T-CELL PROLYMPHOCYTIC LEUKEMIA (T-PLL)
Introduction: T-PLL is a rare aggressive leukemia with a post-thymic T-cell phenotype. It is characterized by the proliferation of neoplastic T-cells in the peripheral blood, lymph nodes, liver, spleen and skin (1). It predominantly occurs in adults over the age of 30 years; median age is 65 years.
Clinical features: Splenomegaly is seen in two thirds of patients. Half of the patients have hepatomegaly and lymphadenopathy. Skin manifestations (maculopapular rash, erythroderma) occur in less than 20% of cases. Peripheral edema particularly periorbital and/or conjunctival, is particularly characteristic of T-PLL. Anemia and thrombocytopenia are common and many patients have lymphocytosis (often in excess of 100x 109/L) with 90% or more being prolymphocytes. LDH levels are high but there is no hypercalcemia, in contrast to HTLV related adult T-cell/ leukemia lymphoma (ATLL). Serology for HTLVI and II are negative.
Morphology: Peripheral blood examination is diagnostic and shows small to medium sized cells with non-granular basophilic cytoplasm, round to oval nuclei and visible nucleolus. The nuclei can be very irregular at times (cerebriform). The presence of cytoplasmic blebs is very common.
Skin: perivascular or diffuse dermal infiltrate without epidermotropism.
Spleen: dense red pulp infiltrate.
Lymph nodes: diffuse infiltrate, often paracortical, sometimes with sparing of follicles.
Immunophenotype: Flow cytometric immunophenotypic analysis shows a post-thymic immunophenotype, TdT and CD1a are negative while CD2, CD3 and CD7 (bright) are positive. CD4+/CD8- is the most common phenotype (60%), with coexpression of both CD4 and CD8 being the next common and unique to T-PLL. CD52 is positive. Immunohistochemical expression of TCL1 oncogene is useful for detecting residual T-PLL on bone marrow sections after therapy.
Antigen receptor genes: T-cell receptor (TCR) genes TRB@ and TRG@ are clonally rearranged.
Genetics: Recurrent chromosomal abnormalities of chromosome 14 are seen in 75% of cases; inversion 14 (most common), t (14; 14), both result in activation and expression of TCL-1 proto-oncogene. Also seen is t(X; 14) (q28; q11), in 20% of cases involving TCL1 gene (chromosome 14) and MTCP-1 (chromosome X). Trisomy 8 or iso8q is seen in two-thirds of cases. Abnormalities of ATM gene (chromosome 11q23) are also frequent.
Treatment and Prognosis: Currently, the best treatment is alemtuzumab, monoclonal antibody anti-CD52 antibody, followed by consolidation with a stem cell transplant where possible. The use of the alemtuzumab has improved the outcome and survival in T-PLL, allowing for high-dose therapy options aimed at eradicating the disease. The most important predictor of outcome is response to alemtuzumab therapy. In a series of 86 patients, non-responders had a median survival of only 4 months (2).
Differential diagnosis: B-PLL, T-cell large granular lymphocytic lymphoma (T-LGL), ATLL, Sezary syndrome and PTCL. B-PLL is immunophenotypically easy to differentiate (CD19, CD20, CD22, CD79a and CD79b positive). The HTLV I and II are negative in T-PLL as compared to ATLL. Also CD7 is mostly negative in ATLL. It is also very important to look at all the clinical data and laboratory information to differentiate T-PLL from other entities.
Treatment plan: The patient was started on alemtuzumab, (CAMPATH -1 H) and until now received 22 doses. The plan is to proceed with a non ablative matched unrelated donor transplant.
Contributed by Sarika Jain, MD and Fiona Craig, MD