Joanna Drozd-Sokołowska

Update on the Incidence of Metamizole Sodium-Induced Blood Dyscrasias in Poland

Metamizole sodium (metamizole) is a popular non-opioid analgesic and a common non-prescription product in Poland. Controversy exists regarding the level of risk of agranulocytosis or aplastic anaemia associated with its use. Two previous pharmacovigilance studies conducted in Poland found the risk was low. Twenty-four of the 25 haematology centres that provide specialist care for the 30 million adults in Poland participated in this prospective 12-month study. Twenty-one cases of agranulocytosis, 48 of aplastic anaemia, 15 of neutropenia and 11 of pancytopenia were reported. Of these cases, three (two agranulocytosis; one aplastic anaemia) were judged as being possibly related to metamizole. Crude estimates of the rate of agranulocytosis and aplastic anaemia associated with metamizole were 0.16 and 0.08 cases/million person-days of use, respectively. Ongoing national safety surveillance in Poland shows that, despite the possibility of drug-induced blood dyscrasias with metamizole, the risk is very low.

Pre-existing arterial hypertension as a risk factor for early left ventricular systolic dysfunction following (R)-CHOP chemotherapy in patients with lymphoma

Experimental studies in animals suggest that arterial hypertension may be a specific risk factor predisposing to anthracycline cardiotoxicity. The aim was determination of the effect of pre-existing arterial hypertension on the development of early left ventricular systolic dysfunction (LVSD) directly after rituximab, cyclophosphamide, doxorubicin, vincristin, prednisone ([R]-CHOP) chemotherapy in patients with lymphomas.The study included 208 patients with non-Hodgkins lymphoma receiving conventional doxorubicin. LVSD was defined as a decrease of left ventricular ejection fraction below 50% and at least by 10 percentage points from baseline value. Patients with pre-existing hypertension more frequently developed new LVSD (19.7% vs. 6.6%; P = .004), pitting edema of the ankles (23.9% vs. 9.5%; P = .005), and nycturia (21.1% vs. 7.3%; P = .004) compared with patients without hypertension. As a consequence, the hypertension subgroup suffered from more delays of subsequent chemotherapy cycles (26.8% vs. 14.6%; P = .03), more reductions of doxorubicin doses (18.3% vs. 8.8%; P = .05), and premature discontinuations of chemotherapy (16.9% vs. 7.3%; P = .03). On logistic regression analyses, hypertension was one of the most important risk factors for developing new LVSD after (R)-CHOP chemotherapy.Arterial hypertension confers a significant risk of early LVSD in lymphoma patients treated with (R)-CHOP chemotherapy, interfering with its recommended schedule of administration.

Efficacy and toxicity of compassionate ibrutinib use in relapsed/refractory chronic lymphocytic leukemia in Poland: analysis of the Polish Adult Leukemia Group (PALG)

El_ zbieta Iskierka-Ja_ zd_ zewska, Marek Hus, Krzysztof Giannopoulos, El_ zbieta Mądro, Jadwiga Hołojda, Magdalena Piotrowska, Jan M. Zaucha, Weronika Piszczek, Agnieszka Szeremet, Małgorzata Wojciechowska, Paweł Steckiewicz, Wanda Knopi nska-Posłuszny, Marek Osowiecki, Joanna Drozd-Sokołowska, Beata Kumiega, Sławomira Kyrcz-Krzemie n, Janusz Hałka, Marek Dudzi nski, Paulina Wieszczy, Tadeusz Robak, Krzysztof Warzocha and Krzysztof Jamroziak Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland; Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; Experimental Hematooncology Department, Medical University of Lublin & Hematology Department, St. Johns Cancer Center, Lublin, Poland; Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland; Department of Hematology, Specialist District Hospital, Legnica, Poland; Department of Hematology, Cracow University Hospital, Cracow, Poland; Department of Oncological Propaedeutics, Medical University of Gdansk, Gdansk, Poland & Gdynia Oncology Center, Gdynia, Poland; Department of Hematology, Copernicus Hospital, Torun, Poland; Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland; Department of Hematology, Specialist District Hospital, Olsztyn, Poland; Department of Hematology, Holycross Cancer Center, Kielce, Poland; Department of Hematology, Independent Public Health Care of the Ministry of the Internal Affairs with the Oncology Centre, Olsztyn, Poland; Department of Lymphoid Malignancies, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland; Department of Haematooncology, Oncology Centre of the Podkarpackie Province, Brzozow, Poland; Department of Hematology and Bone Marrow Transplantation, Silesian Medical University Hospital SPSKM, Katowice, Poland; Department of Hematology, Military Institute of Medicine, Warsaw, Poland; Department of Hematology, Specialist District Hospital, Rzeszow, Poland; Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland

Demographic, Hematologic, and Clinical Features of Myelodysplastic Syndrome Patients: Results from the First Polish Myelodysplastic Syndrome Registry.

Epidemiological studies on myelodysplastic syndromes (MDS) in Middle-Eastern Europe are scarce. No data about the demographic, clinical, and laboratory features of Polish MDS patients have been published. The aim of this study was to assess the epidemiological data and toxic exposure of Polish MDS patients and their association with hematological parameters and clinical outcomes. For 15 months, 966 living MDS patients were enrolled at 24 centers (12 university and 12 community hospitals). Follow-up was conducted for the next 55 months. The percentage of patients older than 80 years (16%) was between the values for Eastern and Western countries. In patients younger than 55 years, a female predominance was observed (male/female ratio 0.70:1 vs. 1.29:1; p < 0.001). Female patients had higher platelet counts (160 × 109/l vs. 111 × 109/l; p < 0.001). Patients exposed to chemicals were younger than patients without such exposure; their median age at MDS diagnosis was 66 vs. 70 years (p = 0.037). Smokers had significantly lower hemoglobin concentrations (8.6 vs. 9.1 g/dl; p = 0.032) and lower platelet counts (99 × 109/l vs. 137 × 109/l; p < 0.001) than nonsmokers. We provide the first description of the characteristics of Polish MDS patients. Females predominated in the group aged <60 years and they had higher platelet counts. The course of the disease is affected by toxic exposure and smoking.

Factors determining the risk of severe (WHO grades 3 and 4) hemorrhage in hematologic patients.

Hemorrhage is a frequent cause of death in hematologic patients. Factors influencing its occurrence are still not precisely defined. Hence, the objectives of this report were to define these factors in a group of patients suffering from severe (WHO grades 3 and 4) hemorrhage, hospitalized in the Department of Hematology, Oncology and Internal Medicine, The Medical University of Warsaw, Poland.

Sinusitis in patients undergoing allogeneic bone marrow transplantation – a review

INTRODUCTION Sinusitis is a common morbidity in general population, however little is known about its occurrence in severely immunocompromised patients undergoing allogeneic hematopoietic stem cell transplantation. OBJECTIVE The aim of the study was to analyze the literature concerning sinusitis in patients undergoing allogeneic bone marrow transplantation. METHODS An electronic database search was performed with the objective of identifying all original trials examining sinusitis in allogeneic hematopoietic stem cell transplant recipients. The search was limited to English-language publications. RESULTS Twenty five studies, published between 1985 and 2015 were identified, none of them being a randomized clinical trial. They reported on 31-955 patients, discussing different issues i.e. value of pretransplant sinonasal evaluation and its impact on post-transplant morbidity and mortality, treatment, risk factors analysis. CONCLUSION Results from analyzed studies yielded inconsistent results. Nevertheless, some recommendations for good practice could be made. First, it seems advisable to screen all patients undergoing allogeneic hematopoietic stem cell transplantation with Computed Tomography (CT) prior to procedure. Second, patients with symptoms of sinusitis should be treated before hematopoietic stem cell transplantation (HSCT), preferably with conservative medical approach. Third, patients who have undergone hematopoietic stem cell transplantation should be monitored closely for sinusitis, especially in the early period after transplantation.

Atypical chronic myeloid leukaemia: A case of an orphan disease—A multicenter report by the Polish Adult Leukemia Group

Atypical chronic myeloid leukaemia (aCML) belongs to myelodysplastic/myeloproliferative neoplasms. Because of its rarity and changing diagnostic criteria throughout subsequent classifications, data on aCML are very scarce. Therefore, we at the Polish Adult Leukemia Group performed a nationwide survey on aCML. Eleven biggest Polish centres participated in the study. Altogether, 45 patients were reported, among whom only 18 patients (40%) fulfilled diagnostic criteria. Among misdiagnosed patients, myelodysplastic/myeloproliferative syndrome unclassifiable and chronic myelomonocytic leukaemia were the most frequent diagnoses. Thirteen patients were male, median age 64.6 years (range 40.4‐80.9). The median parameters at diagnosis were as follows: white blood cell count 97 × 109/L (23.8‐342) with immature progenitors amounting at 27.5% (12‐72), haemoglobin 8.6 g/dL (3.9‐14.9), and platelet count 66 × 109/L (34‐833). Cytoreductive treatment was used in all patients, and 2 patients underwent allogeneic hematopoietic stem cell transplantation. The median overall survival was 14.1 months (95% CI, 7.2), with median acute myeloid leukaemia‐free survival of 13.3 months (95% CI, 3.6‐22.6). Cumulative incidence of acute myeloid leukaemia transformation after 1 year in aCML group was 12.5% (95% CI, 0%‐29.6%). To conclude, aCML harbours a poor prognosis. Treatment options are limited, with allogeneic hematopoietic stem cell transplantation being the only curative method at present, although only a minority of patients are transplant eligible. Educational measures are needed to improve the quality of diagnoses.

Are Myelodysplastic Syndromes Underdiagnosed in Poland? A Report by the Polish Adult Leukaemia Group

The epidemiology of myelodysplastic syndromes (MDS) differs among countries. Here, we present the first epidemiological indices determined for Poland.

Red Blood Cell Transfusion Dependency and Hyperferritinemia Are Associated with Impaired Survival in Patients Diagnosed with Myelodysplastic Syndromes: Results from the First Polish MDS-PALG Registry

BACKGROUND Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis, cytopenias and a risk of progression to acute myeloid leukemia (AML). Anemia is the most frequent cytopenia diagnosed in patients with MDS. Regular RBC transfusions are the only treatment option for about 40% of patients. Transfusion-dependent patients develop secondary iron overload. The influence of serum ferritin (SF) concentration on survival and acute myeloid leukemia transformation in MDS patients remains controversial. The data for the Central European population is scarce and so far there is no description for Poland. OBJECTIVES The aim of this study was to perform a retrospective analysis of the relationship of SF concentration with red blood cell transfusion dependency, survival and transformation to acute myeloid leukemia. MATERIAL AND METHODS We retrospectively evaluated the data of the 819 MDS patients (58% male; median age 70 years) included in the MDS Registry of the MDS Section of the Polish Adult Leukemia Group (PALG). RESULTS Analyses were performed on 190 patients diagnosed with MDS, maximal 6 months before inclusion to the registry in order to avoid selection bias (a shorter survival of higher risk MDS patients). Patients with hyperferritinemia higher than 1000 ng/L vs. patients with SF concentration lower than 1000 ng/L had a median survival of 320 days vs. 568 days, respectively (p log-rank = 0.014). The following factors were found to significantly worsen survival: RBC-transfusion dependence (p = 0.0033; HR 2.67L), platelet transfusion dependence (p = 0.0071; HR 3.321), hemoglobin concentration lower than 10 g/dL (p = 0.0036; HR 2.97), SF concentration higher than 1000 ng/L (p = 0.0023; HR = 2.94), platelet count lower than 10 G/L (p = 0.0081 HR = 5.04), acute leukemia transformation (p = 0.0081; HR 1.968). CONCLUSIONS Taking into account the relatively low number of patients in previous studies exploring hyperferritinemia in MDS, the results of the first Polish MDS Registry provide important insights. Hyperferritinemia higher than 1000 ng/L can be an important indicator of poor prognosis in MDS.

Atypical chronic myeloid leukaemia – a rare subtype of myelodysplastic/myeloproliferative neoplasm

Atypical chronic myeloid leukaemia (aCML) belongs to the group of myelodysplastic/myeloproliferative neoplasms. Changing diagnostic criteria and the rarity of the disease, with incidence approximately 100-times lower than the incidence of BCR-ABL1-positive chronic myeloid leukaemia, result in limited knowledge on aCML. At present the diagnosis is made based on the presence of granulocytic lineage dysplasia and precisely defined quantitative peripheral blood criteria, after exclusion of other molecularly defined myeloid neoplasms. Distinctive cytogenetic and molecular changes for aCML are missing, although recently SETBP1 mutations were described in a significant proportion of patients. The majority of patients are male and elderly. The prognosis of aCML patients is very bad, with median overall survival ranging between 10.8 and 25 months, and acute myeloid leukaemia-free survival amounting to approximately 11 months. No treatment recommendations can be made based upon current evidence, although allogeneic haematopoietic stem cell transplantation seems to be able to induce long-term remission in eligible patients.