Abstract Hodgkin lymphoma (HL) is a B‐cell‐derived malignancy often affecting young adults. Allocation into risk groups is based on staging with positron emission tomography and computed tomography (PET/CT) and the presence or absence of risk factors. Standard treatment for early‐stage favorable classic HL (cHL) consists of two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), followed by 20 Gy involved‐site radiotherapy (IS‐RT). Two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) or a procarbazine‐free eBEACOPP variant plus two cycles of ABVD, followed by 30 Gy IS‐RT in the case of PET/CT positivity and no further treatment in the case of PET/CT negativity after chemotherapy should be considered in patients with early‐stage unfavorable cHL ≤ 60 years. If a less intensive approach is preferred and in individuals > 60 years, four cycles of A(B)VD followed by 30 Gy IS‐RT can be given. In advanced cHL, brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) for four (in the case of PET/CT negativity after two cycles) or six cycles (in the case of PET/CT positivity after two cycles), followed by PET/CT‐guided 30 Gy IS‐RT should be considered in patients ≤ 60 years. Six cycles of nivolumab and AVD (N‐AVD) followed by PET/CT‐guided 30 Gy IS‐RT represents a less intensive alternative for younger patients and the preferred approach for patients > 60 years. Patients with cHL recurrence should receive checkpoint inhibitor‐containing salvage treatment followed by high‐dose chemotherapy and autologous stem cell transplantation if eligible. Treatment of nodular lymphocyte‐predominant HL differs from cHL in some situations and may contain an anti‐CD20 antibody. This guideline aims at providing recommendations for diagnosis, staging, treatment, and follow‐up of HL.

Cancer remains a leading global cause of death, with critically ill cancer patients constituting a substantial proportion of ICU admissions. Historically restrictive ICU admission policies have shifted due to advances in oncology and critical care, leading to declining mortality. However, managing critically ill cancer patients remains complex, requiring collaboration between hematologists/oncologists and intensivists. Emerging evidence on risk assessment, organ support, and tailored critical care underscores the need for updated guidance. This consensus statement provides evidence-based, multidisciplinary recommendations to standardize best practices while allowing for individualized care, aiming to improve survival and quality of life in this high-risk population.

BACKGROUND:In early-stage favorable Hodgkin lymphoma (ES-HL), lymph node involvement patterns (NIP) have not been investigated until now. Adding finer granularity to the current disease classification system evaluated through systematically incorporating NIP alongside established clinical variables may help to identify distinct patient subgroups and improve the understanding of ES-HL. METHODS:A total of 3715 patients with ES-HL treated within the German Hodgkin Study Group HD10, HD13, and HD16 studies was retrospectively analyzed (stage I/II without risk factors). Involved lymph node regions were categorized into predefined anatomical areas, and the distribution patterns of affected lymph node regions were explored. Associations of patterns with baseline characteristics, histology, and 5-year progression-free survival (PFS) were analyzed using univariate and multivariable models. RESULTS:Despite 22 possible combinations, 91.6% of patients presented with one of the six most common NIP. They differed in terms of age, sex distribution, weight, hemoglobin levels, and histologic subtype composition. For example, the combination of cervical and mediastinal involvement was more frequent in younger patients, females, enriched for nodular sclerosis histology, and associated with superior 5-year PFS compared to other patterns (95.1% vs 91.9%, p < .001). Conversely, the combination of cervical and axillary involvement was associated with decreased 5-year PFS (85.3% vs 93.4%, p < .001) and was enriched for male sex and nodular lymphocyte-predominant Hodgkin lymphoma. CONCLUSIONS:Different presentation phenotypes exhibit distinct clinicopathologic characteristics and have prognostic impact in ES-HL. Further studies integrating molecular profiling are warranted to elucidate root mechanisms and possibly refine risk group allocation.

The LP-IPS including four (age, stage, splenic involvement, hemoglobin; 1 point for each factor) and the GHSG score comprising three (sex, albumin, variant histopathological growth pattern (GP); 2 points for sex, 1 point for albumin and variant GP) risk factors represent prognostic tools for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). A comparison of the scores has not been conducted until now. We thus performed an analysis comprising 583 NLPHL patients treated within GHSG studies. In addition to the LP-IPS and the original GHSG score, a modified GHSG score (GP DE replacing GP CDEF as risk factor variant GP) was also investigated. Low-risk vs high-risk groups were defined as 0-1 vs 2-4 points for the LP-IPS and 0-2 vs 3-4 points for the GHSG scores. Regarding progression-free survival (PFS) and overall survival (OS), Cox regression analyses revealed hazard ratios (HR) for the high-risk vs low-risk groups of 2.71 (95%-CI: 1.76-4.18) and 8.24 (95%-CI: 3.7-18.34) for the LP-IPS, 1.59 (95%-CI: 1.04-2.45) and 2.45 (95%-CI: 1.1-5.45) for the original and 1.97 (95%-CI: 1.25-3.09) and 4.15 (95%-CI: 1.86-9.23) for the modified GHSG score. The combination of the LP-IPS and the modified GHSG score (low-risk/low-risk vs high-risk/high-risk) resulted in high HR for the high-risk/high-risk group in terms of both PFS (HR: 3.74; 95%-CI: 2.09-6.7) and OS (HR: 13.52; 95%-CI: 5.03-36.35). Thus, the LP-IPS represents the most reliable standalone risk score for NLPHL. The combination of the LP-IPS and the modified GHSG score may help to further characterize specific risk groups.

Abstract We evaluated outcomes by management type for patients with stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in the Global NLPHL One Working Group retrospective database of 2243 patients with stages I to IV disease diagnosed from 1992 to 2021 at 38 international institutions. A total of 779 patients had stage IA disease with median age of 35 years (range, 3-89) and median follow-up of 6.1 years. The 6-year progression-free survival (PFS) and overall survival were 86.3% and 97.7%, respectively. Outcomes were analyzed for the 2 groups: complete resection and unresected disease. Patients with a complete resection and observation alone (n = 99) had a 6-year PFS of 65.5% vs 90.5% for those who received radiotherapy (RT) (n = 53). Patients with unresected disease (n = 627; 80.5%) had a 6-year PFS of 62.0% for rituximab alone (n = 31), 89.6% for RT alone (n = 325), 76.8% for ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) alone (n = 40), and 94.3% for ABVD plus RT (n = 130). A total of 127 patients relapsed (16.3%), of which 25 (19.7%) had transformation. Our analysis suggests the following: (1) RT improves the PFS in patients with completely resected disease; (2) rituximab or ABVD alone does not appear to achieve a durable response; and (3) chemotherapy was not observed to add additional PFS benefit when used in combination with RT. Thus, for stage IA NLPHL, RT alone is likely sufficient for definitive treatment.

Das nodulär Lymphozyten-prädominante Hodgkin-Lymphom (NLPHL) ist ein seltenes Lymphom mit einer Inzidenz von 0,1–0,2/100.000 pro Jahr. Pathophysiologie und klinisches Erscheinungsbild unterscheiden sich vom klassischen Hodgkin-Lymphom. Im vorliegenden Artikel wird ein Überblick über biologische und histologische Charakteristika des NLPHL sowie aktuelle Therapiekonzepte gegeben. Es wurde eine selektive Literaturrecherche durchgeführt. Das NLPHL stellt eine definierte, eigenständige Lymphomentität dar. Biologie und Pathologie sowie die Expression von Oberflächenmarkern unterscheiden sich vom klassischen Hodgkin-Lymphom, was beispielsweise im Fall von CD20 Einfluss auf die therapeutischen Möglichkeiten hat. In einigen Situationen unterscheidet sich die Behandlung des NLPHL von der des klassischen Hodgkin-Lymphoms. Patient*innen im Stadium IA ohne Risikofaktoren werden lediglich bestrahlt, für alle anderen frühen und mittleren Stadien sind die Ergebnisse mit Ansätzen, die auch beim klassischen Hodgkin-Lymphom zum Einsatz kommen, sehr gut. Das NLPHL in fortgeschrittenen Stadien wird entweder intensiv BEACOPP-basiert (Bleomycin, Etoposid, Doxorubicin, Cyclophosphamid, Vincristin, Procarbazin, Prednison) oder mit Protokollen, die aus dem Bereich der B‑Zell-Non-Hodgkin-Lymphome bekannt sind (v. a. R‑CHOP: Rituximab, Cyclophosphamid, Doxorubicin, Vincristin, Prednison), behandelt. Im Fall eines Rezidivs kann auf eine Hochdosis-Chemotherapie mit autologer Stammzelltransplantation oft verzichtet werden. Zusammengefasst ist eine präzise histopathologische Diagnostik inklusive Analyse von Oberflächenmarkern die Grundlage für die Wahl der optimalen Therapie. Die Prognose nach einer stadien- und risikoadaptierten Behandlung ist beim NLPHL sehr gut. Die meisten Patient*innen überleben langfristig.

The European Group for Blood and Bone Marrow transplantation Practice Harmonization and Guidelines Committee together with the Lymphoma Working Party convened 23 experts in Hodgkin lymphoma, transplantation, and radiation oncology, to develop consensus recommendations on the use of autologous and allogeneic haematopoietic cell transplantation (HCT) in relapsed or refractory Hodgkin lymphoma. Through a structured literature review and a 2-day workshop in Berlin, Germany, on Sept 29 and 30, 2025, the panel established guidance across major clinical decision points. The outcome of this review and workshop include the following recommendations. Salvage therapy should include brentuximab vedotin or checkpoint inhibitors, or both, with metabolic complete response preferred before autologous HCT. BEAM (carmustine, etoposide, cytarabine and melphalan) remains the most commonly used conditioning regimen, and autologous HCT continues to be the standard for chemosensitive relapse. Peri-transplantation radiotherapy could be considered for PET-positive or residual disease. Brentuximab vedotin consolidation is recommended for patients at high-risk. Allogeneic HCT is advised for eligible patients who relapse after autologous HCT, ideally with reduced intensity conditioning and post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis. Routine maintenance after allogeneic HCT is not recommended; relapse management should be tailored and can involve donor lymphocyte infusion, brentuximab vedotin, checkpoint inhibitors, chemotherapy, radiotherapy, or clinical trial enrolment.

Intensive multiagent treatment regimens have substantially improved outcomes in advanced-stage classic Hodgkin lymphoma (cHL). Brentuximab vedotin (BV), etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (BrECADD) demonstrated the highest efficacy in cHL reported to date in a randomised phase III trial. Cytotoxic agents are conventionally administered during the first 4 days of a 21-day cycle. A total of four cycles are applied to patients with a complete response after two cycles, otherwise six cycles. We developed a condensed BrECADD protocol, reducing intravenous administration days to only three (-25%). Between January 2024 and July 2026, 30 patients received 132 cycles of 3-day BrECADD at our institution. Primary objective was to describe feasibility and safety; secondary objectives included response, progression-free survival (PFS) and overall survival (OS). Grade ≥3 adverse events occurred in 23 patients (77%), predominantly haematological. Six patients (20%) had grade ≥3 infections (four viral, two bacterial) and six (20%) had pathogen-unspecified febrile neutropenia. Twenty-four patients (80%) required only four BrECADD cycles. There were no treatment discontinuations. After a median follow-up of 18 months (range 4-29), 1-year PFS and OS rates were both 100%. Based on these encouraging results, the condensed 3-day protocol is considered feasible and we recommend it for future BrECADD use.

ABSTRACT:Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening condition. Caplacizumab substantially shortens the time to clinical response, yet delayed platelet count recovery is occasionally observed, raising concerns about iTTP refractoriness. This retrospective multicenter study analyzed 204 acute iTTP episodes reported to the German REACT (Retrospective Evaluation of Acquired Thrombotic Thrombocytopenic Purpura in Caplacizumab-Treated Patients) 2020 and ATMAR (Austrian Thrombotic Microangiopathy Registry) registries, all treated with caplacizumab. Refractoriness was assessed using the 2017 International Working Group criteria and the more stringent definition by the French Reference Center for Thrombotic Microangiopathies. We evaluated time to platelet recovery and presence of confounding clinical conditions, potentially accounting for persistent thrombocytopenia, in all episodes. By day 5 after caplacizumab initiation, 171 of 204 patients (83.8%) achieved a clinical response, and the remaining 33 of 204 (16.2%) showed at least a doubling of the platelet count. Only 3 patients (1.5%) met laboratory criteria for refractoriness. In all cases, plausible alternative causes were present (eg, missed doses, infection). No patient was refractory without a confounding factor. In 8 of 204 patients (3.9%) we observed a markedly prolonged thrombocytopenia (≥10 days) and identified confounding conditions in all cases. In the stratified Cox model, the presence of alternative causes of thrombocytopenia was the only independent determinant of delayed platelet count normalization (hazard ratio, 0.16; 95% confidence interval, 0.09-0.28; P< .001). In the context of caplacizumab-based therapy, true refractoriness is rare. Delayed platelet count recovery is predominantly attributable to concomitant clinical conditions. Careful clinical assessment and context-sensitive interpretation of treatment response before escalating iTTP-specific therapy may avoid unnecessary treatment intensification and associated risks.

PURPOSE:Positron emission tomography (PET)-guided therapy with 4-6 cycles of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) is highly effective in younger patients with advanced-stage classic Hodgkin lymphoma (AS-cHL). We report feasibility and efficacy of PET-guided BrECADD as first-line treatment in older patients with AS-cHL. PATIENTS AND METHODS:Patients with AS-cHL aged 61-75 years were enrolled in a phase II single-arm cohort of the HD21 trial (ClinicalTrials.gov identifier: NCT02661503). Patients with negative PET/computed tomography after 2×BrECADD (PET2) received a total of 4×BrECADD, while PET2-positive patients received 6×BrECADD. The primary end point was the centrally reviewed complete remission (CR) rate after the end of chemotherapy (EOC). Secondary end points included feasibility, adverse events, treatment-related morbidity (TRMB), progression-free survival (PFS), overall survival (OS), and health-related quality of life (HRQoL). RESULTS:Between June 2020 and April 2023, 85 patients were enrolled, of whom 83 with a median age of 67 years (range, 61-75) were analyzed in the intention-to-treat cohort. Most prevalent ≥grade 3 toxicities included leukopenia (n = 80 [96%]), thrombocytopenia (n = 71 [86%]), anemia (n = 57 [69%]), and febrile neutropenia (n = 46 [55%]). Forty-eight (60%) of 80 patients with centrally reviewed PET2 were scheduled for 4×BrECADD and 32 (40%) for 6×BrECADD. Of these, 71 patients (89%) received the target number of cycles. Sixty-eight patients (82%; 95% CI, 72 to 90) achieved CR at EOC. PFS and OS estimates at 2 years were 91.5% (95% CI, 85 to 98) and 90.8% (95% CI, 84 to 98), respectively. No death was attributed to study treatment. Initially, impaired HRQoL scores improved during follow up and on average reached population reference values. CONCLUSION:PET-guided BrECADD in older patients is feasible and effective. With a PFS rate on par with that of younger patients, short duration, and limited anthracycline exposure, BrECADD is a valuable treatment option also for older patients with AS-cHL.

Histopathological growth patterns (GP) in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have previously been divided into GP AB (typical) vs CDEF (variant). However, it is unclear whether this division is optimal. We thus investigated alternative GP grouping approaches (GP ABC vs DEF; GP ABCF vs DE). Overall, 583 NLPHL patients who had first-line treatment within GHSG trials were included in the analysis. Median age was 39 years; 74% of patients were male; 76% presented with early-stage and 24% with advanced-stage disease. The 5-year and 10-year progression-free survival (PFS) estimates for all patients were 85.9% and 76.6%; overall survival (OS) estimates were 95.8% and 94.5%. Significant PFS and OS differences were detected for the comparison GP ABCF vs DE with worse outcomes for the GP DE group (HR: 1.7; 95%-CI: 1.1-2.7; HR: 2.5; 95%-CI: 1.1-5.7). No PFS and OS differences were observed for the comparisons GP AB vs CDEF and GP ABC vs DEF. Median time to death was shorter and death more often due to NLPHL in the GP DE (13 months; 66.7%) than in the GP ABCF (31 months; 5.6%) group. Hence, the division of GP into GP ABCF vs DE allows an optimized GP-based risk group discrimination in NLPHL.