Symptomatic Osteonecrosis as a Treatment Complication in Hodgkin Lymphoma

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Though osteonecrosis has been previously studied in childhood ALL, it has not been evaluated as a side effect of treatment for Hodgkin lymphoma.
Though osteonecrosis has been previously studied in childhood ALL, it has not been evaluated as a side effect of treatment for Hodgkin lymphoma.

Osteonecrosis is a pertinent long-term complication of Hodgkin lymphoma (HL) treatment that regularly requires surgical intervention for appropriate management, according to a study published in Leukemia.

Many HL patients can be cured with first-line treatment developed in recent years, causing the focus of clinical research in HL to shift toward the reduction of long-term sequelae after treatment. Avascular osteonecrosis is a potentially devastating long-term treatment complication that has not been studied as comprehensively in HL as it has been in other diseases, such as childhood acute lymphoblastic leukemia.

To study the incidence, risk factors, and timing of osteonecrosis in HL, the authors of this study actively followed 11,330 patients with HL who had been treated within the German Hodgkin Study Group trials HD10-15 or HD 18. Of these patients, 5611 had early-stage HL and 5719 had advanced-stage HL.

Follow-up visits were scheduled every 3 months for the first year after treatment, every 6 months for the second to fifth year after treatment, and once a year thereafter. Secondary outcomes included localization, intervention, and outcome of osteonecrosis.

The researchers categorized the affected areas for each case of osteonecrosis as well as the number of affected areas for each patient with osteonecrosis. The researchers also classified the treatment received by each patient as conservative or surgical and the severity of each patient's symptoms by NCI CTCAE V 4.0 grades. Finally, the researchers analyzed the total dose of prednisone, a corticosteroid, administered to each patient during the clinical trials.

The cumulative incidence of osteonecrosis was found to be 0.2% in early-stage HL (11/5611 patients) and 1.0% in advanced-stage HL (55/5719 patients). Most patients had 2 affected areas, and the femoral head and proximal femur were the most frequently affected area. Symptom severity was almost evenly distributed between NCI CTCAE V 4.0 grade 2 and 3 (45.5% vs 54.5%), and 83.3% of osteonecrosis cases occurred within 3 years after chemotherapy initiation.

The researchers found corticosteroid dose to be the most harmful risk factor for osteonecrosis, with early-stage HL patients receiving 0.8 g total prednisone and advanced-stage HL patients receiving 6.8 g total prednisone. Male gender conferred additional risk of osteonecrosis; 2980 patients with early-stage HL (53.1%) and 3481 advanced-stage patients (60.9%) were male.

The researchers suggested that attempts should be made to reduce corticosteroid dose for patients with HL. They concluded that “[osteonecrosis] is not common enough in the HL population to warrant regular screening” but that “clinicians should be aware of [osteonecrosis]…and evaluate patients with suggestive symptoms with appropriate methods.”

Reference

1. Borchmann S, Muller H, Haverkamp H, et al. Symptomatic osteonecrosis as a treatment complication in Hodgkin lymphoma: an analysis of the German Hodgkin Study Group (GHSG) [published online August 21, 2018]. Leukemia. doi: 10.1038/s41375-018-0240-8

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