Transplant and Nontransplant Salvage Therapy in Pediatric Relapsed or Refractory Hodgkin Lymphoma: The EuroNet-PHL-R1 Phase 3 Nonrandomized Clinical Trial.

Importance: The current standard-of-care salvage therapy in relapsed/refractory classic Hodgkin lymphoma (cHL) includes consolidation high-dose chemotherapy (HDCT)/autologous stem cell transplant (aSCT).

Objective: To investigate whether presalvage risk factors and fludeoxyglucose-18 (FDG) positron emission tomography (PET) response to reinduction chemotherapy can guide escalation or de-escalation between HDCT/aSCT or transplant-free consolidation with radiotherapy to minimize toxic effects while maintaining high cure rates.

Design, Setting, And Participants: EuroNet-PHL-R1 was a nonrandomized clinical trial that enrolled patients younger than 18 years with first relapsed/refractory cHL across 68 sites in 13 countries in Europe between January 2007 and January 2013.

Semen analysis and reproductive hormones in boys with classical Hodgkin lymphoma treated according to the EuroNet-PHL-C2 protocol.

Study Question: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters?

Summary Answer: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility.

What Is Known Already: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy.

Fertility-Preserving Treatments and Patient- and Parental Satisfaction on Fertility Counseling in a Cohort of Newly Diagnosed Boys and Girls with Childhood Hodgkin Lymphoma.

Purpose: The purpose of this study is to evaluate the use of fertility-preserving (FP) treatments and fertility counseling that was offered in a cohort of newly diagnosed children with classical Hodgkin lymphoma (cHL).

Methods: In this observational study, boys and girls with cHL aged ≤ 18 years with scheduled treatment according to the EuroNet-PHL-C2 protocol were recruited from 18 sites (5 countries), between January 2017 and September 2021. In 2023, a subset of Dutch participants (aged ≥ 12 years at time of diagnosis) and parents/guardians were surveyed regarding fertility counseling.

The impact of treatment for childhood classical Hodgkin lymphoma according to the EuroNet-PHL-C2 protocol on serum anti-Müllerian Hormone.

Study Question: What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)?

Summary Answer: Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL.

What Is Known Already: Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy.

Prevention of activated brown adipose tissue on F-FDG-PET scans of young lymphoma patients: results of an ancillary study within the EuroNet-PHL-C2 trial.

Activated brown fat (aBAT) is known to affect the evaluation of F-FDG PET scans, especially in young patients. The aim of this study was to determine factors influencing the occurrence of aBAT, and to investigate the effectiveness of the two preventive measures, warming and beta-blocker (propranolol) administration. Five-hundred-twenty-eight F-FDG-PET scans of 241 EuroNet-PHL-C2 trial patients from 41 nuclear medicine departments in Germany and Czech Republic were screened for aBAT.

Differentiation between rebound thymic hyperplasia and thymic relapse after chemotherapy in pediatric Hodgkin lymphoma.

Background: Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification.

Assessment of Waldeyer's ring in pediatric and adolescent Hodgkin lymphoma patients-Importance of multimodality imaging: Results from the EuroNet-PHL-C1 trial.

Background: In the EuroNet Pediatric Hodgkin Lymphoma (EuroNet-PHL) trials, decision on Waldeyer's ring (WR) involvement is usually based on clinical assessment, that is, physical examination and/or nasopharyngoscopy. However, clinical assessment only evaluates mucosal surface and is prone to interobserver variability. Modern cross-sectional imaging technology may provide valuable information beyond mucosal surface, which may lead to a more accurate WR staging.

Semen analysis and treatment risk factors in long-term survivors of childhood cancer.

The objective of this study was to compare semen quality (sperm density, progressive motility and spermia) between long-term childhood cancer survivors and a control group of males. The second objective was to correlate the semen analysis of the survivors with cancer treatment and endocrine status. The semen quality of 143 survivors (median age, 23.

Comparison of Interim PET Response to Second-Line Versus First-Line Treatment in Classic Hodgkin Lymphoma: Contribution to the Development of Response Criteria for Relapsed or Progressive Disease.

In first-line treatment of Hodgkin lymphoma (HL), Deauville scores 1-3 define complete metabolic remission. Interim F-FDG PET is also used for relapse-treatment adaptation; however, PET response criteria are not validated for relapse treatment. We performed a pairwise comparative analysis of early response to first- and second-line treatments in 127 patients with classic HL who experienced relapse.

Risk and Response Adapted Treatment Guidelines for Managing First Relapsed and Refractory Classical Hodgkin Lymphoma in Children and Young People. Recommendations from the EuroNet Pediatric Hodgkin Lymphoma Group.

The objective of this guideline is to aid clinicians in making individual salvage treatment plans for pediatric and adolescent patients with first relapse or refractory (R/R) classical Hodgkin lymphoma (cHL). While salvage with standard dose chemotherapy followed by high dose chemotherapy and autologous stem cell transplant is often considered the standard of care in adult practice, pediatric practice adopts a more individualized risk stratified and response adapted approach to salvage treatment with greater use of non-transplant salvage. Here, we present on behalf of the EuroNet Pediatric Hodgkin Lymphoma group, evidence and consensus-based guidelines for standardized diagnostic, prognostic and response procedures to allocate children and adolescents with R/R cHL to stratified salvage treatments.

Accelerated atherosclerosis, hyperlipoproteinemia and insulin resistance in long-term survivors of Hodgkin lymphoma during childhood and adolescence.

Long-term survivors of Hodgkin lymphoma during childhood or adolescence (HL survivors) are at high risk of developing treatment-related late cardiovascular sequelae. In our study we evaluated the presence of modifiable cardiovascular risk factors (hypertension, hyperlipoproteinemia, hyperinsulinemia, obesity), endothelial and inflammatory markers (E-selectin, PAI-1, hs-CRP) and atherosclerotic changes in the common carotid arteries. Assessment was performed in 80 young adult Hodgkin lymphoma long-term survivors at more than 10 years after the potentially cardiovascular toxic anticancer treatment (median age at evaluation 34.

F-FDG PET Response of Skeletal (Bone Marrow and Bone) Involvement After Induction Chemotherapy in Pediatric Hodgkin Lymphoma: Are Specific Response Criteria Required?

To determine whether the current F-FDG PET response criterion for skeletal involvement in Hodgkin lymphoma (HL) is suitable, we performed a systematic evaluation of the different types of skeletal involvement and their response on PET after 2 cycles of chemotherapy (PET-2). A secondary objective was to observe the influence of the initial uptake intensity (measured as qPET) and initial metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. The initial PET scans of 1,068 pediatric HL patients from the EuroNet-PHL-C1 trial were evaluated for skeletal involvement by central review.

Inter-Reader Reliability of Early FDG-PET/CT Response Assessment Using the Deauville Scale after 2 Cycles of Intensive Chemotherapy (OEPA) in Hodgkin's Lymphoma.

Purpose: The five point Deauville (D) scale is widely used to assess interim PET metabolic response to chemotherapy in Hodgkin lymphoma (HL) patients. An International Validation Study reported good concordance among reviewers in ABVD treated advanced stage HL patients for the binary discrimination between score D1,2,3 and score D4,5. Inter-reader reliability of the whole scale is not well characterised.

Expression of the active caspase-3 in children and adolescents with classical Hodgkin lymphoma.

Unlabelled: The aim of the study was to determine whether the expression of active caspase-3 in neoplastic Hodgkin and Reed-Sternberg (H/RS) cells correlates with the treatment response and provides prognostic information on treatment outcome. In this retrospective study, we included 56 patients with classical Hodgkin lymphoma treated at the Department of Paediatric Haematology and Oncology between January 2000 and June 2005. Active caspase-3 was detected by immunohistochemistry in primary biopsy specimens.

qPET - a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma.

Background: Interim FDG-PET is used for treatment tailoring in lymphoma. Deauville response criteria consist of five ordinal categories based on visual comparison of residual tumor uptake to physiological reference uptakes. However, PET-response is a continuum and visual assessments can be distorted by optical illusions.