Immunophenotypic characterization of T-cell prolymphocytic leukemia.

OBJECTIVES: To review clinical data, cytogenetic findings, and flow cytometric analysis in 20 patients with T-cell prolymphocytic leukemia (T-PLL), a rare, aggressive, mature T-cell leukemia with poor prognosis and short survival. METHODS: Using multiparameter flow cytometry with a large combination of antibodies, we summarize the immunophenotypic features of T-PLL, including unusual immunophenotypic variants, and illustrate immunophenotypic clues that may help distinguish this entity from other T-cell malignancies. RESULTS: By flow cytometry, T-PLL is characterized by a postthymic mature T-cell immunophenotype with a variety of abnormalities that usually allow distinction from other mature T-cell leukemias. CONCLUSIONS: Although definitive diagnosis of T-PLL requires a systemic approach with integration of clinical data, morphology, immunophenotype, cytogenetics/fluorescence in situ hybridization, and molecular features, our results indicate immunophenotyping by multiparameter flow cytometry greatly facilitates diagnosis and assists with subclassification of this mature T-cell leukemia.

T-cell prolymphocytic leukemia in Japan: is it a variant?

T-cell prolymphocytic leukemia (T-PLL) is characterized by a post-thymic immunophenotype, salient chromosome abnormalities, and an aggressive clinical course. However, cases in which these features are absent have been occasionally reported in Japan. Here, clinical and biological features of 13 T-PLL cases, diagnosed between 1992 and 2009 in the Tohoku region of Japan, were compared with three Western series. Median age was 64 (range 40-78) years old, and the male to female ratio (12:1) was higher than that of the Western series (P < 0.04). Presented manifestations were similar to those of Western cases, but central nervous system involvement, which is rare in Western cases, was observed in 3 of 13 cases (23 %) (P < 0.04). Immunophenotypic patterns were similar to those of Western cases, but HLA-DR was positive in 6 of 9 cases (67 %), which is distinct from Western cases (0-9 %) (P < 0.002). By chromosome analyses, 14q11 abnormality and trisomy 8q, which are common among Western cases (70-80 %), were not observed in any cases (P < 0.002). Morphologically, seven were classified as typical type, five as a small-cell variant, and one as a cerebriform variant. Seven cases experienced an aggressive course, whereas six experienced an indolent course over a median follow-up of 50 months. In contrast to Western cases, clinical courses were closely correlated with morphological types; 86 % of typical types were aggressive, whereas 83 % of small-cell types were indolent (P = 0.025). On the basis of these observations, together with previous Japanese cases in the literature, we propose that Japanese cases of T-PLL may constitute a variant.

T-cell prolymphocytic leukemia: update and focus on alemtuzumab (Campath-1H).

T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell lymphoproliferative disorder. While the etiology of T-PLL is unknown, recent progress in unraveling the molecular basis of leukemogenesis has been substantial and may yield novel therapeutic targets. T-PLL is a distinct disease entity and the diagnosis can be readily made based on characteristic clinical features and laboratory findings. Prior to the appearance of pentostatin and alemtuzumab in clinical protocols, outcome for T-PLL patients was exceedingly poor with median survival measured in months. While the use of alemtuzumab in particular has improved remissions, the disease remains incurable. Future collaborative efforts investigating novel treatment approaches will be crucial to improving survival for patients with this disease.

T-cell prolymphocytic leukaemia: does the expression of CD8+ phenotype justify the identification of a new subtype? Description of two cases and review of the literature.

T-cell chronic lymphocytic leukaemia (T-CLL) has recently been reclassified under the heading of T-cell prolymphocytic leukaemia (T-PLL) because of its unfavourable clinical course, independently of the morphologic features. This rare neoplasm usually shows CD4+/CD8- phenotype. Herein we report on two cases of T-PLL with CD8 expression that correspond to a possible variant of the disease first proposed by Hui et al. in 1987. These cases presented with malignant cells showing immunophenotypic features that can be easily identified and distinguished from other peripheral T-cell leukemias. However, the total number of cases studied is inadequate for defining a discrete clinico-pathologic entity with characteristic clinical features and cytogenetical abnormalities. An international collaboration in which tissue from similar cases is referred to a central pathologist for immunophenotyping and cytogenetical study, and clinical data are centrally compiled, may assist in defining this rare malady as a discrete clinico-pathologic entity.

Chronic lymphatic leukemias of T and NK cell type.

T cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) and large granular lymphocyte leukemia of T or NK cell type (T-LGL or NK-LGL leukemia) are chronic lymphoproliferative diseases derived from post-thymic immunocompetent lymphoid cells. T-PLL is morphologically characterized by a prominent central nucleolus in a medium-sized cell expressing a mature T cell immunophenotype. Clonal genetic changes involving chromosome 14 and T cell receptor gene rearrangements are characteristics of these diseases. They are usually progressive and there is no efficient treatment available. The classification of some cases presenting with a morphological picture similar to B-CLL, but with immunophenotypic and clinical features resembling T-PLL, as T-CLL is still controversial. The phenotypic profiles and the establishment of clonality are the hallmarks of defining T-LGL leukemia and NK-LGL leukemia. The CD3+/CD57+/CD56- immunophenotype and the clonal rearrangement of the T cell receptor genes characterize T-LGL leukemia, which presents clinically with a rather indolent course of disease, complicated by frequent infections secondary to neutropenia. NK-LGL leukemia cells express CD3-/CD56+/CD57-, but in most cases clonality cannot easily be established. Clinically the patient may either present with constitutional symptoms and suffer a short and aggressive course of disease or may have a more chronic disease similar to T-LGL leukemia. Therefore, it may be reasonable to subdivide NK-LGL proliferation into the more aggressive 'NK-LGL leukemia/lymphoma' and 'chronic NK cell lymphocytosis'.

T-cell form of chronic lymphocytic leukaemia: a reaffirmation of its existence.

Early in the 1980s three categories of T-cell chronic lymphocytic leukaemia were recognized: CD4+ CD8- knobby type, CD4- CD8+ azurophilic type and CD4+ CD8- adult T-cell leukaemia (ATL) type. Both azurophilic and ATL types were later shown to be distinctive disorders, whereas the knobby type has been largely neglected and even considered non-existent by some authors. In this report we describe two patients with leukaemia of CD3+ CD4+ CD8- post-thymic T lymphocytes presenting with marked lymphocytosis, generalized lymphadenopathy and hepatosplenomegaly. We believe that CLL of the post-thymic T-lymphocytes is a distinct entity, and merits a separate designation from other T-cell leukaemias.

Chronic lymphoproliferative disorders: classification and diagnosis.

The chronic lymphoproliferative disorders are morphologically, immunologically and clinically heterogeneous. Common features of these processes include T, B or natural killer cell immunophenotypes and terminal deoxy-nucleotidyl transferase negativity. The B cell lymphocytic disorders include B-chronic lymphocytic leukaemia, B cell prolymphocytic leukaemia, chronic lymphocytic leukaemia-prolymphocytic leukaemia, non-Hodgkin's lymphoma (including mantle cell lymphoma) in leukaemic phase, hairy cell leukaemia and splenic lymphoma with villous lymphocytes. The T cell chronic lymphoproliferative disorders include prolymphocytic leukaemia, adult T cell leukaemia-lymphoma, large granulated lymphocyte leukaemia and Sézary syndrome. Occasionally, a lymphocytic proliferation is encountered that does not satisfy the morphological or immunophenotypical criteria for any of the above categories. These processes are best left unclassified.

Chemical composition and tissue distribution of the human CDw44 glycoprotein.

The CDw44 glycoprotein was purified from 2.3 x 10(11) CD3+ CD4+ CD8- T-chronic lymphocytic leukaemia (CLL) cells using F10-44-2 monoclonal antibody affinity chromatography, DEAE-Sepharose anion-exchange chromatography, passage down carboxymethyl (CM)-Sepharose cation-exchange columns, wheat germ lectin affinity chromatography and gel-permeation chromatography. On elution in non-ionic detergents from the DEAE column, two distinct peaks of antigen activity were obtained. The CDw44 glycoprotein in each peak was a glycoprotein of 85,000 MW, but the amino acid composition of the peaks was noticeably different. Carbohydrate compositions showed that each peak contained approximately 30% (w/w) carbohydrate, the composition suggesting both O-linked and complex N-linked glycans. Modulation studies with the F10-44-2 antibody on normal peripheral blood mononuclear cells (PBMC) demonstrated that the CDw44 glycoprotein of T cells consisted of one fraction that was readily modulated, and the other which was resistant to modulation. Detailed tissue distribution studies for CDw44 were performed using the F10-44-2 antibody on frozen sections of human tissues. CDw44 has a restricted tissue distribution, but is found on many highly diverse cell types (e.g. T lymphocytes, smooth muscle cells, some secretory glands, skin epithelial cells).