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Journal of Hematology Apr 2023B-cell prolymphocytic leukemia (B-PLL) is a rare B-cell neoplasm that typically presents with splenomegaly, a rising white blood cell count, and may or may not have B...
B-cell prolymphocytic leukemia (B-PLL) is a rare B-cell neoplasm that typically presents with splenomegaly, a rising white blood cell count, and may or may not have B symptoms. The diagnosis usually requires a bone marrow biopsy and aspirate with flow cytometry and cytogenetic studies. At least 55% of the lymphocytes in the peripheral blood must be prolymphocytes to be defined as B-PLL. A thorough differential diagnosis would include mantle cell lymphoma, chronic lymphocytic leukemia (CLL) with prolymphocytes, hairy cell leukemia, and splenic marginal zone lymphoma. B-PLL is managed with regimens utilized for CLL, such as ibrutinib and rituximab but is tailored for each individual. The authors report a rare case of B-PLL in a patient with no known history of CLL. The authors discuss this entity in context of the 2017 and 2022 World Health Organization (WHO) classifications, the latter of which no longer recognizes B-PLL as a distinct entity. The authors hope that this article helps practitioners with the diagnosis and treatment of B-PLL. Perhaps with better recognition, and better documentation of histopathologic features of these rare cases going forward, it may prove to be a distinct entity again in future classifications.
PubMed: 37187496
DOI: 10.14740/jh1096 -
American Journal of Hematology Jun 2023T-cell prolymphocytic leukemia (T-PLL) is a rare, post-thymic T-cell neoplasm with a diverse clinical course. T-PLL is typically associated with a poor prognosis;...
T-cell prolymphocytic leukemia (T-PLL) is a rare, post-thymic T-cell neoplasm with a diverse clinical course. T-PLL is typically associated with a poor prognosis; however, a subset of patients have inactive disease on initial presentation. There is a lack of accurate delineation of the disease based on initial clinical presentation and pathological assessment, hindering clinical decision-making. To characterize and delineate disease subtypes based on initial clinical presentation and pathologic assessment, we retrospectively reviewed 81 patients with T-PLL treated at our institution. We compared patients with T-PLL who initially presented with a relatively indolent or stable disease course to those with an aggressive disease course. Clinicopathologic characteristics, overall survival (OS), and prognostic factors were analyzed. Patients with inactive disease had a significantly longer OS than patients with active disease. At diagnosis, presence of B symptoms, low hemoglobin, low platelet count, lymphocyte doubling time of fewer than 3 months, and abnormal cytogenetics were associated with shorter OS. Cell morphology, immunophenotype, absolute lymphocyte count, lactate dehydrogenase levels, involvement of liver, spleen, skin or central nervous system, presence of TCL1 rearrangement or inv (14)/t(14;14), presence of chromosome 8 abnormalities, and presence of deletion of 11q were not associated with significant OS difference among the patients. Receiving alemtuzumab as first-line treatment and consolidation with allogeneic hematopoietic stem cell transplant were associated with better outcomes. T-PLL inactive and active disease subtypes can exhibit overlapping yet different clinical and pathological features. We describe several prognostic factors at diagnosis that can be used for risk stratification and aid in guiding treatment decisions.
Topics: Humans; Leukemia, Prolymphocytic, T-Cell; Prognosis; Retrospective Studies; Hematopoietic Stem Cell Transplantation; Chromosome Aberrations; Disease Progression
PubMed: 36964941
DOI: 10.1002/ajh.26918 -
Cancer Control : Journal of the Moffitt... Jan 1998BACKGROUND: T-cell prolymphocytic leukemia (T-PLL) is a post-thymic T-cell malignancy with aggressive clinical course. Although T-PLL has been referred to under...
BACKGROUND: T-cell prolymphocytic leukemia (T-PLL) is a post-thymic T-cell malignancy with aggressive clinical course. Although T-PLL has been referred to under different designations, it is a distinct clinico-biological entity and should be distinguished from other T-cell disorders. METHODS: The literature on T-PLL is reviewed. Experience on the clinical and laboratory features, differential diagnosis, and therapy on a large series of T-PLL patients is presented. RESULTS: T-PLL affects adults and occurs more frequently in men. The principal disease characteristics are organomegaly, skin lesions, and a raised lymphocyte count. Immunological markers show a post-thymic T-cell phenotype (TdT- CD2+ CD5+ CD3ñ) with strong expression of CD7. A CD4+ CD8- phenotype is seen in two thirds of cases. CD4 and CD8 are coexpressed in 25%, and a CD4- CD8+ phenotype is rare. Cytogenetics show a recurrent abnormality inv(14)(q11;q32) that is always associated to other aberrations (particularly iso8q or trisomy 8). Differential diagnosis between T-PLL and other T-cell malignancies is based on a constellation of clinical and laboratory features. Generally, T-PLL patients are refractory to the therapy used in lymphoid disorders. Median survival is short but is improving with the use of 2'-deoxycoformycin and the humanized monoclonal antibody, anti-CDw52 (Campath-1H). CONCLUSIONS: T-PLL is a distinct T-cell disorder with characteristic clinical and laboratory features and a poor prognosis. A precise diagnosis of this disease is important in determining patient management and treatment.
PubMed: 10761013
DOI: 10.1177/107327489800500102 -
Haematologica Jan 2022T-cell prolymphocytic leukemia (T-PLL) is mostly characterized by aberrant expansion of small- to medium-sized prolymphocytes with a mature post-thymic phenotype, high...
T-cell prolymphocytic leukemia (T-PLL) is mostly characterized by aberrant expansion of small- to medium-sized prolymphocytes with a mature post-thymic phenotype, high aggressiveness of the disease and poor prognosis. However, T-PLL is more heterogeneous with a wide range of clinical, morphological, and molecular features, which occasionally impedes the diagnosis. We hypothesized that T-PLL consists of phenotypic and/or genotypic subgroups that may explain the heterogeneity of the disease. Multi-dimensional immuno-phenotyping and gene expression profiling did not reveal clear T-PLL subgroups, and no clear T-cell receptor a or β CDR3 skewing was observed between different T-PLL cases. We revealed that the expression of microRNA (miRNA) is aberrant and often heterogeneous in T-PLL. We identified 35 miRNA that were aberrantly expressed in T-PLL with miR-200c/141 as the most differentially expressed cluster. High miR- 200c/141 and miR-181a/181b expression was significantly correlated with increased white blood cell counts and poor survival. Furthermore, we found that overexpression of miR-200c/141 correlated with downregulation of their targets ZEB2 and TGFβR3 and aberrant TGFβ1- induced phosphorylated SMAD2 (p-SMAD2) and p-SMAD3, indicating that the TGFβ pathway is affected in T-PLL. Our results thus highlight the potential role for aberrantly expressed oncogenic miRNA in T-PLL and pave the way for new therapeutic targets in this disease.
Topics: Gene Expression Profiling; Humans; Leukemia, Prolymphocytic, T-Cell; Lymphocytes; MicroRNAs; Transforming Growth Factor beta; Zinc Finger E-box Binding Homeobox 2
PubMed: 33596640
DOI: 10.3324/haematol.2020.263756 -
Blood Jul 1993Three distinct clinical syndromes occur in patients with increased numbers of circulating LGL. Patients with T-LGL leukemia have clonal proliferations of CD3+ LGL... (Review)
Review
Three distinct clinical syndromes occur in patients with increased numbers of circulating LGL. Patients with T-LGL leukemia have clonal proliferations of CD3+ LGL typically associated with chronic neutropenia and autoimmune features. NK-LGL leukemia is characterized by clonal CD3- LGL proliferation with an acute clinical presentation marked by massive hepatosplenomegaly and systemic illness. However, most patients with increased numbers of CD3- LGL do not have clinical features of NK-LGL leukemia and have a chronic clinical course. X-linked gene analyses have supported a polyclonal LGL lymphocytosis in this syndrome. Further studies are needed to determine whether clonal progression can occur in these patients.
Topics: CD3 Complex; Clone Cells; Female; Hematopoiesis; Humans; Killer Cells, Natural; Leukemia, Prolymphocytic, T-Cell; Leukocyte Count; Lymphocyte Subsets; Lymphoproliferative Disorders; Male; Middle Aged; Prognosis; T-Lymphocytes
PubMed: 8324214
DOI: No ID Found -
Journal of the Royal Society of Medicine Feb 1979
Topics: Aged; Antineoplastic Agents; Humans; Leukapheresis; Leukemia, Lymphoid; Leukocyte Count; Male; Splenectomy
PubMed: 552479
DOI: 10.1177/014107687907200215 -
Frontiers in Public Health 2021Follow-up observation of radiation accident in which a worker developed acute radiation disease and eventually died of leukemia. The case provided key practical...
Follow-up observation of radiation accident in which a worker developed acute radiation disease and eventually died of leukemia. The case provided key practical information for the study on clinical effects of radiation on the health of workers. We observed and followed-up the progression and effect of radiation exposure at various stages in a 28-year-old male patient. We examined the chromosomal morphology, white blood cell count, and sperm count. Laboratory tests for leukemia diagnosis and other clinical parameters were performed. After the patient was irradiated, the white blood cell level decreased, the sperm count dropped to 0, and the libido completely disappeared. The patient's chromosome aberration cell rate and total chromosome aberration cell rate were 7.33 and 7.66%, respectively. Examination of leukemia diagnostic experiments revealed that abnormal cells accounted for 60%; bone marrow examination showed that prolymphocytes abnormally proliferated, accounting for 89%, and had positive extracellular iron staining. After the initial treatment, the patient's white blood cell level increased and was finally maintained at a normal level, the sperm count returned to normal levels, and libido was restored. The patient died of acute lymphoblastic leukemia 34 years after the exposure. More attention has been paid to the long-term effects of ionizing radiation-induced malignant tumors. The occupational protection of radiographic inspection workers should be strengthened to reduce and avoid occupational injuries to protect the health and safety of workers.
Topics: Adult; Chromosome Aberrations; Humans; Male; Occupational Exposure; Occupations; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiation Exposure
PubMed: 34055721
DOI: 10.3389/fpubh.2021.657564 -
Blood Aug 1995We studied 25 T-cell chronic lymphocytic leukemia (T-CLL) cases collected over a 15-year period. Immunophenotypic analysis was performed in each case; 12 cases were... (Review)
Review
We studied 25 T-cell chronic lymphocytic leukemia (T-CLL) cases collected over a 15-year period. Immunophenotypic analysis was performed in each case; 12 cases were evaluated by cytogenetics, and gene rearrangement studies were performed in 14 cases. The median age was 57 years with a male predominance (M:F, 15:10). The median presenting lymphocyte count was 36.3 x 10(9)/L (range, 3.9 to 438 x 10(9)/L). Fourteen patients (56%) had shotty adenopathy and ten (40%) had mild-to-moderate splenomegaly at presentation; four (16%) had erythematous skin lesions. The lymphocytes were predominantly small; some cases had a minor component of medium-sized cells (< 10%). The nuclear: cytoplasmic ratios were uniformly high with round to oval nuclei; however, a wide spectrum of nuclear outlines could be found, ranging from minimally to markedly convoluted. Nucleoli were either absent or small and inconspicuous. These lymphocytes did not have the morphology of prolymphocytes and did not contain cytoplasmic granules. Bone marrow infiltration was generally in an interstitial pattern; the degree of involvement ranged from 15% to 90%. Immunophenotyping showed that the lymphocytes were mature T-cells with a predominant CD4+ immunophenotype. Three cases displayed a CD8+ immunophenotype. The patients were treated with a variety of chemotherapeutic regimens with only a minimal response observed in two of 20 patients. We conclude that T-CLL is an uncommon chronic lymphoproliferative disorder (CLPD) that can be morphologically similar to B-CLL, is distinct from T-prolymphocytic leukemia, and has an aggressive clinical course that is refractory to therapy. It may also be difficult to distinguish T-CLL from other T-CLPD, especially the leukemic phase of peripheral T-cell lymphoma and some cases of Sézary syndrome.
Topics: Adult; Aged; Bone Marrow; Female; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Humans; Immunophenotyping; Leukemia, Prolymphocytic, T-Cell; Male; Middle Aged; Survival Analysis
PubMed: 7620169
DOI: No ID Found -
Molecular Pathology : MP Jun 1997To evaluate the morphofunctional characteristics of lymph node cells from patients with Hodgkin's disease by measuring silver stained nucleolar organiser regions... (Comparative Study)
Comparative Study
AIM
To evaluate the morphofunctional characteristics of lymph node cells from patients with Hodgkin's disease by measuring silver stained nucleolar organiser regions (AgNORs).
METHODS
Nucleoli in Hodgkin's and Reed-Sternberg (HRS) cells, lymphocytes and prolymphocytes were investigated in cytological smears and histological sections of lymph nodes from 32 patients with Hodgkin's disease, and from 34 patients with reactive lymphadenopathy. According to the Rye histological classification of Hodgkin's disease, three cases were the lymphocyte predominant (LP) type, 14 the nodular sclerosing (NS) type, and 15 the mixed cellularity (MC) type. The investigation was done before treatment, by means of a one step silver staining method. In each case, 50 to 100 HRS cells, lymphocytes, and prolymphocytes were evaluated to determine the mean numbers of nucleoli and AgNORs per nucleus. The nonparametric Wilcoxon Mann-Whitney test was used to compare the groups.
RESULTS
The mean numbers of nucleoli and AgNORs were higher in lymphocytes and prolymphocytes compared with those from reactive lymph nodes used as controls. Numbers of nucleoli and AgNORs were higher (not significant) in the NS type of Hodgkin's disease than in the MC type. There was a significant increase in numbers of nucleoli in HRS cells, and their AgNOR counts were increased. The greatest number of nucleoli in HRS cells was found in the NS type. Furthermore, the nucleolar activity of HRS cells was greater in the NS type compared with the MC type (50.2 (SEM 3.9) v 37.7 (2.9) AgNORs per nucleus (p = 0.025)). Comparative analysis of cytological and histological samples showed that the AgNOR score was significantly higher in touch imprints than in tissue sections with tumours of the same histological type.
CONCLUSIONS
Assessment of cell activity in Hodgkin's disease patients by silver staining is more convenient and informative in lymph node imprints than in histological sections. The highest expression of interphase ribosomal RNA cistrons found in NS HRS cells is probably explained by their high proliferative activity and elevated production of transforming growth factor 1 which is known to be the most potent cytokine present in the NS subtype of Hodgkin's disease.
Topics: Adolescent; Adult; Aged; Female; Histocytological Preparation Techniques; Hodgkin Disease; Humans; Lymph Nodes; Lymphocytes; Male; Middle Aged; Nucleolus Organizer Region; Reed-Sternberg Cells; Silver Staining; Statistics, Nonparametric; Stem Cells
PubMed: 9292150
DOI: 10.1136/mp.50.3.149 -
The Permanente Journal 2016B-cell prolymphocytic leukemia (B-PLL) is a rare, aggressive leukemia distinct from chronic lymphocytic leukemia, with median survival of only 3 years. B-PLL is... (Review)
Review
INTRODUCTION
B-cell prolymphocytic leukemia (B-PLL) is a rare, aggressive leukemia distinct from chronic lymphocytic leukemia, with median survival of only 3 years. B-PLL is resistant to most chemotherapy and newer targeted therapies such as alemtuzumab and thalidomide. Phenylethyl isothiocyanate (PEITC) is a natural compound from horseradish with evidence for therapeutic potential in multiple leukemia types.
CASE PRESENTATION
Here we present a case report of a 53-year-old man whose chronic lymphocytic leukemia transformed to end-stage B-PLL, disqualifying him for allogenic stem cell transplantation. He was treated with PEITC followed by salvage R-CHOP (Rituximab, Cyclophosphamide, Hydroxydaunorubicin [doxorubicin hydrochloride], Oncovin [vincristine sulfate], Prednisone or Prednisolone) chemotherapy, which led to normalized white blood cell count and disease stabilization that requalified him for allogenic peripheral stem-cell transplant therapy. We conducted a systematic review to analyze and interpret the potential contribution of PEITC to his unexpectedly favorable R-CHOP response. Following sequential 8 weeks of PEITC/pentostatin and 6 cycles of R-CHOP, the patient received allogenic peripheral blood stem cell transplant on an outpatient basis and remains well at the time of this publication, with no evidence of CD20+ small B-cells.
DISCUSSION
Given the limited data for R-CHOP in B-PLL, this patient's recovery suggests presensitization of B-PLL cells toward R-CHOP, potentially justifying further investigation.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Isothiocyanates; Leukemia, Prolymphocytic, B-Cell; Male; Middle Aged; Outcome Assessment, Health Care; Salvage Therapy
PubMed: 27168399
DOI: 10.7812/TPP/15-153