RARE DISEASE
Nodular lymphocyte predominant Hodgkin lymphoma
Nodular lymphocyte predominant Hodgkin lymphoma
Nodular lymphocyte predominant Hodgkin lymphoma
Synonyms: NLPHL
Synonyms: NLPHL
Synonyms: NLPHL
Drug discovery
0
drugs
With orphan designations
Overview
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare CD20+ B-cell malignancy representing 5-10% of Hodgkin lymphomas [1][4]. Characterized by lymphocyte-predominant "popcorn cells" lacking CD15/CD30 expression [1][6], it typically presents as early-stage peripheral lymphadenopathy with male predominance [4][16]. While indolent, it carries a 5-25% lifetime risk of transforming to diffuse large B-cell lymphoma [4][16]. Treatment ranges from observation to targeted anti-CD20 therapy and radiotherapy, with >90% 10-year survival in localized disease [2][10].
Therapies
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
307 drug discovery papers about Nodular lymphocyte predominant Hodgkin lymphoma, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
307 drug discovery papers about Nodular lymphocyte predominant Hodgkin lymphoma, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
cell therapies
2025-01-25 | CD4+CD8+ double-positive T cells in immune disorders and cancer: Prospects and hurdles in immunotherapy.
CD4+ and CD8+ T cells play critical roles in both innate and adaptive immune responses, managing and modulating cellular immunity during immune diseases and cancer. Their well-established functions have led to significant clinical benefits. CD4+CD8+ double-positive (DP) T cells, a subset of the T cell population, have been identified in the blood and peripheral lymphoid tissues across various species. They have gained interest due to their involvement in immune disorders, inflammation, and cancer. Although mature DP T cells are present in healthy individuals and contribute to disease contexts, their molecular characteristics and pathophysiological roles remain debated. Notably, the number of DP T cells in the blood is higher in older adults compared to younger individuals, and these cells can stimulate inflammation and viral infections through increased secretion of interleukin (IL)-10, interferon gamma (IFN-γ), and transforming growth factor beta (TGF-β). In cancer, DP T cells have been observed to infiltrate cutaneous T cell lymphomas and are found in greater numbers in nodular lymphocyte predominant Hodgkin lymphoma, melanoma, hepatocellular carcinoma, and breast cancer. The higher prevalence of DP T cells in advanced cancers, coupled with their strong lytic activity and distinct cytokine profile, suggests that these cells may play a crucial role in modulating immune responses to cancer. This insight offers a potential new approach for enhancing the identification and selection of antigen-reactive T cells in immune-based treatments. This review provides a comprehensive overview of the origin, distribution, transcriptional regulation during developmental stages, and functions of DP T cells. A deeper understanding of the diversity and roles of DP T cells may pave the way for their development as a promising tool for immunotherapy in the management of immune disorders and metastatic cancers.
2022-12-16 | Individualized patient care in nodular lymphocyte-predominant Hodgkin lymphoma.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma that has traditionally been considered a subgroup of Hodgkin lymphoma. However, morphology, surface marker expression, genetics, and clinical course are different from classic Hodgkin lymphoma. While most patients experience indolent disease with slow progression, some patients can also have more aggressive disease. Nevertheless, outcomes are excellent, and excess mortality due to NLPHL is at most very low. The treatment of newly diagnosed NLPHL has historically mirrored that of classic Hodgkin lymphoma. However, evidence for deviations from that approach has emerged over time and is discussed herein. Less evidence is available for the optimal management of relapsed patients. So-called variant histology has recently emerged as a biological risk factor, providing at least a partial explanation for the observed heterogeneity of NLPHL. Considering variant histology together with other risk factors and careful observation of the clinical course of the disease in each patient can help to assess individual disease aggressiveness. Also important in this mostly indolent disease are the preferences of the patient and host factors, such as individual susceptibility to specific treatment side effects. Considering all this together can guide individualized treatment recommendations, which are paramount in this rare disease.
2018-11-15 | The Effects of the Therapeutic Regimen Used in Hodgkin Lymphoma and the Correlation with Prognosis Factors
The Hodgkin lymphoma treatment is adapted to the disease type, disease stage and to an evaluation of the risk. The treatment is focused on the adjustment of the therapy to each patient depending on the age, toxicity risk on short and long term and the relapse risk. The study proposes the evaluation of the response to the treatment further to the administration of different therapeutic regimens as well as the correlation with the negative diagnosis factors of Hodgkin lymphoma. This is a retrospective study on 71 patients diagnosed with Hodgkin lymphoma in the Hematology Department of Timisoara between January 2014 and December 2017. The data obtained have been collected from a database and processed with the SPSS 20.0. software . In our study there were included 71 patients diagnosed with Hodgkin lymphoma with a medium age of 42.12�16.45 years old. By the time of the diagnosis, the patients showed the following hematological, biochemical and immunological parameters. The response to treatment is influenced by the presence of the negative prognosis factors : the age of �40 years old, extralymphatic infiltration, VSH ] 50mm/h , presence of general B signs, more than 3 lymph node sites affected, bulky disease and Ann-Arbor III and IV stages. The treatment of Hodgkin lymphoma is guided by the traditional clinic prognostic factors and by the laboratory which often represent a substitute marker for the biological characteristics which many times are not included in the standard evaluation.
2018-04-01 | Tandem Autologous Hematopoietic Cell Transplantation for Patients with Primary Progressive or Recurrent Hodgkin Lymphoma: A SWOG and Blood and Marrow Transplant Clinical Trials Network Phase II Trial (SWOG S0410/BMT CTN 0703)
Based on promising pilot data a phase II tandem autologous hematopoietic stem cell transplant (AHSCT) trial for relapsed/refractory Hodgkin lymphoma (HL) was performed in the US intergroup setting to determine if long-term progression-free survival (PFS) could be improved. Patients were enrolled after salvage therapy and stem cell collection. Sensitivity to salvage was defined by 1999 Standardized Response Criteria and did not include fluorodeoxyglucose-positron emission tomography. Cycle 1 consisted of melphalan 150 mg/m2 with half of the stem cells. For stable disease or better, patients received cycle 2 consisting of single doses of etoposide 60 mg/kg and cyclophosphamide 100 mg/kg and either total body radiation 12 Gy in 8 fractions over 4 days or BCNU 150 mg/m2/day for 3 days with the remaining stem cells. Of 98 enrolled patients, 89 were eligible and treated: 82 completed both cycles of AHSCT, 47 (53%) had primary refractory HL, and 72 (81%) were resistant to salvage therapy. There were no treatment-related deaths in the first year after AHSCT. With a median follow-up of 6.2 years (range, 2 to 7.7) for eligible patients who remained alive, the 2-year and 5-year PFS were 63% (95% CI, 52% to 72%) and 55% (95% CI, 44% to 64%) respectively; the 2-year and 5-year overall survival were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Univariate Cox regression analysis showed Zubrod performance status and lactate dehydrogenase levels > 1 times upper limit of normal at the time of enrollment were significantly associated with PFS. The observed 5-year PFS of 55% suggests the tandem approach appears to be effective in treating HL patients demonstrated to have poor prognosis in prior single AHSCT trials. This trial was registered at www.clinicaltrials.gov as NCT00233987.
2017-10-03 | High dose chemotherapy and autologous stem cell transplantation in nodular lymphocyte‐predominant Hodgkin lymphoma: A retrospective study by the European society for blood and marrow transplantation‐lymphoma working party
Abstract Whilst autologous stem cell transplantation (auto‐SCT) is considered standard of care for relapsed/refractory classical Hodgkin lymphoma, the role of auto‐SCT in nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) is not well defined due to limited data. We report the first study on auto‐SCT for NLPHL with a larger cohort. Eligible for this retrospective registry study were patients reported to the EBMT between 2003 and 2013, aged 18 or older with relapsed/refractory NLPHL who underwent first auto‐SCT with disease chemosensitive to salvage therapy. NLPHL transformed to diffuse large B cell lymphoma were excluded. Sixty patients (83% male; median age 40 years) met the eligibility criteria. The median time between diagnosis and transplant was 21 months (IQR 13–58), and the median number of prior treatment lines was 2 (range 1–5), including rituximab in 63% of the patients. At auto‐SCT, 62% of the patients were in complete remission (CR) and 38% in partial remission. Seventy‐two percent of the patients received BEAM as high‐dose therapy. With a median follow‐up of 56 months (range 3–105), 5‐year progression‐free and overall survival (OS) were 66% and 87%, respectively. Univariate comparisons considering age, time from diagnosis to transplant, prior chemotherapy lines, and prior rituximab use failed to identify significant predictors for any survival endpoint except for being in CR at the time of auto‐SCT (vs PR, P = .049) for OS. Auto‐SCT in patients with relapsed/refractory NLPHL who are sensitive to salvage therapy gives excellent disease control and long‐term survival independent of the time interval between diagnosis and transplant.
antibodies
2026-05-22 | Treatment outcomes of Hodgkin lymphoma in the Czech Republic.
The aim of this analysis was to assess the efficacy of treatment and its impact on prognosis of patients with Hodgkin's lymphoma (HL) enrolled in the Czech HL Registry. Overall 2,241 patients with classical HL (cHL) and 130 patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) treated between 2000 and 2024 were analyzed. Median age at diagnosis was 37 years in cHL and 42 years in NLPHL. The most common chemotherapy regimen in early and intermediate stages was ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in combination with radiotherapy (RT). Moreover, two cycles of escalated BEACOPP (bleomycin, etoposide doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) combined with two cycles of ABVD and RT were used in patients aged < 60 years in intermediate stages. The most common therapy in advanced stages was escalated BEACOPP (4-8 cycles) in patients aged < 60 years and ABVD (6-8 cycles) in patients aged ≥ 60 years. Patients with NLPHL were treated with RT alone or with combination of rituximab and chemotherapy or with a combination of RT based on clinical stages. The 10-year progression-free survival (PFS) and overall survival (OS) in patients with cHL aged < 60 years were: in early stages 91.5% and 94.2%, in intermediate stages 91.0% and 96.6% and in advanced stages 83.9% and 92.6%, respectively. The 10-year PFS and OS in cHL ≥ 60 years were: in early stages 67.0% and 74.2%, in intermediate stages 36.4% and 45.7%, in advanced stages 41.6% and 52.0%, respectively. The 10-year PFS and OS in NLPHL patients were 77.5% and 95.8%. Based on the data from the Czech HL Registry, the prognosis of HL patients aged < 60 years is excellent: the 10-year OS is achieved in more than 90% of cases. Median OS of patients aged ≥ 60 years is 10 years. Implementation of checkpoint inhibitors or brentuximab vedotin into the first-line treatment will further improve its efficacy and reduce the toxicity.
2026-04-01 | Promising outcomes of R-CHOP therapy in pediatric nodular lymphocyte-predominant Hodgkin lymphoma: perspectives from a rare subtype.
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare sub-type of Hodgkin lymphoma (HL). Due to its rarity, the standard of care for these patients remains poorly defined. Our cohort aimed to evaluate the outcomes of pediatric NLPHL patients treated with the R-CHOP regimen throughout 8 years' single center experience. A retrospective cohort study including pediatric patients aged <18 years diagnosed with NLPHL and treated at the Children Cancer Hospital Egypt, between July 2014 and June 2022. In total, 66 patients were included. Twelve patients (18%) with stage IA underwent surgical excision alone. Four of these patients experienced disease progression but achieved a complete response after receiving R-CHOP. Fifty-four patients received R-CHOP as first-line therapy, with early-stage disease received 3-4 cycles, while those with advanced-stage disease received 6 cycles. For this group, the 5-year overall (OS) and event free survival (EFS) were 100% and 91.5%, respectively. The 5-year EFS was not significantly affected by the variant histology pattern among patients received R-CHOP. Patients with stage 3 peripheral disease without risk factors demonstrated outcomes comparable to those with early-stage disease and no risk factors, achieving an excellent 5-year EFS rate of 100%. No significant toxicity was reported, except for grade 3-4 neutropenia. R-CHOP is an effective and well-tolerated regimen for treating pediatric NLPHL, demonstrating high OS and EFS rates. Patients with early stage disease achieved particularly favorable outcomes, supporting consideration of treatment de-escalation in this subgroup.
2025-12-01 | Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) in a Young Woman: A Rare Subtype Managed Without Chemotherapy
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma, comprising approximately 5–7% of cases. Unlike classical HL, NLPHL is characterized by CD20-positive “popcorn” cells (LP cells), lacks Epstein-Barr virus association, and tends to follow an indolent course. Accurate diagnosis is critical, as the therapeutic approach differs substantially. We report an early-stage NLPHL case in a young woman managed successfully without chemotherapy, emphasizing the value of histopathological precision and risk-adapted therapy. A 33-year-old woman presented with a painless cervical swelling. Physical examination revealed enlarged left cervical and supraclavicular lymph nodes. She had no B symptoms such as fever, night sweats, or weight loss. Blood counts and biochemistry were within normal limits. An excisional biopsy of a lymph node was performed, followed by immunohistochemistry and whole-body 18F-FDG PET-CT for staging. Bone marrow aspiration and biopsy were also conducted to rule out marrow involvement. Histopathological examination demonstrated nodular architecture containing scattered lymphocyte-predominant (LP) cells. Immunophenotyping revealed strong CD20 and Pax5 expression, with negativity for CD3 and CD15. CD21 staining highlighted an expanded follicular dendritic cell meshwork, confirming the diagnosis of NLPHL. PET-CT showed FDG-avid lymph nodes localized to the left cervical and supraclavicular regions, with a maximum SUV of 27.9. No pathological uptake was seen in the mediastinum, abdomen, bones, or spleen. Bone marrow biopsy was normocellular without evidence of infiltration. The disease was staged as Stage IA (non-bulky), CD20-positive NLPHL. The patient was treated with rituximab monotherapy (375 mg/m 2 weekly for 4 doses), followed by involved-field radiotherapy (30 Gy) to the involved nodal regions. Given her age and reproductive status, fertility preservation was discussed before initiating treatment. The plan aimed to minimize long-term toxicity while maintaining curative potential. This case illustrates several important themes. First, accurate histological subtyping allowed for a deviation from standard chemotherapy-based HL protocols. Second, the use of rituximab and radiotherapy alone is an emerging and evidence-supported strategy for early-stage NLPHL, particularly in CD20-positive, non-bulky cases. Third, the patient’s demographic—young and female—makes chemotherapy-free management especially attractive given concerns about fertility and late effects. Finally, the case has strong educational value, highlighting the need to distinguish NLPHL from classical HL and indolent B-cell lymphomas, both histologically and metabolically. This case demonstrates how a rare Hodgkin lymphoma subtype can be successfully managed with a chemotherapy-free, targeted approach. It reinforces the importance of accurate subtyping and risk-adapted treatment in delivering personalized care, especially in young patients where fertility and quality of life are key considerations
2025-12-01 | TREATMENT APPROACH AND OUTCOMES IN CHILDREN AND ADOLESCENTS WITH NODULAR LYMPHOCYTE-PREDOMINANT HODGKIN LYMPHOMA: THE ITALIAN ASSOCIATION OF PEDIATRIC HEMATOLOGY AND ONCOLOGY (AIEOP) EXPERIENCE.
Introduction Nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is a rare subtype of Hodgkin lymphoma, which accounts for about 5% of pediatric/adolescent Hodgkin lymphomas [ 1 ] [ 2 ]. Currently, patients diagnosed in Italy with nLPHL are collected in the AIEOP-LHPL2019 retrospective/prospective study. Methods This is an observational study recruiting all stage nLPHL, since november 2019. Patients are treated according to clinician discretion, following study suggestions. About 10 new cases/year are diagnosed in AIEOP Centers. Results To date, 83 patients from 28 AIEOP centers have been observed, to which 11 additional new diagnoses were added in the last year. 82/83 patients have been evaluated. Eighty percent of cases had the histology centrally revised. Patients, 68M/15F (M 81.9%), mean age 12.8aa (range 2.9-17.9aa), 66% age>12aa, presented stage I-IIA disease in 66/83 (79.5%), only 2/83 (2.4%) patients presented B symptoms. Treatment: 16 stage IA patients were treated with surgery alone, 38 (stage IA+IIA+IIIA) received 3-6 CVP cycles, 8 patients 3-6 Rituximab+CVP, and 20 different therapies (ABVD±R, R-CHOP, OEPA, COPP/ABV). No patient has been treated with RT. A total of 14/82 patients received first-line rituximab therapy. 20/82 (24.4%) patients, including 2 stage IIB-IIIB, 6 stage IA, and 12 stage IIA, presented persistent/progressive/recurrent disease after first-line therapy. With 100% OS and 76% EFS at a median follow-up of 56.4 months, nLPHL is confirmed to be a disease with good prognosis; 66% of patients received low intensity treatment (surgery and/or CVP). 20/82 (24.4%) patients developed recurrences, namely 14 relapses, 3 persistent diseases after first line treatment and 3 disease progressions. Both patients with stage IIB-IIIB developed disease progression after being treated with intensive chemotherapy (R-ABVD and OEPA+R-CHOP respectively). It’s interesting to note that all the remaining 18 patients with recurrences had stage I/IIA while no cases of recurrences occurred for IIIA/IVA stages. Conclusion The current case series of AIEOP Centers with 83 patients represent one of the largest in the nLPHL scenario. According to literature [ 3 ] [ 4 ] and confirmed in our experience, in the majority of patients, sparing of anthracycline and radiotherapy is possible, and the addition of rituximab seems to offer a promising chance [ 5 ]. The rare presence of B symptoms at onset, seems to identify a disease with a more severe prognosis. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2025-12-01 | Nodular Lymphocyte Predominant Hodgkin Lymphoma Involving the Stomach and Bones
Introduction NLPHL typically presents as early stage disease with localized peripheral lymphadenopathy. Primary extranodal NLPHL is exceedingly rare. Here we present the diagnostic challenges of an adolescent with NLPHL. Methods Case report Results A 17 year old Hispanic male presented with a two-months history of vomiting, abdominal pain and weight loss of 6 pounds, without fever or night sweats. A CT scan showed a mass in between the liver and the spleen and around the gastroesophageal (GE) junction. In the upper stomach and lower esophagus mucosal thickening was noted. In addition, splenomegaly, periaortic lymphadenopathy, cervical and supraclavicular lymphadenopathy was present. No mediastinal adenopathy was noted. The PET/CT scan showed FDG avidity in all areas of CT involvement and uncovered multiple bone involvement in the vertebri, sacrum, pelvis, proximal femurs and humerus. An esophagogram showed an apple-core lesion involving the distal stomach and gastric fundus. An upper esophago-gastroduodenoscopy showed an exophytic mass in the stomach. Biopsies showed necrotic tissue. Bone marrow biopsy was negative. Histopathological diagnosis was challenging. The specimen underwent 3 pathological consultations. The process took 8 weeks 1) presence of large cells with uniform CD30 expression and weak PAX5 favoring cHL but also good preservation of B cell program (positive CD79a, BOB1 and OCT2), apparent CD45 expression, and variable CD20. 2) most consistent with NLPHL variant patern D, and T cells with aberrant CD20 expression. 3) large cells that retain B cell programming expressing CD20, CD19, OCT2 and BOB1 but also strong CD30 expression, but with CD45 positivity. Cells also expressed MEF2B and negative for STAT6 both favoring NLPHL. CD20 appeared weakly expressed on T-cells population. Overall findings are consistent with NLPHL. The patient was treated with Bv-AVEPC x5. PET2 showed incomplete metabolic response with DS of 4 in the GE junction, spleen and bones. All areas of involvement showed decrease in size. PET5 showed complete metabolic response of all sites. He then receive 6 doses of Rituximab every 3 weeks. End of therapy PET scan was negative. Radiation therapy was spared. Six months after completing treatment, the patient remained in remission [ 1 ] [ 2 ]. Conclusion This case highlights a rare case of NLPHL with extranodal involvement in the stomach and bones and the challenges of histopathological diagnosis with implications in delay in proper treatment. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
small molecules
2026-06-03 | EuroNet-PHL-LP1: Complete resection or low-dose chemo for pediatric low-risk nodular lymphocyte-predominant Hodgkin lymphoma.
Children and adolescents with early-stage nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) have a 5-year event-free survival (EFS) of about 77% after complete lymph node resection and around 89% with anthracycline-containing chemotherapy. We investigated whether patients with early-stage nLPHL can be successfully treated with surgical resection alone or with low-intensity, anthracycline-free CVP chemotherapy for those with unresectable nodal disease. EuroNet-PHL-LP1 was a prospective phase III trial enrolling patients under 18 years with stage IA/IIA nLPHL. Completely resected lymph nodes led to active surveillance. Patients with unresectable disease received three cycles of CVP (cyclophosphamide, vinblastine, prednisone). In CVP-cohort-1, treatment cessation required a negative 18F -FDG-PET. An amendment in 2014 omitted PET for end-of-treatment response; CT and/or MRI alone defined response in CVP-cohort-2. The primary endpoint was 5-year EFS, with death, relapse, second malignancy and PET-positivity counting as events; for CVP-cohort-2, progression-free survival (PFS) was primary. Among 267 registered patients (2009-2018), 247 were evaluable. Seventy-eight underwent resection only; their 5-year EFS/PFS was 79.5%. Six of 18 patients who relapsed after surgical resection re-entered the CVP arm. In CVP-cohort-1, 51/82 (62%) achieved a complete metabolic response (CMR). 5-year EFS was 56.4%, while 5-year PFS in the CMR group was 91.3%. In contrast, PFS in 84 CVP-cohort-2 patients was 64.7%. During CVP, 68.3% of patients experienced grade 3-4 neutropenia. No treatment-related deaths were reported. Excellent outcomes were achieved after complete resection and with low-intensive, anthracycline-free chemotherapy if 18F-FDG-PET showed CMR after chemotherapy. This strategy now constitutes the EuroNet-PHL standard of care for early-stage nLPHL. The trial was registered under EudraCT-No.: 2007-004092-19.
2026-03-24 | Paraneoplastic Hepatitis Associated with Relapsed Nodular Lymphocyte-Predominant Hodgkin Lymphoma.
Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an indolent B-cell lymphoma with long-term survival and a tendency for late relapse. Hepatic manifestations of varying etiologies have been described in lymphoproliferative disorders. However, paraneoplastic hepatitis is rare, and reports typically describe acute presentations. We describe an unusual case of paraneoplastic hepatitis with an indolent and progressive clinical course occurring in the setting of relapsed NLPHL. Case Presentation: A 32-year-old man with a history of NLPHL was found to have marked transaminase elevation with preserved liver function during routine follow-up. Extensive evaluation excluded viral, autoimmune, and metabolic causes of liver disease. Liver biopsy demonstrated confluent and bridging necrosis with lymphoplasmacytic infiltrates, without evidence of direct lymphoma involvement. Excisional biopsy of a cervical lymph node revealed relapse of NLPHL without histologic transformation. Treatment with corticosteroids resulted in partial biochemical improvement, and subsequent rituximab monotherapy achieved lymphoma remission. Despite this, low-grade transaminase elevation persisted, and follow-up imaging and liver biopsy demonstrated progression to fibrosis, suggesting a tendency towards chronicity. Conclusions: Paraneoplastic hepatitis should be considered in patients with NLPHL who present with unexplained liver abnormalities. This report illustrates a fibrosing form of paraneoplastic hepatitis associated with NLPHL and broadens the clinical spectrum of paraneoplastic hepatic injury. Early recognition, histological confirmation, and tailored immunosuppressive management are critical to optimizing hepatic and lymphoma-related outcomes.
2025-12-01 | Successful treatment of children and adolescents with stage IA/IIA lymphocyte–predominant Hodgkin Lymphoma after complete resection alone or low dose, anthracyclin-free chemotherapy: Results of the EuroNet-PHL-LP1 trial
Introduction Children and adolescents with early-stage lymphocyte-predominant Hodgkin lymphoma (nLPHL) have a 5-year event-free survival of about 77% after complete resection of a single lymph-node and 89% after anthracycline-containing low-intensity chemotherapy and 18 F-FGD-PET-based radiotherapy [ 1 ]. We investigated whether patients with LPHL stage IA/IIA can be cured by resection alone or a very low-anthracycline-free chemotherapy. Methods The EuroNet-PHL-LP1 trial was a prospective uncontrolled phase III study in early stage NLPHL for patients under 18 years of age. Patients presenting in stage IA/IIA with complete resection entered into follow-up. Patients without complete resection received 3 cycles of chemotherapy consisting of Cyclophosphamide, Vinblastine and Prednisone (CVP) and received no further treatment if 18 F-FDG-PET was negative (CVP-cohort 1). After an amendment reacting to an unexpectedly high 18 F-FDG-PET positivity rate, 18 F-FDG-PET was omitted and all patients without residual disease determined by CT or MRI (CVP-cohort 2) received no further treatment. The primary endpoint was event-free survival (EFS) defined by a positive FGD-PET (CVP-cohort-1), secondary malignancy or death of any cause. Secondary endpoints were overall survival (OS) or progression-free survival (PFS). For CVP-cohort-2, EFS and PFS coincide since no secondary malignancy occurred. We report 5-year rates. Results Between Dec 15, 2009 and Oct 31, 2018, 267 patients were registered and 247 patients were enrolled onto EuroNet-PHL-LP1. Of these, 87 patients were treated with resection alone and PFS was 79.5% (95%CI; 71,2% – 88,7%). In the CVP-treatment cohort-1, 51 of 82 patients were in complete metabolic response (CMR) after chemotherapy (approximately Deauville scores 1-2). EFS in CVP-cohort-1 was only 56.4% (95%CI; 46.5% – 68.4%), however PFS in the 18 F-PET-negative group of CVP- cohort -1 was 91.3% (95%CI; 83.6% – 99.9%). In contrast, PFS in 84 patients of the CVP-cohort-2 was 64.7% (95%CI; 55.1% – 76.0%). The most common grade 3-4 adverse events were neutropenia in 68.3% of patients treated with CVP. There were no treatment-related deaths. Conclusion Patients with nLPHL with stages IA/IIA have an excellent prognosis after complete resection. 18 F-FDG-PET response is predictive. Patients with incomplete resection have an excellent prognosis with low-intensive, anthracycline-free chemotherapy if 18 F-FGD-PET becomes negative at the end of chemotherapy. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2025-12-01 | Nodular Lymphocyte Predominant Hodgkin Lymphoma: Experience of the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG)
Introduction Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare clinical entity. To investigate the clinical course and treatment of NLPHL, a survey was conducted among centers participating in the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). Methods A questionnaire was sent to all 17 Polish centers, and clinical data were analyzed. Results Between 2010 and 2024, 39 pediatric patients aged 5.6–18.0 years (median: 12.3 years) with confirmed NLPHL were registered in Poland. NLPHL occurred predominantly in males (n=35). All disease stages were observed, with stage I (n=8) and stage II (n=23) being the most common. In most patients (n=26), supradiaphragmatic involvement was noted. Seven patients with localized, resectable stage IA disease were treated. Five underwent complete primary resection; two received surgery alone, although one relapsed and was treated with CVP chemotherapy. The other five received additional chemotherapy after resection. Three patients had incomplete resections and received CVP chemotherapy, with one relapse observed. CVP chemotherapy was administered to 23 patients with stage IIA disease. After three cycles, four relapses occurred and were managed with R-CHOP± radiotherapy. All treatments have led to durable remissions so far. Advanced disease was noted in nine patients (eight boys, one girl) aged 8.8–17.9 years (median: 12.2). Various chemotherapy protocols were used, including rituximab in three cases and without rituximab in five. Two relapses were treated with R-CHOP; one patient underwent autologous stem cell transplantation due to poor response. Relapse-free survival rates were 72.1% for early-stage (IA and IIA) and 85.7% for advanced-stage disease. No deaths were reported. Conclusion The outcomes of NLPHL treatment in Poland are consistent with those reported in other countries; however, further improvement and standardized treatment approaches for NLPHL patients in Poland are needed. Special attention should be given to patients eligible for primary surgical resection. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2025-10-01 | IgG4-Related Tubulointerstitial Nephritis and Proliferative Glomerulonephritis (GN) with IgG2, IgG3, and IgG4 Deposits in a Patient with Treated T Cell-Rich Large B Cell Lymphoma
Introduction: IgG4-related kidney disease (IgG4-RKD) most commonly presents as tubulointerstitial nephritis (TIN) with occasional glomerular involvement. Recent literature suggests an association between IgG4-RKD and hematologic malignancies. We report a unique case of IgG4-TIN with concurrent immune complex mediated proliferative GN in a patient with prior treated lymphoma. Case Description: A 77-year-old man with stage 3a CKD and history of nodular lymphocyte-predominant Hodgkin lymphoma (treated with R-CHOP, DICE, and autologous stem cell transplant, in remission) presented with AKI and petechial rash. Following recent travel to Mexico, he developed spreading petechial rash, joint pains and fevers. Laboratory testing showed elevated BUN, creatinine (3.5 mg/dL, baseline 1.4), mild anemia, thrombocytopenia (55K), proteinuria, low C3 and C4. Imaging revealed new lymphadenopathy. Skin biopsy showed urticarial dermatitis; biopsy from right inguinal lymph node showed chronic inflammation without lymphoma. Kidney biopsy revealed a dominant IgG4-positive plasma cell-rich interstitial infiltrate consistent with IgG4-TIN, and diffuse proliferative GN with polyclonal IgG, including IgG2, IgG3 and dominant IgG4 immune deposits (Figure 1, 2). No evidence of thrombotic microangiopathy or lymphoid malignancy was found. Extensive rheumatologic and infectious workup was negative. High-dose corticosteroids led to rapid improvement in renal function and resolution of symptoms. AKI recurred upon rapid steroid taper and improved with re-initiation of steroid. Discussion: This case highlights the rare coexistence of IgG4-TIN and proliferative GN with polyclonal IgG immune deposits in a patient with prior large B-cell lymphoma. While IgG4-RD is more commonly associated with membranous nephropathy, proliferative GN with MPGN-like features remains rare. The temporal association with treated lymphoma raises consideration for a paraneoplastic or immune reconstitution-related phenomenon. Early steroid therapy was associated with rapid clinical response.
proteins
2023-05-04 | B-cell receptor reactivity against <i>Rothia mucilaginosa</i> in nodular lymphocyte-predominant Hodgkin lymphoma
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1* 07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver- and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA'-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL.
2009-11-13 | A recombinant adenovirus type 35 fiber knob protein sensitizes lymphoma cells to rituximab therapy
Abstract Many tumors, including lymphomas, up-regulate expression of CD46 to escape destruction by complement. Tumor cells are therefore relatively resistant to therapy by monoclonal antibodies, which act through complement-dependent cytotoxicity (CDC). From an Escherichia coli expression library of adenovirus type 35 fiber knob mutants, we selected a variant (Ad35K++) that had a higher affinity to CD46 than did the natural Ad35 fiber knob. We demonstrated that incubation of lymphoma cells with recombinant Ad35K++ protein resulted in transient removal of CD46 from the cell surface. Preincubation of lymphoma cells with Ad35K++ sensitized cells to CDC, triggered by the CD20-specific monoclonal antibody rituximab. In xenograft models with human lymphoma cells, preinjection of Ad35K++ dramatically increased the therapeutic effect of rituximab. Blood cell counts and organ histology were normal after intravenous injection of Ad35K++ into mice that express human CD46. The presence of polyclonal anti-Ad35K++ antibodies did not affect the ability of Ad35K++ to enhance rituximab-mediated CDC in in vitro assays. The Ad35K++-based approach has potential implications in monoclonal antibody therapy of malignancies beyond the combination with rituximab.
2003-05-01 | Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin’s lymphoma
BackgroundImmunotoxins (ITs) consist of cell binding ligands coupled to toxins or their subunits. Hodgkin's lymphoma (HL) is an excellent target for ITs since lymphocyte activation markers such as CD25 and CD30 are expressed in large numbers. The ITs RFT5.dgA (anti CD25) and Ki-4.dgA (anti CD30) were constructed by linking the monoclonal antibodies RFT5 and Ki-4 to deglycosylated ricin A-chain (dgA). Both ITs showed potent specific activity against HL cells in vitro and in vivo in animal models, and were subsequently evaluated in phase I/II clinical trials in humans.Patients and methodsIn two separate trials, the ITs were administered i.v. four times every other day over 4 h. The objectives of the phase I trials included the determination of the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, antitumor activity and immune response against the IT.ResultsTwenty-seven patients with refractory HL were included in the phase I/II study of RFT5.dgA and 17 patients were included in the phase I study of Ki-4.dgA. The MTD of RFT5.dgA was 15 mg/m2, whereas that of Ki-4.dgA was 5 mg/m2. DLTs were related to vascular leak syndrome, consisting of edema, tachycardia, dyspnea, weakness and myalgia. Measurement of serum levels of RFT5.dgA demonstrated a Cmax of 0.2–9.7 µg/ml with a half-life (t½) varying from 4 to 10.5 h. Peak serum concentration of Ki-4.dgA ranged from 0.23 to 1.7 µg/ml. In both trials ∼60% of patients developed human anti-mouse and/or anti-dgA antibodies. Seventeen of 18 patients treated at the MTD of RFT5.dgA were evaluable for clinical response. Responses included two partial remissions (PR), one minor response (MR) and five stable diseases (SD). Fifteen of 17 patients treated with Ki-4.dgA were evaluable for clinical response. Responses included one PR, one MR and two SD.ConclusionsRFT5.dgA and Ki-4.dgA showed moderate efficacy in heavily pretreated refractory patients with HL. Ki-4.dgA was less well tolerated than RFT5.dgA. This might be due, at least in part, to the formation of Ki-4.dgA/sCD30 complexes.
2001-05-01 | Transfection of caspase-3 in the caspase-3–deficient Hodgkin's disease cell line, KMH2, results in enhanced sensitivity to CD95-, TRAIL-, and ARA-C–induced apoptosis
BackgroundCD95(Fas/apo-1) is a cell surface protein member of the tumor necrosis factor receptor family that serves an important role in the induction of apoptosis in several cell types. Although expression of CD95 has been detected on Hodgkin/Reed Sternberg (HRS) cells in situ, our understanding of the biological significance of this molecule in Hodgkin's disease (HD) is limited.DesignWe analyzed both CD95-related apoptotic signaling and its effects on the expression of several factors involved in the regulation of apoptotic mechanisms including: caspase-3, caspase-8, bcl-2, bcl-x, and Bax in HD cell lines (L-428, L-540, HDLM-2, HS-445, and KM-H2).ResultsHD cell lines showed similar expression levels of CD95 and all but KM-H2 demonstrated variable increases in apoptosis after CD95 stimulation by the agonistic monoclonal antibody, CH11. There was no significant correlation between CD95 sensitivity and constitutive expression levels of caspase-8, bcl-2, bcl-x, and Bax. Caspase-3 transcript was demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR) in all cell lines but protein was at low to nearly undetectable levels in KM-H2 cells. Transfection of KM-H2 cells with pro–caspase-3 resulted in a markedly enhanced apoptotic response to CD95 stimulation that was blocked by pretreatment with the caspase-3 inhibitor, DEVD-FMK. In addition, pro–caspase-3–transfected KM-H2 cells showed significantly increased sensitivity to other caspase-3–dependent apoptotic stimuli, including the death-inducing ligand, TRAIL, and the chemotherapeutic agent, Ara-C.ConclusionThese data demonstrate that caspase-3 expression plays an important role in CD95-mediated apoptosis in HD cell lines. Furthermore, lack of or decreased expression of caspase-3 in HD cells impairs their apoptotic response not only to CD95 but also to other caspase-3–dependent apoptotic stimuli.
cell therapies
2025-01-25 | CD4+CD8+ double-positive T cells in immune disorders and cancer: Prospects and hurdles in immunotherapy.
CD4+ and CD8+ T cells play critical roles in both innate and adaptive immune responses, managing and modulating cellular immunity during immune diseases and cancer. Their well-established functions have led to significant clinical benefits. CD4+CD8+ double-positive (DP) T cells, a subset of the T cell population, have been identified in the blood and peripheral lymphoid tissues across various species. They have gained interest due to their involvement in immune disorders, inflammation, and cancer. Although mature DP T cells are present in healthy individuals and contribute to disease contexts, their molecular characteristics and pathophysiological roles remain debated. Notably, the number of DP T cells in the blood is higher in older adults compared to younger individuals, and these cells can stimulate inflammation and viral infections through increased secretion of interleukin (IL)-10, interferon gamma (IFN-γ), and transforming growth factor beta (TGF-β). In cancer, DP T cells have been observed to infiltrate cutaneous T cell lymphomas and are found in greater numbers in nodular lymphocyte predominant Hodgkin lymphoma, melanoma, hepatocellular carcinoma, and breast cancer. The higher prevalence of DP T cells in advanced cancers, coupled with their strong lytic activity and distinct cytokine profile, suggests that these cells may play a crucial role in modulating immune responses to cancer. This insight offers a potential new approach for enhancing the identification and selection of antigen-reactive T cells in immune-based treatments. This review provides a comprehensive overview of the origin, distribution, transcriptional regulation during developmental stages, and functions of DP T cells. A deeper understanding of the diversity and roles of DP T cells may pave the way for their development as a promising tool for immunotherapy in the management of immune disorders and metastatic cancers.
2022-12-16 | Individualized patient care in nodular lymphocyte-predominant Hodgkin lymphoma.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma that has traditionally been considered a subgroup of Hodgkin lymphoma. However, morphology, surface marker expression, genetics, and clinical course are different from classic Hodgkin lymphoma. While most patients experience indolent disease with slow progression, some patients can also have more aggressive disease. Nevertheless, outcomes are excellent, and excess mortality due to NLPHL is at most very low. The treatment of newly diagnosed NLPHL has historically mirrored that of classic Hodgkin lymphoma. However, evidence for deviations from that approach has emerged over time and is discussed herein. Less evidence is available for the optimal management of relapsed patients. So-called variant histology has recently emerged as a biological risk factor, providing at least a partial explanation for the observed heterogeneity of NLPHL. Considering variant histology together with other risk factors and careful observation of the clinical course of the disease in each patient can help to assess individual disease aggressiveness. Also important in this mostly indolent disease are the preferences of the patient and host factors, such as individual susceptibility to specific treatment side effects. Considering all this together can guide individualized treatment recommendations, which are paramount in this rare disease.
2018-11-15 | The Effects of the Therapeutic Regimen Used in Hodgkin Lymphoma and the Correlation with Prognosis Factors
The Hodgkin lymphoma treatment is adapted to the disease type, disease stage and to an evaluation of the risk. The treatment is focused on the adjustment of the therapy to each patient depending on the age, toxicity risk on short and long term and the relapse risk. The study proposes the evaluation of the response to the treatment further to the administration of different therapeutic regimens as well as the correlation with the negative diagnosis factors of Hodgkin lymphoma. This is a retrospective study on 71 patients diagnosed with Hodgkin lymphoma in the Hematology Department of Timisoara between January 2014 and December 2017. The data obtained have been collected from a database and processed with the SPSS 20.0. software . In our study there were included 71 patients diagnosed with Hodgkin lymphoma with a medium age of 42.12�16.45 years old. By the time of the diagnosis, the patients showed the following hematological, biochemical and immunological parameters. The response to treatment is influenced by the presence of the negative prognosis factors : the age of �40 years old, extralymphatic infiltration, VSH ] 50mm/h , presence of general B signs, more than 3 lymph node sites affected, bulky disease and Ann-Arbor III and IV stages. The treatment of Hodgkin lymphoma is guided by the traditional clinic prognostic factors and by the laboratory which often represent a substitute marker for the biological characteristics which many times are not included in the standard evaluation.
2018-04-01 | Tandem Autologous Hematopoietic Cell Transplantation for Patients with Primary Progressive or Recurrent Hodgkin Lymphoma: A SWOG and Blood and Marrow Transplant Clinical Trials Network Phase II Trial (SWOG S0410/BMT CTN 0703)
Based on promising pilot data a phase II tandem autologous hematopoietic stem cell transplant (AHSCT) trial for relapsed/refractory Hodgkin lymphoma (HL) was performed in the US intergroup setting to determine if long-term progression-free survival (PFS) could be improved. Patients were enrolled after salvage therapy and stem cell collection. Sensitivity to salvage was defined by 1999 Standardized Response Criteria and did not include fluorodeoxyglucose-positron emission tomography. Cycle 1 consisted of melphalan 150 mg/m2 with half of the stem cells. For stable disease or better, patients received cycle 2 consisting of single doses of etoposide 60 mg/kg and cyclophosphamide 100 mg/kg and either total body radiation 12 Gy in 8 fractions over 4 days or BCNU 150 mg/m2/day for 3 days with the remaining stem cells. Of 98 enrolled patients, 89 were eligible and treated: 82 completed both cycles of AHSCT, 47 (53%) had primary refractory HL, and 72 (81%) were resistant to salvage therapy. There were no treatment-related deaths in the first year after AHSCT. With a median follow-up of 6.2 years (range, 2 to 7.7) for eligible patients who remained alive, the 2-year and 5-year PFS were 63% (95% CI, 52% to 72%) and 55% (95% CI, 44% to 64%) respectively; the 2-year and 5-year overall survival were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Univariate Cox regression analysis showed Zubrod performance status and lactate dehydrogenase levels > 1 times upper limit of normal at the time of enrollment were significantly associated with PFS. The observed 5-year PFS of 55% suggests the tandem approach appears to be effective in treating HL patients demonstrated to have poor prognosis in prior single AHSCT trials. This trial was registered at www.clinicaltrials.gov as NCT00233987.
2017-10-03 | High dose chemotherapy and autologous stem cell transplantation in nodular lymphocyte‐predominant Hodgkin lymphoma: A retrospective study by the European society for blood and marrow transplantation‐lymphoma working party
Abstract Whilst autologous stem cell transplantation (auto‐SCT) is considered standard of care for relapsed/refractory classical Hodgkin lymphoma, the role of auto‐SCT in nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) is not well defined due to limited data. We report the first study on auto‐SCT for NLPHL with a larger cohort. Eligible for this retrospective registry study were patients reported to the EBMT between 2003 and 2013, aged 18 or older with relapsed/refractory NLPHL who underwent first auto‐SCT with disease chemosensitive to salvage therapy. NLPHL transformed to diffuse large B cell lymphoma were excluded. Sixty patients (83% male; median age 40 years) met the eligibility criteria. The median time between diagnosis and transplant was 21 months (IQR 13–58), and the median number of prior treatment lines was 2 (range 1–5), including rituximab in 63% of the patients. At auto‐SCT, 62% of the patients were in complete remission (CR) and 38% in partial remission. Seventy‐two percent of the patients received BEAM as high‐dose therapy. With a median follow‐up of 56 months (range 3–105), 5‐year progression‐free and overall survival (OS) were 66% and 87%, respectively. Univariate comparisons considering age, time from diagnosis to transplant, prior chemotherapy lines, and prior rituximab use failed to identify significant predictors for any survival endpoint except for being in CR at the time of auto‐SCT (vs PR, P = .049) for OS. Auto‐SCT in patients with relapsed/refractory NLPHL who are sensitive to salvage therapy gives excellent disease control and long‐term survival independent of the time interval between diagnosis and transplant.
antibodies
2026-05-22 | Treatment outcomes of Hodgkin lymphoma in the Czech Republic.
The aim of this analysis was to assess the efficacy of treatment and its impact on prognosis of patients with Hodgkin's lymphoma (HL) enrolled in the Czech HL Registry. Overall 2,241 patients with classical HL (cHL) and 130 patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) treated between 2000 and 2024 were analyzed. Median age at diagnosis was 37 years in cHL and 42 years in NLPHL. The most common chemotherapy regimen in early and intermediate stages was ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in combination with radiotherapy (RT). Moreover, two cycles of escalated BEACOPP (bleomycin, etoposide doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) combined with two cycles of ABVD and RT were used in patients aged < 60 years in intermediate stages. The most common therapy in advanced stages was escalated BEACOPP (4-8 cycles) in patients aged < 60 years and ABVD (6-8 cycles) in patients aged ≥ 60 years. Patients with NLPHL were treated with RT alone or with combination of rituximab and chemotherapy or with a combination of RT based on clinical stages. The 10-year progression-free survival (PFS) and overall survival (OS) in patients with cHL aged < 60 years were: in early stages 91.5% and 94.2%, in intermediate stages 91.0% and 96.6% and in advanced stages 83.9% and 92.6%, respectively. The 10-year PFS and OS in cHL ≥ 60 years were: in early stages 67.0% and 74.2%, in intermediate stages 36.4% and 45.7%, in advanced stages 41.6% and 52.0%, respectively. The 10-year PFS and OS in NLPHL patients were 77.5% and 95.8%. Based on the data from the Czech HL Registry, the prognosis of HL patients aged < 60 years is excellent: the 10-year OS is achieved in more than 90% of cases. Median OS of patients aged ≥ 60 years is 10 years. Implementation of checkpoint inhibitors or brentuximab vedotin into the first-line treatment will further improve its efficacy and reduce the toxicity.
2026-04-01 | Promising outcomes of R-CHOP therapy in pediatric nodular lymphocyte-predominant Hodgkin lymphoma: perspectives from a rare subtype.
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare sub-type of Hodgkin lymphoma (HL). Due to its rarity, the standard of care for these patients remains poorly defined. Our cohort aimed to evaluate the outcomes of pediatric NLPHL patients treated with the R-CHOP regimen throughout 8 years' single center experience. A retrospective cohort study including pediatric patients aged <18 years diagnosed with NLPHL and treated at the Children Cancer Hospital Egypt, between July 2014 and June 2022. In total, 66 patients were included. Twelve patients (18%) with stage IA underwent surgical excision alone. Four of these patients experienced disease progression but achieved a complete response after receiving R-CHOP. Fifty-four patients received R-CHOP as first-line therapy, with early-stage disease received 3-4 cycles, while those with advanced-stage disease received 6 cycles. For this group, the 5-year overall (OS) and event free survival (EFS) were 100% and 91.5%, respectively. The 5-year EFS was not significantly affected by the variant histology pattern among patients received R-CHOP. Patients with stage 3 peripheral disease without risk factors demonstrated outcomes comparable to those with early-stage disease and no risk factors, achieving an excellent 5-year EFS rate of 100%. No significant toxicity was reported, except for grade 3-4 neutropenia. R-CHOP is an effective and well-tolerated regimen for treating pediatric NLPHL, demonstrating high OS and EFS rates. Patients with early stage disease achieved particularly favorable outcomes, supporting consideration of treatment de-escalation in this subgroup.
2025-12-01 | Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) in a Young Woman: A Rare Subtype Managed Without Chemotherapy
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma, comprising approximately 5–7% of cases. Unlike classical HL, NLPHL is characterized by CD20-positive “popcorn” cells (LP cells), lacks Epstein-Barr virus association, and tends to follow an indolent course. Accurate diagnosis is critical, as the therapeutic approach differs substantially. We report an early-stage NLPHL case in a young woman managed successfully without chemotherapy, emphasizing the value of histopathological precision and risk-adapted therapy. A 33-year-old woman presented with a painless cervical swelling. Physical examination revealed enlarged left cervical and supraclavicular lymph nodes. She had no B symptoms such as fever, night sweats, or weight loss. Blood counts and biochemistry were within normal limits. An excisional biopsy of a lymph node was performed, followed by immunohistochemistry and whole-body 18F-FDG PET-CT for staging. Bone marrow aspiration and biopsy were also conducted to rule out marrow involvement. Histopathological examination demonstrated nodular architecture containing scattered lymphocyte-predominant (LP) cells. Immunophenotyping revealed strong CD20 and Pax5 expression, with negativity for CD3 and CD15. CD21 staining highlighted an expanded follicular dendritic cell meshwork, confirming the diagnosis of NLPHL. PET-CT showed FDG-avid lymph nodes localized to the left cervical and supraclavicular regions, with a maximum SUV of 27.9. No pathological uptake was seen in the mediastinum, abdomen, bones, or spleen. Bone marrow biopsy was normocellular without evidence of infiltration. The disease was staged as Stage IA (non-bulky), CD20-positive NLPHL. The patient was treated with rituximab monotherapy (375 mg/m 2 weekly for 4 doses), followed by involved-field radiotherapy (30 Gy) to the involved nodal regions. Given her age and reproductive status, fertility preservation was discussed before initiating treatment. The plan aimed to minimize long-term toxicity while maintaining curative potential. This case illustrates several important themes. First, accurate histological subtyping allowed for a deviation from standard chemotherapy-based HL protocols. Second, the use of rituximab and radiotherapy alone is an emerging and evidence-supported strategy for early-stage NLPHL, particularly in CD20-positive, non-bulky cases. Third, the patient’s demographic—young and female—makes chemotherapy-free management especially attractive given concerns about fertility and late effects. Finally, the case has strong educational value, highlighting the need to distinguish NLPHL from classical HL and indolent B-cell lymphomas, both histologically and metabolically. This case demonstrates how a rare Hodgkin lymphoma subtype can be successfully managed with a chemotherapy-free, targeted approach. It reinforces the importance of accurate subtyping and risk-adapted treatment in delivering personalized care, especially in young patients where fertility and quality of life are key considerations
2025-12-01 | TREATMENT APPROACH AND OUTCOMES IN CHILDREN AND ADOLESCENTS WITH NODULAR LYMPHOCYTE-PREDOMINANT HODGKIN LYMPHOMA: THE ITALIAN ASSOCIATION OF PEDIATRIC HEMATOLOGY AND ONCOLOGY (AIEOP) EXPERIENCE.
Introduction Nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is a rare subtype of Hodgkin lymphoma, which accounts for about 5% of pediatric/adolescent Hodgkin lymphomas [ 1 ] [ 2 ]. Currently, patients diagnosed in Italy with nLPHL are collected in the AIEOP-LHPL2019 retrospective/prospective study. Methods This is an observational study recruiting all stage nLPHL, since november 2019. Patients are treated according to clinician discretion, following study suggestions. About 10 new cases/year are diagnosed in AIEOP Centers. Results To date, 83 patients from 28 AIEOP centers have been observed, to which 11 additional new diagnoses were added in the last year. 82/83 patients have been evaluated. Eighty percent of cases had the histology centrally revised. Patients, 68M/15F (M 81.9%), mean age 12.8aa (range 2.9-17.9aa), 66% age>12aa, presented stage I-IIA disease in 66/83 (79.5%), only 2/83 (2.4%) patients presented B symptoms. Treatment: 16 stage IA patients were treated with surgery alone, 38 (stage IA+IIA+IIIA) received 3-6 CVP cycles, 8 patients 3-6 Rituximab+CVP, and 20 different therapies (ABVD±R, R-CHOP, OEPA, COPP/ABV). No patient has been treated with RT. A total of 14/82 patients received first-line rituximab therapy. 20/82 (24.4%) patients, including 2 stage IIB-IIIB, 6 stage IA, and 12 stage IIA, presented persistent/progressive/recurrent disease after first-line therapy. With 100% OS and 76% EFS at a median follow-up of 56.4 months, nLPHL is confirmed to be a disease with good prognosis; 66% of patients received low intensity treatment (surgery and/or CVP). 20/82 (24.4%) patients developed recurrences, namely 14 relapses, 3 persistent diseases after first line treatment and 3 disease progressions. Both patients with stage IIB-IIIB developed disease progression after being treated with intensive chemotherapy (R-ABVD and OEPA+R-CHOP respectively). It’s interesting to note that all the remaining 18 patients with recurrences had stage I/IIA while no cases of recurrences occurred for IIIA/IVA stages. Conclusion The current case series of AIEOP Centers with 83 patients represent one of the largest in the nLPHL scenario. According to literature [ 3 ] [ 4 ] and confirmed in our experience, in the majority of patients, sparing of anthracycline and radiotherapy is possible, and the addition of rituximab seems to offer a promising chance [ 5 ]. The rare presence of B symptoms at onset, seems to identify a disease with a more severe prognosis. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2025-12-01 | Nodular Lymphocyte Predominant Hodgkin Lymphoma Involving the Stomach and Bones
Introduction NLPHL typically presents as early stage disease with localized peripheral lymphadenopathy. Primary extranodal NLPHL is exceedingly rare. Here we present the diagnostic challenges of an adolescent with NLPHL. Methods Case report Results A 17 year old Hispanic male presented with a two-months history of vomiting, abdominal pain and weight loss of 6 pounds, without fever or night sweats. A CT scan showed a mass in between the liver and the spleen and around the gastroesophageal (GE) junction. In the upper stomach and lower esophagus mucosal thickening was noted. In addition, splenomegaly, periaortic lymphadenopathy, cervical and supraclavicular lymphadenopathy was present. No mediastinal adenopathy was noted. The PET/CT scan showed FDG avidity in all areas of CT involvement and uncovered multiple bone involvement in the vertebri, sacrum, pelvis, proximal femurs and humerus. An esophagogram showed an apple-core lesion involving the distal stomach and gastric fundus. An upper esophago-gastroduodenoscopy showed an exophytic mass in the stomach. Biopsies showed necrotic tissue. Bone marrow biopsy was negative. Histopathological diagnosis was challenging. The specimen underwent 3 pathological consultations. The process took 8 weeks 1) presence of large cells with uniform CD30 expression and weak PAX5 favoring cHL but also good preservation of B cell program (positive CD79a, BOB1 and OCT2), apparent CD45 expression, and variable CD20. 2) most consistent with NLPHL variant patern D, and T cells with aberrant CD20 expression. 3) large cells that retain B cell programming expressing CD20, CD19, OCT2 and BOB1 but also strong CD30 expression, but with CD45 positivity. Cells also expressed MEF2B and negative for STAT6 both favoring NLPHL. CD20 appeared weakly expressed on T-cells population. Overall findings are consistent with NLPHL. The patient was treated with Bv-AVEPC x5. PET2 showed incomplete metabolic response with DS of 4 in the GE junction, spleen and bones. All areas of involvement showed decrease in size. PET5 showed complete metabolic response of all sites. He then receive 6 doses of Rituximab every 3 weeks. End of therapy PET scan was negative. Radiation therapy was spared. Six months after completing treatment, the patient remained in remission [ 1 ] [ 2 ]. Conclusion This case highlights a rare case of NLPHL with extranodal involvement in the stomach and bones and the challenges of histopathological diagnosis with implications in delay in proper treatment. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
small molecules
2026-06-03 | EuroNet-PHL-LP1: Complete resection or low-dose chemo for pediatric low-risk nodular lymphocyte-predominant Hodgkin lymphoma.
Children and adolescents with early-stage nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) have a 5-year event-free survival (EFS) of about 77% after complete lymph node resection and around 89% with anthracycline-containing chemotherapy. We investigated whether patients with early-stage nLPHL can be successfully treated with surgical resection alone or with low-intensity, anthracycline-free CVP chemotherapy for those with unresectable nodal disease. EuroNet-PHL-LP1 was a prospective phase III trial enrolling patients under 18 years with stage IA/IIA nLPHL. Completely resected lymph nodes led to active surveillance. Patients with unresectable disease received three cycles of CVP (cyclophosphamide, vinblastine, prednisone). In CVP-cohort-1, treatment cessation required a negative 18F -FDG-PET. An amendment in 2014 omitted PET for end-of-treatment response; CT and/or MRI alone defined response in CVP-cohort-2. The primary endpoint was 5-year EFS, with death, relapse, second malignancy and PET-positivity counting as events; for CVP-cohort-2, progression-free survival (PFS) was primary. Among 267 registered patients (2009-2018), 247 were evaluable. Seventy-eight underwent resection only; their 5-year EFS/PFS was 79.5%. Six of 18 patients who relapsed after surgical resection re-entered the CVP arm. In CVP-cohort-1, 51/82 (62%) achieved a complete metabolic response (CMR). 5-year EFS was 56.4%, while 5-year PFS in the CMR group was 91.3%. In contrast, PFS in 84 CVP-cohort-2 patients was 64.7%. During CVP, 68.3% of patients experienced grade 3-4 neutropenia. No treatment-related deaths were reported. Excellent outcomes were achieved after complete resection and with low-intensive, anthracycline-free chemotherapy if 18F-FDG-PET showed CMR after chemotherapy. This strategy now constitutes the EuroNet-PHL standard of care for early-stage nLPHL. The trial was registered under EudraCT-No.: 2007-004092-19.
2026-03-24 | Paraneoplastic Hepatitis Associated with Relapsed Nodular Lymphocyte-Predominant Hodgkin Lymphoma.
Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an indolent B-cell lymphoma with long-term survival and a tendency for late relapse. Hepatic manifestations of varying etiologies have been described in lymphoproliferative disorders. However, paraneoplastic hepatitis is rare, and reports typically describe acute presentations. We describe an unusual case of paraneoplastic hepatitis with an indolent and progressive clinical course occurring in the setting of relapsed NLPHL. Case Presentation: A 32-year-old man with a history of NLPHL was found to have marked transaminase elevation with preserved liver function during routine follow-up. Extensive evaluation excluded viral, autoimmune, and metabolic causes of liver disease. Liver biopsy demonstrated confluent and bridging necrosis with lymphoplasmacytic infiltrates, without evidence of direct lymphoma involvement. Excisional biopsy of a cervical lymph node revealed relapse of NLPHL without histologic transformation. Treatment with corticosteroids resulted in partial biochemical improvement, and subsequent rituximab monotherapy achieved lymphoma remission. Despite this, low-grade transaminase elevation persisted, and follow-up imaging and liver biopsy demonstrated progression to fibrosis, suggesting a tendency towards chronicity. Conclusions: Paraneoplastic hepatitis should be considered in patients with NLPHL who present with unexplained liver abnormalities. This report illustrates a fibrosing form of paraneoplastic hepatitis associated with NLPHL and broadens the clinical spectrum of paraneoplastic hepatic injury. Early recognition, histological confirmation, and tailored immunosuppressive management are critical to optimizing hepatic and lymphoma-related outcomes.
2025-12-01 | Successful treatment of children and adolescents with stage IA/IIA lymphocyte–predominant Hodgkin Lymphoma after complete resection alone or low dose, anthracyclin-free chemotherapy: Results of the EuroNet-PHL-LP1 trial
Introduction Children and adolescents with early-stage lymphocyte-predominant Hodgkin lymphoma (nLPHL) have a 5-year event-free survival of about 77% after complete resection of a single lymph-node and 89% after anthracycline-containing low-intensity chemotherapy and 18 F-FGD-PET-based radiotherapy [ 1 ]. We investigated whether patients with LPHL stage IA/IIA can be cured by resection alone or a very low-anthracycline-free chemotherapy. Methods The EuroNet-PHL-LP1 trial was a prospective uncontrolled phase III study in early stage NLPHL for patients under 18 years of age. Patients presenting in stage IA/IIA with complete resection entered into follow-up. Patients without complete resection received 3 cycles of chemotherapy consisting of Cyclophosphamide, Vinblastine and Prednisone (CVP) and received no further treatment if 18 F-FDG-PET was negative (CVP-cohort 1). After an amendment reacting to an unexpectedly high 18 F-FDG-PET positivity rate, 18 F-FDG-PET was omitted and all patients without residual disease determined by CT or MRI (CVP-cohort 2) received no further treatment. The primary endpoint was event-free survival (EFS) defined by a positive FGD-PET (CVP-cohort-1), secondary malignancy or death of any cause. Secondary endpoints were overall survival (OS) or progression-free survival (PFS). For CVP-cohort-2, EFS and PFS coincide since no secondary malignancy occurred. We report 5-year rates. Results Between Dec 15, 2009 and Oct 31, 2018, 267 patients were registered and 247 patients were enrolled onto EuroNet-PHL-LP1. Of these, 87 patients were treated with resection alone and PFS was 79.5% (95%CI; 71,2% – 88,7%). In the CVP-treatment cohort-1, 51 of 82 patients were in complete metabolic response (CMR) after chemotherapy (approximately Deauville scores 1-2). EFS in CVP-cohort-1 was only 56.4% (95%CI; 46.5% – 68.4%), however PFS in the 18 F-PET-negative group of CVP- cohort -1 was 91.3% (95%CI; 83.6% – 99.9%). In contrast, PFS in 84 patients of the CVP-cohort-2 was 64.7% (95%CI; 55.1% – 76.0%). The most common grade 3-4 adverse events were neutropenia in 68.3% of patients treated with CVP. There were no treatment-related deaths. Conclusion Patients with nLPHL with stages IA/IIA have an excellent prognosis after complete resection. 18 F-FDG-PET response is predictive. Patients with incomplete resection have an excellent prognosis with low-intensive, anthracycline-free chemotherapy if 18 F-FGD-PET becomes negative at the end of chemotherapy. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2025-12-01 | Nodular Lymphocyte Predominant Hodgkin Lymphoma: Experience of the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG)
Introduction Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare clinical entity. To investigate the clinical course and treatment of NLPHL, a survey was conducted among centers participating in the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). Methods A questionnaire was sent to all 17 Polish centers, and clinical data were analyzed. Results Between 2010 and 2024, 39 pediatric patients aged 5.6–18.0 years (median: 12.3 years) with confirmed NLPHL were registered in Poland. NLPHL occurred predominantly in males (n=35). All disease stages were observed, with stage I (n=8) and stage II (n=23) being the most common. In most patients (n=26), supradiaphragmatic involvement was noted. Seven patients with localized, resectable stage IA disease were treated. Five underwent complete primary resection; two received surgery alone, although one relapsed and was treated with CVP chemotherapy. The other five received additional chemotherapy after resection. Three patients had incomplete resections and received CVP chemotherapy, with one relapse observed. CVP chemotherapy was administered to 23 patients with stage IIA disease. After three cycles, four relapses occurred and were managed with R-CHOP± radiotherapy. All treatments have led to durable remissions so far. Advanced disease was noted in nine patients (eight boys, one girl) aged 8.8–17.9 years (median: 12.2). Various chemotherapy protocols were used, including rituximab in three cases and without rituximab in five. Two relapses were treated with R-CHOP; one patient underwent autologous stem cell transplantation due to poor response. Relapse-free survival rates were 72.1% for early-stage (IA and IIA) and 85.7% for advanced-stage disease. No deaths were reported. Conclusion The outcomes of NLPHL treatment in Poland are consistent with those reported in other countries; however, further improvement and standardized treatment approaches for NLPHL patients in Poland are needed. Special attention should be given to patients eligible for primary surgical resection. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2025-10-01 | IgG4-Related Tubulointerstitial Nephritis and Proliferative Glomerulonephritis (GN) with IgG2, IgG3, and IgG4 Deposits in a Patient with Treated T Cell-Rich Large B Cell Lymphoma
Introduction: IgG4-related kidney disease (IgG4-RKD) most commonly presents as tubulointerstitial nephritis (TIN) with occasional glomerular involvement. Recent literature suggests an association between IgG4-RKD and hematologic malignancies. We report a unique case of IgG4-TIN with concurrent immune complex mediated proliferative GN in a patient with prior treated lymphoma. Case Description: A 77-year-old man with stage 3a CKD and history of nodular lymphocyte-predominant Hodgkin lymphoma (treated with R-CHOP, DICE, and autologous stem cell transplant, in remission) presented with AKI and petechial rash. Following recent travel to Mexico, he developed spreading petechial rash, joint pains and fevers. Laboratory testing showed elevated BUN, creatinine (3.5 mg/dL, baseline 1.4), mild anemia, thrombocytopenia (55K), proteinuria, low C3 and C4. Imaging revealed new lymphadenopathy. Skin biopsy showed urticarial dermatitis; biopsy from right inguinal lymph node showed chronic inflammation without lymphoma. Kidney biopsy revealed a dominant IgG4-positive plasma cell-rich interstitial infiltrate consistent with IgG4-TIN, and diffuse proliferative GN with polyclonal IgG, including IgG2, IgG3 and dominant IgG4 immune deposits (Figure 1, 2). No evidence of thrombotic microangiopathy or lymphoid malignancy was found. Extensive rheumatologic and infectious workup was negative. High-dose corticosteroids led to rapid improvement in renal function and resolution of symptoms. AKI recurred upon rapid steroid taper and improved with re-initiation of steroid. Discussion: This case highlights the rare coexistence of IgG4-TIN and proliferative GN with polyclonal IgG immune deposits in a patient with prior large B-cell lymphoma. While IgG4-RD is more commonly associated with membranous nephropathy, proliferative GN with MPGN-like features remains rare. The temporal association with treated lymphoma raises consideration for a paraneoplastic or immune reconstitution-related phenomenon. Early steroid therapy was associated with rapid clinical response.
proteins
2023-05-04 | B-cell receptor reactivity against <i>Rothia mucilaginosa</i> in nodular lymphocyte-predominant Hodgkin lymphoma
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1* 07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver- and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA'-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL.
2009-11-13 | A recombinant adenovirus type 35 fiber knob protein sensitizes lymphoma cells to rituximab therapy
Abstract Many tumors, including lymphomas, up-regulate expression of CD46 to escape destruction by complement. Tumor cells are therefore relatively resistant to therapy by monoclonal antibodies, which act through complement-dependent cytotoxicity (CDC). From an Escherichia coli expression library of adenovirus type 35 fiber knob mutants, we selected a variant (Ad35K++) that had a higher affinity to CD46 than did the natural Ad35 fiber knob. We demonstrated that incubation of lymphoma cells with recombinant Ad35K++ protein resulted in transient removal of CD46 from the cell surface. Preincubation of lymphoma cells with Ad35K++ sensitized cells to CDC, triggered by the CD20-specific monoclonal antibody rituximab. In xenograft models with human lymphoma cells, preinjection of Ad35K++ dramatically increased the therapeutic effect of rituximab. Blood cell counts and organ histology were normal after intravenous injection of Ad35K++ into mice that express human CD46. The presence of polyclonal anti-Ad35K++ antibodies did not affect the ability of Ad35K++ to enhance rituximab-mediated CDC in in vitro assays. The Ad35K++-based approach has potential implications in monoclonal antibody therapy of malignancies beyond the combination with rituximab.
2003-05-01 | Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin’s lymphoma
BackgroundImmunotoxins (ITs) consist of cell binding ligands coupled to toxins or their subunits. Hodgkin's lymphoma (HL) is an excellent target for ITs since lymphocyte activation markers such as CD25 and CD30 are expressed in large numbers. The ITs RFT5.dgA (anti CD25) and Ki-4.dgA (anti CD30) were constructed by linking the monoclonal antibodies RFT5 and Ki-4 to deglycosylated ricin A-chain (dgA). Both ITs showed potent specific activity against HL cells in vitro and in vivo in animal models, and were subsequently evaluated in phase I/II clinical trials in humans.Patients and methodsIn two separate trials, the ITs were administered i.v. four times every other day over 4 h. The objectives of the phase I trials included the determination of the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, antitumor activity and immune response against the IT.ResultsTwenty-seven patients with refractory HL were included in the phase I/II study of RFT5.dgA and 17 patients were included in the phase I study of Ki-4.dgA. The MTD of RFT5.dgA was 15 mg/m2, whereas that of Ki-4.dgA was 5 mg/m2. DLTs were related to vascular leak syndrome, consisting of edema, tachycardia, dyspnea, weakness and myalgia. Measurement of serum levels of RFT5.dgA demonstrated a Cmax of 0.2–9.7 µg/ml with a half-life (t½) varying from 4 to 10.5 h. Peak serum concentration of Ki-4.dgA ranged from 0.23 to 1.7 µg/ml. In both trials ∼60% of patients developed human anti-mouse and/or anti-dgA antibodies. Seventeen of 18 patients treated at the MTD of RFT5.dgA were evaluable for clinical response. Responses included two partial remissions (PR), one minor response (MR) and five stable diseases (SD). Fifteen of 17 patients treated with Ki-4.dgA were evaluable for clinical response. Responses included one PR, one MR and two SD.ConclusionsRFT5.dgA and Ki-4.dgA showed moderate efficacy in heavily pretreated refractory patients with HL. Ki-4.dgA was less well tolerated than RFT5.dgA. This might be due, at least in part, to the formation of Ki-4.dgA/sCD30 complexes.
2001-05-01 | Transfection of caspase-3 in the caspase-3–deficient Hodgkin's disease cell line, KMH2, results in enhanced sensitivity to CD95-, TRAIL-, and ARA-C–induced apoptosis
BackgroundCD95(Fas/apo-1) is a cell surface protein member of the tumor necrosis factor receptor family that serves an important role in the induction of apoptosis in several cell types. Although expression of CD95 has been detected on Hodgkin/Reed Sternberg (HRS) cells in situ, our understanding of the biological significance of this molecule in Hodgkin's disease (HD) is limited.DesignWe analyzed both CD95-related apoptotic signaling and its effects on the expression of several factors involved in the regulation of apoptotic mechanisms including: caspase-3, caspase-8, bcl-2, bcl-x, and Bax in HD cell lines (L-428, L-540, HDLM-2, HS-445, and KM-H2).ResultsHD cell lines showed similar expression levels of CD95 and all but KM-H2 demonstrated variable increases in apoptosis after CD95 stimulation by the agonistic monoclonal antibody, CH11. There was no significant correlation between CD95 sensitivity and constitutive expression levels of caspase-8, bcl-2, bcl-x, and Bax. Caspase-3 transcript was demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR) in all cell lines but protein was at low to nearly undetectable levels in KM-H2 cells. Transfection of KM-H2 cells with pro–caspase-3 resulted in a markedly enhanced apoptotic response to CD95 stimulation that was blocked by pretreatment with the caspase-3 inhibitor, DEVD-FMK. In addition, pro–caspase-3–transfected KM-H2 cells showed significantly increased sensitivity to other caspase-3–dependent apoptotic stimuli, including the death-inducing ligand, TRAIL, and the chemotherapeutic agent, Ara-C.ConclusionThese data demonstrate that caspase-3 expression plays an important role in CD95-mediated apoptosis in HD cell lines. Furthermore, lack of or decreased expression of caspase-3 in HD cells impairs their apoptotic response not only to CD95 but also to other caspase-3–dependent apoptotic stimuli.
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