No abstract

A 32-year-old man presented with a 7-month history of progressive painless, nonpruritic skin and soft tissue lesion on his left leg. He had no systemic or B symptoms. The physical examination showed a violaceus lesion soft in consistency on the left leg (Figures 1 and 2).MRI showed an oval lesion with hypointensity signal in T1 and hyperintensity in T2, with homogeneous enhance postcontrast study, and diffusion-restriction. There was no palpable lymphadenopathy or hepatosplenomegaly. The skin lesion was biopsied and showed atypical cells (Figure 3). Immunohistochemical analysis showed cells that were positive for CD4, CD56, CD123, SPIB, TdT, and negative for MNDA (Figure 4), which supported the diagnosis of blastic plasmacytoid dendritic-cell neoplasm (BPDCN). Complete blood count was unremarkable and peripheral blood smear did not show immature cells. Bone marrow aspirate/biopsy did not reveal the presence of neoplastic plasmacytoid dendritic cells. An 18 (F)-FDG-PET- F I G U R E 1 Extensive violaceus lesion on the internal side of the left legThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Despite the Janus kinase/signal transducers and activators of transcription (JAK/ STAT) pathway being frequently altered in T-ALL/LBL, no specific therapy has been approved for T-ALL/LBL patients with constitutive signalling by JAK/STAT, so there is an urgent need to identify pathway members that may be potential therapeutic targets. In the present study, we searched for JAK/STAT pathway members potentially modulated through aberrant methylation and identified SOCS3 hypermethylation as a recurrent event in T-ALL/LBL. Additionally, we explored the implications of SOCS3 deregulation in T-ALL/LBL and demonstrated that SOCS3 counteracts the constitutive activation of the JAK/STAT pathway through different molecular mechanisms. Therefore, SOCS3 emerges as a potential therapeutic target in T-ALL/LBL.

Waldenström macroglobulinemia (WM) is a slowly progressive hematologic malignancy that usually responds rapidly to treatment. Being a lymphoplasmacytoid neoplasm, it is associated with a monoclonal IgM component, which may be associated with multiple manifestations and symptoms. We report the case of a 77-year-old woman diagnosed with WM following the development of severe and sudden pancytopenia associated with a cold agglutinin syndrome. In order to treat the WM and the underlying hemolysis, treatment with rituximab, corticosteroids and cyclophosphamide was started. Despite the improvement in hemolysis parameters, pancytopenia persisted, and we started a second line with ibrutinib. During treatment the patient developed an uncommon invasive fungal infection (IFI) with bone marrow granulomatosis and myelofibrosis. This case shows an unusual clinical course with a poor hematopoietic response to treatment and a large number of intercurrent complications.

Background: There is a high unmet medical need for therapeutic options for patients suffering from myeloproliferative neoplasms (MPN), who have failed or are not eligible to available treatment options. Ropeginterferon-alfa-2b (P1101) is a novel, third generation pegylated interferon-alfa, recently approved by EMA to treat polycythemia vera (PV). Ropeginterferon-alfa-2b is also in the late stages of development in several countries for treatment of PV and other MPNs. Aims: Ropeginterferon-alfa-2b is a new and attractive treatment option for patients suffering from MPN who have exhausted all therapeutic options and require treatment. The Compassionate Use Program (CUP) was approved and initiated in Taiwan with the purpose of granting access to P1101 to patients with MPN disease with no therapeutic options who are not eligible to enroll in existing clinical trials for their disease. Methods: Patients were identified that had the potential to benefited from P1101 therapy and were eligible according to the protocol. Patients were treated at a starting dose of 250 ug with subsequent dose escalation every 2 weeks over a 6-week period to 350 ug, 450 ug and 500 ug. Dose adjustments were permitted based on tolerability and efficacy. Results: The CUP currently contains 15 patients from two academic hospitals: 9 with PV, 2 with post-PV myelofibrosis (MF), two with pre-fibrotic MF, one with primary MF, and one essential thrombocythemia patient. The driver mutation was JAK2 in 13 patients, CALR in one, and another one was triple negative. Pre-treatment with hydroxyurea and/or anagrelide was reported in 13 patients. P1101 was given for > 12 weeks to 14 patients (range 4 -64 weeks). The highest administered dose of P1101 was: 500 ug in 11 patients (time to highest dose -6 weeks in 9 patients, 10 weeks -in 1 and 20 weeks in another patient); 250 ug, 350 ug and 450 ug in three other patients. The need to decrease or temporarily interrupt P1101 therapy occurred in 4 patients, all due to transaminase(s) elevation. Notably, these events did not require permanent discontinuation of therapy and could be alleviated by appropriate dose modifications. The majority of observed adverse events were of grade 1 and included fatigue, arthralgia, myalgia, chills and dizziness. Grade 2 events included elevation of transaminases (in 3 patients), dizziness, pruritus and lower limbs pain (in 1 patient each). One patient developed elevation of transaminases of grade 3. Normalization of blood parameters within complete hematologic response range was observed in 3 PV and 2 post-PV MF patients. Two PV patients fulfilled the partial response criteria. In other patients, decrease of platelet count (even in previously treatment-resistant thrombocytosis) and symptomatic improvement were also observed. No major cardiovascular events were recorded. One pre-PMF patient transformed into MF (grade 5). No patients progressed to acute myelogenous leukemia (AML) during the observation. Summary/Conclusion: In this cohort of MPN patients, not amenable for establishe...