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Introduction: Blood stream infections (BSI) frequently cause morbidity and mortality in allogeneic (allo) hematopoietic cell transplant (HCT) recipients. Characteristics of causative organisms shortly before death have not been previously described. Early treatment with antimicrobial agents targeting the recent surge in multidrug‐resistant (MDR) pathogens may lead to better outcomes. Methods: This is retrospective study including 529 allo HCT recipients who died between 2000 and 2013. All patients who had BSI that happened 72 hours before death were included. BSI and criteria for antimicrobial resistance were defined according to the Centers for Disease Control and Prevention and the National Healthcare Safety Network surveillance criteria. Results: Overall, 104 BSI were identified from 91 patients. Bacterial infections accounted for 87% of the infections which were comprised by 37% gram‐negative organisms and 50% gram‐positive bacteria. The most common species were Enterococcus (30%), Staphylococcus (16%), and Pseudomonas (16%). Most enterococci were vancomycin resistant (87%), 100% of staphylococci were resistant to methicillin, and 64% of Pseudomonas were MDR. Over time there was a significant increase in vancomycin‐resistant enterococcal (P =.01) and gram‐negative BSI (P =.01). Blood stream infections were either the primary or secondary cause of death in 53% of patients. Conclusions: In allo HCT recipients, vancomycin‐resistant enterococcal infections caused the majority of BSI 72 hours prior to death. Our findings provide information that may guide empiric antibiotic coverage in critically ill HCT recipients. [ABSTRACT FROM AUTHOR]

Summary: Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma (MM) is lacking in the current literature. We evaluated 258 patients with relapsed MM, diagnosed from 2008 to 2015, to investigate the prognostic impact of deep immunoparesis on post‐relapse survival. On qualitative immunoparesis assessment, no, partial and full immunoparesis was present in 9%, 30% and 61% of patients, respectively. Quantitative immunoparesis was assessed by computing the average relative difference (ARD) between polyclonal immunoglobulin(s) and corresponding lower normal limit(s), with greater negative values indicating deeper immunoparesis. The median ARD was −39%, with an optimal cut‐off of −50% for overall survival (OS) by recursive partitioning analysis. Deep immunoparesis (ARD ≤–50%) was associated with a higher tumour burden at first relapse compared to none/shallow [ARD >−50%] immunoparesis. The OS (P = 0·007) and progression‐free survival (PFS; P < 0·001) differed significantly between the deep and none/shallow immunoparesis groups. Kaplan–Meier estimates for 3‐year OS were 36% and 46%, and for 2‐year PFS were 17% and 27%, respectively. On multivariable analysis (MVA) for PFS, both qualitative and quantitative immunoparesis retained negative prognostic impact independently. However, only quantitative immunoparesis was independently prognostic for OS on MVA. Depth of immunoparesis in relapsed MM is an important prognostic factor for post‐relapse survival in the era of novel agents and continuous therapy. [ABSTRACT FROM AUTHOR]

Summary: The treatment for relapsed/refractory multiple myeloma (RRMM) continues to be challenging despite recent therapeutic advancements. Venetoclax, an inhibitor of the anti‐apoptotic protein BCL‐2, is a promising agent, especially in patients harbouring t(11;14). Our objective was to review our experience with venetoclax‐based regimens at our institution. All ten RRMM patients treated with venetoclax were included and had a median of six prior lines of therapy. The overall response rate was 78% and one patient with cardiac amyloidosis and MM achieved a cardiac organ response. Haematologic toxicities requiring red blood cell and platelet transfusion and non‐haematologic toxicities, most commonly gastrointestinal upset, were observed. [ABSTRACT FROM AUTHOR]

Background: Infections are the most common cause of non‐relapse mortality in adult allogeneic hematopoietic stem cell transplant (allo HSCT) recipients. Acute gastrointestinal graft‐vs‐host disease (GI GVHD) often leads to friable mucosa as well as treatment interventions which can increase risk of infection. Our primary objective was to describe the relationship between increasing grades of acute GI GVHD and incidence of bloodstream infections (BSI). Methods: We reviewed 441 adults who underwent allo HSCT from 2011 to 2017 and were clinically diagnosed with GI GVHD, non‐GI GVHD, or no GVHD based on the modified Glucksberg scale within the first 100 days of transplantation. The maximum grades of acute GI GVHD and non‐GI GVHD were used in the analysis. BSI was defined based on the presence of a blood culture positive for bacteria or fungi and treatment with antibiotics. The incidence of BSI within the first 180 days of transplantation was estimated with the cumulative incidence method. Fine and Gray regression was used to assess association between clinical grade of acute GI GVHD and BSI risk, adjusting for grade of non‐GI GVHD and for other significant baseline patient risk factors for BSI identified by multivariable analysis. Results are shown as hazard ratio (HR) and 95% confidence interval (CI). A similar analysis was conducted in 130 patients with histologic grade of acute GI GVHD. Results: Overall BSI incidence by day 180 was 32%; gram‐negative bacilli were the predominant organisms, followed by gram‐positive cocci and fungi. Patients with grade 4 acute GI GVHD had higher risk of BSI as compared to patients with no GI GVHD (HR 2.98, CI 1.65‐5.37, P <.001), while those with grade 3 acute GI GVHD had similar BSI risk (HR 0.89, CI 0.36‐2.21, P =.81). Grade of GI GVHD had no association with risk of non‐BSI. Results were similar in patients with histologic grade acute GI GVHD. Patients who developed BSI or non‐BSI had significantly higher overall mortality risk compared to those without infectious complications (HR 2.52, CI 1.92‐3.31, P <.001 for BSI; HR 1.60, CI 1.20‐2.13, P =.001 for non‐BSI). Conclusions: Grade 4 acute GI GVHD is associated with a higher risk of BSI, which is in turn associated with a higher risk of overall mortality in this population. Understanding the relationships between acute GI GVHD, BSI, and overall mortality can guide future treatment strategies for adult allo HSCT recipients. [ABSTRACT FROM AUTHOR]

Background: Obesity has implications for hematopoietic progenitor cell (HPC) mobilization, chemotherapy administration, and medication dosing. We analyzed the impact of obesity on HPC mobilization as well as key outcomes that are associated with cell dose in autologous hematopoietic cell transplantation (AHCT) recipients. Methods: We conducted a retrospective cohort study on 556 consecutive eligible AHCT recipients at our institution from 1/2004 to 12/2009. Patients were categorized into four groups based on the body mass index (BMI): underweight (BMI < 18.5), normal (18.5‐24.9), overweight (25.0‐29.9), or obese (≥30.0). Primary endpoints of interest included HPC mobilization, neutrophil and platelet recovery, hospital stay and survival. Results: The diagnoses were mostly non‐Hodgkin lymphoma, multiple myeloma, and Hodgkin lymphoma. The majority of the patients had received three or less prior chemotherapy regimens and had not received prior radiation therapy. Most patients had chemosensitive disease at time of transplant. For HPC mobilization regimen, 68% received chemotherapy and G‐CSF, 32% received G‐CSF alone. Busuflan/etoposide/cyclophosphamide, melphalan, and busulfan/cyclophosphamide were used for conditioning. Obesity did not correlate with HPC mobilization and had no association with neutrophil or platelet recovery, or length of transplant hospitalization. On multivariable analysis, obese patients demonstrated better survival than those who were not obese. Conclusion: Obese AHCT recipients had similar rates of HPC mobilization, neutrophil and platelet engraftment and length of transplant hospitalization, and experienced better survival compared with recipients with lower BMI. High BMI by itself should not be considered as a contraindication to AHCT. [ABSTRACT FROM AUTHOR]

Abstract: Background: Peripheral blood progenitor cell (PBPC) mobilization with chemotherapy in addition to Granulocyte‐Colony Stimulating Factor (G‐CSF) improves cell collection compared to G‐CSF alone; however, it is associated with increased risk of neutropenic fever (NF). Methods: We analyzed risk factors for post‐priming NF and NF association with autologous stem cell transplant outcomes. Between 1998 and 2008, 593 adult patients with lymphoma underwent PBPC mobilization with etoposide and G‐CSF. Results: Median age was 51 years (range 18–77) and 372 (63%) were male. Diagnoses were 457 (77%) non‐Hodgkin lymphoma and 136 (23%) Hodgkin lymphoma. Of 554 (93%) transplanted patients, majority were in complete or partial remission at time of transplant (88%). Overall, 141 (24%) patients were hospitalized for NF. Nine patients (6%) had bacteremia, 4 (3%) had pneumonia, 2 (<1%) had herpes simplex viral infections, and the remaining 126 (90%) had no identified infection source. NF patients had lower likelihood of proceeding to transplant (86% vs. 96%, P < .001), lower CD34+ cell dose collection (median 7.23 × 106 CD34+ cells/kg vs. 8.98 × 106 CD34+ cells/kg, P = .002), and were more likely to require > 4 days of apheresis (48% vs. 37%, P < .001). NF was associated with a higher 30‐day readmission rate following transplant hospitalization (17% vs. 9%, P = .012). Conclusion: NF during etoposide priming is associated with lower likelihood of proceeding to transplant, lower CD34+ cell dose collection, more apheresis days required for collection and a higher 30‐day readmission rate following transplant discharge. [ABSTRACT FROM AUTHOR]

Background Chemoradiotherapy results in excellent outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC). This trial compared 2 chemoradiotherapy regimens. Methods Patients with locally advanced HNSCC were treated with radiation (70-74.4 Gy), and randomized to arm A: cisplatin 100 mg/m2 on radiotherapy (RT) days 1, 22, and 43, or arm B: cisplatin (20 mg/m2/day) and 5-fluorouracil (5-FU; 1000 mg/m2/day) continuous 96-hour infusions on RT weeks 1 and 4. The primary endpoint was relapse-free survival (RFS). Results Between February 2008 and October 2011, 69 patients were enrolled in this study. The study prematurely closed when a scheduled interim analysis showed superior outcomes in both arms and futility of continuation. Eighty-three percent of patients had oropharyngeal cancer, of these, 86% were human papillomavirus (HPV)/p16+. The 3-year Kaplan-Meier outcome estimates (median follow-up, 41 months) for arms A and B were: RFS 87% versus 80% ( p = .24), overall survival 97% versus 85% ( p = .013), locoregional control 96% versus 94% ( p = .52), and distant metastatic control 91% versus 87% ( p = .9). Conclusion Multiagent was not superior to single-agent chemoradiotherapy. Overrepresentation of HPV/p16+ patients resulted in better than expected outcomes. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1583-1589, 2015 [ABSTRACT FROM AUTHOR]

Sessile serrated adenomas/polyps ( SSA/Ps) are precursors of colon cancer, particularly those that exhibit microsatellite instability. Distinguishing SSA/Ps from the related, but innocuous, microvesicular hyperplastic polyp ( MVHP) can be challenging. In this study seven gastrointestinal pathologists reviewed 109 serrated polyps and identified 60 polyps with histological consensus. Microarray analysis was performed on six distal consensus MVHPs < 9 mm, six proximal consensus SSA/Ps > 9 mm, and six normal colon biopsies (three proximal, three distal). Comparative gene expression analysis confirmed the close relationship between SSA/Ps and MVHPs as there was overlapping expression of many genes. However, the gene expression profile in SSA/Ps had stronger and more numerous associations with cancer-related genes compared with MVHPs. Three genes ( TFF2, FABP6, and ANXA10) were identified as candidates whose expression can differentiate SSA/Ps from MVHPs, and the differences in expression were confirmed by quantitative RT-PCR. As ANXA10 showed the most promise in differentiating these polyps, the expression of ANXA10 was evaluated by immunohistochemistry in consensus SSA/Ps ( n = 26), MVHPs ( n = 21), and normal colon ( n = 9). Immunohistochemical expression of ANXA10 was not identified in separate samples of normal colon or in the normal colonic epithelium adjacent to the serrated polyps. Consistent with the microarray and quantitative RT-PCR experiments, immunohistochemical expression of ANXA10 was markedly increased in SSA/Ps compared to MVHPs ( p < 0.0001). An ANXA10 score ≥ 3 has a sensitivity of 73% and a specificity of 95% in the diagnosis of an SSA/P. In conclusion, we show that SSA/Ps and MVHPs have significant overlap in gene expression, but also important differences, particularly in cancer-related pathways. Expression of ANXA10 may be a potential marker of the serrated pathway to colon cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background This phase II study tested the addition of the oral epidermal growth factor receptor gefitinib to multiagent concurrent chemoradiotherapy regimen in head and neck squamous cell cancer (HNSCC). Methods Patients with stage III-IV HNSCC received hyperfractionated radiation (72-74.4 Gy at 120 cGy twice daily), with concurrent 96-hour infusions of cisplatin 20 mg/m2/day and fluorouracil 1000 mg/m2/day given during weeks 1 and 4. Daily gefitinib 250 mg was started on day 1 of radiation and continued for 2 years. Results were retrospectively compared with our previous study using identical chemoradiotherapy without gefitinib. Results Sixty patients were enrolled in the study; 80% had stage IV disease and 68% had oropharyngeal primary tumors. The full course of gefitinib was not tolerated by 42%; there were 5 treatment-related deaths (8%). With a median follow-up of 54 months, 2- and 3-year overall survival estimates were 80% and 71%, respectively. Projected distant metastatic control at 2 and 3 years was 88%. When compared with our historical cohort, acute toxicities including renal dysfunction and unplanned rehospitalization were worse in the study patients. Projected outcome estimates did not differ between the 2 cohorts. Conclusions Addition of gefitinib to concurrent chemoradiotherapy was difficult to complete, did not improve outcomes, and increased toxicity. © 2011 Wiley Periodicals, Inc. Head Neck, 2011 [ABSTRACT FROM AUTHOR]

Background Constitutive activation of STAT5 (by phosphorylation) has been identified in a number of malignancies, including acute myeloid leukemia ( AML). Objectives We investigated whether the level of phosphorylated STAT5 ( pSTAT5) expression correlates with clinical outcome in AML. Methods Adult patients with newly diagnosed AML receiving induction chemotherapy and with an available diagnostic bone marrow were evaluated. Results Forty-two percent of patients had pSTAT5 expression >0 on immunohistochemical analysis of fixed bone marrow core biopsies. In multivariable analyses, controlling for age, history of antecedent hematologic disorder, cytogenetic risk, and WBC at diagnosis, pSTAT5 expression was significantly associated with an increased risk of death ( HR 1.96, 95% CI 1.19-3.23, P = 0.008) and of relapse after achieving complete remission ( HR 2.31, 95% CI 1.16-4.63, P = 0.018). Conclusions Validation of pSTAT5's prognostic value requires additional study in a larger group of uniformly treated patients. However, our data suggests that targeting this signaling pathway in AML may improve the outcome of patients. [ABSTRACT FROM AUTHOR]

Background The reported decreasing benefit with increasing age from concurrent chemoradiotherapy in head and neck cancer patients prompted this retrospective review. Methods Two courses of cisplatin-based concurrent chemoradiotherapy were given to fit patients ≥70 years with locoregionally advanced cancers. Clinical characteristics, treatment, and outcomes were compared with those for an identically treated cohort <70 years. Results There were 44 patients ≥70 and 137 patients <70 years. Clinical characteristics, treatment and toxicities were similar except that the elderly were less likely to receive both chemotherapy courses, experienced more myelosuppression, required more unplanned hospitalization, and were feeding-tube dependent longer. Projected 5-year disease-specific survival (71% vs 74%) and freedom from recurrence (69% v. 71%) were nearly identical. Conclusions Although these selected elderly patients experienced greater myelosuppression and supportive care requirements, outcomes were the same as in younger patients. Age alone should not be considered a contraindication to aggressive chemoradiotherapy for this disease. © 2011 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

Summary Hereditary atypical hemolytic uremic syndrome (aHUS), a dramatic disease frequently leading to dialysis, is associated with germline mutations of the CFH, CD46, or CFI genes. After identification of the mutation in an affected aHUS patient, single-site gene testing of relatives is the preventive care perspective. However, clinical data for family counselling are scarce. From the German-Speaking-Countries-aHUS-Registry, 33 index patients with mutations were approached for permission to offer relatives screening for their family-specific mutations and to obtain demographic and clinical data. Mutation screening was performed using direct sequencing. Age-adjusted penetrance of aHUS was calculated for each gene in index cases and in mutation-positive relatives. Sixty-one relatives comprising 41 parents and 20 other relatives were enrolled and mutations detected in 31/61. In total, 40 research participants had germline mutations in CFH, 19 in CD46 and in 6 CFI. Penetrance at age 40 was markedly reduced in mutation-positive relatives compared to index patients overall with 10% versus 67% ( P < 0.001); 6% vs. 67% ( P < 0.001) in CFH mutation carriers and 21% vs. 70% ( P= 0.003) in CD46 mutation carriers. Age-adjusted penetrance for hereditary aHUS is important to understand the disease, and if replicated in the future, for genetic counselling. [ABSTRACT FROM AUTHOR]

Background: Pancreatic adenocarcinoma is a malignancy with a dismal prognosis. Previous studies have suggested that in pancreatic cancer, human equilibrative nucleoside transporter 1 (hENT-1) and ribonucleoside reductase subunit M1 (RRM1) expression may have prognostic value as well as predictive value with sensitivity to gemcitabine. This study investigated the prognostic value of hENT-1 and RRM1 expression in resected pancreatic cancer.Methods: Eighty-four patients who underwent pancreaticoduodenectomy from 2000 to 2005 were included in this study. Patients were followed for a median of 60 months (range, 44-110). Total RNA was isolated from macrodissected paraffin-embedded tumors. hENT-1 and RRM1 expression levels in tumors were evaluated by quantitative reverse transcription-polymerase chain reaction (QRT-PCR), normalized to 2 reference genes, and expressed as ΔCt (low ΔCt means high expression). Univariate and multivariable prognostic factors for overall survival (OS) and progression-free survival (PFS) were identified via Cox proportional hazards analysis.Results: Univariate analysis identified hENT-1, overall stage, lymphovascular invasion, perineural invasion, and adjuvant therapy as prognostic factors for both PFS and OS. Multivariate analysis confirmed the association of low expression of hENT-1 (ΔCt > 0.2027) (P = .007), perineural invasion (P = .021), and lack of adjuvant treatment (P < 0.001) with worse OS. Multivariate analysis also confirmed the association of low expression of hENT-1 (ΔCt > 0.5391) with worse PFS (P = .016) in addition to overall stage (P = .013), perineural invasion (P = .042), and lack of adjuvant treatment (hazard ratio 2.31, P = .029). RRM1 expression was not associated with OS or PFS in the current cohort.Conclusions: Low expression of hENT-1 was associated with worse OS and PFS in patients with resected pancreatic adenocarcinoma independent of gemcitabine therapy. [ABSTRACT FROM AUTHOR]

Early and reliable prediction of the likelihood of achieving adequate stem cell collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) would improve collection efficiency, prevent unnecessary aphereses, and permit appropriate treatment alterations. No previous study has reported a threshold CD34+ cell collection quantity on Day 1 or 2 of leukapheresis that could predict successful stem cell collection. We performed a retrospective analysis of all MM patients undergoing first attempt of stem cell collection at our institution from 2001 through 2008. Recursive partitioning analysis was used to identify Day 1 or Day 1+2 CD34+ collection quantity that predicted failure to reach target ≥2 × 106 CD34+ cells/kg within five days of collection. Totally, 172 patients were included in the analysis. Patients underwent mobilization with G-CSF or G-CSF+ chemotherapy. 23 of 172 patients (13.4%) failed to collect sufficient (≥2 × 106 CD34+ cells/kg) CD34+ cells after five days of apheresis: 22 of 29 who collected ≤0.70 × 106 CD34+ cells/kg and 1 of 143 who collected >0.70 × 106 CD34+ cells/kg (75.9% vs. 0.7%, P < 0.001) on Day 1. Collection failure occurred in 23 of 30 patients who collected ≤1.54 × 106 CD34+ cells/kg and 0 of 142 who collected >1.54 × 106 CD34+ cells/kg (76.7% vs. 0%, P < 0.001) on Days 1 + 2. Day 1 CD34+ cell collection quantity identifies patients unlikely to achieve adequate collection for ASCT. Patients who collect ≤0.70 × 106 CD34+ cells/kg on day 1 could be considered for treatment modifications to improve CD34+ collection, such as early administration of plerixafor or large volume apheresis. J. Clin. Apheresis, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the preferred treatment modality for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). To assess long-term outcomes of these patients, we retrospectively analysed data from 309 consecutive patients who underwent ASCT for DLBCL between 1994 and 2006. We found that non-relapse mortality (NRM) became the major cause of death beginning approximately 8 years after ASCT. The most common causes of NRM during the study period were respiratory failure (31%), infection (13%), cardiac toxicity (15%) and secondary malignancy (15%). The strongest predictor of relapse mortality (RM) was disease status at transplant: patients who were in second or greater complete or partial remission had a higher risk of RM than those in first complete or partial remission [hazard ratio (HR) 3·7, P < 0·001], as did those who were relapsed or refractory (HR 4·9, P < 0·001). We describe the longest reported follow-up of a large cohort of DLBCL patients uniformly-treated with ASCT. Although relapse was initially the more likely cause of death, NRM exceeded RM after 8 years. After ASCT, surviving patients have significantly increased risk mortality rates relative to the general population and this excess risk persists over time. [ABSTRACT FROM AUTHOR]

The article presents a study regarding the medical case of 16 haemotological malignancy patients. The study uses total body irradiation (TBI), etoposide and antithymocyte globulin (ATG) to conduct multiple unit umbilical cord blood transplantation (MU-UCBT). The result shows that three patients experienced early deaths and one had graft failure but was infused with cryopreserved remission autologous bone marrow and remains alive in complete remission for 1056 days.

The developments in apheresis technologies and techniques and their clinical applications worldwide are technologically, sociologically, and economically motivated. As in the past apheresis surveys, the statistics have highlighted both the differences by geographic region in clinical practice and in the type of technologies utilized. While a national view of apheresis is very important, an international view may be more representative overall of this therapeutic modality than national results that are highly dependent on the local economics and the available technologies. These regional differences have provided a basis for scientific and clinical assessment of these apheresis technologies and their clinical outcomes, and have impacted the marketing and business developments of new technologies worldwide. The results of the International Apheresis Registry for 2007 report data from 20 centers on five continents. The survey collected data exclusively via a secure internet website on 1735 patients for a total of 6787 treatments. As with our prior registry for 2005, information on stem cell infusions was gathered. Information collected included patients demographics, medical history, treatment diagnoses, treatment specifics (type, methodology, access type, anticoagulants, drugs, and equipment usage), side effects, clinical response, and payment provider. As in prior International Apheresis Registries for 1983, 2000, 2002, and 2005, the survey results highlight the regional differences in apheresis usage and treatment methodologies indicating that an international overview of apheresis may be more representative of the impact of this therapeutic modality. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) with cyclophosphamide, etoposide and oral busulfan (BuCyVP) is an effective therapy for relapsed or refractory non-Hodgkin lymphoma (NHL). Substituting intravenous for oral busulfan reduces variability in drug exposure, potentially improving the safety and efficacy of the BuCyVP regimen. We retrospectively compared the outcomes of 604 consecutively treated patients who underwent ASCT for NHL with BuCyVP using oral ( n = 468) or IV ( n = 136) busulfan, without measurement of busulfan levels for pharmacokinetic (PK) analysis. Patients who received oral busulfan experienced more severe oral mucositis and a higher incidence of nonrelapse mortality. Median overall survival (OS) after ASCT was 72 months with oral busulfan but was not reached for the IV busulfan group. IV busulfan was associated with a lower rate of relapse, and superior relapse-free survival (RFS) and OS. In multivariate models, the route of busulfan administration was an independent prognostic factor for relapse ( P = 0·01), RFS ( P = 0·002) and OS ( P = 0·001). IV busulfan appears to provide better efficacy and lower toxicity than oral busulfan in ASCT with BuCyVP for NHL. Whether PK-based busulfan dosing can achieve further improvements in this setting is worthy of study. [ABSTRACT FROM AUTHOR]

Atypical hemolytic uremic syndrome (aHUS) is caused by several susceptibility genes. A registry including analyses of susceptibility genes, familial occurrence and genotype-phenotype correlation should provide classification insights. Registry data of 187 unrelated index patients included age at onset, gender, family history, relapse of aHUS and potentially triggering conditions. Mutation analyses were performed in the genes CFH, CD46 and CFI and in the six potential susceptibility genes, FHR1 to FHR5 and C4BP. Germline mutations were identified in 17% of the index cases; 12% in CFH, 3% in CD46 and 2% in CFI. Twenty-nine patients had heterozygous mutations and one each had a homozygous and compound heterozygous mutation. Mutations were not found in the genes FHR1-5 and C4BP. In 40% of the patients with familial HUS a mutation was found. Penetrance by age 45 was 50% among carriers of any mutation including results of relatives of mutation-positive index cases. The only risk factor for a mutation was family history of HUS (p = 0.02). enetrance of aHUS in carriers of mutations is not complete. Occurrence of homo- and heterozygous mutations in the same gene suggests that the number of necessary DNA variants remains unclear. Among clinical information only familial occurrence predicts a mutation. [ABSTRACT FROM AUTHOR]

Elevated pretransplant serum ferritin levels have been associated with an increased incidence of morbidity and mortality after allogeneic haematopoietic stem cell transplantation (HCT). We studied 222 patients who underwent myeloablative allogeneic HCT in whom pretransplantation serum ferritin levels were available. Pretransplantation ferritin > 1910 μg/l was associated with lower overall survival ( P = 0·003), lower relapse-free survival ( P = 0·003), decreased chronic graft- versus-host disease (GVHD) ( P = 0·019) and increased non-relapse mortality (NRM) ( P = 0·042). Similar results were obtained when pretransplantation ferritin was analysed as a continuous variable and by quartiles. Our results indicate that an elevated pretransplant ferritin level adversely impacts transplantation outcomes. The adverse impact of elevated ferritin on NRM and survival was despite its association with lower incidences of acute and chronic GVHD, which are major causes of NRM. The association of ferritin with iron overload and its influence on HCT outcomes requires further prospective validation. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To determine whether vocal cord fixation precludes nonsurgical management of T3/T4 laryngeal carcinoma. Study Design: A retrospective chart review. Methods: Between 1989 and 2005 patient records with T3/T4 squamous cell carcinoma of the larynx with vocal cord fixation at presentation were reviewed. All were treated with a concomitant cisplatin-based chemoradiotherapy protocol and were part of the institutional head and neck cancer chemoradiotherapy registry. Only patients with adequate pre- and post-treatment fiberoptic evaluations were included. Charts were reviewed for demographics and tumor characteristics; return of vocal cord function; local, regional, or distant recurrence after treatment; and need for salvage surgery. The Kaplan-Meier method was used to estimate outcomes, and the log-rank test was used to compare those patients whose vocal cords remained fixed to those with recovery of function. Results: Twenty-three patients met the inclusion criteria, 19 males and 4 females. The median age was 59 years (range, 39-73). Fourteen patients had T3 and nine had T4 tumors. Twelve patients recovered full range of mobility, three had partial recovery, and eight did not recover motion. The median follow-up was 68 months (range, 34-191). Comparing patients with post-treatment partial or fully mobile cords to those with persistent fixation revealed the following: A projected five-year overall survival of 100% versus 25%, ( P < .001), freedom from recurrence of 86.7 versus 25% ( P < .001), local control without surgery of 86.7% versus 30% ( P = .003), and survival with functional larynx of 86.7% versus 25% ( P = .008), respectively. Conclusions: Nonsurgical therapy in patients with pretreatment vocal cord fixation is feasible. However, persistence of vocal cord fixation after definitive chemoradiotherapy is a poor prognostic sign and early surgical intervention should be considered. Laryngoscope, 2009 [ABSTRACT FROM AUTHOR]

The article cites a study which examines the sensitivity of breast magnetic resonance imaging (MRI) in patients with an early-stage breast cancer. Methods used in the study were based on the conduction of contrast-enhanced MRI for breast cancer detection and medical records reassessment. Results show that synchronous cancers were not invasive in 70-years old patient with early-stage breast cancer as observed by MRI.

Background. Determining which patients benefit from larynx preservation strategies remains problematic. We reviewed our experience using multiagent concurrent chemoradiotherapy to identify clinical predictors for success. Methods. Cisplatin and fluorouracil were given during weeks 1 and 4 of radiation to 115 patients with locoregionally advanced larynx or hypopharynx squamous cell cancer without cartilage invasion or laryngeal destruction. Laryngectomy was reserved for local failure. Results. The 5-year Kaplan–Meier projected overall survival was 58%, survival with larynx preservation 52%, local control without surgery 82%, local control (including surgical salvage) 94%, and survival with functional larynx 49%. Local control without surgery was superior in patients with T1-2 versus T3-4 tumors (97% vs 77%, p = .032). No other clinical parameters proved predictive of local control. Conclusion. Larynx preservation was successful in all subsets of appropriately selected patients. Although local failure was more likely in patients with T3-4 tumors, it was infrequent and surgical salvage was effective. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [ABSTRACT FROM AUTHOR]

The article presents a study which is aimed at identifying predictors of outcome and rates of successful discharge for patients with acute leukemia admitted to intensive care units (ICUs) in the U.S. Accordingly, it analyzes 90 patients with acute leukemia who were admitted to an ICU from 2001 to 2004. It mentions respiratory compromise as the most common reason for ICU transfer for all patients. Meanwhile, it concludes that a diagnosis of acute leukemia should not disquality patients from an ICU admission.

The developments in apheresis technologies and techniques and their clinical applications worldwide are technologically, sociologically, and economically motivated. In past apheresis surveys the statistics have highlighted both the differences by geographic region in clinical practice and in the types of technologies utilized. While a national view of apheresis is very important, an international view may be more representative overall of this therapeutic modality than national results that are highly dependent on the local economics and the available technologies. These regional differences have provided a basis for scientific and clinical assessment of these apheresis technologies and their clinical outcomes, and have impacted the marketing and business developments of new technologies worldwide. The results of the International Apheresis Registry for 2005 reporting from 22 centers on 5 continents are presented. The survey collected data exclusively via a secure internet website on 1133 patients for a total of 6501 treatments. Unlike our prior registries, information on stem cell infusions was gathered. Information gathered included patient demographics, medical history, treatment diagnoses, treatment specifics (type, methodology, access type, anticoagulants, drugs, and equipment usage), side-effects, clinical response, and payment provider. As in the prior International Apheresis Registries for 1983, 2000, and 2002 the survey results highlight the regional differences in apheresis usage and treatment methodologies, indicating that an international overview of apheresis may be more representative of the impact of this therapeutic modality. [ABSTRACT FROM AUTHOR]

The non-relapse mortality of autologous stem cell transplant is low enough that the procedure has been extended to older patients with non-Hodgkin's lymphoma. We treated 537 non-Hodgkin's lymphoma patients with high-dose chemotherapy consisting of busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplant. Sixteen patients were identified who died of pulmonary complications at a five-year incidence of 3.6%. Risk factors for pulmonary mortality included older age and lower baseline DCO and FEV1. We conclude that high-dose busulfan is associated with pulmonary mortality after autologous transplant, particularly in older patients. [ABSTRACT FROM AUTHOR]

Authors from Cleveland assessed the impact of warm ischaemia on renal function, using their large database of laparoscopic partial nephrectomies for tumour. While agreeing that renal hilar clamping is essential for precise excision of the tumour, and other elements of the operation, the authors indicate that warm ischaemia may potentially damage the kidney. However, they found that there were virtually no clinical sequelae from warm ischaemic of up to 30 min. They also found that advancing age and pre-existing renal damage increased the risk of postoperative renal damage.To assess the effect of warm ischaemia on renal function after laparoscopic partial nephrectomy (LPN) for tumour, and to evaluate the influence of various risk factors on renal function.Data were analysed from 179 patients undergoing LPN for renal tumour under warm ischaemic conditions, with clamping of the renal artery and vein. Renal function was primarily evaluated in two groups of patients: 15 with tumour in a solitary kidney, who were evaluated by serial serum creatinine measurements; and 12 with two functioning kidneys undergoing unilateral LPN, and evaluated by renal scintigraphy before and 1 month after LPN to quantify differential renal function. Also, in all 179 patients, mean serum creatinine data at baseline, 1 day after LPN, at hospital discharge, and at the last follow-up were provided as supportive evidence. Logistic regression analyses were used to assess the effect of various risk factors on renal function after LPN, i.e. patient age, baseline serum creatinine, tumour size, solitary kidney status, duration of warm ischaemia, pelvicalyceal suture repair, urine output and intravenous fluids during LPN.In the group of patients with a solitary kidney the mean warm ischaemia time was 29 min, kidney parenchyma excised 29%, and serum creatinine at baseline, discharge, the peak after LPN and at the last follow-up (mean 4.8 months) 1.3, 2.3, 2.8, and 1.8 mg/dL, respectively. One patient (6.6%) required temporary dialysis. In the second group, assessed by renal scintigraphy, the function of the operated kidney was reduced by a mean of 29%, commensurate with the amount of parenchyma excised. For all 179 patients, a combination of age≥70 years and a serum creatinine level after LPN of≥1.5 mg/dL correlated with a higher serum creatinine after LPN. On logistic regression, baseline serum creatinine and solitary kidney status were the only variables significant for serum creatinine status after LPN.The bloodless field provided by renal hilar clamping is important for precise tumour excision, pelvicalyceal suture repair and securing parenchymal haemostasis during LPN. However, renal hilar clamping causes warm ischaemia. These data indicate that the clinical sequelae of warm ischaemic renal injury of≈ 30 min are minimal. Advancing age and pre-existing azotaemia increase the risk of renal dysfunction after LPN, especially when the warm ischaemia exceeds 30 min. [ABSTRACT FROM AUTHOR]

Presents a survey on the scientific and clinical assessment of apheresis technologies in the U.S. Highlights of the regional differences in apheresis usage and treatment specifics; Responses of medical directors of apheresis centers to the survey; Treatment diagnosis of myasthenia gravis.

Objective.—To evaluate the effectiveness of intravenous valproate in managing moderate to severe headaches. Background.—Despite major strides in the understanding of primary headache disorders, there have been few additions to acute headache management other than introduction of the triptans. An intravenous antiepileptic preparation, sodium valproate, has been reported to be effective in the management of status epilepticus and acute headache. Methods.—Between March 13, 2000 and October 11, 2000, we prospectively treated, in a nonrandomized and open-label study, every patient with a moderate to severe headache (4 or greater on a visual analog scale of head pain from 1 to 10) who wanted treatment with intravenous valproate. Using a verbal visual analog scale for pain (0 = no headache and 10 = most severe headache), we measured head pain before treatment and at time of discharge. The treating nurse monitored vital signs and side effects. A positive response was defined as a 50% or greater reduction at discharge in baseline pain. Information was collected regarding patient demographics, type of headache (according to criteria of the International Headache Society and that recently proposed for chronic headache), observation time in the treatment suite, cumulative dose of valproate, and use of concurrent medications. Univariable and multivariable correlates of response to treatment were identified using logistic regression analysis. Results .—One hundred thirty treatments were given to 89 women and 17 men, aged 17 to 76 years; 92 patients received only one treatment. Valproate doses ranged between 300 and 1200 mg. Thirty-three patients (31%) presented with episodic migraine, with or without aura; 45 patients (42%) presented with chronic daily headache with a history of episodic migraine, with or without aura (transformed migraine); 22 (21%) with unclassifiable chronic headache; 2 (2%) with episodic cluster headache; and 4 (4%) with chronic tension-type headache. For first treatments only, 61 patients (57.5%) responded to treatment, whereas for all treatments, 82 patients (63.1%) responded. Age and gender did not affect likelihood of response, whereas increasing duration of treatment and the additional use of analgesics were each negatively associated with response. Among headache types, unclassifiable chronic headache segregated from all other classified headaches in terms of poor response. Aside from rare dizziness (n = 2) and one spell interpreted as a pseudoseizure, no side effects were noted. Conclusions.—Intravenous valproate is a safe, rapidly effective, abortive headache agent. It appears to be an effective analgesic for identifiable primary headaches, especially episodic headache, and less effective for unclassifiable chronic headache. Randomized, double-blind, controlled studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Antibiotic allergy de‐labeling using penicillin allergy skin testing (PAST) can reduce the use and cost of alternative, non‐β‐lactam antibiotics in general inpatient populations. This strategy's role in hematopoietic stem cell transplant (HSCT) recipients is unclear. Methods: This study aimed to determine the effect of a pre‐transplant PAST protocol on antibiotic use, days of therapy (DOT), and cost in an immunocompromised population at a single center from 7/1/2010‐2/1/2019. Patients who received chimeric antigen receptor (CAR) T‐cell therapy and those who underwent transplantation in the outpatient setting were excluded. Results: Of 1560 patients who underwent inpatient HSCT during the study period, 208 reported β‐lactam allergy (136/844 [16%] pre‐ and 72/716 [10%] post‐implementation; P <.001). PAST was performed on 7% and 54% of HSCT recipients pre‐ and post‐implementation, respectively. Only two positive PAST were noted. There were no adverse reactions to PAST. There were no significant differences in the disease and transplant characteristics between the two groups. Days of therapy and cost of alternative antibiotics significantly decreased post‐implementation (mean 788 vs 627 days, P =.01; mean $24 425 vs $17 518, P =.009). Conclusion: Penicillin allergy skin testing adjudicates reported β‐lactam allergy in HSCT recipients, lowering use, DOT, and cost of alternative antibiotics and promoting effective formulary agents to treat immunocompromised HSCT recipients. [ABSTRACT FROM AUTHOR]

Background: The spectrum of infectious complications in autologous hematopoietic cell transplant recipients (AHCT) with multiple myeloma has not been well described in the recent era of novel agent induction and improved supportive care. Methods: We conducted a retrospective cohort study of 413 adult myeloma AHCT recipients at our institution from 2007‐2016 to describe the cumulative incidence and risk factors for various infections and FN occurring within the first 100 days after AHCT. Additionally, landmark analysis was done among 404 patients who survived at least 100 days after transplant admission to estimate the association of infections with subsequent non‐relapse mortality (NRM), overall survival (OS), and relapse‐free survival (RFS). Results: Cumulative incidences (95% CI) of infection events by day 100 were: FN 43% (38‐48), any infection 21% (17‐25), bacterial 17% (14‐21), viral 4% (3‐7) and fungal 1% (0.5‐3), central line‐associated blood stream infection 3% (2‐6), and Clostridium difficile colitis 6% (4‐8). Patients with infection had a longer initial transplant hospitalization (median 17 vs 16 days, P < 0.01), more readmissions (31% vs 8%, P < 0.01), and spent more days in hospital in first 100 days (median 18 vs 16 days, P < 0.01). A 100‐day mortality was low and similar between groups (2% vs 1%, P = 0.28). In landmark analysis of 404 100‐day survivors, OS was worse among patients with early infections (hazard ratio 1.54 [1.03‐2.30], P = 0.03), although there was no difference in NRM and RFS. Conclusions: Notwithstanding advances in supportive care, early infectious complications remain a relevant source of morbidity and require attention in myeloma AHCT recipients. [ABSTRACT FROM AUTHOR]

Abstract: The developments in apheresis technologies and techniques and their clinical applications worldwide are technologically, sociologically, and economically driven. In the past, apheresis survey statistics have highlighted both the differences by geographical region in clinical practices and in the types of technologies utilized. While a national view of apheresis is critically important, an international view of apheresis may be more representative overall of this therapeutic modality than national results that are highly dependent on the local economics and the available technologies. These regional differences have provided a basis for the scientific and clinical assessments of these apheresis technologies and their clinical outcomes and have impacted the marketing and business developments of new technologies worldwide. The results of the International Apheresis Registry for 2000 reporting on 39 centers on 4 continents are presented. This survey collected data on 1,080 patients for a total of 15,257 treatments. Information gathered included patient demographics, medical history, treatment diagnoses, treatment specifics (type, methodology, access type, anticoagulants, drugs, equipment usage), side effects, clinical response, and payment provider. As in the prior International Apheresis Registry for 1983, the survey results highlighted the regional differences in apheresis usage and treatment specifics, indicating that an international overview of apheresis may be more representative of the impact of this therapeutic modality. [ABSTRACT FROM AUTHOR]