Bone Marrow Transplant Recipients Research Articles

Acute Myocardial Infarction in a 13-Year-Old Boy after Bone Marrow Transplantation

BackgroundAdvances in bone marrow transplantation (BMT) present a unique opportunity for treating leukemia in children. It has also increased the risk of long-term complications in the lungs, genitourinary tract, and nervous system. Coronary artery disease is the most common type of heart disease in older adults, but is not generally acknowledged as a complication of BMT, especially in young patients. Case ReportWe report the occurrence of acute myocardial infarction in a 13-year-old boy, approximately 5 years after he received a half-matched related bone marrow transplant from his father for T-cell lymphoblastic leukemia. Acute myocarditis was suspected early in the clinical course on the basis of his age and clinical presentations, such as atypical chest pain and dyspnea. Follow-up coronary angiography revealed a total occlusion of the right coronary artery, as well as diffused lesions of the left main, anterior descending, and circumflex branch. Fortunately, he was discharged from the hospital in satisfactory general condition after complex treatment.Why Should An Emergency Physician Be Aware of This? In this case, its rarity and poor clinical recognition were the main reasons for delayed diagnosis, which led to a delay to coronary angiography. Given the high mortality in cardiovascular complications among BMT recipients, the correct diagnostic assessment in such cases becomes particularly relevant.

A Visual Case-Oriented Analysis of Stress-Related Symptoms in Caregivers of Allogeneic Bone Marrow Transplantation Recipients.

To describe trends in caregiver stress and stress-related symptoms (anxiety, depression, fatigue, and sleep disturbance) across 12 weeks post-transplantation. 11 caregivers were recruited from a National Cancer Institute-designated comprehensive cancer center's bone marrow transplantation (BMT) outpatient clinic in the southeastern United States. A visual case-oriented analysis was conducted on data from 11 caregivers' weekly self-reported data to identify trends after allogeneic BMT. The authors identified three primary trends as follows: U-shaped (highest symptoms at start of transplantation and end of study; n = 3), negatively sloped (highest symptoms at beginning of transplantation and decreasing over time; n = 2), and V-shaped predischarge (highest symptoms at start of transplantation and right before discharge home; n = 4). Two caregivers did not have postdischarge data because of patient death prior to study completion. Caregivers may benefit from additional support to manage their stress-related symptoms at the start of transplantation and just before discharge.

Vaccination Coverage among Immunocompromised Patients in a Large Health Maintenance Organization: Findings from a Novel Computerized Registry

Immune-compromised patients (IPs) are at high risk for infections, some of which are preventable by vaccines. Specific vaccines are recommended for IP; however, the vaccination rate is suboptimal. The aim of this study is to describe the development of an IP registry and to assess vaccination rates in this population. A population-based registry of IPs was developed using an automated extraction of patient electronic health-record data in Maccabi Healthcare Services (MHS), an Israeli health maintenance organization serving over 2.4 million members. Included in the registry were patients receiving immunosuppressive therapy (IT); patients living with HIV (PLWH); solid organ and bone marrow transplant recipients (TR); patients with advanced kidney disease (AKD), and asplenic patients. We evaluated the full schedule for each vaccine’s uptake rates for influenza, pneumococcal, meningococcal, and hepatitis B. On 1 October 2019, 32,637 adult immune-compromised patients were identified by the registry. Of them, 1647 were PLWH; 2354 were asplenic; 5317 had AKD; 23,216 were on IT; and 1824 were TR. Their mean age was 57 and 52.4% were females. The crude rate of immune compromise among adult MHS members was 2%. Vaccine coverage rate was overall low for PCV13, with only 11.9% of all IPs in the registry having received one dose. Influenza and PPV23 vaccination rates were higher (45% and 39.4%, respectively). Only 5.3% of all IPs received all three vaccines. Overall, low vaccination coverage was found among IPs. Our registry can serve to identify target-patient populations for interventions and monitor their effectiveness.

Risk factors of healthcare-associated infections in recipients of bone marrow transplant

Bone marrow recipients are the most immunocompromizied patients who are susceptible to multiple infections. It is especially true for long-term episodes of drug-associated granulocytopenia. Our research goal was to identify risk factors of healthcare-associated infections (HAIs) in patients after bone marrow transplantation (BMT). Risk factors of developing HAIs were identified by accomplishing an analytical epidemiological “case – control” study with 973 patients participating in it. They all underwent BMT in the Hematology, Chemotherapy and Bone Marrow Transplantation Department of the Pirogov National Medical and Surgical Center on a period from 2015 to 2018. The following diseases were diagnosed in them: lymphoma (n = 158), multiple myeloma (n = 96), and multiple sclerosis (n = 719). HAIs cases were selected based on the standard (epidemiological) case definition in accordance with the Federal Clinical Recommendations on Epidemiological Surveillance over HAIs approved by the National Association of Experts responsible for Control over Healthcare-Associated Infections. Retrospective analysis established 75 HAIs cases or 7.7 % of the total number of the analyzed patients after BMT. Catheter-related bloodstream infections took the leading place among all the HAIs accounting for 52.0 ± 2.4 %. They were followed by bloodstream infections, 28.0 ± 3.1 %; lower respiratory tracts infections, 17.0 ± 3.2 %; and post-injection complications, 3.0 ± 0.6 %. Oncological diseases were established to cause HAIs in bone marrow recipients more frequently (ОR = 5.603; 95 % CI = 3.422÷9.174) than multiple sclerosis (ОR = 0.178; 95 % CI = 0.109÷0.292). This indicates that an underlying disease has its influence on a risk of infectious complications. We established a direct correlation between HAIs frequency and contamination with opportunistic microorganisms detected in objects in the hospital environment (r = 0.79, p = 0.01). This calls for implementing up-to-date disinfection provided for such objects.

Editorial introductions.

Current Opinion in Infectious Diseases was launched in 1988. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of infectious diseases is divided into 11 sections that are reviewed once a year. Each section is assigned to a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Genovefa A. PapanicolaouGenovefa A. PapanicolaouDr Genovefa A. Papanicolaou is the Director of Clinical Trials in the Infectious Disease Service at Memorial Sloan Kettering Cancer Center and Professor at Weill Cornell Medical College of Cornell University in New York, USA. Dr Papanicolaou is the current Chair of the Infectious Disease special Interest Group (ID-SIG) of the American Society for Transplantation and Cellular Therapy (ASTCT). Her research focuses on viral infections after stem cell transplantation and particularly cytomegalovirus (CMV). Her areas of interest are novel therapeutics, biomarkers and personalized infection management. Dionysios NeofytosDionysios NeofytosDionysios Neofytos is an Infectious Disease specialist with expertise in infectious disease complications in patients with hematologic malignancies and bone marrow and solid organ transplant recipients. Since the completion of his training in Infectious Diseases at Thomas Jefferson University Hospital in Philadelphia, PA, USA, in 2006 he has joined the Faculty and worked as an attending physician with the Transplant Infectious Disease Services at the Johns Hopkins University in Baltimore, MD, USA, and the Memorial Sloan Kettering Cancer Center in New York, NY, USA. Since 2016, he joined the Division f Infectious Diseases at the University Hospital of Geneva, in Geneva, Switzerland. His research and area of expertise are focusing on the epidemiology, diagnosis and management of viral and invasive fungal infections in immunocompromised hosts. Trish M. PerlTrish M. PerlTrish M. Perl, MD, MSc, is the H. Ben and Isabelle T. Decherd Chair in Internal Medicine (Infectious Diseases and Geographic Medicine) at UT Southwestern Medical Center in Dallas TX, USA. Dr Perl received her Medical Degree from the University of North Carolina (Chapel Hill), USA, and a Master of Science from McGill University in Montreal, Canada. She trained in Internal Medicine at the Royal Victoria Hospital and in Infectious Diseases and Clinical Epidemiology at the University of Iowa, USA. She rose through the ranks to Professor of Medicine at Johns Hopkins University School of Medicine, USA, and Epidemiology at the Bloomberg School of Public Health and is recognized globally for her innovation and research in healthcare associated infections, antimicrobial resistance, and their transmission and prevention. As the Hospital Epidemiologist at Johns Hopkins Hospital and Health System Epidemiologist, she developed extensive practical and research experience. Internationally, she has helped with outbreak management and mitigation including SARS, MERS CoV, Ebola and consults on guideline development and strategies to prevent emerging threats in healthcare. She is actively involved in monitoring the COVID-19 pandemic and supporting the national and local response.

Psychological processing among caregivers of allogeneic bone marrow transplant recipients: Qualitative findings from a longitudinal study

Purpose To describe caregiver psychological processing during the 12 weeks after transplant and the potential role of positive emotions in caregiving experiences. Methods We conducted a longitudinal qualitative descriptive study and interviewed 11 BMT caregivers monthly for 12-weeks post-transplant about their experiences and psychological processing. We analyzed 38 interviews using directed content analysis based on guiding theories and inductive in vivo coding to develop themes. Results The majority of participants appraised caregiving as a challenge that needed to be met. Caregivers described feeling positive emotions throughout the time after transplant (gratitude, interest, and hope). We identified two new themes: mirroring (caregiver feelings reflecting patient status) and emotion regulation (hiding negative emotions and displaying positive emotions when with the patient). Implications Findings provide further evidence that interventions focused on emotion regulation and positive emotion experiences during caregiving to reduce the negative effects of caregiving related stress may be promising.

Practical Applications of Prolonged Private Equity Holding Periods: Six Years is the New Normal

AIM--To determine whether there are characteristic immunohistological changes in the colonic mucosa in acute graft versus host disease (GvHD). METHODS--Consecutive allogeneic (n = 11) and autologous (n = 11) bone marrow transplant recipients underwent endoscopic biopsy of sigmoid mucosa before transplant and on day 30 post-transplant. Immunohistochemical staining and quantitation of intraepithelial and lamina propria mononuclear cells were undertaken using a panel of monoclonal antibodies and a Streptavidin-biotin alkaline phosphatase staining technique. RESULTS--In the allogeneic group (nine of whom had clinical acute GvHD) there was a fivefold increase in lamina propria CD16+ mononuclear cells (3.1 +/- 4.3 to 17.0 +/- 12.2 per 100 lamina propria nucleated cells), compared with autologous transplant recipients in whom this rise was twofold (5.5 +/- 4.6 to 10.6 +/- 7.1 per 100 lamina propria nucleated cells). The CD16+ mononuclear cells had morphological appearances of tissue macrophages, but in neither the allogeneic nor autologous groups was there an increase in total macrophage numbers (CD14+). In patients with acute GvHD the lamina propria CD4+:CD8+ lymphocyte ratio fell (1.97 +/- 1.12 to 1.07 +/- 1.01), primarily because of a fall in the number of lamina propria CD4+ lymphocytes. In both allogeneic and autologous groups there was a fall in intraepithelial lymphocyte numbers, but there was no change in CD19+ (B cell), CD25+ (interleukin-2 receptor positive) or CD56+ (natural killer) cell numbers. CONCLUSION--Following bone marrow transplantation, there appears to be upregulation of lamina propria tissue macrophage CD16 (an Fc receptor for IgG), a change which is more noticeable after allogeneic transplantation and which may be related to the development of acute GvHD. In patients with acute GvHD there was a fall in the lamina propria CD4+:CD8+ lymphocyte ratio. If these changes are functionally important, they may have significant implications for understanding the pathogenesis of GvHD.

Effect of Cryopreservation in Unrelated Bone Marrow and Peripheral Blood Stem Cell Transplantation in the Era of the COVID-19 Pandemic: An Update from the Japan Marrow Donor Program

During the COVID-19 pandemic, donor grafts are frequently cryopreserved to ensure that a graft is available before starting a conditioning regimen. However, there have been conflicting reports on the effect of cryopreservation on transplantation outcomes. Also, the impact of cryopreservation may differ in bone marrow (BM) transplantation (BMT) and peripheral blood stem cell (PBSC) transplantation (PBSCT). In this retrospective study, we analyzed the clinical data of both cryopreserved unrelated BMTs (n = 235) and PBSCTs (n = 118) and compared these with data from a large control cohort without cryopreservation including 4133 BMTs and 720 PBSCTs. Among the patients with cryopreserved grafts, 10 BMT recipients (4.3%) and 3 PBSCT recipients (2.5%) did not achieve neutrophil engraftment after transplantation, including 4 of the former and all 3 of the latter who died early before engraftment. In a multivariate analysis, cryopreservation was not associated with neutrophil engraftment in BMT but significantly delayed neutrophil engraftment in PBSCT (hazard ratio [HR], .82; 95% confidence interval [CI], .69 to .97; P = .023). There was an interaction with borderline significance between cryopreservation and the stem cell source (P = .067). Platelet engraftment was delayed by cryopreservation after both BMT and PBSCT. Only 2 cryopreserved grafts (<1%) were unused during the study period. The cryopreservation of unrelated donor BM and PBSC grafts is associated with a slight delay in neutrophil and platelet engraftment but an acceptable rate of graft failure. PBSC grafts may be more sensitive to cryopreservation than BM grafts. Cryopreservation is a reasonable option during COVID-19 pandemic, provided that the apheresis and transplantation centers are adept at cryopreservation.© 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Ruxolitinib Treatment in an Adolescent With Chronic Graft-Versus-Host Disease Mimicking Eosinophilic Gastrointestinal Disorders: A Case Report

Eosinophilic gastrointestinal disorders (EGIDs) are well-documented entities in pediatric solid organ transplantation. However, the diseases are rare after bone marrow transplantation (BMT). We present an adolescent male with hemoglobin E-β-thalassemia who underwent BMT and developed chronic graft-versus-host disease (GVHD) mimicking EGIDs. Initially, the patient presented with a presumed diagnosis of eosinophilic gastroenteritis (subserosal type) and received corticosteroids for 12 weeks. Six months after corticosteroids cessation, he again developed abdominal pain, treated with corticosteroids, azathioprine, and a six-food elimination diet. Still, he later had similar symptoms with persistent hypereosinophilia. The patient was subsequently diagnosed with chronic GVHD after excluding various potential causes. Ruxolitinib also led to significant clinical improvement and the disappearance of eosinophilia. The differential diagnosis of chronic GVHD should be a concern in BMT recipients with persistent gastrointestinal symptoms and eosinophilia. Ruxolitinib may be a treatment option in children with a steroid-refractory disease.

Recognizing Pediatric ARDS: Provider Use of the PALICC Recommendations in a Tertiary Pediatric ICU.

For almost 50 years, pediatricians used adult guidelines to diagnose ARDS. In 2015, specific criteria for pediatric ARDS were defined. However, it remains unclear how frequently providers recognize pediatric ARDS and whether recognition affects adherence to consensus recommendations. This was a mixed-method, retrospective study of mechanically ventilated pediatric subjects after the release of the pediatric ARDS recommendation statement. Pediatric ARDS cases were identified according to the new criteria. Provider recognition was defined by documentation in the medical record. Pediatric ARDS subjects with and without provider recognition were compared quantitatively according to clinical characteristics, adherence to lung-protective ventilation (LPV), adjunctive therapies, and outcomes. A qualitative document analysis (QDA) was performed to evaluate knowledge and beliefs surrounding the Pediatric Acute Lung Injury Consensus Conference recommendations. Of 1,983 subject encounters, pediatric ARDS was identified in 321 (16%). Provider recognition was present in 97 (30%) cases and occurred more often in subjects who were older, had worse oxygenation deficits, or were bone marrow transplant recipients. Recognition rates increased each studied year. LPV practices did not differ based on provider recognition; however, subjects who received it were more likely to experience permissive hypoxemia and adherence to extrapulmonary recommendations. Ultimately, there was no differences in outcomes between the provider recognition and non-provider recognition groups. Three themes emerged from the QDA: (1) pediatric ARDS presents within a complex, multidimensional context, with potentially competing organ system failures; (2) similar to historical conceptualizations, pediatric ARDS was often considered a visual diagnosis, with measures of oxygenation unreferenced; and (3) emphasis was placed on non-evidence-based interventions, such as pulmonary clearance techniques, rather than on consensus recommendations. Among mechanically ventilated children, pediatric ARDS was common but recognized in a minority of cases. Potential opportunities, such as an opt-out approach to LPV, may exist for improved dissemination and implementation of recommended best practices.

Efficacy of Inspiratory Muscle Training on Respiratory Muscle Strength in Hematopoietic Stem Cell Recipients: A Systematic Review and Meta-analysis

Objective: To investigate whether inspiratory muscle training improves respiratory muscle strength and function and reduces dyspnea and fatigue in hematopoietic stem cell recipients. Design: A systematic review and meta-analysis of randomized controlled trials. Participants: People with hematological neoplasms who underwent hematopoietic stem cell transplantation. Intervention: Inspiratory muscle training with POWER breath Plus, POWERbreathe, Classic, and Threshold devices, with a load of 40% of the maximum inspiratory pressure. Outcome Measures: The primary outcomes were maximal inspiratory pressure, maximal expiratory pressure, forced expiratory volume in the first second of expiration (FEV1), forced vital capacity (FVC), and the FEV1/FVC ratio. Secondary outcomes were dyspnea, fatigue, respiratory rate, peripheral O2 saturation, quality of life, and functional capacity. Results: The search identified 3 eligible studies with a sample of 108 participants. Maximal inspiratory pressure was higher in the intervention group in the 3 studies reviewed, with an average difference of −9.3 cm H2O, −31.94 cm H2O, and −16 cm H2O in relation to the control group after inspiratory muscle training. One study found an improvement in the distance covered in the 6-minute walk test (34.22 m) and in the distance covered in the modified incremental shuttle walking test (66.43 m) in the intervention group. Limitation: This systematic review includes only 3 randomized controlled clinical trials. Conclusion: Inspiratory muscle training is effective in increasing inspiratory muscle strength and functional capacity in bone marrow transplant recipients. However, its effects on fatigue and dyspnea remain uncertain.

Expression of glucocorticoid and androgen receptors in bone marrow–derived hematopoietic and nonhematopoietic murine endometrial cells

To determine whether bone marrow (BM)-derived cells engrafting the murine endometrium express the glucocorticoid receptor (GR) and androgen receptor (AR). Recent data demonstrate that BM is a long-term source of multiple hematopoietic and nonhematopoietic endometrial cell types. Important roles for glucocorticoids and androgens in regulating endometrial functions, including decidualization and early embryo attachment/invasion, have very recently emerged. Whether endometrial cells of BM origin express glucocorticoid or ARs has not been previously studied. Animal study. Basic science laboratory. Wild-type C57BL/6J male mice expressing enhanced green fluorescent protein (GFP) and syngeneic wild-type C57BL/6J female mice aged 6-9 weeks. Murine bone marrow transplant. Bone marrow cells were harvested from adult wild-type C57BL/6 mice and subjected to flow cytometry to identify the percentage of hematopoietic and nonhematopoietic cells expressing GR or AR. Uterine tissue sections from lethally irradiated syngeneic adult female C57BL/6 mice that had been recipients of BM transplants from adult male transgenic donor mice ubiquitously expressing GFP were studied. Immunohistochemistry was performed in the uterine tissue sections of the recipient mice at 5, 9, and 12 months after transplant using specific anti-GR, anti-AR, anti-GFP, anti-CD45 (pan leukocyte marker), and anti-F4/80 (murine macrophage marker) primary antibodies. Confocal laser microscopy was used to localize and quantitate BM-derived (GFP+) cell types in the endometrial stromal and epithelial compartments and determine whether BM-derived cell types in the murine endometrium express GR or AR. Hematopoietic cells comprised 93.6%-96.6% of all cells in the BM, of which 98.1% ± 0.2% expressed GR and 92.2% ± 4.4% expressed AR. Nonhematopoietic cells comprised 0.4%-1.3% of BM, of which 52.8% ± 5.9% expressed GR and 48.9% ± 3.4% expressed AR. After BM transplant, the proportion of cells originating from BM in the endometrial stromal compartment increased over time, reaching 13.5% ± 2.3% at 12 months after transplant. In the epithelial compartments, <1% of the cells were of BM origin at 12 months after transplant. Most (60%-72%) GR+ and/or AR+ BM-derived cells in the stroma were hematopoietic (CD45+) cells, of which 37%-51% were macrophages. Nonetheless, 28%-33% of GR+ cells, and 28%-40% of AR+ BM-derived cells, were nonhematopoietic (CD45-) stromal cells of BM origin. A substantial number of BM-derived cells express GR and AR, suggesting a role for these cells in both glucocorticoid-regulated and androgen-regulated endometrial functions, such as proliferation and/or decidualization.

Epigenetic downregulation of Socs2 contributes to mutant N-Ras-mediated hematopoietic dysregulation.

ABSTRACTRAS mutations occur in a broad spectrum of human hematopoietic malignancies. Activating Ras mutations in blood cells leads to hematopoietic malignancies in mice. In murine hematopoietic stem cells (HSCs), mutant N-RasG12D activates Stat5 to dysregulate stem cell function. However, the underlying mechanism remains elusive. In this study, we demonstrate that Stat5 activation induced by a hyperactive Nras mutant, G12D, is dependent on Jak2 activity. Jak2 is activated in Nras mutant HSCs and progenitors (HSPCs), and inhibiting Jak2 with ruxolitinib significantly decreases Stat5 activation and HSPC hyper-proliferation in vivo in NrasG12D mice. Activation of Jak2-Stat5 is associated with downregulation of Socs2, an inhibitory effector of Jak2/Stat5. Restoration of Socs2 blocks NrasG12D HSC reconstitution in bone marrow transplant recipients. SOCS2 downregulation is also observed in human acute myeloid leukemia (AML) cells that carry RAS mutations. RAS mutant AML cells exhibited suppression of the enhancer active marker H3K27ac at the SOCS2 locus. Finally, restoration of SOCS2 in RAS mutant AML cells mitigated leukemic growth. Thus, we discovered a novel signaling feedback loop whereby hyperactive Ras signaling activates Jak2/Stat5 via suppression of Socs2.

Occult alloimmunization to the D antigen (RhD) related to graft versus host disease and its treatment.

Alloimmunization to red blood cell (RBC) antigens post-allogeneic stem cell transplantation (allo-SCT) appears to be quite rare. The D antigen (RhD) is considered the most immunogenic RBC antigen with possibly a third of RhD-negative individuals exposed to RhD-positive RBC transfusions becoming alloimmunized. Though variable, most are detectable within a year of exposure, and the median time between exposure and detection is estimated to be about a month. We report the detection of anti-D in an allogeneic bone marrow transplant (allo-BMT) recipient about five years following last exposure to RhD-positive RBC.

Loss of SIRT1 inhibits hematopoietic stem cell aging and age-dependent mixed phenotype acute leukemia

Aging of hematopoietic stem cells (HSCs) is linked to various blood disorders and malignancies. SIRT1 has been implicated in healthy aging, but its role in HSC aging is poorly understood. Surprisingly, we found that Sirt1 knockout improved the maintenance of quiescence of aging HSCs and their functionality as well as mouse survival in serial bone marrow transplantation (BMT) recipients. The majority of secondary and tertiary BMT recipients of aging wild type donor cells developed B/myeloid mixed phenotype acute leukemia (MPAL), which was markedly inhibited by Sirt1 knockout. SIRT1 inhibition also reduced the growth and survival of human B/myeloid MPAL cells. Sirt1 knockout suppressed global gene activation in old HSCs, prominently the genes regulating protein synthesis and oxidative metabolism, which may involve multiple downstream transcriptional factors. Our results demonstrate an unexpected role of SIRT1 in promoting HSC aging and age-dependent MPAL and suggest SIRT1 may be a new therapeutic target for modulating functions of aging HSCs and treatment of MPAL.

Donor plasmacytoid dendritic cells limit graft-versus-host disease through vasoactive intestinal polypeptide expression

AbstractVasoactive intestinal polypeptide (VIP), an anti-inflammatory neuropeptide with pleiotropic cardiovascular effects, induces differentiation of hematopoietic stem cells into regulatory dendritic cells that limit graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. We have previously shown that donor plasmacytoid dendritic cells (pDCs) in bone marrow (BM) donor grafts limit the pathogenesis of GVHD. In this current study we show that murine and human pDCs express VIP, and that VIP-expressing pDCs limit T-cell activation and expansion using both in vivo and in vitro model systems. Using T cells or pDCs from transgenic luciferase+ donors in murine bone marrow transplantation (BMT), we show similar homing patterns of donor pDCs and T cells to the major sites for alloactivation of donor T cells: spleen and gut. Cotransplanting VIP-knockout (KO) pDCs with hematopoietic stem cells and T cells in major histocompatibility complex mismatched allogeneic BMT led to lower survival, higher GVHD scores, and more colon crypt cell apoptosis than transplanting wild-type pDCs. BMT recipients of VIP-KO pDCs had more T helper 1 polarized T cells, and higher plasma levels of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α than recipients of wild-type pDCs. T cells from VIP-KO pDC recipients had increasing levels of bhlhe40 transcripts during the first 2 weeks posttransplant, and higher levels of CyclophilinA/Ppia transcripts at day 15 compared with T cells from recipients of wild-type pDCs. Collectively, these data indicate paracrine VIP synthesis by donor pDCs limits pathogenic T-cell inflammation, supporting a novel mechanism by which donor immune cells regulate T-cell activation and GVHD in allogeneic BMT.

The improvement in overall survival from unrelated donor transplantation in Australia and New Zealand is driven by a reduction in non-relapse mortality: A study from the ABMTRR.

Unrelated donors (UDs) are the commonest source for allogeneic transplantation (alloSCT), with higher non-relapse mortality (NRM) than siblings. We analyzed data from the Australasian Bone Marrow Transplant Recipient Registry from adults receiving a first UD alloSCT during 2001-2015, to determine whether and how NRM has changed. Predictors of outcome were determined using cox regression, accounting for time-interactions and competing risks. A total of 2308 patients met inclusion criteria. Changes over time included increasing age, utilization of peripheral blood cells, reduced intensity conditioning, and T-cell depletion. Three-year OS increased significantly from 44% in 2001-2005 to 58% in 2011-2015 (p < 0.001). This was attributed to a reduction in NRM from 35% to 24% (p < 0.001) with no change in relapse. Factors associated with increased NRM included age, male sex, CMV seropositivity, HLA mismatch, transplant more than 6 months from diagnosis, and T-cell depletion when administered during 2001-2005. Survival following UD SCT has improved by almost 15% over the past decade, driven by improvements in NRM. This has occurred despite increasing recipient age and appears to be due to better donor selection, reduced delays to transplantation, and improved prevention and management of GVHD.

Necrotizing fungal preseptal cellulitis secondary to Candida orthopsilosis in a diabetes mellitus patient – A rare case report and review of literature

Non-albicans candida infection is an emerging threat in immunocompromised patients like those with diabetes mellitus, bone marrow transplant recipients, or HIV-positive patients. We report a rare case of necrotizing preseptal cellulitis extending to the cheek caused by Candida orthopsilosis in a young diabetic patient. Fungal etiology must be considered as a possible cause of preseptal and facial cellulitis in the setting of uncontrolled diabetes mellitus, which is unresponsive to broad-spectrum antibiotics even in the absence of a local nidus of infection in the paranasal sinuses or oral cavity.

Effects of Chemotherapy on Neuroinflammation, Neuronal Damage, Neurogenesis, and Behavioral Performance in Bone Marrow Transplantation Recipient Mice.

As bone marrow transplant (BMT) is gradually applied to the study of central nervous system (CNS) disease, it is needed to investigate the proper dose of chemotherapy to eradicate bone marrow cells while bringing little damage to brain. In the present study, we established a BMT model with varied busulfan and cyclophosphamide (Bu-Cy) dosages. The recipient mice's chimera rate, neuronal death, neuroinflammation, and behavioral functions were all investigated. Chimerism of peripheral blood cells was shown to rise with Bu-Cy treatment doses, with 60.7% in the Bu(20mg/kg)/Cy(100mg/kg) group and 93.0% in the Bu(35mg/kg)/Cy(100mg/kg) group. Recipients with Bu(35mg/kg)/Cy(100mg/kg) therapy had brain injury, increased neuroinflammation, diminished neurogenesis and cognitive abnormalities, whereas animals given a lesser dosage had no such brain damages. Conclusively, considering the chimerism and the possibility to damage brain, we recommend Bu(20mg/kg)/Cy(100mg/kg) is the ideal dose in BMT for studying CNS diseases in the C57/BL6 mouse strain.

High-dose chemotherapy for relapsed germ cell tumours: outcomes in low-volume specialized centres.

To report treatment patterns and survival outcomes of patients with relapsed and refractory metastatic germ cell tumours (GCTs) treated with high-dose chemotherapy (HDCT) and autologous stem-cell transplantation in low-volume specialized centres within the widely dispersed populations of Australia and New Zealand between 1999 and 2019. We conducted a retrospective analysis of 111 patients across 13 institutions. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. We reviewed treatment regimens, survival outcomes, deliverability and toxicities. Primary endpoints included overall (OS) and progression-free survival (PFS). Cox proportional hazards models were used to test the association of survival outcomes with patient and treatment factors. The median (range) age was 30 (14-68) years and GCT histology was non-seminomatous in 84% of patients. International Prognostic Factors Study Group (IPFSG) prognostic risk category was very low/low, intermediate, high and very high in 18%, 36%, 25% and 21% of patients, respectively. Salvage conventional-dose chemotherapy (CDCT) was administered prior to HDCT in 59% of patients. Regimens included paclitaxel, ifosfamide, carboplatin and etoposide (50%), carboplatin and etoposide (CE; 28%), carboplatin, etoposide and ifosfamide (CEI; 6%), carboplatin, etoposide and cyclophosphamide (CEC; 5%), CEC-paclitaxel (6%) and other (5%). With a median follow-up of 4.4 years, the 1-, 2- and 5-year PFS rates were 62%, 57% and 52%, respectively, and OS rates were 73%, 65% and 61%, respectively. There were five treatment-related deaths. Progression on treatment occurred in 17%. In a univariable analysis, worse International Germ Cell Cancer Collaborative Group (IGCCCG) and IPFSG prognostic groups were associated with inferior survival outcomes. An association of inferior survival was not found with the number of high-dose cycles received nor when HDCT was delivered after salvage CDCT. This large dual-national registry-based study reinforces the efficacy and deliverability of HDCT for relapsed and refractory metastatic GCT in low-volume specialized centres in Australia and New Zealand, with survival outcomes comparable to those found in international practice.