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Some patients with high ST2 levels, a marker for endothelial injury that is seen in graft-versus-host disease (GVHD), may have a response to treatment aimed at thrombotic microangiopathy. To the Editor: Vander Lugt et al. (Aug. 8, 2013, issue) 1 report an association between elevated levels of ST2 protein, a marker of endothelial injury, at the time of diagnosis of graft-versus-host disease (GVHD) and resistance to glucocorticoid therapy among the recipients of hematopoietic stem-cell transplantation (HSCT). The authors found a strong association between ST2 levels at day 14 after transplantation, a point well before the onset of GVHD, and the rate of death at 6 months among patients without a relapse in disease, but the cause of increased mortality was not clear. Transplant-associated thrombotic microangiopathy (TA-TMA) is triggered by . . .

Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for many malignancies, hemoglobinopathies, metabolic diseases, bone marrow failure syndromes, and primary immune deficiencies. Despite the significant improvement in survival afforded by HSCT, the therapy is associated with major short and long-term morbidity and mortality. Cardiovascular complications such as cardiomyopathy, arrhythmias, pulmonary hypertension, and pericardial effusions are increasingly recognized as potential outcomes following HSCT. The incidence of cardiac complications is related to various factors such as age, co-morbid medical conditions, whether patients received cardiotoxic chemotherapy prior to HSCT, the type of HSCT (autologous versus allogeneic), and the specific conditioning regimen. Thus, the cardiovascular evaluation has become a core component of the pre-transplant assessment, however, the practice differs from center to center as national guidelines and contemporary high-quality studies are lacking. We review the incidence of cardiotoxicity in pediatric and adult HSCT, potential mechanisms of injury, and effects on long-term outcomes. We also discuss the possible therapeutic approaches when disease arises, as well as the indications and need for surveillance before, during, and after transplantation.

Disparities in access to hematopoietic cell transplant (HCT) are well established. Prior studies have identified barriers, such as referral and travel to an HCT center, that occur before consultation. Whether differences in access persist after evaluation at an HCT center remains unknown. The psychosocial assessment for transplant eligibility may impede access to transplant after evaluation. We performed a single-center retrospective review of 1102 patients who underwent HCT consultation. We examined the association between race/ethnicity (defined as Hispanic, non-Hispanic Black, non-Hispanic White, and Other) and socioeconomic status (defined by zip code median household income quartiles and insurance type) with receipt of HCT and Psychosocial Assessment of Candidates for Transplantation (PACT) scores. Race/ethnicity was associated with receipt of HCT (p = 0.02) with non-Hispanic Whites comprising a higher percentage of HCT recipients than non-recipients. Those living in higher income quartiles and non-publicly insured were more likely to receive HCT (p = 0.02 and p < 0.001, respectively). PACT scores were strongly associated with income quartiles (p < 0.001) but not race/ethnicity or insurance type. Race/ethnicity and socioeconomic status impact receipt of HCT among patients evaluated at an HCT center. Further investigation as to whether the psychosocial eligibility evaluation limits access to HCT in vulnerable populations is warranted.

Male infertility is defined as a failure to conceive after 12 months of unprotected intercourse owing to suspected male reproductive factors. Non-malignant red blood cell disorders are systemic conditions that have been associated with male infertility with varying severity and strength of evidence. Hereditary haemoglobinopathies and bone marrow failure syndromes have been associated with hypothalamic–pituitary–gonadal axis dysfunction, hypogonadism, and abnormal sperm parameters. Bone marrow transplantation is a potential cure for these conditions, but exposes patients to potentially gonadotoxic chemotherapy and/or radiation that could further impair fertility. Iron imbalance might also reduce male fertility. Thus, disorders of hereditary iron overload can cause iron deposition in tissues that might result in hypogonadism and impaired spermatogenesis, whereas severe iron deficiency can propagate anaemias that decrease gonadotropin release and sperm counts. Reproductive urologists should be included in the comprehensive care of patients with red blood cell disorders, especially when gonadotoxic treatments are being considered, to ensure fertility concerns are appropriately evaluated and managed.Haemoglobinopathies, systemic iron imbalances, bone marrow failure syndromes and nutritional deficiencies causing abnormalities in red blood cell physiology have been associated with male infertility. In this Review, the authors explore the effects of erythrocyte disorders and their treatment on male reproductive health.

As hematopoietic cell transplantation (HCT) and cellular therapy expand to new indications and international access improves, the volume of HCT performed annually continues to rise. Parallel improvements in HCT techniques and supportive care entails more patients surviving long-term, creating further emphasis on survivorship needs. Survivors are at risk for developing late complications secondary to pre-, peri- and post-transplant exposures and other underlying risk-factors. Guidelines for screening and preventive practices for HCT survivors were originally published in 2006 and updated in 2012. To review contemporary literature and update the recommendations while considering the changing practice of HCT and cellular therapy, an international group of experts was again convened. This review provides updated pediatric and adult survivorship guidelines for HCT and cellular therapy. The contributory role of chronic graft-versus-host disease (cGVHD) to the development of late effects is discussed but cGVHD management is not covered in detail. These guidelines emphasize special needs of patients with distinct underlying HCT indications or comorbidities (e.g., hemoglobinopathies, older adults) but do not replace more detailed group, disease, or condition specific guidelines. Although these recommendations should be applicable to the vast majority of HCT recipients, resource constraints may limit their implementation in some settings.

Clostridioides difficile infection (CDI) is common after allogeneic hematopoietic cell transplantation (alloHCT). The determination of incidence, risk factors, and impact of CDI on alloHCT outcomes is an unmet need. The study examines all patients aged 2 years and older who received first alloHCT for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic syndrome (MDS) between 2013 and 2018 at US centers and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) data registry. In total, 826 patients with CDI and 6723 controls from 127 centers were analyzed. The cumulative incidence of CDI by day 100 was 18.7% (99% CI: 15–22.7%) and 10.2% (99% CI: 9.2–11.1%) in pediatric and adult patients, respectively, with a median time to diagnosis at day +13. CDI was associated with inferior overall survival (OS) (p = 0.0018) and a 2.58-fold [99% CI: 1.43–4.66; p < 0.001] increase in infection-related mortality (IRM). There was a significant overlap in the onset of acute graft versus host disease (aGVHD) and CDI. IRM increased to >4 fold when CDI + aGVHD was considered. Despite advances in the management of CDI, increased IRM and decreased OS still results from CDI.

With increasing cancer incidence among individuals of reproductive age, preserving fertility has become a critical aspect of cancer care. This narrative review explores the impact of contemporary cancer therapies, including immunotherapies and targeted agents, on reproductive health, highlighting clinical fertility outcomes and underlying biological mechanisms. We outline the epidemiology and treatment strategies for malignancies common in adolescents and young adults (AYAs), including breast, melanoma, lung, gynaecologic, colorectal cancers and haematologic malignancies. Basic reproductive physiology in males and females is reviewed, including the hypothalamic–pituitary–gonadal axis, ovarian follicle and oocyte development, and spermatogenesis. Clinical data related to fertility and reproductive outcomes in patients receiving immunotherapy or targeted therapy are summarised, along with proposed mechanisms of gonadotoxicity from both conventional chemotherapy and newer drug classes. Special emphasis is placed on immunotherapy, such as checkpoint inhibitors, cell-based therapies (eg, chimeric antigen receptor T cells, tumour-infiltrating lymphocytes) and monoclonal antibodies, and small-molecule inhibitors, including kinase inhibitors (eg, BRAF, MEK, epidermal growth factor receptor), poly (ADP-ribose) polymerase inhibitors, epigenetic modifiers and apoptosis promoters (eg, BCL-2 inhibitors). Despite their growing use, these therapies are poorly studied in terms of reproductive safety, with available evidence being limited, heterogeneous and often lacking baseline fertility assessments or long-term follow-up. This uncertainty complicates counselling and decision-making, requiring a precautionary approach to fertility preservation. Multidisciplinary collaboration incorporating oncology, reproductive medicine, psychology and ethics is essential for individualised, ethically sound care. Emerging technologies such as organ-on-chip systems and induced pluripotent stem cell models offer promising avenues for mechanistic insight. To advance the field, future efforts must focus on prospective cohort studies, robust preclinical models and interim clinical guidelines to support informed fertility-related care for cancer patients.

Acute kidney injury (AKI) is a common complication in pediatric hematopoietic stem cell transplantation (HSCT). Serum creatinine is an imprecise biomarker of AKI. We hypothesized that combining creatinine with serum cystatin C (cysC) and urinary neutrophil gelatinase-associated lipocalin (NGAL) more effectively characterizes AKI during the first 28 days of HSCT and better identifies patients at risk of adverse outcomes than creatinine alone. We prospectively assessed the type and severity of AKI in 80 consecutive allogeneic HSCT patients using weekly creatinine, cysC, and NGAL. We combined the biomarkers to define 7 Composite Types of AKI, including All Positive AKI (simultaneously detected creatinine, cysC, and NGAL AKI). Outcomes included renal replacement therapy and transplant-related mortality. In all, 75% of patients had AKI by at least one measure; 33% developed >1 type of AKI. Mild AKI often preceded Severe AKI. Patients with creatinine or NGAL AKI that were Severe or Repeated tended to have worse outcomes. The five patients with All Positive AKI had the highest rates of morbidity and mortality. AKI evaluation with creatinine, cysC, and NGAL provides a comprehensive profile of early AKI and narrowly identifies patients at highest risk of adverse outcomes, providing opportunities for early, impactful intervention.

Background Pegaspargase (PEG‐ASP) is an integral component of therapy for acute lymphoblastic leukemia (ALL) but is associated with hepatotoxicity that may delay or limit future therapy. Obese and adolescent and young adult (AYA) patients are at high risk. Levocarnitine has been described as potentially beneficial for the treatment or prevention of PEG‐ASP‐associated hepatotoxicity. Methods We collected data for patients age ≥10 years who received levocarnitine during induction therapy for ALL, compared to a similar patient cohort who did not receive levocarnitine. The primary endpoint was conjugated bilirubin (c.bili) >3 mg/dl. Secondary endpoints were transaminases >10× the upper limit of normal and any Grade ≥3 hepatotoxicity. Results Fifty‐two patients received levocarnitine for prophylaxis (n = 29) or rescue (n = 32) of hepatotoxicity. Compared to 109 patients without levocarnitine, more patients receiving levocarnitine were obese and/or older and had significantly higher values for some hepatotoxicity markers at diagnosis and after PEG‐ASP. Levocarnitine regimens varied widely; no adverse effects of levocarnitine were identified. Obesity and AYA status were associated with an increased risk of conjugated hyperbilirubinemia and severe transaminitis. Multivariable analysis identified a protective effect of levocarnitine on the development of c.bili >3 mg/dl (OR 0.12, p = 0.029). There was no difference between groups in CTCAE Grade ≥3 hepatotoxicity. C.bili >3 mg/dl during induction was associated with lower event‐free survival. Conclusions This real‐world data on levocarnitine supplementation during ALL induction highlights the risk of PEG‐ASP‐associated hepatotoxicity in obese and AYA patients, and hepatotoxicity's potential impact on survival. Levocarnitine supplementation may be protective, but prospective studies are needed to confirm these findings. Patients who are adolescents or young adults and/or who are obese are at higher risk for pegaspargase‐induced hepatotoxicity. Levocarnitine supplementation may reduce the risk for hepatoxicity during induction therapy for acute lymphoblastic leukemia.