Hodgkin's Disease Research Articles

The Association between Allergies and Hematologic Tumors — A Review

Introduction: Dysfunctions of the immune system in allergic diseases and hematological malignancies are the subject of many studies due to the mechanisms that link them. Chronic inflammation created in the immune response in an allergic reaction has been associated with developing neoplastic diseases. Aim of the study: This review examines the potential correlation between Allergies and Hematologic Tumors: acute lymphoblastic leukemia, childhood leukemias, non-Hodgkin and Hodgkin lymphomas. Material and methods: An English-language literature review was conducted, analyzing studies from the PubMed database up to October 2024 regarding the correlation between Allergies and Hematologic Tumors. The review was performed using the PubMed database, with 50 works used. Conclusions: The relationship between allergies and hematological tumors is unclear. According to some studies, this relationship does not exist; some state, however, that allergic diseases show correlations with hematological malignancies. The results of these studies do not provide a clear answer to whether this is a positive or negative relationship. Some studies suggest that allergies reduce the risk of hematological malignancies, while others contradict this, suggesting that allergies may increase the risk of hematological tumors. The results of studies showing an increased risk of hematological malignancies in people suffering from allergies can be due to the hypothesis of antigenic stimulation, which may explain the mechanism of correlation between those diseases. This hypothesis suggests that chronic immune stimulation predisposes to hematologic malignancies such as multiple myeloma, non-Hodgkin's lymphoma (NHL), and leukemia by promoting the development of randomly occurring pro-oncogenic mutations in actively dividing immune cells. Different results on this potential correlation showed that further studies are necessary.

Disseminated vaccine-strain varicella-zoster virus reactivation in an adolescent with secondary immunodeficiency: a case report and literature review.

Routine childhood immunization against varicella-zoster virus has led to a dramatic reduction in the incidence of primary varicella. However, there are rare, yet significant cases reported of reactivated Oka-strain varicella, primarily in immunocompromised hosts. A 16-year-old female with Hodgkin's lymphoma developed a vesicular rash shortly after completing all chemotherapy treatment. Swabs obtained from the vesicles were positive for varicella-zoster virus. By the time of hospitalization, the patient developed a disseminated rash involving multiple dermatomes. Subsequent polymerase chain reaction confirmed Oka vaccine-strain varicella-zoster virus. The patient had previously received a primary series of immunizations against varicella in 2008 and 2012, with her 2nd dose given 11 years prior to her development of vaccine-strain herpes zoster and 10 years prior to her diagnosis of Hodgkin's lymphoma, respectively. The patient was treated with parenteral acyclovir upon hospitalization and monitored clinically for cutaneous disease progression as well as sequelae. After 8 days of inpatient treatment, her rash had stopped spreading with no new lesions. All earlier lesions had crusted over. No serious sequelae of disease such as pneumonitis, hepatitis, encephalitis, or meningitis occurred, and she made a complete recovery. There are individual and community-wide benefits to childhood immunization against varicella. This case highlights an unusual presentation of disseminated vaccine-strain herpes zoster in an adolescent with secondary immunodeficiency 11 years after completing primary immunization. In addition, this case informs pediatricians of complications that can arise in immunized subjects if they become immunosuppressed years later. The only way to distinguish between wild-type and vaccine-strain herpes zoster was by viral genotyping. Providers should be cognizant of potential vaccine virus reactivation in their differential. Considerations for work-up and management should include infection control and viral resistance in refractory cases.

Congestive heart failure after anthracycline‐containing treatment for Hodgkin lymphoma: A Swedish matched cohort study

AbstractIntroductionCongestive heart failure (CHF) is a known complication after anthracyclines and radiotherapy for classical Hodgkin lymphoma (cHL). Contemporary cHL treatment may be associated with less risk because radiotherapy use and techniques have changed substantially over time.MethodsIn this study, Swedish cHL patients diagnosed in 2000–2018, and treated with adriamycin [doxorubicin], bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, Adriamycin [doxorubicin], cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), were matched 1:10 to the general population on birth year and sex to investigate relative rates and cumulative risks of CHF.ResultsA total of 1994 cHL patients were included, with a median age of 34 years. The median follow‐up was 8.1 years. The CHF rate was higher for patients versus comparators (adjusted hazard ratio [HR] = 3.02, 95% confidence interval [CI]: 2.26–4.02). Patients treated with ≤200 mg/m2 of anthracyclines had HR of 2.89 (95% CI: 1.51–3.47) versus 3.91 (95% CI: 2.72–5.60) for >200 mg/m2. Treatment with ABVD was associated with a significantly higher CHF rate (adjusted HR = 3.25, 95% CI: 2.31–4.23), while BEACOPP was not (adjusted HR = 1.95, 95% CI: 0.91–4.16). The increase in relative rates translated to the absolute scale, with an increased risk persisting up to 18 years for low cumulative doses.ConclusionThese findings highlight that cHL survivors still face a substantial excess risk of CHF in the modern treatment era and that focus on cardiovascular health remains relevant.

Feasibility of Using 18F-FDG PET/CT Radiomics and Machine Learning to Detect Drug-Induced Interstitial Lung Disease

Background: Bleomycin is an oncolytic and antibiotic agent used to treat various human cancers because of its antitumor activity. Unfortunately, up to 46% of the patients treated with bleomycin develop drug-induced interstitial lung disease (DIILD) and potentially life-threatening interstitial pulmonary fibrosis. Tools and biomarkers for predicting and detecting DIILD are limited. Therefore, we aimed to evaluate the feasibility of 18F-FDG PET/CT, PET radiomics, and machine learning in distinguishing DIILD in an explorative pilot study. Methods: Eighteen Hodgkin’s lymphoma (HL) patients, of whom 10 developed DIILD after treatment with bleomycin, were retrospectively included. Five diffuse large B-cell lymphoma (DLBCL) patients were included as a control group since they were not treated with bleomycin. All patients underwent 18F-FDG PET/CT scans before (baseline) and during treatment (interim). Structural changes were assessed by changes in Hounsfield Units (HUs). The 18F-FDG PET scans were used to assess metabolic changes by examining the feasibility of 504 radiomics features, including the mean activity of the lungs (SUVmean). A Random Forest (RF) classifier evaluated the identification and prediction of DIILD based on PET radiomics features. Results: HL patients who developed DIILD showed a significant increase in standard SUV metrics (SUVmean; p = 0.012, median increase 37.4%), and in some regional PET radiomics features (texture strength; p = 0.009, median increase 101.6% and zone distance entropy; p = 0.019, median increase 18.5%), while this was not found in HL patients who did not develop DIILD and DLBCL patients. The RF classifier correctly identified DIILD in 72.2% of the patients and predicted the development of DIILD correctly in 50% of the patients. There were no significant differences in HUs over time within all three patient groups. Conclusions: Our explorative longitudinal pilot study suggests that certain regional 18F-FDG PET radiomics features can effectively identify DIILD in HL patients treated with bleomycin, as significant longitudinal increases were observed in SUVmean, texture strength, and zone distance entropy after the development of DIILD. The metabolic activity of these features did not significantly increase over time in DLBCL patients and HL patients who did not develop DIILD. This indicates that 18F-FDG PET radiomics, with and without machine learning, might serve as potential biomarkers for detecting DIILD.

FoxO1 signaling in B cell malignancies and its therapeutic targeting.

FoxO transcription factors (FoxO1, FoxO3a, FoxO4, FoxO6) are a highly evolutionary conserved subfamily of the 'forkhead' box proteins. They have traditionally been considered tumor suppressors, but FoxO1 also exhibits oncogenic properties. The complex nature of FoxO1 is illustrated by its various roles in B cell development and differentiation, immunoglobulin gene rearrangement and cell-surface B cell receptor (BCR) structure, DNA damage control, cell cycle regulation, and germinal center reaction. FoxO1 is tightly regulated at a transcriptional (STAT3, HEB, EBF, FoxOs) and post-transcriptional level (Akt, AMPK, CDK2, GSK3, IKKs, JNK, MAPK/Erk, SGK1, miRNA). In B cell malignancies, recurrent FoxO1 activating mutations (S22/T24) and aberrant nuclear export and activity have been described, underscoring the potential of its therapeutic inhibition. Here, we review FoxO1's roles across B cell and myeloid malignancies, namely acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt lymphoma (BL), Hodgkin lymphoma (HL), and multiple myeloma (MM). We also discuss preclinical evidence for FoxO1 targeting by currently available inhibitors (AS1708727, AS1842856, cpd10).

NCMP-22. CO-OCCURRENCE OF MULTIPLE SCLEROSIS AND HODGKIN LYMPHOMA. IS THERE A COMMON PATHOPHYSIOLOGY?

Abstract BACKGROUND Multiple sclerosis (MS) and Hodgkin lymphoma (HL) share common epidemiology, genetics and immunological factors. Both affect immune activation, cell proliferation and lymphocyte-mediated immunity. However, occurrence of these two distinct clinical conditions is rare. We present a case of a woman with transverse myelitis fulfilling criteria for MS with synchronous HL. CASE REPORT A 37-year-old woman presented to the emergency room with bilateral leg weakness, numbness and urinary retention. A contrasted MRI of the brain and thoracic spine showed non-specific, non-enhancing white-matter lesions in the brain, and patchy areas of peripheral contrast-enhancement with T2-hyperintensity in the thoracic cord. Treatment with steroid infusion resulted in mild improvements of leg weakness and numbness. Cerebrospinal fluid (CSF) demonstrated oligoclonal bands (OCB) and increased IgG index. Serum was positive for JCV antibody. Due to the atypical MRI findings, namely the peripheral nature of thoracic contrast-enhancement, we were concerned for other inflammatory or autoimmune etiologies. A computed tomography of the chest, abdomen and pelvis revealed a large mediastinal mass and enlarged lymph nodes. A biopsy revealed classic HL. Three-months later, a follow-up MRI brain showed worsening contrast-enhanced lesions. A repeat CSF study revealed normal OCBs and IgG index. CSF was negative for malignant cells and JC virus DNA. To rule out a rare possibility of central nervous system HL, a biopsy of an enhancing brain lesion was obtained, which showed focal gliosis and focal perivascular lymphocytic infiltrates. No malignant cells were observed. She was diagnosed with multiple sclerosis and started systemic chemotherapy (doxorubicin, bleomycin, dacarbazine and vinblastine) for HL. CONCLUSIONS We report a case of an atypical transverse myelitis with HL. Although familial genetic clustering has been described, other potential common risk-factors between MS and HL are Epstein-Barr Virus infection and immunologic overlap, particularly in the context of lymphocyte-mediated immunity.

Evaluation of the effectiveness of hematopoietic blood stem cell mobilization using empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases: the experience of several centers in the Russian Federation. A retrospective study

Aim. To evaluate the effectiveness of autologous hematopoietic stem cell (HSC) mobilization with empegfilgrastim in patients with lymphoproliferative diseases (LPDs) and to identify prognostic factors affecting the effectiveness of mobilization. Materials and methods. The paper analyzes the effectiveness of HSC mobilization with Extimia® by JSC "BIOCAD" (INN: empegfilgrastim) in patients with LPDs. The study included 89 patients with LPDs (Hodgkin's lymphoma, B- and T-cell lymphomas, plasma cell tumors) who were treated in 5 research centers of the Russian Federation (in Moscow and St. Petersburg). The median age of patients was 39 (18–67) years. In 26 (29%) patients, HSC mobilization was performed "in a stable state of hematopoiesis" using only pegylated granulocyte colony-stimulating factor (PEG-G-CSF), and in 63 (71%) patients after chemotherapy (CT). Empegfilgrastim was administered as a single dose of 7.5 mg subcutaneously in two regimens: 24 hours after the end of CT or at a random time. Results. Two groups of patients were identified, analyzed, and compared: those with ineffective (n=23, 26%) and effective (n=66, 74%) HSC mobilization. Univariate and multivariate statistical analyses (binary logistic regression and multiple bidirectional binary logistic regression, respectively) were sequentially performed to determine the factors associated with ineffective mobilization. In a one-factor analysis, we studied the sex, age, diagnosis, bone/bone marrow involvement, the number of previous CT lines, the status of the disease (remission/no remission), the history of radiation therapy, the time interval from the administration of empegfilgrastim to the decision to perform leukapheresis, the mode of granulocytopoiesis stimulation ("in a stable state of hematopoiesis" or after CT), the leukocyte and platelet counts. The subsequent multifactorial analysis of the two selected parameters (diagnosis and time interval from drug administration to the decision to perform leukapheresis) showed the following statistically significant risk factors for ineffective mobilization: T-cell lymphoma; T-cell lymphoma versus other (combination) diagnoses (B-cell lymphoma, Hodgkin's lymphoma and plasma cell tumor): p=0.046, Wald test, odds ratio 4.18 (95% confidence interval 0.96–19.4). The time interval from the administration of empegfilgrastim to the first leukapheresis in the effective mobilization group depended on the diagnosis. The longest period was observed in patients with plasma cell tumors and the shortest in those with T-cell lymphomas: 10 (4–10) vs 5.5 (4–6) [p=0.01, Kruskal–Wallis test]. Empegfilgrastim proved equally effective for HSC mobilization both "on stable hematopoiesis" and after CT. Conclusion. The results of the first multicenter experience with Extimia® by JSC "BIOCAD" (INN: empegfilgrastim) to mobilize autologous HSCs in LPD patients demonstrate its high efficacy with a favorable safety and tolerability profile: 74% (66/89) successful mobilizations after a single administration of a fixed dose of the drug.

A Decade of Prevalence and Clinicopathological Insights Into Classical Hodgkin Lymphoma: A Study From an Indonesian Tertiary Hospital

A Decade of Prevalence and Clinicopathological Insights Into Classical Hodgkin Lymphoma: A Study From an Indonesian Tertiary Hospital

EPID-21. PRIMARY INTRAMEDULLARY LYMPHOMA OF SPINAL CORD (PILSC): A SYSTEMATIC REVIEW OF CASE REPORTS AND CASE SERIES FROM 2000 TO 2023

Abstract BACKGROUND AND OBJECTIVE Primary CNS lymphoma accounts for three percent of all newly diagnosed CNS tumours and 1-3% of all non-Hodgkin’s lymphomas. The oncologic origin of primary intramedullary lymphoma of the spinal cord (PILSC) is an enigma. We aim to determine the clinical manifestations, disease course and management of PILSC. MATERIALS AND METHODS A comprehensive literature search using PubMed Central and Google Scholar, was done, retrieving 17 case reports and two case series of 21 patients with PILSC and included using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, published between 2000 and 2023. RESULTS About 90.48% patients inflicted with PILSC were adult, with male predominance, 61.90%. The most common complaint at presentation was neurological deficit of motor type in 32.14% patients. MRI proved to be helpful in 76.19% cases, with spinal cord enlargement and high signal intensity in 19.04% cases. Adjuvant chemotherapy and radiotherapy was acquired by 52.38% and 38.09% patients. Non-Hodgkin type was reported in 90.47% cases and Hodgkin lymphoma was seen in 9.52% patients. Diffuse large B cell lymphoma was culprit in 41.10% cases. Five out of 21 cases had variable post-operative complications. The average follow-up was 16.16 months. CONCLUSION PILSC is a multifaceted neoplasm in all its clinico-pathological aspects of presentation. Although rare, PILSC can involve adult and paediatric populations with a clear male preponderance. The MRI findings are not reliable to make a preliminary diagnosis. Like other lymphomas, the role of chemoradiotherapy is clearly more significant than surgical intervention in improving patient prognosis. Histopathologically, it can be Non-Hodgkin or Hodgkin, B-cell type or T-cell type and has a wide array of immunohistochemistry positivity.

Sexual dysfunction among long-term survivors of Hodgkin lymphoma.

Survival rates from childhood cancer continue to increase, with an ongoing interest in long-term survivorship. Although infertility and gonadal failure are well recognized in Hodgkin lymphoma (HL) survivors, sexual dysfunction is less studied. The objective of this study was to compare the prevalence of sexual dysfunction in HL survivors with that in matched community controls. Long-term survivors of HL (n=186; female, 51.61%; mean age at diagnosis. 14.41 years [range, 3.01-22.60 years]; current mean±standard deviation age, 36.73±7.93 years) and matched community controls (n=182; female, 50.55%; mean±standard deviation age, 36.41±9.02 years) completed a comprehensive, in-person clinical assessment, laboratory battery, and the International Index of Erectile Function or the Female Sexual Function Index questionnaire. Male survivors had increased levels of erectile dysfunction (18.89% vs. 6.67%; p=.0239) but indicated no difference in sexual desire. Female survivors had a higher prevalence of sexual dysfunction compared with female controls (46.88% vs. 15.22%; p<.0001) and an increased prevalence of moderate-to-severe loss of sexual desire (38.04% vs. 23.26%; p=.0361). Female survivors with sexual dysfunction indicated increased levels of anxiety (p=.0184), depression (p=.0153), and worse physical and mental health (p=.0141 and p=.0419, respectively). Male survivors with erectile dysfunction had higher rates of anxiety and impaired physical health (p=.0147 and p=.0266, respectively). Sexual dysfunction was prevalent in this childhood and adolescent Hodgkin lymphoma survivor cohort and was associated with effects on quality of life. Health care providers must recognize the need for screening and intervention in this group to hopefully contribute to improved overall quality of life.

Long-term follow-up of bulky classic Hodgkin lymphoma managed with ABVD and PET-guided RT demonstrates excellent outcomes in PET-negative cases.

The outcome of 221 patients with bulky (≥10 cm) classic Hodgkin lymphoma (cHL) treated with doxorubicin, bleomycin, vinblastine, dacarbazine and consolidative radiotherapy (RT) only in those with a positive end-of-treatment (EOT) positron emission tomography (PET) scan was evaluated. With a median follow-up of 9.6 years, 5- and 10-year progression-free survival (PFS) in EOT PET-negative cases were 94.0% and 90.4%, respectively, and in PET-positive cases, 5/10-year PFS was 64.6% (p < 0.001), with 15% overall receiving RT. Five-year PFS for Deauville (D) score DX/D1-3 was 93.6%, compared with D4 66.7% (p < 0.001) and D5 33.3% (p < 0.001). Omission of RT in EOT PET-negative cases is associated with excellent long-term outcomes in bulky cHL.

Erratum: Circulating Tumor DNA Sequencing for Biologic Classification and Individualized Risk Stratification in Patients With Hodgkin Lymphoma.

Erratum: Circulating Tumor DNA Sequencing for Biologic Classification and Individualized Risk Stratification in Patients With Hodgkin Lymphoma.

Risk of Cardiovascular Disease in Patients With Classical Hodgkin Lymphoma: A Danish Nationwide Register-Based Cohort Study.

Risk of cardiovascular disease (CVD) in patients with classical Hodgkin lymphoma (cHL) undergoing contemporary treatment is unclear. cHL patients ≥ 18 years at diagnosis treated with doxorubicin-containing chemotherapy between 2000 and 2022 were matched 1:5 with comparators on birth year, sex, and Charlson Comorbidity Index at time of matching (score of 0 or ≥ 1). Cause-specific cumulative incidence of a composite of CVDs with corresponding 95% confidence intervals (CIs) were computed with death and lymphoma relapse as competing events (i.e., by censoring individuals at such occurrences) using the Aalen-Johansen estimator. A total of 1905 patients and 9525 comparators with a median follow-up of 10 years (interquartile range, [IQR]: 5.9-17.4). Median age was 39 years (IQR: 27-56), median cumulative doxorubicin dose was 250 mg/m2 (IQR: 200-300). The CVD cumulative incidences were 4.7% (95% CI: 3.6-5.7) for patients versus 2.6% (95% CI: 2.3-2.9) for comparators at 5 years, 8.9% (95% CI: 7.2-10.5) versus 5.5% (95% CI: 4.9-6.0) at 10 years, and 17.0% (95% CI: 14.1-19.9) versus 8.2% (95% CI: 7.4-9.0) at 15 years. CVD remains a substantial effect after contemporary treatment for cHL, suggesting that awareness of symptoms and a low threshold for referral to diagnostic examination are still important measures during survivorship.

Assessment of fitness for bleomycin use and management of bleomycin pulmonary toxicity in patients with classical Hodgkin lymphoma: A British Society for Haematology Good Practice Paper.

This good practice paper (GPP) is intended to support clinicians in assessing patient fitness for bleomycin and in management of bleomycin pulmonary toxicity (BPT) where it occurs. Bleomycin, originally developed as an antibiotic in the 1960s, has been a cornerstone of therapy for classical Hodgkin lymphoma (CHL) since results of its use in combination with doxorubicin, vincristine and dacarbazine (ABVD) were first published by Bonadonna etal in 1975 1. The same author recognised high rates of respiratory morbidity in these patients 2, and bleomycin-;related pulmonary toxicity (BPT) is now a well-;recognised and feared complication with its use. ABVD and BEACOPP/ BEACOPDac (bleomycin, cyclophosphamide, etoposide, doxorubicin, vincristine and prednisolone, with procarbazine or dacarbazine) are standard first-;line treatments in CHL patients, but considerable variation remains in assessing patient fitness for bleomycin both clinically and with respiratory investigations. A recent survey of British haematologists regularly using bleomycin revealed that 87.5% have no local protocols for assessing patients in an evidence-;based fashion, with wide variations in practice captured in the same survey (personal data). A working group was established and a literature review undertaken with the goal of presenting practical recommendations for clinicians regarding bleomycin use based on available evidence and expert opinion.

Vanishing Bile Duct Syndrome in Pediatric Hodgkin Lymphoma: First Statistical Analysis of All Published Cases in Children and a Case Report.

Hodgkin lymphoma with vanishing bile duct syndrome is a rare paraneoplastic syndrome and has never been studied in the pediatric population. The objectives of this study were to determine the clinical characteristics of this rare condition in children through a literature review, and a descriptive analysis of all published cases with the index case report. All reported cases fulfilling the inclusion criteria were found through a literature search, and analyzed in descriptive statistics. A total of 10 cases were included in the study with a median age of 9.5 years and a male-to-female ratio of 9:1. The median duration of symptoms was 5.5 weeks with 3 cases having jaundice before the symptoms of lymphoma. The median bilirubin level was 8.4mg/dL. Seven cases received modified chemotherapy, and 5 used ursodeoxycholic acid. The survival rate was 50%. Normalization of liver functions after the lymphoma treatment was observed in 4 cases and was the only statistically significant factor (P=0.01) associated with the outcome. This is a rare entity in the pediatric population with a guarded prognosis comparable to the adult counterparts but a marked male predominance.

COVID-19 infection in children with blood cancer: A systematic review.

Blood cancer is the most common type of cancer and the leading cause of death by disease past infancy among children. Children with blood cancer are vulnerable population to viral infections such as coronavirus disease 2019 (COVID-19). To estimate the incidence of COVID-19 in children with blood cancer and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with blood cancer with COVID-19 illness. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature for studies on the development of COVID-19 in children with blood cancer, published from December 1, 2019 to April 30, 2023, with English language restriction. Of the 3077 papers that were identified, 155 articles were included in the systematic review (83 case report, 54 cohort and 18 case-series studies). Studies involving 1289 children with blood cancer with confirmed COVID-19 were analysed. Leukaemias (1141 cases) were the most frequent types of blood cancer observed in children who developed COVID-19, followed by non-Hodgkin's lymphomas (59 cases), Hodgkin's lymphomas (36 cases), Langerhans cell histiocytosis (7 cases), myelodysplastic syndrome (7 cases) and myeloid neoplasm (1 case). Among all 1289 blood cancer paediatric cases who transmitted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some children were documented to be admitted to the intensive care unit (ICU) (n = 175, 13.6%), intubated and placed on mechanical ventilation (MV) (n = 111, 8.6%), suffered acute respiratory distress syndrome (ARDS) (n = 144, 11.2%) or died (n = 111, 8.6%). Overall, COVID-19 in children with different types of blood cancer resulted in no or low severity of disease in 78.6% of all included cases (COVID-19 severity: asymptomatic = 238, mild = 601, or moderate = 171). Treatment for COVID-19 was not necessary in a small number of children with blood cancer (n = 94, 7.3%). Fatality in children with blood cancer with COVID-19 was reported in any of the included blood cancer categories for leukaemias (n = 99/1141, 8.7%), non-Hodgkin's lymphomas (n = 7/59, 11.9%), Hodgkin's lymphomas (n = 2/36, 5.5%), myelodysplastic syndrome (n = 1/7, 14.3%) or myeloid neoplasm (n = 1/1, 100%). Fatality rate in children with blood cancer infected with SARS-CoV-2 was the highest in patients with Hispanic ethnicity (n = 44/111, 39.6%) and COVID-19-related fatality was highest in male patients (76.5% of deceased patients). Most studies reported to alter the intensity and regimen of anticancer treatment in children with blood cancer during course of SARS-CoV-2 infection, however, many studies have reported to successfully treat COVID-19 without any changes to the anticancer treatment. Globally, leukaemias were the most prevalent and myeloid neoplasms were the least prevalent blood cancer types in children who developed SARS-CoV-2 infection. Children with blood cancer infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the healthy pediatric populations. Mortality in children with blood cancer and infected with SARS-CoV-2 was highest in cases belonging to male gender and Hispanic ethnicity. However, children with blood cancer tend to have milder COVID-19 symptoms and are less likely to be hospitalized and have better prognosis when compared to adults. Continuation of anticancer treatment in individual paediatric blood cancer patients with COVID-19 seems to be possible.

A large cohort from an immunology reference center and an algorithm for the follow-up of chronic neutropenia.

Chronic neutropenia causes involve nutritional deficiencies and inborn errors of immunity(IEI), such as severe congenital neutropenia. To classify common chronic neutropenia causes in a pediatric immunology unit. We enrolled 109 chronic neutropenia patients admitted to a pediatric immunology department between 2002-2022. We recorded clinical/laboratory features and genetic characteristics. The male/female ratio was 63/46. Fifty-eight patients had parental consanguinity(57.4%). 26.6% (n = 29) patients had at least one individual in their family with neutropenia. Common symtpoms at presentation were upper respiratory tract infections(URTI)(31.1%), oral aphthae(23.6%), skin infections(23.6%), pneumonia(20.8%), and recurrent abscesses(12.3%). Common infections during follow-up were URTI(56.8%), pneumonia(33%), skin infections(25.6%), gastroenteritis(18.3%), and recurrent abscesses(14,6%). Common long-term complications were dental problems(n = 51), osteoporosis(n = 22), growth retardation(n = 14), malignancy(n = 16)[myelodysplastic syndrome(n = 10), large granulocytic leukemia(n = 1), acute lymphoblastic leukemia(n = 1), Hodgkin lymphoma(n = 1), EBV-related lymphoma(n = 1), leiomyosarcoma(n = 1), and thyroid neoplasm(n = 1)]. We performed a genetic study in 86 patients, and 69(71%) got a genetic diagnosis. Common gene defects were HAX-1(n = 26), ELA-2 (ELANE)(n = 10), AP3B1(n = 4), and ADA-2(n = 4) gene defects. The IEI ratio(70.6%) was high. GCSF treatment(93.4%), immunoglobulin replacement therapy(18.7%), and HSCT(15.9%) were the treatment options. The mortality rate was 12.9%(n = 14). The most common long term complications were dental problems that is three times more common in patients with known genetic mutations. We prepared an algorithm for chronic neutropenia depending on the present cohort. An important rate of inborn errors of immunity, especially combined immunodeficiency(11.9%) was presented in addition to congenital phagocytic cell defects. Early diagnosis will allow us tailor the disease-specific treatment options sooner, preventing irreversible consequences.

PPM1D/Wip1 is amplified, overexpressed, and mutated in human non-Hodgkin's lymphomas.

Wip1, is a p53-dependent Ser/Thr phosphatase involved in the timely termination of DDR. The PPM1D gene encoding Wip1 is deregulated and thus gained an oncogene character in common human solid tumors and cell lines. This study assessed the oncogenic potential of the PPM1D gene in human non- Hodgkin's lymphomas (NHL), the most common hematological malignancy worldwide. FFPE human lymphoid hyperplasia (LH) (n = 17) and NHL tumor lymph node samples (n = 65) and human NHL cell lines were used to assess the oncogenic potential of the PPM1D gene in the present study. Copy number gain and mRNA expression analysis of the PPM1D/Wip1 gene were assessed by qRT-PCR analysis. Mutational analysis of Exon 6 of the PPM1D gene was performed by PCR amplification and Sanger sequencing. Expressions of Wip1 and p53 proteins were assessed by immunohistochemistry and Western blot analysis. We found that PPM1D gained gene copy number in NHL tumors by 0.7-8 times compared to the control (p < 0.01). Increased PPM1D/Wip1 gene copy number was associated with higher mRNA and protein expression in human NHL samples (p < 0.01). Overexpression of Wip1 in NHL tumors and NHL cell lines was associated with amplification level and was unaffected by p53 status. Furthermore, a heterozygous type insertion mutation was detected in exon 6 (c.1553_1554insA) of the PPM1D gene particularly in DLBCL samples. Wip1 may have oncogenic potential, perhaps playing a role in the onset and progression of human NHL. The possible significance of Wip1 overexpression to chemotherapy response in NHL remains an intriguing question that requires more exploration.

Fertility Preservation in Postpubertal Males Undergoing Cancer Treatment in a Middle-Income Country: Is it Possible Despite the Barriers?

Increased survival rates in childhood cancer have led to an emphasis on the importance of treatment-related infertility. Fertility preservation methods should be explained to every patient and their families (PaFs) before treatment. Establishing good communication with PaFs is crucial in this regard despite many barriers such as cultural and financial barriers. Routine feasibility of sperm preservation (SP) in adolescent males newly diagnosed with cancer was evaluated after the implementation of reimbursement for the procedure and storage by the national healthcare system. Males <18 years of age planned to undergo cancer treatment between 2021 and 2023 were included. Patient and their families were informed by the treating physician about the disease, treatment modality, side effects, the importance of SP, and the method. Information about the purpose and technique of SP was provided to the patient alone in a comfortable environment. Questions from PaFs were answered, and consent was obtained. The procedure and storage cost was covered by the social security institution. Seventeen patients (median age 15) (15 with bone/soft tissue sarcoma, 1 brain tumor, and 1 Hodgkin lymphoma) were included. There were no refusals for SP. Eleven patients were able to provide sperm samples. Of the 6 patients who could not provide sperm, 3 stated embarrassment, 2 anxiety, and 1 cancer-related pain. Increasing awareness among physicians about the importance of treatment-related infertility, allocating sufficient time to inform PaFs about fertility preservation, and providing information taking into account societal or socio-cultural factors will contribute to preventing treatment-related infertility. Establishing close communication with the Reproductive Health Center (RHC), along with the rapid and cost-free nature of the procedure, enhances success.

Correction to: Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: Correlation with FDG‐PET/CT

Correction to: Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: Correlation with FDG‐PET/CT