Engineering T cells to suppress acute GVHD and leukemia relapse after allogeneic hematopoietic stem cell transplantation.

Acute graft-versus-host disease (aGVHD) limits the therapeutic benefit of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and requires immunosuppressive prophylaxis that compromises antitumor and antipathogen immunity. OX40 is a costimulatory receptor upregulated on circulating T cells in aGVHD and plays a central role in driving the expansion of alloreactive T cells. Here, we show that OX40 is also upregulated on T cells infiltrating GVHD target organs in a rhesus macaque model, supporting the hypothesis that targeted ablation of OX40+ T cells will mitigate GVHD pathogenesis. We thus created an OX40-specific cytotoxic receptor that, when expressed on human T cells, enables selective elimination of OX40+ T cells. Because OX40 is primarily upregulated on CD4+ T cells upon activation, engineered OX40-specific T cells mediated potent cytotoxicity against activated CD4+ T cells and suppressed alloreactive T-cell expansion in a mixed lymphocyte reaction model. OX40 targeting did not inhibit antiviral activity of memory T cells specific to Epstein-Barr virus, cytomegalovirus, and adenoviral antigens. Systemic administration of OX40-targeting T cells fully protected mice from fatal xenogeneic GVHD mediated by human peripheral blood mononuclear cells. Furthermore, combining OX40 targeting with a leukemia-specific chimeric antigen receptor in a single T cell product provides simultaneous protection against leukemia and aGVHD in a mouse xenograft model of residual disease posttransplant. These results underscore the central role of OX40+ T cells in mediating aGVHD pathogenesis and support the feasibility of a bifunctional engineered T-cell product derived from the stem cell donor to suppress both disease relapse and aGVHD following allo-HSCT.

Invasive fusariosis in patients with leukaemia in the era of mould-active azoles: increasing incidence, frequent breakthrough infections and lack of improved outcomes.

OBJECTIVES: Historically, patients with leukaemia and invasive fusariosis (IF) have experienced poor outcomes in the setting of persistent immunosuppression. Herein, we retrospectively reviewed the incidence, presentation and outcomes of IF that are scarcely studied in contemporary cohorts of leukaemia patients. METHODS: We identified adult leukaemia patients with proven or probable IF at MD Anderson Cancer Center during 2009-21. Independent risk factors for 42 day mortality after IF diagnosis were determined using a multivariable logistic regression model. Combined with historical data, the annual IF incidence density over the past 23 years was estimated using Poisson regression analysis. RESULTS: Among 140 leukaemia patients with IF (114 proven), 118 patients (84%) had relapsed/refractory leukaemia and 124 (89%) had neutropenia at IF diagnosis. One hundred patients (71%) had pulmonary IF, 88 (63%) had disseminated IF and 48 (34%) had fungaemia. Coinfections were common (55%). Eighty-nine patients (64%) had breakthrough IF to mould-active triazoles. Most patients (84%) received combination antifungal therapy. Neutrophil recovery [adjusted OR (aOR), 0.04; 95% CI, 0.01-0.14; P < 0.0001], pulmonary IF (aOR, 3.28; 95% CI, 1.11-9.70; P = 0.032) and high SOFA score (aOR, 1.91 per 1-point increase; 95% CI, 1.47-2.50; P < 0.0001) were independent predictors of 42 day mortality outcomes. From 1998 to 2021, IF incidence density increased significantly at an annual ratio of 1.03 (95% CI, 1.01-1.06; P = 0.04). CONCLUSIONS: IF is predominantly seen in patients with relapsed/refractory leukaemia and increasingly seen as a breakthrough infection to mould-active triazoles. Despite frequent combination antifungal therapy, high mortality rates have persisted in patients with lasting neutropenia.

Impact of an antimicrobial stewardship programme on antibiotic utilization and resistance burden in patients with acute leukaemia: an 11-year longitudinal cohort study using interrupted time-series analysis.

BACKGROUND: Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia. OBJECTIVES: To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms. METHODS: We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions. RESULTS: A total of 3296 BSI episodes with 454 419 days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [-70.03 DOT/1000 patient-days (PD), P = 0.036] and a decreasing trend (-11.65 DOT/1000 PD per quarter, P < 0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: -0.06 BSI/1000 PD per quarter, P = 0.002). The decreasing trend was more significant for Enterobacterales: ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of -0.06 BSI/1000 PD and -0.08 BSI/1000 PD per quarter, respectively (all P < 0.05). However, Pseudomonas aeruginosa BSI increased. CONCLUSIONS: Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales.

Prolonged cytopenias after immune effector cell therapy and lymphodepletion in patients with leukemia, lymphoma and solid tumors.

BACKGROUND AIMS: The success of chimeric antigen receptor (CAR) T-cell therapy in treating B-cell malignancies has led to the evaluation of CAR T-cells targeting a variety of other malignancies. Although the efficacy of CAR T-cells is enhanced when administered post-lymphodepleting chemotherapy, this can trigger bone marrow suppression and sustained cytopenia after CD19.CAR T-cell therapy. Additionally, systemic inflammation associated with CAR T-cell activity may contribute to myelosuppression. Cytopenias, such as neutropenia and thrombocytopenia, elevate the risk of severe infections and bleeding, respectively. However, data on the incidence of prolonged cytopenias after immune effector therapy in the solid tumor context remain limited. OBJECTIVE: We compared the incidence of prolonged cytopenias after immune effector therapy including genetically modified T-cells, virus-specific T-cells (VSTs) and NKT-cells, as well non-gene-modified VSTs for leukemia, lymphoma, and solid tumors (ST) to identify associated risk factors. METHODS: A retrospective analysis was conducted of 112 pediatric and adult patients with relapsed and/or refractory cancers who received lymphodepleting chemotherapy followed by immune effector therapy. Patients treated with 13 distinct immune effector cell therapies through 11 single-center clinical trials and 2 commercial products over a 6-year period were categorized into 3 types of malignancies: leukemia, lymphoma and ST. We obtained baseline patient characteristics and adverse events data for each participant, and tracked neutrophil and platelet counts following lymphodepletion. RESULTS: Of 112 patients, 104 (92.9%) experienced cytopenias and 88 (79%) experienced severe cytopenias. Patients with leukemia experienced significantly longer durations of severe neutropenia (median duration of 14 days) compared with patients with lymphoma (7 days) or ST (11 days) (P = 0.002). Patients with leukemia also had a higher incidence of severe thrombocytopenia (74.1%), compared with lymphoma (46%, P = 0.03) and ST (14.3%, P < 0.0001). Prolonged cytopenias were significantly associated with disease type (63% of patients with leukemia, 44% of patients with lymphoma, and 22.9% of patients with ST, P = 0.006), prior hematopoietic stem cell transplant (HSCT) (66.7% with prior HSCT versus 38.3% without prior HSCT, P = 0.039), and development of immune effector cell-associated neurotoxicity syndrome (ICANS) (75% with ICANS versus 38% without ICANS, P = 0.027). There was no significant association between prolonged cytopenias and cytokine release syndrome. CONCLUSIONS: Immune effector recipients often experience significant cytopenias due to marrow suppression following lymphodepletion regardless of disease, but prolonged severe cytopenias are significantly less common after treatment of patients with lymphoma and solid tumors.

Risk of Lymphoma and Leukemia in Thyroid Cancer Patients: A Retrospective Cohort Study in Germany.

Thyroid cancer is the ninth most common cancer worldwide. While differentiated thyroid cancer (DTC) has a high survival rate, concerns arise regarding optimal treatment strategies and potential long-term risks, including second primary malignancies (SPMs), associated with therapies such as radioiodine (RAI). The aim of the present study was to investigate the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia in Germany. This retrospective cohort study used the IQVIA TM Disease Analyzer database and included adults with a first documented diagnosis of thyroid cancer between January 2005 and December 2021 as well as propensity score matched individuals without thyroid cancer in 1284 general practices. Univariate Cox regression models were performed to examine the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia. A total of 4232 thyroid cancer patients (mean age: 54.2 years; 73.6% female) and 21 160 controls (mean age: 54.2 years; 72.6% female) were available for analyses. Thyroid cancer was significantly associated with a higher lymphoma incidence (HR: 3.35, 95% CI: 2.04-5.52), especially in men (HR: 5.37) and those aged 61-70 years. Leukemia incidence was not significantly associated with thyroid cancer (HR: 1.79, 95% CI: 0.91-3.53), although associations were notable in younger age groups. Thyroid cancer is positively associated with a risk of subsequent lymphoma, highlighting the need for vigilant surveillance and tailored treatment strategies. While the association with leukemia is less pronounced, close surveillance remains critical, especially in younger patients.

Fever at Time of Leukemia Diagnosis in Children: Predictor of Bloodstream Infection or Catheter Removal?

PURPOSE: To assess the incidence of fever at diagnosis in children with leukemia and determine if fever at diagnosis is a predictor of bloodstream infection (BSI) or central venous access device (CVAD) removal for infection either within the first 30 days or between 30 and 90 days after CVAD insertion. MATERIALS AND METHODS: One hundred fifty-one patients with acute leukemia (July 1, 2018, to December 31, 2020) who underwent a CVAD insertion within 2 weeks of diagnosis were included. Patient data included demographic characteristics, fever at diagnosis, CVAD type, antibiotics before and/or on the day of CVAD insertion, BSI incidence, BSI rates per 1,000 catheter days, and need for catheter removal after CVAD insertion within 30 days and between 30 and 90 days. RESULTS: Patients with fever at diagnosis had a significantly higher incidence of BSI within the first 30 days after CVAD insertion (17/23) than that among patients without fever (6/23) (P = .046) at diagnosis. No statistically significant difference was observed in the incidence of BSI between 30 and 90 days after CVAD insertion between patients with fever (5/11) and those without fever at diagnosis (6/11) (P = .519). Fever at diagnosis was not a predictor of CVAD removal within 30 days (9 patients required CVAD removal; 7/9 had fever and 2/9 had no fever) (P = .181) or between 30 and 90 days (4 patients required CVAD removal; 1/4 had fever and 3/4 had no fever at diagnosis) (P = .343) after insertion. CONCLUSIONS: Fever at diagnosis in patients with leukemia is not a predictor of CVAD removal for infection.

Assessing the impact of COVID-19 on acute leukemia patients: a comparative analysis of hematological and biochemical parameters.

BACKGROUND: The impact of COVID-19 infection on the blood system remains to be investigated, especially with those encountering hematological malignancies. It was found that a high proportion of cancer patients are at an elevated risk of encountering COVID-19 infection. Leukemic patients are often suppressed and immunocompromised, which would impact the pathology following COVID-19 infection. Therefore, this research aims to bring valuable insight into the mechanism by which COVID-19 infection influences the hematological and biochemical parameters of patients with acute leukemia. METHODS: This retrospective investigation uses repeated measures to examine changes in hematological and biochemical parameters among patients with acute leukemia before and after COVID-19 infection at a major Saudi tertiary center. The investigation was conducted at the Ministry of National Guard-Health Affairs in Riyadh, Saudi Arabia, on 24 acute leukemia patients with COVID-19 between April 2020 and July 2023. The impact of COVID-19 on clinical parameters, comorbidities, and laboratory values was evaluated using data obtained from the electronic health records at four designated time intervals. The relative importance of comorbidities, testing preferences, and significant predictors of survival was ascertained. RESULTS: The majority of leukemic COVID-19-infected patients, primarily detected through PCR tests, were diagnosed with acute lymphoblastic leukemia (70.8%). The hematological and biochemical parameters exhibited stability, except for a brief increase in ALT and a sustained rise in AST. These changes were not statistically significant, and parameters remained normal at all time points. Additionally, an increase in monocyte count was shown at time point-3, as well as platelet counts at time point 2. CONCLUSION: While this study did not detect statistically significant effects of COVID-19 on biochemical and hematological parameters in acute leukemia patients, further investigation is needed to fully understand the potential adverse reactions and modifications following COVID-19 infection.

How I treat: Coronavirus disease 2019 in leukemic patients and hematopoietic cell transplant recipients.

Among immunocompromised hosts, leukemia patients, and hematopoietic cell transplant recipients are particularly vulnerable, facing challenges in balancing coronavirus disease 2019 (COVID-19) management with their underlying conditions. In this How I Treat article, we discuss how we approach severe acute respiratory syndrome coronavirus 2 infections in daily clinical practice, considering the existing body of literature and for topics where the available data are not sufficient to provide adequate guidance, we provide our opinion based on our clinical expertise and experience. Diagnostic approaches include nasopharyngeal swabs for polymerase chain reaction testing and chest computed tomography scans for symptomatic patients at risk of disease progression. Preventive measures involve strict infection control protocols and prioritizing vaccination for both patients and their families. Decisions regarding chemotherapy or hematopoietic cell transplantation in leukemia patients with COVID-19 require careful consideration of factors such as COVID-19 severity and treatment urgency. Treatment protocols include early initiation of antiviral therapy, with nirmatrelvir/ritonavir or remdesivir. For cases of prolonged viral shedding, distinguishing between viable and non-viable viruses remains challenging but is crucial for determining contagiousness and guiding management decisions. Overall, individualized approaches considering immune status, clinical presentation, and viral kinetics are essential for effectively managing COVID-19 in leukemia patients.

Association of clonal haematopoiesis with severe postoperative complications in patients undergoing radical oesophagectomy.

BACKGROUND: Clonal haematopoiesis (CH) is an age-associated clonal expansion of blood cells driven by leukaemia-associated somatic mutations. Although CH has been reported to be a risk factor for leukaemia and a number of non-haematopoietic diseases, its role in perioperative medicine remains unexplored. METHODS: This was a single-centre, prospective, observational study. Patients undergoing radical oesophagectomy were enrolled, and peripheral blood samples were collected for DNA sequencing. Patients with haematopoietic somatic mutations (variant allele frequencies ≥1%) in the DNMT3A gene, TET2 gene, or both were defined as CH carriers. The primary outcome was the incidence of severe postoperative complications (Clavien-Dindo classification ≥3). The secondary outcomes included the major types of postoperative complications, mortality, and other common perioperative variables. RESULTS: Clonal haematopoiesis was found in 21.2% (33/156) of the patients (mean age: 66 yr [range: 26-79 yr]; 83% males). Some 14/33 (42.4%) patients with CH had severe postoperative complications, compared with patients without CH carriers (28/123 [22.8%]; P=0.024). Multivariable logistic regression analysis showed that CH was associated with an increased risk of developing severe postoperative complications (odds ratio, 3.63; 95% confidence interval, 1.37-9.66; P=0.010). Among the major postoperative complications, the incidence of pulmonary complications was significantly higher in the patients with CH than in those without CH (15 in 33 [45.5%] vs 30 in 123 [24.4%], P=0.018). CONCLUSIONS: Clonal haematopoiesis was associated with a higher incidence of severe postoperative complications in patients undergoing radical oesophagectomy, suggesting that clonal haematopoiesis can play an important role in perioperative medicine. CLINICAL TRIAL REGISTRATION: ChiCTR2100044175 (Chinese Clinical Trial Registry, http://www.chictr.org.cn/showproj.aspx?proj=123193).

Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant.

PURPOSE: Leukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM). METHODS: Whole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes. RESULTS: In P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response." CONCLUSIONS: We identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.

Cutaneous fusarium disease and leukaemias: A systematic review.

The present study analyses the clinical characteristics of patients diagnosed with cutaneous fusarium through a systematic review of cases reported in literature. A total of 39 cases were included, of which 53% were men, 30% were women, and in 17% the sex was not specified. The age ranged from 5 to 85 years. Most cases were reported in Brazil, followed by Japan and United States of America. The most common agent was Fusarium solani, in 37.5% of the patients. Most of the affected individuals had acute myeloid leukaemia and some of the predisposing factors, which included induction chemotherapy, febrile neutropenia, and bone marrow transplantation. The clinical topography of the lesions was located in 27.5% and disseminated in 72.5%, with the most observed clinical feature outstanding the presence of papules and nodules with central necrosis in 47% of the cases. Longer survival was demonstrated in those treated with more than three antifungals. It is concluded that cutaneous fusarium is a complex and challenging clinical entity, infection in patients with leukaemias underscores the need for thorough care to decrease morbidity and mortality.

The Effect of Regular Oral Care Protocol on Preventing or Decreasing Severity of Oral Mucositis in Acute Leukemia Patient: A Prospective Trail.

This article reports a study designed to evaluate the effectiveness of regular oral care protocol developed specifically for adults in intensive care to prevent mucositis. Data were collected using oral mucositis assessment scale, oral cavity assessment tool, and the National Cancer Institute Common Toxicity Criteria. The results indicated that oral mucositis can be reduced through the practice of administering oral care in accordance with oral health care guidelines. Oral care implemented in line with an evidence-based oral care guide and frequent observation of patients is the most important step in preventing oral mucositis.

Early Onset Psychosis in a Pediatric Oncology Setting: A Case Report.

Schizophrenia (SCZ) and schizoaffective disorder (SHZ) are psychiatric disorders commonly identified in individuals in their late adolescence or early adulthood. Comorbidities are common, though a concurrent diagnosis of leukemia, one of the most frequently occurring cancers of adolescence, has not yet been described in such cases. This case study outlines the clinical presentation, course, and treatment response of two 17-year-old male adolescents whose psychotic disorders complicated their leukemia treatment. The first patient was diagnosed with leukemia and subsequently with SCZ while undergoing leukemia treatment. The second patient was diagnosed with SHZ prior to the onset of leukemia. The case study will follow the methodology of Robert E. Stake (Abma & Stake, 2014), as the two cases share a leukemia diagnosis and the reported mental health impact connected with cancer-directed treatment. Early identification and treatment are critical for both psychotic disorders and cancers, often impacting the long-term prognosis. However, when co-occurring, their interplay can present unique challenges to care.

Pharmacological inhibition of the mixed lineage leukemia 1-menin interaction aggravates acute kidney injury induced by folic acid and ischemia-reperfusion in mice.

Mixed lineage leukemia 1 (MLL1) is a methyltransferase that induces histone H3 lysine 4 trimethylation (H3K4me3) and partially exerts its untoward functional effects by interacting with multiple subunits including menin and WD repeat-containing protein 5 (WDR5). In this study, we investigated the role and mechanisms of MLL1 in murine models of acute kidney injury induced by folic acid (FA) and ischemia-reperfusion. Injury to the kidney elevated the expression of MLL1, menin, WDR5, and H3K4Me3, which was accompanied by increased serum creatinine and blood urea nitrogen, renal tubular injury, and apoptosis. Pharmacological inhibition of MLL1 activity with MI503 to disrupt the interaction between MLL1 with menin further increased serum creatinine and blood urea nitrogen levels, enhanced expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, and induced more apoptosis in the kidney following FA and ischemia-reperfusion injury. In contrast, MI503 treatment decreased the expression of vimentin and proliferating cell nuclear antigens. Similarly, treatment with MM102 to disrupt the interaction between MLL1 and WDR5 also worsened renal dysfunction, aggravated tubular cell injury, increased apoptosis, and inhibited cellular dedifferentiation and proliferation in mice following FA injection. Moreover, MI503 inhibited FA-induced phosphorylation of epidermal growth factor receptor, signal transducer and activator of transcription 3, and extracellular signal-regulated kinase-1/2 in injured kidneys. Collectively, these data suggest that MLL1 contributes to renal protection and functional recovery and promotes renal regeneration through a mechanism associated with activation of the epidermal growth factor receptor signaling pathway.NEW & NOTEWORTHY Mixed lineage leukemia 1 (MLL1) is a methyltransferase that induces histone H3 lysine 4 trimethylation and exerts its functional roles by interacting with multiple subunits. In this study, we demonstrated that inhibition of MLL1 activity by MI503 or MM102 aggravated renal injury and apoptosis and suppressed renal tubular cell dedifferentiation and proliferation, suggesting that MLL1 activation during acute kidney injury acts as an intrinsic protective mechanism to mediate renal tubular cell survival and regeneration.

Epstein-Barr virus reactivation correlates with worse outcomes for patients exposed to hepatitis B virus after haploidentical hematopoietic stem cell transplantation.

Hepatitis B virus (HBV)has a high, chronic infection rate in Asian populations, but only few studies have analyzed the effect of Epstein-Barr virus (EBV) or Cytomegalovirus (CMV) reactivation in patients exposed to HBV after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This study aimed to assess the clinical outcomes of these patients. We conducted a retrospective research including 61 patients exposed to HBV after undergoing haplo-HSCT. The patients were classified into two groups: the CMV reactivation group and no CMV reactivation group. The results were compared between the two groups using the K-W test for continuous variables, Pearson's chi-square test for categorical variables, Kaplan-Meier curves to estimate overall survival (OS) and leukemia-free survival (LFS), and a Cox proportional hazards model to analyze multivariable influences. The 3-year cumulative HBV reactivation rate was 8.2%. The median duration of HBV reactivation was 16 months (16-22 months) after haplo-HSCT. The CMV reactivation group had a higher cumulative incidence of HBV reactivation than the group without CMV reactivation. The EBV reactivation was substantially higher in the CMV reactivation group compared to that in the no CMV reactivation group (37.0% vs.5.9% respectively; P = 0.002). Furthermore, EBV reactivation was a risk factor for 1-year LFS and 1-year OS. Based on our data, EBV reactivation was related to worse outcomes in patients exposed to HBV after haplo-HSCT, whereas CMV reactivation was not.

Fertility preservation in pediatric leukemia and lymphoma: A report from the Children's Oncology Group.

Certain chemotherapy agents, radiation, and surgery can all negatively impact future fertility. Consults regarding treatment-related risk for infertility and gonadal late effects of these agents should occur at the time of diagnosis as well as during survivorship. Counseling on fertility risk has traditionally varied significantly across providers and institutions. We aim to provide a guide to standardize the assignment of gonadotoxic risk, which can be used in counseling patients both at the time of diagnosis and in survivorship. Gonadotoxic therapies were abstracted from 26 frontline Children's Oncology Group (COG) phase III protocols for leukemia/lymphoma, in use from 2000-2022. A stratification system based on gonadotoxic therapies, sex, and pubertal status was used to assign treatments into minimal, significant, and high level of increased risk for gonadal dysfunction/infertility. Risk levels were assigned to protocols and different treatment arms to aid oncologists and survivor care providers in counseling patients regarding treatment-related gonadotoxicity. Males were most commonly at high risk, with at least one high-risk arm in 14/26 protocols (54%), followed by pubertal females (23% of protocols) and prepubertal females (15% of protocols). All patients who received direct gonadal radiation or hematopoietic stem cell transplant (HSCT) were considered at high risk. Partnering with patients and their oncology/survivorship team is imperative for effective fertility counseling both prior to and post treatment, and this comprehensive guide can be used as a tool to standardize and improve reproductive health counseling in patients undergoing COG-based leukemia/lymphoma care.

Evolution of neuroimaging findings in angioinvasive cerebral aspergillosis in a pediatric patient with leukemia during long-term observation.

The central nervous system is one of the most common sites of aspergillosis involvement in immunocompromised people, just after sinopulmonary infections. Neuroimaging modalities are crucial for the diagnosis of cerebral aspergillosis (CA). Here, we describe a rare case of concurrent mixed aspergillosis infection with Aspergillus fumigatus and Aspergillus niger in a 2-year-old leukemic boy. The first neuroimaging finding, which was followed by focal seizures, was recognized as extensive cerebral hemorrhage in the absence of thrombocytopenia and coagulopathy. As the patient survived for more than 4 months after diagnosis, we were able to perform a neuroimaging evaluation during long-term observation. In serial neuroimaging studies, a secondary fungal abscess was observed at the site of hemorrhagic infarctions. Finally, the patient died from bacterial sepsis. In this case study, we try to categorize the neuroimaging findings of CA into distinct phases to better understand how CA changes over time.

Daily serum phosphate increase as early and reliable indicator of kidney injury in children with leukemia and lymphoma developing tumor lysis syndrome.

BACKGROUND: Tumor lysis syndrome (TLS) and its most serious complication, acute kidney injury (AKI) are one of the emergency conditions in onco-hematology. It is difficult to predict the degree of kidney involvement. Therefore, we studied children with leukemia and lymphoma treated in four Hungarian tertiary centers (inpatient university clinics) retrospectively (2006-2016) from a nephrological aspect. METHOD: Data of 31 pediatric patients were obtained from electronic- and paper-based medical records. Physical status, laboratory test results, treatments, and outcomes were assessed. Patients were analyzed according to both "traditional" TLS groupings, as laboratory TLS or clinical TLS, and nephrological aspect based on pRIFLE classification, as mild or severe AKI. RESULTS: Significant differences were found between the changes in parameters of phosphate homeostasis and urea levels in both classifications. Compared to age-specific normal phosphate ranges, before the development of TLS, hypophosphatemia was common (19/31 cases), while in the post-TLS period, hyperphosphatemia was observed (26/31 cases) most frequently. The rate of daily change in serum phosphate level was significant in the nephrological subgroups, but peaks of serum phosphate level show only a moderate increase. The calculated cut-off value of daily serum phosphate level increased before AKI was 0.32 mmol/L per ROC analysis for severe TLS-AKI. The 24-h urinalysis data of eight patients revealed transiently increased phosphate excretion only in those patients with TLS in whom serum phosphate was elevated in parallel. CONCLUSION: Daily serum phosphate level increase can serve as a prognostic factor for the severity of pediatric TLS, as well as predict the severity of kidney involvement. A higher resolution version of the Graphical abstract is available as Supplementary information.

Persistent Rhinovirus Infection in a Child With Leukemia.

Human Rhinovirus (HRV) is one of the most common pathogens causing acute respiratory tract infections in infants and children. Several reports suggest that HRV has the potential to cause chronic infection after an acute viral infection in an immunosuppressed patient. Although chronic HRV infection has been reported in lung transplant recipients, patients with hypogammaglobulinemia and cystic fibrosis, the duration and severity of HRV infection remain unclear. In this study, we present a case of persistent HRV infection in a stem cell transplanted leukemia patient. This report raises several questions regarding the risk factors, duration, and severity of persistent HRV infection in acute leukemia patients, which warrants prospective and longitudinal studies.