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The bone marrow (BM) is responsible for generating and maintaining lifelong output of blood and immune cells. In addition to its key hematopoietic function, the BM acts as an important lymphoid organ, hosting a large variety of mature lymphocyte populations, including B cells, T cells, natural killer T cells, and innate lymphoid cells. Many of these cell types are thought to visit the BM only transiently, but for others, like plasma cells and memory T cells, the BM provides supportive niches that promote their long-term survival. Interestingly, accumulating evidence points toward an important role for mature lymphocytes in the regulation of hematopoietic stem cells (HSCs) and hematopoiesis in health and disease. In this review, we describe the diversity, migration, localization, and function of mature lymphocyte populations in murine and human BM, focusing on their role in immunity and hematopoiesis. We also address how various BM lymphocyte subsets contribute to the development of aplastic anemia and immune thrombocytopenia, illustrating the complexity of these BM disorders and the underlying similarities and differences in their disease pathophysiology. Finally, we summarize the interactions between mature lymphocytes and BM resident cells in HSC transplantation and graft-versus-host disease. A better understanding of the mechanisms by which mature lymphocyte populations regulate BM function will likely improve future therapies for patients with benign and malignant hematologic disorders., (© 2021 by The American Society of Hematology.)

Background: In children, the complications of severe acute respiratory syndrome coronavirus 2 infection occur less frequently than in adults but the characteristics of this disease in oncology patients are not well characterized., Methods: This was a retrospective study in patients younger than 18 years of age with coronavirus disease 2019 (COVID-19) and cancer diagnoses between April and September 2020. Demographic variables, laboratory, and radiologic findings and complications of each case were identified. A descriptive analysis was performed., Results: A total of 33 patients were identified; the median age was 10 years. Fifteen patients (42%) were in chemotherapy at the time of the infection diagnosis, in two patients the chemotherapy protocol was permanently suspended. The most common symptom was fever in 20 patients (60%). Seven patients (21.2%) showed mild pneumonia, four patients (12.1%) severe pneumonia, and three cases (9.0%) were classified as critical. In the evaluated cohort, five patients (15.1%) died, and in two of those, death was caused by COVID-19 infection., Conclusions: Children with an oncologic disease, the search for COVID cases should be oriented to patients with fever, including febrile neutropenia, the presence of respiratory symptoms, and the search for epidemiologic contact. A higher frequency of complications and mortality attributed to COVID-19, two in pediatric oncohematologic patients was found. Institutional strategies to detect the infection early and lower institutional infection are indicated., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Brief measures of physical function such as gait speed may be useful to optimize treatment intensity for older adults who have blood cancer; however, little is known about whether such assessments are already captured within oncologists' "gestalt" assessments., Methods: Gait speed was assessed in 782 patients ≥75 years of age who had blood cancer, with results reported to providers after treatment decisions were made; 408 patients required treatment when different intensities were available per National Comprehensive Cancer Network (NCCN) guidelines. We performed structured abstractions of treatment intensity recommendations into standard intensity, reduced intensity, or supportive care, based on NCCN guidelines. We modeled gait speed and survival using Cox regression and performed ordinal logistic regression to assess predictors of NCCN-based categorizations of oncologists' treatment intensity recommendations, including gait speed., Results: The median survival by gait speed category was 10.8 months (<0.4 m/s), 18.6 months (0.4-0.6 m/s), 34.0 months (0.6-0.8 m/s), and unreached (>0.8 m/s). Univariable hazard ratios (HRs) for death increased for each lower category compared with ≥0.8 m/s (0.6-0.8 m/s: HR, 1.76; 0.4-0.6 m/s: HR, 2.30; <0.4 m/s: HR, 3.31). Gait speed predicted survival in multivariable Cox regression (all P < .05). In multivariable models including age, sex, and Eastern Cooperative Oncology Group performance status, gait speed did not predict oncologists' recommended treatment intensity (all P > .05) and did not add to a base model predicting recommended treatment intensity., Conclusion: In older adults with blood cancer who presented for treatment, gait speed predicted survival but not treatment intensity recommendation. Incorporating gait speed into decision making may improve optimal treatment selection., (© 2020 American Cancer Society.)

Background: The effect of a peritransplant multidirectional walking intervention to target losses in physical function and quality of life (QOL) has not been investigated., Purpose: This study examined the effects of a novel multidirectional walking program on physical function and QOL in adults receiving a hematopoietic stem cell transplant (HSCT)., Methods: Thirty-five adults receiving an autologous or allogeneic HSCT were randomized to a multidirectional walking (WALK) or usual care (CONT) group. The WALK group received supervised training during hospitalization; the CONT group received usual care. Patients were assessed at admission (t0), 3 to 5 d post-HSCT (t1), and 30 d post-HSCT (t2). Physical function measures included the 6-min walk test (6MWT), the Physical Performance Test, and the Timed Up and Go test. Health-related QOL was collected using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire., Results: There were no significant between-group changes for physical function or QOL. However, after the intervention (t1 to t2), the WALK group showed significant improvement in aerobic capacity (6MWT, P = 0.01), physical (P < 0.01) and functional well-being (P = 0.04), and overall QOL scores (P < 0.01). The CONT group saw no significant changes in physical function or QOL. Effect sizes showed the WALK group had a larger positive effect on physical function and QOL. Minimal clinically important differences in the 6MWT and FACT-BMT were exceeded in the WALK group., Conclusion: A multidirectional walking program during the transplant period may be effective at increasing aerobic capacity and QOL for patients receiving HSCT compared with no structured exercise., (Copyright © 2020 by the American College of Sports Medicine.)

Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) that lack a 5' end cap or a 3' end poly-(A) tail and form a circular structure through covalent bonds. Compared to linear RNAs, circRNAs are more conservative and stable, and their distribution is spatiotemporally regulated. circRNAs, as a new type of competitive endogenous RNA (ceRNA), are involved in many disease processes and are also related to the occurrence and development of tumors. Over the past three years, the role of circRNAs in hematological malignancies has received increasing attention. Related research has shown that circRNAs may regulate the occurrence and development of hematological malignancies and contribute to drug resistance through a variety of molecular mechanisms. Therefore, to lay the foundation and point out directions for further research on circRNAs, this article systematically reviews the research progress on circRNAs in leukemia, lymphoma, and myeloma., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

DNA repair plays an essential role in protecting cells that are repeatedly exposed to endogenous or exogenous insults that can induce varying degrees of DNA damage. Any defect in DNA repair mechanisms results in multiple genomic changes that ultimately may result in mutation, tumor growth, and/or cell apoptosis. Furthermore, impaired repair mechanisms can also lead to genomic instability, which can initiate tumorigenesis and development of hematological malignancy. This review discusses recent findings and highlights the importance of DNA repair components and the impact of their aberrations on hematological malignancies.

Background: Tattoos may cause a variety of adverse reactions in the body, including immune reactions and infections. However, it is unknown whether tattoos may increase the risk of lymphatic cancers such as non-Hodgkin lymphoma (NHL) and multiple myeloma., Methods: Participants from two population-based case-control studies were included in logistic regression models to examine the association between tattoos and risk of NHL and multiple myeloma., Results: A total of 1,518 participants from the NHL study (737 cases) and 742 participants from the multiple myeloma study (373 cases) were included in the analyses. No statistically significant associations were found between tattoos and risk of NHL or multiple myeloma after adjusting for age, sex, ethnicity, education, body mass index, and family history., Conclusions: We did not identify any significant associations between tattoos and risk of multiple myeloma, NHL, or NHL subtypes in these studies., Impact: Though biologically plausible, tattoos were not associated with increased risk of NHL or multiple myeloma in this study. Future studies with greater detail regarding tattoo exposure may provide further insights., (©2020 American Association for Cancer Research.)

The inhibition of the DNA damage response (DDR) pathway in the treatment of cancer has recently gained interest, and different DDR inhibitors have been developed. Among them, the most promising ones target the WEE1 kinase family, which has a crucial role in cell cycle regulation and DNA damage identification and repair in both nonmalignant and cancer cells. This review recapitulates and discusses the most recent findings on the biological function of WEE1/PKMYT1 during the cell cycle and in the DNA damage repair, with a focus on their dual role as tumor suppressors in nonmalignant cells and pseudo-oncogenes in cancer cells. We here report the available data on the molecular and functional alterations of WEE1/PKMYT1 kinases in both hematological and solid tumors. Moreover, we summarize the preclinical information on 36 chemo/radiotherapy agents, and in particular their effect on cell cycle checkpoints and on the cellular WEE1/PKMYT1-dependent response. Finally, this review outlines the most important pre-clinical and clinical data available on the efficacy of WEE1/PKMYT1 inhibitors in monotherapy and in combination with chemo/radiotherapy agents or with other selective inhibitors currently used or under evaluation for the treatment of cancer patients.

Context and Objectives: This study aimed to assess the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) in young women who underwent allogeneic hematopoietic stem cell transplantation (HSCT)., Participants and Methods: This retrospective cohort included 234 female patients with premature ovarian insufficiency (POI) who underwent allogeneic HSCT between April 2009 and April 2016 at Seoul St. Mary's Hospital in Seoul, Korea. Inclusion criteria included adult patients who were age 40 years or younger at the time of transplantation and were followed for at least 3 years after HSCT., Results: At the first and second years after HRT, there was a significant increase in the BMD of the lumbar spine of the HRT group (n = 170) compared to that of the non-HRT group (n = 64) (P = .033 and P = .047, respectively). The BMD of the lumbar spine significantly increased from baseline by 4.16 ± 4.39% and 5.42 ± 5.86% after 1 and 2 years of HRT, respectively (P = .037 and P = .021). The BMD of the femoral neck and total hip also showed a significant percentage increase from baseline after 2 years of HRT. These changes were significant even in the presence of graft-versus-host disease or steroid exposure. For HRT that was initiated within 12 months after HSCT, the increase in BMD in the lumbar spine was greatest after 2 years of HRT., Conclusions: These results support that early and active hormonal therapy might be beneficial for BMD in female HSCT recipients with POI., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neurotoxic treatments (including proteasome inhibitors, immunomodulatory drugs and vinca-alkaloids) are often used in the treatment of hematologic malignancy. Peripheral neuropathy can be part of a paraneoplastic syndrome accompanying the disease but more commonly is a consequence of treatment with neurotoxic therapies, and produces sensory, motor, autonomic nerve dysfunction or a combination, leading to pain, loss of sensation and functional disability. This review provides an update on peripheral neuropathy in hematologic malignancy, including risk factors, mechanisms and treatment options. We examine the clinical features and risk factors for peripheral neuropathy following bortezomib, thalidomide, brentuximab vedotin and vinca alkaloid treatment, as well as related compounds. We review the current data on pharmacogenetic risk factors for the development of toxicity and highlight areas of future research., Competing Interests: Declaration of competing interest Professor Lazarus is a consultant and promotional speaker for Seattle Genetics and Bristol-Myers Squibb and a consultant for Celgene Corporation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hematopoiesis is a complex, orderly and conserved developmental process, coordinated by multiple factors including transcription factors and signaling pathways. Dysregulation of any of these factors may cause developmental or functional defects in the blood system, leading to the pathogenesis of blood diseases. Zebrafish hematopoiesis and the underlying molecular mechanisms are highly conserved with those in mammals. The use of zebrafish to recapitulate abnormal changes in pathogenic factors can build models of related blood diseases, thus providing powerful tools for exploring the molecular mechanisms of pathogenesis and progression, visualization of tumorigenesis and high-throughput chemical screening. In this review, we summarize the zebrafish models of blood diseases and their applications. These disease models not only help to improve our understanding of the pathophysiology of the blood system and the molecular mechanisms on pathogeneses of blood diseases, but also provide new ideas for the treatment of clinically relevant hematological malignancies.

Stem cells in the bone marrow differentiate to ultimately become mature, functioning blood cells through a tightly regulated process (hematopoiesis) including a stem cell niche interaction and feedback through the immune system. Mutations in a hematopoietic stem cell can create a cancer stem cell leading to a less controlled production of malfunctioning cells in the hematopoietic system. This was mathematically modelled by Andersen et al. (2017) including the dynamic variables: healthy and cancer stem cells and mature cells, dead cells and an immune system response. Here, we apply a quasi steady state approximation to this model to construct a two dimensional model with four algebraic equations denoted the simple cancitis model. The two dynamic variables are the clinically available quantities JAK2V617F allele burden and the number of white blood cells. The simple cancitis model represents the original model very well. Complete phase space analysis of the simple cancitis model is performed, including proving the existence and location of globally attracting steady states. Hence, parameter values from compartments of stem cells, mature cells and immune cells are directly linked to disease and treatment prognosis, showing the crucial importance of early intervention. The simple cancitis model allows for a complete analysis of the long term evolution of trajectories. In particular, the value of the self renewal of the hematopoietic stem cells divided by the self renewal of the cancer stem cells is found to be an important diagnostic marker and perturbing this parameter value at intervention allows the model to reproduce clinical data. Treatment at low cancer cell numbers allows returning to healthy blood production while the same intervention at a later disease stage can lead to eradication of healthy blood producing cells. Assuming the total number of white blood cells is constant in the early cancer phase while the allele burden increases, a one dimensional model is suggested and explicitly solved, including parameters from all original compartments. The solution explicitly shows that exogenous inflammation promotes blood cancer when cancer stem cells reproduce more efficiently than hematopoietic stem cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Children and adolescents with haematological malignancies (PedHM) are characterized by a severe loss of exercise ability during cancer treatment, lasting throughout their lives once healed and impacting their social inclusion prospects. The investigation of the effect of a precision-based exercise program on the connections between systems of the body in PedHM patients is the new frontier in clinical exercise physiology. This study is aimed at evaluating the effects of 11 weeks (3 times weekly) of combined training (cardiorespiratory, resistance, balance and flexibility) on the exercise intolerance in PedHM patients. Two-hundred twenty-six PedHM patients were recruited (47% F). High or medium frequency participation (HAd and MAd) was considered when a participant joined; > 65% or between 30% and < 64% of training sessions, respectively. The "up and down stairs'' test (TUDS), "6 min walking" test (6MWT), the "5 Repetition Maximum strength" leg extension and arm lateral raise test (5RM-LE and 5RM-ALR), flexibility (stand and reach), and balance (stabilometry), were performed and evaluated before and after training. The TUDS, the 5RM-LE and 5RM-ALR, and the flexibility exercises showed an increase in HAd and MAd groups (P < 0.05), while the 6MWT and balance tests showed improvement only in HAd group (P < 0.0001). These results support the ever-growing theory that, in the case of the treatment of PedHM, 'exercise is medicine' and it has the potential to increase the patient's chances of social inclusion.

CD47, or integrin-associated protein, is a cell surface ligand expressed in low levels by nearly all cells of the body. It plays an integral role in various immune responses as well as autoimmunity, by sending a potent "don't eat me" signal to prevent phagocytosis. A growing body of evidence demonstrates that CD47 is overexpressed in various hematological malignancies and its interaction with SIRPα on the phagocytic cells prevents phagocytosis of cancer cells. Additionally, it is expressed by different cell types in the tumor microenvironment and is required for establishing tumor metastasis. Overexpression of CD47 is thus often associated with poor clinical outcomes. CD47 has emerged as a potential therapeutic target and is being investigated in various preclinical studies as well as clinical trials to prove its safety and efficacy in treating hematological neoplasms. This review focuses on different therapeutic mechanisms to target CD47, either alone or in combination with other cell surface markers, and its pivotal role in impairing tumor growth and metastatic spread of various types of hematological malignancies.

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., (© 2020 by The American Society of Hematology.)

Haematological malignancies were previously thought to be driven solely by genetic or epigenetic lesions within haematopoietic cells. However, the niches that maintain and regulate daily production of blood and immune cells are now increasingly being recognized as having an important role in the pathogenesis and chemoresistance of haematological malignancies. Within haematopoietic cells, the accumulation of a small number of recurrent mutations initiates malignancy. Concomitantly, specific alterations of the niches, which support haematopoietic stem cells and their progeny, can act as predisposition events, facilitating mutant haematopoietic cell survival and expansion as well as contributing to malignancy progression and providing protection of malignant cells from chemotherapy, ultimately leading to relapse. In this Perspective, we summarize our current understanding of the composition and function of the specialized haematopoietic niches of the bone marrow during health and disease. We discuss disease mechanisms (rather than malignancy subtypes) to provide a comprehensive description of key niche-associated pathways that are shared across multiple haematological malignancies. These mechanisms include primary driver mutations in bone marrow niche cells, changes associated with increased hypoxia, angiogenesis and inflammation as well as metabolic reprogramming by stromal niche cells. Consequently, remodelling of bone marrow niches can facilitate immune evasion and activation of survival pathways favouring malignant haematopoietic cell maintenance, defence against excessive reactive oxygen species and protection from chemotherapy. Lastly, we suggest guidelines for the handling and biobanking of patient samples and analysis of the niche to ensure that basic research identifying therapeutic targets can be more efficiently translated to the clinic. The hope is that integrating knowledge of how bone marrow niches contribute to haematological disease predisposition, initiation, progression and response to therapy into future clinical practice will likely improve the treatment of these disorders.

Myeloproliferative neoplasms are acquired hematological malignancies, mainly affecting the adult and whose morbidity and mortality stems from haemostasis disorders. The most frequently encountered complications include thrombosis, affecting preferentially the arterial territory, but also atypical locations such as splanchnic vein thrombosis. The pathophysiology of these thromboses is complex and involves different actors: blood cells, endothelium and flow conditions. Numerous studies have been conducted to identify risk factors for thrombosis. To date, only two risk factors have been validated through prospective studies (age over 60 years old, history of thrombotic events) and allow classification of patients as "low risk" and "high risk" as the basis for current treatment recommendations. Haemorrhagic manifestations, less frequent than thrombosis, are mainly related to an alteration of primary haemostasis and are therefore manifested by mucocutaneous bleeding. In these patients, platelet dysfunctions and/or acquired Willebrand syndromes can be found. The pathophysiology of thrombosis and platelet dysfunction during myeloproliferative neoplasms remains to date partially unknown. In this review, we offer to focus on physiopathological mechanisms as well as the latest advances in their understanding., (Copyright © 2020 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Introduction : Cognitive impairment caused by chemotherapies, a condition known as chemobrain, is a possible side effect that affects alertness, learning, memory, and concentration. Areas covered : Chemobrain has been principally investigated as a possible side-effect among cancer patients. However, numerous drugs used to treat hematological malignancies can determine the appearance of chemobrain. In this review, we have examined some commonly used drugs for the treatment of hematological malignancies which are known to have a deleterious action on cognitive functions.Numerous mechanisms have been suggested, comprising the direct neurotoxicity of chemotherapeutic drugs, oxidative stress, genetic predisposition, cytokine-provoked damage, histone modifications, immune alteration, and the action of chemotherapeutic on trophic factors and structural proteins of brain cells. Expert commentary : Cognitive dysfunction provoked by the treatment of hematological diseases is an actual challenge in clinical practice. Actually, there are no totally efficient and innocuous treatments for this syndrome. It is important that further investigations specify the existence of predictors and gravity factors to pre- and post-therapy cognitive change and identify the influence of tumor treatments on the cognitive alterations in long-term, cancer survivors. Moreover, future studies are needed to analyze the interactions between genetic risk, amyloid accumulation, intrinsic brain networks, and chemotherapy.

Chronic inflammation has profound tumor-promoting effects. Inflammatory cells are the key players in immunosurveillance against tumors, and immunosuppression is known to increase the risk of tumors. Autoimmune diseases, which manifest as loss of self-tolerance and chronic immune dysregulation, provide a perfect environment for tumor development. Aside from managing the direct inflammatory consequences of autoimmune pathogenesis, cancer risk profiles should be considered as a part of a patient's treatment. In this review, we describe the various associations of malignancies with autoimmune diseases, specifically systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and Sjögren's syndrome, as well as discuss the mechanisms contributing to the pathogenesis of both disorders.

Purpose: Muscle dysfunction such as loss of muscle mass and decreased muscle strength is often observed in patients with hematologic malignancies. However, specific factors associated with muscle function have not been identified. The purpose of this study was to identify significant factors affecting muscle function in patients with hematologic malignancies., Methods: This was a cross-sectional, observational study. Eighty-eight inpatients with hematologic malignancies undergoing chemotherapy were recruited. Participants were evaluated for muscle thickness and isometric knee extensor strength as indicators of muscle function, physical activity, physical symptoms, psychological distress, and self-efficacy at the start date of rehabilitation. Multiple regression analysis with muscle function as the dependent variable and clinical information and other evaluation items as explanatory variables was performed., Results: Lymphocyte count, the geriatric nutritional risk index, and physical activity were significant factors associated with muscle thickness, while physical activity and self-efficacy were significant factors associated with isometric knee extensor strength., Conclusions: Nutritional status, physical activity, and self-efficacy were significant factors associated with muscle function in patients with hematologic malignancies. Rehabilitation intervention focusing on improving physical activity and nutritional status should be considered necessary for enhancing muscle function in patients with hematologic malignancies.

A decrease in cancer deaths has resulted in the possibility of child bearing for many young adult cancer survivors. Most antitumor treatment modalities are detrimental to female fertility, and methods for fertility preservation before gonadotoxic treatment, including cryopreservation of oocytes, embryos and ovarian tissue, have therefore been developed. This review focuses on the ovarian function of cancer patients, the safety and efficacy of fertility preservation methods, and the pregnancy outcomes of these patients. Breast cancer and hematological tumors constitute the majority of cancers in reproductive-aged female oncology patients. Ovarian function may not be impacted by breast cancer cells, while in patients with hematological malignancies, decreases in anti-Müllerian hormone and antral follicle counts have been demonstrated. In most cases, patients can undergo ovarian stimulation without delaying treatment, and a new stimulation protocol known as dual stimulation, which may be more efficient, has now been developed. Birth outcomes are also acceptable in cancer patients.

Our previous research confirmed that patients with malignant hematopoietic disease already had a low hemoglobin level before allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no study has determined whether a correlation exists between exercise load, hemoglobin level, and muscle oxygen saturation (SmO 2 ), during exercise. Therefore, the purpose of this study was to investigate whether near-infrared spectroscopy (NIRS)-derived SmO 2 is associated with exercise load, as determined by a dynamometer, before allo-HSCT. This study included 19 male patients who received allo-HSCT in Hyogo College of Medicine Hospital (Japan) between November 2009 and October 2012. Patients performed isometric repeated dorsiflexion at 50% maximum voluntary contraction for 180 s to determine exercise load, and SmO 2 was evaluated during exercise at the same time using NIRS (BOM-L1TRW, Omega Wave, Inc., Japan). The hemoglobin level was also evaluated before allo-HSCT. Patients with hematopoietic disease before allo-HSCT already had a low hemoglobin level. There was a significant correlation between exercise load and ∆SmO 2 ; however, the hemoglobin level was not correlated with exercise load. In these patients, exercise load might be affected by muscle oxygen consumption rather than by the hemoglobin level. This finding shows that NIRS can used to assess fatigue in patients with malignant hematopoietic disease.

Purpose: To present the findings of combined oral assessment and gustometry testing of a series of head and neck and hematologic malignancies in patients with self-reported taste change after cytotoxic therapies., Methods: Patients with acute myeloid leukemia (AML), multiple myeloma (MM), and head and neck cancer (HNC) were evaluated for taste function. Chemical gustometry was conducted assessing chemosensory qualities that included sweet, sour, salty, bitter, umami, and spicy. NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 and the Scale of Subjective Total Taste Acuity (STTA) were used to describe taste symptoms. Saliva flow rates were measured to determine the presence of hyposalivation. Patients were provided treatment trials for taste dysfunction, including zinc supplements, or medications that included clonazepam, megestrol acetate, and the cannabinoid dronabinol., Results: According to STTA, hematology cases reported the incidence of grades 2 and 3 taste disturbances as 60% and 40%, respectively. For HNC patients, the incidence of grades 2 and 3 was 44% each. Gustometry tests confirmed dysgeusia in all patients evaluated. In the hematology group, 80% of patients exhibited a decrease in sweet taste perception, and no patients correctly identified umami taste. In the HNC group, most patients could not identify salt taste, 66% of patients reported "no sensation" with spicy taste, bitter taste was reduced in some, and increased or altered in others, while only one patient could identify umami taste. In the hematologic and HNC patient groups, 80% and 66% reported grade 2 dry mouth, respectively, according to CTCAE 4.0. After treatment for taste dysfunction, 71% of all patients in the present study reported improvements in taste function., Conclusions: Persisting dysgeusia in cancer survivors may be assessed by patient report and taste testing. The taste most affected in our patients was umami. Treatment trials with current interventions for dysgeusia appeared effective and should be considered in cancer survivors. Understanding taste and flavor function during and following cancer treatment is important in developing rational prospective preventive and interventional strategies.

Purpose: The aim of this study was to evaluate seizure outcome in children with hematological malignancies and PRES and to identify prognostic factors that could help manage the syndrome., Method: We retrospectively reviewed the report data of 21 patients diagnosed with hematological malignancy or aplastic anemia and PRES between 2008 and 2018. Basic demographic data, oncology treatment, presymptomatic hypertension before PRES manifestation, neurological status, seizure type, and EEG and MRI findings at PRES onset and at the one-year follow-up visit were studied. Patients who developed remote symptomatic seizures or epilepsy were identified., Results: We included 21 children (11 females and 10 males) in the study. Sixteen patients (76.2%) were diagnosed with ALL and the rest individually with AML, CML, T-lymphoma, Burkitt lymphoma, and severe aplastic anemia. Presymptomatic hypertension (PSH) was evaluated in 19 patients and was present in 18 (94.7%). The duration was 9 h and more in 16 patients (88.8%); the severity was grade II in 12 patients (66.7%). Seizures as the initial symptom of PRES were present in 17 patients (80.9%). Four patients (19.0%) were assessed with remote symptomatic seizures. Two of them (9.5%) had ongoing seizures at the one-year follow-up visit and were diagnosed with epilepsy. The presence of gliosis on follow-up MRI indicated worse outcome with development of epilepsy (without statistical significance)., Conclusions: PRES syndrome has an overall good prognosis and the evolution to epilepsy is rare. The severity and duration of PSH or seizure severity and EEG findings at PRES onsetwere not associated with worse neurological outcomes in this study., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

As people age, their tissues accumulate an increasing number of somatic mutations. Although most of these mutations are of little or no functional consequence, a mutation may arise that confers a fitness advantage on a cell. When this process happens in the hematopoietic system, a substantial proportion of circulating blood cells may derive from a single mutated stem cell. This outgrowth, called "clonal hematopoiesis," is highly prevalent in the elderly population. Here we discuss recent advances in our knowledge of clonal hematopoiesis, its relationship to malignancies, its link to nonmalignant diseases of aging, and its potential impact on immune function. Clonal hematopoiesis provides a glimpse into the process of mutation and selection that likely occurs in all somatic tissues., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Myeloid-derived suppressor cells (MDSCs) are newly identified immature myeloid cells that are characterized by the ability to suppress immune responses and expand during cancer, infection, and inflammatory diseases. Although MDSCs have attracted a lot of attention in the field of tumor immunology in recent years, little is known about their multiple roles in hematological malignancies as opposed to their roles in solid tumors. This review will help researchers better understand the various characteristics and functions of MDSCs, as well as the potential therapeutic applications of MDSCs in hematological malignancies, including lymphoma, multiple myeloma, leukemia, and hematopoietic stem cell transplantation.

Chaperone-mediated autophagy (CMA) ensures the selective degradation of cellular proteins endowed with a KFERQ-like motif by lysosomes. It is estimated that 30% of all cellular proteins can be directed to the lysosome for CMA degradation, but only a few substrates have been formally identified so far. Mechanistically, the KFERQ-like motifs present in substrate proteins are recognized by the molecular chaperone Hsc70c (Heat shock cognate 71 kDa protein cytosolic), also known as HSPA8, and directed to LAMP2A, which acts as the CMA receptor at the lysosomal surface. Following linearization, the protein substrate is next transported to the lumen of the lysosomes, where it is degraded by resident proteases, mainly cathepsins and eventually recycled to sustain cellular homeostasis. CMA is induced by different stress conditions, including energy deprivation that also activates macro-autophagy (MA), that may make it difficult to decipher the relative impact of both pathways on cellular homeostasis. Besides common inducing triggers, CMA and MA might be induced as compensatory mechanisms when either mechanism is altered, as it is the often the case in different pathological settings. Therefore, CMA activation can compensate for alterations of MA and vice versa. In this context, these compensatory mechanisms, when occurring, may be targeted for therapeutic purposes. Both processes have received particular attention from scientists and clinicians, since modulation of MA and CMA may have a profound impact on cellular proteostasis, metabolism, death, differentiation, and survival and, as such, could be targeted for therapeutic intervention in degenerative and immune diseases, as well as in cancer, including hematopoietic malignancies. The role of MA in cancer initiation and progression is now well established, but whether and how CMA is involved in tumorigenesis has been only sparsely explored. In the present review, we encompass the description of the mechanisms involved in CMA, its function in the physiology and pathogenesis of hematopoietic cells, its emerging role in cancer initiation and development, and, finally, the potential therapeutic opportunity to target CMA or CMA-mediated compensatory mechanisms in hematological malignancies., Competing Interests: The authors declare no conflicts of interest.

Objective: While some regard an association between motor neuron disease (MND) and malignancy as co-incidental, others have argued that it could represent a distinct clinical entity. The present study undertook in depth phenotyping along with assessment of cortical function to further explore disease pathophysiology in MND with malignancy (MND-M) patients., Methods: Clinical features along with assessment of peripheral and cortical function was undertaken in 13 MND-M and results were compared to sporadic and familial MND cohorts., Results: From a cohort 13 patients (10 males; aged 65.2 ± 2.0 years), 38.5% were diagnosed with a haematological malignancy. The lower motor neuron phenotype predominated in the in the MND-M patients (χ 2  = 10.8, P < 0.01), with the upper motor neuron (UMN) score being significantly reduced in MND-M patients compared to sporadic and familial MND cohorts (χ 2  = 6.84, P < 0.01). The neurological deficits did not respond to treatment of the underlying malignancy in the majority of MND-M (92%) patients, and as such there were no significant differences in survival between the cohorts. Despite a paucity of UMN signs, cortical hyperexcitability was evident in MND-M patients, as indicated by reduction in short interval intracortical inhibition (P < 0.01) and increase in motor evoked potential amplitude (P < 0.01), that were similar to findings in sporadic and familial MND cohorts., Conclusions: The present study suggests that MND-M falls within the spectrum of MND., Significance: The concept of a co-incidental association between MND and malignancy is supported through the present study by the presence of cortical dysfunction, combined with clinical findings that can be explained within the spectrum of abnormality evident in classical MND phenotypes., (Copyright © 2019 International Federation of Clinical Neurophysiology. All rights reserved.)

The aim was to assess the level of physical activity and the quality of life of children undergoing cancer treatment, during and after the completion of the treatment. Eighty-eight children aged 11-15 were enrolled. Three groups of children were assessed, i.e., children undergoing cancer treatment ( n = 30), children after cancer treatment ( n = 28), and healthy children ( n = 30). The level of physical activity in children was assessed using the questions from the Health Behavior in School-Aged Children (HBSC) questionnaire. The assessment of children's quality of life was conducted using the KIDSCREEN-10 Index. The chi-square test was used to assess the statistical significance of the differences in the results between the study groups in the case of both HBSC and KIDSCREEN-10 questionnaires. Children undergoing cancer treatment did not perform any physical activity of at least 60 min (in total) per day, during the week. Therefore, they did not meet the recommendations related to the appropriate level of daily physical activity (Moderate-to-Vigorous Physical Activity; MVPA). Children after cancer treatment and healthy children significantly more frequently undertook physical activity. The quality of life of children with cancer is significantly lower and different from the quality of life of healthy children.

Objective: Neuroimaging studies of hematologic cancer patients report altered activity in dorsal attention and central executive networks. To determine the consequences of these altered brain networks, we evaluated neurophysiological correlates of attention and working memory in hematologic cancer patients prior to initiating treatment., Methods: Hematologic cancer patients (19-80 years) were excluded for premorbid cognitive impairment, prior non-hematologic cancer diagnosis, and prior chemotherapy. Attention was manipulated by presenting an irrelevant spatial cue prior to visual search displays. Working memory was manipulated by presenting irrelevant distractors within memory displays. Electroencephalogram was recorded during task performance., Results: Patients (n = 28) and controls (n = 15) were balanced on age, gender, and education. Spatial cues evoked larger N2pc amplitudes, a correlate of spatial attention, in patients than controls (p < .05; Cohen's d > 0.7). Memory distractors evoked larger contralateral delay activity amplitudes, a correlate of working memory load, in patients (p = .028; Cohen's d = 1.1) but not controls (p = .64)., Conclusions: Prior to initiating treatment, hematologic cancer patients demonstrated poor control over spatial attention and working memory, consistent with altered dorsal attention and central executive network activity., Significance: Hematologic cancer patients may be at a higher risk for selecting, processing, and storing distracting information that would compete with more immediate goal-related behaviors., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

In total, 74 pediatric oncology patients with hematologic malignancies (n=56) or solid tumors (n=18) and a median age of 78.5 months were included in this prospective study. The aims were to assess malnutrition risks and nutritional status over a 6-month treatment period measured at regular intervals. The rate of patients with high risk for malnutrition at diagnosis was 28.4% by Screening Tool for Risk of Impaired Nutritional Status and Growth tool and 36.5% by Pediatric Yorkhill Malnutrition Score. Body mass index (BMI) z-scores at diagnosis showed 12.3% undernutrition (<-2 SD) and 6.8% overnutrition (>2 SD), which changed to 6.7% and 11.1% at the sixth month, respectively. Malnutrition (BMI<5th age percentile) was detected in 13.7% at diagnosis. Despite an initial deterioration noted in BMI, BMI for age percentile, and z-scores at month 1 in all malignancy subgroups (at month 3 for acute lymphoblastic leukemia), the scores improved later on. There was an increase in weight from baseline in 88.2% of patients over 6 months. This study revealed a decrease in the prevalence of undernutrition and malnutrition over a 6-month treatment period with improved anthropometrics despite an initial deterioration in all malignancy subgroups and even in patients with high risk for malnutrition at baseline screening. Solid tumors and acute lymphoblastic leukemia seem to be associated with higher likelihood of undernutrition and overnutrition, respectively, during treatment.

Objective: In this study, we investigated the muscle function of patients with haematological malignancy and healthy controls and examined the effect of cachexia on muscle function., Methods: Seventy-one patients with haematological malignancy, hospitalised for chemotherapy, and 71 healthy controls underwent examination of skeletal muscle mass (SMM; total body and upper and lower limbs), handgrip strength and isometric knee extensor strength. Patients with haematological malignancy were divided into three groups based on Glasgow Prognostic Score: non-cachexia (n = 31), pre-cachexia (n = 23) and cachexia (n = 17) groups. The evaluation items were compared among the groups., Results: Patients with haematological malignancy had lower SMM of the total body and lower limbs, handgrip strength and isometric knee extensor strength than healthy controls. There was no significant difference in SMM of the upper limbs among the groups. When classifying patients with haematological malignancy according to GPS, there was no significant difference among the three groups for any of the evaluation items., Conclusions: In patients with haematological malignancy, although significant muscle wasting and weakness were observed in the lower limbs, the effect of cachexia was minimal. The reduction in muscle function involved disuse syndrome, which accompanied a decline in physical activity., (© 2018 John Wiley & Sons Ltd.)

Myeloablative conditioning allogeneic hematopoietic cell transplantation (HCT) puts patients at greater risk for significant cognitive and quality of life decline compared with recipients of reduced-intensity conditioning or autologous HCT. Vorinostat, a histone deacetylase inhibitor, has been shown to have neuroprotective and neurorestorative effects in preclinical models of neurologic diseases. Thus, within the context of a myeloablative conditioning phase II clinical trial of vorinostat combined with tacrolimus and methotrexate for graft-versus-host disease prophylaxis, we conducted an ancillary study to evaluate feasibility of assessing associations between vorinostat and neurocognitive function and quality of life (ClinicalTrials.gov NCT02409134). Nine patients (mean age, 53 years; range, 36 to 66) underwent computerized neuropsychological testing (Cogstate) and completed surveys of mood (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), and quality of life (Functional Assessment of Cancer Therapy-General). Control cohorts from a separate concurrent longitudinal study (19 autologous and 18 allogeneic HCT patients, who matched the vorinostat patients on relevant medical and demographic variables) completed the same test battery. All allogeneic patients received busulfan-based myeloablative conditioning and were transplanted with HLA-matched unrelated donors. The total neurocognitive performance score of vorinostat patients did not change significantly across the study duration (ie, baseline, day 30, day 100, and day 160). Depression, anxiety, and quality of life also did not differ significantly across time. In univariate analyses (analysis of variance), vorinostat-treated patients showed no difference in neurocognitive function or quality of life compared with autologous and allogeneic control subjects. However, when medical variables were accounted for in a linear mixed effects regression model, the total neurocognitive performance of vorinostat-treated patients was comparable with autologous control subjects. Notably, autologous control subjects performed significantly better than allogeneic control subjects (estimate, .64; standard error, .23; P ≤ .01). Moreover, a smaller percentage of vorinostat-treated patients were classified as mildly, moderately, or severely impaired across neurocognitive domains as well as time points compared with both control cohorts. Thus, vorinostat may have neurorestorative or neuroprotective effects in the HCT setting. Accordingly, we recognize the need for a future, full-scale randomized controlled trial to further examine this hypothesis., (Copyright © 2018. Published by Elsevier Inc.)

Telomeres are repetitive DNA sequences protecting physical ends of linear chromosomes against degradation and end-to-end chromosomal fusion. Telomeres shorten with each cell division, which regulates the cellular lifespan in somatic cells and limits their renewal capacity. Cancer cells are often able to overcome this physiological barrier and become immortal with unlimited replicative capacity. In this review, we present current knowledge on the role of telomeres in human aging with a focus on their behavior in hematological malignancies of adults. Associations of telomere length to age-related diseases and to the prevention of telomere shortening are also discussed.

Despite clinical advances, late onset pulmonary complications in adult recipients of allogenic stem cell transplantation are a major cause of morbidity and mortality. Reported incidence and risk factors in the literature vary broadly and are partly contradictory. Identification of pretransplant factors associated with major complications would be helpful to define individual treatment strategies and early initiation of preventive measures. To evaluate incidence and risk factors of late onset noninfectious pulmonary complications, with special regard to small airways disease (SAD) and bronchiolitis obliterans syndrome (BOS), indicating graft-versus-host disease, following myeloablative versus nonmyeloablative allogenic stem cell transplantation. We reviewed the clinical records and assessed the course of lung function and pulmonary complications in adults who underwent allogenic stem cell transplantation for hematological malignancies between 1999 and 2015 using nonmyeloablative (n = 179) or myeloablative (n = 130) conditioning at the Division of Hematology of the Medical University of Graz. All patients underwent body plethysmography pulmonary function test (PFT), diffusion capacity for carbon monoxide, and arterial blood gas analysis before and repeatedly after transplant. SAD was defined as maximal expiratory flow at 50% and 25% of forced vital capacity <70% predicted. Ventilatory disorders and gas transfer abnormalities were common before and after allogenic stem cell transplantation, independent of conditioning regimen. SAD was common in the nonmyeloablative (34%) and myeloablative (29%) groups. The 100-day post-transplant mortality was significantly associated with reduced pretransplant total lung capacity <80%. Mortality 100 days post-transplant was significantly associated with pretransplant SAD and a pretransplant smoking history. In this subset, a smoking history was independently associated with increased mortality, with a 5-year mortality of 45% compared with 26% in never-smokers. Pretransplant SAD was not predictive for the later development of BOS. Smoking history, pretransplant restrictive PFT, and pre-existing SAD are important risk factors for death following allogenic stem cell transplantation. However, pretransplant SAD is not a predictor of long-term complications, including BOS., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Purpose: Patients with hematological malignancies often present with reduced muscle and physical functions, which are caused by the disease or related treatment. Moreover, patients with hematological malignancies rapidly develop low hemoglobin levels, and this may affect muscle and physical functions. This study aimed to identify the influence of hemoglobin levels on muscle and physical functions in patients with hematological malignancies., Methods: Using a cross-sectional study design, this study included 60 patients with hematological malignancies (mean age = 68.0 ± 10.2 years, women 56.7%) who were hospitalized for chemotherapy- and radiotherapy-related side effects and underwent examination for skeletal muscle mass (SMM), muscle strength, physical function, activities of daily living (ADLs), psychological status, and quality-of-life (QOL), including physical symptoms. Participants were divided into 3 groups according to tertiles of hemoglobin levels: low (n = 19), middle (n = 20), and high (n = 21). Evaluation items were compared among the 3 groups., Results: There was no significant difference among the 3 groups in terms of SMM. The low hemoglobin group showed significantly higher values of fatigue and dyspnea and lower values of muscle strength, ADLs, and QOL than the high hemoglobin group., Conclusions: Hemoglobin levels did not affect SMM; however, muscle weakness, decrease in physical function, physical symptoms such as fatigue and dyspnea, and decline in ADLs and QOL were observed in patients with low hemoglobin levels.

Background: Identifying people who are at risk of deteriorating and dying is essential to inform goals of care, appropriate treatment decisions, patient autonomy, and effective end-of-life care. Limited literature exists on predicting survival near the end of life for people with a hematological malignancy., Objective: To identify the key clinical indicators that signal a person with a hematological malignancy is at high risk of deteriorating and dying., Design, Setting, Participants: Eleven clinical indicators identified in a Delphi approach were tested via a retrospective case-control study. Each indicator was assessed for at each in-patient admission between living (n = 236) and deceased (n = 120) people with a hematological malignancy who were admitted to a large tertiary hospital between 1st July 2014 and 31st December 2015., Results: Six clinical indicators were independently associated with mortality in the final three months of life: declining performance status (Odds Ratio [OR] 7.153, 95% Confidence Intervals [CI] 3.281-15.597, p = < 0.001); treatment limitations of the hematological malignancy (OR 7.855, 95% CI 3.528-17.489, p = < 0.001); relapse, refractory or persistent disease (OR 3.749, 95% CI 1.749-8.039, p = 0.001); presence of two or more comorbidities (OR 2.991, 95% CI 1.319-6.781, p = 0.009); invasive fungal infections (OR 4.887, 95% CI 1.197-19.949, p = 0.027); and persistent infections (OR 6.072, 95% CI 2.551-14.457, p = < 0.001)., Conclusions: This study has identified six clinical indicators that signal a person with a hematological malignancy is at high risk of deteriorating and dying and may benefit from an assessment of palliative needs and proactive planning, along-side appropriate treatment.

Polycomb group (PcG) proteins are the key epigenetic regulators of normal hematopoiesis and the dysregulation of their functions is closely involved in the pathogenesis of hematological malignancies. These proteins function in the multimeric complexes called polycomb repressive complex (PRC) 1 and 2. In addition to canonical PRC1, four noncanonical PRC1 complexes have been identified. In contrast to canonical PRC1, which is recruited to its target sites in a manner dependent on H3K27me3, noncanonical PRC1 complexes are recruited to their target sites independently of H3K27me3. Among them, PRC1.1, consisting of PCGF1, RING1A/B, KDM2B, and BCL6 corepressor (BCOR) or BCLRL1, regulates diverse biological processes, including pluripotency, reprogramming, and hematopoiesis. PRC1.1 has been implicated in myelopoiesis and lymphopoiesis and is targeted by somatic gene mutations in various hematological malignancies. These findings revealed the more complex regulation of epigenetic cellular memory by PcG proteins than we expected and propose PRC1.1 as a novel therapeutic target in hematological malignancies., (Copyright © 2018 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

This study aimed to investigate the effects of low-intensity exercise therapy (LIET) on the physical and mental symptoms and functions in patients with haematological malignancies undergoing chemotherapy. Forty-four patients hospitalised for chemotherapy performed LIET. The exercise intensity of LIET was defined as achieving <40% of the predicted maximum heart rate calculated using the Karvonen formula. LIET consisted of aerobic and resistance training, which was carried out on weekdays. The intervention was omitted in the case of poor general health status and strong patient refusal. Muscular and physical function, activities of daily living (ADLs), psychological distress and quality of life (QOL) were evaluated upon initiation of rehabilitation and at discharge. Participants were divided into high- and low-frequency groups according to their LIET frequency. Two-way repeated-measures analysis of variance was used for statistical analysis. In the high-frequency group, muscle function was maintained, while physical function, ADLs, psychological distress and QOL were significantly improved. However, in the low-frequency group, muscle function of the lower limb was significantly reduced and no other improvement was observed. Low-intensity exercise therapy could be a potential treatment strategy for patients with haematological malignancies undergoing chemotherapy who are unable to perform mid- or high-intensity exercise., (© 2018 John Wiley & Sons Ltd.)

In many types of solid tumours, the aberrant expression of the cell adhesion molecule N-cadherin is a hallmark of epithelial-to-mesenchymal transition, resulting in the acquisition of an aggressive tumour phenotype. This transition endows tumour cells with the capacity to escape from the confines of the primary tumour and metastasise to secondary sites. In this review, we will discuss how N-cadherin actively promotes the metastatic behaviour of tumour cells, including its involvement in critical signalling pathways which mediate these events. In addition, we will explore the emerging role of N-cadherin in haematological malignancies, including bone marrow homing and microenvironmental protection to anti-cancer agents. Finally, we will discuss the evidence that N-cadherin may be a viable therapeutic target to inhibit cancer metastasis and increase tumour cell sensitivity to existing anti-cancer therapies.

Purpose: This study explores the feasibility and preliminary effectiveness of an exercise program in people scheduled for hematopoietic stem cell transplantation (HSCT)., Methods: In this controlled clinical trial, we compare pre-transplantation exercise to no exercise in the waiting period for an allogeneic of autologous HSCT. The supervised individually tailored exercise program (4-6 weeks) consisted of aerobic endurance, muscle strength, and relaxation exercises, administered twice a week in the period prior to HSCT. Feasibility was determined based on inclusion rate, attrition rate, adherence to intervention, safety, and satisfaction (0-10). Preliminary effectiveness was determined primarily by self-perceived physical functioning, quality of life (QOL), and fatigue. Secondary outcomes were global perceived effect (GPE), blood counts, hospital stay, and physical fitness., Results: Forty-six patients were eligible, of whom 29 (69%) participated: 14 in the intervention group and 15 in the control group. The adherence rate to training was 69%. No adverse events or injuries occurred. Satisfaction of training conditions was high (mean 9.2 ± 1.3). Positive (follow-up) trends in favor of the intervention group were found for self-perceived physical functioning, QOL, fatigue, GPE, blood counts, and hospital stay., Conclusion: Exercise prior to HSCT is safe and feasible, and positive trends suggest favorable preliminary effectiveness. Adherence to the exercise program needs to be optimized in a future trial.

Bones provide both skeletal scaffolding and space for hematopoiesis in its marrow. Previous work has shown that these functions were tightly regulated by the nervous system. The central and peripheral nervous systems tightly regulate compact bone remodeling, its metabolism, and hematopoietic homeostasis in the bone marrow (BM). Accumulating evidence indicates that the nervous system, which fine-tunes inflammatory responses and alterations in neural functions, may regulate autoimmune diseases. Neural signals also influence the progression of hematological malignancies such as acute and chronic myeloid leukemias. Here, we review the interplay of the nervous system with bone, BM, and immunity, and discuss future challenges to target hematological diseases through modulation of activity of the nervous system., (Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.)

Several new antifungal agents have become available for primary fungal prophylaxis of neutropenia fever in hematological malignancy patients. Our aim was to synthesize all evidence on efficacy and enable an integrated comparison of all current treatments. We performed a systematic literature review to identify all publicly available evidence from randomized controlled trials (RCT). We searched Embase, PubMed, the Cochrane Central Register of Controlled Clinical Trials, and the www.ClinicalTrials.gov website. In total, 54 RCTs were identified, including 13 treatment options. The evidence was synthesized using a network meta-analysis. Relative risk (RR) was adopted. Posaconazole was ranked highest in effectiveness for primary prophylaxis, being the most favorable in terms of (i) the RR for reduction of invasive fungal infection (0.19; 95% confidence interval [CI], 0.11 to 0.36) and (ii) the probability of being the best option (94% of the cumulative ranking). Posaconazole also demonstrated its efficacy in preventing invasive aspergillosis and proven fungal infections, with RR of 0.13 (CI, 0.03 to 0.65) and 0.14 (CI, 0.05 to 0.38), respectively. However, there was no significant difference among all of the antifungal agents in all-cause mortality and overall adverse events. Our network meta-analysis provided an integrated overview of the relative efficacy of all available treatment options for primary fungal prophylaxis for neutropenic fever in hematological malignancy patients under myelosuppressive chemotherapy or hematopoietic cell transplantation. On the basis of this analysis, posaconazole seems to be the most effective prophylaxis option until additional data from head-to-head randomized controlled trials become available., (Copyright © 2018 American Society for Microbiology.)

S-phase kinase-associated protein 2 (SKP2) is a well-studied F-box protein and a critical part of the Skp1-Cul1-Fbox (SCF) E3 ligase complex. It controls cell cycle by regulating the expression level of p27 and p21 through ubiquitination and proteasomal degradation. SKP2-mediated loss of p27Kip1 is associated with poor clinical outcome in various types of cancers including hematological malignancies. It is however well established that SKP2 is an oncogene, and its targeting may be an attractive therapeutic strategy for the management of hematological malignancies. In this article, we have highlighted the recent findings from our group and other investigators regarding the role of SKP2 in the pathogenesis of hematological malignancies.

Background: Epithelial-mesenchymal transition is an important process in embryonic development, fibrosis, and cancer metastasis. During the progression of epithelial cancer, activation of epithelial-mesenchymal transition is tightly associated with metastasis, stemness and drug resistance. However, the role of epithelial-mesenchymal transition in non-epithelial cancer is relatively unclear., Main Body: Epithelial-mesenchymal transition transcription factors are critical in both myeloid and lymphoid development. Growing evidence indicates their roles in cancer cells to promote leukemia and lymphoma progression. The expression of epithelial-mesenchymal transition transcription factors can cause the differentiation of indolent type to the aggressive type of lymphoma. Their up-regulation confers cancer cells resistant to chemotherapy, tyrosine kinase inhibitors, and radiotherapy. Conversely, the down-regulation of epithelial-mesenchymal transition transcription factors, monoclonal antibodies, induce lymphoma cells apoptosis., Conclusions: Epithelial-mesenchymal transition transcription factors are potentially important prognostic or predictive factors and treatment targets for leukemia and lymphoma.