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Keywords: eosinophilia; chronic lymphocytic leukaemia; prognostic factors EN eosinophilia chronic lymphocytic leukaemia prognostic factors e81 e84 4 02/02/21 20210201 NES 210201 Blood eosinophilia may be an early sign of a haematological malignancy.1,2 Temporary eosinophilia occurs as an adverse event in chronic lymphocytic leukaemia (CLL) during fludarabine treatment,3 whereas persistent eosinophilia in CLL with a I TP53 i mutation may be a prognostic factor for variant Richter transformation.4 A dose-dependent association between eosinophil counts and the risk of CLL has been reported.5 Several prognostic factors have been established and the clinical staging systems6 have been superseded in the era of targeted treatment by molecular markers,7 but the predictive properties of eosinophilia at CLL diagnosis have not previously been analysed. Patients with a blood eosinophil count outside the normal range (<0-10 × 10 SP 9 sp /l or >0-50 × 10 SP 9 sp /l) had a significantly shorter TFS compared with patients with an eosinophil count within the normal range when adjusting for CLL-IPI variables and sex. [Extracted from the article]

Background: Chronic myeloid leukemia (CML) is rarely diagnosed in pregnant women.Case Report: We report a case of a pregnant woman who presented with a leukocyte count of 250 × 109 cells/L at gestational age (GA) 26 weeks and was diagnosed with CML in the chronic phase. Because the patient deliberately opted out of interferon α and tyrosine kinase inhibitor treatment, the main goal was to reduce the leukocyte count to postpone delivery beyond the number of weeks considered severely premature and avoid thromboembolic complications while continuously evaluating the clinical safety of the mother and fetus. Hence therapeutic leukapheresis was initiated, and we report the first application of an apheresis approach for this procedure using the Spectra Optia instrument without sedimentation agents. Leukapheresis was conducted 2 to 4 times per week for 9 weeks.Results: During treatment the leukocyte count decreased remarkably, and the patient developed lymphopenia together with a paradoxical increase in her blood platelet count. Premature labor was induced at GA 35 weeks, and a healthy boy was delivered. Thereafter, the patient initiated imatinib treatment and was in major molecular and complete cytogenetic remission after 1 year. Despite the remarkable reduction of the leukocyte count, we observed a pronounced increase in expression of BCR-ABL1 transcripts, implying the need for close monitoring of patients with CML during pregnancy.Conclusions: We report a pregnant woman who was diagnosed with CML and treated solely with apheresis procedures using the Spectra Optia instrument for 9 weeks, ensuring the safe delivery of her child. [ABSTRACT FROM AUTHOR]

Abstract: Interferon‐α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation‐mediated toxicity, leading to treatment discontinuation in 10‐30% of patients. Ruxolitinib, a potent anti‐inflammatory agent, has demonstrated benefit in myelofibrosis (MF) and polycythemia vera (PV) patients. Combination therapy (CT) with these two agents may be more efficacious than monotherapy with either, potentially improving tolerability of interferon‐α2 as well. We report the preliminary results from a phase II study of CT with pegylated interferon‐α2 and ruxolitinib in 50 MPN patients (PV, n = 32; low‐/intermediate‐1‐risk MF, n = 18), the majority (n = 47) being resistant and/or intolerant to interferon‐α2 monotherapy. Objectives included remission (2013 revised criteria encompassing histologic, hematologic, and clinical responses), complete hematologic response (CHR), molecular response, and toxicity. Follow‐up was 12 months. Partial remission (PR) and sustained CHR were achieved in 9% and 44% of PV patients, respectively. In MF patients, complete or partial remission was achieved in 39%, and sustained CHR in 58%. The median JAK2V617F allele burden declined significantly in both groups. Hematologic toxicity was the most common adverse event and was managed by dose reduction. Thirty‐seven serious adverse events were recorded in 23 patients; the discontinuation rate was 20%. We conclude that CT with interferon‐α2 and ruxolitinib is efficacious in patients with low‐/intermediate‐1‐risk MF and, to a lesser extent, in patients with PV. These preliminary results encourage phase III studies as well as a study with CT in newly diagnosed MPN patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Patients with Philadelphia chromosome‐negative myeloproliferative neoplasms (MPNs) have higher risks of developing thromboembolisms compared to the general population. International guidelines on the management of MPNs therefore include recommendations concerning thromboembolism prophylaxis. In clinical practice, strict adherence to guidelines may be challenging and dependent on factors such as physician experience, outpatient clinic setting, and access to therapy; however, no data exist on physician adherence or patient compliance to thromboembolism prophylaxis in MPNs. Objectives: The Nordic Myeloproliferative Neoplasm Study Group (NMPN) performed a survey among Nordic hematology specialists with the aim of documenting the implementation of international recommendations in a region of Northern Europe with similar healthcare systems. Results: The study showed that Nordic specialists managed their patients in accordance with international guidelines concerning medical intervention, but to a lesser degree regarding the management of additional cardiovascular risk factors. The survey also drew attention to the common clinical dilemma of combining antiaggregatory agents with vitamin K antagonists (VKA), or novel oral anticoagulants (NOAC), as well as phlebotomy limits in female polycythemia vera patients. Conclusions: The results of this study highlight the importance of considering all risk factors for thrombosis and an optimal collaboration with the primary healthcare sector. [ABSTRACT FROM AUTHOR]

Purpose To study the circulation in the retinal vessels in patients with blood dyscrasia due to myeloproliferative neoplasms using non-invasive retinal imaging. Methods Prospective consecutive case series of seven treatment-naïve patients with chronic myeloid leukaemia ( n = 2), polycythemia vera ( n = 4), essential thrombocytosis ( n = 1) examined before and after cytoreductive treatment. We investigated retinal circulation with motion-contrast imaging, retinal oximetry and spectral-domain optical coherence tomography. Results Retinal venous blood velocity increased by 8.14% ( CI95 3.67% to 12.6%, p = 0.004) and retinal arterial oxygen saturation increased by 7.23% ( CI95 2.9% to 11.6%, p = 0.010) at follow-up (mean 12 weeks, range 5-14 weeks) where complete haematological remission had been achieved by cytoreductive treatment. Abnormal optical coherence tomography reflectivity patterns were present at baseline in patients with chronic myeloid leukaemia and were replaced by normal patterns at follow-up. Retinopathy, in the form of cotton-wool spots and retinal haemorrhages, was found at presentation in the two patients with chronic myeloid leukaemia and in one patient with polycythemia vera. The retinopathy had resolved at follow-up in all patients. Conclusion With non-invasive retinal imaging, we were able to demonstrate increased retinal venous blood velocity, increased retinal arterial blood oxygenation and normalization of intravascular reflectivity patterns after successful treatment of myeloproliferative neoplasms. Larger prospective studies are needed to assess the prognostic value of these non-invasive imaging methods in predicting circulatory complications in myeloproliferative neoplasms. [ABSTRACT FROM AUTHOR]

Madelung A, Bzorek M, Bondo H, Zetterberg E, Bjerrum O W, Hasselbalch H C, Scheding S & Ralfkiaer E (2012) Histopathology 60, 554-560 A novel immunohistochemical sequential multi-labelling and erasing technique enables epitope characterization of bone marrow pericytes in primary myelofibrosis Aim: In Philadelphia (Ph)-negative chronic myeloproliferative neoplasms, increased microvascular density, bizarre vessel architecture and increased number of pericytes are among the distinct histopathological features. The aim of this study was to characterize bone marrow pericytes in primary myelofibrosis (PMF) using a novel multi-labelling immunohistochemical technique. Methods and results: Bone marrow biopsies from a normal donor ( n = 1) and patients with PMF ( n = 3) were subjected to an immunohistochemical sequential multi-labelling and erasing technique (SE-technique). Antigens of interest in the first and/or second layer were detected with an immunoperoxidase system and visualized with aminoethylcarbazole. After imaging, erasing and blocking of immunoreagents, the slides were stained with a traditional double immunolabelling procedure. In addition, we applied a Photoshop® colour palette, creating a single composite image of the sequential staining procedures. We successfully applied four layers of antibodies on one slide using CD146, smooth muscle actin, CD34, CD271 and Ki67 in different combinations. The SE-technique significantly improves morphological and phenotypical studies in bone marrow specimens. Conclusions: To our knowledge, the SE-technique is the first to multi-label antigens, identifying vessel and pericyte architecture in bone marrow by light microscopy. This technique may unravel novel aspects of the composition of the microvessel structures in patients with PMF and related neoplasms. [ABSTRACT FROM AUTHOR]

Gene expression profiling studies have unraveled deregulation of several genes that might be of pathogenetic importance for the development and phenotype of the Philadelphia-negative chronic myeloproliferative neoplasms. In the context of interferon-alpha2 as a promising therapeutic agent, we focused upon the transcriptional profiling of interferon-associated genes in patients with essential thrombocythemia (ET) ( n = 19), polycythemia vera (PV) ( n = 41), and primary myelofibrosis (PMF) ( n = 9). Using whole-blood transcriptional profiling and accordingly obtaining an integrated signature of genes expressed in several immune cells (granulocytes, monocytes, B cells, T cells, platelets), we have identified a number of interferon-associated genes to be significantly deregulated but with a highly significant deregulation of interferon-inducible gene 27 (IFI27) (ET, PV, and PMF, fold change 8, 16, and 30, respectively). The striking deregulation of IFI genes may reflect a hyperstimulated but insufficient immune system being most enhanced in patients with advanced myelofibrosis, in whom the IFI27 gene displayed an exceedingly high expression. The interferon signature may reflect primary myelofibrosis as the burn-out phase of chronic inflammation which ultimately elicits clonal evolution and expansion owing to an exaggerated but incompetent antitumor immune response. Finally, IFI27 may be a novel biomarker of disease activity and tumor burden in patients with CMPNs. [ABSTRACT FROM AUTHOR]