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A 64-year-old man with no significant medical history was admitted to the intensive care unit with leukocytosis of 1.3 million/uL with differential of 100 percent lymphocytosis as part of work-up for fatigue and dizziness. He had anemia (hemoglobin 8.6 g/dL) and thrombocytopenia (platelets 24,000/mm³). Physical examination revealed hepatosplenomegaly (19 cm and 22 cm, respectively) without lymphadenopathy and was otherwise unremarkable. The blood smear demonstrated numerous atypical intermediate-size mature lymphoid cells with small nucleoli and knobbed cytoplasmic blebs (Figure 1). Flow cytometric analysis demonstrated a population of mature T cells with CD4⁺/CD8⁺ co-expression (88.7%). The neoplastic lymphocytes were positive for TCL1 by immunohistochemistry, and cytogenetics revealed a complex karyotype including inv14(q11.2q32), with fluorescent in situ hybridization (FISH) demonstrating TCL1 rearrangement.

From Abbas HA, et al. Cytoplasmic blebs in T-cell prolymphocytic leukemia. N Engl J Med. 2019;380:2360. Reused with permission from the author.

What is the most likely diagnosis?

1. Chronic lymphocytic leukemia (CLL)
2. Acute lymphocytic leukemia
3. T-cell prolymphocytic leukemia (T-PLL)
4. B-cell prolymphocytic leukemia
5. T-cell large granular lymphocytic leukemia

Response:

Answer: C

T-PLL is a rare T cell leukemia affecting less than one person per 1 million, with a median age of 65 years at presentation. Patients with T-PLL usually present with significant lymphocytosis exceeding 100 × 10⁹/L, hepatosplenomegaly, and nodal and extranodal involvement (including skin, lungs, and central nervous system). T-PLL used to be managed similarly to CLL despite differences in biological and clinical characteristics.

Recently, consensus criteria for diagnosis, staging, and treatment response assessment of T-PLL was introduced.¹ The diagnostic work-up of T-PLL requires evaluating the peripheral blood smear, immunophenotyping, and testing for genomic alterations. Some of the histologic features noted in T-PLL include the small nucleoli and knobbing of the cytoplasmic blebs. Immunophenotypically, T-PLL can have co-expression of CD4 and CD8, which is an unusual finding in T cells. Cytoplasmic expression of TCL1 is another notable finding in T-PLL cells. Importantly, alterations in chromosome 14 and TCL1 are seen in more than 90 percent of patients.

Approximately 20 percent of patients may have an indolent, nonproliferative disease that is asymptomatic and may not require systemic treatment. The remaining 80 percent who have active disease usually have constitutional symptoms, increasing leukocytosis, and/or extranodal involvement.
Treatment of T-PLL includes alemtuzumab (anti-CD52), which has a 90 percent overall response rate and a progression-free survival of eight to 11 months.¹ Other treatments include pentostatin and systemic steroids. When remission is achieved, allogeneic stem cell transplantation should be considered in appropriate candidates, as most patients unfortunately eventually relapse.

In summary, T-PLL is a rare leukemia that is difficult to diagnose and has limited treatment options and poor prognosis. The rarity of the disease and its resemblance to CLL and other lymphocytic leukemias may delay its diagnosis and treatment. Following expert opinion and updated consensus for diagnosis, staging, and treatment is paramount.

References:

1. Staber PB, Herling M, Bellido M, et al. . Blood. 2019;134:1132-1143.
2. Abbas HA, Han X. . N Engl J Med. 2019;380:2360.

Case written by Hussein Abbas, MD, PhD of MD Anderson Cancer Center, Houston, TX.