Clinical Practice Guideline

for

HODGKIN’S DISEASE

Developed for the

Aerospace Medical Association

by their constituent organization

American Society of Aerospace Medicine Specialists

Overview: Hodgkin’s Disease (HD) is a neoplasm of lymphoid tissue defined histopathologically by the malignant Reed-Sternberg cell. Four histologic types (lymphocyte predominant, nodular sclerosis, mixed cellularity, and lymphocyte depletion) are distinguished on the basis of the appearance and relative proportions of Reed-Sternberg cells, lymphocytes, and fibrosis. The anatomic extent of disease and, to a lesser degree, the histologic subtype are the primary factors determining the presenting features, prognosis, and optimal therapy of HD.

The incidence of HD in the U.S. has been stable over the past decade. About 7,900 cases were diagnosed in 1993, an incidence of 3.2 per 100,000 population. The incidence is higher in men than women, higher in whites than blacks, and shows an increased risk with higher socioeconomic status. Unlike most malignancies, HD has a bimodal age-incidence curve. Rates rise through early life, peaking in the third decade and declining until age 45, after which the incidence increases steadily. The nodular sclerosis subtype predominates in young adults, while the mixed cellularity subtype is more common in the pediatric population and at older ages.

Several large studies have demonstrated a three-fold increased risk for HD with a prior history of serologically confirmed infectious mononucleosis (in particular elevated titers of Epstein-Barr virus). An increased risk for HD among siblings and close relatives supports a genetic basis for increased susceptibility.

The staging of HD is classified using the four-stage Ann Arbor classification. Stage I is involvement of a single lymph node region or extra-lymphatic site. Stage II is involvement of two or more lymph node regions or extra-lymphatic sites on the same side of the diaphragm. Stage III is involvement of lymph node regions on both sides of the diaphragm with or without splenic involvement. Stage IV is diffuse or disseminated involvement of one or more extra-lymphatic organs or tissues. The absence or presence of fever, night sweats, and/or unexplained loss of 10% or more of body weight in the 6 months preceding diagnosis are denoted by the suffix letters A or B.

Treatment for HD may involve radiotherapy, chemotherapy, or both. Radiotherapy is usually delivered in the mantle region (cervical, supraclavicular, infraclavicular, axillary, mediastinal, and hilar nodes), the para-aortic/splenic region, and the pelvic region. Chemotherapy regimes consist of MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) or ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). Recently, bone marrow transplantation has been used as therapy for refractory HD with limited success.

Prognosis varies depending primarily on stage of disease and histologic subtype. For limited-stage disease (Stages I or II), the cure rate after treatment is 85% to 90%. For advanced disease (III or IV) the cure rate ranges from 65% to 85%. Histologic subtypes lymphocyte predominance and nodular sclerosis usually carry a better prognosis than mixed cellularity, which in turn has a better prognosis than lymphocyte depletion. Age greater than 40 years , B systemic symptoms, and extensive tumor burden are other factors that have been repeatedly documented as poor prognostic factors. Relapse after successful treatment occurs in 25% to 40% and greater than 90% of the relapses occur within 2 to 4 years.

Aeromedical Concerns: The risk for sudden incapacitation is minimal as disease involvement of the CNS or heart is rare. Although the most common presentation of HD is a superficial nontender mass, initial manifestations may include hemoptysis (intrathoracic involvement) or neurologic symptoms from spinal cord compression. The greatest concern is for the potentially rapid (weeks to months) degradation in mental and physical status when the HD and/or treatment protocol is aggressive. Damage to the cardiopulmonary, neurologic, endocrine, and reticuloendothelial systems may occur as a result of the disease or therapy.

Treatment and Aeromedical Disposition: Initial presentation, as a minimum, should include CBC, CXR, ECG, PFT, and Hematology/Oncology consultation. The diagnosis will be reviewed by appropriate consultation, such as the AFIP or major cancer center. Additional evaluation should be based on radio-/chemotherapeutic courses given, adequate staging and prognosis. The aviator should be without major symptoms or medication / complication / sequelae that would affect aeromedical safety.

Experience: The USAF aircrew waiver file lists eleven members with HD in remission and nine received waivers (8 of the 9 received FCII waiver). Although these numbers are small, the possibility of returning to flying status after effective treatment of HD is good. Medical certification is not granted during active disease. Generally medical certification is not granted for one year after chemotherapy/radiotherapy treatment. Normally, in civil aviation medical certification is not granted for Stage III or IV disease. Yearly current status evaluations are required for at least 5 yr. after treatment. The way the FAA has its current pathology coding system Hodgkin’s and Non-Hodgkin’s Lymphoma are counted together. As of November 2005, the FAA has granted 121 First-class, 96 Second-class, and 249 Third-class medical certificates.

References:

Eyre HJ. Hodgkin’s Disease. Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN (eds). Wintrobe’s Clinical Hematology 1993; 9:2082-142.

Foon KA, Fisher RI. Lymphoma. Beutler E, Lichtman MA, Coller BS, Kipps TJ (eds). Williams Hematology. 1995; 5:1076-96.

Hartge P, Devesa SS, Fraumeni JF. Hodgkin’s and Non-Hodgkin’s Lymphomas. Cancer 1994; 19-20:423-53.

August 2, 2006