INTRODUCTION: We analyzed the incidence, risk factors of central nervous system (CNS) relapse, and outcome of CNS involvement in patients with peripheral T-cell lymphomas (PTCL) from the Czech Lymphoma Study Group Registry NiHiL (Clinical Trial gov. NCT03199066). MATERIALS AND METHODS: Out of 1,040 patients with PTCL, we identified 29 patients (2.79%) with CNS involvement: 2 patients with primary CNS T cell lymphoma, 11 patients with CNS and systemic disease at diagnosis, and 16 patients (1.54%) at CNS relapse. The most common histology with CNS disease was PTCL, not otherwise specified. Progression-free survival (PFS) was defined as the time interval from diagnosis to progression or death. PFS-2 was defined as the interval from the date of a new relapse until the next relapse. RESULTS: Patients with testicular involvement received intrathecal prophylaxis with methotrexate. High-dose methotrexate-based treatment was administered in 44.8% of patients with CNS disease. Median follow-up was 71.3 months. The difference between the median PFS of 1,027 patients without initial CNS disease (32.6 months) and 11 patients with initial CNS and systemic disease (4.8 months) was significant (p = 0.04). The difference between the median PFS2 in CNS relapses (10.1 months) and 493 relapses outside of CNS (9.1 months) was not significant (p = 0.6). Risk factors for CNS relapses included the following: involvement of more than one extranodal site (p = 0.008), soft tissue involvement (p = 0.003), testicular involvement (p = 0.046), and the presence of B symptoms (p = 0.035). The difference between the median OS of 1,027 patients without initial CNS disease (46.0 months) and 11 patients with initial CNS and systemic disease (18.2 months) was significant (p = 0.02). The median OS2 in CNS relapses was 11.8 months and that in relapses outside of CNS was 21.3 months. CNS involvement was not associated with a significantly worse OS compared to relapsed/refractory patients without CNS involvement (p = 0.1). CONCLUSIONS: The incidence of CNS disease at the time of diagnosis and at relapse in PTCL is low and usually associated with other systemic involvement. The prognosis of PTCL with initial CNS involvement is significantly worse when compared to patients without CNS disease at diagnosis. The outcome of CNS relapse is comparable with relapsed PTCL outside of CNS. The optimal treatment is not defined yet.

• Klíčová slova
• CNS prophylaxis, central nervous system, leptomeningeal infiltration, methotrexate, peripheral T-cell lymphoma,
• Publikační typ
• časopisecké články MeSH

T-cell malignancies can be divided into precursor (T-acute lymphoblastic leukemia/lymphoblastic lymphoma, T-ALL/LBL) and mature T-cell neoplasms, which are comprised of 28 different entities. Most of these malignancies are aggressive with rather poor prognosis. Prognosis of relapsed/refractory (R/R) disease is especially dismal, with an expected survival only several months after progression. Targeted therapies, such as antiCD30 immunotoxin brentuximab vedotin, antiCD38 antibody daratumumab, and anti-CCR4 antibody mogamulizumab are effective only in subsets of patients with T-cell neoplasms. T-cells equipped with chimeric antigen receptor (CAR-Ts) are routinely used for treatment of R/R B-cell malignancies, however, there are specific obstacles for their use in T-cell leukemias and lymphomas which are fratricide killing, risk of transfection of malignant cells, and T-cell aplasia. The solution for these problems relies on target antigen selection, CRISPR/Cas9 or TALEN gene editing, posttranslational regulation of CAR-T surface antigen expression, and safety switches. Structural chromosomal changes and global changes in gene expression were observed with gene-edited products. We identified 49 studies of CAR-based therapies registered on www.clinicaltrials.gov. Most of them target CD30 or CD7 antigen. Results are available only for a minority of these studies. In general, clinical responses are above 50% but reported follow-up is very short. Specific toxicities of CAR-based therapies, namely cytokine release syndrome (CRS), seem to be connected with the antigen of interest and source of cells for manufacturing. CRS is more frequent in antiCD7 CAR-T cells than in antiCD30 cells, but it is mild in most patients. More severe CRS was observed after gene-edited allogeneic CAR-T cells. Immune effector cell associated neurotoxicity (ICANS) was mild and infrequent. Graft-versus-host disease (GvHD) after allogeneic CAR-T cells from previous hematopoietic stem cell donor was also observed. Most frequent toxicities, similarly to antiCD19 CAR-T cells, are cytopenias. CAR-based cellular therapy seems feasible and effective for T-cell malignancies, however, the optimal design of CAR-based products is still unknown and long-term follow-up is needed for evaluation of their true potential.

• Klíčová slova
• CAR-T cells, T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma, T-cell lymphoma, chimeric antigen receptor (CAR), immunotherapy, therapy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH