pentostatin and Leukemia--Prolymphocytic--T-Cell

Sezary syndrome (SS) presents clinically as erythroderma, which may be pigmented, and pruritic, associated with peripheral lymphadenopathies. Erythroderma may also occur in a broad range of reactive and malignant conditions including T-cell prolymphocytic leukemia (T-PLL). We report a case initially diagnosed as SS but ultimately diagnosed as T-PLL based upon skin involvement.. A 70-year-old man was referred by his hematologist for management of SS. Physical examination revealed lymphadenopathies and mild diffuse erythema without infiltration. His WBC count was elevated at 8.3 G/L. A peripheral blood smear showed Sezary-like cells. Flow cytometry of peripheral blood revealed prolymphocytic T-cells staining positively for CD2, CD3, CD4 and CD7. Cytogenetic studies showed chromosomal abnormalities in terms of number and structure with missing chromosomes 6 and13, as well as deletion of chromosome 17. Finally, a diagnosis of T-PLL was made. Pentostatin was initiated pending treatment with alemtuzumab, but the patient's overall condition deteriorated rapidly and he died 10 days later.. Diagnosis of LPLT is based upon a number of factors. In the case presented herein, the clinically atypical nature of the skin lesions prompted the dermatologist to review the diagnosis. The morphology of the circulating T-lymphocytes and their immunologic and phenotypic characteristics finally ruled out the diagnosis of Sezary syndrome, while their association with compatible cytogenetic anomalies enabled a diagnosis of prolymphocytic leukemia to be made instead.. Prolymphocytic leukemia involves complex differential diagnosis with regard to Sezary syndrome, posing potential pitfalls for hematologists and dermatologists.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Capecitabine; Chromosome Deletion; Combined Modality Therapy; Delayed Diagnosis; Diagnostic Errors; Fatal Outcome; Humans; Immunophenotyping; Leukemia, Prolymphocytic, T-Cell; Male; Neoplasms, Second Primary; Pentostatin; Rectal Neoplasms; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes

T-cell prolymphocytic leukemia is a rare postthymic malignancy with distinctive clinical, morphologic, immunophenotypic, and cytogenetic features. The clinical course is typically aggressive with poor response to conventional chemotherapy and short survival. Treatment with purine analogues and alemtuzumab has resulted in significantly higher response rates and improved survival. Nevertheless, responses are relatively short, and the only potential curative treatment is allogeneic stem cell transplantation. The age and comorbidities of many of the patients has limited this option, but the growing use of nonmyeloablative transplantation has now widened the patient eligibility for this approach.

Topics: Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Agents; Female; Gene Expression Regulation, Leukemic; Humans; Immunophenotyping; Leukemia, Prolymphocytic, T-Cell; Male; Medical Oncology; Middle Aged; Pentostatin; Stem Cell Transplantation; Transplantation, Homologous; Treatment Outcome

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.

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antimetabolites, Antineoplastic; Chromosome Aberrations; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 8; Chromosomes, Human, X; Clinical Trials as Topic; Diagnosis, Differential; Disease Progression; Female; Humans; Immunotherapy; In Situ Hybridization, Fluorescence; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; Male; Pentostatin; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptors, Antigen, T-Cell, alpha-beta; Treatment Outcome

Topics: Drug Evaluation; Europe; Humans; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; Mycosis Fungoides; Pentostatin; Prospective Studies; Remission Induction; Sezary Syndrome; Skin Neoplasms

Topics: Bridged Bicyclo Compounds, Heterocyclic; Humans; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; Pentostatin; Sulfonamides; T-Lymphocytes

To present a case of T-cell chronic lymphocytic leukemia (T-CLL) manifesting as an intraocular lymphoma.. Interventional case report.. We performed a vitreous biopsy in a 67-year-old woman who presented with blurred vision and vitreous cellular infiltration. Morphologic, immunohistochemical, flow cytometry, and molecular analysis by polymerase chain reaction of vitreous fluid, peripheral blood, bone marrow aspirate, and biopsy were performed.. Cytofluorographic and molecular analysis of vitreous cells demonstrated a monoclonal T-cell population consistent with a T-cell intraocular lymphoma. Systemic evaluation established diagnosis of T-cell CLL.. T-CLL is a rare disease with an aggressive clinical course. We present a case of T-cell intraocular lymphoma as the initial manifestation of an otherwise asymptomatic T-CLL.

Topics: Aged; Antibiotics, Antineoplastic; Biomarkers, Tumor; Biopsy; Bone Marrow Cells; Diagnosis, Differential; DNA, Neoplasm; Eye Neoplasms; Female; Flow Cytometry; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Immunohistochemistry; Leukemia, Prolymphocytic, T-Cell; Lymphoma, T-Cell, Peripheral; Pentostatin; Polymerase Chain Reaction; Tomography, Optical Coherence; Vitrectomy; Vitreous Body

Deoxycoformycin (DCF) is a specific inhibitor of adenosine deaminase (ADA) and has been shown to be active in lymphoid neoplasms. Cytotoxicity is thought to be mediated by the accumulation of deoxyadenosine (AdR) and deoxyadenosine triphosphate (dATP) which inhibits ribonucleotide reductase and DNA synthesis in rapidly proliferating cells. Others suggested mechanisms leading to cell death particularly in non-dividing cells include depletion of ATP and NAD pools, inhibition of S-adenosylhomocysteine (SAH) hydrolase and induction of DNA strand breaks. In patients with high leukemic counts who were subsequently treated with DCF, we have studied (a) the levels of ADA, ecto-5'-nucleotidase (5NT), deoxyadenosine kinase (AdR-kinase) and SAH-hydrolase in the leukemic cells; [b) the in-vitro effects of DCF on dATP, ATP, NAD, SAH-hydrolase levels and on DNA strand breaks; and (c) the correlation between these parameters with clinical response to DCF. No significant difference in ADA, 5NT, AdR-kinase and SAH-hydrolase activities could be found between responders and non-responders. Incubation of the leukemic cells in vitro with DCF caused an inhibition of ADA, an accumulation of dATP, a moderate reduction in ATP and NAD levels, a suppression of SAH-hydrolase activity and an increase in DNA strand breaks in practically all the leukemic samples, irrespective of clinical response. Our results show that neither measurement of these enzymes nor studies of these biochemical sequelae of ADA inhibition in vitro predicts clinical responsiveness to DCF therapy.

Topics: Adenosine Deaminase Inhibitors; Adenosine Triphosphate; Adenosylhomocysteinase; Antineoplastic Agents; Coformycin; Deoxyadenine Nucleotides; DNA Damage; Humans; Hydrolases; Leukemia; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; NAD; Nucleoside Deaminases; Pentostatin; Ribonucleosides