Long-Smoldering T-prolymphocytic Leukemia: A Case Report and a Review of the Literature.

T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically presents at an advanced stage, with marked leukocytosis, B symptoms, hepatosplenomegaly, and bone marrow failure. It usually follows an aggressive course from presentation, and the prognosis is often considered dismal; the median overall survival is less than one year with conventional chemotherapy. This case report describes a patient with T-PLL who, after an unusually protracted inactive phase, ultimately progressed to a highly invasive, organ-involving disease. After initial treatments failed, a novel treatment approach resulted in a significant response.

Post-transplant lymphoproliferative disorder presenting as T-prolymphocytic leukemia: a case report.

INTRODUCTION: Post-transplant lymphoproliferative disorder is a serious disorder which occurs post hematopoietic stem cell transplant or solid organ transplantation. T-prolymphocytic leukemia is a T cell type monomorphic post-transplant lymphoproliferative disorder which accounts for only 2% of all mature lymphocytic leukemias in adults over the age of 30. CASE PRESENTATION: A 59-year-old man of Chinese ethnicity presented to our hematology unit with headache, lethargy, and exertional dyspnea for the past 1 month. He underwent an uneventful cadaveric renal transplant 20 years ago for chronic glomerulonephritis-induced end-stage renal disease. He had been on long-term immunosuppressants since then consisting of orally administered prednisolone 10 mg daily and orally administered cyclosporine A 50 mg twice daily. On examination, he was pale with a palpable liver and spleen. He had a functioning renal graft. Marrow flow cytometry confirmed T-prolymphocytic leukemia with lymphocytes expressing CD2, CD3, CD7, CD52, and TCL-1. His human T-cell lymphotropic virus and Epstein-Barr virus serology and deoxyribonucleic acid (DNA) were negative. He was treated with one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy to which he failed to respond. In view of his renal allograft, he was not suitable for alemtuzumab due to the risk of nephrotoxicity. He was given orally administered venetoclax but he died on day 17 due to severe auto tumor lysis syndrome. CONCLUSION: The place of immunophenotyping in the diagnosis and treatment of this disorder is of significant importance. More research needs to be carried out to further comprehend the pathophysiology and treatment modalities for this disorder.

Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course.

Translocations involving MYC are rare in chronic lymphocytic leukemia (CLL), and up to now, their prognostic significance remains unclear. We report the characteristics of 21 patients with CLL and nine patients with prolymphocytic leukemia (PLL), diagnosed in multiple centers (n = 13), which showed an MYC translocation demonstrated by fluorescence in situ hybridization. The prevalence was estimated to be <1%. Advanced age and male predominance were observed. Morphological analysis frequently revealed the presence of prolymphocytes. A typical "CLL-immunophenotype" was found in four of nine cases with PLL. Moreover, CD5 and CD23 were frequently expressed in PLL. The latter findings are atypical for PLL and may suggest transformation or progression of an underlying CLL. MYC translocations were frequently observed with concomitant adverse cytogenetic markers, such as del(11q) (n = 8/30) and/or del(17p)/monosomy 17 (n = 7/30). In addition, the presence of unbalanced translocations (n = 24 in 13/30 cases) and complex karyotype (n = 16/30) were frequent in cases with MYC translocations. Altogether, del(17p)/monosomy 17, del(11q), and/or complex karyotype were observed in 22 of 30 patients. Survival outcome was poor: the median time to treatment was only 5 months, and overall survival (OS) from clinical diagnosis and from genetic detection was 71 and 19 months, respectively. In conclusion, CLL/PLL with MYC translocations is a rare entity, which seems to be associated with adverse prognostic features and unfavorable outcome.

[B-cell chronic lymphocytic leukaemia and the similar states]. / Chronická B-lymfatická leukemie a jí podobné stavy.

B-cell chronic lymphocytic leukaemia and the similar diseases are seen predominantly in patients above the age 50 years, i.e. at the age when the patients also have other co-morbidities. The knowledge of these diseases on molecular level has improved significantly over the last decade. Molecular and biological prognostic factors are available in routine everyday practice. Assessment of these factors enables prediction of prognosis and, in some cases, also the response to therapy. The aim of the present review is to provide the medical community with the main information on this disease as patients with B-cell chronic lymphocytic leukaemia and similar disease states are of older age and very often suffer from a range of co-morbidities. Consequently, care for these patients involves physicians from various specialities. The aim of the following text is to present a clear overview of the basic information about this group of diseases that might be useful to all physicians who provide care to patients with B-cell chronic lymphocytic leukaemia and similar conditions. Since monoclonal immunoglobulin is sometimes identified in patients with these diseases, it is important to consider these conditions in the differential diagnosis of the states with the presence of monoclonal immunoglobulin.

Differential diagnosis in chronic lymphocytic leukaemia.

The diagnosis of chronic lymphocytic leukaemia (CLL) is based on clinical and laboratory features. Morphology and immunophenotype are the key initial diagnostic tests. In cases with atypical features, these investigations should be complemented with cytogenetics and/or histology to confirm the diagnosis and to exclude other B-cell disorders. Morphologically, CLL can be classified into typical and atypical forms. Cell-marker studies provide a robust foundation to establish the diagnosis as the lymphocytes have a distinct immunophenotypic signature. Although no single antigen is exclusively expressed in CLL cells, when several markers are compounded into a scoring system the results allow firming up of the diagnosis. Other immunological markers, such as CD38 or ZAP-70, have an important prognostic impact. Fluorescence in-situ hybridization (FISH) analysis also provides prognostic information, chiefly by detecting 17 (p53 locus) and 11q deletion, and may determine the type of therapy.

Current treatment options in prolymphocytic leukemia.

Prolymphocytic leukemia (PLL) is a rare lymphoproliferative disorder characterized by marked leukocytosis and splenomegaly. PLL accounts for approximately 2% of chronic lymphoid leukemias. The clinical course is progressive in the majority of cases due to the resistance of the disease to conventional chemotherapy. The disease is divided according to the cell of origin into the B- (B-PLL) and T-cell (T-PLL) types. T-PLL and B-PLL are morphologically identical, but lymphadenopathy and skin involvement are more common in T-PLL than in B-PLL. Approximately 80% of cases are of B-cell phenotype. T-PLL has a more aggressive course, poorer response to chemotherapy, and shorter median survival than B-PLL. PLL has poorer prognosis than chronic lymphocytic leukemia (CLL), and the patients with static disease for a longer period of time are rare. In general, B-PLL patients have better prognosis than T-PLL patients. PLL is still considered an incurable disease. Similarly to CLL, treatment is not indicated in asymptomatic patients. In previous decades, splenectomy, splenic irradiation, leucapheresis, and alkylating agents used alone or in combination with other cytotoxic agents have been used for the treatment of PLL. Subsequently, purine nucleoside analogs (fludarabine, cladribine, and pentostatin) have been introduced for the therapy of these disorders. More recently, monoclonal antibodies, especially alemtuzumab, have been found more effective, especially in T-PLL. Finally, high-dose chemotherapy followed by allogenic or autologous stem cell transplantation seems to be an effective, probably curative, strategy for the treatment of selected patients with PLL. In this review, current therapeutic strategies in PLL are presented.

Mature T-cell leukemias including T-prolymphocytic leukemia, adult T-cell leukemia/lymphoma, and Sézary syndrome.

The 2005 Society for Hematopathology/European Association for Haematopathology Workshop Session 1 was devoted to case presentations with discussions of 3 types of mature T-cell leukemias--T-cell prolymphocytic leukemia, adult T-cell leukemia/lymphoma, and Sézary syndrome. These 3 disorders are clonal proliferations of postthymic alphabeta T cells that are often characterized by systemic manifestations and a leukemic blood picture. The application of clinical, morphologic, immunophenotypic, and genetic studies to the assessment and characterization of these 3 disorders is presented, along with specific diagnostic recommendations and differential diagnostic considerations.

Production of vascular endothelial growth factor in T-cell prolymphocytic leukemia.

We describe a 79-year-old man who had massive pleural effusion and a proliferation of prolymphocytic leukemia cells in the peripheral blood, bone marrow, and pleural effusion fluid. Immunophenotyping of leukemia cells revealed either CD3+CD4+CD8-CD25+ or CD3+CD4+CD8+CD25+. The antibody against human T-cell lymphotropic virus type I was negative. A diagnosis of T-PLL was made. The level of VEGF in the plasma or pleural effusion fluid was very high. Moreover, polymerase chain reaction analysis demonstrated an expression of VEGF mRNA in the leukemia cells, indicating a production of VEGF from leukemia cells and its involvement in the pathogenesis of T-PLL.

Complex karyotype including chromosomal translocation (8;14) (q24;q32) in one case with B-cell prolymphocytic leukemia.

We report a case of a 64-year-old white female patient, who presented with symptomatic anemia (Hgb: 6.8g/dl), thrombocytopenia (platelets: 94,000/mcl) and leukocytosis (WBC: 156,000/mcl). Peripheral blood smear revealed markedly increased white blood cell count with predominance of atypical lymphoid cells of intermediate size, moderately dense chromatin, and prominent large single nucleoli. Bone marrow aspirate smear showed predominance (78%) of atypical lymphoid cells morphologically identical to those seen in the peripheral blood. The bone marrow core biopsy was hypercellular and packed with prominent infiltrate of prolymphocytes. Immunophenotypic analysis revealed a population of monoclonal cells (75% of all -erythroid cells) characterized by CD45+, CD19+, CD20+, CD5+, HLA-DR+, CD10-, CD23+/-, CD38+ and FMC7-. The abnormal cells were restricted to kappa light chain immunoglobulin with low intensity. Cytogenetic study showed an abnormal clone of eight cells with the following karyotype: 45,X,-X,add(8)(p11.2),t(8;14)(q24;q32),add(20)ql3[8]/46,XX[12]. The relative rarity of B-PLL and the heterogeneity of clinical and laboratory parameters make it difficult to define the natural history and prognosis in all cases. The optimal treatment for B-PLL is still unknown and to date there are no reports of chromosomal abnormalities as a prognostic factor. The patient was treated with six cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Complete remission was achieved according to the criteria defined by National Cancer Institute Working Group for CLL.

Periorbital edema as the initial presentation of T-cell prolymphocytic leukemia.

A 57-year-old woman presented with a history of progressive bilateral upper and lower eyelid edema. Laboratory tests revealed T-cell prolymphocytic leukemia. Despite systemic treatment, she died 2 weeks after presentation. This life-threatening disorder should be added to the differential diagnosis of eyelid edema.

Mature T-cell leukemias.

Mature T-cell and NK-cell leukemias are a group of relatively uncommon neoplasms derived from mature or postthymic T-cells accounting for a relatively small percentage of lymphoid malignancies. The recent availability of modern immunophenotypic and molecular tools has allowed a better distinction of these disorders from their B-cell counterparts. Similarly, identification of recurrent cytogenetic abnormalities, as well as plausible mechanisms through which these molecular events influence cellular signaling pathways, have created further insight into the pathogenesis of these disorders. Furthermore, the availability of new agents such as alemtuzumab has generated significant interest in devising specific therapeutic strategies for these malignancies. Herein, we review the clinical and pathological features of mature T-cell leukemias.

T- cell prolymphocytic leukemia - a rare case.

T- cell Prolymhocytic leukemia (T-PLL) is a rare mature post-thymic T-cell malignancy that is usually reported in the elderly and follows an aggressive course. A 68 year old male presented with a history of weakness and weight loss of two months duration. Clinical examination revealed pallor, enlarged cervical and axillary lymph nodes and splenomegaly. He also had a maculo- papular skin rash. There was marked leucocytosis, anemia and thrombocytopenia (WBC 445 x 103 sub/ml, Hb 8.5 gm/dl, Platelet 25 x 103 sub/microl) with 60% prolymphocytes in the peripheral blood. Bone marrow was hypercellular with an excess of prolymphocytes. Flow cytometric analysis of the bone marrow showed positivity for CD2, CD3, CD4, CD5 and CD 7. T- PLL is a rare T cell disorder with characteristic clinical and laboratory features. Currently, no optimal treatment exists although there has been some success with 2'- deoxycoformycin or Campath-1H.