Skeletal Disorders as Late Complications in Hodgkin Lymphoma Survivors

Background: Long-term complications of musculoskeletal system are rare in adult Hodgkin lymphoma (HL) survivors, thus is uncertain whether these complications are treatment-related.

Aim: The goal of this study was to analyze risk, frequency and type of skeletal damage in HL survivors.

Methods: The study comprises of a retrospective analysis of 170 patients (pts) suffered from HL, and treated in an oncological center in Poland between 1979–2005. There were 88 females and 82 males, median age 30.5 years (range 16–72). According to the Ann Arbor clinical staging system there were 22 cases (12.5%) in CSI, 95 cases (55.8%) in CSII, 26 cases (15.4%) in CSIII and 27 cases (15.8%) in CSIV. Fifty six percent of the patients presented B-symptoms, and 60% had bulky disease. Vast majority of cases were diagnosed as classical HL, with histologic subtypes of nodular sclerosis grade 1 in 45%, nodular sclerosis grade 2 in 14%, mixed cellularity in 21%, lymphocyte depletion in 5.2%, and lymphocyte-rich in 7%. However 5.8% of the cases were unclassified by a histopathologist. Chemotherapy with a median of 6 cycles/patient was given to 93.5% of cases (ABVD – 29.4%, MOPP/ABV – 37.6%, MOPP – 24.1%, other – 2.25%). Chemoradiotherapy was given to 61.8% of pts. Radiotherapy alone (mantle-field or involved-field), with a median dose of 40 Gy (range 21–46.8) received 6.5% of pts. For statistical analysis we used Kaplan-Meier method and log-rank test

Results: With a median follow-up of 242 months (range 0–439) a skeletal disorder (SD) was detected in 27 (15.8%) of the patients. Median time to identify SD was 29.5 months. Skeletal disorders were diagnosed as follows: osteoarthritis (11 pts), avascular (aseptic) necrosis of bone (3 pts), osteoporosis (3 pts), osteopenia (3 pts), rheumatoid arthritis (2 pts), vertebral osteochondritis (2 pts), idiopathic (nontraumatic) subluxation of wrist (1 patient), fibrosis of vertebral body (1 patient), and inflammation of nucleus pulposus (1 patient). In the statistical analysis there was no relationship between the risk of SD and: sex, bulky disease, B symptom, involvement of extralymphatic organ, histologic subtype, radiotherapy, chemotherapy, and chemotherapeutic regimen. However, we found an association of SD risk with clinical stage. The difference between CSI and CSIII was statistically significant (p = 0.0235). There were no differences between CSII and CSIII (p = 0.0564), as well as CSIII and CSIV (p = 0.0787).

Conclusions: In our group of adult HL survivors skeletal disorders caused substantial amount of long-term complications. We found no relationship between treatment modality and the risk of a skeletal disorder, despite high median dose of radiotherapy and extensive use of alkylating agents. The association between skeletal disorder and more advanced clinical stage is difficult to explain, however it might suggest a possible role of initial tumor burden and excessive crosstalk between cancer and reactive immune/inflammatory cells.