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Background: Carfilzomib is a second-generation proteasome inhibitor (PI) used for combination therapy with dexamethasone and/or lenalidomide in patients with relapsed or refractory multiple myeloma. Reports indicate that PIs have a unique toxicity profile that includes thrombocytopenia as a hematologic adverse event; however, its occurrence has not yet been quantified systematically. Objectives: The main objective of our systematic review and meta-analysis is to investigate the incidence of thrombocytopenia in patients with multiple myeloma after treatment with carfilzomib. Design: Selection of studies and meta-analysis of trials was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data sources and methods: Two investigators performed an independent literature search of PubMed, Web of Science, SciFinder, the Cochrane Central Register of Controlled Trials, as well as the US and EU clinical trials registries. The cumulative incidence and overall relative risk were calculated with the random effect model using RevMan and R statistical software. Results: The analysis included a total of 9237 patients, 2516 patients in single-arm studies and 6721 patients in randomized controlled trials (RCTs). A total of 47 studies were included; among these, 14 were RCTs. Analysis of currently available data showed that treatment with carfilzomib may increase the incidence of all-grade thrombocytopenia, and this correlated with the dose used. With supportive therapy alone, the incidence is 26%. The addition of carfilzomib to the treatment results in a 37% increase in incidence, whereas with bortezomib, the increase is slightly lower at 34%. Surprisingly, when treatment with carfilzomib and bortezomib was compared, bortezomib was found to be more likely to exacerbate high-grade thrombocytopenia (7%) than carfilzomib (3%). Conclusion: Clarification of these associations suggests that clinicians should be aware of the potential risk of high-grade thrombocytopenia occurring and monitor patients closely to take appropriate measures. Trial registration: Registered in PROSPERO under the number CRD42022314378.

S transfuzijo povezana reakcija presadka proti gostitelju (angl. Transfusion associated graft versus host disease, TA-GvHD) je redek, vendar resen in življenje ogrožajoč zaplet po transfuziji krvnih pripravkov. Posledica, kolikor do nje pride, je bolnikova smrt v več kot 90 % primerov. Po transfuziji krvi se osebi z imunsko pomanjkljivostjo limfociti T iz darovalčeve krvi odzovejo na celične in tkivne antigene prejemnika krvi. Zato darovalčevi limfociti T aktivirajo in uničijo tarčne celice v tkivih prejemnika. Vzrok, da se imunske celice prejemnika ne odzovejo tako, da bi onemogočile darovalčeve limfocite T, je pomanjkljivost imunskega odziva pri prejemniku in le izjemoma vprašanje skladnosti HLA med prejemnikom in darovalcem. Obsevanje krvnih pripravkov z ionizirajočimi žarki je najbolj učinkovita metoda za preprečevanje TA-GvHD. Patogensko inaktiviranje s psoralenom in UVA-žarki je enakovredno obsevanju, vendar se zaenkrat uporablja samo za trombocitne pripravke. Zato je pomembno, da lečeči zdravnik prepozna bolnike, pri katerih lahko nastane TA-GvHD in za njih naroča zgolj obsevane krvne pripravke. Obsevamo eritrocite, granulocite ter trombocite, kadar niso patogensko inaktivirani. Sveže zmrznjene plazme, krioprecipitata, zdravil iz krvi, kot so albumin, imunoglobulini, faktorji strjevanja krvi ... ter eritrocitov po odmrzovanju ne obsevamo, ker je vsebnost limfocitov T zanemarljiva. Priporočen osrednji obsevalni odmerek je znotraj 25–50 Gy.

Slabokrvnost je najbolj pogost simptom v nosečnosti. Zaradi razvoja zarodka in hitre rasti ploda se močno povečajo potrebe organizma po železu in vitaminih. Zato je slabokrvnost zaradi pomanjkanja železa daleč najbolj razširjena oblika slabokrvnosti v nosečnosti. Anemija v nosečnosti je opredeljena z ravnijo hemoglobina (Hb), ki je manjša od 110 g/L. V normalni nosečnosti se sestava krvi pomembno spremeni. Povečanje celokupnega volumna krvi in hemostatske spremembe so fiziološke spremembe, ki omogočajo, da porodnica brez posledic prenese normalno izgubo krvi med porodom. Plazemski volumen se v nosečnosti poveča za 50 %, masa eritrocitov pa za 18 – 25 %, odvisno od razpoložljivega železa. Te spremembe povzročijo razredčitev koncentracije hemoglobna, kar poznamo kot fiziološko slabokrvnost v nosečnosti. Fiziološka slabokrvnost doseže vrh v 32. tednu nosečnosti. Zaradi fizioloških sprememb odkrijemo s presejalnimi testi v nosečnosti mnogo slabokrvnosti, ki bi sicer ostale neodkrite. Povečane ali spremenjene prehranske in presnovne zahteve v nosečnosti povzročijo, da je slabokrvnost zaradi pomanjkanja železa (sideropenična anemija) bolj pogosta. Prva nepravilnost v biokemičnih izvidih, ki kaže na pomanjkanje železa v nosečnosti, je zmanjšana koncentracija feritina (na pomanjkanje železa lahko sklepamo že, ko je vrednost feritina manjša od 20–30 g/L). Feritin je stabilen in zadovoljivo zrcali zaloge železa, za razliko od vrednosti serumskega železa. Zato učinkovito dodajanje železovih pripravkov in s tem preprečevanje sideropeničnih anemij lahko pričnemo že zelo zgodaj. Tako na zelo enostaven način učinkovito preprečimo nastanek zapletov v nosečnosti, ob porodu in v poporodnem obdobju. Slabokrvnost v nosečnosti je povezana s višjo pogostnostjo za prezgodnji porod, nizko porodno težo, z nujnostjo uporabe transfuzije ob in po porodu ter s poporodno depresijo.

Mesenchymal stem cells (MSCs) have attracted great interest in the field of kidney transplantation due to their immunomodulatory and reparative properties. In registered clinical trials, MSCs have been used before, at the time of, or early after transplantation and have been reported to be well-tolerated with no serious safety concerns. No results are available on the use of MSCs in the late post-transplant period. Here, we present a case report of a severe systemic complication mimicking capillary leak syndrome with ultimate kidney transplant failure after autologous transplantation of MSCs used as rescue treatment of late antibody-mediated kidney allograft rejection.

CMML is clinically diverse malignant clonal hematopoietic stem cell disorder characterized by persistent peripheral monocytosis, bone marrow dysplasia and with features of both myelodysplastic and myeloproliferative neoplasms (1). Generally, long term prognosis is poor with a median overall survival of 30 months and a relatively high risk of leukemic transformation, up to 30 % (2). Hypomethylating agents belong to a class of drugs which inhibit DNA methyltransferase and consequently reduce DNA methylation. Utilization of HMA in CMML has been reported with seemingly unsatisfying results with overall response rates between 30 and 60% and median overall survival between 12 and 37 months (3,4). Previously only a few predictive factors (increased bone marrow blast count and proliferative features) were found to be associated with shorter survival (5). Surprisingly only age, but none of the other disease characteristics, was a prediction for a response(6). In this case report, we describe an effective long term use of azacitidine in a patient with CMML and tried to find factors, which may contribute to long term azacitidine efficacy.

Extramedullary plasmacytoma of the head and neck is a rare indolent neoplasm. Radiotherapy is often the preferred treatment option with excellent local control and survival. The risk of local recurrence or transformation to multiple myeloma is 10- 30%. In our case-cohort, thorough, sensitive initial evaluation for disseminated clonal disease and the incorporation of surgery led to excellent results with no recurrences or systemic progression.

Incidenca levkemij, odkritih v nosečnosti, znaša od 1/10.000 do 1/100.000. Nemalokrat je ob odkritju bolezni z zdravljenjem s citostatiki potrebno začeti takoj. Citostatiki so za plod teratogeni, zato moramo pred pričetkom zdravljenja pretehtati vse možnosti in izbrati najbolj sprejemljivo. Predstavljamo primera akutne mieloične levkemije (AML) in kronične mieloične levkemije (KML), odkrita v nosečnosti, ki smo ju obravnavali v Univerzitetnem kliničnem centru v Ljubljani. Gre za edina primera v zadnjih desetih letih v Sloveniji. Bolnico z AML, podvrsta akutna promielocitna levkemija (APL), smo ob začetku 2. trimesečja nosečnosti zdravili z daunorubicinom in all-transretinoično kislino (ATRA). Glede na našo izkušnjo se zdi, da so priporočila za zdravljenje APL v nosečnosti realna, izvedljiva in predvsem varna za bolnico in plod. Pri bolnici s KML, ki je prvič prišla k nam tik pred porodom, je bila v ospredju izrazita levkocitoza 335 × 109/L, trombocitoza in splenomegalija. Zavračala je vse načine zdravljenja, v prvi vrsti levkoferezo. Kljub vsemu je brez porodnih zapletov rodila zdravega otroka. Porod je bil zaradi povečane vranice in posledične nevarnosti za njeno rupturo dokončan s carskim rezom. Na osnovi naše izkušnje lahko zaključimo, da ni moč priporočiti, pri kako velikem številu levkocitov je za mati in plod koristno začeti zdraviti z levkoferezo. Enako tudi ni jasno, kakšno tveganje za rupturo vranice v teh primerih predstavlja poskus vaginalnega poroda. Uganka ostaja tudi vprašanje, kolikokrat se zaradi levkemij različnih oblik poveča tveganje za trombembolični dogodek v nosečnosti, ki že sama po sebi nagiba k trobozam.

Abstract. The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future.

Background: Iron deficiency anaemia (IDA) is the most prevalent type of anaemia and a common cause for patient referrals to the haematology outpatient clinic. The aim of this study was to determine the number of patients with IDA treated at the Haematology Outpatient Clinic of the UMC Ljubljana in the period of two years, as well as to inquire into the causes for their referrals to the clinic, patient characteristics, their complete blood count results at initial examination, the prescribed therapy, the number and the causes of their follow-up visits. We draw special attention to the IDA onset mechanism, the microcytic anaemia therapy principles and the indications prompting a referral of an IDA patient to the haematology specialist. Methods: We undertook a retrospective analysis of the medical records of patients who were referred to the Haematology outpatient clinic of the UMC Ljubljana for examination in the two-year period between 1 January 2014 and 31 December 2015 and had been diagnosed with IDA on the basis of their clinical picture and their CBC values. Data were collected with the Hipokrat IT system and statistically evaluated with Microsoft Excel. Results: In the period relevant for our research, 277 patients of those who were referred to the Haematology outpatient clinic for medical examination were diagnosed with IDA. 11.6 % of these patients were male and 88.4 % female; 62.1 % of the female patients were of childbearing age. IDA was specified as the referral diagnosis in the cases of no more than 39 % of the patients referred to the specialist outpatient clinic, whilst the medical condition of the remaining percentage of patients was not identified by the referring doctor. Comorbidities were observed in 50.2 % of the patients, and for 62.5 % of the patients a follow-up appointment was scheduled by the treating haematologist. Of all patients, 63.5 % were treated with an intravenous iron preparation during their first examination at the outpatient clinic and a transfusion of erythrocytes was administered during such an examination to 4.3 % of the patients. Conclusion: Patients with IDA were often treated at our Haematology Outpatient Clinic in the relevant two-year period. The data indicates a poor recognition rate of this prevalent type of anaemia. IDA is not a blood disorder and the referral of IDA patients to the Haematology Outpatient Clinic is justified in the case of severe microcytic anaemia, when the patient does not respond to the oral or intravenous iron replacement therapy or if a concomitant change in the CBC persists despite the effective treatment with iron preparations.

Introduction. In the period from 01.01.2014 to 31.12.2015 at Clinical Department of Hematology, University Medical Centre Ljubljana, we treated 73 multiple myeloma patients with first autologous hematopoietic stem cell transplantation (HSCT).Methods and results. Age of patients ranged from 27 to 72 years with the median age of 60 years. Induction treatment at the time of diagnosis consisted of: VD (bortezomib, dexamethasone) 60/73 patients (82%), VCD (bortezomib, cyclophosphamide, dexamethasone) 10/73 patients (14%) and VTD (bortezomib, thalidomide, dexamethasone) 3/73 (5%) patients. As part of induction therapy, patients received from 1 to 9 cycles of treatment. Response to induction therapy prior to HSC(hematopoietic stem cells) collection was as follows: CR(complete remission )7/73(10%), VGPR (very good partial response) 28/73(38%), PR (partial response) 23/ 73(32%), SD (stable disease) 11/73(15%) andPD (progressive disease) 4/73(5%) patients. Response to induction therapy immediately prior to autologous HSCT: CR9/73 (12%), VGPR32/73 (44%), PR17/73(23%), SD 8/73(11%) and PD6/73(8%) patients. Response to induction therapy and the first autologous HSCT at D+100 after HSCT: CR9/67 (13%), VGPR 34/67 (51%), PR 12/67 (18%), SD 3/67 (4 %) and PD 7/67 (10%) patients (in 6 patients data are missing, because they are not mature yet). With single HSCT 63 patients were treated, while 10 patients received double or second HSCT. The overall mortality of patients treated during the period from 01.01.2014 to 31.12. 2015 was 6/73 or 8.2%.Conclusions. The treatment of multiple myeloma with autologous HSCT remains the cornerstone of efficiency,as demonstrated by the increasing share of the most desired responses to treatment, ie. CR and VGPR. The treatment mortality rate was within expectation limits.

As a precious biological substance, donated blood has to be used in a sustainable, safe and efficient manner. Therefore good transfusion practice in modern surgery, anaesthesiology and intensive care is of key importance. New therapeutic methods, operations, transplantation of organs and hematopoietic stem cells often require intensive and long term supportive therapy including transfusions of blood components. Nowadays, transfusion service is confronted with continuously increasing demand for sufficient quantity of safe high quality blood, and on the other hand with limited resources of blood. The article deals with the current modern approaches for optimization of transfusion practice and Patient Blood Management that have to be implemented in Slovenian hospitals.

Complete blood count is basic investigation in medicine. It gives us necessary information for acutely sick patient's diagnostic and treatment. We describe the most frequent etiology of red, white and thrombocyte cell lines abnormalities and give notice on conditions who require immediate measures.We had analyzed 1297 complete blood count results of patients who sought medical help in Emergency setting of Ljubljana's health care center from 1.1. 2014 to 31.1. 2014.Every fourth patient treated in the emergency setting had abnormalities in complete blood count. The most frequent finding was leucocytosis, following normocyte anemia and erytrocite's morphological abnormalities without laboratory signs of anemia. Every tenth patient had abnormalities in two or three cell lines.Complete blood count is probably the most basic investigation in medicine. From the results we can suspect on many different pathologies. Differential blood count should be ordered if we find abnormalities in complete blood count. Physicians should read and evaluate complete blood count with the same dedication as we read electrocardiogram.

AbstractBackground: Thrombotic microangiopathy (TMA) is a rare syndrome that leads to excessive formation of blood clots, microthrombosis and is accompanied by non-autoimune haemolytic anemia and thrombocytopenia. Only few cases describing TMA caused by cancer are being reported in the literature.Patient: A 42-year old male patient with metastatic carcinoma of sigma and several accompanying diagnoses (pulmonary embolism, deep vein thrombosis, cerebrovascular insult) had later developed clinical and laboratory signs of TMA. TMA was unresponsive to plasmapheresis, which was discontinued and first cycle of chemotherapy was applied. The patient died soon after. The autopsy did not provide any additional information about the disease, there were no signs of malignant bone marrow infiltration.Conclusion: The diagnosis of secondary TMA remains a diagnostic and therapeutic challenge. It appears as a rare complication in patients with cancer. Treatment is difficult because the cause of TMA (malignancy) is hard to remove. Patients with cancer do not respond to plasmapheresis, which often delays the application of chemotherapy, the only effective treatment for TMA. Consequently this condition has poor prognosis.

Multiple myeloma is the second most common hematologic malignancy in western world. There are every year around 120 newly diagnosed patients in Slovenija and their survival is on the path of sustained improvement. After year 2006, we are presenting new 2015 uptodated new slovenian guidelines, dealing with diagnostics and treatment of multiple myeloma.

Human cytomegalovirus can be transmitted by direct contact and iatrogenically by transfusion of blood components and by transplanted tissues or organs. After a primary, mostly asymptomatic infection, it remains latent in the body in CD34 + hematopoietic stem cells of the bone marrow and in peripheral blood monocytes. Symptomatic CMV infection or viral reactivation with involvement of different organs can develop in immunocompromised patients. Prevention of CMV transmission by transfusion of blood components is important in patients at increased risk: intrauterine and neonatal transfusions, pregnant women, children with immune deficiency, patients with hemopoietic progenitor stem cell and organ transplants. The most important approaches to the prevention of CMV transmission are a selection of safe donors, serological testing for CMV antibodies, leukodepletion, pathogen inactivation, and rational use of blood. None of these measures are 100 % efficient, but they can complement each other.

Background: Essential thrombocythemia (ET) is a chronic Ph negative myeloproliferative neoplasm characterized by thrombocytosis, bone marrow megakaryocyte proliferation, JAK 2 V617F mutation in 50–60 % of patients and MPL mutation in 3–5 % of patients. Higher mortality of ET patients is caused by vascular complications, such as thrombosis, microvascular disorders and bleeding events. The goal of treatment is the prevention of thrombosis and haemorrhage. The research was aimed to provide insight into the number of patients and the ways they were treated in the last four years at our clinic. Method: Data from patients diagnosed with ET in the period from 1 January 2008 to 31 December 2011at the Haematology Department of the UMC Ljubljana were collected. The data were analysed in MS Excel. Results: During the period between January 2008 and December 2011 there were 245 new ET patients (35 % males and 65 % females) diagnosed and treated at our clinic. Average age of patients was 65 years. The number of patients with JAK 2 mutation present was 124 (50 %). 180 patients met criteria for ET, while for another 65 the data were insuficient or presence of reactive causes was determined. Patients > 60 years old, who already suffered thrombosis or bleeding events and whose thrombocyte concentration results exceeded 1500x10/9/L were grouped as patients with clear criteria for ET and high risk for thrombosis. The number of patients was 132; 49 patients were qualified for the group with minor risk for complications. Risk factors for cardiovascular disease, which causes upward risk for thrombosis, were determined in 47 % of all patients. The majority of patients received treatment with low-dose aspirin. Cytoreductive therapy with hydroxyurea and anagrelide. A few patients received treatment with a combination of hydroxyurea and anagrelide. Only some patients received interferon alpha or busulfane. One patient presented with transition into primary myelofibrosis and another one with transition into acute leukemia. Conclusions: In the analyzed group of patients, we have established the incidence of the disease in all age groups . The disease affects women at a higher rate. The results comply with so far known facts and research. The presence of JAK2 mutation is consistent with known statistic facts. The proportion of reactive trombocytoses reffered to as ET is outstanding (26.5 %). The fact that the shares of patients treated with hydroxyurea and anagrelide are practically equal is unusual. According to the expectations and guidelines it would be expected that anagrelide is introduced as a second-line treatment. In our four-year observation period, transitions to primary myelofibrosis and acute leukemia were considerably low.

Background: Autologous stem cell transplant is a standard of care for hematologic malignacies. Mobilization and collection of hemopoietic stem cells (HSC) is a prerequisite for its success. Between 5–30 % of healthy donors and up to 60 % of high risk patients for poor mobilization are not able to collect sufficient amount of HSC for the procedure. Bone marrow infiltration, irradiation, age and prior treatment with melphalan, fludarabine, lenalidomide or any high dose chemotherapy are risk factors for poor mobilization. In case of collection failure, a CXCR4 antagonist plerixafor (Mozobil) can be successfuly used with up to 70 % collection rate in this high-risk patient group. Methods: Hipokrat program with its medical database was used to retrospectively analyse data on patients treated with plerixafor at the Department of Hematology, UMC Ljubljana. Basic statistics were applied to the collected data. Results: From 2008 until November 2011 we treated 16 patients with a median age of 57 years (range 21–71). They were diagnosed with multiple myeloma (n = 13/81.3 %), lymphoplasmacytic immunocytoma (6.3 %), mantle cell lymphoma (6.3 %) and Burkitt’s lymphoma (6.3 %). At the time of mobilization three (18.8 %) patients were in complete remission, four (25.0 %) in very good partial remission, six (37.6 %) in partial remisson, two (12.5 %) had stable disease, while in one (6.3 %) the disease status was not assessed. The patients were treated with bortezomib (n = 13/81.3 %), irradiation (n = 7/43.8 %), cyclophosphamide (n = 5/31.8 %), purine analogoues (n = 3/18.8 %), revlimid (n = 3/18.8 %) and thalidomide (n = 1/6.3 %). Ten (62.5 %) patients underwent previous attempt of mobilzation and only one collected > 2x106/kg CD34+ HSC. On the day of plerixafor administration, median CD34+ HSC blood count was 8.7 x106/l (2.0–50.04) and after plerixafor 27.15 x106/l (13.9–307.11). Ten (62.5 %) patients required two administrations of plerixafor. Median collected CD34+ HSC were 2.34 x106/kg (0.98–6,73). Three (18.8 %) patients failed to mobilize. Conclusions: Plerixafor is a new highly successful mobilizing agent in high-risk patients or patients with previously failed mobilization. According to our experience, 13 (81 %) poor mobilizers collected a sufficient amount of HSC on plerixafor to proceed to transplant.

Background: Multiple myeloma (MM) is an incurable malignant clonal plasma cell disorder. Allogeneic stem-cell transplantation (SCT) is a possible treatment for limited number of patients. It is associated with high treatment-related mortality (TRM), mainly due to complications related to graft versus host disease (GVHD). Methods: We retrospectively analyzed all patients that were treated by allogeneic stem-cell transplantation at our departement between the years 1998 until the end of 2011. Results: In the period from 1 January 1998 to 31 December 2011, 22 multiple myeloma patients were treated by allogeneic SCT. Their median age was 46 years, ranging from 36 to 66 years. There were 11 (50 %) women and 11 (50 %) men. Prior to allogeneic SCT, 1/22 (4.5 %) patients had a complete response (CR), 9/22 (40.9 %) had a very good partial response (VGPR), 7/22 (31.8 %) a partial response (PR) and 5/22 (22.7 %) had a progressive disease (PD); 8/22 (36.3 %) had acute GVHD, and the same number of patients developed chronic GHVD; 9/22 (40.9 %) had cytomegalovirus reactivation. At the time of analysis, 13/22 (59 %) patients were still alive. Among those, 11/13 (84.6 %) had a CR or VGPR, 1/13 (7.7 %) a PR, 1/14 (7.7 %) had a stable disease. 9/22 (40.9 %) patients died: 5/9 (55.5 %) due to GVHD, 3/9 (33.3 %) due to disease progression, and 1/9 (11.1 %) following infection. Conclusions: Because of high TRM and impaired quality of life due to chronic GVHDrelated complications, allogeneic SCT is still reserved for a small group of MM patients. These are usually younger patients at high risk of progression and early relapse of the disease. We do not recommend allogeneic SCT to patients with late stages of the disease who are refractory to the prior therapy. It is also very important to achieve a low tumor burden (CR, VGPR) prior to allogeneic SCT

Background: Invasive aspergillosis (IA) is a common opportunistic infection in patients with critical neutropenia. Mostly, patients are located on hematological wards. In Slovenija, because of unsuitable hospital enviroment the problem of IA is huge. With clinical observational study OSPIA (»Observational Study of Patients with Invasive Aspergillosis«) we tried to evaluate prevention, diagnostics and treatment of IA. Methods: During three-year period we included 55 patients with IA. Besides the primary disease, we evaluated risk factors, prevention measures, diagnostic approaches and treatment of IA. Results: In most cases, patients had acute leukemia and major risk factor was critical neutropenia. Because of inadequate hospital conditions, almost every patient received prophylaxis with posoconasol. The most frequently used diagnostic procedure is test for galactomannan antigenemia, followed by radiological approach. Most casas were treated with amphothericin, followed with caspofungin. The treatment was not effective in cases of therapy-refractory primary hematological disease. Conclusions: In Slovenia, IA remains a huge problem in patients with critical neutropenia. The primary reason lays in inadequate hospital treatment conditions for hematological patients. The latter we try to mitigate with posoconasole prophylaxis.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disorder resulting from antibody- and T-cell-mediated destruction of the platelets and suppression of platelet production in the bone marrow. According to the International Consensus report, in order to be diagnosed with ITP, patient is required to have isolated thrombocytopenia with a platelet count below 100 × 109/L, with no other obvious cause for this condition and no other disease that could cause secondary immune thrombocytopenia. Methods: We retrospectively analysed patients who were treated de novo for ITP at the Departement of Hematology of the University Medical Centre Ljubljana (UMC) between the period from 1 January 2008 to 31 December 2012. We excluded those who did not meet the criteria for diagnosis of ITP. Afterwards we analyzed the type and response to treatment and the incidence of bleeding. Splenecomised patients were analysed separately. Results: In the four-year period we treated 153 patients diagnosed with ITP. 113/153 were included in the study, while 40/153 (26 %) were excluded. Bleeding incidents were recorded in 47/113 (41.5 %), but none of them were life threatening or fatal. 14/113 (12.4 %) were treated by splenectomy. Conclusions: Since ITP is a diagnosis of exclusion, many patient do not meet all the criteria for firm diagnosis. Considering low platelet counts, life threathening or even fatal bleedings are rare. Corticosteroids are standard first-line treatment. Nevertheless, many patients do not need any treatment at the time of diagnosis. At our centre splenectomy is often used as a second line treatment. In patients with refractory ITP or those who are not good candidates for splenectomy, we also use thrombopoetin receptors agonists or rituximab.

Backgrounds: Multiple myeloma (MM) among the most frequent lymphoproliferative disorders in the developed world. As to Slovenia, we have no available data regarding patients who are diseased and are receiving treatment. Methods: Data were collected with PC Windows Excel and the survival analysed with SPSS 16.0. Data were collected for the period from 1 January 2008 to 31 December 2011. Patients’ age, sex, their distribution among regions in Slovenia, MM subtype and cytogenetic abnormalities were collected. Patients were categorised according to the prognostic ISS international scoring system (score 1, 2 or 3); we colllected the type and therapeutic response to MM induction treatment and subsequent autologous or allogenic HSCT if performed. Results: During the four-year period we treated 350 patients with MM, 188 males (53.7 %) and 162 females (46.3 %); 171/350 (49 %) patients were younger than 70 years (mean age 59 years) and 179/350 patients (51 %) older than 70 years (mean age 79.5 years); 191/350 (54.6 %) were from Ljubljana region. MM incidenca for Ljubljana is 7.5 patients/year/100,000 inhabitants. In 56.9 % the main subtype was IgG, followed by Bence Jones subtype in 21.2 % and by IgA subtype in 18.9 % . ISS scoring system was evaluable in only 134/350 patients (38.2 %). 9.4 % patients were in group 1, 11.4 % in group 2 and 17.4 % in most unfavourable group 3. In 232/350 patients (66.3 %) the result of FISH (»flourescent in situ hibridisaton«) cytogenetics were performed and further evaluated in 213/232 patients. 60/213 (28.2 %) patients had no FISH detected abnormalities. In others, most frequent were del(13), amp(15q), amp(1q), del(17p), t(4;14), del (6q), … (47.9 %, 44.7 %, 33.3 %, 10.4 %, 9.4 %, 9.1 %). In most patients chromosomal rearrangements were complex and not isolated ones. Among the latter, the most frequent was del(13) in 61/213 patients (28.6 %). 209/350 (59.7 %) patients received a combination of bortezomib and dexamethasone (VD) as first induction treatment, followed by VAD scheme (vincristine, adriamycin, dexamethasone) in 17.1 % and TD (thalidomide dexamethasone), AP (melphalan, methylprednisolone) and VMP (bortezomib, melphalan, methylprednisolone) in 6.3 %, 5.4 % and 4.6 %. With all treatment regimens we achieved a complete remission (CR) of MM in 7.4 % of patients, very good partial response (VGPR) in 16.3 % of patients, partial response (PR) in 42.3 %, but in 18.6 % of patients MM parameters remained stable (SD) or even progressed in 7.1 % of patients (PD). After the induction treatment, 125/350 patients (35.7 %) proceeded to treatment with autologous HSCT and 1/350 (0.3 %) with allogeneic HSCT. 126/350 (36 %) patients relapsed after induction, HSCTtreated patients included. In the context of reinduction treatment, most frequently VD, followed by RD (lenalidomide, dexamethasone), AP and TD were used. 27/350 patients (7.7 %) were at that point treated with tandem autologous HSCT and 6/350 (1.7 %) with allogeneic HSCT. 104/350 patiens died. Average survival for the whole group was 31.6 months and median survival 46.1 months. Survival is statistically longer (p < 0.0001) in patients who had ISS score 1, achived CR or VGPR after induction and were treated with autologous HSCT. Conclusions: The incidence of MM and treatment-related results of MM in Slovenia are expected and comparable with similar data from Western countries. It is important to note that most important contributors are the availability of newer drugs (bortezomib, lenalidomide, thalidomide) in Slovenia and treatment with autologous HSCT.

Fresh frozen plasma (FFP) is a blood component obtained from processed whole blood or collected by plasmapheresis and afterwards stored in frozen state. Indications for the clinical use of FFP are single coagulation factor deficiencies (such as F V and F XI), multiple coagulation factors deficiency (most frequent as a consequence of massive hemorrhage), coagulopathy caused by advanced liver disease, warfarin mediated coagulopathy and thrombotic thrombocytopenic purpura. Standard FFP treatment dose in mentioned indications is generally 10–20 ml/kg of patient body weight. During the treatment attention should be paid to possible FFP treatment related adverse effects. Most frequent are allergic reactions. We should not consider FFP as a treatment approach in clinical situations where equally effective and safer treatment modalities are available.

BACKGROUNDPatient’s anamnesis is of primary importance in determining hemostatic disorders. Based on anamnestic data, a clinician may decide for further laboratory tests. We must consider an acquired bleeding disorder in a patient with unusual, unexpected and prolonged bleeding episodes. In this article we will describe two rare acquired hemostatic disordes.TWO CASE REPORTSOur first patient had prolonged bleeding after a pacemaker implantation. We diagnosed him with acquired von Willebrand syndrome. Further on, the patient required a planned surgical procedure. In our second case we describe a patient with unusual and excessive skin bruising and prolonged bleeding after teeth extractions. He was diagnosed with acquired hemophilia.CONCLUSIONIn the assessment of a patient with a potential acquired bleeding disorder we must first rule out the most common causes, such as iatrogenic ones. But, because of high morbidity and mortality rates, we must also be aware of some rare acquired bleeding disorders. In case of uncertainty, we should consult with a hematologist.

Abstract: The use of granulocyte concentrate (GC) is usually the last therapeutic approach in patients with severe neutropenia, unresponsive to treatment with wide spectrum antibiotics and antimycotics. Because of the routine usage of granulocyte colony-stimulating factor, this therapeutic approach is nowadays more and more frequent and more effective. Therefore it is necessary to have an updated knowledge of this blood component. In the article, we present the whole process from collection and processing to treatment with GC.

There is predominate opinion among physicians managing type 1 Gauchers' disease (GD) that cardiac involvement is not an issue in these patients. In order to follow this hypothesis, we prospectively investigated 15 adult imiglucerase-treated type 1 GD patients by echocardiography, Doppler, and tissue Doppler echocardiography. This was a case-controlled study with 18 matched healthy volunteers. The obtained data was correlated with the levels of NT-proBNP (brain natriuretic peptide). None of the GD patients had clinical signs of heart disease. In 3 of the 15 patients, we observed echocardiographic signs of aortic and mitral valve calcification. The left ventricular systolic function was within normal limits. Compared to the control group, there was no statistically significant difference observed in the most sensitive indices of left ventricular diastolic function, parameter Em (P=.095), and E/Em ratio (P=.097), as demonstrated by tissue Doppler echocardiography. However, there was a positive correlation between the E/Em ratio and NT-proBNP plasma levels (P=.009). In conclusion, the prospective echocardiographic study of type 1 GD patients did not validate any left ventricular dysfunction. But, the E/Em ratio showed a strong statistical correlation with the most sensitive indicators of heart failure, NT-proBNP. Research on larger groups of patients and the usage of even more sensitive methods as strain-rate imaging will be necessary to confirm eventual myocardial involvement in GD patients.

Backgrounds: Ebstein’s anomaly of tricuspid valve is a rare congenital heart anomaly. Surgical implantation of artefi cial tricuspid valve is a standard treatment modality. Common late complication of such surgical procedure is artefi cial valve thrombosis. Th is is a life threatening condition, which demands surgical intervention promptly. Conclusions: In following article, we describe a case of a patient with Ebstein’s anomaly and late artefi cial tricuspid valve thrombosis. Th e case was complicated with a mild form of haemophilia C, a rare coagulation disorder. Genetic analysis was also performed.

BACKGROUND Recent advances in the treatment of malign haematological deseases with chemotherapyhave led to significant improvement in prognosis and quality of life of the pacients. Thesame drugs can lead to development of serious cardiac side effects, especially the syndromeof heart failure. Anthracycline drugs are best known for their cardiotoxicity, the role ofother drugs is less well understood. CONCLUSIONS Predisposing factors to cardiotoxicity should be taken into consideration when dealingwith such pacients. Careful history, clinical examination, electrocardiography, echocardiography and NT-proBNP measurement should be performed prior and at the end of thetreatment with cardiotoxic drugs. Pacients with slightest clinical, laboratory or echocardiographic parameters of developing heart failure should immediately be reffered to a cardiologist to start with appropriate treatment

BACKGROUND Iron deficiency anemia is the most frequently encountered type of anemia and is often thecause of visit to the outpatient clinic. Besides the expected changes in complete blood count,we were interested in reactive thrombocytosis and leucopenia in analyzed patients. METHODS We retrospectively analyzed 35 patients diagnosed with microcytic anemia, that were sentto our outpatient clinic in the period of 21 months. The average age was 41 years, rangingfrom 21 to 74 years. There were 34 females and one male in the group. We only includedpatients with initial and follow-up laboratory test results that included complete bloodcount, serum iron, ferritin levels, and total iron binding capacity (TIBC). RESULTS After oral iron replacement therapy, the blood hemoglobin levels and serum ferritin levelsreturned to the normal range in all our patients. Initially, thrombocytosis was present in20/35 patients and persisted only in 4 after successful treatment. There was only one caseof initial leucopenia that was corrected with iron deficiency anemia correction. CONCLUSIONS Iron deficiency anemia is often accompanied by reactive thrombocytosis and not so oftenby leucopenia. In most cases they are transient if the treatment of iron deficiency anemia issuccessful

BACKGROUND Multiple myeloma (MM) is an incurable disease and autologous hematopoetic stem celltransplantation (HSCT) is the most effective treatment modality. It’s effectivity is evenhigher, when we treat patients with two consecutive autologous HSCT. We present ourexperiences with tandem autologous HSCT in patients with MM. METHODS During the period from 1. 1. 2003 untill 1. 11. 2007 we treated 62 MM patients. After induction therapy and stem cell collection we performed tandem autologous HSCT withinsix-month period. Treatment results were followed with biochemical parameters, monoclonal globulin peak and free light chains in serum. RESULTS Complete remission after induction was achieved in 1/62 (1,6 %) patients, after first HSCTin 6/62 (9.6 %) and after second HSCT in 24/62 (39 %) patients. Putting together CR andPR (partial remission) at three treatment steps, this was achieved in 32/62 (51 %), 51/62(82 %) and 55/62 (89 %) patients. 1/62 (1.6 %) patients died during the treatment. Meantime until relaps was 31,4 months (24.7–38.2 months; 95 % confidence interval) and forsurvival 50,2 months (44.0–56.4 months; 95 % confidence interval). Median relaps timewas 23 months (5.6–40.4 months; 95 % confidence interval), and median time for survival was not reached yet. CONCLUSIONS Treatment of MM patients with tandem autologous HSCT is highly effective treatment modality and our center’s experiences/results are comparable with other transplant centersworldwide. But in Slovenija, we must strictly perform all HSCT related investigations aswell as improve reporting all treatment related data to transplant center

BACKGROUND Yeasts of the genus Candida are among the most frequent causative agents of opportunisticinfections. In the last decades, the increased incidence of fungal infections led to increasedconsumption of antifungal agents. Our study compared the sensitivity of Candidaalbicans and Candida glabrata isolated in two time periods 1992–1996 and 2003–2005.The aim of our study was to determine whether the sensitivity of yeasts changed due toincreased consumption of antifungal agents. METHODS All isolates were isolated from surveillance specimens of patients, hospitalized in the Departmentof Hematology, University Clinical Center Ljubljana. In all yeast isolates minimalinhibitory concentrations (MIC) of fluconazole, voriconazole, itraconazole and amphotericinB were determined using the E-test. Mann-Whitney’s U test was used for statisticalanalysis. RESULTS Statistical comparison generally indicated lower antifungal drug sensitivity of yeasts inyears 1992–1996, in comparison to the period 2003–2005. MICs of all tested antifungalagents in C. albicans isolates were higher in years 1992–1996. Differences in MICs ofitraconazole and voriconazole were observed in C. glabrata isolates. MICs of itraconazolewere higher in years 1992–1996 and MICs of voriconazole were higher in years 2003–2005. However, no statistically significant differences in MICs of fluconazole and amphotericinB were observed.We have also studied the influence of antifungal prophylactic therapy on MICs of antifungalagents. For C. albicans the influence was shown for fluconazole and amphotericin B,while we could not show any influence for C. glabrata, most probably due to low number ofisolates. CONCLUSIONS According to the results of our study, the hypothesis about decreased sensitivity of yeastsdue to increased consumption of antifungal agents in the last decades was rejected

Background From 20 to 50% of patients who survive an acute episode of the acquired form of thrombotic thrombocytopenic purpura relapse but clinical and laboratory markers of recurrence are not well established.Design and Methods In 109 patients enrolled in an international registry we evaluated, in the frame of a retrospective cohort study, the predictive role of the metalloprotease ADAMTS13 as measured in plasma during remission. Anti-ADAMTS13 antibodies and von Willebrand factor were also evaluated in a smaller number of the same patients.Results Median values of ADAMTS13 activity and antigen were significantly lower in patients with recurrent thrombotic thrombocytopenic purpura than in those with no recurrence (activity: 12% vs. 41%; p=0.007; antigen: 36% vs. 58%; p=0.003). A severe deficiency of ADAMTS13 activity (10% or less) was associated with a higher likelihood of recurrence (odds ratio 2.9; 95% confidence interval 1.3 to 6.8; p=0.01). Anti-ADAMTS13 antibodies were also more prevalent in patients with recurrent thrombotic thrombocytopenic purpura (odds ratio 3.1; 95% confidence interval 1.4 to 7.3; p=0.006). The presence during remission of both severe ADAMTS13 deficiency and anti-ADAMTS13 antibodies increased the likelihood of recurrence 3.6 times (95% confidence interval 1.4 to 9.0; p=0.006). The presence of ultralarge von Willebrand factor multimers and of associated diseases or conditions did not increase recurrence.Conclusions Survivors of an acute episode of acquired thrombotic thrombocytopenic purpura with severely reduced levels of ADAMTS13 and/or with anti-ADAMTS13 antibodies during remission have an approximately three-fold greater likelihood of developing another episode of thrombotic thrombocytopenic purpura than patients with higher protease activity and no antibody.

Background. Recombinant factor VIIa can induce hemostasis and controls bleeding in surgery in hemophilia inhibitor patients and in other hemostatic disorders, e.g. thrombocytopenia, platelet function disorders, coagulation disorders due to drugs and liver disease, in trauma and surgical patients. We describe the use of rF VIIa in bleeding episodes and surgery in four hemophilia A inhibitor patients.Patients and methods. We used rF VIIa in 6 bleeding episodes and in 3 surgical procedures (intracerebral and subdural hematoma, hematoma of the sculp) in four hemophilia inhibitor patients. 90 µg/kg b.w. rF VIIa was given every 2 hours for 24–82 hours, then the time interval was gradually changed to 6 hours.The treatement duration depends on the site and severity of bleeding and surgery. The traditional assays are not suitable for monitoring the hemostatic effect of rF VIIa.Results and discussion. The reason for rF VIIa treatement were inhibitors in hemophilia, necessity for treatement for several days and surgery. In muscle, joint, gastrointestinal bleeding rF VIIa was effective but not in hematuria and thoracic wall bleeding with haemorhagic shock. The surgery itself went smoothly.Conclusions. rF VIIa controls spontaneous and posttraumatic bleedings, even the longlasting ones in hemophilia A (and B) patients with inhibitors. It prevents bleeding in major surgery. Adult patients should be treated first with standard doses of 90 µg/kg b.w. every 2 hrs for 24–48 hrs. Than time interval is gradually prologed to 6 hrs. The traditional assays are not suitable for monitoring the hemostatic effect of rF VIIa. Close monitoring is required in all patients to determine efficacy and insure safety of treatement.

Background. Essential thrombocythemia (ET) is a chronic myeloproliferative disease with a platelet count within the range of 400–2000 × 109/L. Higher percentage of platelets in the circulation of patients with ET express also activation markers on their membranes. Two of such markers are P-selectin and activated fibrinogen on platelet membranes. Because of frequent thrombembolic and also bleeding related complications, treatment of ET is mandatory. Patients whose platelet count is less than 1000 × 109/L and who did not suffer any thrombembolic complication during the course of the disease, are ussually treated with an antiaggregation drug, acetylsalicylic acid 100 mg/daily orally. Clopidogrel is an adenosyn-di-phosphate (ADP) receptor antagonist in platelets. There is no routine clinical data about clopidogrel treatment in the patients with ET and only sporadic case reports can be find in the literature.Patients and methods. In our clinical study we compared antiaggregational effects of acetylsalicylic acid and clopidogrel, by measuring the P-selectin level and activated fibrinogen expression on platelet membranes.There were 35 ET patients included, within the age range between 21 and 78 years and with platelet counts within 451–952 × 109/L. None of the patients did suffer any thrombembolic complication during the course of the disease. During the sequential 14 day periods, patients received acetylsalicylic acid 100 mg/daily orally, followed by clopidogrel 75 mg/daily orally and ultimativelly, together acetylsalicylic acid 100 mg/daily orally plus clopidogrel 75 mg/daily orally. After each fourteen days period the level of P-selectin and activated fibrinogen activated platelets were determined with monoclonal antibodies on flow cytometer. Statistical evaluation was calculated on the difference of average values between the two small, independent pair groups with the t-test.Results. When the patients stopped with acetylsalicylic acid and began with clopidogrel, the percentage of P-selectin exposure on platelet membranes was statistically significant lower (t-value 1.99; p < 0.05). We also noticed statistically significant lower P-selectin exposure in the period, during which patients received acetylsalicylic acid plus clopidogrel, versus the period, during which they received acetylsalicylic acid only (t-value 2.11; p < 0.05). But there was no statistically significant difference in P-selectin exposure within the periods, during which patients received clopidogrel versus acetylsalicylic acid plus clopidogrel (t-value 0.19; p > 0.05). Percentages of activated fibrinogen exposures on platelet membranes were in all clinical study periods comparable and no statistically significant differences between them were noticed (for each pair-relation p > 0.05).Conclusions. In patients with ET clopidogrel statistically significant (p < 0.05) lowers the percentage of P-selectin exposure on platelet membranes. Acetylsalicylic acid has no influence on P-selectin expression and also the combination of acetylsalicylic acid and clopidogrel, does not have higher P-selectin lowering efficacy, than clopidogrel itself. Acetylsalicylic acid and clopidogrel alone, nor in combination don’t have any influence on the expression level of activated fibrinogen on platelet membranes. To conclude, that clopidogrel may be an alternative to acetylsalicylic acid in patients with ET, who can not tolerate acetysalicylic acid because of it’s side-effects.

Background. Recombinant factor VIIa (rFVIIa), which is currently registered only for the treatment of haemophilia A and B patients with inhibitors, is seen increasingly as a possible universal haemostatic agent in untractable bleedings. One possible mechanism for the efficacy rFVIIa may be a consequence of it’s from the tissue factor (TF) and from the level of disfunction in haemostatic system independant activity, which generates »thrombin burst« formation. It seems that rFVIIa remains active only at the site of tissue injury/bleeding.Conclusions. There are two components of bleeding in surgery and trauma patients. One is bleeding from large calibre arteries and veins which requires surgical intervention. The other, which goes along with the first one, is coagulopathic bleeding. The latter is a consequence of consumptional and dilutional coagulopathy, hypothermia, multitransfusion syndrom and metabolic disbalances in patients. rFVIIa effects coagulopathic component of the bleeding. For effective treatment with rFVIIa in such patients, replacement therapy with erythrocytes, platelets and fresh frozen plasma is mandatory and requires a haematologist assistance in the treatment strategy.Most reported cases of effective rFVIIa usage are from the field of traumatology. Until now, there have been no universal recommendations when to start treatment with rFVIIa in a bleeding trauma patient. Most experience with rFVIIa are from Israel and their recommendations are perhaps the most valuable ones. rFVIIa was used several times during intra-operative and post-operative bleeding episodes. There are reports of clinical studies and usage in patients with/ after prostate surgery, cardiovascular operations and liver transplants.There are data about effective rFVIIa usage in neurology and neurosurgery patients (intracranial haemorrhages), obstetrics and gynecology field. Possible future indications are thrombocytopenias, thrombocytopathias (Glanzmann thrombastenia) and also bleeding episodes, as consequences of widespread anticoagulant therapy with oral anticoagulants, heparins, new pentasaccharides and lepirudin.

Background. Autoimmune cytopenias, thrombocytopenia, anemia and neutropenia, are rare but serious complications after stem cell transplantation (SCT). There are only a few reports concerning their treatment. We performed splenectomy in two patients with severe autoimmune cytopenias after allogeneic SCT resistant to immunosuppressive treatment.Patients, methods and results. First patient had unrelated alloSCT at Royal Free Hospital London for chronic granulocytic leukemia (CGL) in July 2000. Post-transplant period was complicated with cytomegalovirus reactivation and septicemia. Seven months later RBC and platelet counts went down. Direct Coomb’s test was intermittently positive. She was resistant to steroids and high dose immunoglobulin. Splenectomy was performed in February 2001. After splenectomy hemoglobin concentration and platelet count improved. Her blood counts remained stable with hemoglobin about 110 g/L and platelets over 100 x109/L. She continued therapy with Itraconazol, Valacyclovir and Penicillin. Three months later she was readmitted for E. Coli fulminated septic infection with fatal outcome.Second patient had related alloSCT at University Medical Centre Ljubljana for CGL in January 2003. Post-transplant course was uneventful. Seven months later he was readmitted for retinal bleeding with severe thrombocytopenia with positive anti-platelet antibodies. He was resistant to steroids and high dose immunoglobulin. Splenectomy was performed in September 2003. His platelet count normalized and remains stable so far. He continues therapy with Itraconazol, Valacyclovir and Penicillin and didn’t experience any serious infection.Conclusions. We assume that splenectomy is an efficient treatment for resistant immune cytopenias after alloSCT. However, severe late infections may compromise the outcome.

Background. Invasive aspergillosis is the most f requent and the most greatly feared infectious complication in neutropenic hematological patients. In order to prevent exogeneous aspergillus infection in such patients, their environment should be as free as possible from aspergillus spores, i.e. considerably below 1,0 CFU/m3.Methods. With the air sampling at different points of Haematology Department in the Ljubljana Clinical Center we wished to compare concentration of spores of Aspergillus spp. and to define an efficacy of hygienic-sanitary measures at those points.Results. Air sampling revealed that there is no essential difference in concentration of spores of Aspergillus spp. between external and internal air and also among different spaces at Haematology Department. The concentration of spores of Aspergillus spp. varied between 0.0 and 19.2 CFU/m3.Conclusions. Concentrations of spores of Aspergillus spp. in different units of Haematology Department are extremely high and unacceptable. This is probably the consequence of the different external and internal environment factors. However, we may conclude that the most influential factor is unfiltered air.

Background. Vincristin is an important and frequently used chemoterapeutic drug in the treatment of malignant lymphoproliferative disease. Among its side effects are well known bone marrow supression and polyneuropathia. But common physicians are not familiar with vincristine bowel peristaltics inhibitory effect.Patient and methods. This study presents 64-years old patient with acute lymphoblastic leukemia (ALL) who was treated with chemotherapy which included vincristine. Two weeks after the treatment started paralytic ileus developed which was later sucessfully treated with laxatives and prokynetic drugs. Secondary causes for ileus development were excluded. Literature data was reviewed and a higher incidence of paralytic ileus in vincristine treated patients was found, especially when they are given concomitant itraconazole. Our patient received concommitant itraconazole as a part of antifungal prophylaxis against invasive aspergillosis which is a perceived routine on hematological departments.Conclusions. Vincristine treated patients should be carefully observed regarding bowel peristaltics and obstipation. If obstipation or even paralytic ileus developes, we must stop vincristine therapy. All patients receiving vincristine must receive fluconazol instead of itraconazol as a part of antifungal prophylaxis.

Background. Beside greater susceptibility to infections, acute graft host disease is a consequence of the activation of donor T-cells against host antigens. Most common target organs are skin, liver and intestinal mucosis.Methods. In the 6-year period between January 1995 and December 2000, 49 patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT) in Transplant unit, Department of Hematology, Clinical Centre Ljubljana. The standard GVHD prophylaxis regimen consisted of cyclosporine and short-course methotrexate. Severe, grade III-IV aGVHD with skin and/or gastrointestinal and/or liver involvement appeared in 16 (32%) of the 49 patients.Results. Among the 16 patients with severe aGVHD, 14 had liver involvement, ten gastrointestinal and eight skin involvement. One patient had skin involvement only, the rest of them had combined involvement of two or three organ systems. Routine first-line treatment for aGVHD, given to all 16 pts with severe forms of the disease, was methylprednisolone (MP) 2mg/ kg. Six patients with predominant skin involvement responded to MP. Other ten patients with mainly liver and gastrointestinal involvement needed second or even third line aGVHD treatment. These were anti-thymocyte globulin (ATG) and/or monoclonal antibodies (OKT3) and/or mycophenolate mofetil (MMF) and/or FK506 (tacrolimus). Seven patients died of advanced aGVHD and treatment related infection.Conclusions. Based on our experiences, we conclude that in critically ill patients with severe aGVHD, neutropenia and high risk for opportunistic infection, each day of ineffective MP therapy may have fatal consequences. Simultaneous institution of a combination of corticosteroids and a second-line drug might prove more appropriate for patients with a severe form of aGVHD.

Background. Treatment of thrombotic thrombocytopenic purpura (TTP) with plasma exchange (PE) has reduced mortality rates from 90% in untreated patients to less than 20%. Despite primary effective PE, relapses occur in up to 40% of patients. Beside PE, second line treatment options are corticosteroids, vincristine, defibrotide, prostacycline. We describe two patients with relapsing TTP treated successfully with splenectomy.Patients and methods. Case 1. A 20–year female was diagnosed in October 2000 with idiopathic chronic relapsing TTP. First episode of PE plus methylprednisolone treatment led to complet remission. Subsequent relapses occured 3, 6 and 8 months after first TTP episode. Every relaps was effectivelly treated with PE and methylprednisolone. Because of more and more frequent TTP relapses laparoscopic splenectomy was performed. Currently, 7 months after splenectomy she is in complet TTP remission.Case 2. A 18–year female, was diagnosed in January 1997 with idiopathic TTP. After PE and methylprednisolone complete remission was established. Relaps occured after nearly three years. Later on, TTP got chronic course with neurological clinical symptoms and plateled drops as soon as PE treatment was withdrawn. Besides PE and methylprednisolone she received also defibrotide. Because of chronic, PE dependant TTP, laparoscopic splenectomy was performed. Today, 15 months after splenectomy she is in complete TTP remission.Conclusions. In idiopathic relapsing and chronic TTP, PE treatment only is usually not sufficient for durable remission. Second line TTP treatment drugs have limited efficacy. Based on our experience in patients with relapsing and/or chronic TTP, laparoscopic splenectomy should be considered as a first treatment option, especialy in junger patients.

Background. ALL is a malignant blood disease and lymphoblasts have origin in B or T lymphatic cell line. In 1997 established new World Health Organisation classification (WHO classification) of malignant haematological diseases realizes the importance of cellular immunological markers (immunophenotype) and chromosomal abnormalities (cytogenetics). Based on both findings we may distribute the patients in low, intermediate and high risk groups and the outcome of such distribution is risk adopted ALL treatment strategy. On Clinical department of haematology (CDH) we have decided to overview immunophenotype characteristics of all ALL patients during the January 1, 1995–December 31, 2001 period.Methods and results. During the January 1, 1995–December 31, 2001 period on CDH we have treated 44 patients: 22 males and 22 females. With flow cytometer Coulter Epics XL MCS we have performed first primary antibody panel for acute leukemias antigens (CD2, CD7, CD10, CD19, CD34, cCD3, cCD13, cCD22, MPO, TdT), followed by secondary panel. The later have included antigen CD20, CD23, membrane and/or cytoplasmatic immunoglobulins or their light chains monoclonal antibodies for B-ALL and antigen CD3, CD4, CD5 and CD8 monoclonal antibodies for T-ALL subsets. Besides immunophenotyping we have evaluated all ALL patients also morphologically according to FAB classification (French-AmericanBritish classification), which is an old classification based solely on morphology.32/44 (73%) patients have had immunophenotypic B-ALL, and 12/44 (27%) T-ALL. Subgroups distribution of B-ALL immunophenotype were: pro-B 4/44 (9%), »common«-B 18/44 (41%), pre-B 5/44 (11.5%) and mature B 5744 (11.5%) and for T-ALL immunophenotype were: pro-T 2/44 (4.5%), pre-T 5/44 (11.5%), cortical-T 4/44 (9%) and mature-T 1/44 (2%). Our results are quite comparable with the available data from the literature, despite the fact that newest immunological markers such as CD1a, CD79a and CD22 were not available until last year.ALL morphology does not determine ALL immunophenotype, with the exception of L3 subtype, which usually coincidences with mature B immunophenotype. The commonest morphological variant is L2 subtype, which we have seen in 35/44 (80%) patients and was equally distributed among B and T immunophenotypic subgroups.Conclusions. Determination of ALL immunophenotype is one of the cruical tests for the evaluation of long-term ALL prognosis. Because of the later, every newly diagnosed ALL must be immunophenotyped. Immunophenotype is not the only ALL prognostic factor, but in combination with the others such as cytogenetics, patients age, leukocyte count at diagnosis, we can put together »ALL prognostic mosaic«, followed by an optimal ALL treatment strategy.