Low serum albumin level deteriorates prognosis in azacitidine-treated myelodysplastic syndromes patients - results of the PALG study 'PolAZA'.

BACKGROUND: Azacitidine (AZA) is the standard of care for higher-risk myelodysplastic syndrome (HR-MDS) patients ineligible for intensive therapy. Clinical outcome discrepancies reported in clinical trials and real-life settings stimulate the search for new prognostic factors. METHODS: We retrospectively evaluated 315 MDS, 20-30% blast acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) patients treated with azacitidine in 12 centers cooperating within the Polish Adult Leukemia Group (PALG). RESULTS: The median number of AZA cycles was 7 (1-69) and 24% patients received fewer than 4 cycles (early failure, EF). Serum albumin level was an independent predictor of EF occurrence. Complete remission (CR) was obtained in 20% and partial remission (PR) in 12% of patients. Hematologic improvement - erythroid (HI-E), neutrophil (HI-N), or platelet (HI-P) was achieved in 51%, 36%, and 48% of patients, respectively. No factors significantly predicted CR or PR in the multivariate analysis. For HI-E and HI-P, lower LDH level predicted response. Median survival was 15 (13-19) months. Lower serum albumin level, serious infection and receiving <4 AZA cycles independently predicted a worse overall survival (OS) (p < 0.05). CONCLUSION: Serum albumin assessment before azacitidine treatment can help to identify patients with higher risk of early failure and worse clinical outcome.

Autologous peripheral blood stem cell transplantation in dialysis-dependent multiple myeloma patients-DAUTOS Study of the Polish Myeloma Study Group.

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.

Infections due to alphaherpesviruses in early post-transplant period after allogeneic haematopoietic stem cell transplantation: Results of a 5-year survey.

BACKGROUND: Infections caused by human α-herpesviruses usually have a benign course with recurrencies. However, they may become dangerous in immunocompromised hosts. In this case, molecular methods constitute a reliable diagnostic tool enabling rapid assessment of the efficacy of antiviral treatment strategies. OBJECTIVES: We estimated the frequency of alphaherpesviral DNAemia and the viral load during early post-transplantation period after alloHSCT; we also analyzed association of the DNAemia and chosen parameters of the patients. STUDY DESIGN: A cohort of 190 alloHSCT recipients from two hospitals in Warsaw, Poland, was examined weekly during 100-day early post-transplantation period using quantitative real time PCR assays. A total of 2475 sera samples were evaluated for the presence of α-herpesviral DNA in patients, of whom 117 (62%) received unrelated grafts, while the remaining 73 (38%) received grafts from sibling donors. All patients received standard antiviral prophylaxis with acyclovir. In the examined group, anti-HSV-1, anti-HSV-2 and anti-VZV IgGs were examined prior to transplantation, RESULTS: Within the study period, DNA of α-herpesviruses was detected in 44 patients (23.2%). Most patients tested positive for HSV-1 DNA (43 patients, 22.6%), single patient for HSV-2, and no patient positive for VZV. Clinical symptoms such as pneumonia, skin changes, elevated levels of aminotransferases were observed in five patients, four of these patients presented symptoms of GvHD at the same time. (2,6%). Statistics shows that GvHD (P<0.001) and matched unrelated donor as a source of HSCT (P=0.048) are associated with the development of HSV-1 DNAemia. CONCLUSIONS: Although our data demonstrate frequent reactivation of HSV-1 in the early post-transplant period, the rate of symptomatic infections was low. We did not find association between HSV-1 viremia and mortality, but significant association with GvHD and donor source was observed.

Impact of Gut Colonization by Antibiotic-Resistant Bacteria on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective, Single-Center Study.

Gut colonization by antibiotic-resistant bacteria may underlie hard-to-treat systemic infections. There is also accumulating evidence on the immunomodulatory function of gut microbiota after allogeneic stem cell transplantation (alloSCT) and its impact on graft-versus-host disease (GVHD). We investigated the epidemiology and clinical impact of gut colonization after alloSCT and retrospectively analyzed data on 107 alloSCTs performed at a single transplant center. Pretransplant microbiology screening identified colonization in 31% of cases. Colonization had a negative impact on overall survival after alloSCT in univariate (34% versus 74% at 24 months, P < .001) and multivariate (hazard ratio, 3.53; 95% confidence interval, 1.71 to 7.28; P < .001) analyses. Nonrelapse mortality was significantly higher in colonized than in noncolonized patients (42% versus 11% at 24 months, P = .001). Colonized patients more frequently experienced bacteremia (48% versus 24%, P = .01), and more deaths were attributable to infectious causes in the colonized group (42% versus 11% of patients and 67% versus 29% of deaths, P < .05). We observed a significantly higher incidence of grades II to IV acute GVHD in colonized than in noncolonized patients (42% versus 23%, P < .05), especially involving the gastrointestinal system (33% versus 13.5%, P = .07). In summary, we determined that gut colonization by antibiotic-resistant bacteria decreases the overall survival of patients undergoing alloSCT by increasing nonrelapse mortality and the incidences of systemic infection and acute GVHD.

Analysis of the shedding of three ß-herpesviruses DNA in Polish patients subjected to allogeneic hematopoietic stem cell transplantation: Six-year follow up.

BACKGROUND: Infections with human ß-herpesviruses are common worldwide and are still frequent in patients after hematopoietic stem cell transplantation. Some data suggest that HHV-6 and HHV-7 could take part in CMV reactivation from latency and/or progression of CMV disease in immunosupressed patients. OBJECTIVES: The aims of this study were: (1) to summarise retrospectively the results of ß-herpesviruses DNA detection in a large group of adult allogeneic haematopoietic stem cell transplant recipients; and (2) to find a potential correlation between viruses belonging to this subfamily. STUDY DESIGN: AlloHSCT recipients (N=142) were examined in the early post-transplant period (median=89 days). The presence of CMV, HHV-6 and HHV-7 was confirmed through detection and quantification of viral DNA, isolated from 1679 sera samples. RESULTS: CMV DNA alone was detected in 23.9% of patients, while single HHV-6 and HHV-7 were detected in 14.8% and 9.9% of individuals, respectively. The reactivation of more than one virus was identified in 31% of analysed patients. In cases of concurrent infection, HHV-7 was detected at the same time as HHV-6, and both of them were usually reactivated before CMV. The kinetics of virus reactivation and measured viral load may suggest a potential role of HHV-6 and HHV-7 as co-factors in CMV reactivation. CONCLUSIONS: The observed kinetics of virus reactivation may strongly suggest a potential role of HHV-6 and/or HHV-7 as co-factors of CMV reactivation. The co-infection with these ß-herpesviruses could predispose patients after hematopoietic stem cell transplantation to a longer and more severe CMV infection.

Incidence of adenoviral DNAemia in Polish adults undergoing allogeneic haematopoietic stem cell transplantation.

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.

[Usefulness of wide-range microbiological diagnostics proceedings in case of simultaneous infection with four herpesviruses after allogeneic haematopoietic stem cell transplantation--a case report]. / Przydatnosc wielokierunkowej diagnostyki mikrobiologicznej na przykladzie jednoczesnego zakazenia czterema herpeswirusami jako powiklania po allogenicznym przeszczepieniu komórek krwiotwórczych--opis przypadku.

INTRODUCTION: Infections caused with a variety of bacteria, fungi and viruses are still responsible for high level of mortality and morbidity in immunosupressed individuals. A case of fatal post-transplant reactivation with four herpesviruses in 49-year-old immunocompromised male with MDS-RAEB2, subjected to allogeneic haematopoietic stem cell transplantation was described. METHODS: Full microbiological examination of was performed in different types of clinical samples (whole blood, stool). Sera specimens were tested for the presence of different viral DNA using the real-time PCR assays. RESULTS AND CONCLUSIONS: DNA of HSV-1, VZV, HHV-6 and EBV in serum samples was detected using molecular biology techniques. Viral level of HSV-1 and VZV was constantly increasing despite routine applied oral acyclovir therapy. These findings underline the value of real-time PCR technique used in current therapeutic procedures and for monitoring of antiviral therapy with nucleoside analogs. We found that real-time PCR is a useful tool in detection and monitoring of disseminated herpesviral infection, especially for the detection of low-copy viraemia in clinical specimens.