T-cell Prolymphocytic Leukemia Research Articles

CD94 expression patterns in reactive and neoplastic T-cell and NK-cell proliferations

Lymphomas and leukemias of T-cell and NK-cell lineages are highly heterogeneous disorders and lack effective therapeutic strategies. Targeted therapies including anti-CD94 agents are currently under clinical investigation, but studies of CD94 expression on mature T/NK-cell neoplasms are limited. In this study, we investigated the landscape of CD94 protein expression in 15 patients with reactive T/NK-cell proliferations and 124 patients with various T/NK cell neoplasms. CD94 expression was detected at a high level in reactive NK-cells, with a lower level of expression in a subset of reactive CD8 + T-cells; reactive CD4 + T-cells were negative for CD94 expression. All NK-cell neoplasms surveyed had high-level CD94 expression, which was significantly higher than that in T cell neoplasms (p = 0.0174). In neoplastic T-cell proliferations, CD94 expression was positive in all 10 hepatosplenic T-cell lymphoma cases tested, with a high mean fluorescence intensity. Fifty-six percent of T-cell large granular lymphocytic leukemia cases were positive for CD94 expression in a subset of neoplastic cells. All T-cell prolymphocytic leukemia and 97 % of peripheral T-cell lymphoma cases showed no CD94 expression. Our findings demonstrate a broad range of CD94 expression among T/NK-cell neoplasms, in some at levels that suggest therapeutic vulnerability to CD94-targeted therapies.

Deregulation of the Interleukin-7 Signaling Pathway in Lymphoid Malignancies.

The cytokine interleukin-7 (IL-7) and its receptor are critical for lymphoid cell development. The loss of IL-7 signaling causes severe combined immunodeficiency, whereas gain-of-function alterations in the pathway contribute to malignant transformation of lymphocytes. Binding of IL-7 to the IL-7 receptor results in the activation of the JAK-STAT, PI3K-AKT and Ras-MAPK pathways, each contributing to survival, cell cycle progression, proliferation and differentiation. Here, we discuss the role of deregulated IL-7 signaling in lymphoid malignancies of B- and T-cell origin. Especially in T-cell leukemia, more specifically in T-cell acute lymphoblastic leukemia and T-cell prolymphocytic leukemia, a high frequency of mutations in components of the IL-7 signaling pathway are found, including alterations in IL7R, IL2RG, JAK1, JAK3, STAT5B, PTPN2, PTPRC and DNM2 genes.

T-cell prolymphocytic leukemia

T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell lymphoma. The diagnosis of T-PLL is made based on the criteria proposed in 2019 by the T-PLL International Study Group (TPLL-ISG). T-PLL may be diagnosed in an ‘active’ or an ‘inactive’ form. While T-PLL is most often characterized by an aggressive clinical course, approximately 20–30% of patients may have a stable or slowly progressive disease in the initial period. Only the active form requires treatment. The treatment initiation criteria were defined in the consensus proposed by the TPLL-ISG. Data on the effectiveness of various therapeutic approaches comes from small, non-randomized studies. No drug is approved for the treatment of T-PLL. The standard of care in the first line of treatment is intravenous alemtuzumab. Consolidation therapy in eligible patients consists of allogeneic hematopoietic stem cell transplantation, preferably after TBI-based conditioning. In the remaining patients, neither maintenance nor consolidation treatment is recommended. There is no standard therapy for the relapse, although, based on genome studies, many drugs may be potentially effective, including histone deacetylase inhibitors and BCL2 inhibitors.

T-cell prolymphocytic leukemia

T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell lymphoma. The diagnosis of T-PLL is made based on the criteria proposed in 2019 by the T-PLL International Study Group (TPLL-ISG). T-PLL may be diagnosed in an ‘active’ or an ‘inactive’ form. While T-PLL is most often characterized by an aggressive clinical course, approximately 20–30% of patients may have a stable or slowly progressive disease in the initial period. Only the active form requires treatment. The treatment initiation criteria were defined in the consensus proposed by the TPLL-ISG. Data on the effectiveness of various therapeutic approaches comes from small, non-randomized studies. No drug is approved for the treatment of T-PLL. The standard of care in the first line of treatment is intravenous alemtuzumab. Consolidation therapy in eligible patients consists of allogeneic hematopoietic stem cell transplantation, preferably after TBI-based conditioning. In the remaining patients, neither maintenance nor consolidation treatment is recommended. There is no standard therapy for the relapse, although, based on genome studies, many drugs may be potentially effective, including histone deacetylase inhibitors and BCL2 inhibitors.

Cutaneous involvement by T‐cell prolymphocytic leukemia presenting as livedoid vasculopathy

T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive neoplasm derived from post-thymic T-cells. Patients are typically middle aged with a slight male predominance who present with a high white blood cell count, hepatosplenomegaly, lymphadenopathy, and other symptoms typically associated with leukemia. Although cutaneous involvement has been reported in up to 30% of cases of T-PLL, to our knowledge, none have presented with a presentation resembling livedoid vasculopathy. In the correct clinical context, an underlying hematolymphoid neoplasm should be included in the differential diagnosis of a patient presenting with livedoid vasculopathy.

Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia

T cell prolymphocytic leukemia (T-PLL) is a rare disease with aggressive clinical course. Cytogenetic analysis, whole-exome and whole-genome sequencing have identified primary structural alterations in T-PLL, including inversion, translocation and copy number variation. Recurrent somatic mutations were also identified in genes encoding chromatin regulators and those in the JAK-STAT signaling pathway. Epigenetic alterations are the hallmark of many cancers. However, genome-wide epigenomic profiles have not been reported in T-PLL, limiting the mechanistic study of its carcinogenesis. We hypothesize epigenetic mechanisms also play a key role in T-PLL pathogenesis. To systematically test this hypothesis, we generated genome-wide maps of regulatory regions using H3K4me3 and H3K27ac ChIP-seq, as well as RNA-seq data in both T-PLL patients and healthy individuals. We found that genes down-regulated in T-PLL are mainly associated with defense response, immune system or adaptive immune response, while up-regulated genes are enriched in developmental process, as well as WNT signaling pathway with crucial roles in cell fate decision. In particular, our analysis revealed a global alteration of regulatory landscape in T-PLL, with differential peaks highly enriched for binding motifs of immune related transcription factors, supporting the epigenetic regulation of oncogenes and genes involved in DNA damage response and T-cell activation. Together, our work reveals a causal role of epigenetic dysregulation in T-PLL.

Inmunoglobulina intravenosa en el síndrome de activación macrofágica asociado a lupus eritematoso sistémico

BACKGROUND T-cell prolymphocytic leukemia (T-PLL) is a T-cell lymphoproliferative disorder that frequently involves the skin. The objective was to describe two cases of T-PLL with cutaneous involvement and to present a review of the literature concerning the clinical characteristics, differential diagnosis and treatment of these patients. CASE REPORTS 1) 79 year-old man, with a previous diagnosis of T-PLL based on a laboratory incidental finding. He had been treated with alemtuzumab, but it had to be interrupted due to recurrent infections. After interrupting the treatment, the patient developed a symmetrical rash on his extremities. The skin biopsy demonstrated TPLL infiltration. 2) 28 year-old man that presented with asthenia and lymphocytosis. He also showed a purpuric rash on his trunk and facial erythema. Histopathology of the skin and bone marrow confirmed the diagnosis of T-PLL with cutaneous involvement. CONCLUSIONS T-cell prolymphocytic leukemia accounts for 2% of mature leukemias in adults. Skin involvement is reported in 20-50% of the patients. The characteristic features are facial involvement, purpuric lesions and symmetry of the rash, although there are atypical manifestations as well. Differential diagnosis includes other T-cell lymphoproliferative disorders with hematologic and skin involvement, such as Sezary syndrome. Patients with T-PLL may show cutaneous infiltration at the moment of debut or relapse of the disease. The skin is an accessible organ for taking samples to study and diagnose these patients.

BH3 profiling identifies ruxolitinib as a promising partner for venetoclax to treat T-cell prolymphocytic leukemia

Conventional therapies for patients with T-cell prolymphocytic leukemia (T-PLL), such as cytotoxic chemotherapy and alemtuzumab, have limited efficacy and considerable toxicity. Several novel agent classes have demonstrated preclinical activity in T-PLL, including inhibitors of the JAK/STAT and T-cell receptor pathways, as well as histone deacetylase (HDAC) inhibitors. Recently, the BCL-2 inhibitor venetoclax also showed some clinical activity in T-PLL. We sought to characterize functional apoptotic dependencies in T-PLL to identify a novel combination therapy in this disease. Twenty-four samples from patients with primary T-PLL were studied by using BH3 profiling, a functional assay to assess the propensity of a cell to undergo apoptosis (priming) and the relative dependence of a cell on different antiapoptotic proteins. Primary T-PLL cells had a relatively low level of priming for apoptosis and predominantly depended on BCL-2 and MCL-1 proteins for survival. Selective pharmacologic inhibition of BCL-2 or MCL-1 induced cell death in primary T-PLL cells. Targeting the JAK/STAT pathway with the JAK1/2 inhibitor ruxolitinib or HDAC with belinostat both independently increased dependence on BCL-2 but not MCL-1, thereby sensitizing T-PLL cells to venetoclax. Based on these results, we treated 2 patients with refractory T-PLL with a combination of venetoclax and ruxolitinib. We observed a deep response in JAK3-mutated T-PLL and a stabilization of the nonmutated disease. Our functional, precision-medicine–based approach identified inhibitors of HDAC and the JAK/STAT pathway as promising combination partners for venetoclax, warranting a clinical exploration of such combinations in T-PLL.

The miR-200c/141-ZEB2-TGFβ axis is aberrant in human T-cell prolymphocytic leukemia.

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 b 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 TGFbR3 and aberrant TGFb1- induced phosphorylated SMAD2 (p-SMAD2) and p-SMAD3, indicating that the TGFb 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.

Cutaneous Presentation of T-Cell Prolymphocytic Leukemia Mimicking Dermatomyositis

T-cell prolymphocytic leukemia (TPLL) is a rare form of leukemia by T lymphocytes at a post-thymic intermediate stage of development with an α/β immunophenotype. Facial involvement is common in TPLL and displays significant heterogeneity of the lesions' description and location. TPLL also contains a wide array of histology findings, cell cytology, and molecular studies. Here, we describe a TPLL patient who presented with an ill-defined erythematous patch involving the right axilla progressing to the left axilla, upper back, and face that resembled dermatomyositis. The diagnosis of TPLL was established using flow cytometry of bone marrow and peripheral blood, and histopathology of the involved skin. Dermatologists should be aware of these unique features.

T-Cell Prolymphocytic Leukemia: An Overview of Current and Future Approaches.

T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell hematologic neoplasm with a very poor prognosis and limited treatment options to date. Single-agent alemtuzumab remains the first line of therapy for the treatment-naive and relapsed/refractory patients. Prospective clinical trials are difficult to conduct given that these patients have a short life expectancy after the initial diagnosis. As a result, researchers are implementing the use of targeted therapies in vitro and ex vivo followed by in vivo trials on a small subset of patients which are reviewed here. Newer approaches in the treatment of T-PLL are developing based on recognizing the cytogenetic phenotype of each patient and targeting the identified defective genes that are usually involved in the cell cycle regulation such as protooncogenes, tumor suppressors, and deoxyribonucleic acid (DNA) repair genes. These could potentially redirect the management in the near future and improve the overall survival (OS) and the progression-free survival (PFS) for these patients.

Comorbidity in patients with lymphoproliferative diseases

Purpose of the study. To make an informed assessment of comorbidity in patients with lymphoproliferative diseases. To evaluate the effectiveness of comorbidity scales CCI and CIRS-G in patients with lymphoproliferative diseases under treatment. To evaluate the effect of the conducted immunochemotherapy on the general comorbidity in this category of patients.Material and methods. Two scales were used for calculations: Charlson Comorbidity Index (CCI) and Cumulative Illness Rating Scale for Geriatrics (CIRS-G). 127 primary patients with lymphoproliferative diseases aged 19 to 95 years old (the average age was 51.4) were examined from January 2018 till October 2019. The distribution of patients was based on the types of diseases: non-Hodgkin’s lymphomas — 59 (46.46%), Hodgkin’s lymphoma — 35 (27.56%), multiple myeloma — 20 (15.77%), chronic lymphocytic leukemia — 7 (5.51%) people, Waldenstrom’s macroglobulinemia — 3 (2.36%); each of the following diseases: hairy cell leukemia, T-cell leukemia of large granular lymphocytes, T-cell prolymphocytic leukemia - 1, amounted to 0.78% each.Results. Comorbidity was detected in 46 patients who received immunotherapy, chemotherapy, combined chemoradiotherapy, which amounted to 36.22% of the total number of patients. Lesions of the peripheral and central nervous system — 20 (43.48%) patients, were diagnosed most frequently. Immunodefi ciency states — 19 (41.30%) people, came next, and diseases of the cardiovascular system — 12 (26.08%) patients, appeared to be least frequent.Conclusions. When recalculating comorbidity on the CCI and CIRS-G scales, a significant aggravation of comorbidity after treatment, an increase in moderate and severe comorbidity were noted. According to the effectiveness of the CCI and CIRS-G scales in the treated patients, comorbidity is evaluated only approximately, since the Charlson Comorbidity Index does not include polyneuropathy, immunodeficiency states, thrombosis, ischemic heart disease, cardiac arrhythmias, gastritis, and thromboembolic complications and immunodeficiency states are absent in the CIRS-G scale. It is advisable to develop scales for assessing comorbidity, free from disadvantages mentioned above.

Analysis of T-Cell Receptor Beta Chain (Tß) Gene Rearrangements Demonstrates the Monoclonal Nature of T-Cell Chronic Lymphoproliferative Disorders

We investigated the rearrangement patterns of the gene coding for the beta chain of the T cell receptor (T beta) in 11 patients with T-cell derived chronic lymphoproliferative disorders, including T-cell prolymphocytic leukemia (T-PLL) and T-cell chronic lymphocytic leukemia (T-CLL). We found that all five cases of T-PLL, and five of six cases of T-CLL, displayed T beta-gene rearrangements, clearly establishing their monoclonal nature. Clonality could not be determined in one case of T-CLL where the T beta gene was found unrearranged. Our results demonstrate that the majority of cases of both clinically aggressive T-PLL and clinically indolent T-CLL are monoclonal. These results suggest that the analysis of T beta gene rearrangements represents a valid tool for the differential diagnosis and clinical monitoring of T-cell derived chronic lymphoproliferative diseases.

13955 Recalcitrant lower-extremity ulcerations: Importance of rebiopsy

Lower-extremity ulcerations have an estimated prevalence of 1%-2% in the United States and are a common cause of inpatient hospitalization. A systematic approach beginning with the most frequent etiologies is essential to avoiding misdiagnosis and excessive health care expenditure, as more than 90% of cases may be explained by chronic arterial or venous disease alone. The differential diagnosis for the remaining minority of non-healing leg ulcers is extraordinarily broad and includes infection, panniculitis, calciphylaxis, vasculitis or other immune-mediated etiologies (eg, neutrophilic dermatoses such as pyoderma gangrenosum or Behçet disease), and malignancy, among numerous other causes. Herein, we present the case of a 36-year-old woman with a several year history of bilateral lower extremity erythema nodosum (previously responsive to prednisone tapers and hydroxychloroquine) and bilateral leg ulcerations secondary to thrombotic vasculopathy (confirmed on skin biopsy), known chronic venous insufficiency, steroid-induced diabetes mellitus, and obesity was admitted to our hospital with acute on chronic worsening of longstanding leg ulcerations. Physical examination was notable for two large bilateral lower extremity ulcerations accompanied by faintly erythematous, blanching macules and papules coalescing into patches and plaques on the bilateral thighs as well as oral and genital ulcerations. Laboratory evaluation was notable for leukocytosis of unclear significance in the setting of high-dose systemic corticosteroid administration. A repeat skin biopsy revealed an intravascular lymphoid infiltrate ultimately consistent with T-cell prolymphocytic leukemia (T-PLL). Our case demonstrates the importance of repeat skin biopsy in cases of atypically presenting, recalcitrant to therapy, or acutely worsened lower extremity ulcerations.

Micro-RNA networks in T-cell prolymphocytic leukemia reflect T-cell activation and shape DNA damage response and survival pathways.

T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic mature T-cell malignancy. It typically presents with exponentially rising lymphocyte counts, splenomegaly, and bone marrow infiltration. Effective treatment options are scarce and a better understanding of TPLL’s pathogenesis is desirable. Activation of the TCL1 proto-oncogene and loss-of-function perturbations of the tumor suppressor ATM are TPLL’s genomic hallmarks. The leukemic cell reveals a phenotype of active T-cell receptor (TCR) signaling and aberrant DNA damage responses. Regulatory networks based on the profile of microRNA (miR) have not been described for T-PLL. In a combined approach of small-RNA and transcriptome sequencing in 46 clinically and moleculary well-characterized T-PLL, we identified a global T-PLL-specific miR expression profile that involves 34 significantly deregulated miR species. This pattern strikingly resembled miR-ome signatures of TCR-activated T cells. By integrating these T-PLL miR profiles with transcriptome data, we uncovered regulatory networks associated with cell survival signaling and DNA damage response pathways. Despite a miR-ome that discerned leukemic from normal T cells, there were also robust subsets of T-PLL defined by a small set of specific miR. Most prominently, miR-141 and the miR- 200c-cluster separated cases into two major subgroups. Furthermore, increased expression of miR-223-3p as well as reduced expression of miR-21 and the miR-29 cluster were associated with more activated Tcell phenotypes and more aggressive disease presentations. Based on the implicated pathobiological role of these miR deregulations, targeting strategies around their effectors appear worth pursuing. We also established a combinatorial miR-based overall survival score for T-PLL (miROS-T-PLL), that might improve current clinical stratifications.

Venetoclax Has Modest Efficacy in the Treatment of Patients with Relapsed T-Cell Prolymphocytic Leukemia

Venetoclax Has Modest Efficacy in the Treatment of Patients with Relapsed T-Cell Prolymphocytic Leukemia

Mutations in PIGA cause a CD52-/GPI-anchor-deficient phenotype complicating alemtuzumab treatment in T-cell prolymphocytic leukemia.

Infusional alemtuzumab followed by consolidating allogeneic hematopoietic stem cell transplantation in eligible patients is considered a standard of care in T-cell prolymphocytic leukemia (T-PLL). Antibody selection against CD52 has been associated with the development of CD52-negative leukemic T cells at time of relapse. Clinical implications and molecular mechanisms underlying this phenotypic switch are unknown. We performed flow cytometry and real-time-PCR for CD52-expression and next generation sequencing for PIGA mutational analyses. We identified loss of CD52 expression after alemtuzumab treatment in two of 21 T-PLL patients resulting from loss of GPI-anchor expression caused by inactivating mutations of the PIGA gene. One patient with relapsed T-PLL exhibited a single PIGA mutation, causing a CD52-negative escape variant of the initial leukemic cell clone, preventing alemtuzumab-retreatment. The second patient with continued complete remission after alemtuzumab treatment harbored three different PIGA mutations that affected either the non-neoplastic T cell or the mononuclear cell compartment and resulted in symptomatic paroxysmal nocturnal hemoglobinuria. Next generation sequencing of T-PLL cells collected before the initiation of treatment revealed PIGA wild-type sequence reads in all 16 patients with samples available for testing. These data indicate that PIGA mutations were acquired during or after completion of alemtuzumab treatment.

Abstract 5765: Epidemiology and clinicopathology prognostic factors of T-cell prolymphocytic leukemia: Analysis and met-analysis of updated pooled databases

Abstract TPLL is a rare and aggressive T-cell lymphoid malignancy. It typically presents with leukocytosis, hepatosplenomegaly, lymphadenopathy, and skin involvement. The post-thymic malignant lymphocytes often express CD2, CD3, CD4, CD5, and occasionally CD8. CD52 is also frequently and densely expressed and serves as a therapeutic target for the monoclonal antibody, Alemtuzumab. Inv(14) and chromosome 14 translocations (tchr14) are the most frequent cytogenetic abnormalities contributing to the overexpression of the TCL-1 gene product. This analysis was conducted to update and expand our existing knowledge of this rare disease. To study the demographic characteristics, cytogenetic and molecular signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 91 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathology factors on survival. A search of online databases identified all available comparative studies of Alemtuzumab in TPLL to conduct a meta-analysis using an inverse variance method with a fixed-effects model. The median age was 65 (27-89) years, with a peak incidence between ages 71 and 81. Males were 1.8 times more afflicted than females. The median overall survival of the whole group was 21 months. Sex did not impact the overall survival of the group. When compared to supportive care, chemotherapy significantly improved survival (HR:0.29, p=0.0016). Allogeneic stem cell transplant did not confer any survival advantage. Moreover, the presence of SAMHD1 and JAK-STAT mutations did not affect survival. The median survival of inv(14), tchr14, and TCL-1 expression were 29, 12, and 11 months respectively. When compared to tchr14 and TCL-1 expression combined, inv(14) seems to have a borderline significant survival advantage (HR:0.52, p=0.06). Patients who were treated with Alemtuzumab had higher median survival, though not significant, compared to those who did not (29 vs 12 months, p=0.6). To study further the effect of Alemtuzumab on TPLL survivorship, we conducted a meta-analysis of four retrospective comparative series with a total of 144 patients including ours. Alemtuzumab was found to be significantly associated with a survival benefit in patients with TPLL (HR 0.54, p=0.001). This study presents an updated epidemiologic and clinicopathologic data from a pooled cohort of patients with TPLL. It identifies the potential prognostic impact of inv(14), tchr14, and TCL-1 on survival. Furthermore, it confirms the survival advantage conferred by Alemtuzumab in TPLL. Citation Format: Philip A. Haddad, Kevin Gallagher, Dalia Hammoud. Epidemiology and clinicopathology prognostic factors of T-cell prolymphocytic leukemia: Analysis and met-analysis of updated pooled databases [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5765.

T-cell prolymphocytic leukemia: Review of an entity and its differential diagnostic considerations.

T-cell prolymphocytic leukemia (T-PLL) is a rare T-cell leukemia characterized in many patients by marked peripheral lymphocytosis, prominent splenomegaly, and skin lesions. The differential diagnosis is broad and includes other T-cell disorders presenting with similar clinical findings. This review addresses (a) the natural history, demographics, and genetic features of T-PLL; (b) clinical and pathologic differential diagnostic considerations; and (c) recent developments in the T-PLL literature relevant to laboratory professionals.

Comparative analysis of characteristics, survival trends, and associated malignancies of B-cell and T-cell prolymphocytic leukemia: A surveillance, epidemiology, and end results (SEER) based study1998 to 2016.

7558 Background: Prolymphocytic leukemia (PLL) compromises two subsets; B-cell and T-cell, accounting for less than 2% of mature lymphocytic leukemia. Both of them are rare lymphoid neoplasms with a very aggressive clinical course and poor prognosis. Methods: We used SEER program dataset between 1998 and 2016. We divided the patients into 2 groups: B-PLL and T-PLL and identified them using ‘ICD-O-3 histology recode: 9833/3 and 9834/3 respectively. We used SPSS software (version 26, IBM, NY, USA) to calculate overall survival using Kaplan-Meier methods and compare the survival between the two subtypes using the log-rank test. We also used multivariable covariate-adjust cox models to determine the impact of age, sex, race, cause of death, and associated primary malignancies on survival in both types. Results: A retrospective cohort study of 783 patients (295 B-PLL and 488 T-PLL) with overall survival rate of 22.5% (30.2% B-PLL and 18% T-PLL). The overall median survival for PLL was 16 months (95 CI, 13.745-18.255). The median survival of B-PLL (25 months, 95%CI, 15.733-34.267) was much better than T-PLL (14 months, 95%CI, 11.922-16.078). The mean age was 68.7±15.3. Patient age was an independent factor in determining the survival and inversely associated with survival time in both types (p < 0.0001). The survival rate was worst ) among age groups older than 79, between 70-79 years (8.9%, 18.9%) respectively. Although white male patients were more affected in both types, neither sex nor race significantly affected survival (P 0.554, 0.062 respectively). 64.7% of PLL patients died due to cancer. Patients with cancer-related death had significantly shorter survival time in both T-PLL group (HR = 0.351, 95% CI 0.241-0.512) and B-PLL group (HR = 0.682, 95% CI 0.491-0.945). We also found that 24.4% of B-PLL and 19% of T-PLL patients have another associated primary malignancy. Among hematological malignancies, non-hodgkin lymphoma was the commonest. Although associated solid tumors were less common, Prostate cancer and breast cancer were the commonest for both types and lung/bronchus malignancies were more associated with T-PLL. Conclusions: T-PLL subtype has worse prognosis. Age is the most important independent predictor of survival in both types. Although most of affected patients were white males, race and gender have no impact on survival. Non-hodgkin lymphoma is the commonest primary associated malignancy followed by breast and prostate cancer in both types.