The hypomethylating agents azacytidine and decitabine are unaffordable for many patients with MDS. The combination of the DNA methyltransferase inhibitor hydralazine and the histone deacetylase inhibitor valproate has shown preliminary efficacy in MDS. The aim of this study is to evaluate the clinical efficacy and safety of hydralazine/valproate in a case series of MDS patients treated in a compassionate manner. Hydralazine was dosed according to the acetylation genotype of patients (slow acetylators 83 mg daily; fast acetylators 182 mg daily), and valproate was dosed at 30 mg/kg/day. Both drugs were given daily until disease progression. Response and toxicity were evaluated with the International Working Group criteria and CTCAE, version 4, respectively. Survival parameters were estimated with the Kaplan-Meier method. From 2009 to 2012, 14 patients were treated. The median age ± SD was 55.2 ± 19.52 (range 23-87) years. According to the IPSS, cases were graded as intermediate-1 (n = 8/14; 57.2%) or intermediate-2 (n = 6/14; 42.8%). Responses were as follows: five (35.7%) complete response, one (7.1%) partial response, and two (14.28%) became transfusion independent. The mean duration of response ± SD was 60 ± 35.28 months (range 5-94). Three patients progressed to AML. At a median follow-up of 57 months (range 1-106), the median OS was 27 months. At that point, five patients remained on the treatment, one with partial response and four with complete response. The median OS was not reached in the eight patients who saw a clinical benefit from the treatment, in comparison to an OS of 7 months in the six patients who had no treatment. The combination of hydralazine and valproate is safe and effective in MDS, and its further testing is highly desirable.
Extramedullary myeloma (EMM) is defined by the presence of plasma cells outside the bone marrow in a patient with multiple myeloma (MM) (Touzeau & Moreau, 2016). EMM is by itself a rare entity with cases involving central nervous system (CNS) being rarer, it has an estimated incidence of 1-1.8% of all MM cases (Majd et al, 2015). Its presentation in comparison to classical MM has an adverse prognosis including a shorter progression free survival (PFS) (Gozzetti et al, 2015) and overall survival (OS) with a mean life expectancy of 1.5-6 months (Majd et al, 2015). Currently there are not international treatment guidelines for this disease. The aim of this report is to illustrate our experience at a single institution in Mexico, presenting five cases of CNS-EMM treated with proteasome inhibitor (carfilzomib) in combination with thalidomide, dexamethasone plus radiotherapy. The patient's characteristics and the treatment regimen are shown in table 1 and 2. Within three months, following the criteria to the international multiple myeloma working group (IMMWG), all five patients accomplished a positive response (one partial response [PR] four very good partial responses [VGPR]), at sixth months two patients improved their response from previously PR to a VGPR and from VGPR to complete response (CR), one sustained its VGPR and after this period of time two patients had progressive disease (PD) and died due to infectious complications. After the tenth month a third patient also died of infectious complications. By the end of this report two patients still alive, one is being evaluated for autologous stem cell transplantation (ASCT) and the other one wasn't eligible according to European Group for Blood and Marrow Transplantation (EBMT) risk score and will continue treatment without ASCT. Previously reported cases in the literature with old chemotherapy regimens shown to have median survival of 1.5 months (Petersen et al 1999), nowadays the recommended therapy is based on triplet induction therapy followed by high-dose melphalan/ASCT, a triplet consolidation therapy and maintenance treatment with lenalidomide (Touzeau & Moreau, 2016); so far there is no evidence of proteasome inhibitors penetrating the blood brain barrier (Nooka et al, 2013) and this might be the reason why the literature strongly recommends the use of lenalidomide as this one does penetrate into the CSF after oral administration (Muscal et al, 2012), we did not use lenalidomide due to the high monetary cost of the treatment but instead we use thalidomide in combination with carfilzomib and dexamethasone with improved OS in three of our five patients (VGPR + CR). Despite the small number of patients presented in this report and the lack of cytogenetics or FISH information, we think this might be a good therapeutic approached in patients with CNS-EMM, especially in those scenarios with not accessible resources or absence of clinical trials. Further studies evaluating the addition of monoclonal antibodies (daratumumab, elotuzumab) need to be done in order to improve the OS and PFS in this group of patients. Disclosures No relevant conflicts of interest to declare.
This article addresses lettering and signpainting as an important element of visual culture. Following the model of scholarly studies grounded in typographic and architectural history, the article focuses on a set of Amsterdam shop signs painted in a style identified as Krulleletters ("curly letters"), typically associated with the city's bruin cafes ("brown cafes"). The analysis presents this elegant writing as related to a local tradition, and positions it within its social and cultural context in order to explain its visual relevance. Broadly based on Dutch Mannerist calligraphy of the seventeenth century, the Krulleletters appeared for the first time in the early 1950s, probably the creation of lettering artist J.W.J. Visser. The style was soon A typographer, author and translator, Alessandro Colizzi teaches typography and graphic design history at the Université du Québec à Montréal. His interests include typographic history, type design and lettering and information design. He is completing a Ph.D.
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