Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study.

BACKGROUND: We previously reported that the "Endothelial Activation and Stress Index" (EASIX; ((creatinine×lactate dehydrogenase)÷thrombocytes)) measured before start of conditioning predicts mortality after allogeneic hematopoietic stem cell transplantation (alloSCT) when used as continuous score. For broad clinical implementation, a prospectively validated EASIX-pre cut-off is needed that defines a high-risk cohort and is easy to use. METHOD: In the current study, we first performed a retrospective cohort analysis in n=2022 alloSCT recipients and identified an optimal cut-off for predicting non-relapse mortality (NRM) as EASIX-pre=3. For cut-off validation, we conducted a multicenter prospective study with inclusion of n=317 first alloSCTs from peripheral blood stem cell in adult patients with acute leukemia, lymphoma or myelodysplastic syndrome/myeloproliferative neoplasms in the European Society for Blood and Marrow Transplantation network. RESULTS: Twenty-three % (n=74) of alloSCT recipients had EASIX-pre ≥3 taken before conditioning. NRM at 2 years was 31.1% in the high EASIX group versus 11.5% in the low EASIX group (p<0.001). Patients with high EASIX-pre also had worse 2 years overall survival (51.6% vs 70.9%; p=0.002). We were able to validate the cut-off and found that EASIX ≥3 was associated with more than twofold increased risk for NRM in multivariate analysis (HR=2.18, 95% CI 1.2 to 3.94; p=0.01). No statistically significant difference could be observed for the incidence of relapse. CONCLUSIONS: The results of this study provide a prospectively validated standard laboratory biomarker index to estimate the transplant-related mortality risk after alloSCT. EASIX ≥3 taken before conditioning identifies a population of alloSCT recipients who have a more than twofold increased risk of treatment-related mortality.

Pneumocystis Pneumonia After Allogeneic Hematopoietic Cell Transplantation: A Case-Control Study on Epidemiology and Risk Factors on Behalf of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.

Pneumocystis pneumonia (PCP) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). However, allo-HCT procedures have evolved toward older patients, unrelated donors, and reduced-intensity conditioning, possibly modifying the risks. Polymerase chain reaction (PCR), widely used nowadays, is more sensitive than microscopy diagnostic methods. This study aimed to assess the factors associated with PCP in allo-HCT recipients within 2 years of HCT and managed according to current procedures. This multicenter, nested case-control study included PCP cases diagnosed by PCR, cytology, or immunofluorescence on bronchoalveolar lavage fluid between 2016 and 2018. Two controls per case were selected from the ProMISe registry and matched for the center, transplant date, and underlying disease. Fifty-two cases and 104 controls were included among the 5452 patients who underwent allo-HCT in the participating centers. PCP occurred at a median of 11.5 months after transplantation. The mortality rate was 24% on day 30 after the PCP diagnosis and 37% on day 90. The clinical presentation and mortality rates of the 24 patients diagnosed using only PCR were not different from those diagnosed with microscopy methods. Our study demonstrates a substantial incidence of, and mortality from, PCP, after allogeneic HCT despite well-established prophylactic approaches. In our experience, PCP nowadays occurs later after transplant than previously reported, justifying the prolongation of prophylaxis after six months in many cases. Allo-HCT recipients diagnosed with PCR as the only PCP marker should benefit from specific treatment as for other patients.

Allogeneic hematopoietic cell transplantation in patients with CALR-mutated myelofibrosis: a study of the Chronic Malignancies Working Party of EBMT.

Allogeneic hematopoietic cell transplantation (allo-HCT) is curative for myelofibrosis (MF) but assessing risk-benefit in individual patients is challenging. This complexity is amplified in CALR-mutated MF patients, as they live longer with conventional treatments compared to other molecular subtypes. We analyzed outcomes of 346 CALR-mutated MF patients who underwent allo-HCT in 123 EBMT centers between 2005 and 2019. After a median follow-up of 40 months, the estimated overall survival (OS) rates at 1, 3, and 5 years were 81%, 71%, and 63%, respectively. Patients receiving busulfan-containing regimens achieved a 5-year OS rate of 71%. Non-relapse mortality (NRM) at 1, 3, and 5 years was 16%, 22%, and 26%, respectively, while the incidence of relapse/progression was 11%, 15%, and 17%, respectively. Multivariate analysis showed that older age correlated with worse OS, while primary MF and HLA mismatched transplants had a near-to-significant trend to decreased OS. Comparative analysis between CALR- and JAK2-mutated MF patients adjusting for confounding factors revealed better OS, lower NRM, lower relapse, and improved graft-versus-host disease-free and relapse-free survival (GRFS) in CALR-mutated patients. These findings confirm the improved prognosis associated with CALR mutation in allo-HCT and support molecular profiling in prognostic scoring systems to predict OS after transplantation in MF.

Cellular senescence marker p16INK4a and NFKB1 gene polymorphisms in lower gastro-intestinal acute graft versus host disease.

BACKGROUND: Lower gastrointestinal (GI) graft versus host disease (GVHD) represents a severe complication in allogeneic hematopoietic stem cell transplant (HSCT) recipients with high rates of transplant-related mortality. Deregulated innate immunity reactions are the features of its pathogenesis. Cellular senescence has been considered a program of the innate immunity. We focused on lower GI GVHD from the perspective of cellular senescence. OBJECTIVE: We analyzed the impact of p16INK4a expression, a hallmark of cellular senescence, in intestinal biopsies of patients with lower GI GVHD symptoms and NFKB1 gene polymorphisms (rs3774937 C/T and rs3774959 A/G) on HSCT outcome. STUDY DESIGN: Fifty-two single-center patients who presented with symptoms of lower GI GVHD were analyzed in a retrospective manner. Two SNPs located in the NFKB1 gene regions (rs3774937 C/T and rs3774959 A/G) were genotyped from the peripheral blood samples collected before the start of the conditioning. All patients underwent proctosigmoidoscopy with biopsy of the mucosa. The expression of p16INK4a was analyzed in normal intestinal crypts and stroma. RESULTS: Fifty-two patients (50% male) received HSCT for hematological diseases (acute leukemias in 67%) and developed lower GI symptoms. Patients with p16INK4a expression in the intestinal stroma were in lower risk of developing histological grade 3-4 aGVHD (RR 0.18 [95% CI 0.05-0.65]; p = 0.009). The multivariate linear regression confirmed the independent effect of p16INK4a expression on time of the lower GI aGVHD symptoms onset (Coef. 38.9 [95% CI 12.7-65.1]; p = 0.005). The NFKB1 rs3774937 CC and TT/TC genotype were present in 40 and 80% of patients with p16INK4a expression, respectively (p = 0.04). The rs3774959 AA and GG/AG genotype were present among 43 and 82% of patients with p16INK4a expression, respectively (p = 0.02). Expression of p16INK4a was associated with no clinical variable but NFKB1 genotype. CONCLUSIONS: Our results address possible new mechanisms that may lead to better understanding of HSCT-related immune complications. Cellular senescence may bring novel approaches in GVHD diagnostics and therapy.

Prognostic value of a new clinically-based classification system in patients with CMML undergoing allogeneic HCT: a retrospective analysis of the EBMT-CMWP.

Recently a new three-group clinical classification was reported by an International Consortium to stratify CMML patients with regard to prognosis. The groups were defined as follows: (1) Myelodysplastic (MD)-CMML: WBC ≤ 10 × 109/l, circulating immature myeloid cells (IMC) = 0, no splenomegaly; (2) MD/MP (overlap)-CMML: WBC 10-20 × 109/l or WBC ≤ 10 × 109/l but IMC > 0 and/or splenomegaly; (3) Myeloproliferative (MP)-CMML: WBC > 20 × 109/l. By analysing EBMT Registry patients who underwent allo-HCT for CMML between 1997 and 2016, we aimed to determine the impact of this classification on transplantation outcome and to make a comparison with the conventional WHO classification (CMML-0/CMML-1/CMML-2). Patient grouping was based on the data registered at time of transplantation, with IMC replaced by peripheral blasts. Among 151 patients included in the analysis, 38% were classified as MD-CMML, 42% as MD/MP-CMML and 20% as MP-CMML. With a median survival of 17 months in the whole series, MD-CMML patients were distinguished as a low-risk group with higher CR rate at transplant and a longer post-transplant 2-year progression-free survival in comparison to others (44.5% vs 33.5%, respectively), whereas the WHO classification was superior in identifying high-risk patients (CMML-2) with inferior survival outcomes.

NFKB1 gene single-nucleotide polymorphisms: implications for graft-versus-host disease in allogeneic hematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) represents a significant cause of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). NF-kB system is a master regulator of innate immunity responses. It controls the expression of various cytokines and chemokines many of which are involved in GVHD pathogenesis. Chemo(radio) therapy administered during conditioning induces DNA damage and activates DNA damage response (DDR) signaling resulting in irreversible cell cycle arrest - cellular senescence which has been described to be associated with robust pro-inflammatory secretion mostly controlled by NF-kB. The NFKB1 gene encodes the DNA-binding subunit of the NF-kB complex. Using the candidate gene approach, we analyzed possible association of two single-nucleotide polymorphisms (SNPs) rs3774937 C/T and rs3774959 A/G of the NFKB1 gene with GVHD and transplant-related mortality (TRM) occurrence in 109 recipients allografted from HLA-identical donor. Both SNPs in recipients were found to be strongly associated with acute GVHD. Nevertheless, no significant association with chronic GVHD and TRM was found. Presented pilot results contribute to pre-clinical observations and suggest that NF-kB may be an important regulator of HSCT-related inflammatory reactions such as acute GVHD. Novel pathogenic mechanisms of GVHD may arise from perspectives of DDR and cellular senescence where NF-kB plays an essential role.

Allogeneic Stem Cell Transplantation in Patients With FLT3-ITD Mutated AML: Transplantation in CR1 Is the Decisive Factor for Good Outcome.

BACKGROUND: Patients with internal tandem duplication in fms-related tyrosine kinase receptor gene 3 (FLT3-ITD)-mutated acute myeloid leukemia (AML) have a dismal prognosis and the only curative option seems to be allogeneic stem cell transplantation (alloSCT). However, its timing is still matter of debate. PATIENTS AND METHODS: We retrospectively analyzed 73 consecutive AML patients with FLT3-ITD (median age 53, range 20-68 years) allografted with consistent policy to try to refer them all for upfront alloSCT in first complete remission (CR1). RESULTS: With a median follow-up of 44 (range, 5-135) months the 5-year overall survival (OS)/disease-free survival (DFS) probabilities were 49%/47%. The cumulative incidence of relapse and nonrelapse mortality (NRM) were 37% and 14%, respectively. The estimated 5-year OS for patients who received transplantation in CR1 was 62% versus 0% for patients who received transplantation beyond CR1. Multivariable analysis identified stem cell transplantation beyond CR1 as the key factor for poor OS (hazard ratio [HR], 5.41; P < .0001), DFS (HR, 4.41; P = .0002), and high relapse incidence (HR, 8.08; P < .0001). Acute graft versus host disease Grade ≥3 predicted higher NRM (HR, 3.80; P = .059) as well as inferior OS (HR, 2.04; P = .0079). No association of patient age, nucleophosmin status, donor type, conditioning, and other variables on the survival was detected. CONCLUSION: AlloSCT should be regarded with urgency as soon as CR1 is achieved in this subset of AML patients.

Granulocyte transfusions collected after steroid priming for severe infections during neutropenia: A single center experience.

BACKGROUND: There is no universally accepted opinion on the use of granulocyte transfusions collected using apheresis (GTA) in neutropenic patients and severe infection. PATIENTS AND METHODS: The efficacy and safety of GTAs transfused at a single center over 10 years were analyzed retrospectively. GTAs were harvested from voluntary unrelated donors after priming with methylprednisolone using continuous apheresis and hydroxyethylstarch as sedimentation agent. RESULTS: 41 patients with neutropenia and hematologic malignancy (15 females and 26 males aged 22-69 (median 45.5)) were given a median 3.5 GTAs per patient (range: 1-17) containing a median 1.39×1010 granulocyte/GTA (range: 0.65-2.81). The indications for GTA use were soft tissue inflammation, sepsis, and pneumonia in 30, 22, and 14 cases, respectively. After GTA complete (30 patients: 73.2%) or partial (6 patients: 14.6%) healing of the infection was achieved. The success rate was 91.7% in soft tissue infections, 66.7% in invasive fungal infections, and 68% in sepsis. Septic shock (documented in 12 cases) was associated with a poor response (P<0.03; Chi-square test). Clinical worsening was observed in six cases (14.6%); four patients died. No significant short-term side effects of GTA treatment were recorded. CONCLUSIONS: In our study GTAs collected after steroid priming and used for the treatment of infection during severe neutropenia have shown comparable efficacy with several previously reported trials. However retrospective fashion of our study and inhomogeneous group of patients do not allow any firm conclusions. Prospective studies (including patients' registries) are needed for the better clarification of the role and the dose of GTAs necessary for the successful infection management during neutropenia.

HLA-B gene somatic insertion/deletion mutations in patients with acute myelogenous leukaemia.

Loss of heterozygosity is considered to be the most common type of tumour-specific somatic mutation of the human leucocyte antigens (HLA) genes in patients with haematological malignancies. Nevertheless, subtle DNA sequence changes, namely short insertions/deletions, may also abolish the expression of HLA molecules and interfere with routine HLA typing. Two male patients with acute myelogenous leukaemia (AML) were indicated for the search of a suitable donor for allogeneic haematopoietic stem cell transplantation (aHSCT). The patients and their relatives were initially HLA typed by serological and DNA techniques at a low-resolution level. The HLA high-resolution (HR) type was obtained by means of sequencing-based typing (SBT). In both cases, anomalous frameshifts in the sequence were observed in the HLA-B gene, namely in exon 3 (Case 1, heterozygous deletion of two bases) and exon 4 (Case 2, heterozygous insertion of two bases). In the second case, the insertion variant was associated with a loss of HLA-B8 expression. To reveal whether these sequence patterns may be caused by somatic mutations in the malignant cells, blood sample in remission (Case 1) and buccal swab sample (Case 2) were collected from the patients. In an important manner, the SBT in these germline samples revealed common HLA-B*07:02,*15:01 (Case 1) and HLA-B*08:01,*35:02 (Case 2) types with no evidence for the sequence alteration observed in the initial samples. In conclusion, the insertion/deletion sequence variants of the HLA-B gene in two patients were limited to the initial blood samples with a substantial proportion of AML cells and thus may be attributed to the somatic mutation in the malignant cells. HLA somatic mutations should be taken into account in patients with haematological malignancies to prevent HLA mistyping and inappropriate selection of an aHSCT donor.

Graft versus Host Disease: From Basic Pathogenic Principles to DNA Damage Response and Cellular Senescence.

Graft versus host disease (GVHD), a severe immunogenic complication of allogeneic hematopoietic stem cell transplantation (HSCT), represents the most frequent cause of transplant-related mortality (TRM). Despite a huge progress in HSCT techniques and posttransplant care, GVHD remains a significant obstacle in successful HSCT outcome. This review presents a complex summary of GVHD pathogenesis with focus on references considering basic biological processes such as DNA damage response and cellular senescence.

[Prevalence of strains of Staphylococcus epidermidis and other coagulase-negative staphylococci with biofilm-forming ability at a department of hemato-oncology].

OBJECTIVES: Staphylococcus epidermidis and coagulase-negative staphylococci generally are important causative agents of hospital-acquired infections. A significant role in this process is played by their common ability to form biofilm, a highly organized community of microorganisms adhering to inert surfaces. The study aimed to determine the prevalence of these bacterial strains and their ability to form biofilm at the Department of Hemato-Oncology, University Hospital Olomouc. MATERIAL AND METHODS: Over a period of 12 months, samples of air and swabs from surfaces and staff members were collected. The samples were subjected to standard microbiology tests; coagulase-negative staphylococci were identified. Staphylococcus epidermidis strains were confirmed by polymerase chain reaction and subsequently tested for biofilm formation. RESULTS AND CONCLUSIONS: Coagulase-negative staphylococci were found in 81 samples, most commonly swabs from staff members. S. epidermidis accounted for 60 % of all positive results; it was most frequently isolated from surface swabs. Almost half of S. epidermidis strains were able to form biofilm. These strains were found in the environment characterized by cleanliness classes FED-STD-209E (USA) - 10 000 and FED-STD-209E (USA) - 100 000. Thus, they pose a risk for immunocompromised patients staying there. Since coagulase-negative staphylococci were also found in healthcare staff of the department, the staff members may play a key role in the transmission of these microorganisms to patients.

Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic Cell Transplantation in Young Patients With High Cytogenetic Risk Chronic Lymphocytic Leukemia - A Retrospective Analysis From the Chronic Malignancies Working Party of the EBMT.

BACKGROUND: Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free survival (PFS) with kinase- and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell transplantation (alloHCT) may result in sustained PFS, especially in younger patients because of its age-dependent non-relapse mortality (NRM) risk, but outcome data are lacking for this population. PATIENTS AND METHODS: Risk factors for 2-year NRM and 8-year PFS were identified in patients < 50 years in an updated European Society for Blood and Marrow Transplantation registry cohort (n = 197; median follow-up, 90.4 months) by Cox regression modeling, and predicted probabilities of NRM and PFS of 2 reference patients with favorable or unfavorable characteristics were plotted. RESULTS: Predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.1-2.5) and partially human leukocyte antigen (HLA)-mismatched unrelated donor (HR, 2.8; 95% CI, 1.5-5.2). The latter variable also predicted a higher risk of 2-year NRM (HR, 4.0; 95% CI, 1.4-11.6) compared with HLA-matched sibling donors. Predicted 2-year NRM and 8-year PFS of a high cytogenetic risk (del(17p) and/or del(11q)) patient in remission with a matched related donor were 12% (95% CI, 3%-22%) and 54% (95% CI, 38%-69%), and for an unresponsive patient with a female partially HLA-matched unrelated donor 37% (95% CI, 12%-62%) and 38% (95% CI, 13%-63%). CONCLUSION: Low predicted NRM and high 8-year PFS in favorable transplant high cytogenetic risk patients compares favorably with outcomes with KI or BCL2i. Taking into account the amount of uncertainty for predicting survival after alloHCT and after sequential administration of KI and BCL2i, alloHCT remains a valid option for younger patients with high cytogenetic risk chronic lymphocytic leukemia with a well-HLA-matched donor.

Profile of Inflammation-Associated Proteins in Early Post-Transplant Samples of Patients After Allogeneic Hematopoietic Stem Cell Transplantation: a Preliminary Study.

Allogeneic hematopoietic stem cell transplantation (aHSCT) is used as a curative treatment in severe hematological and immunological disorders. Despite clear improvement of the aHSCT outcome, substantial proportion of patients still suffers from severe complications, including graft-versus-host disease (GvHD). The aim of this study was, therefore, to identify inflammation-associated molecules deregulated in the early serum samples of the patients after aHSCT and nominate markers associated with particular aHSCT parameters/complications. Serum concentrations of 92 inflammation-associated proteins were measured in samples obtained from 80 aHSCT patients 14 days after transplantation and from 23 healthy control subjects by a novel sensitive proximity extension assay technology using Proseek Multiplex Inflammation I kit. Serum profiles of inflammatory proteins in patients after aHSCT were substantially different from those observed in control subjects and related to underlying disease status before transplantation. Particularly, the difference between aHSCT patients and controls reached significance level for 57 analytes (40 upregulated, 17 downregulated in aHSCT patients). The concentration of several markers was associated with the level of donor/recipient HLA match (TGF-α: p corr = 0.025, HGF: p corr = 0.036) and with complete donor chimerism at day +30 after allografting (DNER: p corr = 0.042). None of the markers was significantly associated with acute and chronic GvHD after correction. More than half of investigated proteins significantly differed between the samples from aHSCT patients and healthy control subjects as a consequence of the "cytokine storm" after aHSCT. Comparisons of patient's subgroups based on specific biological/clinical parameters revealed much less evident differences; nevertheless, we nominated several markers associated with the level of donor/recipient HLA match and post-transplant chimerism.

Can Rituximab Improve the Outcome of Patients with Nodular Lymphocyte-Predominant Hodgkin's Lymphoma?

BACKGROUND: Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin's lymphoma showing strong CD20 expression. The role of rituximab in treating NLPHL still needs clarification. METHODS: We retrospectively reviewed the outcome of 23 patients with NLPHL treated with rituximab alone or in combination with chemotherapy and/or radiotherapy as part of their first- or second-line treatment. RESULTS: The median follow-up of the whole group was 67 months, and all patients remained alive. Twenty-two patients achieved complete remission after rituximab-based therapy, and one of them relapsed 32 months after treatment. One patient treated with rituximab alone achieved partial remission and progressed 22 months after treatment. CONCLUSION: The prognosis of NLPHL is excellent. Rituximab combined with chemotherapy and/or radiotherapy appears to prevent disease progression/relapse.

ATM gene single nucleotide polymorphisms predict regimen-related gastrointestinal toxicity in patients allografted after reduced conditioning.

Polymorphisms of genes involved in innate and adaptive immunity have become an object of major interest in regard to hematopoietic stem cell transplantation (HSCT) complications. Regimen-related gastrointestinal toxicity (RR-GIT) is the dominant complication during the pre-engraftment period and has been linked to increased risk of graft-versus-host disease (GVHD) development. According to our hypothesis, functional variants of genes participating in DNA damage response (DDR) may have an impact on the extent of tissue damage caused by the conditioning regimen. In our single-center study, we analyzed 62 patients who underwent HSCT from HLA-identical donors after reduced conditioning. The patients were genotyped for 5 single nucleotide polymorphisms (SNPs, rs4585 T/G, rs189037 A/G, rs227092 T/G, rs228590 C/T, and rs664677 T/C) of the ATM gene-the essential member of the DDR pathways, using allele-specific matrix-assisted laser desorption/ionization, time-of-flight (MALDI-TOF) mass spectrometry assay. Because of almost absolute linkage disequilibrium observed among all 5 SNPs, association of 2 major ATM haplotypes (ATM1/ATM2) with RR-GIT and acute GVHD (aGVHD) was analyzed. Importantly, the univariate and multivariate analysis showed that patients homozygous for ATM2 haplotype (rs4585*T, rs189037*A, rs227092*T, rs228590*C, and rs664677*T) are more likely to suffer from high-grade RR-GIT than ATM1 homozygous patients. The association with aGVHD was not significant. To our knowledge, this is the first report showing the ATM gene variability in relation to RR-GIT in the allogeneic HSCT setting.

Monitoring of Microscopic Filamentous Fungi in Indoor Air of Transplant Unit.

AIM: The aim of the study was to control the microbial contamination of indoor air monitored monthly at the Transplant Unit of the University Hospital Olomouc from August 2010 to July 2011. METHODS: The unit is equipped with a three-stage air filtration system with HEPA filters. The MAS-100 air sampler (Merck, GER) was used. Twenty locations were singled out for the purposes of collecting a total of 720 samplings of the indoor air. Swabs of the HVAC diffusers at the sampling locations were always carried out after the sampling of the indoor air. RESULTS: In total, 480 samples of the indoor air were taken for Sabouraud chloramphenicol agar. In 11 cases (2.29%) the cultivation verified the presence of microscopic filamentous fungi. Only two cases involved the sanitary facilities of a patient isolation box; the other positive findings were from the facilities. The most frequent established genus was Aspergillus spp. (4x), followed by Trichoderma spp. (2x) and Penicillium spp. (2x), Paecilomyces spp., Eurotium spp., and Chrysonilia spp. (1x each). In 2 cases the cultivation established sterile aerial mycelium, unfortunately no further identification was possible. A total of 726 swabs of HVAC diffusers were collected (2 positive-0.28%). The study results demonstrated the efficacy of the HVAC equipment. CONCLUSIONS: With the continuing increase in the number of severely immunocompromised patients, hospitals are faced with the growing problem of invasive aspergillosis and other opportunistic infections. Preventive monitoring of microbial air contaminants is of major importance for the control of invasive aspergillosis.

Comparison of reduced conditionings combining fludarabine with melphalan or 3-day busulfan in patients allografted for myeloid neoplasms.

In the present study we compared outcomes of patients with myeloid neoplasms undergoing allogeneic hematopoietic stem cell transplantation after fludarabine-based regimens with melphalan (FM140) or 3-day busulfan (FB3). The FM140 and FB3 combinations were administered to 21 and 27 patients, respectively. Efforts for early reduction (from day +30 to 60) and discontinuation (until day +100 to 130) of prophylactic immunosuppression were a component of the post-transplant approach. Following FB3 patients suffered from more severe stomatitis (P = 0.013). In contrast, other manifestations of regimen-related toxicity were more frequent in the FM140 group (P = 0.048). There were no statistically significant differences in the development of graft-versus-host disease, non-relapse mortality, post-transplant remission rate, or relapse incidence. Two-year disease-free survival rates were comparable in the two cohorts (66 vs. 55 %; P = 0.751), and so were the overall survival rates (64 vs. 62 %; P = 0.715). The outcomes of allografted patients with myeloid neoplasms were comparable after the FM140 and FB3 regimens. Relatively high therapeutic response in both groups may have been influenced by early reduction and discontinuation of prophylactic immunosuppression followed by effective immunological control of the malignant clone.

Reduced relative dose intensity of primary chemotherapy does not influence prognosis of patients with Hodgkin lymphoma.

AIMS: A retrospective analysis of patients with Hodgkin lymphoma (HL) was performed to assess their outcome regarding relative dose intensity (RDI) of chemotherapy administered in primary treatment. METHODS: A total of 194 patients were divided into three groups with different RDI of primary chemotherapy (100%, 90-99% and <90%). Reduced RDI in two groups (90-99% and <90%) was caused by the delay of the interval between the administration of some chemotherapeutic courses. The probability of complete remission (CR), disease relapse, event-free survival (EFS) and overall survival (OS) as the basic parameters of patient outcome were statistically compared. RESULTS: Multivariate analysis showed here were no significant differences in probability of CR (HR 0.9, 95% CI [0.75-1.08], P=0.5), risk of relapse (HR 1.34, 95% CI [0.92-1.94], P=0.11) or death (HR 1.52, 95% CI [0.94-2.5], P=0.13). There were also no significant differences in probability of EFS (mean 13 vs. 10 vs. 12 years, P=0.17; HR 1.54, 95% CI [0.91-2.6], P=0.22) or OS (mean 15 vs. 13 vs. 14 years, P=0.13; HR 1.52, 95% CI [0.93-2.5], P=0.13). CONCLUSION: We found no significant impact of primary chemotherapy delay resulting in reduced RDI on outcome in HL patients.

Soluble interleukin-2 receptor level predicts survival in patients with follicular lymphoma treated with cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy in the rituximab era.

This study analyzed the prognostic significance of soluble interleukin-2 receptor α (sIL-2Rα) levels in 100 prospectively enrolled patients with previously untreated follicular lymphoma. It showed that sIL-2Rα level ≥ 115 pmol/L at the time of treatment initiation correlated with a high Follicular Lymphoma International Prognostic Index-2 (FLIPI-2), bulky disease, advanced clinical stage, number of involved lymph nodes, bone marrow involvement and elevated ß2-microglobulin (B2M) level. When testing all patients, sIL-2Rα ≥ 115 pmol/L was associated with significantly shorter progression-free (PFS; p < 0.03, hazard ratio [HR] 2.04) but not overall (OS; p = 0.06, HR 2.36) survival rates. Subanalysis of patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) ± rituximab showed higher predictive power for both PFS (HR 2.75, 95% confidence interval [CI] 1.24-6.11, p = 0.01) and OS (HR 3.33, 95% CI 1.15-9.63, p = 0.02). In the whole population (n = 100), only B2M proved a significant univariate predictor (p = 0.007, HR = 2.8) of PFS. When testing patients treated with CHOP ± rituximab, sIL-2Rα was found to be the best univariate predictor for PFS among all FLIPI-2 factors (HR = 2.68, p = 0.015). Serum IL-2Rα levels may help to refine risk assessment in the modern immunotherapy era complementary to FLIPI-2 factors.

The availability of HEPA-filtered rooms and the incidence of pneumonia in patients after haematopoietic stem cell transplantation (HSCT): results from a prospective, multicentre, eastern European study.

AIMS AND OBJECTIVES: To establish the availability of High Efficiency Particulate Air (HEPA)- and nonHEPA-filtered rooms in eastern European transplant centres and to investigate the impact on incidence of pneumonia and mortality after haematopoietic stem cell transplantation (HSCT). BACKGROUND: Barrier nursing in HEPA-filtered rooms is generally recommended for patients undergoing HSCT. There are only limited data on the availability of HEPA-filtered rooms and the impact on incidence of pneumonia and mortality. DESIGN: A prospective, observational, international study. METHODS: Monitoring cards were distributed within the East Forum EBMT-Nurses Group cooperating centres, and 689 consecutive patients were registered in 1/2010-6/2012. Patients were monitored for 100 days post-transplant. RESULTS: In patients undergoing autologous HSCT, pneumonia developed in 14/400 (3·5%) and was the cause of death in 2/14 (14%) of patients. There was no significant difference in mortality between HEPA-filtered and nonHEPA-filtered groups (4·5% vs. 4·9%, respectively). 239/400 (59%) transplantations were performed in single-bed rooms [190/239 (79%) HEPA-filtered] and 161 (41%) in two-bed rooms [28/161 (17%) HEPA-filtered]. In allogeneic transplantation, pneumonia developed in 24/289 (8·3%) and was the cause of death in 11/24 (45%) of patients. There was no significant difference in mortality between HEPA-filtered and non-HEPA-filtered groups (14% vs. 17%, respectively). 281/289 (97%) of allogeneic transplantations were performed in single-bed rooms [254/281 (90%) HEPA-filtered], and pneumonia was more frequent in patients on corticosteroids and in rooms without HEPA. CONCLUSION: The incidence of pneumonia in the autologous transplantation setting is low. More pneumonia was observed in the allogeneic HSCT group, especially in patients on corticosteroids. There was a trend towards a lower incidence of pneumonia in allogeneic HSCT patients treated in HEPA-filtered rooms. RELEVANCE TO CLINICAL PRACTICE: Autologous HSCT transplantation may safely be performed without HEPA filtration. HEPA filtration might be preferable in patients undergoing allogeneic transplantation.