CD8 POSITIVE T-CELL PROLYMPHOCYTIC LEUKEMIA (T-PLL) PRESENTING WITH COMPLEX KARYOTYPE WITH A RARE DERIVED CHROMOSOME AND ADDITIONAL SIGNALS IN MYC (8Q), IGH (14Q) AND TP53 (17P) GENES

Abstract

Introduction: T-cell prolymphocytic leukemia (T-PLL) is a rare T-cell leukemia, accounting for approximately 2% of lymphocytic leukemia cases in adults over 30 years of age. It has an aggressive clinical course and poor prognosis, in addition to a low response to conventional chemotherapy and a short survival time. This disease is characterized by post-thymic lymphocyte proliferation with small to regular size. The cells have weak CD3 expression and CD4 expression on the cell membrane occurs in over half of the cases. Co-expression of CD4 and CD8 occurs in about 25% of cases. A smaller proportion of cases have cells with only CD8 expression on the cell membrane. The main feature is severe leukosis in peripheral blood, but involvement of bone marrow, lymph nodes, liver, spleen and skin are not uncommon. Case report: Previously healthy 57-year-old woman presenting with abdominal pain and distension, weight loss, asthenia, and decreased general condition for 2 months. Physical examination revealed splenomegaly (19 cm RCE) and hepatomegaly (18 cm RCD), generalized lymphadenopathies of no more than 2 cm. CBC with Hb 7.5 g/dL, large leukocytosis 472 × 109/L with 92% prolymphocytic cells and platelet count was 31 × 109/L. Multiparametric flow cytometric analysis (MFC) in peripheral blood showed a mature T-cell lineage strongly positive for CD3, CD8, CD7 and CD26, negative for CD4, CD45 RA and RO and NK marker isoforms (CD56, CD57, CD94) but positive for cytoplasmic TCL1. TCR rearrangement evaluation showed clonally CD8 T-cells positive for Vβ chain 8. Conventional cytogenetic examination showed complex karyotype with a rare derived chromosome: der(2)t(1;2)(q21;q37), plus iso chromosome 8q, deletion 11q22, structural changes involving chromosomes 14, 13, 17 and several markers. FISH confirmed additional signals in MYC (8q), IGH (14q) and TP53 (17p) genes. The patient treated with chemotherapy (Fluouracil, Cyclophosphamide and Mitoxantrone), with no response. Since she maintained lymphocytosis, lymphadenomegaly and hepatosplenomegaly, she was treated with Alentuzumab (anti-CD52) with a plan to do 12 cycles, but showed progression within 3 months, requiring discontinuation of the medication. The patient was referred for palliative care in May 2021. Conclusion: We report the case of a patient with T prolymphocytic leukemia presenting with an elevated peripheral blood white blood cell count, complex karyotype with a rare derived chromosome, der(2)t(1;2)(q21;q37), aberrant immunophenotype and progressive disease despite treatment with alemtuzumab.