Osteonecrosis in Korean Paediatric and Young Adults with Acute Lymphoblastic Leukaemia or Lymphoblastic Lymphoma: A Nationwide Epidemiological Study

Abstract

Osteonecrosis (ON) is a serious complication of acute lymphocytic leukaemia (ALL) or lymphoblastic lymphoma (LBL) treatment, and there is little information regarding ON in Korean paediatric and young adult patients. This retrospective cohort study assessed the cumulative incidence of and risk factors for ON using national health insurance claims data from 2008 to 2019 in 4861 ALL/LBL patients. The Kaplan-Meier method was used to estimate the cumulative incidence of ON according to age groups; the Cox proportional hazard regression model was used to identify risk factors related to ON development after diagnosing ALL/LBL. A cause-specific hazard model with time-varying covariates was used to assess the effects of risk factors. Overall, 158 (3.25%) patients were diagnosed with ON, among whom 23 underwent orthopaedic surgeries. Older age, radiotherapy (HR = 2.62, 95% confidence interval (CI) 1.87-3.66), HSCT (HR = 2.40, 95% CI 1.74-3.31), steroid use and anthracycline use (HR = 2.76, CI 1.85-4.14) were related to ON in the univariate analysis. In the multivariate analysis, age and steroid and asparaginase use (HR = 1.99, CI 1.30-3.06) were factors associated with ON. These results suggest that Korean patients with ALL/LBL who used steroids and asparaginase should be closely monitored during follow-up, even among young adult patients.

Keywords: Republic of Korea; acute lymphoblastic leukemia; adolescent and young adult; lymphoblastic lymphoma; osteonecrosis.

Figure 1

Participant enrolment flow diagram. Among 8056 participants, 4861 with ALL/LBL were included in the study. A total of 2967 patients were excluded owing to the washout period.

Figure 2

Age at diagnosis with and without ON among (A) total patients and (B) paediatric patients. (A) The mean age of patients without ON was 14.73 years, and that of patients with ON was 19.41 years (p < 0.0001). (B) The mean age of paediatric patients without ON was 8.20 years, and that of paediatric patients with ON was 13.28 years (p < 0.0001). Dashed horizontal lines reflect the median age at diagnosis of two groups.

Figure 2

Age at diagnosis with and without ON among (A) total patients and (B) paediatric patients. (A) The mean age of patients without ON was 14.73 years, and that of patients with ON was 19.41 years (p < 0.0001). (B) The mean age of paediatric patients without ON was 8.20 years, and that of paediatric patients with ON was 13.28 years (p < 0.0001). Dashed horizontal lines reflect the median age at diagnosis of two groups.

Figure 3

Cumulative incidence of ON according to age at the diagnosis of ALL/LBL in 4861 patients. (A) A 10-year scale, (B) 5-year scale (C) by age and sex. (A) During 10–20-years, the highest CI was noted, and during 15–20 years, patients had the highest CI (B). Girls showed higher CI than boys (C).

Figure 3

Cumulative incidence of ON according to age at the diagnosis of ALL/LBL in 4861 patients. (A) A 10-year scale, (B) 5-year scale (C) by age and sex. (A) During 10–20-years, the highest CI was noted, and during 15–20 years, patients had the highest CI (B). Girls showed higher CI than boys (C).

Figure 3

Cumulative incidence of ON according to age at the diagnosis of ALL/LBL in 4861 patients. (A) A 10-year scale, (B) 5-year scale (C) by age and sex. (A) During 10–20-years, the highest CI was noted, and during 15–20 years, patients had the highest CI (B). Girls showed higher CI than boys (C).

Figure 4

Time from ALL/LBL diagnosis to ON diagnosis. Time from cancer treatment to ON diagnosis was 2.54 (±1.74) years after ALL or LBL diagnosis in all patients. Approximately 90% of patients were diagnosed as having ON in 5 years after primary cancer. (Blue line: Paediatric group (2.69 ± 1.77 years), Red line: Adult group (2.33 ± 1.68 years)).