B-cell Prolymphocytic Leukemia Research Articles

Epigenetic features support the diagnosis of B-cell prolymphocytic leukemia and identify 2 clinicobiological subtypes

AbstractThe recognition of B-cell prolymphocytic leukemia (B-PLL) as a separate entity is controversial based on the current classification systems. Here, we analyzed the DNA methylome of a cohort of 20 B-PLL cases diagnosed according to the International Consensus Classification/World Health Organization HAEM4R guidelines, and compared them with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and normal B-cell subpopulations. Unsupervised principal component analyses suggest that B-PLL is epigenetically distinct from CLL, MCL, and SMZL, which is further supported by robust differential methylation signatures in B-PLL. We also observe that B-PLL can be segregated into 2 epitypes with differential clinicobiological characteristics. B-PLL epitype 1 carries lower immunoglobulin heavy variable somatic hypermutation and a less profound germinal center–related DNA methylation imprint than epitype 2. Furthermore, epitype 1 is significantly enriched in mutations affecting MYC and SF3B1, and displays DNA hypomethylation and gene upregulation signatures enriched in MYC targets. Despite the low sample size, patients from epitype 1 have an inferior overall survival than those of epitype 2. This study provides relevant insights into the biology and differential diagnosis of B-PLL, and potentially identifies 2 subgroups with distinct biological and clinical features.

Understanding splenic B-cell lymphoma/leukaemia with prominent nucleoli: Diagnosis, underpinnings for disease classification and future directions.

The 5th edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5) introduced a new category, splenic B-cell lymphoma/leukaemia with prominent nucleoli (SBLPN). The diagnostic entity B-cell prolymphocytic leukaemia (B-PLL) has been discontinued and the category of hairy cell leukaemia variant (HCLv) has been conceptually reframed. B-PLL and HCLv diagnoses were uncommon. Overlap existed between B-PLL and other indolent lymphomas like chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). HCLv lacked consistent cytomorphological, immunophenotypic and genetic features. To address these issues, the WHO-HAEM5 classification has introduced SBLPN to serve as a temporary holding ground for entities that do not neatly fit into the existing classification. Cases previously classified as CD5-negative B-PLL and HCLv fall under the SBLPN category. Some splenic marginal zone lymphoma and splenic diffuse red pulp small B-cell lymphoma cases with higher number of medium or large nucleolated B cells would also be classified as SBLPN under the WHO-HAEM5. This review explores the rationale for discontinuing B-PLL and HCLv diagnoses. It then examines the concept of SBLPN, offers practical guidance for diagnosis and discusses future directions in classifying splenic B-cell lymphomas.

Racial & Socioeconomic Disparities in Patients with B-Cell Prolymphocytic Leukemia

Racial & Socioeconomic Disparities in Patients with B-Cell Prolymphocytic Leukemia

Analyzing the incidence, survival, and demographic trends of B-cell prolymphocytic leukemia

Analyzing the incidence, survival, and demographic trends of B-cell prolymphocytic leukemia

Obituary for a diagnosis: B-cell prolymphocytic leukaemia (1974-2022).

Obituary for a diagnosis: B-cell prolymphocytic leukaemia (1974-2022).

Immunophenotypic Profile of Chronic Lymphoproliferative Diseases in the State of Rio Grande Do Norte, Northeast, Brazil

INTRODUCTION: Chronic lymphoproliferative diseases (CLPD) are considered as a heterogeneous group of diseases characterized by monoclonal expansion and accumulation of apparently mature lymphocytes, which have a proliferative and/or survival advantage over normal lymphocytes in different organs such as bone marrow, peripheral blood and lymph nodes. This translates into the progressive accumulation of clonal cells and their products, causing peripheral blood and bone marrow lymphocytosis, in addition to lymphadenopathy, splenomegaly or other organomegaly. According to the World Health Organization, which reflects the international consensus and is based on pathological, genetic and clinical factors, lymphoproliferative neoplasms are classified according to the stage of maturation and the lineage where the neoplastic transformation occurs through flow cytometry (FC). OBJECTIVES: The aim of this study was to demonstrate the immunophenotypic diagnostic profiles of patients with CLPD in Rio Grande do Norte, Brazil by FC. METHODOLOGY: Were investigated 884 patients with CLPD of both sexes through CF with a panel of monoclonal antibodies directed to CLPD. In addition, other patient information, such as age, gender, and clinical and hematological data were also collected. RESULTS: The results showed that 89.7% of the cases were B Cell CLPD (B-CLPD) and 10.3% T and natural killer cells (T/NK-CLPD). The distribution of B-CLPD cases were as follows: 487 Chronic lymphocytic leukemia; 18 B-Cell Pro-lymphocytic leukemia; 25 Hairy cell leukemia; 6 variant Hairy cell leukemia; 6 Follicular lymphoma leukemized; 4 Splenic lymphoma with villous lymphocytes; 33 Mantle cell lymphoma; 4 Waldenstrom's macroglobulinemia; 69 Multiple myeloma; 14 Plasma cell leukemia; 11 Burkitt's lymphoma and 117 Leukemic Non-Hodgkin lymphoma (Table 1). The distribution of CLPD-T/NK was as follows: 12 Large granular lymphocytic leukemia; 14 T-Cell prolymphocytic leukemia; 18 Adult T-cell leukemia; 20 Sézary syndrome; and 24 Peripheral T-Cell lymphoma and 2 DLPC-NK (Table 1). DISCUSSION: The B-CLPD are the most commonly observed corresponding to more than 85% of all cases and are characterized by the presence of clonal B lymphocytes with expression of a single type of immunoglobulin light chain (kappa or lambda) in a proportion greater than 1/10, associated the strong positivity of Pam-B antigens such as CD19, CD22 and CD20 and the absence or low expression of Pam-T antigens. However, other antigens such as CD200, CD5, FMC7, CD79b and CD103, among others, may be present or absent, specifically characterizing these entities as Chronic lymphocytic leukemia (weak CD22+; CD200+, CD5+, FMC7-, CD79b-), Hairy cells leukemia (strong CD22+; FMC7+; CD79b+; CD5-; CD200-; CD103+; CD123+; CD11c+ and Follicular lymphoma (strongCD22+/CD20+, CD10+, CD200-, CD79B+, FMC7+). T/NK-CLPD are less frequent and are characterized by the expression of Pan-T antigens CD2, CD3, CD5, CD7, CD28 and TCL-1, with clonality evidenced by strong positivity of TCRα/β in most cases and increase of TCD4+ or TCD8+ lymphocytes in a ratio above 1:10 in most cases. In this group, large granular lymphocyte leukemia (LGLG) is a rare type of T/NK cell CLPD characterized by peripheral and medullary infiltration of large hypergranular lymphocytic cells, comprising about 2-5% of all cases, the most commonly seen being CD8+ T cells. CONCLUSION: The results presented demonstrate that immunophenotyping is a defining technique for clarifying the diagnosis of patients with CPLD, clonality was also successfully characterized in the investigated cases of CPLP of B ,T and NK lineages.

B-Cell Prolymphocytic Leukemia: Two Case Reports and Review of the Literature

B-cell prolymphocytic leukemia is a very rare mature B-cell leukemia occurring in elderly people diagnosed when prolymphocytes comprise more than 55% of the lymphoid cells in peripheral blood. Its evolution is most often aggressive. We report here the cases of two patients with clinical signs dominated by splenomegaly associated with significant hyperlymphocytosis. Their blood smears revealed extensive prolymphocyte invasion suggesting Prolymphocyte leukemia confirmed by immunophenotyping. Both purine analogues and monoclonal antibodies have shown promoting results, however, allogeneic hematopoietic stem cell transplantation remains the only therapeutic means allowing a lasting response. However, it is reserved for young patients with compatible donors. A good understanding of the pathogenesis and a better integration of the molecular data of this hemopathy open the way to the use of new targeted therapies. Prolymphocyte leukemia is a very rare, complex, and often aggressive, mature lymphoid hemopathy. The mean age of onset is 65 years with a predominance of males. We report here the case of a patient with splenomegaly and severe lymphocytosis in whom the smear showed an invasion of 90% of prolymphocytes suggesting Prolymphocyte leukemia confirmed by immunophenotyping.

Progression and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma and B-cell prolymphocytic leukemia: Report from the 2021 SH/EAHP Workshop.

Session 3 of the 2021 Workshop of the Society for Hematopathology/European Association for Haematopathology examined progression and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and B-cell prolymphocytic leukemia (B-PLL). Thirty-one cases were reviewed by the panel. Additional studies such as immunohistochemistry and molecular genetic testing, including whole-exome sequencing and expression profiling, were performed in select cases. Session 3 included 27 CLL/SLL cases and miscellaneous associated proliferations, 3 cases of B-PLL, and 1 case of small B-cell lymphoma. The criteria for -accelerated CLL/SLL are established for lymph nodes, but extranodal disease can be diagnostically challenging. Richter transformation (RT) is a broad term and includes true transformation from original CLL/SLL clone(s) and clonally unrelated neoplasms. The morphologic, immunophenotypic, and genetic spectrum is diverse with classical and highly unusual examples. T-cell proliferations can also be encountered in CLL/SLL. B-cell prolymphocytic leukemia is a rare, diagnostically challenging disease due to its overlaps with other lymphoid neoplasms. The workshop highlighted complexity of progression and transformation in CLL/SLL and B-PLL, as well as diagnostic caveats accompanying heterogeneous presentations of RT and other manifestations of disease progression. Molecular genetic studies are pivotal for diagnosis and determination of clonal relationship, and to predict response to treatment and identify resistance to targeted therapy.

Mycobacterial Spindle Cell Pseudotumor of the Nasal Cavity.

Mycobacterial spindle cell pseudotumor (MSCP) represents an uncommon tumor-like proliferation associated with nontuberculous mycobacterial infection, i.e., M. avium intracellulare, affecting primarily the lymph nodes of immunocompromised men in their 5th decade. Involvement of the nasal cavity by MSCP is exceedingly rare with only 3 well-documented examples in the literature. A 74-year-old, HIV-negative, man presented with a 0.5-cm nodule of the left nasal cavity clinically presenting as a "nasal polyp." His medical history was significant for colonic adenocarcinoma, cutaneous basal cell carcinoma, and chronic lymphocytic leukemia (CLL) transforming to B-cell prolymphocytic leukemia, responsive to chemotherapy. The patient was diagnosed with prostatic adenocarcinoma treated with radiotherapy two months before the nasal lesion was detected. No lymph node enlargement, pulmonary involvement or hepatosplenomegaly were noticed. The nasal nodule was surgically excised and histopathologically examined to rule out metastatic disease or CLL relapse. Microscopically, the lesion comprised a well-circumscribed, monotonous, spindle cell population in a vaguely storiform arrangement mixed with a heavy infiltrate of neutrophils and sparse lymphocytes. The spindle cells featured finely granular rich eosinophilic cytoplasm with rounded, oval to epithelioid, or elongated nuclei with vesicular chromatin and one or two distinct nucleoli. The lesional cells lacked overt cytologic atypia and showed occasional regular mitoses. The surface epithelium was intact or focally ulcerated. By immunohistochemistry, the spindle cell population stained strongly and diffusely for CD68 and was negative for AE1/AE3, SMA, CD34, and PSA. CD3 highlighted scattered lymphocytes. Ziehl-Neelsen stain disclosed numerous intracytoplasmic acid-fast bacilli. A diagnosis of MSCP was rendered. No recurrences were observed during a 24-month follow-up period. Although exceptionally rare, MSCP should be considered in the differential diagnosis of nodular lesions of the nasal cavity that are characterized microscopically by marked spindle cell proliferation in a vague storiform pattern, admixed with a lymphocytic or mixed inflammatory infiltrate. A negative medical history for HIV infection and medication-induced immunosuppression should not preclude a diagnosis of MSCP, particularly in extranodal sites. Once the diagnosis is established, prognosis appears to be excellent for nasal MSCP following conservative surgical excision.

B-cell prolymphocytic leukemia after COVID-19 infection

B-cell prolymphocytic leukemia after COVID-19 infection

De-Novo B-Cell Prolymphocytic Leukemia

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.

230 - Caught in the act: chronic lymphocytic leukemia progression to B-cell prolymphocytic leukemia

230 - Caught in the act: chronic lymphocytic leukemia progression to B-cell prolymphocytic leukemia

B-Cell Prolymphocytic Leukemia: Clinical Profile and Treatment Outcomes at a Tertiary Cancer Center in South India

Introduction: B-cell prolymphocytic leukemia (B-PLL) is a rare lymphoid malignancy considered to have an aggressive course. At diagnosis, most patients have prominent splenomegaly, minor involvement of lymph nodes, and marked leukocytosis with a predominance of prolymphocytes. It is usually treated on similar lines as chronic lymphocytic leukemia. Objectives: The objective of this study was to study the clinicopathological profile and treatment outcomes of B-PLL patients treated at a tertiary cancer center in South India. Materials and Methods: In this retrospective study, the patients diagnosed with B-PLL from August 2020 to July 2022 were included and reviewed for clinical characteristics, pathological findings, and treatment outcomes. The patient's data were collected from hospital medical records and analyzed. Results: Five patients were diagnosed as B-PLL over a period of 2 years. The median age at diagnosis was 52 years. In this series, all the patients presented with high white blood cell (WBC) count ≥50,000 WBC per microliter and splenomegaly was seen in 80%, including massive splenomegaly in 60% of patients. Three patients were treated with bendamustine–rituximab regimen, one patient received single-agent bendamustine, and rest one patient died of tumor lysis syndrome before chemotherapy. Three patients demonstrated partial remission during interim evaluation and rest two patients died of their disease. Conclusion: B-PLL demonstrates a spectrum of clinical features with variation in the extent of the splenomegaly, leukocyte counts, and aggressiveness. This study shows a plethora of clinical features ranging from slowly progressive to rapidly fatal disease.

Bendamustine and rituximab successfully treated B-cell prolymphocytic leukemia: three case reports and a literature review

Bendamustine and rituximab successfully treated B-cell prolymphocytic leukemia: three case reports and a literature review

Clinical features and prognosis of eight patients with splenic diffuse red pulp small B-cell lymphoma

Objective: To investigate the clinical characteristics, response, and prognosis of splenic diffuse red pulp small B-cell lymphoma (SDRPL) . Methods: Eight cases of SDRPL were diagnosed and treated at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, between May 2017 and April 2022. Data on the clinical features, laboratory results, bone marrow and spleen biopsy results, response, and prognosis were collected and analyzed. Results: The median age at diagnosis was 54 (42-69) years. Splenomegaly and lymphocytosis were present in all cases, and PET/CT revealed normal to slightly elevated splenic FDG uptake. All cases were in stage Ⅳ, with spleen, peripheral blood, and bone marrow but no proximal lymph nodes involved. The cytoplasm of neoplastic villous cells was abundant, and splenic pathology showed that small homogenous lymphocytes permeated the splenic sinus and splenic cord, and the white pulp atrophied. Immunohistochemistry was not typical, and B-cell markers including CD19, CD20 and CD79α were positive. After a median follow up of 35.5 (4-60) months, 7 cases were alive after splenectomy with or without chemoimmunotherapy. The patient with CCND3 P284A and MYC S146L mutation developed to B-cell prolymphocytic leukemia (B-PLL) 1 month after splenectomy and died at 16 months of follow-up. Conclusion: A rare indolent B-cell lymphoma that primarily affects the elderly, SDRPL. Most patients achieved long-term survival, but the prognosis of patients who progress to B-PLL was poor.

Prolymphocytic Progression of Chronic Lymphocytic Leukemia in the Era of Novel Targeted Therapies: A Nationwide Veterans Affairs Retrospective Review

Introduction: Chronic lymphocytic leukemia (CLL) with prolymphocytic progression is a new disease entity defined in the 5th edition World Health Organization (WHO) classification as a CD5+ non-mantle B-cell neoplasm with at least 15% prolymphocytes in the peripheral blood or bone marrow, partially replacing the prior classification of B-cell prolymphocytic leukemia (B-PLL). Due to the rarity of prolymphocytic progression, patient characteristics and disease natural history have not been well-described, particularly in the modern era of novel targeted therapies for CLL. In this nationwide multicenter review, we present an initial retrospective analysis of this newly defined disease classification. Methods: An electronic query of the Veterans Affairs (VA) Corporate Data Warehouse and retrospective chart review were performed to identify patients who had CD5+ CLL with ≥ 15% prolymphocytes in the blood or bone marrow between the years 2014 (FDA approval of ibrutinib) and 2022. Responses were retrospectively categorized using the International Workshop on CLL (iwCLL) response criteria. Pearson's chi-squared test was utilized for analysis of categorical variables. Survival was measured with the Kaplan-Meier method and analyses were performed using the Wilcoxon test and Cox regression. Results: Among 36,973 VA patients with ICD-9/10 codes for CLL between 2014-2022, the electronic query and chart review identified 93 patients (0.3%) from 28 different VA sites who met the 2022 WHO classification for prolymphocytic progression based on morphology (Table 1). The median duration of follow-up from the time of prolymphocytic progression was 28.1 months (range, 0.5 - 121.6). The 2-year and 5-year overall survival (OS) from prolymphocytic progression were 66.2% (95% CI, 55.0 - 75.2) and 35.3% (95% CI, 23.1 - 47.7), respectively. Eight patients (9%) had ≥ 55% prolymphocytes, which had formerly been classified as B-PLL. The median years from diagnosis of CLL to reaching ≥ 15% and ≥ 55% prolymphocytes were 3.7 (range, 0 - 28.4) and 3.2 (range, 0.6 - 10.8), respectively. The % prolymphocytes did not impact OS in a Cox regression model. TP53 deletions were detected in 39% of those with 15 - 54% prolymphocytes compared to 67% in ≥ 55% prolymphocytes (p = 0.22). The detrimental impact of TP53 deletion trended towards significance (2-year OS 55.7% vs. 77.3%, p = 0.050) (Fig 1). Fifty patients (54%) were treated with oral BTK, BCL-2, or PI3K inhibitors after prolymphocytic progression (Table 1). The most commonly prescribed therapies were ibrutinib (n = 29), venetoclax (n = 19), and acalabrutinib (n = 8). An anti-CD20 monoclonal antibody was combined with venetoclax in 9 patients (18%). The median lines of therapy prior to initiation of a targeted agent was 1 (range, 0 - 5). At the start of therapy, bulky lymphadenopathy, constitutional symptoms, and splenomegaly were reported in 24%, 32%, and 62% of patients, respectively. In addition, 31% had a hemoglobin < 11 g/dL, 40% had a platelet count < 100 x 109/L, and 60% had an elevated LDH. Among evaluable patients, a partial response (PR) by iwCLL criteria was observed in 13 cases (28%), with another 18 (38%) fulfilling the hematologic criteria for PR but lacking follow-up imaging to confirm improvement in splenomegaly or lymphadenopathy. The median progression free survival (PFS) for patients treated with a targeted agent was 31.4 months. At last follow-up, the median duration of targeted therapy was 13.1 months (range, 0.2 - 94.9), with 18 (36%) remaining on therapy. The most common reasons for discontinuation of therapy were disease progression (n = 14) and drug toxicity (n = 12). After discontinuation of the first targeted agent, 13 patients (26%) received additional treatment, such as another targeted agent (n = 7) or cytotoxic chemotherapy (n = 6). One patient went on to receive an allogeneic stem cell transplantation. There were 22 deaths, with the most common causes being disease progression (n = 11), infection (n = 3), and unknown cause (n = 5). Conclusion: Prolymphocytic progression of CLL represents a newly defined heterogeneous disease with variable presentations and patient survival. As in CLL, TP53 deletions may carry prognostic value. Though few patients had ≥ 55% prolymphocytes, the percent of prolymphocytes did not appear to influence overall survival in this cohort. Oral targeted agents have efficacy in this population and were used in over half of the patients evaluated. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence of Secondary Hematological Malignancies in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: An Analysis of SEER Database

Background: Patients with Chronic lymphocytic leukemia/ Small lymphocytic lymphoma (CLL/SLL) are at risk of experiencing transformation to aggressive hematological malignancies and can develop second primary malignancies. With a dramatic change in the treatment landscape of CLL/SLL, there is paucity of literature on real-world incidence of second hematological malignancies (SHM) in the era of targeted therapy. We analyzed data obtained from Surveillance, Epidemiology, and End Results (SEER) database to estimate the incidence of SHM in patients with CLL/SLL. Method We used SEER 17 registry to identify adult patients with an index diagnosis of CLL/SLL between January 2000- December 2019, and subsequent diagnosis (>2months after index diagnosis) of any SHM. International Classification of Disease code for Oncology (ICD-O-3) was used to identify codes assigned to CLL/SLL (9823/3) and 11 types of SHM [9650/3: Classical Hodgkin lymphoma(HL), 9673/3: Mantle cell lymphoma(MCL), 9680/3: Diffuse large B-cell lymphoma (DLBCL), 9687/3: Burkitt lymphoma (BL), 9689/3: Splenic marginal zone lymphoma (SMZL), Acute lymphoblastic leukemia/lymphoma (ALL: consisting of 9811/3: B lymphoblastic leukemia/lymphoma, 9728/3: Precursor B-lymphoblastic lymphoma, 9836/3: Precursor B-cell lymphoblastic leukemia and 9837/3: T lymphoblastic leukemia/lymphoma), 9833/3: B-cell prolymphocytic leukemia(B-PLL), 9834/3: T-cell prolymphocytic leukemia(T-PLL), 9861/3: Acute myeloid leukemia (AML), 9863/3: Chronic myeloid leukemia (CML), 9989/3: Myelodysplastic syndrome (MDS)]. We considered SHM as any blood malignancy with diagnosis after treated or untreated CLL/SLL. Patients with CLL/SLL who had unknown survival time or a simultaneous diagnosis of another hematological malignancy were excluded. A data cut-off time point (December, 2019) was used to estimate survival duration (in months) and vital status (dead or alive). Additional data including demographics and treatment details were extracted using SEER Stat v 8.4.0.1 software. Statistical analyses were performed using IBM-SPSS Statistics v 28.0.1.1(15). The reverse Kaplan Meier method was used to calculate median follow-up duration. Chi-squared test was used to calculate difference between categorical variables. Kaplan Meier method and log rank test were used to estimate overall survival (OS). Result 1.8% of adult patients with CLL/SLL (1390 of 78,943) had SHM during the study period. 1255 patients met eligibility criteria (CLL/SLL patients with unknown survival duration (n=3), simultaneous diagnosis of other hematological malignancy (n=3) and a gap of <2months between SHM diagnosis and index diagnosis (n=129) were excluded). Of the 1255 patients, 63.7% (799) were males and 90% (1130) had White race. Median ages at the time of diagnosis of CLL/SLL and SHM were 65 and 70 years respectively. DLBCL (57.2% [n=718]), MCL (10.8% [n=136]), and MDS (8.69% [n= 109]) were the most frequently reported SHMs. Median (95% Confidence Interval) follow-up duration after CLL/SLL and SHM diagnosis were 153 (145.0-160.9) and 58 (53.4-62.6) months respectively. Gender association with SHM was not statistically significant (p =0.146). 394 (31.4%) patients received chemotherapy (CT) for CLL/SLL, while 861 (68.6%) patients either did not receive treatment or status was unknown. OS subsequent to any SHM diagnosis was 12 (95%CI 10.1-13.9) months. OS was lowest for AML [3(1.3-4.6)], and highest for SMZL [113(82.7-143.3)]. Patients who did not receive chemotherapy (for CLL) or details were unknown lived longer subsequent to SHM diagnosis compared to patients who received chemotherapy for CLL/SLL (Median survival months (95%CI): 13(10-16) vs 10(8-12), p =0.034, hazard ratio = 1.159 (95% CI: 1.007-1.334) (Figure). Conclusion SHM were seen in approximately 2% of CLL/SLL patients, predominantly among males and white race. Overall survival after the diagnosis of SHM is around 1 year. Improvement in overall survival with newer targeted therapies for CLL/SLL necessitates robust strategies for surveillance of SHM. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Treatment and Overall Survival Outcomes of Patients with B-Cell Prolymphocytic Leukemia

Background B-cell prolymphocytic leukemia (B-PLL) is a rare hematologic malignancy, accounting for <1% of all chronic B-cell leukemia cases, and is generally associated with aggressive features and poor clinical outcomes. Given its low incidence, there is limited data available regarding practice patterns and treatment outcomes in this population. We aimed to evaluate, on a national scale, the trends and overall survival outcomes of patients with B-PLL. Methods The National Cancer Database was used to identify patients with B-cell PLL from 2004-2019. For patients receiving treatment, the use of single or multiagent therapy and upfront transplant was compared, with the utilization of immunotherapy identified for patients diagnosed 2013 or later, corresponding to the recoding of rituximab and alemtuzumab. Kaplan-Meier and Cox regression analysis was used to compare overall survival (OS) for all B-PLL pts. Survival was compared by year of diagnosis, with diagnosis in 2004-2014 considered to be prior to the availability novel therapies, 2015 and later associated with the introduction of BTK and PI3K inhibitors and 2017 as considered having access to venetoclax. Multivariate analysis was performed adjusting for age, co-morbidity score, facility type, and insurance status. Results Of the 950 B-PLL patients identified, the median age of diagnosis was 72 years (interquartile range 62-80) with 42% of patients being ≥75 years old. The majority (88%) identified as White and were male gender (62%). For those with treatment data available (68%; N=646), the majority of patients (72%) received frontline systemic therapy at diagnosis, whereas 14% were managed with active surveillance, and 14% did not receive any form of treatment. Of the 467 patients receiving upfront treatment, 45% of these patients were treated with single agent therapy, 41% received multiagent chemotherapy, and 14% had an unspecified therapy. For those with transplant and immunotherapy data available, 186 patients received immunotherapy and 39 patients were treated with transplant in the front-line. B-PLL patients were more likely to receive treatment if managed at an academic center (OR 2.34; 95% CI 1.45-3.80, p<0.001), and less likely to receive treatment with each increased year of age (OR 0.95; 95% CI 0.94-0.97, p<0.001) or with increased comorbidity burden (OR 0.52 for Charlson-Deyo comorbidity score ≥2, 95% CI 0.28-0.98, p<0.001). With a median follow-up of 1.5 years, B-PLL patients had a median OS of 2.8 years (95% CI 2.3-3.3), with a 1-, 5-, and 10- year survival of 67%, 39%, and 26%, respectively. Patients managed with upfront active surveillance had a median OS of 7.8 years (95% CI 6.7-9.0 years, p<0.001), and patients who underwent upfront treatment had a median OS of 2.1 years (95% CI 1.5-2.7, p<0.033), with a 1-,5-, and 10- year OS of 65%, 36%, and 29%, respectively (all p<0.03). Patients who did not receive disease directed therapy due to death, hospice care, or contraindication, had a median OS of 1.3 years (95% CI 0.3-2.3). For patients treated with immunotherapy and diagnosed 2013 or later (N=166), median OS was 2.9 years (95% CI 1.8-3.9). On multivariate analysis, factors associated with increased risk of death included increased age (Hazard Ratio [HR] 1.04, 95% CI 1.03-1.05) and higher comorbidity score (HR 1.40, 95% CI 1.27-1.54) (all p<0.001). When examining survival trends by year of diagnosis, patients diagnosed prior to BTK and PI3K inhibitor availability (N=646) had no statistically significant difference in OS compared to those diagnosed 2015 or after (N=149) with a median OS of 2.7 years vs. 3.4 years (p=0.432). Additionally, patients diagnosed 2017-2019, with availability of venetoclax (N=175), also had no significant improvement in median OS (2.6 years; 95% CI 1.7-3.5, p=0.885) referenced to diagnosis from 2004-2014. Conclusions These data comprise the largest study to date evaluating patient outcomes with B-PLL. We found that this disease primarily affects elderly patients with a higher incidence in males compared to females. Though the incorporation of novel therapies in recent years has increased therapy options in B-PLL, these data show no significant improvement in overall survival. The continued poor outcomes of this aggressive disease suggests that there is still a high need for clinical research and novel therapeutic options for these patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Venetoclax induces deep and durable minimal residual disease‐negative remission in high‐risk TP53 disrupted B prolymphocytic leukaemia

B-cell prolymphocytic leukaemia (B-PLL) is an aggressive B-cell lymphoproliferative disease with few clinically proven targeted treatments. Due to the rarity of the condition, there is a paucity of clinical trial data and none that involve targeted inhibitors. We present a unique case of relapsed refractory B-PLL treated to a sustained minimal residual disease-negative remission with venetoclax monotherapy, to add to the current evidence base and rationale for future studies using BCL-2 inhibitors in B-PLL.

A new case of trisomy 5 with complex karyotype abnormalities in B-cell prolymphocytic leukemia: a case study

BackgroundThe B-cell prolymphocytic leukemia (B-PLL) diagnosis is challenging due to the superposition with mature B-cell leukemia and/or lymphoma.ObjectiveAn insight case study of trisomy 5 with complex karyotype abnormalities in B-cell prolymphocytic leukemia.Subject and methodsA 72-year-old man was referred to the Hematology Department, Qilu Hospital, Shandong University, because of persistent fever (10 days) and lymphocytosis. A detailed diagnostic methods including complete blood count, bone marrow aspiration, flow cytometry, conventional karyotype analysis, fluorescence in situ hybridization (FISH), quantitative real-time polymerase chain reaction (qRT-PCR), next-generation sequencing technology (NGS) used to detect 41 kinds of mutant genes related to hematological malignancies were conducted and reasonable therapeutic regimens including emergent leukapheresis accompanied by basification of urine and hydrotherapy, followed by a regimen of cyclophosphamide and dexamethasone.ResultsSubject white blood cell count was 143.43 × 109/L, and 56% prolymphocytes. He did not show lymphadenopathy but splenomegaly. Immunophenotyping of prolymphocytes was CD5(+low), CD10(−), CD11c(−), CD19(+), CD20(+), cCD22(+), CD23(−), cCD79a(+), CD79b(+), FMC7(±), CD43(−), CD3(−), CD56(−), CD103(−), HLA-DR(+), and Lambda(+). R-banding and FISH revealed that leukemia cells carried extra chromosome 5. Considering the rare occurrence of trisomy 5 found in prolymphocytic leukemia, especially in Asians, with rapid disease progression. We know that median survival of B-PLL is three years after diagnosis, while survival time of this patient was only 1 month.ConclusionThis study could provide the firsthand materials for precision, medicine and mechanism research in cytogenetics and molecular biology. It inferred that trisomy 5 might be a poor prognosis indicator, providing directions for clinical practice in the foreseeable future.