Two Distinct Clinical Courses and Outcomes in T-Cell Prolymphocytic Leukemia

Introduction: T-cell prolymphocytic leukemia (T-PLL) is a rare type of mature T-cell neoplasm with a poor prognosis. Up to 30% of patients initially present with indolent disease course that may be observed until progression to T-PLL with aggressive behavior. We aimed to compare the clinicopathologic characteristics and outcomes of patients with initially indolent versus aggressive disease. We hypothesized that patients with indolent disease have less cytogenetic abnormalities and a favorable overall survival (OS).

Methods: We identified 65 patients diagnosed with T-PLL between 2004 and 2020 who were treated at Moffitt Cancer Center. Clinical presentation, laboratory parameters, and bone marrow biopsy at the time of diagnosis were retrospectively reviewed. Patients were categorized into two groups: indolent or aggressive disease type. Patients were considered indolent if they did not have symptoms requiring immediate treatment such as B symptoms or fatigue, symptomatic lymphadenopathy, symptomatic organomegaly, hyperlymphocytosis, organ dysfunction, or cytopenias requiring transfusions. Patients with 3 or more chromosomal abnormalities were considered to have complex cytogenetics. Clinicopathologic characteristics were compared using Chi-square test. OS and factors that are potential influencers of survival were compared using the Kaplan Meier curve as well as Cox Proportional Hazards regression.

Results: Of the 65 patients with T-PLL, 32 (49%) presented with indolent disease and 33 (51%) presented with aggressive disease. The median age at diagnosis was 68 years (range 43-88 years). Patients with aggressive disease presented with a higher WBC compared to those with indolent disease, with median WBC 79.7 x 10 ⁹/L and 22.9 x 10 ⁹/L, respectively (p=<0.001). Patients with aggressive disease also presented with a higher absolute lymphocyte count (ALC), with median ALC 47.8 x 10 ⁹/L and 15.4 x 10 ⁹/L (p=<0.001) (Table 1). Extra-nodal, skin, and CNS involvement was not significantly different between disease types. Flow cytometry was similar between indolent and aggressive disease with the exception with the exception of CD56 and CD57 which were rare and only observed in aggressive disease. Patients with aggressive disease were more likely to have complex karyotype compared to patients with indolent disease (p=0.023). FISH results for inversion 14 and trisomy 8 were similar between disease types. Median time from diagnosis to initial treatment was 379 days for indolent and 44 days for those with aggressive disease. 36 (55%) patients were treated with Alemtuzumab as first line treatment. A total of 15 (23%) patients ultimately underwent allogeneic hematopoietic stem cell transplant (HSCT). The median OS for the entire cohort was 30 months. The median OS for indolent and aggressive disease was 44 and 24 months, respectively (p=0.015, Figure 1). The median OS for patients who underwent HSCT compared to those who did not was 99 and 24 months, respectively (p=0.002). Among patients with indolent disease, those who underwent HSCT had a significantly longer median OS of 153 compared to 34 months for those who did not (p=0.022). There was a trend toward improved OS in patients with aggressive disease who underwent HSCT compared to those that did not (35 vs 16 months; p=0.08). In addition, there was a trend toward improved OS with earlier treatment (<12 months) in the indolent group (383 versus 86 months, p= 0.155). On multivariate analysis (Table 2), factors that negatively affected overall survival were aggressive disease type (HR 3.0, p=0.018), presence of inversion 14 (HR 2.5, p=0.032), presence of B symptoms (HR 2.4, p=0.036), and absence of HSCT (HR 0.2, p=0.001).

Conclusion: Patients with T-PLL who present with aggressive disease, inversion 14, B symptoms, and those who are unable to undergo bone marrow transplant have lower overall survival. Characteristics that predict a more aggressive disease phenotype at diagnosis are high WBC, high ALC, presence of B symptoms, and complex karyotype.

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Figure 1

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