Lymphocyte Depleted Hodgkin Lymphoma

Earn CME/CE in your profession:

Continuing Education Activity

Lymphocyte-depleted classic Hodgkin lymphoma is the rarest subtype of classic Hodgkin lymphoma, accounting for 1% to 1.5% of classic Hodgkin lymphoma cases in western countries. Most patients with lymphocyte-depleted classic Hodgkin lymphoma experience B symptoms such as unexplained fever more than 100.4 F (38 C), drenching night sweats, and unexplained loss of more than 10% of body weight over 6 months. The 5-year progression-free survival and overall survival rates are significantly lower in these patients than those with other subtypes of classic Hodgkin lymphoma. This activity describes the evaluation and management of lymphocyte-depleted classic Hodgkin lymphoma and reviews the role of the interprofessional team in evaluating and treating patients with this condition.


  • Identify the etiology of lymphocyte-depleted classic Hodgkin lymphoma.
  • Outline appropriate evaluation of lymphocyte-depleted classic Hodgkin lymphoma and proper referral.
  • Review the management options available for lymphocyte-depleted classic Hodgkin lymphoma.
  • Summarize some interprofessional team strategies for improving care coordination and communication to improve outcomes in patients with lymphocyte-depleted classic Hodgkin lymphoma.


Lymphocyte-depleted classic Hodgkin lymphoma is the rarest subtype of classic Hodgkin lymphoma globally, although it may be more common in developing countries.[1][2][3] The diagnosis of lymphocyte-depleted classic Hodgkin lymphoma could be challenging, and the disease might be misdiagnosed as more aggressive B-cell or T-cell lymphomas.[4] Patients with this disease present more often with unfavorable risk factors and have poorer survival rates than those with other subtypes of classic Hodgkin lymphoma.[5][6]


Although certain viral infections such as Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) have been associated with this disease, no specific causal link has been identified.[6][7][8]


Lymphocyte-depleted classic Hodgkin lymphoma is regarded as the rarest subtype of classic Hodgkin lymphoma, accounting for 1% to 1.5% of classic Hodgkin lymphoma cases in Western countries.[5][9] However, it may be more common in the developing world.[3] Approximately 40% of cases are diagnosed in patients aged 60 years and older.[9] Younger patients aged 18 to 39 years are also affected by the disease seen in 28% of cases.[9] It is twice as common in men as in women.[6] At the time of presentation, 64% of patients have an advanced-stage disease (stage III-IV).[6]


The etiology of lymphocyte-depleted classic Hodgkin lymphoma has not been established. However, genetic factors and viral infections such as EBV and HIV may play a role in the pathogenesis of this disease.[6][7][8][10]

1. Genetic Disorders

Various gene mutations and chromosomal abnormalities in classic Hodgkin lymphoma affect transcription factors, signaling molecules, tumor suppressor genes, and immune regulators. These result in the transformation of germinal center B-cells to characteristic Hodgkin/Reed-Sternberg (HRS) cells.[11] 

1.1. Genetic Abnormality

A genetic amplification or copy number gain of chromosome 9p24.1 leads to overexpression of programmed death-ligand 1 and 2 (PD-L1 and PD-L2).[10] Moreover, amplification of Janus activated kinase 2 (JAK2) locus induces Janus activated kinase - signal transducers and activators of transcription (JAK-STAT) signaling, leading to increased transcription of PD-L1.[10] The signaling between PD-L1 on HRS cells and programmed cell death-1 (PD-1) receptors on T-cells results in T-cell dysfunction, exhaustion, and subsequent apoptosis.[12] The resultant immunosuppressive tumor microenvironment allows HRS cells to evade an effective anti-tumor immune response.[13]

1.2. Aberrant Signaling

Constitutive activation of nuclear factor-kappa B (NF-kappaB) in HRS cells is hypothesized to stimulate proliferation, encourage migration, and inhibit apoptosis of malignant cells.[14] Cooperation of NF-kappaB with activator protein 1 complex (AP-1) causes increased expression of cyclin D2, c-met, and chemokine receptor 7 (CCR7), thus promoting HRS cell proliferation.[15] Additionally, loss-of-function mutations of suppressors of cytokine signaling-1 (SOCS-1) are associated with constitutive activation of JAK-STAT signaling and nuclear phospho-STAT5 accumulation.[16] 

2. Viral Infections

2.1. Epstein-Barr Virus

EBV infection is present in 60% to 72% of patients with lymphocyte-depleted classic Hodgkin lymphoma, which is relatively more common than other subtypes of classic Hodgkin lymphoma.[6][7] Besides, EBV has been shown to play a significant role in the pathogenesis of this disease. Latent membrane protein 1 (LMP 1) of EBV induces PD-L1 expression on EBV-infected B-cells through several survival pathways such as the JAK-STAT signaling pathway, NF-kappaB, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways.[17][18][19][20] 

Moreover, LMP 1 acts as a functional homolog of CD40.[21] CD40 ligand on activated T-cells typically interacts with CD40 on antigen-presenting cells, leading to a T-cell-dependent immune response.[22] However, in EBV infection, LMP 1 imitates helper T-cell function and allows EBV-infected B-cells to undergo activation, proliferation, and differentiation in the absence of T-cells.[23] 

2.2. Human Immunodeficiency Virus

Approximately 15% of patients with lymphocyte-depleted classic Hodgkin lymphoma have HIV infection that induces chronic B-cell activation via interacting with CD40-ligand-bearing virions, HIV-associated proteins such as gp120, p17, and nef, and altering cytokine production and release.[8][24][25][26] Failure to recognize and eradicate EBV-infected B-cells, caused by HIV infection with associated immune dysfunction, also contributes to malignant transformation.[27] Moreover, the HIV p17 protein variant induces EBV oncoprotein, which then leads to the uncontrolled proliferation of B-cells infected with EBV.[27]


The lymphocyte-depleted classic Hodgkin lymphoma diagnosis requires a histopathologic finding of characteristic HRS cells with abundant basophilic cytoplasm and a distinctive bi-nucleate morphology resembling owl's eyes appearance.[28] Lymphocyte infiltration is minimally seen in this subtype. The two morphological variants are diffuse fibrosis and reticular variant. The former has abundant HRS cells in a hypocellular background with disordered fibrosis, abundant histiocytes, and few plasma cells or eosinophils, while the latter has numerous HRS cells frequently associated with anaplastic and pleomorphic features.

History and Physical

Most patients experience B symptoms such as unexplained fever of more than 100.4 °F (38 °C), drenching night sweats, and unexplained loss of more than 10% of body weight over 6 months.[5] They typically present with an extensive symptomatic disease with a predilection for retroperitoneal lymph nodes, abdominal organs including subdiaphragmatic regions, and bone marrow.[28]


For a definitive diagnosis of lymphocyte-depleted classic Hodgkin lymphoma, an excisional lymph node biopsy is generally preferred over a core-needle biopsy.[29][30] However, a fine-needle aspiration biopsy (FNAB) is inadequate to establish the diagnosis.[31][32] Immunophenotyping is also required for a definitive diagnosis, and the HRS cells are positive for CD30 in almost all cases.[6][7] The neoplastic cells are also positive for CD15 and PAX5. A positive CD20 can be detected in 20% of cases. They are usually negative for CD3, CD45, and CD79a. Up to 60% to 72% of lymphocyte-depleted classic Hodgkin lymphoma cases may be positive in LMP 1 of EBV.

Proper staging is important to assess the extent of the disease and to guide therapy. Positron emission tomography (PET) and computed tomography (CT) scans are routinely done for staging evaluation in Hodgkin lymphoma, but contrast-enhanced CT scans can also be used.[33][34] A bone marrow biopsy is no longer mandatory for the routine staging of Hodgkin lymphoma.[35] The 2014 Lugano classification is described as follows:[36]

  • Stage I: A single lymph node, a group of adjacent lymph nodes, or single extranodal lesions without nodal involvement
  • Stage II: Two or more lymph node groups on the same side of the diaphragm or limited contiguous extranodal involvement
  • Stage II bulky: Stage II as above with a bulky feature defined as a single nodal mass of 10 centimeters or greater than a third of the transthoracic diameter
  • Stage III: Nodes on both sides of diaphragm or nodes above diaphragm with spleen involvement
  • Stage IV: Additional noncontiguous extra lymphatic involvement

Treatment / Management

Clinical outcomes of classic Hodgkin lymphoma have been improving with the advancement of chemotherapy, radiation therapy, and targeted therapies.[37] The therapeutic approach is based on the age of patients, the extent of disease, high-risk features, comorbidities, potential toxicities, and survivorship.

1. Risk Stratification

Patients are generally classified into 3 groups: early-stage favorable (stage I–II without unfavorable factors), early-stage unfavorable (stage I–II with any of the unfavorable factors), and advanced-stage disease (stage III-IV). The National Comprehensive Cancer Network defines unfavorable factors for early-stage disease as the presence of B symptoms, erythrocyte sedimentation rate ≥ 50 millimeters per hour, bulky mediastinal disease (mediastinal mass ratio > 0.33, or adenopathy > 10 centimeters), and > 3 sites of disease.[38][39][40]

The International Prognostic Score (IPS) helps determine the clinical management and predict prognosis for those with advanced-stage disease.[41] It is a seven-factor scoring system, which includes: serum albumin < 4 grams per deciliter, white-cell count ≥ 15,000/cubic millimeter, age ≥ 45 years, lymphocyte count < 600/cubic millimeter, or < 8% of white-cell count, hemoglobin < 10.5 grams per deciliter, male sex, and stage IV disease. Patients with high-risk scores (IPS ≥ 4) were found to have 5-year freedom from progression (FFP) of 65%, while those with low-risk scores (IPS 0 to 3) had a 5-year FFP of 81%.[42]

2. Risk-Adapted Initial Therapy

2.1. Early-Stage Hodgkin Lymphoma

Two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy followed by 20 Gy of involved-field radiation therapy (IFRT) is generally considered as the standard therapy for early-stage favorable Hodgkin lymphoma.[43] For those with an unfavorable prognosis, ABVD for 4 cycles with a subsequent 30 Gy of IFRT is considered as the standard initial regimen.[44] The total number of chemotherapy cycles and the role of radiation therapy vary in both favorable and unfavorable patient groups depending on the initial response to chemotherapy and the therapeutic plan (chemotherapy alone versus combined modality therapy). Note that the omission of radiation therapy is associated with a slightly higher risk of disease relapse.[45][46] Cautions must be taken when using bleomycin in elderly patients due to a substantial risk of severe pulmonary toxicity.[47]

2.2. Advanced-Stage Hodgkin Lymphoma

Six cycles of ABVD is a preferred therapeutic approach for adult patients with advanced-stage Hodgkin lymphoma.[48] Other regimens that may be considered include escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and brentuximab vedotin, an anti-CD30 antibody-drug conjugate, combined with AVD (doxorubicin, vinblastine, and dacarbazine).[49][50]

3. Response-Adapted Therapy

After 2 cycles of ABVD, patients typically undergo the first interim response assessment using PET/CT scans.[51] The results are then interpreted using the Deauville criteria that utilize a 5-point scoring system.[52] The scale depends on the visual comparison of fluorodeoxyglucose (FDG) uptake in involved sites to that of mediastinum and liver. The interpretation is as follows:

  • Score 1: no uptake
  • Score 2: uptake is equal to or below mediastinum
  • Score 3: uptake is above mediastinum but equal to or below the liver
  • Score 4: uptake is moderately higher than liver
  • Score 5: uptake is markedly higher than liver, any new lesions, or both
  • Score X: new areas of uptake that are unlikely to be related to lymphoma

Depending on the Deauville score, further management is individualized for each patient.[52] Bleomycin can safely be omitted from ABVD regimen in patients who achieved a negative interim PET/CT scan.[47][53][54] In contrast, a biopsy is warranted for patients with a positive interim PET/CT scan, particularly Deauville score 5, to confirm a refractory disease or to establish the definitive diagnosis.[36]

4. End-of-Treatment Assessment

At the end of treatment, PET/CT scans help establish remission status using the Deauville criteria.[36][52][55] A score of 1 to 3 represents a complete metabolic remission irrespective of the size of a residual mass. A residual PET-positivity could represent inflammatory changes or persistent disease, and these patients could undergo further evaluation by biopsy, subsequent radiation therapy, or can potentially be observed.[56]

5. Relapsed or Refractory Hodgkin Lymphoma

A diagnosis of relapsed or refractory Hodgkin lymphoma must be confirmed histologically by biopsy.[36] Patients with a relapsed or refractory Hodgkin lymphoma are treated with an alternative chemotherapy regimen, such as ICE (ifosfamide, carboplatin, and etoposide).[57][58] High-dose chemotherapy and autologous stem cell rescue (HDT/ASCR) is the standard of care for patients with chemosensitive disease. Risk factors for relapse or progression after transplantation includes primary refractory disease, remission duration of <1 year following frontline therapy, and the presence of extranodal disease at relapse.[59] Consolidative brentuximab vedotin, with a duration of 1 year, is indicated for patients with high-risk features. Additional therapeutic options include brentuximab vedotin, PD-1 monoclonal antibodies such as nivolumab and pembrolizumab, and allogeneic stem cell transplantation.[60][61][62][63][64]

Differential Diagnosis

Lymphadenopathy can be seen in various conditions such as infection, autoimmune disorders, and malignancies. Patients with lymphadenopathy should undergo proper workups. A definitive diagnosis requires a biopsy with histopathological and immunohistochemical examinations. It is prudent to obtain adequate tissue for histopathologic analysis, particularly for patients with suspected Hodgkin lymphoma, to yield a definitive diagnosis.[65]


Patients with lymphocyte-depleted classic Hodgkin lymphoma have more adverse risk factors than those with other subtypes of classic Hodgkin lymphoma. The 5-year progression-free survival and overall survival rates are significantly lower in these patients than those with other subtypes of classic Hodgkin lymphoma.[5]


In long-term survivors of Hodgkin lymphoma, the most serious late complications include secondary cancers, cardiovascular diseases especially in patients treated with mediastinal irradiation and/or anthracycline-based chemotherapy, hypothyroidism related to mediastinal irradiation, and infertility particularly associated with BEACOPP regimen.[66][67][68][69][70][71] Timely recognition and proper management of these potential long-term complications among survivors of lymphoma are crucial to mitigate treatment-related morbidity and mortality.

Deterrence and Patient Education

Being diagnosed with lymphocyte-depleted classic Hodgkin lymphoma and undergoing treatment can have significant psychosocial impacts on patients and their families. These can bring dramatic changes in their physical, spiritual, emotional, and interpersonal dimensions. Every clinic visit should include screening and assessing the emotional and social concerns of patients and their families. They should also be well-informed of the types of treatment, such as combined modality therapy versus chemotherapy alone, pros and cons of each treatment, side effects, supportive measures, regular follow-up, and long-term management plan.

Furthermore, as some chemotherapeutic agents are known to affect fertility, patients should be counseled for options such as sperm banking and egg freezing to preserve fertility. Regular follow-up with primary care physicians and oncologists is also important to monitor treatment response and treatment-related toxicities such as cardiotoxicity and pulmonary toxicity.

Enhancing Healthcare Team Outcomes

A patient-centered teamwork approach is of vital importance when managing patients with lymphocyte-depleted classic Hodgkin lymphoma. An interprofessional team comprising of primary care physicians, oncologists, nursing staff, radiologists, palliative services, social workers, and case managers should work together in every step of treatment to provide comprehensive care for patients and their families, in prevention and management of complications, regular follow-up, survivorship care, psychosocial support, and in end-of-life care.

Article Details

Article Author

Aye M. Thida

Article Editor:

Aung M. Tun


6/27/2022 11:41:33 PM



Shimabukuro-Vornhagen A,Haverkamp H,Engert A,Balleisen L,Majunke P,Heil G,Eich HT,Stein H,Diehl V,Josting A, Lymphocyte-rich classical Hodgkin's lymphoma: clinical presentation and treatment outcome in 100 patients treated within German Hodgkin's Study Group trials. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005 Aug 20;     [PubMed PMID: 16009944]


Allemani C,Sant M,De Angelis R,Marcos-Gragera R,Coebergh JW, Hodgkin disease survival in Europe and the U.S.: prognostic significance of morphologic groups. Cancer. 2006 Jul 15;     [PubMed PMID: 16770772]


Sultan S,Irfan SM,Parveen S,Ali S, Clinico-Hematological Findings for Classical Hodgkin's Lymphoma: an Institutional Experience. Asian Pacific journal of cancer prevention : APJCP. 2016;     [PubMed PMID: 27644653]


Kant JA,Hubbard SM,Longo DL,Simon RM,DeVita VT Jr,Jaffe ES, The pathologic and clinical heterogeneity of lymphocyte-depleted Hodgkin's disease. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1986 Mar     [PubMed PMID: 3754003]


Klimm B,Franklin J,Stein H,Eichenauer DA,Haverkamp H,Diehl V,Fuchs M,Borchmann P,Engert A, Lymphocyte-depleted classical Hodgkin's lymphoma: a comprehensive analysis from the German Hodgkin study group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011 Oct 10;     [PubMed PMID: 21911729]


Karube K,Niino D,Kimura Y,Ohshima K, Classical Hodgkin lymphoma, lymphocyte depleted type: clinicopathological analysis and prognostic comparison with other types of classical Hodgkin lymphoma. Pathology, research and practice. 2013 Apr;     [PubMed PMID: 23478005]


Tzankov A,Zimpfer A,Pehrs AC,Lugli A,Went P,Maurer R,Pileri S,Dirnhofer S, Expression of B-cell markers in classical hodgkin lymphoma: a tissue microarray analysis of 330 cases. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2003 Nov;     [PubMed PMID: 14614054]


Shiels MS,Koritzinsky EH,Clarke CA,Suneja G,Morton LM,Engels EA, Prevalence of HIV Infection among U.S. Hodgkin lymphoma cases. Cancer epidemiology, biomarkers     [PubMed PMID: 24326629]


Major A,Jackson MW,Smith DE,Kamdar M,Rabinovitch R, Inferior outcomes and treatment disparities in elderly patients with classical Hodgkin lymphoma: a national cancer data base analysis. Leukemia     [PubMed PMID: 30501432]


Roemer MG,Advani RH,Ligon AH,Natkunam Y,Redd RA,Homer H,Connelly CF,Sun HH,Daadi SE,Freeman GJ,Armand P,Chapuy B,de Jong D,Hoppe RT,Neuberg DS,Rodig SJ,Shipp MA, PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 Aug 10     [PubMed PMID: 27069084]


Marafioti T,Hummel M,Foss HD,Laumen H,Korbjuhn P,Anagnostopoulos I,Lammert H,Demel G,Theil J,Wirth T,Stein H, Hodgkin and reed-sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription. Blood. 2000 Feb 15     [PubMed PMID: 10666223]


Keir ME,Butte MJ,Freeman GJ,Sharpe AH, PD-1 and its ligands in tolerance and immunity. Annual review of immunology. 2008;     [PubMed PMID: 18173375]


Weber J, Immune checkpoint proteins: a new therapeutic paradigm for cancer--preclinical background: CTLA-4 and PD-1 blockade. Seminars in oncology. 2010 Oct;     [PubMed PMID: 21074057]


Hinz M,Lemke P,Anagnostopoulos I,Hacker C,Krappmann D,Mathas S,Dörken B,Zenke M,Stein H,Scheidereit C, Nuclear factor kappaB-dependent gene expression profiling of Hodgkin's disease tumor cells, pathogenetic significance, and link to constitutive signal transducer and activator of transcription 5a activity. The Journal of experimental medicine. 2002 Sep 2     [PubMed PMID: 12208876]


Mathas S,Hinz M,Anagnostopoulos I,Krappmann D,Lietz A,Jundt F,Bommert K,Mechta-Grigoriou F,Stein H,Dörken B,Scheidereit C, Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B. The EMBO journal. 2002 Aug 1     [PubMed PMID: 12145210]


Weniger MA,Melzner I,Menz CK,Wegener S,Bucur AJ,Dorsch K,Mattfeldt T,Barth TF,Möller P, Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation. Oncogene. 2006 Apr 27     [PubMed PMID: 16532038]


Green MR,Rodig S,Juszczynski P,Ouyang J,Sinha P,O'Donnell E,Neuberg D,Shipp MA, Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clinical cancer research : an official journal of the American Association for Cancer Research. 2012 Mar 15;     [PubMed PMID: 22271878]


Kube D,Holtick U,Vockerodt M,Ahmadi T,Haier B,Behrmann I,Heinrich PC,Diehl V,Tesch H, STAT3 is constitutively activated in Hodgkin cell lines. Blood. 2001 Aug 1;     [PubMed PMID: 11468177]


Guasparri I,Bubman D,Cesarman E, EBV LMP2A affects LMP1-mediated NF-kappaB signaling and survival of lymphoma cells by regulating TRAF2 expression. Blood. 2008 Apr 1;     [PubMed PMID: 18230756]


Dutton A,Reynolds GM,Dawson CW,Young LS,Murray PG, Constitutive activation of phosphatidyl-inositide 3 kinase contributes to the survival of Hodgkin's lymphoma cells through a mechanism involving Akt kinase and mTOR. The Journal of pathology. 2005 Mar;     [PubMed PMID: 15714459]


Lam N,Sugden B, CD40 and its viral mimic, LMP1: similar means to different ends. Cellular signalling. 2003 Jan     [PubMed PMID: 12401515]


Grewal IS,Flavell RA, The role of CD40 ligand in costimulation and T-cell activation. Immunological reviews. 1996 Oct     [PubMed PMID: 9010720]


Rastelli J,Hömig-Hölzel C,Seagal J,Müller W,Hermann AC,Rajewsky K,Zimber-Strobl U, LMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1. Blood. 2008 Feb 1;     [PubMed PMID: 18006702]


Imbeault M,Ouellet M,Giguère K,Bertin J,Bélanger D,Martin G,Tremblay MJ, Acquisition of host-derived CD40L by HIV-1 in vivo and its functional consequences in the B-cell compartment. Journal of virology. 2011 Mar;     [PubMed PMID: 21177803]


Curreli S,Krishnan S,Reitz M,Lunardi-Iskandar Y,Lafferty MK,Garzino-Demo A,Zella D,Gallo RC,Bryant J, B cell lymphoma in HIV transgenic mice. Retrovirology. 2013 Aug 28;     [PubMed PMID: 23985023]


Vendrame E,Hussain SK,Breen EC,Magpantay LI,Widney DP,Jacobson LP,Variakojis D,Knowlton ER,Bream JH,Ambinder RF,Detels R,Martínez-Maza O, Serum levels of cytokines and biomarkers for inflammation and immune activation, and HIV-associated non-Hodgkin B-cell lymphoma risk. Cancer epidemiology, biomarkers     [PubMed PMID: 24220912]


Martorelli D,Muraro E,Mastorci K,Dal Col J,Faè DA,Furlan C,Giagulli C,Caccuri F,Rusnati M,Fiorentini S,Carbone A,Caruso A,Dolcetti R, A natural HIV p17 protein variant up-regulates the LMP-1 EBV oncoprotein and promotes the growth of EBV-infected B-lymphocytes: implications for EBV-driven lymphomagenesis in the HIV setting. International journal of cancer. 2015 Sep 15;     [PubMed PMID: 25704763]


Slack GW,Ferry JA,Hasserjian RP,Sohani AR,Longtine JA,Harris NL,Zukerberg LR, Lymphocyte depleted Hodgkin lymphoma: an evaluation with immunophenotyping and genetic analysis. Leukemia     [PubMed PMID: 19455461]


Kiliçarslan A,Doğan M,Süngü N,Karakök E,Karabekmez L,Akyol M,Doğan HT, Can Cutting-Needle Biopsy Be an Alternative to Excisional Biopsy in Lymph Node Pathologies? Turk patoloji dergisi. 2017 Feb 4;     [PubMed PMID: 28272688]


Johl A,Lengfelder E,Hiddemann W,Klapper W, Core needle biopsies and surgical excision biopsies in the diagnosis of lymphoma-experience at the Lymph Node Registry Kiel. Annals of hematology. 2016 Aug;     [PubMed PMID: 27236576]


Hehn ST,Grogan TM,Miller TP, Utility of fine-needle aspiration as a diagnostic technique in lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004 Aug 1;     [PubMed PMID: 15284254]


Caraway NP, Strategies to diagnose lymphoproliferative disorders by fine-needle aspiration by using ancillary studies. Cancer. 2005 Dec 25;     [PubMed PMID: 16222688]


Bednaruk-Młyński E,Pieńkowska J,Skórzak A,Małkowski B,Kulikowski W,Subocz E,Dzietczenia J,Zalewska M,Leśniewski-Kmak K,Zaucha R,Wróbel T,Zaucha JM, Comparison of positron emission tomography/computed tomography with classical contrast-enhanced computed tomography in the initial staging of Hodgkin lymphoma. Leukemia & lymphoma. 2015 Feb     [PubMed PMID: 24794802]


Barrington SF,Kirkwood AA,Franceschetto A,Fulham MJ,Roberts TH,Almquist H,Brun E,Hjorthaug K,Viney ZN,Pike LC,Federico M,Luminari S,Radford J,Trotman J,Fosså A,Berkahn L,Molin D,D'Amore F,Sinclair DA,Smith P,O'Doherty MJ,Stevens L,Johnson PW, PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study. Blood. 2016 Mar 24     [PubMed PMID: 26747247]


Blodgett TM,Ames JT,Torok FS,McCook BM,Meltzer CC, Diffuse bone marrow uptake on whole-body F-18 fluorodeoxyglucose positron emission tomography in a patient taking recombinant erythropoietin. Clinical nuclear medicine. 2004 Mar     [PubMed PMID: 15162984]


Cheson BD,Fisher RI,Barrington SF,Cavalli F,Schwartz LH,Zucca E,Lister TA, Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014 Sep 20;     [PubMed PMID: 25113753]


Shanbhag S,Ambinder RF, Hodgkin lymphoma: A review and update on recent progress. CA: a cancer journal for clinicians. 2018 Mar     [PubMed PMID: 29194581]


Hoppe RT,Advani RH,Ai WZ,Ambinder RF,Aoun P,Bello CM,Benitez CM,Bernat K,Bierman PJ,Blum KA,Chen R,Dabaja B,Forero A,Gordon LI,Hernandez-Ilizaliturri FJ,Hochberg EP,Huang J,Johnston PB,Kaminski MS,Kenkre VP,Khan N,Maloney DG,Mauch PM,Metzger M,Moore JO,Morgan D,Moskowitz CH,Mulroney C,Poppe M,Rabinovitch R,Seropian S,Smith M,Winter JN,Yahalom J,Burns J,Ogba N,Sundar H, Hodgkin Lymphoma Version 1.2017, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN. 2017 May     [PubMed PMID: 28476741]


Tubiana M,Henry-Amar M,Hayat M,Burgers M,Qasim M,Somers R,Sizoo W,Van der Schueren E, Prognostic significance of the number of involved areas in the early stages of Hodgkin's disease. Cancer. 1984 Sep 1     [PubMed PMID: 6378359]


Henry-Amar M,Friedman S,Hayat M,Somers R,Meerwaldt JH,Carde P,Burgers JM,Thomas J,Monconduit M,Noordijk EM, Erythrocyte sedimentation rate predicts early relapse and survival in early-stage Hodgkin disease. The EORTC Lymphoma Cooperative Group. Annals of internal medicine. 1991 Mar 1     [PubMed PMID: 1992877]


Moccia AA,Donaldson J,Chhanabhai M,Hoskins PJ,Klasa RJ,Savage KJ,Shenkier TN,Slack GW,Skinnider B,Gascoyne RD,Connors JM,Sehn LH, International Prognostic Score in advanced-stage Hodgkin's lymphoma: altered utility in the modern era. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012 Sep 20     [PubMed PMID: 22869887]


Papakonstantinou I,Kosmidou M,Papathanasiou K,Koumpis E,Kapsali E,Milionis H,Vassilakopoulos TP,Papoudou-Bai A,Hatzimichael E, Paraneoplastic Intrahepatic Cholestasis in Supradiaphragmatic Classical Hodgkin Lymphoma Successfully Treated With Brentuximab Vedotin: A Case Report and Review of the Literature. In vivo (Athens, Greece). 2021 Jul-Aug;     [PubMed PMID: 34182468]


Engert A,Plütschow A,Eich HT,Lohri A,Dörken B,Borchmann P,Berger B,Greil R,Willborn KC,Wilhelm M,Debus J,Eble MJ,Sökler M,Ho A,Rank A,Ganser A,Trümper L,Bokemeyer C,Kirchner H,Schubert J,Král Z,Fuchs M,Müller-Hermelink HK,Müller RP,Diehl V, Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. The New England journal of medicine. 2010 Aug 12     [PubMed PMID: 20818855]


Eich HT,Diehl V,Görgen H,Pabst T,Markova J,Debus J,Ho A,Dörken B,Rank A,Grosu AL,Wiegel T,Karstens JH,Greil R,Willich N,Schmidberger H,Döhner H,Borchmann P,Müller-Hermelink HK,Müller RP,Engert A, Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010 Sep 20     [PubMed PMID: 20713848]


Radford J,Illidge T,Counsell N,Hancock B,Pettengell R,Johnson P,Wimperis J,Culligan D,Popova B,Smith P,McMillan A,Brownell A,Kruger A,Lister A,Hoskin P,O'Doherty M,Barrington S, Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. The New England journal of medicine. 2015 Apr 23     [PubMed PMID: 25901426]


André MPE,Girinsky T,Federico M,Reman O,Fortpied C,Gotti M,Casasnovas O,Brice P,van der Maazen R,Re A,Edeline V,Fermé C,van Imhoff G,Merli F,Bouabdallah R,Sebban C,Specht L,Stamatoullas A,Delarue R,Fiaccadori V,Bellei M,Raveloarivahy T,Versari A,Hutchings M,Meignan M,Raemaekers J, Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017 Jun 1     [PubMed PMID: 28291393]


Böll B,Goergen H,Behringer K,Bröckelmann PJ,Hitz F,Kerkhoff A,Greil R,von Tresckow B,Eichenauer DA,Bürkle C,Borchmann S,Fuchs M,Diehl V,Engert A,Borchmann P, Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016 May 5     [PubMed PMID: 26834240]


Skoetz N,Will A,Monsef I,Brillant C,Engert A,von Tresckow B, Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma. The Cochrane database of systematic reviews. 2017 May 25     [PubMed PMID: 28541603]


Borchmann P,Goergen H,Kobe C,Lohri A,Greil R,Eichenauer DA,Zijlstra JM,Markova J,Meissner J,Feuring-Buske M,Hüttmann A,Dierlamm J,Soekler M,Beck HJ,Willenbacher W,Ludwig WD,Pabst T,Topp MS,Hitz F,Bentz M,Keller UB,Kühnhardt D,Ostermann H,Schmitz N,Hertenstein B,Aulitzky W,Maschmeyer G,Vieler T,Eich H,Baues C,Stein H,Fuchs M,Kuhnert G,Diehl V,Dietlein M,Engert A, PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group. Lancet (London, England). 2018 Dec 23     [PubMed PMID: 29061295]


Connors JM,Jurczak W,Straus DJ,Ansell SM,Kim WS,Gallamini A,Younes A,Alekseev S,Illés Á,Picardi M,Lech-Maranda E,Oki Y,Feldman T,Smolewski P,Savage KJ,Bartlett NL,Walewski J,Chen R,Ramchandren R,Zinzani PL,Cunningham D,Rosta A,Josephson NC,Song E,Sachs J,Liu R,Jolin HA,Huebner D,Radford J, Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. The New England journal of medicine. 2018 Jan 25     [PubMed PMID: 29224502]


Cerci JJ,Pracchia LF,Linardi CC,Pitella FA,Delbeke D,Izaki M,Trindade E,Soares J Jr,Buccheri V,Meneghetti JC, 18F-FDG PET after 2 cycles of ABVD predicts event-free survival in early and advanced Hodgkin lymphoma. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2010 Sep     [PubMed PMID: 20720036]


Barrington SF,Mikhaeel NG,Kostakoglu L,Meignan M,Hutchings M,Müeller SP,Schwartz LH,Zucca E,Fisher RI,Trotman J,Hoekstra OS,Hicks RJ,O'Doherty MJ,Hustinx R,Biggi A,Cheson BD, Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014 Sep 20;     [PubMed PMID: 25113771]


Johnson P,Federico M,Kirkwood A,Fosså A,Berkahn L,Carella A,d'Amore F,Enblad G,Franceschetto A,Fulham M,Luminari S,O'Doherty M,Patrick P,Roberts T,Sidra G,Stevens L,Smith P,Trotman J,Viney Z,Radford J,Barrington S, Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. The New England journal of medicine. 2016 Jun 23     [PubMed PMID: 27332902]


Taparra K,Liu H,Polley MY,Ristow K,Habermann TM,Ansell SM, Bleomycin use in the treatment of Hodgkin lymphoma (HL): toxicity and outcomes in the modern era. Leukemia & lymphoma. 2020 Feb     [PubMed PMID: 31517559]


Zaucha JM,Chauvie S,Zaucha R,Biggii A,Gallamini A, The role of PET/CT in the modern treatment of Hodgkin lymphoma. Cancer treatment reviews. 2019 Jul     [PubMed PMID: 31260900]


Novo M,Nowakowski GS,Habermann TM,Witzig TE,Micallef IN,Johnston PB,Inwards DJ,Botto B,Ristow KM,Young JR,Vitolo U,Ansell SM, Persistent mediastinal FDG uptake on PET-CT after frontline therapy for Hodgkin lymphoma: biopsy, treat or observe? Leukemia & lymphoma. 2020 Feb     [PubMed PMID: 31556355]


Linch DC,Winfield D,Goldstone AH,Moir D,Hancock B,McMillan A,Chopra R,Milligan D,Hudson GV, Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial. Lancet (London, England). 1993 Apr 24     [PubMed PMID: 8096958]


Schmitz N,Pfistner B,Sextro M,Sieber M,Carella AM,Haenel M,Boissevain F,Zschaber R,Müller P,Kirchner H,Lohri A,Decker S,Koch B,Hasenclever D,Goldstone AH,Diehl V, Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet (London, England). 2002 Jun 15     [PubMed PMID: 12086759]


Moskowitz CH,Nademanee A,Masszi T,Agura E,Holowiecki J,Abidi MH,Chen AI,Stiff P,Gianni AM,Carella A,Osmanov D,Bachanova V,Sweetenham J,Sureda A,Huebner D,Sievers EL,Chi A,Larsen EK,Hunder NN,Walewski J, Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (London, England). 2015 May 9     [PubMed PMID: 25796459]


Kaloyannidis P,Hertzberg M,Webb K,Zomas A,Schrover R,Hurst M,Jacob I,Nikoglou T,Connors JM, Brentuximab vedotin for the treatment of patients with relapsed or refractory Hodgkin lymphoma after autologous stem cell transplantation. British journal of haematology. 2020 Feb     [PubMed PMID: 31588564]


Armand P,Engert A,Younes A,Fanale M,Santoro A,Zinzani PL,Timmerman JM,Collins GP,Ramchandren R,Cohen JB,De Boer JP,Kuruvilla J,Savage KJ,Trneny M,Shipp MA,Kato K,Sumbul A,Farsaci B,Ansell SM, Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018 May 10     [PubMed PMID: 29584546]


Chen R,Zinzani PL,Lee HJ,Armand P,Johnson NA,Brice P,Radford J,Ribrag V,Molin D,Vassilakopoulos TP,Tomita A,von Tresckow B,Shipp MA,Lin J,Kim E,Nahar A,Balakumaran A,Moskowitz CH, Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019 Oct 3     [PubMed PMID: 31409671]


Sureda A,Robinson S,Canals C,Carella AM,Boogaerts MA,Caballero D,Hunter AE,Kanz L,Slavin S,Cornelissen JJ,Gramatzki M,Niederwieser D,Russell NH,Schmitz N, Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008 Jan 20     [PubMed PMID: 18086796]


Gaudio F,Mazza P,Carella AM,Mele A,Palazzo G,Pisapia G,Carluccio P,Pastore D,Cascavilla N,Specchia G,Pavone V, Outcomes of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin Lymphomas: A Retrospective Multicenter Experience by the Rete Ematologica Pugliese (REP). Clinical lymphoma, myeloma & leukemia. 2019 Jan     [PubMed PMID: 30293754]


Bertoglio P,Lomangino I,Querzoli G,Bonalumi A,Bogina GS,Terzi AC, Primary Hodgkin lymphoma of the lung arising with hemoptysis and pulmonary consolidation: a case report. Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace. 2021 Jun 10;     [PubMed PMID: 34121376]


Swerdlow AJ,Higgins CD,Smith P,Cunningham D,Hancock BW,Horwich A,Hoskin PJ,Lister TA,Radford JA,Rohatiner AZ,Linch DC, Second cancer risk after chemotherapy for Hodgkin's lymphoma: a collaborative British cohort study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011 Nov 1     [PubMed PMID: 21969511]


Franklin J,Pluetschow A,Paus M,Specht L,Anselmo AP,Aviles A,Biti G,Bogatyreva T,Bonadonna G,Brillant C,Cavalieri E,Diehl V,Eghbali H,Fermé C,Henry-Amar M,Hoppe R,Howard S,Meyer R,Niedzwiecki D,Pavlovsky S,Radford J,Raemaekers J,Ryder D,Schiller P,Shakhtarina S,Valagussa P,Wilimas J,Yahalom J, Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials. Annals of oncology : official journal of the European Society for Medical Oncology. 2006 Dec     [PubMed PMID: 16984979]


Aleman BM,van den Belt-Dusebout AW,De Bruin ML,van 't Veer MB,Baaijens MH,de Boer JP,Hart AA,Klokman WJ,Kuenen MA,Ouwens GM,Bartelink H,van Leeuwen FE, Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood. 2007 Mar 1     [PubMed PMID: 17119114]


Mauch P,Ng A,Aleman B,Carde P,Constine L,Diehl V,Dinshaw K,Gospodarowicz M,Hancock S,Hodgson D,Hoppe R,Liang R,Loeffler M,Specht L,Travis LB,Wirth A,Yahalom J, Report from the Rockefellar Foundation Sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9-16, 2003, Bellagio, Italy. European journal of haematology. Supplementum. 2005 Jul     [PubMed PMID: 16007872]


Behringer K,Breuer K,Reineke T,May M,Nogova L,Klimm B,Schmitz T,Wildt L,Diehl V,Engert A, Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin's Lymphoma Study Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005 Oct 20     [PubMed PMID: 16234521]


van der Kaaij MA,Heutte N,Le Stang N,Raemaekers JM,Simons AH,Carde P,Noordijk EM,Fermé C,Thomas J,Eghbali H,Kluin-Nelemans HC,Henry-Amar M, Gonadal function in males after chemotherapy for early-stage Hodgkin's lymphoma treated in four subsequent trials by the European Organisation for Research and Treatment of Cancer: EORTC Lymphoma Group and the Groupe d'Etude des Lymphomes de l'Adulte. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2007 Jul 1     [PubMed PMID: 17515571]