Original Article

Assessing Prognostic Factors in Hodgkin's Lymphoma: Multistate Illness-Death Model


Background: Hodgkin's lymphoma (HL) is a unique cancer of lymphocytes that has unknown reason. As lymphocytes are found throughout the lymphatic system, HL can start almost anywhere in the body. It usually starts in a group of lymph nodes in one part of the body; it usually spreads in a predictable form, from one group of lymph nodes to the next. Eventually, it can spread to almost any tissue or organ in the body through the lymphatic system or the bloodstream. So it's important to evaluate the prognostic factors of mortality and recurrence. The aim of this study is to use multistate model to consider the event history of patients and assess important prognostic factors.
Materials and Methods: We performed a retrospective review on 389 patients with Hodgkin's disease referred to the Oncology and Hematology Center, Shafa Hospital, Ahvaz during 2002 and 2012. An illness – death model was fitted to assess the hazard of transitions during the course of the disease for each prognostic factor.
Results: The results showed that the prevalence rate was higher in male population ≥50 years of age with a hemoglobin level of less than 10.5 g per deciliter and diagnosis of advanced stage of disease. The risk of death for males was twice more than females (HR=2.07). Moreover, patients with mediastina and spleen involvement were more than others in danger of death (1.66 and 1.36, respectively).
Conclusion: In conclusion, the multistate model offers an appropriate method to consider the event history of patients and determine main prognostic factors, which play an important role in rapid diagnosis and choosing the best treatment choice for each patient.


Greenberg MS, Glick M. Burket's Oral Medicine: Diagnosis & Treatment: PMPH-USA; 2003. PP 448-450.

Connors JM. Clinical manifestations and natural history of Hodgkin’s lymphoma. The Cancer Journal. 2009;15(2):124-8.

Ahmadzadeh A, Yekaninejad MS, Jalili MH, et al. Evaluating the survival rate and the secondary malignancies after treating hodgkin's lymphoma patients with chemotherapy regimens. Int J Hematol Oncol Stem Cell Res. 2014; 8(2):21-26.

Asvadi Kermani I, Dehdillani M. Hodgkin’s Disease: Assessment of Treatment and Survival Rates. Rjms. 2005; 12(45):7-14.

Poplack DG, Pizzo DG. Principles and practice of pediatric oncology. 3rd ed: Lippincott-raven. 1997

Hougaard P. Multi-state Models: A Review. Lifetime Data Anal. 1999;5(3):239-64.

Putter H, van der Hage J, de Bock GH, et al. Estimation and prediction in a multi‐state model for breast cancer. Biom J. 2006; 48(3):366-80.

Conlon A, Taylor J, Sargent DJ. Multi‐state models for colon cancer recurrence and death with a cured fraction. Stat Med. 2014; 33(10):1750-66.

Omar RZ, Stallard N, Whitehead J. A parametric multistate model for the analysis of carcinogenicity experiments. Lifetime Data Anal. 1995;1(4):327-46.

Meira-Machado LF, de Uña-Álvarez J, Cadarso-Suárez C, et al. Multi-state models for the analysis of time-to-event data. Stat Methods Med Res. 2009; 18(2):195-222.

Broët P, de la Rochefordière A, Scholl SM, et al. Analyzing prognostic factors in breast cancer using a multistate model. Breast Cancer Res Treat. 1999;54(1):83-9.

Sutradhar R, Barbera L, Seow H, et al. Multistate analysis of interval-censored longitudinal data: application to a cohort study on performance status among patients diagnosed with cancer. Am J Epidemiol. 2011;173(4):468-75.

Brierley JD, Rathmell AJ, Gospodarowicz MK, et al. Late relapse after treatment for clinical stage I and II Hodgkin's disease. Cancer. 1997;79(7):1422-7.

Cuccaro A, Bartolomei F, Cupelli E, et al. Prognostic factors in hodgkin lymphoma. Mediterr J Hematol Infect Dis. 2014; 6(1): e2014053.

Massini G, Siemer D, Hohaus S. EBV in Hodgkin lymphoma. Mediterr J Hematol Infect Dis. 2009; 1(2):2009013.

Diepstra A, van Imhoff GW, Schaapveld M, et al. Latent Epstein-Barr virus infection of tumor cells in classical Hodgkin's lymphoma predicts adverse outcome in older adult patients. J Clin Oncol. 2009;27(23):3815-21.

Jarrett RF, Stark GL, White J, et al. Impact of tumor Epstein-Barr virus status on presenting features and outcome in age-defined subgroups of patients with classic Hodgkin lymphoma: a population-based study. Blood. 2005;106(7):2444-51.

Stark GL, Wood KM, Jack F, et al. Hodgkin's disease in the elderly: a population‐based study. Br J Haematol. 2002; 119(2):432-40.

Moccia AA, Donaldson J, Chhanabhai M, et al. International Prognostic Score in advanced-stage Hodgkin's lymphoma: altered utility in the modern era. J Clin Oncol. 2012; 30(27):3383-8.

Hasenclever D, Diehl V, Armitage JO, et al. A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med. 1998; 339(21):1506-14.

Bierman PJ, Lynch J, Bociek RG, et al. The International Prognostic Factors Project score for advanced Hodgkin’s disease is useful for predicting outcome of autologous hematopoietic stem cell transplantation. Ann Oncol. 2002; 13(9):1370-7.

Bierman PJ, Bagin R, Jagannath S, et al. High dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin's disease: Long term follow-up in 128 patients. Ann Oncol. 1993;4(9):767-73.

Horning SJ, Chao NJ, Negrin RS, et al. High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices. Blood. 1997;89(3):801-13.

Wheeler C, Eickhoff C, Elias A, et al. High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes. Biol Blood Marrow Transplant. 1997; 3(2):98-106.

Brice P, Bouabdallah R, Moreau P, et al. Prognostic factors for survival after high-dose therapy and autologous stem cell transplantation for patients with relapsing Hodgkin’s disease: analysis of 280 patients from the French registry. Bone marrow transplant. 1997; 20(1):21-6.

Lazarus HM, Rowlings PA, Zhang MJ, et al. Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol. 1999; 17(2):534-45.

Sweetenham J, Taghipour G, Milligan D, et al. High-dose therapy and autologous stem cell rescue for patients with Hodgkin’s disease in first relapse after chemotherapy: results from the EBMT. Bone marrow transplant. 1997;20(9):745-52.

Sweetenham JW, Carella AM, Taghipour G, et al. High-dose therapy and autologous stem-cell transplantation for adult patients with Hodgkin's disease who do not enter remission after induction chemotherapy: results in 175 patients reported to the European Group for Blood and Marrow Transplantation. J Clin Oncol.1999; 17(10):3101-9.

Sureda A, Arranz R, Iriondo A, et al. Autologous stem-cell transplantation for Hodgkin’s disease: results and prognostic factors in 494 patients from the Grupo Espanol de Linfomas/Transplante Autologo de Medula Osea Spanish Cooperative Group. J Clin Oncol. 2001; 19(5):1395-404.

MacLennan KA, Vaughan Hudson B, Easterling MJ, et al. The presentation haemoglobin level in 1103 patients with Hodgkin's disease (BNLI report no. 21). Clin Radiol. 1983;34(5):491-5.

Lumley M, Milligan D, Knechtli C, et al. High lactate dehydrogenase level is associated with an adverse outlook in autografting for Hodgkin's disease. Bone marrow transplant. 1996;17(3):383-8.

Aalen O, Borgan O, Gjessing H. Survival and event history analysis: a process point of view: Springer Science & Business Media; 2008. PP 18 - 25.

IssueVol 12, No 1 (2018) QRcode
SectionOriginal Article(s)
Hodgkin's lymphoma Multistate model Prognostic factors Markov illness-death model

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How to Cite
Javanmardi F, Saki-Malehi A, Ahmadzadeh A, Rahim F. Assessing Prognostic Factors in Hodgkin’s Lymphoma: Multistate Illness-Death Model. Int J Hematol Oncol Stem Cell Res. 2018;12(1):57-64.