Prospective Study on Incidence, Risk Factors, and  Long-Term Outcome of Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia

Winkel, M.L. te; Pieters, Rob; Hop, Wim C. J.; Groot-Kruseman, Hester A. de; Lequin, Maarten H.; Sluis, Inge M. van der; Bökkerink, J.P.M.; Leeuw, Jan A.; Bruin, Marrie C.A.; Egeler, R. Maarten; Veerman, A. J. P.; Heuvel‐Eibrink, Marry M. van den

doi:10.1200/jco.2011.37.3217

Cited by 137 publications

(182 citation statements)

References 31 publications

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“…15 The controversy concerning incidence rate appears to be the consequence of retrospective studies. 3,12 In our study, the overall incidence of ON was 1.2%, although this percentage has to be reinterpreted in relation to the three levels of risk and gender. In fact, the incidence was 0 in the standard-risk patients, 2% for intermediaterisk patients, and 3% for patients classified as high-risk.…”

Section: Discussionmentioning

confidence: 94%

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Osteonecrosis as a complication in pediatric patients with acute lymphoblastic leukemia

et al. 2016

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Osteonecrosis is a significant adverse effect of treatment administered to children suffering from acute lymphoblastic leukemia (ALL) that may have a negative effect on the quality of life. The purpose of this study is to evaluate the rate of secondary vascular osteonecrosis (ON) in a population of pediatric patients with ALL treated with corticosteroids and cytostatic agents. A retrospective analysis of prospectively collected data of the medical records of 328 patients with ALL identified 4 cases with ON, corresponding to 1.2% of all cases observed. Of the 4 patients identified in our study 3 were girls and 1 was a boy, aged from 10 to 16 years old (average age at diagnosis, 12 years). Median time between the diagnosis of ALL and ON was 12.5 months (range, 12 to 36 months). Regarding the lesion size of ON, in all cases the femoral head (monolateral in 1 case and bilateral in 3 cases) was involved and was associated with the scapula-humeral joint in one case. ON of the weight-bearing joints has been identified as a severe complication in children with leukemia that may be associated with the development of articular surface collapse, subsequent debilitating arthritis, sometimes needing arthroplasty. For this reason it is very important to implement prevention strategies, especially in adolescent girls treated with steroids and chemotherapy. An early diagnosis of ON and careful orthopedic follow-up are necessary in order to avoid bone deformations related to the late start or the wrong therapy.

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Section: Discussionmentioning

confidence: 94%

“…12 Recent studies Article demonstrate a constant and growing attention to these issues and the need to better define the causes and possible correlations with treatment regimens. 13 It is still unclear the progression of ON, the risk factors and the incidence rate.…”

Section: Discussionmentioning

confidence: 99%

Osteonecrosis as a complication in pediatric patients with acute lymphoblastic leukemia

et al. 2016

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“…corticosteroids 23 and folate antagonists, 24 irradiation, physical inactivity, and nutritional deficiencies. 25 Although osteonecrosis and BMD loss have been extensively investigated during and after treatment of pediatric ALL, 6,[15][16][17] it is unknown whether these two osteogenic side effects occur together in individual ALL patients, or whether they may aggravate each other's development.…”

Section: Introductionmentioning

confidence: 99%

“…6,7,26 Our aim was to examine whether osteonecrosis and BMD decline occur together and whether these two osteogenic side-effects Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence each other's development.…”

Section: Introductionmentioning

confidence: 99%

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Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia

den¹,

Pluijm²,

Fiocco³

et al. 2015

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ABSTRACTmay influence each other's development during treatment for pediatric ALL. Methods Study populationThis study is based on a subset of a previously described cohort. The children (4-18 years old) had newly diagnosed ALL and were treated in The Netherlands according to the Dutch Childhood Oncology Group (DCOG) -ALL9 protocol between January 1997 and November 2004.17,26 As previously described, patients were stratified into a non-high-risk treatment group and a high-risk group. 26 Briefly, high-risk criteria were: white blood cell count higher than 50×10 9

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Final results of a single institution experience with a pediatric‐based regimen, the augmented Berlin–Frankfurt–Münster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper‐CVAD regimen

et al. 2016

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Several studies reported improved outcomes of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric-based ALL regimens. This prompted the prospective investigation of a pediatric Augmented Berlin–Frankfurt–Münster (ABFM) regimen, and its comparison with hyper-fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone (hyper-CVAD) in AYA patients. One hundred and six AYA patients (median age 22 years) with Philadelphia chromosome- (Ph) negative ALL received ABFM from October 2006 through March 2014. Their outcome was compared to 102 AYA patients (median age 27 years), treated with hyper-CVAD at our institution. The complete remission (CR) rate was 93% with ABFM and 98% with hyper-CVAD. The 5-year complete remission duration (CRD) were 53 and 55%, respectively (P = 0.98). The 5-year overall survival (OS) rates were 60 and 60%, respectively. The MRD status on Day 29 and Day 84 of therapy was predictive of long-term outcomes on both ABFM and hyper-CVAD. Severe regimen toxicities with ABFM included hepatotoxicity in 41%, pancreatitis in 11%, osteonecrosis in 9%, and thrombosis in 19%. Myelosuppression-associated complications were most significant with hyper-CVAD. In summary, ABFM and hyper-CVAD resulted in similar efficacy outcomes, but were associated with different toxicity profiles, asparaginase-related with ABFM and myelosuppression-related with hyper-CVAD.

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Prospective Study on Incidence, Risk Factors, and Long-Term Outcome of Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia

Abstract: Six percent of pediatric patients with ALL developed symptomatic osteonecrosis during or shortly after treatment. Older age and female sex were risk factors. After a median follow-up of 5 years, 60% of patients had persistent symptoms.

Cited by 137 publications

References 31 publications

Osteonecrosis as a complication in pediatric patients with acute lymphoblastic leukemia

Osteonecrosis as a complication in pediatric patients with acute lymphoblastic leukemia

Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia

Final results of a single institution experience with a pediatric‐based regimen, the augmented Berlin–Frankfurt–Münster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper‐CVAD regimen

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