Bisphosphonate treatment in children with acute lymphoblastic leukemia and osteonecrosis - radiological and clinical findings in a national cohort.

Background: Osteonecrosis (ON) is a recognized complication of childhood ALL, but its optimal management remains unestablished. This study evaluated the effect of bisphosphonate (BP) treatment on the evolution of ON lesions in childhood ALL.Material and Methods: We included a national cohort of ALL patients diagnosed with symptomatic ON before 18 years of age and treated with BPs (N = 10; five males). Patients were followed both clinically and with serial MRIs. ON lesions were graded according to the Niinimäki classification.Results: The 10 patients had a total of 55 ON lesions. The median age was 13.3 years at ALL diagnosis and 14.8 years at ON diagnosis. Four patients had received HSCT before the ON diagnosis. BPs used were pamidronate (N = 7), alendronate (N = 2) and ibandronate (N = 1). The duration of BP treatment varied between 4 months and 4 years. In 4/10 patients, BP treatment was given during the chemotherapy. BPs were well-tolerated, with no severe complications or changes in kidney function. At the end of follow up 13/55 (24%) ON lesions were completely healed both clinically and radiographically; all these lesions were originally graded 3 or less. In contrast, ON lesions originally classified as grade 5 (joint destruction; N = 4) remained at grade 5. All grade 5 hip joint lesions needed surgical treatment. During BP treatment, the pain was relieved in 7/10 patients. At the end of follow-up, none of the patients reported severe or frequent pain.Conclusion: BP treatment was safe and seemed effective in relieving ON-induced pain in childhood ALL. After articular collapse (grade 5) lesions did not improve with BP treatment. Randomized controlled studies are needed to further elucidate the role of BPs in childhood ALL-associated ON.

Young patients with hematologic and lymphatic malignancies have an increased risk of hip and knee arthroplasty.

Background Skeletal complications such as osteonecrosis (ON) are potential adverse events in patients treated for cancer, especially in those treated for hematologic and lymphatic malignancies (HLMs). ON may damage the hip or knee joints and may lead to arthrosis requiring total joint arthroplasty (TJA). The aim of this study was to address the risk of TJA in patients with cancer, especially those treated for HLM, in a nationwide population-based setting. Material and methods All patients who had undergone TJA after cancer diagnosis between the years 2000 and 2012 were identified by linking the Arthroplasty Register and the Cancer Registry. Standardized incidence ratios (SIRs) of TJAs were calculated to assess whether patients with any cancer, but especially HLM, have increased risk for TJA when compared with the general population. Results In patients with HLM or other cancer, the overall SIRs were similar compared with the general population. However, in HLM patients under 50 years of age, the SIR was 7.6, and in patients under 35 years of age, it was 45.5. The corresponding SIRs in patients with other cancers were 3.6 and 6.6, respectively. The highest SIRs, including all age groups, were among patients with acute lymphoblastic leukemia (SIR = 4.5) and acute myeloid leukemia (SIR = 1.9). Discussion HLMs imply an increased risk for TJA compared with the general population. The risk is especially high in patients younger than 50 years, regardless of the type of HLM. Young patients with HLM, as well as their healthcare providers, should be aware of the highly increased risk of skeletal complications requiring TJA.

Osteonecrosis in children treated for lymphoma or solid tumors.

PURPOSE: The purpose of this study was to find out the incidence of and clinical risk factors for magnetic resonance imaging (MRI)-detected osteonecrosis (ON) in children treated for lymphoma or solid tumors. PATIENTS AND METHODS: The development of ON was studied in 32 childhood cancer patients who underwent MRI scanning of the lower extremities at the end of their treatment. The underlying malignancy was Wilms tumor in 8 patients, non-Hodgkin lymphoma (NHL) in 8, Hodgkin disease (HD) in 7, rhabdomyosarcoma in 6, and other occasional solid tumors in 3 patients. RESULTS: Six of the 32 patients (19%) had ON. The mean age of the patients with ON at diagnosis was 12.7 years compared with 5.8 years for the patients without ON (P<0.001). All the patients with ON had either HD (4 patients) or NHL (2 patients). Two (33%) of the patients with ON were symptomatic. CONCLUSIONS: ON in MRI was found to be a common complication in children after treatment for HD or NHL. The risk for ON seems to be very low in patients with other solid tumors even when they receive high cumulative doses of dexamethasone.

High body mass index increases the risk for osteonecrosis in children with acute lymphoblastic leukemia.

PURPOSE: The aim of the study was to determine the incidence of and clinical risk factors for radiographic osteonecrosis (ON) in children treated for acute lymphoblastic leukemia (ALL) using the Nordic ALL protocols. PATIENTS AND METHODS: Ninety-seven consecutive patients with childhood ALL were studied prospectively by magnetic resonance imaging (MRI) of the lower extremities at the end of the treatment. RESULTS: Twenty-three (24%) of the 97 patients had ON. Seven of the patients (30%) were symptomatic, and three patients (13%) required surgical interventions. Multiple logistic regression analysis showed that high body mass index (BMI; P = .04), female sex (P = .01), older age at diagnosis (P < .001), and higher cumulative dexamethasone dose (P = .03) were independent risk factors for radiographic ON. The cumulative prednisone dose did not differ significantly between the patients with and without ON. The incidence of radiographic ON decreased significantly, from 36% to 7%, when the duration of dexamethasone exposure during the delayed-intensification phase was shortened from 3 to 4 weeks to 2 weeks with a taper (P = .001). CONCLUSION: ON as determined by MRI was found to be a common complication in children and adolescents after treatment with the Nordic ALL protocols. Revision of the ALL protocols by shortening the single exposure to dexamethasone has diminished the risk for ON remarkably. High BMI was identified as a new significant risk factor for ON.