The statement of the Polish Society of Allergology experts on the treatment of difficult-to-treat asthma

The main objective of asthma treatment is to control symptoms of the disease; however, despite the availability of guidelines and many groups of medications, the degree of control of this condition is insufficient. In difficult-to-treat asthma, the optimal control cannot be achieved due to reasons independent of the disease. Factors worsening asthma control include: inadequate treatment plan (low therapy adherence and compliance), inappropriate inhalation technique, insufficient symptom control using the available classes of medications, incomplete response to treatment (non-responders, steroid-resistance), incorrect diagnosis of asthma or comorbidities, and environmental factors. In order to achieve the optimal asthma control, it is recommended to: take therapeutic decisions with the patient, assess the probability of non-compliance, perform detailed diagnostics and initiate treatment of concomitant diseases, carry out differential diagnosis of conditions mimicking asthma, educate the patient as to the inhalation technique and check it, eliminate unfavourable environmental factors, and modify current treatment. New treatment options for patients with asthma include: ultra-long-acting beta2-agonists, long-acting muscarine receptor antagonists (LAMA), monoclonal antibodies, and non-pharmacological interventions. The only LAMA approved for treatment of asthma is tiotropium bromide. The analyses performed demonstrated a high efficacy of tiotropium in terms of improved lung function parameters and prolonged time to the first asthma exacerbation. It is recommended as an add-on therapy at asthma treatment steps 4 and 5 according to GINA (Global Initiative for Asthma) 2014. The optimal asthma control is important from the medical as well as the economical point of view.The main objective of asthma treatment is to control symptoms of the disease; however, despite the availability of guidelines and many groups of medications, the degree of control of this condition is insufficient. In difficult-to-treat asthma, the optimal control cannot be achieved due to reasons independent of the disease. Factors worsening asthma control include: inadequate treatment plan (low therapy adherence and compliance), inappropriate inhalation technique, insufficient symptom control using the available classes of medications, incomplete response to treatment (non-responders, steroid-resistance), incorrect diagnosis of asthma or comorbidities, and environmental factors. In order to achieve the optimal asthma control, it is recommended to: take therapeutic decisions with the patient, assess the probability of non-compliance, perform detailed diagnostics and initiate treatment of concomitant diseases, carry out differential diagnosis of conditions mimicking asthma, educate the patient as to the inhalation technique and check it, eliminate unfavourable environmental factors, and modify current treatment. New treatment options for patients with asthma include: ultra-long-acting beta2-agonists, long-acting muscarine receptor antagonists (LAMA), monoclonal antibodies, and non-pharmacological interventions. The only LAMA approved for treatment of asthma is tiotropium bromide. The analyses performed demonstrated a high efficacy of tiotropium in terms of improved lung function parameters and prolonged time to the first asthma exacerbation. It is recommended as an add-on therapy at asthma treatment steps 4 and 5 according to GINA (Global Initiative for Asthma) 2014. The optimal asthma control is important from the medical as well as the economical point of view

Skuteczna chemioterapia indukująco-konsolidująca u 20-letniej chorej na ostrą białaczkę promielocytową niewyrażającej zgody na przetoczenia preparatów krwiopochodnych z powodu przekonań religijnych

This paper describes a case of 20 years old woman with acute promyelocytic leukemia who refused to accept blood transfusion because of religious beliefs. Individualized induction chemotherapy with daunorubicin, cladribine, cytarabine and all-trans retinoic acid was administered and complete remission was achieved. Grade 4 leukopenia, anemia and thrombocytopenia was observed during induction chemotherapy. Then three consecutive consolidation cycles were given without important complications. In control molecular analysis after induction-consolidation therapy there was no PML-RARA fusion gene detected.W pracy opisano przypadek 20-letniej chorej na ostrą białaczkę promielocytową, która z powodu przekonań religijnych nie wyrażała zgody na przetaczanie preparatów krwiopochodnych. U pacjentki zastosowano zindywidualizowane leczenie indukujące daunorubicyną, cytarabiną, kladrybiną i kwasem all-trans retinowym, uzyskując całkowitą remisję (CR). W trakcie chemioterapii indukującej obserwowano jedynie toksyczność hematologiczną pod postacią leukopenii, niedokrwistości i małopłytkowości 4. stopnia. Po uzyskaniu CR chora otrzymała kolejno trzy kursy chemioterapii konsolidującej bez istotnych powikłań. W kontrolnym badaniu molekularnym po zakończeniu chemioterapii indukująco-konsolidującej nie stwierdzono obecności genu fuzyjnego PML-RARA

Results of Polish Adult Leukemia Study Group (PALG) project assessing TP53 mutations with next-generation sequencing technology in relapsed and refractory chronic lymphocytic leukemia patients — an 18-month update

Indtroduction and methods: In chronic lymphocytic leukemia (CLL), molecular and cytogenetic diagnostics are crucial for the determination of accurate prognosis and treatment choice. Among different genetic aberrations, del(17p13) or TP53 mutations constitute high-risk factors, and early identification of such defects is a high priority for CLL patients. While cytogenetic diagnostics is well-established and accessible for the majority of CLL patients in Poland, molecular diagnostics of TP53 mutations is performed only in a few ERIC-certified centers (eight as of September 2020), and only two of these employ next-generation sequencing (NGS) for routine analysis of TP53 status in CLL patients. Here we report the interim results of a project assessing TP53 mutations with NGS technology in relapsed or refractory CLL patients with confirmed negative del(17p13) status. 249 patients from 32 clinical centers were included in the study. Results: NGS analysis revealed TP53 mutations in 42/249 (17%) patients, half of whom (21/249, 8.5%) had subclonal mutations (VAF ≤10%). These results are in line with published data in relapsed/refractory CLL patients. Conclusions: The results of the project demonstrated the feasibility and accuracy of NGS testing in CLL patients despite several initial logistical and technical obstacles. Our study also proved that, with appropriate funding, CLL patients from any hematological center in Poland can have access to state-of-the-art molecular diagnostic

Skuteczność zastosowania ruksolitynibu u chorej z wtórnym włóknieniem szpiku w przebiegu wieloletniej czerwienicy prawdziwej powikłanej zakrzepicą w układzie wrotnym

Management of mielofibrosis remain still as open task, especially in case of disease lasting many years and complicated by thrombosis in portal vein. The history of treatment started from 1996, and is a good example for adjusting various treatment methods for existing possibilities and patient needs. Therapy using ruxolitinib caused clinical improvement, decrease of portal hypertension symptoms with clinical stability and circulation improvement.Leczenie chorych na włóknienie szpiku pozostaje otwartym problemem, zwłaszcza w sytuacji wieloletniego przebiegu choroby powikłanej zakrzepicą w układzie wrotnym. Przedstawiona historia leczenia chorej, u której choroba rozpoczęła się w 1996 roku, ilustruje konieczność stosowania różnych form leczenia dostosowanych do aktualnych możliwości i potrzeb chorego. Zastosowanie w ostatnim czasie ruksolitynibu spowodowało poprawę stanu klinicznego chorej, a także zmniejszenie objawów nadciśnienia wrotnego, ze stabilizacją kliniczną i stopniową normalizacją krążenia

Bezpieczeństwo stosowania ruksolitynibu w przypadku wielu schorzeń współistniejących

Bezpieczeństwo stosowania ruksolitynibu u chorych obciążonych wieloma schorzeniami współistniejącymi jest wciąż zagadnieniem otwartym. W opisanym przypadku zastosowano ruksolitynib u pacjentki obciążonej wrzodziejącym zapaleniem jelita grubego, sarkoidozą, nadciśnieniem tętniczym i chorobą niedokrwienną serca. Terapia tym lekiem nie nasiliła przebiegu obserwowanych przewlekłych schorzeń ani nie spowodowała konieczności zmiany leczenia chorób towarzyszących. Leczenie ruksolitynibem wywołało redukcję wielkości śledziony, poprawę stanu klinicznego chorej, ustąpienie dolegliwości bólowych lewego podżebrza

Evolution of the therapy strategies in hairy cell leukemia — 22 years lasting case study

Białaczka włochatokomórkowa (HCL) jest rzadką chorobą limfoproliferacyjną, w której rokowanie poprawiło się w ostatnich latach. Wielu autorów wskazuje na dużą skuteczność leczenia analogami puryn, takimi jak kladrybina i pentostatyna. Trzeba zdawać sobie jednak sprawę, że zdarzają się przypadki charakteryzujące się nawrotowością, a nawet opornością. W pracy przedstawiono przypadek wieloletniego nawrotowego przebiegu HCL u dorosłego mężczyzny, u którego w trakcie leczenia stosowano kolejne metody terapeutyczne. Przy rozpoznaniu w 1989 roku obserwowano naciek w szpiku kostnym i krwi obwodowej z leukocytozą i limfocytozą, powiększenie obwodowych węzłów chłonnych i splenomegalię. Początkowo wykonano splenektomię, prowadzono leczenie interferonem alfa. Po kolejnej progresji zastosowano skutecznie monoterapię kladrybiną w dawce 0,1 mg/kg mc./dobę przez 5 dni w cyklach co 4 tygodnie, po której uzyskano całkowitą remisję (CR) choroby. Wznowę obserwowano po 16 latach i powtórnie zastosowano leczenie kladrybiną, uzyskując CR. Wobec ryzyka ponownej wznowy w kolejnym rzucie leczenia rozważa się zastosowanie w przyszłości leczenia skojarzonego z przeciwciałami monoklonalnymi. Hematologia 2011; 2, 3: 284–289Hairy cell leukemia (HCL) is a rare lymphoproliferative disease in which prognosis has improved markedly during last decades. Many authors indicated spectacular therapeutic effects of purine analogues, including cladribine and pentostatine. However, refractory or relapsing cases still could be observed. In this paper we present a case of adult patient with relapsing HCL who was treated with different therapeutic methods in the course of his disease. At the time of diagnosis in 1989, an infiltration of the bone marrow and peripheral blood, lymphadenopathy and splenomegaly were noted. After initial treatment with interferon alpha, splenectomy with subsequent prolonged administration of interferon alpha were used, with transient clinical response. Upon the progression of the disease, cladribine at a dose of 0,1 mg/kg daily on days 1–5 in every 4 weeks was administered and patient obtained complete remission (CR). Relapse was observed 16 years later when cladribine was used again with CR achievement. Taking into consideration the risk of another disease relapse in the future, possible therapeutic attitudes, including monoclonal antibodies, are discussed. Hematologia 2011; 2, 3: 284–28

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease

Background/Aims: One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. Methods: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. Results: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. Conclusion: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency