The experience of patients with hematological malignancy in their terminal stage: a phenomenological study from Jordan's perspective.

BACKGROUND: Patients diagnosed with hematological malignancies residing in low-middle-income countries undergo significant physical and psychological stressors. Despite this, only 16% of them receive proper care during the terminal stages. It is therefore crucial to gain insight into the unique experiences of this population. AIM: To have a better understanding of the needs and experiences of adult patients with advanced hematological malignancy by exploring their perspectives. METHODS: A qualitative interpretive design was employed to collect and analyze data using a phenomenological approach. The study involved in-depth interviews with ten participants aged between 49 and 65 years, utilizing a semi-structured approach. RESULTS: Two primary themes emerged from the participants' experiences of reaching the terminal stage of illness: "Pain, Suffering, and Distress" and "Spiritual Coping." The first theme encompassed physical and emotional pain, suffering, and distress, while the second theme was centered on the participants' spiritual coping mechanisms. These coping mechanisms included seeking comfort in religious practices, relying on spiritual support from family and friends, and finding solace in their beliefs and faith. CONCLUSION: Patients with hematological malignancies in the terminal stages of their disease experience severe pain, considerable physical and psychosocial suffering, and spiritual distress. While they require support to cope with their daily struggles, their experiences often go unnoticed, leading to disappointment and loss of dignity. Patients mainly rely on their spirituality to cope with their situations. Healthcare providers must acknowledge these patients' needs and provide more holistic and effective care.

Bleeding Risk of Acupuncture for Patients with Hematological Malignancies Accompanying Thrombocytopenia: A Retrospective Chart Review.

Introduction: In recent years, it has been reported that acupuncture is useful for alleviating the symptoms of patients with hematological malignancies, but the safety of acupuncture for such patients has not been established. This study evaluated the risk of bleeding from acupuncture in patients with hematological malignancies accompanying thrombocytopenia. Methods: The authors performed a retrospective investigation of the medical records of patients with hematological malignancies who received acupuncture during hospitalization at the hematology department of a single medical center in Japan. The bleeding risk at the acupuncture site was evaluated in the following four groups according to the platelet count measured on the day of acupuncture treatment: (1) <20 × 103/µL, (2) 20-49 × 103/µL, (3) 50-99 × 103/µL, and (4) 100 × 103/µL or more. Occurrence of grade 2 or higher bleeding according to the Common Terminology Criteria for Adverse Events, version 5.0, within 24 h from the acupuncture session or before the next session was defined as an event, and the risk of occurrence of bleeding was examined in each group. Results: Of 2423 acupuncture sessions conducted on 51 patients with hematological malignancies, 815 were included in the analysis. Ninety sessions were performed in the <20 × 103/µL platelet count group, 161 in the 20-49 × 103/µL group, 133 in the 50-99 × 103/µL group, and 431 in the 100 × 103/µL or more group. No bleeding event according to the authors' definition occurred in any of these groups. Conclusions: This study is the largest to date to assess the bleeding risk of acupuncture in patients with hematological malignancies accompanying thrombocytopenia. The authors considered that acupuncture could be safely performed without causing serious bleeding for patients with hematological malignancies accompanying thrombocytopenia.

Knowledge, feelings, and willingness to use palliative care in cancer patients with hematologic malignancies and solid tumors: a prospective, cross-sectional study in a comprehensive cancer center in Germany.

PURPOSE: Patients with hematologic malignancies (HM) receive palliative care (PC) less often and later than patients with solid tumors (ST). Patients' lack of knowledge about PC and negative feelings about PC are barriers to their willingness to use PC. Is there a difference between patients with HM and ST in their knowledge and willingness to use PC? METHODS: Two hundred ten patients (85 HM, 125 ST) from an oncology day clinic at a university hospital participated in this cross-sectional, questionnaire-based survey. RESULTS: Patients with HM and ST had high knowledge and mainly positive feelings about PC. More than half of the patients answered that they would feel reassured by the use of PC, and one-third would feel anxious or hopeless. The majority of patients (58.3%) were willing to use PC. There are no significant differences between patients with HM and ST. In multiple regression analysis, perceived chance of cure and feelings of reassurance and anxiety are associated with willingness to use PC, but not with the HM/ST disease group. More than half (53.9%) of the participants would like the treating physician to choose the timing of a discussion about PC. CONCLUSION: Our study shows a high level of knowledge and relatively positive feelings of patients about PC, with no differences between patients with HM or ST. They expect their treating physician to initiate communication about PC. Communication should include the patient's feelings about PC and their chances of a cure.

Patient-reported distress and problems among elderly patients with hematological malignancy in Korea.

PURPOSE: Treatment for hematological malignancies (HMs) and functional decline associated with age can cause distress in elderly patients with HMs. However, information about the nature and effects of distress in this population is scarce. Therefore, this study examined the level of distress, its source, and the practical/familial/physical/emotional problems among elderly patients with HMs. METHODS: We conducted a cross-sectional study of patients with HMs aged ≥ 65 years who visited an outpatient clinic at a tertiary medical center in Korea between November 2019 and March 2020. Patient-reported distress and problems were measured using the distress thermometer (DT) and 39-item Problem List by the National Comprehensive Cancer Network. Descriptive statistics, χ2 test or Fisher's exact test, and multivariate logistic regression analyses were conducted (N = 132). RESULTS: In total, 62.1% of patients had moderate to severe distress (DT score ≥ 4), experiencing an average of nine problems. Significant sources of distress on multivariate logistic analysis included problems with transportation, depression, and constipation, accounting for 47% of distress variance. Most patients had physical (97.0%) or emotional problems (79.5%). Among these, fatigue (60.6%), worry (59.8%), tingling (59.8%), difficulty with mobility (47.0%), and memory/concentration (40.2%) were the most frequently reported problems. CONCLUSIONS: Elderly patients with HMs have a high burden of distress, which is affected by different sources, compared with younger patients with solid tumors. Thus, in this population, assessment and management of distress need to be conducted considering the unique features of their source and burden. Further research on distress should consider the cancer type and population age.

The effect of music therapy interventions on fatigue in patients with hematological cancers: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To systematically synthesize the effect of music therapy interventions applied to patients with hematological cancer on fatigue. METHODS: The searches were conducted on PubMed, Web of Science, EBSCOhost/CINAHL Complete, Science Direct, Scopus, Cochrane Library, Ovid, ProQuest, and Springer Link databases until August 2021 without any year limitation. The review covered the period between 2003 and 2020. Comprehensive Meta-Analysis 3 software was used in the analysis of meta-analysis data. The meta-analysis was carried out following the PRISMA checklist. Risks of bias were examined by two independent researchers using the Cochrane Collaboration tool. RESULTS: Six randomized controlled trials consisting of 279 participants were included in the systematic review and meta-analysis. The count of music therapy interventions in the included studies ranged between 1 and 8 sessions per participant, each of which was 20 to 45 min long. The music therapy interventions applied to patients with hematological cancers were found to be effective in reducing the severity of fatigue (95% Cl = 0.10 ~ 0.57; Hedge's g = 0.03; p = 0.006). CONCLUSIONS: The findings of the meta-analysis indicated that music therapy interventions made important and positive contributions to reducing fatigue in patients with hematological cancer. Music therapy interventions are a convenient method to reduce fatigue because they are comfortable and non-invasive. It will be beneficial to increase the awareness of nurses about the implementation of music therapy interventions. It is recommended that music therapy interventions applied to patients with a diagnosis of hematological cancer should be considered interventions that can be used together with other non-pharmacological or pharmacological methods to reduce fatigue.

The effect of a single session of 30-min mindful breathing in reducing fatigue among patients with haematological cancer - a randomised controlled trial.

BACKGROUND: Patients with haematological cancer had considerable symptom burden, in which fatigue was the most prevalent. Almost 70% of haematological cancer patients reported fatigue. METHODS: We conducted a parallel-group, non-blinded, randomised control trial at the haemato-oncology unit of University Malaya Medical Centre, from 1st October 2019 to 31st May 2020. Patients included were ≥ 18 years, had histopathological diagnosis of haematological cancer, and fatigue score of ≥4 based on the fatigue subscale of Edmonton Symptom Assessment System (ESAS). Patients allocated to the intervention group received standard care plus a guided 30-min mindful breathing session, while those in control group received standard care. The study outcomes include fatigue severity according to the fatigue subscale of ESAS, visual analogue scale of 0 - 10, and Functional Assessment of Chronic Illness Therapy Fatigue Scale Version 4, at minute 0 and minute 30. RESULTS: Of 197 patients screened, 80 were eligible and they were equally randomised into 30-min mindful breathing versus standard care. Lymphoma (58.9%) was the commonest haematological malignancy, followed by multiple myeloma (13.8%), acute leukaemia (11.3%), myeloproliferative neoplasm (6.3%), chronic leukaemia (5.0%) and myelodysplastic syndrome (5.0%). There was no difference in the demographic and clinical characteristics between the 2 groups. At minute 0, both arms of patients had similar ESAS-fatigue score (median, 5) and FACIT-fatigue score (mean ± SD, 24.7 ± 10.6 for intervention group versus 24.7 ± 9.7 for control group). At minute 30, intervention group had lower ESAS-fatigue score (median, 3 versus 5) and FACIT-fatigue score (mean ± SD, 17.1 ± 10.5 versus 24.8 ± 11.3) compared to control group. Both the ESAS-fatigue score reduction (median, - 2 versus 0, p = 0.002) and FACIT-fatigue score reduction (mean ± SD, - 6.7 versus + 0.8; p < 0.001) for the intervention group were statistically significant. The calculated effect size Cohen's d was 1.4 for between-group comparison of differences in total FACIT-fatigue score. CONCLUSIONS: Our results provide evidence that a single session of 30-min mindful breathing was effective in reducing fatigue in haematological cancer patients. On top of all the currently available methods, 30-min mindful breathing can prove a valuable addition. TRIAL REGISTRATION: NCT05029024 , date of registration 15th August 2021. (Retrospectively registered).

Vitamin D supplementation for children with cancer: A systematic review and consensus recommendations.

BACKGROUND: Prevalent vitamin D deficiency (VDD) and low bone mineral density (BMD) have led to vitamin D supplementation for children with cancer, regardless vitamin D status. However, it remains unsettled whether this enhances bone strength. We sought to address this issue by carrying out a systematic review of the literature. METHODS: We conducted a literature search using PubMed, Embase, and Cochrane databases. Studies including children up to 5 years after cancer therapy were assessed for the association between 25-hydroxyvitamin D (25OHD) levels and BMD Z-scores or fractures, and the effect of vitamin D supplementation on BMD or fractures. Evidence quality was assessed using the GRADE methodology. RESULTS: Nineteen studies (16 observational and 3 interventional, mainly involving children with hematologic malignancies) were included. One study which analyzed 25OHD as a threshold variable (≤10 ng/ml) found a significant association between 25OHD levels and BMD Z-scores, while 25OHD as a continuous variable was not significantly associated with BMD Z-scores in 14 observational studies. We found neither a significant association between lower 25OHD levels and fractures (2 studies), nor between vitamin D (and calcium) supplementation and BMD or fracture frequency (3 studies) (very low quality evidence). CONCLUSION: There is a lack of evidence for an effect of vitamin D (and calcium) supplementation on BMD or fractures in children with cancer. Further research is needed; until then, we recommend dietary vitamin D/calcium intake in keeping with standard national guidelines, and periodic 25OHD monitoring to detect levels <20 ng/ml. Vitamin D/calcium supplementation is recommended in children with low levels, to maintain levels ≥20 ng/ml year-long.

Clinical significance of post-treatment viral load of cytomegalovirus in patients with hematologic malignancies.

OBJECTIVES: Patients with hematologic diseases were at high risk for cytomegalovirus (CMV) diseases. In the present study, we compare various prognostic factors during CMV viremia, with specific emphasis on the relationship between viremia eradication and the long-term prognosis of patients after each episode. METHODS: Adult patients with hematologic diseases who had a detectable CMV viral load (VL) (equal to or above 150 copies/mL) were included in the study. Medical records were reviewed for demographic data including age, sex, hematologic and other underlying diseases, status of stem cell transplantation, antiviral medication, serum CMV viral load before and after antiviral treatment. RESULTS: A total of 101 episodes of CMV viremia occurred in patients with hematologic diseases. Comparison of various prognostic factors revealed non-survivors more frequently suffered from pneumonia and concomitant bacterial or fungal infections, had less frequently undergone hematopoietic stem cell transplantation (HSCT), and had higher peak VLs during viremic episodes. After antiviral therapy, eradication of viremia was much less frequently achieved in non-survivors. The Kaplan-Meier curves revealed that patients with detectable end-treatment VL had lower survival rates even if the antivirals were administered for more than 21 days. In a multivariate Cox proportional-hazard model, a detectable VL at the end of antiviral therapy independently predicted mortality within 180 days. CONCLUSIONS: In patients with hematologic diseases suffering CMV viremia, failure to eradicate viremia after antiviral therapy indicates a higher chance of mortality and can be regarded as a useful indicator in evaluating the patient's long-term prognosis.

Enhanced antimicrobial stewardship based on rapid phenotypic antimicrobial susceptibility testing for bacteraemia in patients with haematological malignancies: a randomized controlled trial.

OBJECTIVES: Recently, rapid phenotypic antimicrobial susceptibility testing (AST) based on microscopic imaging analysis has been developed. The aim of this study was to determine whether implementation of antimicrobial stewardship programmes (ASP) based on rapid phenotypic AST can increase the proportion of patients with haematological malignancies who receive optimal targeted antibiotics during early periods of bacteraemia. METHODS: This randomized controlled trial enrolled patients with haematological malignancies and at least one positive blood culture. Patients were randomly assigned 1:1 to conventional (n = 60) or rapid phenotypic (n = 56) AST. The primary outcome was the proportion of patients receiving optimal targeted antibiotics 72 hr after blood collection for culture. RESULTS: The percentage receiving optimal targeted antibiotics at 72 hr was significantly higher in the rapid phenotypic AST group (45/56, 80.4%) than in conventional AST group (34/60, 56.7%) (relative risk (RR) 1.42, 95% confidence interval (CI) 1.09-1.83). The percentage receiving unnecessary broad-spectrum antibiotics at 72 hr was significantly lower (7/26, 12.5% vs 18/60, 30.0%; RR 0.42, 95% CI 0.19-0.92) and the mean time to optimal targeted antibiotic treatment was significantly shorter (38.1, standard deviation (SD) 38.2 vs 72.8, SD 93.0 hr; p < 0.001) in the rapid phenotypic AST group. The mean time from blood collection to the AST result was significantly shorter in the rapid phenotypic AST group (48.3, SD 17.6 vs 83.1, SD 22.2 hr). DISCUSSION: ASP based on rapid phenotypic AST can rapidly optimize antibiotic treatment for bacteraemia in patients with haematological malignancy. Rapid phenotypic AST can improve antimicrobial stewardship in immunocompromised patients.

Medical Cannabis in Cancer Patients: A Survey of a Community Hematology Oncology Population.

OBJECTIVES: Cancer patients are using medical cannabis (MC) to address symptoms; however, little data exist to guide clinicians when counseling patients. We seek to define the patterns of MC use among cancer patients, as well as efficacy and safety of MC. MATERIALS AND METHODS: Cancer patients attending oncology office visits at Beaumont Hospital, Michigan from July to December 2018 were anonymously surveyed. The survey included data regarding demographics, diagnosis, treatment, symptom burden, and MC use. Patients who reported MC use since their cancer diagnosis completed a section on patterns of use, efficacy, and safety. RESULTS: The response rate was 188 of 327 (57.5%). MC use was reported by 46 of 188 (24.5%). A median composite baseline symptom score ranging from 8 (best) to 32 (worst) was higher in patients using MC versus nonusers; 17.5 versus 14.4 (P<0.001). Pain was the symptom with the highest frequency of improvement 34/42 (81%), followed by appetite 34/44 (77.3%), and anxiety 32/44 (73%). MC improved the ability to tolerate treatment in 24/44 (54.5%). Cloudy thinking is the symptom that worsened the most 7/42 (16.7%), with decreased energy being experienced by 4/41 (9.8%) of the users. CONCLUSIONS: MC was utilized by a significant portion of cancer patients in this sample, across age, diagnosis, stage, and treatment. Patients with a higher severity of baseline symptoms were more likely to use MC and report a favorable efficacy profile of MC. Minimal toxicity was reported in this cohort. Prospective studies are needed to define the efficacy and safety of MC.

A systematic literature review of the effects of immunoglobulin replacement therapy on the burden of secondary immunodeficiency diseases associated with hematological malignancies and stem cell transplants.

INTRODUCTION: Secondary immunodeficiency diseases (SID) caused by hematological malignancies (HMs), stem cell transplant (SCT), and associated therapies are mainly characterized by the presence of hypogammaglobulinemia or antibody production deficits. AREAS COVERED: The authors summarized the scientific literature on disease burden of SIDs in patients who had HMs or SCT. Systematic searches were conducted to identify English-language articles from 1994-2020, reporting on clinical, humanistic, and economic burdens of SID due to HMs or SCT. Definitions of SID and serum immunoglobulin G thresholds varied across 24 eligible studies. In most (n = 16) studies, patients received immunoglobulin replacement therapy (IGRT). Several studies found IGRT was associated with significant reductions in rates of infection and antimicrobial use. However, 1 study found no statistically significant difference in antibiotic use with IGRT. Only 3 studies reported on quality of life, and no economic studies were identified. EXPERT OPINION: Overall, the findings show several beneficial effects of IGRT on clinical outcomes and quality of life; however, disparate definitions, infrequent reporting of statistical significance, and scarcity of clinical trial data after the 1990s present areas for further investigation. This paucity indicates an unmet need of current evidence to assess the benefits of IGRT in SID.

Allogeneic bone marrow transplantation with post-transplant cyclophosphamide for patients with HIV and haematological malignancies: a feasibility study.

BACKGROUND: Allogeneic blood or marrow transplantation (alloBMT) is a potentially life-saving treatment for individuals with HIV and haematological malignancies; challenges include identifying donors and maintaining antiretroviral therapy (ART). The objectives of our study were to investigate interventions to expand donor options and to prevent ART interruptions for patients with HIV in need of alloBMT. METHODS: This single-arm, interventional trial took place at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (Baltimore, MD, USA). Individuals with HIV who were at least 18 years of age and referred for alloBMT for a standard clinical indication were eligible. The only exclusion criterion was a history of documented resistance to enfuvirtide. We used post-transplant cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis to expand donor options and an optimised ART strategy of avoiding pharmacoenhancers and adding subcutaneous enfuvirtide during post-transplant cyclophosphamide and during oral medication intolerance. Our primary outcome was the proportion of participants who maintained ART through day 60 after alloBMT. We measured the HIV latent reservoir using a quantitative viral outgrowth assay. This study is registered on ClinicalTrials.gov, NCT01836068. FINDINGS: Between June 1, 2013, and August 27, 2015, nine patients who were referred for transplant provided consent. Two patients had relapsed malignancy before donor searches were initiated. Seven patients had suitable donors identified (two matched sibling, two matched unrelated, two haploidentical, and one single-antigen mismatched unrelated) and proceeded to alloBMT. All patients maintained ART through day 60 and required ART changes (median 1, range 1-3) in the first 90 days. One patient stopped ART and developed HIV rebound with grade 4 meningoencephalitis at day 146. Among six patients who underwent alloBMT and had longitudinal measurements available, the HIV latent reservoir was not detected post-alloBMT in four patients with more than 95% donor chimerism, consistent with a 2·06-2·54 log10 reduction in the HIV latent reservoir. In the two patients with less than 95% donor chimerism, the HIV latent reservoir remained stable. INTERPRETATION: By using post-transplant cyclophosphamide as GVHD prophylaxis, we successfully expanded alloBMT donor options for patients with HIV. Continuing ART with a regimen that includes enfuvirtide post-alloBMT was safe, but life-threatening viral rebound can occur with ART interruption. FUNDING: amfAR (the Foundation for AIDS Research), Johns Hopkins University Center for AIDS Research, and National Cancer Institute.

Candidaemia in haematological malignancy patients from a SEIFEM study: Epidemiological patterns according to antifungal prophylaxis.

BACKGROUND: Candidaemia is an important infectious complication for haematological malignancy patients. Antifungal prophylaxis reduces the incidence of candidaemia but may be associated with breakthrough candidaemia. OBJECTIVE: To analyse the Candida species' distribution and relative antifungal susceptibility profiles of candidaemia episodes in relation to the use of antifungal prophylaxis among Italian SEIFEM haematology centres. METHODOLOGY: This multicentre retrospective observational SEIFEM study included 133 single-species candidaemia episodes of haematological malignancy patients for whom antifungal susceptibility testing results of blood Candida isolates were available between 2011 and 2015. Each participating centre provided both clinical and microbiological data. RESULTS: Non-Candida albicans Candida (NCAC) species were the mostly isolated species (89, 66.9%), which accounted for C parapsilosis (35, 26.3%), C glabrata (16, 12.0%), C krusei (14, 10.5%), C tropicalis (13, 9.8%) and uncommon species (11, 8.3%). C albicans caused the remaining 44 (33.1%) episodes. Excluding 2 C albicans isolates, 23 of 25 fluconazole-resistant isolates were NCAC species (14 C krusei, 6 C glabrata, 2 C parapsilosis and 1 C tropicalis). Fifty-six (42.1%) of 133 patients developed breakthrough candidaemia. Systemic antifungal prophylaxis consisted of azoles, especially fluconazole and posaconazole, in 50 (89.3%) of 56 patients in whom a breakthrough candidaemia occurred. Interestingly, all these patients tended to develop a C krusei infection (10/56, P = .02) or a fluconazole-resistant isolate's infection (14/50, P = .04) compared to patients (4/77 and 10/77, respectively) who did not have a breakthrough candidaemia. CONCLUSIONS: Optimisation of prophylactic strategies is necessary to limit the occurrence of breakthrough candidaemia and, importantly, the emergence of fluconazole-resistant NCAC isolates' infections in haematological malignancy patients.

How I treat pain in hematologic malignancies safely with opioid therapy.

The field of malignant hematology has experienced extraordinary advancements with survival rates doubling for many disorders. As a result, many life-threatening conditions have since evolved into chronic medical ailments. Paralleling these advancements have been increasing rates of complex hematologic pain syndromes, present in up to 60% of patients with malignancy who are receiving active treatment and up to 33% of patients during survivorship. Opioids remain the practice cornerstone to managing malignancy-associated pain. Prevention and management of opioid-related complications have received significant national attention over the past decade, and emerging data suggest that patients with cancer are at equal if not higher risk of opioid-related complications when compared with patients without malignancy. Numerous tools and procedural practice guides are available to help facilitate safe prescribing. The recent development of cancer-specific resources directing algorithmic use of validated pain screening tools, prescription drug monitoring programs, urine drug screens, opioid use disorder risk screening instruments, and controlled substance agreements have further strengthened the framework for safe prescribing. This article, which integrates federal and organizational guidelines with known risk factors for cancer patients, offers a case-based discussion for reviewing safe opioid prescribing practices in the hematology setting.

Considerations for Managing Patients With Hematologic Malignancy During the COVID-19 Pandemic: The Seattle Strategy.

In January 2020, the first documented patient in the United States infected with severe acute respiratory syndrome coronavirus 2 was diagnosed in Washington State. Since that time, community spread of coronavirus disease 2019 (COVID-19) in the state has changed the practice of oncologic care at our comprehensive cancer center in Seattle. At the Seattle Cancer Care Alliance, the primary oncology clinic for the University of Washington/Fred Hutchinson Cancer Consortium, our specialists who manage adult patients with hematologic malignancies have rapidly adjusted clinical practices to mitigate the potential risks of COVID-19 to our patients. We suggest that our general management decisions and modifications in Seattle are broadly applicable to patients with hematologic malignancies. Despite a rapidly changing environment that necessitates opinion-based care, we provide recommendations that are based on best available data from clinical trials and collective knowledge of disease states.

Saprochaete clavata infections in patients undergoing treatment for haematological malignancies: A report of a monocentric outbreak and review of the literature.

Saprochaete clavata is a rare cause of fungaemia with deep organ involvement in patients with haematological malignancies with reported mortality rates of 60%-80%. We describe four cases of S clavata infection in a haematology unit over several months that were treated with voriconazole-based regimens. We also review the literature on factors that could contribute to earlier recognition and effective treatment of S clavata. We included all cases of culture-positive S clavata from sterile sites with associated signs of infection in patients undergoing treatment for a haematological malignancy. Isolates were identified by MALDI-TOF MS, and spectrum profiles were used to prepare clustering analysis of isolates. Susceptibility testing was performed using a commercial microtitre methods. Saprochaete clavata was isolated from the bloodstream in three cases and bronchial alveolar lavage (BAL) fluid in one case. Clustering analysis suggested strains of S clavata were clonal without evidence of divergence although a common source was not identified. Susceptibility testing yielded elevated MICs to fluconazole (8 mg/L) and echinocandins (>1-8 mg/L). All patients were treated with voriconazole-based regimens resulting in survival of 3/4 patients, who continued chemotherapy for their underlying malignancy without evidence of relapse. Saprochaete clavata is a rare but aggressive cause of breakthrough yeast infection in patients undergoing treatment for haematological malignancies, particularly patients with a prior history of echinocandin treatment. Timely initiation of appropriate treatment, aided by more rapid identification in microbiology laboratory, can reduce the risk of deep organ dissemination and patient death.

Multicenter analysis of outcomes in blastic plasmacytoid dendritic cell neoplasm offers a pretargeted therapy benchmark.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematologic malignancy with poor outcomes. Existing data on the clinical behavior of BPDCN are limited because reported outcomes are from small retrospective series, and standardized treatment guidelines are lacking. The interleukin-3 cytotoxin conjugate tagraxofusp was recently tested in phase 1/2 trials that led to US Food and Drug Administration approval, the first ever for BPDCN. However, because there was no matched internal comparator in this or any clinical study to date, results of BPDCN trials testing new drugs are difficult to compare with alternative therapies. We therefore sought to define the clinical characteristics and outcomes of a group of patients with BPDCN treated at 3 US cancer centers in the modern era but before tagraxofusp was available. In 59 studied patients with BPDCN, the median overall survival from diagnosis was 24 months, and outcomes were similar in patients with "skin only" or with systemic disease at presentation. Intensive first-line therapy and "lymphoid-type" chemotherapy regimens were associated with better outcomes. Only 55% of patients received intensive chemotherapy, and 42% of patients underwent stem cell transplantation. Clinical characteristics at diagnosis associated with poorer outcomes included age >60 years, abnormal karyotype, and terminal deoxynucleotidyltransferase (TdT) negativity in the BPDCN cells. We also identified disease responses to pralatrexate and enasidenib in some patients. This study highlights poor outcomes for patients with BPDCN in the modern era and the need for new treatments. Outcomes from ongoing clinical trials for BPDCN can be evaluated relative to this contemporary cohort.

Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematologic malignancies carrying multidrug-resistance bacteria.

Fecal microbiota transplantation is an effective treatment in recurrent Clostridium difficile infection. Promising results to eradicate multidrug-resistant bacteria have also been reported with this procedure, but there are safety concerns in immunocompromised patients. We report results in ten adult patients colonized with multidrug-resistant bacteria, undergoing fecal microbiota transplantation before (n=4) or after (n=6) allogeneic hematopoietic stem cell transplantation for hematologic malignancies. were obtained from healthy related or unrelated donors. Fecal material was delivered either by enema or via nasogastric tube. Patients were colonized or had infections from either carbapenemase-producing bacteria (n=8) or vancomycin-resistant enterococci (n=2). Median age at fecal microbiota transplantation was 48 (range, 16-64) years. Three patients needed a second transplant from the same donor due to initial failure of the procedure. With a median follow up of 13 (range, 4-40) months, decolonization was achieved in seven of ten patients. In all patients, fecal micro-biota transplantation was safe: one patient presented with constipation during the first five days after FMT and two patients had grade I diarrhea. One case of gut grade III acute graft-versus-host disease occurred after fecal microbiota transplantation. In patients carrying or infected by multidrug-resistant bacteria, fecal microbiota transplantation is an effective and safe decolonization strategy, even in those with hematologic malignancies undergoing hematopoietic stem cell transplantation.

Aerobic physical exercise for adult patients with haematological malignancies.

BACKGROUND: Although people with haematological malignancies have to endure long phases of therapy and immobility, which is known to diminish their physical performance level, the advice to rest and avoid intensive exercises is still common practice. This recommendation is partly due to the severe anaemia and thrombocytopenia from which many patients suffer. The inability to perform activities of daily living restricts them, diminishes their quality of life and can influence medical therapy. OBJECTIVES: In this update of the original review (published in 2014) our main objective was to re-evaluate the efficacy, safety and feasibility of aerobic physical exercise for adults suffering from haematological malignancies considering the current state of knowledge. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2018, Issue 7) and MEDLINE (1950 to July 2018) trials registries (ISRCTN, EU clinical trials register and clinicaltrials.gov) and conference proceedings. We did not apply any language restrictions. Two review authors independently screened search results, disagreements were solved by discussion. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing an aerobic physical exercise intervention, intending to improve the oxygen system, in addition to standard care with standard care only for adults suffering from haematological malignancies. We also included studies that evaluated aerobic exercise in addition to strength training. We excluded studies that investigated the effect of training programmes that were composed of yoga, tai chi chuan, qigong or similar types of exercise. We also excluded studies exploring the influence of strength training without additive aerobic exercise as well as studies assessing outcomes without any clinical impact. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results, extracted data and assessed the quality of trials. We used risk ratios (RRs) for adverse events, mortality and 100-day survival, standardised mean differences (SMD) for quality of life (QoL), fatigue, and physical performance, and mean differences (MD) for anthropometric measurements. MAIN RESULTS: In this update, nine trials could be added to the nine trials of the first version of the review, thus we included eighteen RCTs involving 1892 participants. Two of these studies (65 participants) did not provide data for our key outcomes (they analysed laboratory values only) and one study (40 patients) could not be included in the meta-analyses, as results were presented as changes scores only and not as endpoint scores. One trial (17 patients) did not report standard errors and could also not be included in meta-analyses. The overall potential risk of bias in the included trials is unclear, due to poor reporting.The majority of participants suffered from acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), malignant lymphoma and multiple myeloma, and eight trials randomised people receiving stem cell transplantation. Mostly, the exercise intervention consisted of various walking intervention programmes with different duration and intensity levels.Our primary endpoint overall survival (OS) was only reported in one of these studies. The study authors found no evidence for a difference between both arms (RR = 0.67; P = 0.112). Six trials (one trial with four arms, analysed as two sub-studies) reported numbers of deceased participants during the course of the study or during the first 100 to 180 days. For the outcome mortality, there is no evidence for a difference between participants exercising and those in the control group (RR 1.10; 95% CI 0.79 to 1.52; P = 0.59; 1172 participants, low-certainty evidence).For the following outcomes, higher numbers indicate better outcomes, with 1 being the best result for the standardised mean differences. Eight studies analysed the influence of exercise intervention on QoL. It remains unclear, whether physical exercise improves QoL (SMD 0.11; 95% CI -0.03 to 0.24; 1259 participants, low-certainty evidence). There is also no evidence for a difference for the subscales physical functioning (SMD 0.15; 95% CI -0.01 to 0.32; 8 trials, 1329 participants, low-certainty evidence) and anxiety (SMD 0.03; 95% CI -0.30 to 0.36; 6 trials, 445 participants, very low-certainty evidence). Depression might slightly be improved by exercising (SMD 0.19; 95% CI 0.0 to 0.38; 6 trials, 445 participants, low-certainty evidence). There is moderate-certainty evidence that exercise probably improves fatigue (SMD 0.31; 95% CI 0.13 to 0.48; 9 trials, 826 patients).Six trials (435 participants) investigated serious adverse events. We are very uncertain, whether additional exercise leads to more serious adverse events (RR 1.39; 95% CI 0.94 to 2.06), based on very low-certainty evidence.In addition, we are aware of four ongoing trials. However, none of these trials stated, how many patients they will recruit and when the studies will be completed, thus, potential influence of these trials for the current analyses remains unclear. AUTHORS' CONCLUSIONS: Eighteen, mostly small RCTs did not identify evidence for a difference in terms of mortality. Physical exercise added to standard care might improve fatigue and depression. Currently, there is inconclusive evidence regarding QoL, physical functioning, anxiety and SAEs .We need further trials with more participants and longer follow-up periods to evaluate the effects of exercise intervention for people suffering from haematological malignancies. To enhance comparability of study data, development and implementation of core sets of measuring devices would be helpful.

Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study.

BACKGROUND: Triazole resistance is an increasing problem in invasive aspergillosis (IA). Small case series show mortality rates of 50%-100% in patients infected with a triazole-resistant Aspergillus fumigatus, but a direct comparison with triazole-susceptible IA is lacking. METHODS: A 5-year retrospective cohort study (2011-2015) was conducted to compare mortality in patients with voriconazole-susceptible and voriconazole-resistant IA. Aspergillus fumigatus culture-positive patients were investigated to identify patients with proven, probable, and putative IA. Clinical characteristics, day 42 and day 90 mortality, triazole-resistance profiles, and antifungal treatments were investigated. RESULTS: Of 196 patients with IA, 37 (19%) harbored a voriconazole-resistant infection. Hematological malignancy was the underlying disease in 103 (53%) patients, and 154 (79%) patients were started on voriconazole. Compared with voriconazole-susceptible cases, voriconazole resistance was associated with an increase in overall mortality of 21% on day 42 (49% vs 28%; P = .017) and 25% on day 90 (62% vs 37%; P = .0038). In non-intensive care unit patients, a 19% lower survival rate was observed in voriconazole-resistant cases at day 42 (P = .045). The mortality in patients who received appropriate initial voriconazole therapy was 24% compared with 47% in those who received inappropriate therapy (P = .016), despite switching to appropriate antifungal therapy after a median of 10 days. CONCLUSIONS: Voriconazole resistance was associated with an excess overall mortality of 21% at day 42 and 25% at day 90 in patients with IA. A delay in the initiation of appropriate antifungal therapy was associated with increased overall mortality.