Guidelines for Diagnosis and Treatment of Chronic Lymphocytic Leukemia. Krohem B-Cll 2017.

Recent developments in the diagnosis and treatment of chronic lymphocytic leukemia (B-CLL) have led to change of approach in clinical practice. New treatments have been approved based on the results of randomized multicenter trials for first line and for salvage therapy, and the results of numerous ongoing clinical trials are permanently providing new answers and further refining of therapeutic strategies. This is paralleled by substantial increase in understanding the disease genetics due to major advances in the next generation sequencing (NGS) technology. We define current position of the Croatian Cooperative Group for Hematologic Disease on diagnosis and treatment of CLL in the transition from chemo-immunotherapy paradigm into a new one that is based on new diagnostic stratification and unprecedented therapeutic results of B-cell receptor inhibitors (BRI) and Bcl-2 antagonists. This is a rapidly evolving field as a great number of ongoing clinical trials con-stantly accumulate and provide new knowledge. We believe that novel therapy research including genomic diagnosis is likely to offer new options that will eventually lead to time limited therapies without chemotherapy and more effective clinical care for B-CLL based on individualized precision medicine.

Infections in Hospitalised Patients with Multiple Myeloma: Main Characteristics and Risk Factors.

OBJECTIVE: Multiple myeloma is a common haematological malignancy and immune dysfunction is the hallmark of the disease. It leads to an increased infection risk, which is still a major cause of mortality. The infection spectrum and characteristics have evolved with the introduction of novel agents. An understanding of risk factors that increase susceptibility to infections is critical in fighting them. This retrospective investigation aimed to establish the incidence and main characteristics of infections in non-transplanted hospitalised myeloma patients in our department over a 3-year period, as well as factors associated with infections. MATERIALS AND METHODS: A total of 240 hospitalised patients with multiple myeloma (120 males and 120 females; average age: 69 years, range: 41-89 years) who were diagnosed or treated in our department from January 2008 to December 2010 were included in this study and their data were retrospectively analysed. RESULTS: Infections were identified in 17.9% of hospitalised patients. The most common pathogen found was Pseudomonas aeruginosa. The frequency of gram-positive and gram-negative pathogens was similar. In 37.2% of cases, the agent was not isolated. The most common sites of infections were the urinary system and the blood (septicemia). The frequency of infection increased with duration of disease and the rate of reinfection was 41.9%. The patients treated with bortezomib had the highest infection occurrence. Fatal outcome occurred in 9.3% of cases. CONCLUSION: The factors associated with infections in this investigation were female sex, 3B clinical stage of disease, increased serum creatinine and ferritin levels, neutropenia, poor general condition, and presence of catheters. Myeloma patients with one or more of these mentioned risk factors should be monitored with particular care in order to decrease the incidence and severity of infective complications.

Concurrent basal cell and squamous cell carcinomas associated with hydroxyurea therapy.

We report a case of a 76-year-old woman with concurrent onset of two primary cutaneous malignancies, one at the fourth finger and another at the dorsum of the same hand. The patient was on long-term therapy with hydroxyurea (HU) for polycythemia vera. Histopathologic and immunohistochemical studies revealed two different malignant cutaneous lesions, i.e. basal cell carcinoma (positive for bcl-2 and negative for vimentin, EMA and CK5/6) and poorly differentiated sarcomatoid squamous cell carcinoma (positive for vimentin, EMA and cytokeratins CK5/6, and negative for bcl-2). In addition, p53 was positive in approximately 50% of squamous cell carcinoma cells and in almost all basal cell carcinoma cells. The presence of low-risk human papillomavirus (HPV, types 6, 11) was verified by polymerase chain reaction, but only in the surrounding normal skin tissue, whereas HPV infection could not be detected in either carcinoma. In this patient, concurrence of two different skin carcinomas on sun-exposed skin, in the absence of HPV, suggest direct involvement of potentially mutagenic HU therapy, through influence on DNA synthesis and repair mechanisms, in conjunction with ultraviolet exposure. Therefore, we suggest that in patients on HU therapy with cutaneous side effects, referral to a dermatologist should be obligatory.

Placebo in the treatment of pain.

Placebo is the use of the substance or procedure without specific activity for the condition that is trying to be healed. In medicine, benefits of placebo effect are used since 1985 and 1978 placebo effect was first scientifically confirmed. It was found that placebo induced analgesia depends on the release of endogenous opiates in the brain and that the placebo effect can be undone using the opiates antagonist naloxone. Functional magnetic resonance imaging of the brain showed that placebo analgesia was obtained regarding the activation and increased functional relationship between ant. cingulate, prefrontal, orbitofrontal, and insular cortex, nucleus accumlens, amygdala, periaqueduktalne gray matter and spinal cord. Placebo also facilitates descending inhibition of nociceptive reflexes through periacvaeductal gray substance. Placebo effect can be achieved in several ways: by using pharmacological preparations or simulation of operating or other procedures. This phenomenon is associated with perception and expectation of the patient. To achieve the effect of placebo it is essential degree of the suggestions of the person who prescribe a placebo, and the degree of belief of the person receiving the placebo. Expected effect of placebo is to achieve the same effect as the right remedy. Achieved placebo effect depends on the way of presentation. If a substance is presented as harmful, it may cause harmful effects, called 'nocebo" effect. Placebo effect is not equal in all patients, same as the real effect of the drug is not always equal in all patients. Application of placebo in terms of analgesia will cause a positive response in 35% of patients. Almost the same percentage (36%) of patients will respond to treatment with morphine in medium doses (6-8 mg). Therefore, one should remember that response to placebo does not mean that a person simulates the pain and then it is unethical to withhold the correct treatment especially in light of findings that the prefrontal cortex is activated expecting liberation of pain and how this action reduce activities in brain regions responsible for sensation of pain (thalamus, somatosensory cortex and other parts of the cortex). However, the use of placebos is ethically, legally and morally very dubious. The basis for the placebo effect is deception. It undermines honest relationship and trust between doctor and patient which is extremely important for successful treatment. Consciously giving placebos to patients for a condition that can be adequately treated, with prejudice the right of patients to the best care possible, opens up many bioethical issues. Despite all the current knowledge level, placebo effect remains still a scientific mystery.

[Diagnosis and therapy for patients with essential thrombocythemia. Guidelines of Croatian Cooperative Group for hematologic disorders--KROHEM]. / Dijagnosticko-terapijski pristup u bolesnika s esencijalnom trombocitemijom. Smjernice Hrvatske kooperativne grupe za hematoloske bolesti--KROHEM.

Essential thrombocythemia (ET) is a clonal myeloproliferative neoplasm. Croatian Cooperative Group for hematologic disorders, KROHEM proposes the diagnostic and treatment guidelines for ET. Diagnosis of ET is based on the criteria and classification of World Health Organization (WHO). The level of treatment recommendation is based on the UpToDate (web based medical community database) criteria. For ET diagnosis it is mandatory to show sustained increased number of platelets with typical histomorphological changes of megakaryopoiesis in bone marrow. Secondary thrombocytosis and other chronic myeloproliferative neoplasms have to be excluded. Therapy is based on risk factors for ET. The risk factors are number of platelets, patient's age, and the risk levels for thrombosis and bleeding. Patients with low risk (age < 60 years and platelets < 1000 x 10(9)/L) arw not candidates for therapy. In younger group of patients with platelets between 1000 and 1500 x 10(9)/L or more than 1500 x 10(9)/L treatment with anagrelide or hydroxyurea is recommended respectively. In high risk patients hydroxyurea is the first line treatment. Anagrelide is indicated in these patients in the absence of treatment response. Alpha-interferon is recommended for pregnant women with ET and high platelet counts.