Detection of T-Cell Clonality in Bone Marrow in Peripheral T-Cell Lymphoma, Not Otherwise Specified

Introduction: Peripheral T-cell lymphoma, unspecified (PTCL, NOS) is a tumor of mature T-lymphocytes characterized by aggressive course and low response rate to CHOP-like therapy. Bone marrow involvement in PTCL, NOS is detected by histological investigation in about 20-40% of patients and it is considered to be a poor prognostic factor. Importance of T-cell clonality examination in bone marrow as a prognostic and staging factor has been insufficiently studied.

Aim: In order to evaluate the significance T-cell receptor gene γ- and β-chains (TCRG and TCRB) rearrangements for identification of bone marrow involvement; to estimate its value for staging and prognosis; to evaluate the significance of T-cell clonality persistence in bone marrow after initial therapy in patients with PTCL, NOS.

Patients and methods: Bone marrow samples of 27 patients with primary PTCL, NOS (median age 62 years, range 32-77) have been obtained from 2006 till 2014 and were analyzed retrospectively. Morphological examination was performed for all bone marrow samples. Detection of T-cell clonality by revealing rearrangements of TCRB and TCRG were performed by PCR in bone marrow samples of patients before and after initial chemotherapy.

Results: Bone marrow involvement was revealed by histological investigation in 22 (81%) of patients. T-cell clonality was detected by rearrangements of TCRG or TCRB in 26 (96%) patients, including 4 of 5 patients without bone marrow involvement by histology. Rearrangements of TCRG and TCRB were detected in 24 (89%) and 26 (96%) of patients, respectively. Rearrangements of TCRB were observed without rearrangements of TCRG in 2 cases. Interestingly, we detected more than 2 clonal rearrangements present simultaneously in 33% of cases. For monitoring minimal residual disease the examination of T-cell clonality in bone marrow samples was performed in 15 of 27 patients after initial therapy; all these 15 patients achieved complete remission. Persistence of T-cell clonality was observed in 14 of 15 patients after treatment, disease progression was noted in 1-3 months in all these cases.

Conclusion: The examination of T-cell clonality in the bone marrow seems to be important and necessary for staging, monitoring minimal residual disease. Detection of T-cell clonality in bone marrow allows revealing its involvement even without morphological features in primary patients with PTCL, NOS. Persistence of clonal rearrangements in bone marrow after initial therapy shows continuing lesion and necessity for timely therapy escalation for patients with PTCL, NOS.