HAEM5:T-prolymphocytic leukaemia: Difference between revisions

Parastou Tizro, MD, Celeste C. Eno, PhD, Sumire Kitahara, MD

Cedars-Sinai, Los Angeles, CA

* In T-PLL, the rapid growth of the disease necessitates immediate initiation of treatment. The most effective first-line treatment is alemtuzumab, an anti-CD52 antibody with remission rates over 80%. However, these remissions usually last only 1-2 years. To potentially extend remission, eligible patients are advised to undergo allogeneic blood stem cell transplantation (allo-SCT) during their first complete remission, which can lead to longer remission durations of over 4-5 years for 15-30% of patients. Consequently, the prognosis for T-PLL remains poor, with median overall survival times under two years and five-year survival rates below 5%[https://clinicaltrials.gov/study/NCT03989466 . Ongoing studies are exploring molecularly targeted drugs and signaling pathway inhibitors, for routine clinical use in treating T-PLL.]

* T-prolymphocytic leukemia (T-PLL) is an aggressive form of T-cell leukemia marked by the proliferation of small to medium-sized prolymphocytes exhibiting a mature post-thymic T-cell phenotype.<ref name=":5" />

* T-PLL is an uncommon disease, accounting for approximately 2% of all mature lymphoid leukemias in adults. It mainly affects older individuals, with a median onset age of 65 years, ranging from 30 to 94 years. The disorder exhibits a slight male predominance, with a male to female ratio of 1.33:1.<ref name=":5" />

* The most prevalent symptom of the disease is a leukemic presentation, characterized by a rapid, exponential increase in lymphocyte counts, which exceed 100 × 10^9/L in 75% of patients. Approximately 30% of patients may initially experience an asymptomatic, slow-progressing phase, but this typically develops into an active disease state.<ref name=":5" /><ref name=":6" />

* Peripheral blood, bone marrow, spleen (mostly red pulp), liver, lymph node (mostly paracortical), and sometimes skin and serosa (primarily pleura). Extra lymphatic and extramedullary atypical manifestations including skin, muscles and intestines are particularly common in relapse.<ref name=":5" />

* Blood smears in T-PLL typically reveal anemia, thrombocytopenia, and leukocytosis, with atypical lymphocytes in three morphological forms: The most common form (75% of cases) features medium-sized cells with a high nuclear-to-cytoplasmic ratio, moderately condensed chromatin, a single visible nucleolus, and slightly basophilic cytoplasm. In 20% of cases, the cells appear as a small cell variant with densely condensed chromatin and an inconspicuous nucleolus. About 5% of cases exhibit a cerebriform variant with irregular nuclei resembling those in mycosis fungoides. Regardless of the nuclear features, a common morphological characteristic is the presence of cytoplasmic protrusions or blebs.<ref>{{Cite journal|last=Gutierrez|first=Marc|last2=Bladek|first2=Patrick|last3=Goksu|first3=Busra|last4=Murga-Zamalloa|first4=Carlos|last5=Bixby|first5=Dale|last6=Wilcox|first6=Ryan|date=2023-07-28|title=T-Cell Prolymphocytic Leukemia: Diagnosis, Pathogenesis, and Treatment|url=https://pubmed.ncbi.nlm.nih.gov/37569479|journal=International Journal of Molecular Sciences|volume=24|issue=15|pages=12106|doi=10.3390/ijms241512106|issn=1422-0067|pmc=PMC10419310|pmid=37569479}}</ref>Bone marrow aspirates show clusters of these neoplastic cells, with a mixed pattern of involvement including diffuse and interstitial, in trephine core biopsy.<ref name=":6" />

* '''Cytochemistry:''' T-cell prolymphocytes show strong staining with alpha-naphthyl acetate esterase and acid phosphatase, presenting a distinctive dot-like pattern, but cytochemistry is not commonly used for diagnosis.<ref>{{Cite journal|last=Yang|first=K.|last2=Bearman|first2=R. M.|last3=Pangalis|first3=G. A.|last4=Zelman|first4=R. J.|last5=Rappaport|first5=H.|date=1982-08|title=Acid phosphatase and alpha-naphthyl acetate esterase in neoplastic and non-neoplastic lymphocytes. A statistical analysis|url=https://pubmed.ncbi.nlm.nih.gov/6179423|journal=American Journal of Clinical Pathology|volume=78|issue=2|pages=141–149|doi=10.1093/ajcp/78.2.141|issn=0002-9173|pmid=6179423}}</ref>

* '''Immunophenotype:''' T-cell prolymphocytes exhibit a post-thymic T-cell phenotype. In 60% of cases, the cells are CD4+ and CD8-. In 25% of cases, they co-express both CD4 and CD8, while the remaining 15% are CD4- and CD8+.<ref name=":7" />