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Introduction: Multiple myeloma is the third most common blood cancer in Europe and accounts for approx. 10-15% of these cancers. The objective of this study was to determine the incidence, prevalence, mortality and survival in multiple myeloma (ICD code: C90.0) patients in Poland in the years 2008-2017. Material and methods: The analysis used the data on healthcare services provided to patients with multiple myeloma defined with the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) code C90.0 and reported by healthcare entities to the National Health Fund (NFZ). Results: In 2009, the C90.0 incidence per 100,000 inhabitants was 6.4, while in 2017 it was 8.3. The prevalence in the same period increased by 76%, from 13.6/100,000 to 23.9/100,000. The mortality to prevalence ratio gradually decreased from 78% in 2008 to 22.8% in 2017. The 1-year, 3-year and 5-year survival rates in patients with this diagnosis made in the years 2009 and 2013 were 70.5%, 51.5% and 40.2% versus 78.4%, 60.3% and 48.3%, respectively. Conclusions: The incidence and prevalence of multiple myeloma and survival rates in Poland were continuously increasing in the studied period. These trends may result from the aging of Polish society, better recognisability of multiple myeloma and/or improved access to increasingly more effective therapies in Poland. The impact of these factors on the epidemiology of multiple myeloma requires further studies. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of malignant hematopoietic stem cell disorders that are characterized by ineffective blood cell production and a variable risk of transformation into acute myeloid leukemia. In recent years, significant progress in MDS biological research has allowed the addition of new drugs to the few existing therapeutic options. This article presents the recommendations of MDS experts of the Polish Adult Leukemia Group for the treatment of myelodysplastic syndromes, and for the management of conditions that are particularly common in patients with MDS i.e. infections, iron overload, and disease recurrence after hematopoietic cell transplantation. The aim of this study was to present a clear therapeutic algorithm to facilitate decision-making in everyday practice. [ABSTRACT FROM AUTHOR]

Recent developments in the field of targeted therapy have led to the discovery of a new drug, plerixafor, that is a specific inhibitor of the CXCR4 receptor. Plerixafor acts in concert with granulocyte colony-stimulating factor (G-CSF) to increase the number of stem cells circulating in the peripheral blood (PB). Therefore, it has been applied in the field of hematopoietic stem cell mobilization. We analyzed retrospectively data regarding stem cell mobilization with plerixafor in a cohort of 61 patients suffering from multiple myeloma (N = 23), non-Hodgkin's lymphoma (N = 20), or Hodgkin's lymphoma (N = 18). At least one previous mobilization attempt had failed in 83.6% of these patients, whereas 16.4% were predicted to be poor mobilizers. The median number of CD34+ cells in the PB after the first administration of plerixafor was 22/μL (range of 0-121). In total, 85.2% of the patients proceeded to cell collection, and a median of two (range of 0-4) aphereses were performed. A minimum of 2.0 × 10(6) CD34+ cells per kilogram of the patient's body weight (cells/kg b.w.) was collected from 65.6% of patients, and the median number of cells collected was 2.67 × 10(6) CD34+ cells/kg b.w. (0-8.0). Of the patients, 55.7% had already undergone autologous stem cell transplantation, and the median time to neutrophil and platelet reconstitution was 12 and 14 days, respectively. Cases of late graft failure were not observed. We identified the diagnosis of non-Hodgkin's lymphoma and previous radiotherapy as independent factors that contributed to failure of mobilization. The current report demonstrates the satisfactory efficacy of plerixafor plus G-CSF for stem cell mobilization in heavily pre-treated poor or predicted poor mobilizers. [ABSTRACT FROM AUTHOR]

Objectives: Human herpesvirus 7 (HHV-7) is spread worldwide and has been described as a potential pathogen in immunosuppressed patients. Different clinical manifestations have been described including fever and skin rash; HHV-7 may also be a possible cofactor for cytomegalovirus disease in transplant recipients. Materials and Methods: A retrospective review of a group of 58 adult recipients of allogeneic hemopoietic stem cell transplantation was made. Serum samples taken in the range of 0-180 days after transplant were examined for presence of specific HHV-7 sequences using the quantitative real-time PCR method. Results: HHV-7 DNA was detected in plasma samples in 26 (45%) of the 58 recipients between day 20 and day 65 of transplantation. All of them developed fever of unknown origin; also HHV-5 DNA was detected in plasma samples collected from 11 HHV-7-positive patients. None of the described individuals died during detectable HHV-7 or HHV-5 viremia periods. Conclusions: There is a high frequency of detectable HHV-7 viral load in allogeneic stem cell transplant recipients in Poland. Limited availability and sensitivity of serological methods along with the necessity of rapid introduction of antiviral treatment has forced the development of molecular diagnostics. Furthermore, establishment of appropriate procedures for monitoring active HHV-7 infection is important to clarify the virus infection in transplant recipients. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Gut colonization with antibiotic-resistant bacteria (ARB) is associated with a significantly decreased overall survival in adult patients undergoing allo-HCT because of an increased treatment-related mortality. Objective: The objective of this multicenter study was the analysis of impact of gut colonization status and the use of antibiotics on development of gastro-intestinal (GI) graft-versus-host disease (GVHD) of allo-HCT in children. Methods: All consecutive patients who underwent allo-HCT over a period of three years in all pediatric HCT centers in Poland were analyzed for the impact of gut colonization on GI GVHD, with respect to standard of care including prophylaxis of infections and supportive therapy. Results: At the time of allo-HCT, 44.2% of pediatric patients were colonized by ARB. Decontamination therapy with antibiotics was applied in 78% of children. Gut decontamination prophylactic therapy with antibiotics decreased the risk of acute GI GVHD. The use of gentamicin contributed to decreased rate of GVHD, while the use of ciprofloxacin and colistin contributed to increased incidence of GVHD after allo-HCT in children. Sepsis with ARB and non-MFD transplant contributed significantly to worse survival, while neither colonization nor gut decontamination had an impact on overall survival. Conclusions: Gut decontamination therapy contributed to lower incidence of acute GI GVHD in children undergoing allo-HCT, and the use of specific antibiotics might be responsible for this effect. [ABSTRACT FROM AUTHOR]

Salvage autologous hematopoietic stem cell transplantation (auto-HSCT) constitutes a therapeutic option for a group of well-selected patients with relapsed multiple myeloma (MM). However, if an insufficient number of stem cells were harvested and stored before the first auto-HSCT, stem cells need to be remobilized. Patients diagnosed with MM who following relapse after auto-HSCT, had remobilization and afterward, auto-HSCT with remobilized cells were included in this retrospective analysis. Thirty-three patients, 61% males, the median age 61 years, were included. With a median follow-up of 1.8 years, 2-year progression-free survival was 56.2%, non-relapse mortality 4.8%. The 2-year cumulative incidence of t -MDS was 4.9%. Factors important for the outcome were: the quality of response, previous radiotherapy, the time between the first and salvage auto-HSCT. To conclude, salvage auto-HSCT performed with cells procured after the previous auto-HSCT can be efficacious in relapsed MM, especially if a sufficiently long response had been obtained to the first auto-HSCT(s).

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) genes occur in about 20% patients with acute myeloid leukemia (AML), leading to DNA hypermethylation and epigenetic deregulation. We assessed the prognostic significance of IDH1/2 mutations (IDH1/2 + ) in 398 AML patients with normal karyotype (NK-AML), treated with daunorubicine + cytarabine (DA), DA + cladribine (DAC), or DA + fludarabine. IDH2 mutation was an independent favorable prognostic factor for 4-year overall survival (OS) in total NK-AML population (p = 0.03, censoring at allotransplant). We next evaluated the effect of addition of cladribine to induction regimen on the patients' outcome according to IDH1/2 mutation status. In DAC group, 4-year OS was increased in IDH2 + patients, compared to IDH-wild type group (54% vs 33%; p = 0.0087, censoring at allotransplant), while no difference was observed for DA-treated subjects. In multivariate analysis, DAC independently improved the survival of IDH2 + patients (HR = 0.6 [0.37-0.93]; p = 0.024; censored at transplant), indicating that this group specifically benefits from cladribine-containing therapy. In AML cells with R140Q or R172K IDH2 mutations, cladribine restrained mutations-related DNA hypermethylation. Altogether, DAC regimen produces better outcomes in IDH2 + NK-AML patients than DA, and this likely results from the hypomethylating activity of cladribine. Our observations warrant further investigations of induction protocols combining cladribine with IDH1/2 inhibitors in IDH2-mutant.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole potential cure for paroxysmal nocturnal hemoglobinuria (PNH); however, the data on its utility in PNH are limited. This retrospective analysis of patients with PNH who underwent allo-HSCT in 11 Polish centers between 2002 and 2016 comprised 78 patients with PHN, including 27 with classic PNH (cPNH) and 51 with bone marrow failure-associated PNH (BMF/PNH). The cohort was 59% male, with a median age of 29 years (range, 12 to 65 years). There was a history of thrombosis in 12% and a history of hemolysis in 81%, and 92% required erythrocyte transfusions before undergoing allo-HSCT. No patient received eculizumab, and 26% received immunosuppressive treatment. The median time from diagnosis to allo-HSCT was 12 months (range, 1 to 127 months). Almost all patients (94%) received reduced-toxicity conditioning, 66% with treosulfan. The stem cell source was peripheral blood in 72% and an identical sibling donor in 24%. Engraftment occurred in 96% of the patients. With a median follow-up of 5.1 years in patients with cPNH and 3.2 years in patients with BMF/PNH, 3-year overall survival (OS) was 88.9% in the former and 85.1% in the latter (P = not significant [NS]). The 3-year OS for patients with/without thrombosis was 50%/92% (P = NS) in the cPNH group and 83.3%/85.3% (P = NS) in the BMF/PNH group. The 3-year OS for in the BMF/PNH patients with/without hemolysis was 93.9%/62.9% (hazard ratio, .13; P = .016). No other factors impacted OS. After allo-HSCT, the frequency of the PNH clone was reduced to 0%, <1%, and <2.4% in 48%, 48%, and 4% of cPNH patients and in 84%, 11%, and 5% of BMF/PNH patients, respectively. The frequency of acute graft-versus-host disease (GVHD) grade II-IV was 23%, and the cumulative 1-year incidence of extensive chronic GVHD was 10.8% in the BMF/PNH group and 3.7% in the cPNH group. Allo-HSCT is a valid option for PNH patients, effectively eliminating the PNH clone with satisfactory overall survival and acceptable toxicity. Reduced-toxicity conditioning with treosulfan is effective and safe in patients with cPNH and BMF/PNH., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Multiple myeloma (MM) has become a chronic disease in majority of patients, and remission consolidation with autologous hematopoietic stem cell transplant (ASCT) remains the backbone of treatment in transplant-eligible patients., Objective: The aim of this multicenter cross-sectional nationwide retrospective study was to evaluate the epidemiology, etiology, and outcome of infections in patients with MM undergoing ASCT in 13 Polish transplant centers, carried out on behalf of the Infectious Complications Study Group of the Polish Adult Leukemia Group., Methods: A total number of consecutive 1374 patients with MM treated in Polish adult transplant centers from 2012 to 2014 were followed for infectious complications up to day +100 after ASCT in nationwide study., Results: Altogether 490 infection episodes in 336 patients (49% male, aged 21-72 years) were reported, including 145 episodes of neutropenic fever (103 patients) and 34 episodes of clinically documented infections (CDIs) (27 patients). Among microbiologically confirmed infections there were 251 episodes of bacterial infections (180 patients), 42 episodes of fungal infections (38 patients), and 18 episodes of viral infections (17 patients). The overall incidence of infections reached 13.1% for bacterial, 3.6% for fungal, and 1.3% for viral infections. There were 16 cases of infection-related deaths after ASCT (1.2%). The mortality risk factors included multidrug-resistant bacteria etiology (odds ratio [OR], 3.5; P = .033), coexistence of bacterial and fungal infection (OR, 6.3; P = .002), and CDI (OR, 5.5; P = .007)., Conclusion: ASCT in patients with MM was connected with low risk of life-threatening infections. However, multidrug-resistant bacteria bacterial etiology, mixed etiology, and CDI increased the risk of fatal outcome., (Copyright © 2020 Elsevier Inc. All rights reserved.)

BACKGROUND The most common etiological agents of infections in onco-hematological patients are Gram-negative rods resistant to many antimicrobials, including carbapenems. Recently, ceftolozane combined with tazobactam became a novel therapeutic option. The aim of the present study was to analyze the susceptibility to ceftolozane/tazobactam of the clinical strains of these bacteria. MATERIAL AND METHODS Material comprised rectal swabs, urine, and bronchoalveolar lavage fluid obtained from onco-hematological patients hospitalized in a clinical hospital (1050 beds) in Poland. Identification of the isolated bacteria was done by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using the MALDI Biotyper (Bruker). Ceftolozane/tazobactam susceptibility of the isolates was assessed using antimicrobial gradient strips (E-test, BioMérieux). Antimicrobial susceptibility testing and interpretation of the results was done according to the current recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). RESULTS In total, 281 rectal swabs and 116 urine samples were tested for the presence of Gram-negative rods producing ESBL, and 531 rectal swabs and 8 bronchoalveolar lavage fluid samples were tested for the presence of Gram-negative rods resistant to carbapenems. In the analyzed period, 69 non-repetitive strains of bacteria were isolated that were in the spectrum of activity of ceftolozane/tazobactam. Among 44 clinical strains of ESBL(+) Enterobacteriaceae rods, 76% were susceptible to ceftolozane/tazobactam. All 9 strains of non-carbapenemase-producing P. aeruginosa resistant or with decreased susceptibility to carbapenems were susceptible to ceftolozane/tazobactam. CONCLUSIONS Ceftolozane/tazobactam may be an option in the therapy of infections caused by ESBL(+) strains of Enterobacteriaceae as well as non-carbapenemase-producing carbapenem-resistant strains of P. aeruginosa.

Introduction: Dialysis-dependent (DD) multiple myeloma patients (MM) have a poor prognosis and high tumour burden, thus may benefit from autologous peripheral blood stem cell transplantation (auto-PBSCT), however, these patients have an increased risk of toxicity., Aims: To evaluate the outcomes (toxicity, PFS, OS) of high dose therapy followed by auto-PBSCT during an observational study and after propensity score matching., Patients and Methods: Between 2004-2015, 24 DD patients, (aged 38-67 years), ISS 3, treated with auto-PBSCT, requiring dialysis at diagnosis and auto-PBSCT were evaluated, matched and compared to 55 normal renal function MM patients (NRF) with ISS 3 for outcomes of interest., Results: In DD patients compared to NRF patients risk of mucositis (88% vs 55%), infection (79% vs 51%), parenteral nutrition (50% vs 24%), diarrhoea (71% vs 38%), prolonged duration of hospitalisation (medians: 30 vs 21 days), requirement for RBC transfusion (83% vs 36%) were significantly higher, while no significant differences were found in post-transplant response (ORR; 75% vs 87%), 5-year PFS (36% vs 20%) and OS (39% vs 50%). Subgroup analyses based on toxicity supported these results., Conclusions: Despite the increased risk of toxicity in DD patients these events do not significantly affect both the PFS and OS., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Human adenoviruses (HAdV) are important viral pathogens recognized increasingly in immunocompromised hosts, especially in allogeneic haematopoietic stem cell transplant recipients (alloHSCT). The clinical spectrum of HAdV disease ranges from asymptomatic viraemia and mild self-limiting disease to lower respiratory tract infection, multi-organ involvement and even death. Early detection and quantification of HAdV in peripheral blood using real-time PCR (qPCR) assay has been suggested as a useful monitoring tool, but is seldom used for regular surveillance of HAdV in haematology centers. A group of 112 alloHSCT recipients from two hospitals in Warsaw (Poland) was examined in the early post-transplant period using a quantitative qPCR assay. A total of 1,245 serum samples were evaluated for presence of HAdV DNA in patients where 66 (59 %) patients received grafts from unrelated donors whereas the other 46 (41 %) from sibling donors. HAdV sequences were detected in 64 (57 %) of the 112 patients. In 22 of all patients (20 %) HAdV DNA was detected only in a single positive sample, while 42 (37 %) had positive results in two or more subsequent sera. In total, DNAemia was present in 202 sera samples (16 %) with median time to observation of 47 days. Graft-versus-host disease (GvHD) was observed in 18 (28 %) adenovirus-infected transplant recipients and a significant correlation between HAdV infections and GvHD clinical presentation was found (p = 0.018). There is a high prevalence of HAdV infections in HSCT recipients in Poland during early post-transplant period. In consequence, we could only speculate if HAdV DNAemia could be also related to GvHD symptoms, enforcing the important pathogenic role of these viral infections in clinical complications post-alloHSCT.

Human herpesvirus 7 (HHV-7) is widespread around the world and may also be a possible cofactor for cytomegalovirus (CMV) infection in haematopoietic stem cell transplant (HSCT) recipients. In case of viral diseases where specific treatment is available, real-time PCR assays constitute reliable diagnostic tools enabling timely initiation of appropriate therapy and rapid assessment of the efficacy of antiviral treatment strategies. The presence of CMV and HHV-7 was confirmed by the detection of viral DNA isolated from 1,027 plasma samples. A group of 69 allogeneic HSCT (alloHSCT) recipients was examined in early post-transplant period using quantitative real-time PCR methods. Within the study period, 62 % of patients had at least once CMV DNA-emia, while HHV-7 DNA was found in 43 % of subjects. Co-infection between these β-herpesviruses was detected in the plasma samples collected from 18 patients (26 %). Patients with concomitant HHV-7 DNA-emia had significantly higher number of CMV DNA copies compared with those without HHV-7 infection (1986 vs. 432 copies/ml, p < 0.001) but there was no difference in duration of CMV DNA-emia between these groups. On the other hand, while the load of HHV-7 DNA was comparable between patients with CMV DNA-emia and without CMV DNA-emia, the duration of HHV-7 DNA-emia was significantly longer in the first group (38.5 vs. 14 days, p < 0.001). HHV-7 DNA-emia is very frequently detected in Polish alloHSCT recipients. In those, who have subsequent CMV reactivation, the coexistence of the viruses may negatively affect the kinetics of infection with either of them. Therefore the investigation of concomitant HHV-7 DNA-emia could affect the prognosis of post-transplant patients suffering from CMV reactivation.

Objectives: Human herpesvirus 7 (HHV-7) is spread worldwide and has been described as a potential pathogen in immunosuppressed patients. Different clinical manifestations have been described including fever and skin rash; HHV-7 may also be a possible cofactor for cytomegalovirus disease in transplant recipients., Materials and Methods: A retrospective review of a group of 58 adult recipients of allogeneic hemopoietic stem cell transplantation was made. Serum samples taken in the range of 0-180 days after transplant were examined for presence of specific HHV-7 sequences using the quantitative real-time PCR method., Results: HHV-7 DNA was detected in plasma samples in 26 (45%) of the 58 recipients between day 20 and day 65 of transplantation. All of them developed fever of unknown origin; also HHV-5 DNA was detected in plasma samples collected from 11 HHV-7-positive patients. None of the described individuals died during detectable HHV-7 or HHV-5 viremia periods., Conclusions: There is a high frequency of detectable HHV-7 viral load in allogeneic stem cell transplant recipients in Poland. Limited availability and sensitivity of serological methods along with the necessity of rapid introduction of antiviral treatment has forced the development of molecular diagnostics. Furthermore, establishment of appropriate procedures for monitoring active HHV-7 infection is important to clarify the virus infection in transplant recipients., (Copyright © 2010 S. Karger AG, Basel.)

Umbilical cord blood transplantation (UCBT) is known to be associated with increased risk of infections, compared to bone marrow or peripheral blood stem cell transplantation. In viral diseases for which specific treatment is available, real-time PCR assays are reliable diagnostic tools for timely initiation of appropriate therapy and for rapid assessment of the efficacy of antiviral treatment strategies. A retrospective review of samples from a group of seven adult cord blood stem cell recipients was made. Serum samples taken up to 180 days after transplantation were examined with quantitative real-time PCR for measurement of viral load (CMV, HHV-6, and HHV-7). Cytomegalovirus (CMV) DNA was detected in samples taken from four patients (57%) in the period of 20-80 days after transplantation. Products of amplification of human herpesvirus 6 (HHV-6) DNA were found in samples taken between days 25 and 37 following UCBT from only one patient (14%). On the other hand, the majority of patients (n = 6, 86%) had HHV-7 DNA detected in the period 15-58 days after transplantation. Co-infection with HHV-7 was demonstrated at onset of all episodes of microbiologically confirmed CMV or HHV-6 infection. Our observations indicate that real-time PCR is not only useful for monitoring herpesviral infections in transplant recipients, but is also a powerful method for clarifying the relationships between the viral load and clinical symptoms. Further investigation with a much larger group of patients will be needed to confirm these observations and translate them into a clinical approach.