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Summary 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. [ABSTRACT FROM AUTHOR]

Summary: First‐line purine nucleoside analogues (PNAs) in hairy cell leukaemia (HCL) allow deep and long‐lasting responses. We retrospectively analysed 53 HCL patients treated frontline with cladribine and assessed for response at 2 and 6 months after treatment to evaluate the kinetics of response. The estimated median progression‐free survival was significantly different according to the degree of residual HCL infiltrate detected by immunohistochemistry at the bone marrow biopsy at 2 months (≤5% vs. >5%, 247 vs. 132 months, respectively, p = 0.033), but not at 6 months (p = 0.79). Our data suggest a favourable prognostic impact of early marrow HCL clearance in patients treated with cladribine. [ABSTRACT FROM AUTHOR]

Haemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive, excess immune activation syndrome. Diagnosis can be challenging due to its several clinical mimics including sepsis. There are multiple aetiologies of HLH; in adults, it is most commonly triggered by infection, malignancy, drugs and autoimmune processes. Failure to rapidly diagnose and treat this condition can be fatal. The management of HLH includes identifying and removing the trigger, supportive management and immunosuppression. Identifying the trigger is essential to inform the most appropriate type of immunosuppression. Here, we report a case of likely drug-induced HLH in a patient recently treated for hairy cell leukaemia. The culprit drug was thought to be co-trimoxazole and this case report highlights a very rare complication of this commonly used drug. We discuss our management approach with steroid monotherapy and withdrawal of co-trimoxazole. [ABSTRACT FROM AUTHOR]

Background: Hairy cell leukaemia (HCL) is an uncommon, indolent, B-cell, lymphoproliferative disorder typically involving peripheral blood, spleen and bone marrow. It is commonly presenting with pancytopenia, monocytopenia and massive splenomegaly, while accounting for 2% of lymphoid leukaemias. Cases of extranodal lesions caused by HCL are rare, although these have been reported. Here, we report a case of HCL presenting as a paravertebral mass without systemic involvement. Case description: A 58-year-old man was admitted to our hospital due to progressive difficulty walking for a month, without any other symptoms. Blood examination noted mild anaemia with Hb=12.6 g/dl and mild thrombocytopenia of 140,000/ul. Magnetic resonance imaging (MRI) and computed tomography (CT) imaging demonstrated a T6 posterior paravertebral mass lesion, extending into the spinal canal with metastatic bone lesions along the thoracic and lumbar spine. Further imaging study with CT indicated mild splenomegaly (13.4 cm) and an enlarged abdominal lymph node (3.5 cm) near celiac trifurcation. Conclusion: A core-needle biopsy from the paravertebral mass was performed. Results showed small-sized cells with round or oval nuclei, and pale cytoplasm with immunophenotype: B-cell origination with CD20+, Cyclin D1+, DBA.44+, Annexin+ and BRAF+, indicative of HCL.

Atraumatic splenic rupture is a complex surgical pathology owing to its rarity, non-specificity of symptoms and gravity of possible outcomes. This case outlines the investigation and management of a patient with atraumatic splenic rupture secondary to undiagnosed hairy cell leukaemia. While the patient was initially managed conservatively, they went on to have a splenectomy owing to ongoing transfusion requirements. A review of the literature has also been performed and presented to highlight the potential causes of atraumatic splenic rupture and the various options for confirming diagnosis and definitive management. [ABSTRACT FROM AUTHOR]

Hairy cell leukaemia (HCL) diagnosis is based on the morphologic detection of circulating abnormal hairy cells in the peripheral blood and/or bone marrow, an HCL immunological score of 3 or 4 based on the expression of the CD11c, CD25, CD103 and CD123 and also the presence of a BRAF V600E activating mutation in the B‐raf proto‐oncogene (BRAF gene) (7q34). When using new generation sequencing of 21 targeted genes in 124 HCL patients, we identified a cohort of 6/124 (2%) patients with unusual BRAF mutations: two patients presented non‐V600 mutations (BRAF F595L, BRAF W604L respectively) and four other patients silent BRAF mutations. When using droplet digital PCR (ddPCR) three of the four patients with concomitant BRAF V600E and silent mutation were negative. The respective role of these mutations in the occurrence of HCL or its progression remains to be clarified, but BRAF sequencing is necessary in case of negative BRAF V600E by ddPCR. [ABSTRACT FROM AUTHOR]

Background: B-Cell Lymphoproliferative Disorders (B-LPDs) are a group of heterogenous disorders characterised by the accumulation of B-cells in peripheral blood, bone marrow, lymph nodes and spleen. They have a variable disease course and outcome and many share similar features making differential diagnosis challenging. Therefore, accurate diagnosis is fundamental in particular for determining treatment options. Immunophenotyping by flow cytometry plays a crucial role in the diagnosis of B-LPDs. However, overlapping immunophenotyping patterns exist and the use of novel monoclonal antibodies has become increasingly important in immunophenotyping analysis. More recently differential expression of CD200 has been reported in various B-LPDs and that CD200 may improve the differentiation between chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL). In this study CD200 expression is evaluated in different B-LPDs.Methods: A total of 100 samples were collected and analysed by immunophenotyping flow cytometry over a period of 1 year (2017–2018), by a panel of monoclonal antibodies including CD200. The percentage of CD200 and its expression intensity was evaluated and compared between different groups of B-LPDs.Results: All of the 50 cases of CLL expressed CD200 with moderate to bright intensity, 6 MCL cases lacked the expression of CD200. Furthermore, all 5 cases of hairy cell leukaemia (HCL) expressed CD200. Out of all B-LPDs evaluated, CD200 expression in HCL cases was noted to be the brightest. The other 39 cases were not found to be B-LPDs.Conclusion: CD200 has an important role in differentiating CLL from MCL, HCL has a consistent bright expression of CD200. By adding CD200 to the combinations of markers in routine testing panel, Immunophenotyping by flow cytometry can be an effective tool in the diagnosis of B-LPDs especially in cases with atypical immunophenotyping pattern. Our result support that CD200 can be added to routine testing panel as it is useful in differentiating them.

Abstract Classical hairy cell leukemia (HCL‐c) and HCL variant (HCL‐v) are recognized as separate entities with HCL‐v having significantly shorter overall survival. Proteomic studies, shown to be prognostic in various forms of leukemia, have not been performed in HCL. We performed reverse phase protein array‐based protein profiling with 384 antibodies in HCL‐c (n = 12), HCL‐v (n = 4), and normal B‐cells (n = 5) samples. While HCL could be distinguished from normal based on unsupervised hierarchical clustering, overlap in protein expression patterns was seen between HCL‐c and HCL‐v, with ∼10% of the proteins being differentially expressed, suggesting potential therapeutic targets.

Between July 2005and October 2006, eight patients (pts) with hairy cell leukaemia were treated with Vero- cladribine at N.N. Blokhin Cancer Research Center. All pts achieved complete remission (CR). Duration of CR ranges from 1+ to 12+ months in 7 cases. There were no serious adverse events during the treatment and follow-up periods (1-12 months). Vero- cladribine was well tolerated. Anemia (grade IV) was seen in 1 patient and thrombocytopenia (grade I) was seen in another 1 patient. No one patient has febrile neutropenia or infectious complication.

Background: Hairy cell leukaemia (HCL) is an uncommon neoplasm of mature B-lymphoid cells which is characterized by cytopenias, commonly of all three cell lines, with typical hairy cells on peripheral smear and/or bone marrow along with organomegaly. Objective was to document the outcomes of HCL patients treated at a tertiary care hospital in Pakistan. Methods: Medical records of patients from 2004 to 2020 were reviewed and data was collected to assess patient’s demographics, symptomatology, remission rate and overall survival. The record flies of all patients presenting to AFBMTC with HCL were included in the study. The record file with insufficient data were excluded Results: 26 patients with a mean age of 48.12±11.43 years were diagnosed with HCL and treated at AFBMTC. Out of these, 23 (88.4%) were male and 03 (11.5%) females. The main presenting complaints were generalized body aches (34.6%), fever (15.4%), incidental finding of cytopenias (11.5%) and abdominal discomfort (26.9%). Splenomegaly was found in 76.92% while hepatomegaly was found in 46.15% of patients. A total of 12 (46.15%) patients received Cladribine (either intravenous or subcutaneous) and splenectomy was done in 7 (26.92%) as 1st line treatment. Eleven patients out of 12 (83.33%) who received Cladribine and 05 (71.42%) patients out of seven who underwent splenectomy; achieved complete remission (CR) after 1 st line of treatment. One patient received Cladribine as 1st line of treatment but did not respond and CHOP regimen was given as second line. Out of the 26 patients, 5 patients (19.23%) relapsed at a median interval of 5.83±6.6 years. Two patients received Cladribine + Rituximab while 03 patients received cladribine as their salvage therapy. Disease free survival (DFS) of 71.4% among the patients underwent splenectomy while 75.0% among the patients received Cladribine. DFS for combination therapy (included CHOP and CVP) was 66.7% while OS was calculated among patients who received cladribine, splenectomy and combination chemotherapy as 100%, 85.7%, 66.7% respectively. Conclusion: Cladribine has a significant efficacy and encouraging acute and long-term benefits when administered to patients with HCL. A single course of cladribine was able to induce CR in a vast majority of patients. At a median follow up of 4.6 years the OS was 100% with cladribine and 85% with splenectomy. Those who relapsed were successfully retreated with cladribine + Rituximab. [ABSTRACT FROM AUTHOR]

On flow cytometry, HCL cells express brightly mature B-lymphoid cell antigens as CD19, CD20, CD22, CD200, are typically positive for CD11c, CD103, CD123 and CD25, while are usually negative or dim for CD5, CD23, CD10, CD79b and CD27. Three cases (3/71, 4%) - despite expressing CD25, CD11c, and CD200 on all clonal cells (which were 15%, 22% and 37% of total leukocytes, respectively) - had CD103 expressed only on a fraction of leukaemic cells (40%, 27%, and 10.8%, corresponding to 5%, 6% and 4% of total leukocytes) (Figure 1A). Keywords: CD103; flow cytometry; hairy cell leukaemia EN CD103 flow cytometry hairy cell leukaemia e28 e31 4 07/18/22 20220715 NES 220715 Classical hairy cell leukaemia (HCLc) is an uncommon mature B-cell lymphoproliferative neoplasm (MBCLN) comprising about 2% of lymphoid leukaemias. [Extracted from the article]

Hairy cell leukaemia (HCL) is a rare B cell malignancy with an indolent course leading to pancytopaenia due to bone marrow infiltration. It has been proposed that HCL patients are at risk of developing a secondary malignancy, with a marked likelihood of the development of other hematologic malignancies including Hodgkin lymphoma and high-grade non-Hodgkin lymphomas. Here, we present the case of two patients who developed diffuse large B cell lymphoma after a long course of hairy cell leukaemia. In the case of the female patient, we report on the occurrence of a third malignant disease, which is very uncommon. With our case descriptions we contribute to the very small number of similar cases reported.

Nucleoside analogues are highly active in patients with hairy cell leukaemia (HCL); however, patients continue to relapse. This phase II study evaluated the efficacy and safety of cladribine followed by rituximab in patients with untreated HCL (N = 59), relapsed HCL (N = 14) and HCL variant (HCLv, N = 7). Cladribine 5·6 mg/m(2) was given intravenously (IV) daily for 5 d and was followed approximately 1 month later with rituximab 375 mg/m(2) IV weekly for 8 weeks. Complete response rate in patients with untreated HCL, relapsed HCL and HCLv was 100%, 100% and 86%, respectively. With a median follow up of 60 months, 5-year failure-free survival (FFS) in patients with untreated HCL, relapsed HCL and HCLv was 95%, 100% and 64%, respectively. Median duration of response to the cladribine followed by rituximab was significantly longer than the first-line cladribine single agent in patients who received this treatment as second-line treatment (72 months vs not reached, P = 0·004). Almost all patients (94%) achieved negative minimal residual disease (MRD) after the treatment. Positive MRD during the follow up did not necessarily result in clinically relevant relapse. Cladribine followed by rituximab is highly effective even in patients with relapsed disease and HCLv, and can achieve durable remission.

Summary: We investigated the current role of interferon‐alpha (IFNα) in hairy cell leukaemia (HCL) in a retrospective analysis of patients with HCL. A cohort of 74 patients with HCL was divided in to three groups: (A) patients aged >65 years with first‐line treatment; (B) patients with comorbidities with first‐line treatment; (C) patients who were purine analogues resistant. In total, 94% achieved a response, with a complete response rate of 24%. After a median (range) follow‐up of 60 (7–236) months, 55 patients (78%) are still responding. The 5‐year progression‐free survival was 95%, 68%, and 96% in groups A, B and C respectively. A proportion of patients were monitored through their B‐Raf proto‐oncogene, serine/threonine kinase (BRAF)‐V600E status. IFNα remains a possible option in select patients with HCL, where minimal residual disease negativity is achievable. [ABSTRACT FROM AUTHOR]

Experience with angiotensin-receptor neprilysin inhibitors (ARNI) in oncologic patients with heart failure (HF) is limited. We report a case of ARNI started as first-choice therapy in a patient with relapsing hairy cell leukaemia (HCL) and HF with depressed left ventricular ejection fraction (LVEF). A middle-aged male, previously treated with rituximab for HCL, was scheduled for cardiologic screening before starting a new antineoplastic therapy for cancer relapse. The patient had symptomatic HF with reduced LVEF and high NT-proBNP levels. In this patient, early ARNI treatment was well tolerated and produced a rapid and durable improvement of symptoms, LVEF and NT-proBNP levels. Consequently, the oncologic team could start an experimental treatment with obinutuzumab, with complete HCL remission. In conclusion, in this patient with HCL and HF, ARNI therapy was safe and effective, contributing to undelayed cancer treatment. [ABSTRACT FROM AUTHOR]

The recent serious challenges in patient management resulting from the COVID-19 pandemic have emphasised the need to optimise therapy for immunosuppressed patients. HCL- SB V, sb a provisional entity in the latest WHO classification, accounts for 10-20% of HCL patients and 0-5% of B-cell chronic lymphoid malignancies, and corresponds to approximately 60-75 new HCL- SB V sb patients each year in the United States. Keywords: guidelines; diagnosis; hairy cell leukaemia EN guidelines diagnosis hairy cell leukaemia 11 14 4 04/01/21 20210401 NES 210401 A European viewpoint (Xavier Troussard) The British Society for Haematology presents very useful and instructive guidelines for the diagnosis and management of hairy cell leukaemia (HCL) and hairy cell variant (HCL- SB V sb ).1 HCL-like disorders are well-defined entities although overlaps exist between HCL, variant forms of HCL (HCL- SB V sb ), splenic diffuse red pulp lymphoma (SDRPL) and splenic marginal zone lymphoma (SMZL). In newly diagnosed patients, PNAs remain the treatment of choice, but relapses occur in some patients. [Extracted from the article]

Keywords: cell population data; DxH 800; hairy cell leukaemia; machine learning; monocytopenia EN cell population data DxH 800 hairy cell leukaemia machine learning monocytopenia e111 e115 5 02/06/21 20210301 NES 210301 To the Editor, Hairy cell leukaemia (HCL) was firstly described in 1923 [[1]] presenting pancytopenia and circulating "monocytic cells", whose origin in relationship to monocytes or B lymphocytes was controversial until its lymphoid origin was established based on cytochemical studies [[2]]. As an example, mean volume of hairy cells (166.0) (monocyte HCL cluster) is only a 4% smaller than NC monocytes (174.0). Previous analysis of HCL cases using Sysmex instrumentation also found that CPD from hairy cells within the monocyte cluster were different than the expected for normal monocytes [[6]]. [Extracted from the article]

Keywords: Differential diagnosis; BRAF V600E mutation; hairy Cell Leukaemia; Hairy cell variant; therapy EN Differential diagnosis BRAF V600E mutation hairy Cell Leukaemia Hairy cell variant therapy 730 737 8 12/07/20 20201201 NES 201201 Methodology This guideline was compiled according to the BSH process (https://b-s-h.org.uk/guidelines). Cytoplasm is abundant and pale blue, with circumferential "hairy" projections.9 Discrete cytoplasmic vacuoles or rod-shaped inclusions (ribosome lamellar complexes) may be seen.3 Bone marrow aspirate and trephine biopsy Bone marrow aspiration is frequently unsuccessful, reflecting fibrosis induced by the hairy cell infiltrate. In a single-centre follow-up study of 242 patients,41 18 patients treated with cladribine (12 as first-line and six as second-line therapy) who remained in PR after bone marrow reassessment received a repeat treatment with cladribine 4-7 months after initial treatment, leading to CR in 14 patients, of whom all but one remained in CR at a median follow-up of 6 years. Treatment of relapsed or refractory classical HCL Despite the durable remissions achieved with front-line therapy, approximately 50% of patients will relapse. [Extracted from the article]

Summary: For a disease initially described in 1958 as a leukaemic reticulo‐endotheliosis associated with poor outcomes, we have come a long way in our understanding of Hairy cell leukaemia. The vast majority of patients diagnosed with this rare, often diagnostically challenging, leukaemia can now expect a lifespan that is similar to the general population. This article covers some of the highlights from the last 6 decades that have led to our current understanding of this fascinating leukaemia ‐ from elucidation of its B‐cell origin to discovery of the almost universal occurrence of the BRAF V600E mutation; from the initial successes reported with splenectomy to the more recent development of targeted therapies such as Vemurafenib and Moxetumomab Pasudotox. It also pays tribute to some of the outstanding research in this field focusing particularly on the significant contributions made by the clinical and scientific community in the UK. [ABSTRACT FROM AUTHOR]

Abstract We present the case of a patient diagnosed with hairy cell leukaemia (HCL) who subsequently developed biopsy confirmed bone lesions and underwent multiple lines of therapy. The reported incidence of bone lesions in HCL is 3%, and bony involvement can be associated with high tumour burden and aggressive disease. The commonly lytic bone lesions in HCL are difficult to accurately assess for response. Whole body diffusion weighted imaging (WB‐DWI) has been used clinically in multiple myeloma; we postulate clinical utility in HCL, where hypercellularity also applies. In our case, WB‐DWI appears to discriminate sites of active disease from bone response. We present the salient radiological and pathological images. To our knowledge, this is the first description of WB‐DWI in HCL; we support research of WB‐DWI in the staging, prognostication and response assessment of HCL.

Purpose of Review: To summarise diagnostic clinical/laboratory findings and highlight differences between classical hairy cell leukaemia (HCLc) and hairy cell leukaemia variant (HCLv). Discussion of prognosis and current treatment indications including novel therapies, linked to understanding of the underlying molecular pathogenesis. Recent Findings: Improved understanding of the underlying pathogenesis of HCLc, particularly the causative mutation BRAF V600E, leading to constitutive activation of the MEK/ERK signalling pathway and increased cell proliferation. Summary: HCLc is caused by BRAF V600E mutation in most cases. Purine nucleoside analogue (PNA) therapy is the mainstay of treatment, with the addition of rituximab, improving response and minimal residual disease (MRD) clearance. Despite excellent responses to PNAs, many patients will eventually relapse, requiring further therapy. Rarely, patients are refractory to PNA therapy. In relapsed/refractory patients, novel targeted therapies include BRAF inhibitors (BRAFi), anti-CD22 immunoconjugate moxetumomab and Bruton tyrosine kinase inhibitors (BTKi). HCLv has a worse prognosis with median overall survival (OS), only 7–9 years, despite the combination of PNA/rituximab improving front-line response. Moxetumomab or ibrutinib may be a viable treatment but lacks substantial evidence. [ABSTRACT FROM AUTHOR]

Introduction The analysis of the periodic table of elements by Jan Scholten opened the way for a new kind of classification and repertorisation of homeopathic remedies. Thereby, group analysis (resorting to series and stages)makes precise prescriptions possible. This approach appears to yield striking results, even in severe cases. Whereas Hahnemann stressed the emotional state ('Gemüthssymptome', Organon § 210) when choosing a remedy, Scholten 200 years later investigated the mental picture that represents a life conflict or even a life theme that maymaintain the disease process. The person's environment, emotional traumas or a conflict drives him or her to suppress and dissect painful emotions. Such compensations can become subconscious and so strong that they can no longer be controlled; they then influence the patient with a highly destructive energy. Methods We present five case reports, each dealing with an unusual clinical course of severe cancer associated with homeopathic treatment using the Scholten method. Results By presenting these cases, we consider how the constitution (lifelong signs and symptoms of the patient) and the mental state are interwoven and, as a complex mechanism, might provoke disease. Conclusion The appropriate homeopathic remedy, reflecting the Scholten approach, seemed to have beneficial impact on the disease process of the five individuals presented. [ABSTRACT FROM AUTHOR]

Background: B-Cell Lymphoproliferative Disorders (B-LPDs) are a group of heterogenous disorders characterised by the accumulation of B-cells in peripheral blood, bone marrow, lymph nodes and spleen. They have a variable disease course and outcome and many share similar features making differential diagnosis challenging. Therefore, accurate diagnosis is fundamental in particular for determining treatment options. Immunophenotyping by flow cytometry plays a crucial role in the diagnosis of B-LPDs. However, overlapping immunophenotyping patterns exist and the use of novel monoclonal antibodies has become increasingly important in immunophenotyping analysis. More recently differential expression of CD200 has been reported in various B-LPDs and that CD200 may improve the differentiation between chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL). In this study CD200 expression is evaluated in different B-LPDs. Methods: A total of 100 samples were collected and analysed by immunophenotyping flow cytometry over a period of 1 year (2017-2018), by a panel of monoclonal antibodies including CD200. The percentage of CD200 and its expression intensity was evaluated and compared between different groups of B-LPDs. Results: All of the 50 cases of CLL expressed CD200 with moderate to bright intensity, 6 MCL cases lacked the expression of CD200. Furthermore, all 5 cases of hairy cell leukaemia (HCL) expressed CD200. Out of all B-LPDs evaluated, CD200 expression in HCL cases was noted to be the brightest. The other 39 cases were not found to be B-LPDs. Conclusion: CD200 has an important role in differentiating CLL from MCL, HCL has a consistent bright expression of CD200. By adding CD200 to the combinations of markers in routine testing panel, Immunophenotyping by flow cytometry can be an effective tool in the diagnosis of B-LPDs especially in cases with atypical immunophenotyping pattern. Our result support that CD200 can be added to routine testing panel as it is useful in differentiating them., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Al-Zubaidi and Hughes.)

Faisal Basheer, David M Bloxham, Mike A Scott, George A FollowsDepartment of Haematology, Addenbrookes Hospital, University of Cambridge, Cambridge, UKAbstract: Hairy cell leukemia (HCL) is an indolent low-grade B-cell lymphoproliferative disorder that is reasonably sensitive to standard first-line purine analog therapy. However, in many cases, repeat relapses occur, requiring multiple courses of purine analog therapy, promoting eventual drug resistance. This, coupled with the concerning side effects of repeated purine analog exposure, has prompted the search for alternative targets and therapies that may provide deeper remissions. Novel strategies employing immune-mediated targeting via monoclonal antibody therapies and recombinant immunotoxins appear promising in HCL and are currently under investigation. More recently, the concept of targeted kinase inhibition using small-molecule inhibitors in HCL has emerged as another potentially viable option. As a deeper understanding of the aberrant molecular pathways contributing to the pathogenesis of HCL develops, the landscape of management for HCL, particularly in the relapse setting, may change significantly in the future as a result of these promising immunotargets and therapies.Keywords: hairy cell leukemia, immunotargets, therapies

Patients with hairy cell leukaemia ( HCL) have highly favourable outcomes after purine analogue therapy. However, most patients subsequently relapse and require re-treatment. A minority of patients develop purine analogue-refractory disease. Targeted therapies have improved outcomes for such patients. Recently, the BRAF V600E mutation was identified in most patients with classical HCL, resulting in constitutive mitogen-activated protein kinase pathway activation; impressive responses are achieved in heavily pre-treated patients with BRAF inhibition. The CD22-targeted immunoconjugate moxetumomab pasudotox and BTK inhibitor ibrutinib also achieve responses in relapsed and refractory patients. HCL variant and the IGHV4-34 molecular variant of HCL lack BRAF mutation and have inferior outcomes with standard purine analogue therapy. The addition of rituximab to purine analogues achieves very high rates of minimal residual disease-negative complete remission and improves outcomes for patients with HCL variant. Given the rarity of HCL, optimal integration of novel therapies into treatment algorithms will require well-designed, collaborative studies. [ABSTRACT FROM AUTHOR]

Splenectomy is undertaken for diagnosis, and in later stages of management, of patients with a diverse range of lymphomas. High quality histological sections, requiring careful attention to tissue fixation, are needed to assess these lesions adequately. Increasing use of fine-needle aspiration, needle core biopsy and laparoscopic surgery add further diagnostic challenges. In addition to involvement by dissemination of lymphomas based primarily in lymph nodes, bone marrow or other tissues, spleen is the predominant site of disease in several distinctive types of lymphoma. In particular, splenic marginal zone B-cell lymphoma, hairy cell leukaemia and T-cell and macrophage-rich large B-cell lymphoma are recognized as clinicopathologically distinct entities. Research into the cellular and molecular origins of these lymphomas is ongoing; variants and new entities are becoming evident. Histological and immunohistochemical features of the spleen following treatment for lymphoma are complex and may cause diagnostic confusion. Inflammatory and reactive processes in the spleen can also provide clinical, radiological or pathological mimicry of lymphomatous involvement. [ABSTRACT FROM AUTHOR]

Repeated therapy of hairy cell leukaemia ( HCL) with treatments that have potential long-term toxicities has raised concerns regarding increased risk for younger patients. We compared clinical outcomes and disease complications in 63 patients with HCL aged ≤40 years at diagnosis with 268 patients >40 years treated at Memorial Sloan Kettering Cancer Center. The rate of complete remission following initial therapy was 87% and 83% ( P = 0·71) and estimated 10-year overall survival was 100% and 82% ( P = 0·25) in younger and older patients, respectively. Younger patients required therapy earlier and had a significantly shorter time between first and second therapy (median: 63 months vs. 145 months) ( P = 0·008). Younger patients required significantly more lines of therapy during follow-up. The 10-year cumulative incidence of secondary malignancies in young and old patients was 0·205 and 0·287, respectively ( P = 0·22). The incidence of secondary cancers in patients aged >40 years at diagnosis increased with the number of treatments for HCL ( P = 0·018). These results highlight that young patients with HCL have shorter responses to treatment and require more lines of therapy to maintain disease control, while attaining similar long-term survival. This has implications in the design of future clinical trials given our findings that secondary malignancies increase with more chemotherapy exposure. [ABSTRACT FROM AUTHOR]

Hairy cell leukaemia (HCL) is a rare, clonal, chronic lymphoproliferative disorder commonly seen in males in the middle years of life. Pancytopaenia with moderate to massive splenomegaly is the most common clinical presentation. Diagnosis is made on detecting the lymphocytes with abundant cytoplasm which spread into hair-like processes on peripheral blood and bone marrow smears, thus giving the name, “hairy cell leukaemia”. The bone marrow aspirate is frequently a dry tap. The trephine biopsy has the characteristic features of a honey comb appearance and flow cytometry is typically CD103, CD25, FMC7, CD11c, gamma or kappa light chain positive with the classic B lymphocyte markers CD19, CD20, CD79a. Purine analogues followed by granulocyte-colony stimulating factor (G-CSF) to manage the febrile neutropenia is currently the treatment of choice. A 10 year disease free survival is recorded with these management strategies. Experimental use of anti CD20 and CD22 has also shown promising results in the treatment of this disease. We report four cases of HCL diagnosed in a span of two years at the Royal Hospital, Muscat, Oman.