Profilaktyka zakażeń grzybiczych u dzieci poddawanych transplantacjom komórek hematopoetycznych

Invasive fungal infections (IFI) remain a very important cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT) in children. The recent study from Polish pediatric transplant centers revealed that 27.3% of children transplanted in 2012–2013 developed IFI. The highest risk was observed among patients with AML and ALL after allogeneic HSCT. Such results warrant the use of extensive antifungal prophylaxis in this cohort of patients. ECIL-4 guidelines for antifungal prophylaxis in children undergoing HSCT along with clinical practice are presented in the review. Furthermore preventive measures for patients discharged home after HSCT are discussed.     

Zakażenia wirusowe po transplantacji komórek krwiotwórczych

Infections remain one of the most serious problems in patients undergoing stem cell transplantation. With the progress concerning transplant techniques and the supportive treatment we observe decrease in the incidence of infectious complications early after transplant with extended duration and risks later. Viral infections constitute the specific group of complications, strictly related to the immunological reconstitution after the transplantation. Most often appearing infections caused by viruses of Herpesviridae family together with currently binding recommendations concerning the diagnostics, the prevention and the treatment are discussed in the paper.     

Diagnostyka i różnicowanie późnych nieinfekcyjnych powikłań płucnych u chorych po transplantacji allogenicznych komórek krwiotwórczych

The role of pulmonary function monitoring after allogeneic haematopoietic stem cell transplantation and the prognostic significance of detected airflow impairment are discussed by the authors. The purpose of the work is also to clarify the nomenclature and diagnostic criteria of non-infectious pulmonary complications after allotransplant. The incidence and diagnostic criteria of representative conditions, as bronchiolitis obliterans and cryptogenic organizing pneumonia are presented. The significance of radiologic findings, bronchoscopy and lung biopsy in diagnostic strategy is also discussed. We believe that the presented review of the current multidisciplinary knowledge on late non-infectious pulmonary complications in patients after stem cell transplantation may be useful in improving the quality of long-term care of those patients.     

Leczenie zespołów mielodysplastycznych wysokiego ryzyka u dorosłych wg rekomendacji European LeukemiaNet

High-risk myelodysplastic syndromes (MDS) are defined by patients who fall into Intermediate-2 or High-risk group categories in the International Prognostic Scoring System or High/Very high in the revised IPSS (R-IPSS). High-risk MDS carry a major risk of progression to acute myeloid leukemia and short survival. Standard therapies include allogeneic stem cell transplantation, induction therapy (AML-like) and hypomethylating agents. This article presents recent European LeukemiaNet recommendations for treatment of high-risk MDS.     

Wskazania do transplantacji komórek krwiotwórczych u dzieci i młodzieży – rekomendacje Polskiej Pediatrycznej Grupy ds. Transplantacji Komórek Krwiotwórczych – 2014

This article presents the current recommendations from the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation concerning the indications for hematopoietic stem cell transplantation (HSCT) in children and adolescents suffering from hematological malignancies, solid tumours, and congenital or acquired non-malignant disorders. Indications for HSCT are established in context of the recent results of conventional treatment, i.e. obtained with non-HSCT strategies; it means transplantation is justifiable exclusively, when it significantly increases individual patient's chances to be cured, despite of the risk of HSCT-related mortality. Hence, due to the advances of non-transplant treatment strategies as well as progress in the field of HSCT the indications for HSCT require to be regularly up-dated. The recommendations presented in this article are based on the current guidelines from the European Group for Blood and Bone Marrow Transplantation (EBMT), including those from the EBMT Pediatric Diseases Working Party and the EBMT Inborn Errors Working Party, and from the international treatment protocols currently applied in the centers of the Polish Pediatric Leukemia/Lymphoma Study Group and Polish Pediatric Solid Tumours Study Group. The recommendations are addressed not only to the Polish pediatric transplant centers, but first of all to the Polish pediatric centers involved in diagnostics and treatment of the malignancies and non-malignant disorders in children and adolescents with non-transplant strategies, because it is their responsibility to identify as soon as possible indications for HSCT and refer patient at the appropriate time to pediatric transplant center.     

Osoczowe stężenie cytokin limfo-i angiogennych u chorych na chłoniaka rozlanego z dużych komórek B

Angiogenesis and lymphangiogenesis play an important role in the development of diffuse large B-cell lymphoma (DLBCL). Above phenomena are controlled by a number of cytokines among them the most important are vascular endothelial growth factor family members (VEGF), their receptors (VEGF-R) and basic fibroblast growth factor (bFGF). The aim of this study was to evaluate the plasma level of VEGF-C, VEGF-D, VEGF-R3 and bFGF in 55 patients with DLBCL before treatment as well as after chemotherapy with R-CHOP protocol. Control group consisted of 30 healthy subjects. The concentration of VEGF-R3 was significantly higher in patients before treatment than in control group. Concentrations of VEGF-R3 and VEGF-C were significantly higher in patients with higher risk (IPI 3-5) than in subjects with lower risk (IPI 0-2). Additionally, VEGF-R3 was positively correlated with β₂-microglobulin, whereas VEGF-D was correlated positively with LDH and β ₂-microglobulin, and negatively with platelets count and serum albumins concentration. We found no statistical differences between cytokine values after treatment as compared to initial ones. However, our results do not indicate a predictive value of the cytokines studied regarding the issue of DLBCL therapy, they may suggest a role of some lymphangiogesis-involved factors in the disease activity.     

Ocena znaczenia ekspresji błonowej dipeptydylo-peptydazy IV na komórkach hematopoetycznych u chorych ze szpiczakiem plazmocytowym poddawanych mobilizacji komórek krwiotwórczych

Dipeptidyl peptidase IV is a membrane enzyme involved in intracellular interactions governing processes. Proven its effects on engraftment the transplanted allogeneic hematopoietic cells. The aim of this study was to analyze the expression of CD26 in the mobilization of hematopoietic cells for auto-transplantation in multiple myeloma patients. In 30 patients, who, during the 2011–2012, underwent the mobilization of hematopoietic cells, CD26 was determined on CD34 positive cells as well as on lymphocytes, monocytes and granulocytes, before mobilization procedures, as well as on the cells obtained after separation on cell separator. We found a statistically significant increase in the number of mononuclear cells expressing CD26, non-expression of CD26 on granulocytes, both before and during the mobilization procedures. Additionally we found a week expression of CD26 on CD34 positive cells. The obtained results seem to indicate an important role of bone matrix cells expressing CD26 in the process of mobilization of hematopoietic cells in myeloma multiplex patients.     

Postępy w leczeniu chłoniaka Hodgkina u dzieci i młodzieży

Currently over 90% children and adolescents with Hodgkin's lymphoma (HL) can be cured. In the recent 25 years successive improvement of results of treatment was achieved through proper choice of treatment intensity according to precisely defined risk groups. The current strategy of diagnosis and treatment of HL is aimed at balancing between the highest possible cure rates and risk of late complications. On the basis of 40-year experience of Polish Pediatric Leukemia/Lymphoma Study Group and recent data from literature we review current and planned strategies of therapeutic management aimed for improving results of treatment in patients with poor prognosis and reducing rates of late complications in all patients with HL. Currently further reduction of radiotherapy use is considered through limiting its use in the patients with satisfactory results after initial chemotherapy evaluated with the use of positron emission tomography results. Further improvement of therapeutic strategy for HL calls associating individual oncological centers in large groups, which would cooperate in completing research projects.     

Wpływ cytotoksyczny R-amfinazy,endorybonukleazy o działaniu przeciwnowotworowym,na komórki chłoniaka rozlanego z dużych komórek B w warunkach in vitro

Onconase (ONC) and R-Amphinase (R-AM) are enzymes with anti-tumor activity, belonging to pancreatic ribonuclease A family, received from eggs collected from frog Rana pipiens. Both proteins can induce death of some types of neoplastic cells by inhibition of protein synthesis, cell growth and proliferation. The aim of this study was to assess the cytotoxicity of R-AM, used alone or in combination with one of the most active anti-leukemic drug, doxorubicin (DOX), on diffuse large B-cell lymphoma (DLBCL)-derived cell line, Toledo. We found high cytotoxic activity of R-AM against DLBCL cells as well as influence on expression of several apoptosis-regulating proteins. Moreover, we observed increase in proapoptotic activity after combination of R-AM and DOX, compared with both drugs used alone. These results may justify further studies on interactions of R-AM with other drugs active in DLBCL.     

Wczesna niehematologiczna toksyczność po chemioterapii w wysokich dawkach i autologicznym przeszczepieniu komórek krwiotwórczych u chorych na nowotwory limfoidalne powyżej 60. roku życia

Early non-haematological toxicity of high dose therapy (HDT) and autologous haematopoietic cell transplantation (autoHCT) can be more hazardous in older patients (pts) with comorbidities. The aim of the study was to analyze incidence and grade of the organ-related early complications up to 30 days post-transplant period in elderly lymphoma patients. Between January 2005 and November 2011, 44 consecutive lymphoma pts underwent HDT followed by autoHCT. Median age of pts was 62 years (range 60–67). Conditioning regimens were: BEAM(carmustine, etoposide, cytarabine, melphalan) in 16, melphalan 200 in 22, cytarabine, melphalan or cyclophosphamide – in 6 pts. 32% pts had comorbidities: in 71% cardiovascular. Early non-haematologic complications within 30 days after autoHCT were reported in 84% of pts. The most common events were gastrointestinal (77%): 55% pts had prolonged (more than 7 days) diarrhoea grade III—IV, nausea and vomiting occurred in 40% of pts, 50% of pts demonstrated mucositis (grade III—IV in 34% of pts). Neutropenic fever was reported in 59% of pts with sepsis in 1.9% of pts. Cardiac events occurred in 9% of pts. Median hospitalization was 21 days (range 16—45). One patient died from transplanted related toxicity. HDT resulted in high incidence of non-hematologic toxicity in elderly patients during early post-transplant period. The toxicity of this procedure is acceptable, with mortality rate of only 2% in the elderly transplanted patients. The most common toxicities were: neutropenic fever, gastrointestinal toxicity and cardiac complications     

Stare i nowe czynniki ryzyka zakrzepicy u chorych z nadpłytkowością samoistną

Essential Thrombocythemia (ET) is one of the classical Philadelphia negative myeloproliferative neoplasms. Despite the chronic course of the disease, the ET patients had an inferior survival compared to the general population, because of higher mortality, mainly due to thrombotic complications. Besides well known old risk factors, such as old age (>60 year) and previous history of thrombosis, still some new ones appeared. In 2005 the JAK2V617F point mutation was found in 50-60% of ET patients. An increased risk of thrombosis in patients with this mutation has been reported. In this study there is a summary of old and new risk factors which may contribute to thrombotic complications in ET patients.     

Profilaktyka i leczenie zakażeń u chorych na przewlekłą białaczkę limfocytową

Infections have a significant impact on the clinical course of chronic lymphocytic leukemia and are the leading cause of patients’ death. Severe and recurrent infections are associated with impaired immunity connected with the pathogenesis of the disease, older age of patients and immunosuppressive therapy. The infections caused by encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae) dominate in untreated patients, while in patients under therapy, infections are caused by Staphylococcus aureus and Gram-negative bacteria such as: Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae, opportunistic infections are also frequent. It is important not only to treat the infections, but also their appropriate prevention. The article discusses various methods for prevention of infections, including vaccinations.