL-BFM-90 program in adult patients with advanced-stage PBL.

Materials and methods
The study enrolled all patients (22 subjects in total) with advanced-stage PBL monitored by the Research Centre of Haematology in the period from 2007 to 2012; 13 were male and 9 female, aged from 16 to 69 years (median age, 39 years). According to the WHO classification, all patients were diagnosed with DLBCL. The following evaluations were performed for disease staging: physical examination and medical history, complete blood count and blood chemistry, chest and abdominal computed tomography, whole-body positron emission tomography using 18F-fluorodeoxyglucose, magnetic resonance imaging and computed tomography of affected bones. Tumor staging was done according to the Ann-Arbor classification. Local IÅ stage (involvement of 1 bone) was verified in 6 cases (27%), stage IIÅ (involvement of regional lymph nodes) in 3 subjects (13%), and stage IVÅ (multiple bone involvement) in 13 patients (60%). Patients with the IIIÅ stage (distant nodal disease) were not recruited in this study. The main symptoms of the disease included pain and swelling. LDH elevation was observed in 13 cases (60%), Â-symptoms were found in 15 patients (68%), and large-size tumors were seen in 20 subjects (90%). The most common tumor sites were the skull bones, vertebrae, and femur. The average ECOG score for global condition assessment was 2 at the time of CT initiation.
All patients received treatment according to the mNHL-BFM-90 intensive CT program (Reiter A, Schrappe M. et al. Blood 94(10): 3294–3306, 1999).
This program was modified: adriamycin was administered on the 3rd day of course ÀÀ at a dose of 50 mg/m2. Methotrexate was administered on the 1rd day of course C. The dose of methotrexate was reduced to 1.0 g/m2 and the administration time shortened to 12 hours. Leucovorin was administered in 6 hours after the end of the methotrexate infusion until the serum methotrexate concentration fell below 0.1 μmol/L.
The toxicity of this treatment was assessed using the NCIC Common Toxicity Criteria.

Results
Complete remissions were achieved in 20 patients (90%; 95th% CI, 70% to 95%). The mean follow-up period was 23 months (range, 1 to 68 months). Relapses were observed in two patients for 6 and 40 months. Grades 3, 4 haematological toxicity was observed in all study subjects. Non-haematological toxicities were not life-threatening (grades 1, 2). Blood component replacement therapy and administration of leukopoiesis stimulators were required in all patients. No deaths related to mNHL-BFM-90 treatment occurred. No patient was withdrawn from the treatment program. No second malignancies were observed.

Conclusion
The obtained results indicate a high chemosensitivity of PBL. The mNHL-BFM-90 program is the therapy of choice for patients with advanced PBL. Adult patients tolerate the intensive CT program well with complex accompanying therapy being administered.

Disclosures:
No relevant conflicts of interest to declare.