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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: 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.)

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.)

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.

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.)

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.

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.

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.

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.)

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.

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.)

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.

Purpose: The associations of physical activity and television (TV) viewing with mortality risk among individuals with hematologic malignancies remain unclear., Methods: We examined the relations of physical activity and TV viewing time before and after diagnosis with mortality among 5182 U.S. adults aged 50-71 years from the NIH-AARP Diet and Health Study cohort who survived a first primary hematologic cancer between 1995-1996 and 2011., Results: For the pre- and post-diagnosis analyses, we confirmed 2606 and 613 deaths respectively. In multivariable-adjusted Cox proportional hazard regression models, comparing high (≥4 hrs/wk) versus low (<1 hr/wk) activity levels, pre-diagnosis physical activity was associated with 18%-22% reduced risks of all-cause mortality among all hematologic cancer survivors, and survivors of non-Hodgkin lymphoma, myeloma, and leukemia, respectively. Additional control for BMI had little impact on the results, expect for myeloma survivors, for whom the association was no longer significant. Post-diagnosis physical activity was related to risk reductions in mortality ranging from 36%-47%. The associations for TV viewing did not show a clear pattern., Conclusion: Our study suggests that pre- and post-diagnosis physical activity is associated with lower risk of all-cause mortality among hematologic cancer survivors. Further research is required to confirm this observation.

Crosstalk between bone marrow tumour cells and surrounding cells, including bone marrow mesenchymal stromal cells (BM-MSCs), endothelial cells and immune cells, is important for tumour growth in haematological neoplasms. In addition to conventional signalling pathways, extracellular vesicles (EVs), which are endosome-derived vesicles containing proteins, mRNAs, lipids and miRNAs, can facilitate modulation of the bone marrow microenvironment without directly contacting non-tumourous cells. In this review, we discuss the current understanding of EV-mediated cell-cell communication in haematological neoplasms, particularly leukaemia and multiple myeloma. We highlight the actions of tumour and BM-MSC EVs in multiple myeloma. The origin of EVs, their tropism and mechanism of EV transfer are emerging issues that need to be addressed in EV-mediated cell-cell communication in haematological neoplasms.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'., (© 2017 The Author(s).)

Background: Febrile neutropenia (FNP) is a condition defined by fever and neutropenia. There are current only limited data on related cutaneous manifestations. This study aimed to assess cutaneous lesions and their etiologies in a Thai group of FNP patients. Methods: A retrospective analysis was conducted on 43 non-transplant febrile neutropenic patients with concurrent cutaneous lesions, as determined by dermatopathologic studies at Songklanagarind Hospital in Thailand over a five-year period. Results: The mean age was 39 years (SD: 18.8). Approximately 60% were male. The most common underlying disease was a hematologic neoplasm. Twenty-one of the participants had developed FNP within 7.5±8.7 days after presenting with skin lesions. Twenty-two participants had skin lesions 9.0±11.1 days after FNP diagnosis. Cutaneous manifestations were mostly in the form of multiple lesions (67.4%), of which the most common were nodular skin lesions (37.2%) presenting on the lower extremities of the body (58.1%). The dermatopathologic diagnoses included infections which were almost all fungal and leukemia cutis. The development of skin lesions after FNP proved to be a statistically significant risk factor for fungal infection (OR 8.13, P = 0.009), whereas age (over 40 years) proved to be a statistically significant protective factor (OR 0.20, P = 0.04). Conclusions: There are a variety of cutaneous manifestations in FNP, of which the most common were cutaneous nodular skin lesions in the lower extremities. The most frequent infection was fungal in patients under 40 who had developed skin lesions after FNP., (Creative Commons Attribution License)

Purpose: Essential thrombocythemia, polycythemia vera, and myelofibrosis are rare chronic hematological malignancies known as myeloproliferative neoplasms (MPNs) and are characterized by deregulated myeloid lineage cell production, splenomegaly, and heterogeneous symptom profiles. MPN patients suffer from a significant symptom burden (eg, fatigue, depressive symptoms, early satiety) and an impaired overall quality of life (QoL). Current treatments typically include pharmacological approaches, which may come with additional side effects and may be limited by treatment-associated toxicities (ie, cytopenias). Nonpharmacological approaches such as physical activity may be beneficial for reducing symptom burden and improving QoL. To date, no studies have examined physical activity as a nonpharmacological approach in MPN patients despite preliminary evidence supporting its benefit in other hematological cancers. The purpose of this article is to (1) review the literature related to physical activity and specific hematological cancer subtypes and to (2) make suggestions for future research involving physical activity in MPN patients as a symptom management strategy., Methods: A brief review of studies examining physical activity in leukemias, lymphomas, and myelomas (excluding stem-cell transplant patients) was conducted., Results: There is preliminary evidence to suggest that physical activity may be an effective approach to improve patient-reported outcomes (fatigue, depression, anxiety, sleep), physical fitness (cardiovascular fitness, balance, body composition), and overall QoL in other hematological cancers., Conclusions: Based on encouraging findings in other hematological cancers, future research should examine the feasibility and effectiveness of physical activity in MPN patients.

Background: Epidemiological studies of neurological complications in patients with hematological malignancies are scant. The objective of the study was to identify determinants of survival in patients with hematological malignancy and neurological failure., Methods: Post hoc analysis of a prospective study of adults with hematological malignancies admitted for any reason to one of 17 university or university-affiliated participating ICUs in France and Belgium (2010-2012). The primary outcome was vital status at hospital discharge., Results: Of the 1011 patients enrolled initially, 226 (22.4%) had neurological failure. Presenting manifestations were dominated by drowsiness or stupor (65%), coma (32%), weakness (26%), and seizures (19%). Neuroimaging, lumbar puncture, and electroencephalography were performed in 113 (50%), 73 (32%), and 63 (28%) patients, respectively. A neurosurgical biopsy was done in 1 patient. Hospital mortality was 50%. By multivariate analysis, factors independently associated with higher hospital mortality were poor performance status (odds ratio [OR], 3.99; 95%CI, 1.82-9.39; P = 0.0009), non-Hodgkin's lymphoma (OR, 2.60; 95%CI, 1.35-5.15; P = 0.005), shock (OR, 1.95; 95%CI, 1.04-3.72; P = 0.04), and respiratory failure (OR, 2.18; 95%CI, 1.14-4.25; P = 0.02); and factors independently associated with lower hospital mortality were GCS score on day 1 (OR, 0.88/point; 95%CI, 0.81-0.95; P = 0.0009) and autologous stem cell transplantation (OR, 0.25; 95%CI, 0.07-0.75; P = 0.02)., Conclusions: In ICU patients with hematological malignancies, neurological failure is common and often fatal. Independent predictors of higher hospital mortality were type of underlying hematological malignancy, poor performance status, hemodynamic and respiratory failures, and severity of consciousness impairment. Knowledge of these risk factors might help to optimize management strategies.

Background/significance: People with cancer can experience co-occurring related symptoms, labeled symptom clusters. Gastrointestinal (GI) symptoms are common side effects of chemotherapy, but little research has investigated GI symptom clusters. A further gap in symptom cluster research is the lack of studies reporting symptom clusters based on symptom distress ratings., Purpose: To identify distress-based GI symptom clusters and to investigate their relationship to symptom interference with daily life and quality of life (QoL)., Subjects: About 105 adults with hematologic malignancy receiving chemotherapy., Methods: On Day 1 of a cycle of chemotherapy, participants completed a modified version of the Memorial Symptom Assessment Scale assessing 30 clinically relevant symptoms, the M.D. Anderson Symptom Inventory Symptom Interference with Daily Life subscale, and the Fox Simple Quality of Life Scale. Exploratory factor analysis was used to identify distress-based symptom clusters. Symptom clusters with ≥50% GI symptoms were labeled GI symptom clusters. Linear mixed modeling explored relationships between GI symptom clusters and symptom interference with daily life and QoL., Results: Of the six distress-based symptom clusters found, the bloating cluster and appetite cluster were identified as GI symptom clusters. Both the bloating cluster and the appetite cluster were significantly related to symptom interference with daily life, but only the appetite cluster was significantly related to QoL., Conclusions: This research demonstrates the existence of distress-based GI symptom clusters and their relationship to symptom interference and QoL. Future work should explore predictors of distress-based symptom clusters and interventions to manage them., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Hematological malignancies comprise a diverse set of lymphoid and myeloid neoplasms in which normal hematopoiesis has gone awry and together account for ∼10% of all new cancer cases diagnosed in the United States in 2016. Recent intensive genomic sequencing of hematopoietic malignancies has identified recurrent mutations in genes that encode regulators of chromatin structure and function, highlighting the central role that aberrant epigenetic regulation plays in the pathogenesis of these neoplasms. Deciphering the molecular mechanisms for how alterations in epigenetic modifiers, specifically histone and DNA methylases and demethylases, drive hematopoietic cancer could provide new avenues for developing novel targeted epigenetic therapies for treating hematological malignancies. Just as past studies of blood cancers led to pioneering discoveries relevant to other cancers, determining the contribution of epigenetic modifiers in hematologic cancers could also have a broader impact on our understanding of the pathogenesis of solid tumors in which these factors are mutated., (© 2016 Hu and Shilatifard; Published by Cold Spring Harbor Laboratory Press.)

Objectives: Frailty is a geriatric syndrome characterized by decreased physiological reserves and an age-related vulnerability to stressors with higher risk of adverse health outcomes. Comprehensive geriatric assessment (CGA) might detect frailty but is time-consuming, implying the need for initial frailty screening. Most frailty screening tools do not include functional measures. Hand grip strength (HGS) is a reliable surrogate for overall muscle strength and predicts functional decline, morbidity and mortality. No studies are available in cancer patients on HGS as screening tool for frailty. We aimed to assess whether HGS can be used as a screening tool to predict an abnormal CGA and therefore frailty., Methods: Single centre cohort study in 59 patients aged 70 years or more with a haematological malignancy. HGS was measured using a vigorimeter. A patient was considered frail if any of the CGA elements were impaired., Results: Mean HGS before start of therapy in women was 37.0 ± 14.3 kPa and in men 66.1 ± 13.1 kPa. An abnormal CGA was present in 52 subjects (88%). HGS was associated with concurrent abnormal CGA (p = 0.058 in women, p = 0.009 in men). AUC was 0.800 (SE = 0.130) in women and 0.847 (SE = 0.118) in men. Optimal HGS cut-off points for likelihood of abnormal CGA were ≤52 kPa in women and ≤80 kPa in men., Discussion: In older patients with haematological malignancies, impairment in muscle function is present at diagnosis. HGS seems a promising screening tool to identify patients with abnormal CGA.

The process of blood formation, haematopoiesis, depends upon a small number of haematopoietic stem cells (HSCs) that reside in the bone marrow. Differentiation of HSCs is characterised by decreased expression of genes associated with self-renewal accompanied by a stepwise activation of genes promoting differentiation. Lineage branching is further directed by groups of cooperating and counteracting genes forming complex networks of lineage-specific transcription factors. Imbalances in such networks can result in blockage of differentiation, lineage reprogramming and malignant transformation. CCAAT/enhancer-binding protein-α (C/EBPα) was originally identified 30 years ago as a transcription factor that binds both promoter and enhancer regions. Most of the early work focused on the role of C/EBPα in regulating transcriptional processes as well as on its functions in key differentiation processes during liver, adipogenic and haematopoietic development. Specifically, C/EBPα was shown to control differentiation by its ability to coordinate transcriptional output with cell cycle progression. Later, its role as an important tumour suppressor, mainly in acute myeloid leukaemia (AML), was recognised and has been the focus of intense studies by a number of investigators. More recent work has revisited the role of C/EBPα in normal haematopoiesis, especially its function in HSCs, and also started to provide more mechanistic insights into its role in normal and malignant haematopoiesis. In particular, the differential actions of C/EBPα isoforms, as well as its importance in chromatin remodelling and cellular reprogramming, are beginning to be elucidated. Finally, recent work has also shed light on the dichotomous function of C/EBPα in AML by demonstrating its ability to act as both a tumour suppressor and promoter. In the present review, we will summarise the current knowledge on the functions of C/EBPα during normal and malignant haematopoiesis with special emphasis on the recent work.

Background: This study aimed to identify the most prevalent unmet needs of haematological cancer survivors., Methods: Haematological cancer survivors aged 18-80 years at time of recruitment were selected from four Australian state cancer registries. Survivors completed the Survivor Unmet Needs Survey. The most frequently reported "high/very high" unmet needs items were identified, as well as characteristics associated with the three most prevalent "high/very high" unmet needs reported by haematological cancer survivors., Results: A total of 715 eligible survivors returned a completed survey. "Dealing with feeling tired" (17%), was the most frequently endorsed "high/very high" unmet need. Seven out of the ten most frequently endorsed unmet needs related to emotional health. Higher levels of psychological distress (e.g., anxiety, depression and stress) and indicators of financial burden as a result of cancer (e.g., having used up savings and trouble meeting day-to-day expenses due to cancer) were consistently identified as characteristics associated with the three most prevalent "high/very high" unmet needs., Conclusions: A minority of haematological cancer survivors endorsed a "high/very high" unmet need on individual items. Additional emotional support may be needed by a minority of survivors. Survivors reporting high levels of psychological distress or those who experience increased financial burden as a result of their cancer diagnosis may be at risk of experiencing the most prevalent "high/very high" unmet needs identified by this study.

Objective: Hematological malignancies encompass a large spectrum of disease entities whose treatment by chemo/radiotherapy could lead to thyroid complications. To the best of our knowledge, no study has simultaneously addressed thyroid function, autoimmunity and nodularity. Therefore, we decided to conduct one., Materials and Methods: We evaluated 82 Caucasian patients (36 women and 46 men), who were treated at our Oncology division for hematological malignancies (multiple myeloma, chronic myeloid leukemia, chronic lymphatic leukemia, non-Hodgkin lymphoma and polycythemia vera) and compared them with a control group of 104 patients. Patients who had received or were receiving external head/neck radiotherapy were excluded. All oncological patients and control individuals underwent thyroid ultrasonography and thyroid function and autoimmunity tests., Results: A lower prevalence of enlarged thyroid and nodules were found in patients with respect to controls. The rate of thyroid nodules was the highest in multiple myeloma and polycythemia vera, and the lowest in chronic lymphatic leukemia. Non-Hodgkin lymphoma patients had the smallest thyroid nodules while men with multiple myeloma the biggest ones. No patient had hypothyroidism, while 5.6% of patients had subclinical hyperthyroidism. In contrast, within the control group the rates of hypothyroidism and hyperthyroidism, overt and subclinical, were 3.8%, 20.2%, 0% and 0% respectively. Moreover, the overall rate of thyroid autoantibody positiveness in patients was significantly lower than controls., Conclusion: In our experience, we found a significantly lower prevalence of thyroid abnormalities in hematologic patients who underwent chemotherapy, but not radiotherapy, with respect to controls.

The aim of the present study was to assess the prevalence of hyper-metabolic infection sites revealed by fluorine-18 ((18)F) fluorodeoxyglucose (FDG) positron-emission tomography (PET) combined with computed tomography (CT) in patients with febrile neutropenia (FN). Forty-eight consecutive patients with haematological malignancies and persistent FN (temperature ≥ 38°C and neutrophil count <500 cells/μl for more than two days) as a consequence of intensive chemotherapy were prospectively included. Pathological FDG uptakes identified 31 foci of infections located in the lungs (n=15, 48.4 %), colon (n=4, 12.9%), pancreas (n=2, 6.5%), skin (n=3, 9.7%), ear-nose-throat area (n=5, 16.1%), central venous catheter tract (n=1, 3.2%) and gallbladder (n=1, 3.2%). These pathological FDG uptakes were observed in half of the 48 patients (n=24). Among the 38 patients with a clinical diagnosis of infection, 23 showed a pathological FDG uptake, resulting in a FDG-PET/CT sensitivity of 61% (95% CI, 43-76%). Our study confirmed the ability of FDG-PET/CT to diagnose infections in patients with persistent FN., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Utilizing geriatric screening tools for the identification of vulnerable older patients with cancer is important. The aim of this study is to evaluate the hospitalization risk of elderly hematologic cancer patients based on geriatric assessment and laboratory parameters., Materials and Methods: In this cross sectional study 61 patients with hematologic malignancies, age 65 years and older, were assessed at a hematology outpatient clinic. Standard geriatric screening tests; activities of daily living (ADL), instrumental activities of daily living (IADL), Mini Nutritional Assessment (MNA), Mini Mental State Examination (MMSE), timed up and go test (TUG), geriatrics depression scale (GDS) were administered. Demographic and medical data were obtained from patient medical records. The number of hospitalizations in the following six months was then recorded to allow analysis of associations with geriatric assessment tools and laboratory parameters., Results: The median age of the patients, 37 being males, was 66 years. Positive TUG test and declined ADL was found as significant risk factors for hospitalization (p=0.028 and p=0.015 respectively). Correlations of hospitalization with thrombocytopenia, vitamin B12 and folic acid deficiency were statistically significant (p=0.004, p=0.011 and p=0.05 respectively)., Conclusions: In this study, geriatric conditions which are usually unrecognized in a regular oncology office visit were identified. Our study indicates TUG and ADL might be use as predictive tests for hospitalization in elderly oncology populations. Also thrombocytopenia, and vitamin B12 and folic acid deficiencies are among the risk factors for hospitalization. The importance of vitamin B12 and folic acid vitamin replacement should not be underestimated in this population.

Background: Cancer-related mortality remains the second most common cause of death in Poland. In many cases, the occurrence of treatment-related complications requires admission to the intensive care unit (ICU). The aim of this study was to assess the clinical application of the APACHE II, SAPS II and SOFA scales to evaluate the risk of death in patients with haematological malignancies treated in the ICU., Methods: This study's analysis included 99 patients, who were each assigned to one of the following two groups: surviving patients who were discharged from the ICU (n = 24); and patients who died in the ICU (n = 75). Analysis was performed using demographic, clinical and laboratory data obtained during the patient's admission to the ICU and also during the first 24 hours of intensive therapy. Patient assessment was performed using the APACHE II, SAPS II and SOFA scoring systems as well as other clinical variables., Results: Univariate logistic regression identified the following risk factors of death in patients with haematological malignancies: systolic (P = 0.006), diastolic (P = 0.01) and mean arterial pressure values (P = 0.009); occurrence of acute kidney injury; neutrophil (P = 0.009) and platelet count in the peripheral blood (P = 0.001); and the SAPS II (P = 0.00005), SOFA (P = 0.00009) and APACHE II (P = 0.0007) scores. SAPS II score was the only independent risk factor of patient death in multivariate analysis (P = 0.0004; unitary OR 1.052 [95% CI: 1.022-1.082])., Conclusion: Of all the applied patient assessment scales, only the SAPS II score was found to be useful in subjects with haematological malignancies hospitalised in the ICU.

The histone methyltransferase Enhancer of Zeste Homologue 2 (EZH2), a component of the polycomb group complex, is vital for stem cell development, including hematopoiesis. Its primary function, to deposit the histone mark H3K27me3, promotes transcriptional repression. The activity of EZH2 influences cell fate regulation, namely the balance between self-renewal and differentiation. The contribution of aberrant EZH2 expression to tumorigenesis by directing cells toward a cancer stem cell (CSC) state is increasingly recognized. However, its role in hematological malignancies is complex. Point mutations, resulting in gain-of-function, and inactivating mutations, reported in lymphoma and leukemia, respectively, suggest that EZH2 may serve a dual purpose as an oncogene and tumor-suppressor gene. The reduction of CSC self-renewal via EZH2 inhibition offers a potentially attractive therapeutic approach to counter the aberrant activation found in lymphoma and leukemia. The discovery of small molecules that specifically inhibit EZH2 raises the exciting possibility of exploiting the oncogenic addiction of tumor cells toward this protein. However, interference with the tumor-suppressor role of wild-type EZH2 must be avoided. This review examines the role of EZH2 in normal and malignant hematopoiesis and recent developments in harnessing the therapeutic potential of EZH2 inhibition.

Reduced-intensity (RIT) conditioning regimens are gaining increased attention as a result of their advantages and efficacy. However, no data are available regarding whether these regimens improve patient quality of life (QoL). In our study, health-related QoL (HRQoL) was retrospectively assessed in 111 patients with hematological malignancies. Analysis of the Quality of Life Questionnaire indicated that 35 of the RIT patients were able to perform their normal work and returned to their baseline levels of function 2 to 3 months after transplantation. In the myeloablative (MA) group, only 24 patients were able to resume work, and these patients returned to their baseline levels of function 6 to 8 months after transplantation (68.6% vs. 40.0%, P = 0.004). Grade III-IV organ toxicity occurred in 20% of the RIT patients and in 52% of the MA patients (P = 0.001), and the cumulative incidences of grades III-IV acute graft-versus-host disease (GVHD) were 13.7% and 35.0% in RIT and MA patients, respectively (P = 0.015). In conclusion, the RIT conditioning regimens were well tolerated by the patients, with a low incidence of transplant-related mortality (TRM) and serious acute GVHD. In addition, these regimens minimized procedure-related toxicity, improved QoL and did not influence lymphocyte reconstitution; however, OS was similar for both regimens because the relapse rate was relatively increased in the RIT groups.

Background Aims: The number of hematopoietic stem cells (HSCs) is critical for transplantation. The ex vivo expansion of mobilized peripheral blood (MPB) HSCs is of clinical value for reconstitution to meet clinical need., Methods: This study proposed a simple, defined, stromal-free and serum-free culture system (SF-HSC medium) for clinical use, which is composed of Iscove's modified Dulbecco's medium, cytokine cocktails and serum substitutes. This study also characterized the cellular properties of expanded MPB CD133(+) HSCs from patients with hematologic malignancies and healthy donors by surface antigen, colony-forming cell, long-term culture-initiating cell, gene expression and in vivo engraftment assays., Results: The expanded fold values of CD45(+) white blood cells and CD34(+), CD133(+), CD34(+)CD38(-), CD133(+)CD38(-), CD34(+)CD133(+), colony-forming and long-term culture-initiating cells at the end of 7-day culture from CD133(+) MPB of hematologic malignancies were 9.4-fold, 5.9-fold, 4.0-fold, 35.8-fold, 21.9-fold, 3.8-fold, 11.8-fold and 6.7-fold, and values from healthy donor CD133(+) MPB were 20.7-fold, 14.5-fold, 8.5-fold, 83.8-fold, 37.3-fold, 6.2-fold, 19.1-fold and 14.6-fold. The high enrichment of CD38(-) cells, which were either CD34(+) or CD133(+), sustained the proliferation of early uncommitted HSCs. The expanded cells showed high levels of messenger RNA expression of HOBX4, ABCG2 and HTERT and had the in vivo ability to re-populate NOD/SCID mice., Conclusions: Our results demonstrated that an initial, limited number of MPB CD133(+) HSCs could be expanded functionally in SF-HSC medium. We believe that this serum-free expansion technique can be employed in both basic research and clinical transplantation., (Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the nutritional status of patients admitted to hospital for the first time the hematology service and who have not received treatment for cancer, to know if the nutritional status assessed by the EGS-GP and serum albumin related mortality of patients, Methods: A longitudinal, prospective, analytical. EGS-Through GP assessed the nutritional status of patients, we used SPSS 19.0 for data analysis., Results: Evaluaron 119 patients, 52.1% female and 47.9% male. The most common diagnosis was non-Hodgkin lymphoma in 43.7%. According to the EGS-GP 50.4% of patients had some degree of malnutrition or was at risk of suffering of which: 31.1% had moderate and 19.3% had severe malnutrition. The 49.6% of patients had an adequate nutritional status. 30.3% of the patients who died, 37% had severe malnutrition and 50% severe decrease in albumin concentration., Conclusions: The prevalence of malnutrition in hematological patients treated at the National Cancer Institute of Mexico that have not received medical treatment was high. There is an association between nutritional status and mortality in this patient group., (Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.)

QTc prolongation is a risk factor for development of torsades de pointes (TdP). Combination therapy with fluoroquinolones and azoles is used in patients with hematologic malignancies for prophylaxis and treatment of infection. Both drug classes are implicated as risk factors for QTc prolongation. The cumulative effect on and incidence of QTc prolongation for this combination have not been previously described. A retrospective chart review was performed with hospitalized inpatients from 1 September 2008 to 31 January 2010 comparing QTc interval data from electrocardiogram (ECG) assessment at baseline and after the initiation of combination therapy. Ninety-four patients were eligible for inclusion. The majority, 88 patients (93.6%), received quinolone therapy with levofloxacin. Fifty-three patients (56.4%) received voriconazole; 40 (42.6%) received fluconazole. The overall mean QTc change from baseline was 6.1 (95% confidence interval [CI], 0.2 to 11.9) ms. Twenty-one (22.3%) of the studied patients had clinically significant changes in the QTc while receiving combination fluoroquinolone-azole therapy. Statistically significant risk factors for clinically significant changes in QTc were hypokalemia (P = 0.03) and a left-ventricular ejection fraction of <55% (P = 0.02). Low magnesium (P = 0.11), exposure to 2 or more drugs with the potential to prolong the QTc interval (P = 0.17), and female sex (P = 0.21) trended toward significance. Combination therapy with fluoroquinolone and azole antifungals is associated with increased QTc from baseline in hospitalized patients with hematologic malignancies. One in five patients had a clinically significant change in the QTc, warranting close monitoring and risk factor modification to prevent the possibility of further QTc prolongation and risk of TdP.

HIV is associated with an excess cancer risk, particularly of lymphoid malignancies. Modern therapeutics has changed the landscape of HIV disease and typical opportunistic complications of AIDS are now largely avoided. Although the risk of lymphoma has decreased, it still remains high. Nevertheless, treatment outcomes have improved due both to improvements in HIV medicine and in cancer therapeutics for the common lymphomas occurring in those with HIV infection. Other hematologic malignancies are rarely seen in HIV-infected patients, but the standardized risk ratio for many of these cancers is higher than in the background population. Principles of cancer care and appreciation for HIV infection as a comorbid condition can guide physicians in setting realistic goals and treatment for this patient population. In many cases, expected outcomes are very similar to the HIV-unrelated patients and therapeutic planning should be based on this understanding. Treatment tolerance can be predicted based on the status of the HIV disease and the cancer therapy being administered. For those hematologic cancers in which transplantation is part of standard care, this modality should be considered an option in those with HIV infection.

The impact of cancer therapy on the reproductive potential of patients is increasingly recognized because survival rates of patients have clearly improved in recent years. Different fertility preservation methods, either generally accepted or still experimental, are currently available, and counseling of patients requires a delicate balance between the efficacy and side effects of the proposed method and the characteristics of both the tumor and the therapy. Deeper knowledge of the effects of cancer therapy on the reproductive potential of patients over time is required to identify the most appropriate fertility preservation method. In this paper, we report a case-control study in which female patients who were diagnosed with hematological malignancies and treated with chemotherapy and/or radiotherapy were compared with age-matched controls in terms of ovarian reserve, as measured by ultrasound examination and hormonal status. By stratifying patients for gonadotoxicity of the therapy received and time elapsed from the end of the therapy, we report that patients treated with low gonadotoxic therapies, while being similar to age-matched controls in their ovarian reserve when evaluated within a few years from the end of the therapy, show a clear impairment over longer times. We also report that anti-Müllerian hormone is the most sensitive hormonal parameter in detecting changes in ovarian reserve when compared with follicle-stimulating hormone or inhibin-B. This study stresses the importance of accurate counseling at the time of diagnosis of cancer and emphasizes the risks of infertility with low gonadotoxic therapies that may reduce the reproductive window of survivors.

IL-21, the newest member of the common γ-chain family of cytokines, has pleiotropic biological effects through regulating a variety of immune cells. Recently, the role of IL-21 in the treatment of cancers has been widely investigated. Conducted phase I trials in metastatic malignant melanoma and renal cell carcinoma have shown that rIL-21 has a favorable antitumor activity. Expression of IL-21 and IL-21R has also been found in many types of hematological malignancies, such as chronic lymphocytic leukemia (CLL), multiple myeloma (MM) and lymphoma. Through binding with IL-21R, IL-21 induces activation of different JAK/STAT signal transduction pathways and regulates proliferation or apoptosis of tumor cells. In this review, we will discuss the expression of IL-21/IL-21R and its effect in different types of hematological malignancies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Chronic GVHD is one of the most severe complications of allogeneic HSCT. The sclerotic skin manifestations of cGVHD (ScGVHD) result from inflammation and fibrosis of the dermis, subcutaneous tissue, or fascia, leading to significant functional disability. Risk factors and clinical markers associated with ScGVHD remain largely unexamined. By using a single-visit, cross-sectional design, we evaluated 206 patients with cGVHD at the National Institutes of Health. Most patients manifested severe (ie, 63% National Institutes of Health score "severe"), refractory disease (median treatments = 4). ScGVHD was detected in 109 (52.9%) patients. ScGVHD was associated with greater platelet count (P < .001) and C3 (P < .001), and decreased forced vital capacity (P = .013). Total body irradiation (TBI) was associated with development of ScGVHD (P = .002). TBI administered in reduced-intensity conditioning was most strongly associated with ScGVHD (14/15 patients, P < .0001). Patients with ScGVHD had significant impairments of joint range of motion and grip strength (P < .001). Greater body surface area involvement was associated with poorer survival (P = .015). We conclude that TBI, particularly in reduced-intensity regimens, may be an important risk factor for ScGVHD. Widespread skin involvement is associated with significant functional impairment, distressing symptoms, and diminished survival. This trial is registered at http://www.clinicaltrials.gov as NCT00331968.