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Blood Jul 2004The current World Health Organization (WHO) classification of hematopoietic malignancies defines several types of mature T-cell leukemia including T-cell prolymphocytic...
The current World Health Organization (WHO) classification of hematopoietic malignancies defines several types of mature T-cell leukemia including T-cell prolymphocytic leukemia (T-PLL), Sezary syndrome (SS), and T-cell large granular lymphocytic (T-LGL) leukemia. These neoplasms can show overlapping features with each other and with T-cell lymphomas involving peripheral blood (PB). We analyzed the spectrum of clinicopatho-logic features in 102 mature T-cell leukemias and compared them to 10 hepatosplenic T-cell lymphomas that involved PB. T-PLL, defined as a T-cell leukemia showing rapidly rising PB lymphocyte counts, was the only tumor type expressing the oncoprotein TCL1 (71% of cases) and could present with relatively low lymphocyte levels or small tumor cell morphology. SS, defined by accompanying erythrodermic skin disease, was frequently associated with peripheral eosinophilia but could also develop high numbers of prolymphocytes, especially late in the disease course. T-LGL leukemia, defined by accompanying cytopenias or autoimmune phenomena (or both), had the best clinical outcome and generally showed the lowest circulating lymphocyte levels with only a few cases developing marked lymphocytosis. Using the dominant clinical or phenotypic feature, we describe here the degree of overlap among currently recognized WHO categories and identify areas where further clarification is needed. Our results indicate that incorporation of additional criteria, such as TCL1 expression status and hematologic parameters, can assist in a more accurate classification.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Marrow; DNA-Binding Proteins; Female; Follow-Up Studies; Humans; Immunophenotyping; Leukemia, T-Cell; Lymphocyte Count; Male; Middle Aged; Proto-Oncogene Proteins; T-Lymphocytes; Transcription Factors; World Health Organization
PubMed: 15044256
DOI: 10.1182/blood-2004-01-0002 -
Journal of Clinical and Experimental... 2015T-cell prolymphocytic leukemia, small cell variant (T-PLL-s), is a rare lymphoid neoplasm associated with a poor prognosis. We encountered a case of T-PLL-s with a...
T-cell prolymphocytic leukemia, small cell variant (T-PLL-s), is a rare lymphoid neoplasm associated with a poor prognosis. We encountered a case of T-PLL-s with a characteristic phenotype. A 67-year-old female was referred to our hospital because of lymphocytosis in August 2013. Hepatosplenomegaly, lymphadenopathy, and skin lesions were absent. Hematologic examination revealed a white blood cell count of 17.9 × 10(9)/L with 81.2% mature lymphocytes, which were small with a high nuclear/cytoplasmic ratio, lacking a nucleolus and cytoplasmic granules. Anemia and thrombocytopenia were not observed. Flow cytometric analysis showed that these lymphocytes were positive for CD2, cyCD3, CD4, CD5, CD7, CD21, and CD38 (partially), but negative for smCD3, smTCR-αβ and -γδ, cyTCR-β, CD1a, CD8, CD25, HLA-DR, and terminal deoxynucleotidyl transferase. Polymerase-chain reaction analysis of cells from both the peripheral blood and the bone marrow demonstrated monoclonal rearrangement of TCR-γ. A possible rearranged band of the TCR-β gene was observed by Southern blot analysis. The karyotype of the marrow cells was 46, XX. A diagnosis of T-PLL-s, possibly at the stage of cytoplasmic CD3 expression in the ontogenesis of T-cells, was made. The patient has been asymptomatic, and the white blood cell count has gradually increased during one-year observation, being 69.0 × 10(9)/L with 89.7% lymphocytes in August 2014.
Topics: Aged; Antigens, CD; Blood Cell Count; Cell Transformation, Neoplastic; Female; Humans; Immunophenotyping; Leukemia, Prolymphocytic, T-Cell; Neoplasm Staging; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes
PubMed: 26106002
DOI: 10.3960/jslrt.55.17 -
Annals of Oncology : Official Journal... Jan 19942-chlorodeoxyadenosine (2-CDA) is a new purine analogue which has been shown to be highly active in lymphoproliferative disorders. In this clinical trial we assessed... (Clinical Trial)
Clinical Trial
BACKGROUND
2-chlorodeoxyadenosine (2-CDA) is a new purine analogue which has been shown to be highly active in lymphoproliferative disorders. In this clinical trial we assessed 2-CDA toxicity and response rate in patients with various haematological malignancies who were heavily pre-treated and mostly refractory to standard treatment regimens.
PATIENTS AND METHODS
Twenty-two refractory patients, 51 relapsing after standard chemotherapy and seven non-pre-treated patients were treated in a non-randomized prospective phase II multicentric study. Their median age was 54 years (range 18-84) and 56 of them were male. Thirty-one had non-Hodgkin's lymphoma (NHL), 11 chronic lymphocytic leukaemia (CLL), 1 prolymphocytic leukaemia (PLL), 13 hairy-cell leukaemia (HCL), 2 mycosis fungoides (MF), 3 multiple myeloma, 7 acute myeloblastic leukaemia (AML), 2 acute lymphoblastic leukaemia (ALL), 6 chronic myeloid leukaemia (CML) in blast crisis, 2 Hodgkin's disease, 1 Waldenström's macroglobulinemia and 1 Langerhans histiocytosis. 2-CDA 0.1 mg/kg/day was given as a continuous intravenous infusion for 7 days and recycled every 4 weeks.
RESULTS
One hundred thirty-two courses of 2-CDA were administered to 80 patients, 76 of whom were evaluable for response. A) Toxicity: Myelosuppression: Neutropenia to over 50% of initial value occurred in 46% of patients, thrombocytopenia in 8%, and lymphopenia < 0.5 x 10(9)/l was seen in 41%. Infections occurred in 34/80 patients (43%). The risk of severe infections (WHO grades 3-4) correlated with increasing number of years after first diagnosis (p = 0.01) and low lymphocyte counts on days 1 and/or 14 (p = 0.04); 21 infections were opportunistic. B) Response: 70% patients with lymphoproliferative disorders of low malignancy attained complete or partial response (low-grade NHL 12/16, CLL + PLL 9/12, HCL 13/13, MF 2/2, myeloma 0/3); in patients with AML, ALL, CML in myeloid (n = 4) or lymphoid (n = 2) blast crisis and high-grade lymphoma responses were seen in only 11%. Response was inversely related to the number of pretreatments (p = 0.045). In responding NHL patients the mean lymphocyte count on day 14 of cycle 1 was significantly lower (median 0.6 x 10(9)/l) than that of non-responders (1.2 x 10(9)/l, p = 0.04).
CONCLUSION
2-CDA had a high activity even in heavily pretreated and refractory patients with low-grade lymphoproliferative disorders. In contrast to previously published studies, infections, mainly opportunistic, were a serious side effect in our study. In patients with severe lymphopenia at therapy initiation, the value of prophylactic anti-infective treatment should be studied.
Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Bone Marrow Diseases; Chronic Disease; Cladribine; Female; Humans; Immunocompromised Host; Incidence; Leukemia; Lymphoma; Male; Middle Aged; Opportunistic Infections; Prospective Studies; Treatment Outcome
PubMed: 7909685
DOI: 10.1093/oxfordjournals.annonc.a058693 -
Blood Advances Nov 2019This is the first report of successful treatment of therapy-resistant leptomeningeal T-PLL with intrathecal alemtuzumab. Intrathecal alemtuzumab is a potentially safe...
This is the first report of successful treatment of therapy-resistant leptomeningeal T-PLL with intrathecal alemtuzumab. Intrathecal alemtuzumab is a potentially safe and efficacious therapeutic alternative for treatment of leptomeningeal T-PLL.
Topics: Alemtuzumab; Antineoplastic Agents, Immunological; Biopsy; Blood Cell Count; Combined Modality Therapy; Drug Resistance, Neoplasm; Female; Humans; Immunophenotyping; Injections, Spinal; Leukemia, Prolymphocytic, T-Cell; Meningeal Neoplasms; Middle Aged; Molecular Targeted Therapy; Retreatment; Treatment Outcome
PubMed: 31698446
DOI: 10.1182/bloodadvances.2019000289 -
Case Reports in Hematology 2013Prolymphocytic transformation of chronic lymphocytic leukemia is a rare but recognized entity. We present the case of a 76-year-old gentleman with a previous diagnosis...
Prolymphocytic transformation of chronic lymphocytic leukemia is a rare but recognized entity. We present the case of a 76-year-old gentleman with a previous diagnosis of chronic lymphocytic leukemia who presented with fatigue, fever, and a white blood cell count of 500 000 with prolymphocytes on peripheral blood examination. Chlorambucil and dexamethasone were initiated. He developed progressive anemia during his admission with no clear cause on initial CT examination. Bilateral hip pain began several days later and he was unfortunately diagnosed with a large spontaneous retroperitoneal hemorrhage postmortem. This condition is rare and generally occurs in those receiving therapeutic anticoagulation or dialysis, with known bleeding disorders or vascular malformation, none of which were present in our patient. Pathology revealed marked leukemoid engorgement of the vessels of many organs with prolymphocytes. We discuss the potential etiologies and relationships between these critical diagnoses.
PubMed: 24024050
DOI: 10.1155/2013/802376 -
Case Reports in Oncology 2023T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive disease with a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) followed by alemtuzumab...
T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive disease with a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) followed by alemtuzumab administration is the most promising treatment for T-PLL but is associated with a high risk of infections as alemtuzumab strongly suppresses cellular immunity, leading to high transplant-related mortality and unsatisfactory survival rates. In addition, for patients without human leukocyte antigen-matched donors, haploidentical stem cell transplantation (haplo-SCT) using post-transplant cyclophosphamide (PTCy) has been used because of the ready availability of donors and achievement of results comparable to those of transplantation with human leukocyte antigen-matched donors. However, there are no reports on the efficacy and safety, including infectious complications, of haplo-SCT with PTCy after alemtuzumab therapy in patients with. Here, we describe a 66-year-old Japanese male patient with T-PLL treated successfully with haplo-SCT after induction therapy of alemtuzumab for T-PLL. Approximately 3 months after the achievement of complete remission with alemtuzumab for T-PLL, haplo-SCT with reduced-intensity conditioning and PTCy was performed. Infectious complications were improved by early therapeutic interventions, and peripheral T cell counts gradually recovered. The patient was alive for more than 16 months after allo-SCT with no signs of relapse. Thus, haplo-SCT using PTCy should be considered as an option after alemtuzumab treatment for T-PLL.
PubMed: 37900793
DOI: 10.1159/000531471 -
Cancer May 2004Patients with chronic lymphocytic leukemia (CLL) that transforms to Richter syndrome (RS) frequently show atypical lymphocytes in bone marrow; however, a diagnosis of RS...
BACKGROUND
Patients with chronic lymphocytic leukemia (CLL) that transforms to Richter syndrome (RS) frequently show atypical lymphocytes in bone marrow; however, a diagnosis of RS requires confirmation of the presence of sheets of large cells in bone marrow or lymph nodes.
METHODS
In this study, the authors evaluated the clinical significance of scattered large cells in bone marrow. They assessed the possibility of predicting transformation to RS in bone marrow smears by counting the percentages of prolymphocytes and large cells in 78 patients with CLL and 29 patients with lymph node biopsy-confirmed RS.
RESULTS
The percentage of large cells was found to be correlated with decreasing survival in a continuous fashion (P = 0.006). It is interesting to note that patients who had > 7% large cells in the bone marrow and elevated beta(2)-microglobulin (beta(2)-M) levels (> 5 mg/L) had a survival duration identical to that of patients with RS, and these factors together were a strong predictor of RS (P < 0.001).
CONCLUSIONS
Patients with CLL who had bone marrow that contained > 7% large cells and who had beta(2)-M levels > 5 mg/L had a disease that was similar to RS, and the combination of large cells and beta(2)-M can be used as a surrogate marker for RS.
Topics: Adult; Aged; Aged, 80 and over; Biopsy; Bone Marrow Cells; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymph Nodes; Lymphocytes; Male; Middle Aged; Survival Rate; Syndrome; beta 2-Microglobulin
PubMed: 15139060
DOI: 10.1002/cncr.20251 -
Journal of Clinical and Experimental... 2014An 80-year-old man was referred to our department because of lymphocytosis. His white cell count was 17.1 × 10(3)/μL, with 64% prolymphocytes. He did not exhibit...
An 80-year-old man was referred to our department because of lymphocytosis. His white cell count was 17.1 × 10(3)/μL, with 64% prolymphocytes. He did not exhibit splenomegaly or lymphadenopathy. Prolymphocytes were CD5(+), CD10(-), CD19(+), CD20(+), CD21(+weak), CD22(+), CD23(-), and HLA-DR(+), and expressed μδ/λ cell-surface immunoglobulins. G-banding and fluorescence in situ hybridization using c-MYC and immunoglobulin heavy-chain (IgH) gene probe revealed that leukemia cells carried the t(8;14)(q24;q32)/c-MYC-IgH fusion gene, and breakage and reunion occurred within the non-coding region of c-MYC exon 1 as well as the α switch region of IgH. Nine months after the initial presentation, the patient's hemoglobin level fell to 5.7 g/dL. Coombs' test was positive and marked hypoplasia of erythroid precursors was detected in his bone marrow. The patient was treated with prednisolone followed by 4 weekly doses of rituximab, which led to resolution of the anemia and complete response of the underlying leukemia. The role of t(8;14)(q24;q32)/c-MYC-IgH in the pathogenesis of B-cell prolymphocytic leukemia (B-PLL) may not be identical to that in aggressive lymphoid neoplasms, and, in the present case, autoantibodies targeting both mature red cells and erythroid precursors may have been concurrently produced in the setting of B-PLL.
Topics: Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 8; Humans; Leukemia, Prolymphocytic, B-Cell; Male; Red-Cell Aplasia, Pure; Translocation, Genetic
PubMed: 25501113
DOI: 10.3960/jslrt.54.219 -
The Journal of Clinical Investigation Aug 1977In a young woman with ulcerative colitis, hypoimmunoglobulinemia, and humoral immunodeficiency, lymphocyte counts vary between 600 and 1,000 per mm(3) with 0.5-1.5% bone...
In a young woman with ulcerative colitis, hypoimmunoglobulinemia, and humoral immunodeficiency, lymphocyte counts vary between 600 and 1,000 per mm(3) with 0.5-1.5% bone marrow-derived (B) cells and 98-99% thymus-derived (T) cells. Anti-lymphocyte antibodies were detected by immunofluorescence and by microlymphocytotoxicity with increased reactivity at +4 degrees C. They belonged to the IgM class and were polyclonal. Studies performed with various normal lymphocyte subpopulations, several lymphoblastoid cell lines and lymphocytes from immunodeficiency patients showed that these antibodies reacted with B cells. The corresponding antigen(s) is distinct from membrane-bound immunoglobulins, is not an alloantigen, and is probably unrelated to the la-like molecules. Pokeweed mitogen stimulated B cells appear to lose this antigen. Cells from various lymphoproliferative disorders were tested. T-derived and "non T-non-B" leukemic cells did not react with the antibody. Malignant cells from B-derived lymphomas and prolymphocytic leukemias were reactive. The incidence of positivity of the leukemic cells among patients with common B chronic lymphocytic leukemia was surprisingly low (one-third of the patients). The autoantibody nature of the anti-B-cell antibodies and their pathogenic role in the genesis of the patient's hypoimmunoglobulinemia was demonstrated by the effect of removal of antibodies by massive plasmaphereses which were followed by a dramatic and transitory increase of B-cell figures. Whereas most primary immunodeficiency syndromes appear to result from an arrest in the differentiation capabilities of immunologically competent cells, autoantibodies to circulating B lymphocytes may be incriminated in the pathogenesis of some cases of hypogammaglobulinemia.
Topics: Adult; Autoantibodies; B-Lymphocytes; Colitis, Ulcerative; Female; Humans; Immune Adherence Reaction; Immunologic Deficiency Syndromes; Palatine Tonsil; T-Lymphocytes; Thymus Gland
PubMed: 301527
DOI: 10.1172/JCI108789 -
BMJ Case Reports Dec 2020A 64-year-old man had a several year history of B prolymphocytic leukaemia (PLL) which behaved indolently and had not required any treatment. Five years after diagnosis,...
A 64-year-old man had a several year history of B prolymphocytic leukaemia (PLL) which behaved indolently and had not required any treatment. Five years after diagnosis, he developed hypoalbuminaemia associated with severe lower-limb oedema, consistent with systemic capillary leak syndrome (SCLS). He recovered spontaneously but went on to have three further increasingly severe and protracted episodes over the subsequent 18 months. There was no identifiable precipitating factor for these episodes, but his peripheral lymphocyte count continued to increase slowly. The start of treatment for his PLL with chemoimmunotherapy was followed by a rapid resolution of residual oedema and normalisation of serum albumin. He has had no further attacks of SCLS in the 14 months since he started therapy for PLL. SCLS is a rare consequence of haematological malignancy which may show an excellent response to treatment of the haematological disease.
Topics: Antineoplastic Combined Chemotherapy Protocols; Capillary Leak Syndrome; Cyclophosphamide; Edema; Humans; Hypoalbuminemia; Leukemia, Prolymphocytic, B-Cell; Male; Middle Aged; Rituximab; Serum Albumin, Human; Treatment Outcome; Vidarabine
PubMed: 33370989
DOI: 10.1136/bcr-2020-237939