A patient with white blood cell counts more than a million: A diagnostic and therapeutic challenge

Prolymphocytic leukemias (PLLs) are rare mature lymphoid disorders of B- and T-cell subtypes with distinct features and an aggressive clinical course. PLL represents only 2% of all mature lymphocytic leukemias in adults. T-PLL represents 20% of all PLLs cases. T-cell prolymphocytic leukemia (T-PLL) is more rare and more rapidly progressive and aggressive than B-PLL; it is generally resistant to conventional chemotherapy, and historically the median survival has been about 7 months. Clinicians will often only see a case of T-PLL once every 5 to 10 years, which makes recognition of the disorder difficult. The prognosis is poor and there is no curative therapy. We report a 77-year-old male patient with de novo T-PLL presenting with WBC count of 1,115,000. We will discuss the clinical, morphologic, immunophenotypic and cytogenetic features of this rare entity. A distinctive hematologic aspect of T-PLL is a rapidly rising white blood cell count with a doubling time of weeks to months. The key morphologic feature in the diagnosis of T-PLL is a population of more than 55% prolymphocytes in the peripheral blood. The diagnosis can be made on peripheral blood by flow cytometry where a monoclonal lymphocyte population will show positivity for T-cell markers. T-PLL is characterized by complex chromosomal abnormalities, which suggests that chromosomal aberrations might occur progressively during the course of the disease, thus explaining the aggressive nature of this condition. The main challenge as a clinician treating T-PLL is to deliver long-term disease-free survival. The most important predictor of outcome is response to alemtuzumab therapy (Campath). Knowledge of the disrupted pathways and mechanisms underlying activation and proliferation in T-PLL has raised the possibility of developing future and promising treatment approach that targets these pathways and signals by the use of future molecule inhibitors. T-PLL is a rare disease and careful attention should be given to correctly diagnose this T-cell leukemia. Physicians should be aware of this unusual entity. With the advent of alemtuzumab, although much progress has been made in the treatment of this disease, autologous or allogeneic hematologic stem cell transplant (HSCT) still remains the only hope for cure.