Treatment of nodular lymphocyte-predominant Hodgkin lymphoma
- Peter M Mauch, MD
Peter M Mauch, MD
- Professor of Radiation Oncology
- Harvard Medical School
- Ann S LaCasce, MD
Ann S LaCasce, MD
- Associate Professor of Medicine
- Harvard Medical School
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma (HL). This disorder is differentiated from all other forms of HL, which are commonly referred to as classical Hodgkin lymphomas (CHL), by characteristic pathologic and clinical features.
NLPHL represents a more indolent disease than CHL, and therefore is managed uniquely. Since this disease is rare, most information concerning treatment and outcome has come from reports of single institutions or pooled, multi-institutional retrospective analyses.
Treatment and prognosis of NLPHL are reviewed here. The epidemiology, pathogenesis, clinical presentation, pathology, and diagnosis of NLPHL are discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma".) Treatment of the other Hodgkin lymphoma subtypes is discussed separately.
After the diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is confirmed, the patient should undergo a work-up and staging evaluation similar to that performed for patients with classical Hodgkin lymphomas (CHL). Staging is performed using the Ann Arbor staging system with Cotswolds modifications (table 1) [1,2]. This system is described at length separately. (See "Staging and prognosis of Hodgkin lymphoma" and "Clinical manifestations, pathologic features, and diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma".)
Historically, patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have been treated like patients with classical Hodgkin lymphomas (CHL), and many of the large randomized studies that have guided treatment of patients with CHL have included small numbers of patients with NLPHL. NLPHL differs from CHL in terms of natural history, response to treatment, and prognosis , and therapeutic approaches may be distinct from CHL. Our approach is generally consistent with that proposed by the National Comprehensive Cancer Network (NCCN) .
- Carbone PP, Kaplan HS, Musshoff K, et al. Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res 1971; 31:1860.
- Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 1989; 7:1630.
- Nogová L, Reineke T, Brillant C, et al. Lymphocyte-predominant and classical Hodgkin's lymphoma: a comprehensive analysis from the German Hodgkin Study Group. J Clin Oncol 2008; 26:434.
- http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf (Accessed on April 01, 2014).
- Miettinen M, Franssila KO, Saxén E. Hodgkin's disease, lymphocytic predominance nodular. Increased risk for subsequent non-Hodgkin's lymphomas. Cancer 1983; 51:2293.
- Hansmann ML, Zwingers T, Böske A, et al. Clinical features of nodular paragranuloma (Hodgkin's disease, lymphocyte predominance type, nodular). J Cancer Res Clin Oncol 1984; 108:321.
- Pellegrino B, Terrier-Lacombe MJ, Oberlin O, et al. Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology. J Clin Oncol 2003; 21:2948.
- Murphy SB, Morgan ER, Katzenstein HM, Kletzel M. Results of little or no treatment for lymphocyte-predominant Hodgkin disease in children and adolescents. J Pediatr Hematol Oncol 2003; 25:684.
- Mauz-Körholz C, Gorde-Grosjean S, Hasenclever D, et al. Resection alone in 58 children with limited stage, lymphocyte-predominant Hodgkin lymphoma-experience from the European network group on pediatric Hodgkin lymphoma. Cancer 2007; 110:179.
- Appel BE, Chen L, Buxton AB, et al. Minimal Treatment of Low-Risk, Pediatric Lymphocyte-Predominant Hodgkin Lymphoma: A Report From the Children's Oncology Group. J Clin Oncol 2016; 34:2372.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- Wirth A, Yuen K, Barton M, et al. Long-term outcome after radiotherapy alone for lymphocyte-predominant Hodgkin lymphoma: a retrospective multicenter study of the Australasian Radiation Oncology Lymphoma Group. Cancer 2005; 104:1221.
- Hall GW, Katzilakis N, Pinkerton CR, et al. Outcome of children with nodular lymphocyte predominant Hodgkin lymphoma - a Children's Cancer and Leukaemia Group report. Br J Haematol 2007; 138:761.
- Chera BS, Olivier K, Morris CG, et al. Clinical presentation and outcomes of lymphocyte-predominant Hodgkin disease at the University of Florida. Am J Clin Oncol 2007; 30:601.
- Haas RL, Girinsky T, Aleman BM, et al. Low-dose involved-field radiotherapy as alternative treatment of nodular lymphocyte predominance Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys 2009; 74:1199.
- Chen RC, Chin MS, Ng AK, et al. Early-stage, lymphocyte-predominant Hodgkin's lymphoma: patient outcomes from a large, single-institution series with long follow-up. J Clin Oncol 2010; 28:136.
- Eichenauer DA, Plütschow A, Fuchs M, et al. Long-Term Course of Patients With Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Report From the German Hodgkin Study Group. J Clin Oncol 2015; 33:2857.
- Bodis S, Kraus MD, Pinkus G, et al. Clinical presentation and outcome in lymphocyte-predominant Hodgkin's disease. J Clin Oncol 1997; 15:3060.
- Regula DP Jr, Hoppe RT, Weiss LM. Nodular and diffuse types of lymphocyte predominance Hodgkin's disease. N Engl J Med 1988; 318:214.
- Schlembach PJ, Wilder RB, Jones D, et al. Radiotherapy alone for lymphocyte-predominant Hodgkin's disease. Cancer J 2002; 8:377.
- Yahalom J, Mauch P. The involved field is back: issues in delineating the radiation field in Hodgkin's disease. Ann Oncol 2002; 13 Suppl 1:79.
- Specht L, Yahalom J, Illidge T, et al. Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Biol Phys 2014; 89:854.
- Diehl V, Sextro M, Franklin J, et al. Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease. J Clin Oncol 1999; 17:776.
- Nogová L, Reineke T, Eich HT, et al. Extended field radiotherapy, combined modality treatment or involved field radiotherapy for patients with stage IA lymphocyte-predominant Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG). Ann Oncol 2005; 16:1683.
- Wilder RB, Schlembach PJ, Jones D, et al. European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease. Cancer 2002; 94:1731.
- Engert A, Franklin J, Eich HT, et al. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol 2007; 25:3495.
- Savage KJ, Skinnider B, Al-Mansour M, et al. Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood 2011; 118:4585.
- van Grotel M, Lam KH, de Man R, et al. High relapse rate in children with non-advanced nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL or nodular paragranuloma) treated with chemotherapy only. Leuk Lymphoma 2006; 47:1504.
- Canellos GP, Mauch P. What is the appropriate systemic chemotherapy for lymphocyte-predominant Hodgkin's lymphoma? J Clin Oncol 2010; 28:e8.
- Biasoli I, Stamatoullas A, Meignin V, et al. Nodular, lymphocyte-predominant Hodgkin lymphoma: a long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the Adult Lymphoma Study Group. Cancer 2010; 116:631.
- Jackson C, Sirohi B, Cunningham D, et al. Lymphocyte-predominant Hodgkin lymphoma--clinical features and treatment outcomes from a 30-year experience. Ann Oncol 2010; 21:2061.
- Borg-Grech A, Radford JA, Crowther D, et al. A comparative study of the nodular and diffuse variants of lymphocyte-predominant Hodgkin's disease. J Clin Oncol 1989; 7:1303.
- Pappa VI, Norton AJ, Gupta RK, et al. Nodular type of lymphocyte predominant Hodgkin's disease. A clinical study of 50 cases. Ann Oncol 1995; 6:559.
- Crennan E, D'Costa I, Liew KH, et al. Lymphocyte predominant Hodgkin's disease: a clinicopathologic comparative study of histologic and immunophenotypic subtypes. Int J Radiat Oncol Biol Phys 1995; 31:333.
- Orlandi E, Lazzarino M, Brusamolino E, et al. Nodular lymphocyte predominance Hodgkin's disease: long-term observation reveals a continuous pattern of recurrence. Leuk Lymphoma 1997; 26:359.
- Ha CS, Kavadi V, Dimopoulos MA, et al. Hodgkin's disease with lymphocyte predominance: long-term results based on current histopathologic criteria. Int J Radiat Oncol Biol Phys 1999; 43:329.
- Feugier P, Labouyrie E, Djeridane M, et al. Comparison of initial characteristics and long-term outcome of patients with lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma at clinical stages IA and IIA prospectively treated by brief anthracycline-based chemotherapies plus extended high-dose irradiation. Blood 2004; 104:2675.
- Trudel MA, Krikorian JG, Neiman RS. Lymphocyte predominance Hodgkin's disease. A clinicopathologic reassessment. Cancer 1987; 59:99.
- Tefferi A, Zellers RA, Banks PM, et al. Clinical correlates of distinct immunophenotypic and histologic subcategories of lymphocyte-predominance Hodgkin's disease. J Clin Oncol 1990; 8:1959.
- Friedman DL, Constine LS. Late effects of treatment for Hodgkin lymphoma. J Natl Compr Canc Netw 2006; 4:249.
- Hancock SL, Hoppe RT. Long-Term Complications of Treatment and Causes of Mortality After Hodgkin's Disease. Semin Radiat Oncol 1996; 6:225.
- Zsófia M, Katalin K, Judit V, et al. What is the price of survival in Hodgkin's lymphoma? Long-term follow-up of cured patients. Hematol Oncol 2007; 25:178.
- Fanale MA, Lai CM, McLaughlin P, et al. Outcomes of nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL) patients treated with R-CHOP [abstract]. Blood (ASH Annual Meeting Abstracts) 2010; 116:2812.
- Xing KH, Connors JM, Lai A, et al. Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis. Blood 2014; 123:3567.
- Rehwald U, Schulz H, Reiser M, et al. Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody rituximab is effective and well tolerated: results of a phase 2 trial of the German Hodgkin Lymphoma Study Group. Blood 2003; 101:420.
- Schulz H, Rehwald U, Morschhauser F, et al. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood 2008; 111:109.
- Eichenauer DA, Fuchs M, Pluetschow A, et al. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood 2011; 118:4363.
- Ekstrand BC, Lucas JB, Horwitz SM, et al. Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood 2003; 101:4285.
- Advani RH, Horning SJ, Hoppe RT, et al. Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol 2014; 32:912.
- Karuturi M, Hosing C, Fanale M, et al. High-dose chemotherapy and autologous stem cell transplantation for nodular lymphocyte-predominant Hodgkin lymphoma. Biol Blood Marrow Transplant 2013; 19:991.
- Nogová L, Reineke T, Josting A, et al. Lymphocyte-predominant and classical Hodgkin's lymphoma--comparison of outcomes. Eur J Haematol Suppl 2005; :106.
- Hartmann S, Eichenauer DA, Plütschow A, et al. The prognostic impact of variant histology in nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG). Blood 2013; 122:4246.
- Küppers R, Rajewsky K, Zhao M, et al. Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci U S A 1994; 91:10962.
- Tamaru J, Hummel M, Zemlin M, et al. Hodgkin's disease with a B-cell phenotype often shows a VDJ rearrangement and somatic mutations in the VH genes. Blood 1994; 84:708.
- Delabie J, Tierens A, Wu G, et al. Lymphocyte predominance Hodgkin's disease: lineage and clonality determination using a single-cell assay. Blood 1994; 84:3291.
- Coleman M, Kaufmann T, Nisce LZ, Leonard JP. Treatment of nonlaparotomized (clinical) stage I and II Hodgkin's disease patients by extended field and splenic irradiation. Int J Radiat Oncol Biol Phys 2000; 46:1235.
- Chan WC. Cellular origin of nodular lymphocyte-predominant Hodgkin's lymphoma: immunophenotypic and molecular studies. Semin Hematol 1999; 36:242.
- Kenderian SS, Habermann TM, Macon WR, et al. Large B-cell transformation in nodular lymphocyte-predominant Hodgkin lymphoma: 40-year experience from a single institution. Blood 2016; 127:1960.
- Al-Mansour M, Connors JM, Gascoyne RD, et al. Transformation to aggressive lymphoma in nodular lymphocyte-predominant Hodgkin's lymphoma. J Clin Oncol 2010; 28:793.
- Braeuninger A, Küppers R, Strickler JG, et al. Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells. Proc Natl Acad Sci U S A 1997; 94:9337.
- Huang JZ, Weisenburger DD, Vose JM, et al. Diffuse large B-cell lymphoma arising in nodular lymphocyte predominant Hodgkin lymphoma: a report of 21 cases from the Nebraska Lymphoma Study Group. Leuk Lymphoma 2004; 45:1551.
- STAGE IA/IIA DISEASE
- Natural history
- Surgical excision alone
- Radiation therapy
- - Reduced volume RT
- - RT technique
- RT with or without chemotherapy
- Chemotherapy alone
- Recurrent disease
- Treatment related complications
- STAGE IB/IIB DISEASE
- STAGE III/IV DISEASE
- Combination chemotherapy
- Palliative RT
- Relapsed/refractory disease
- Impact of histopathology
- Transformation to NHL
- SUMMARY AND RECOMMENDATIONS