Osteonecrosis in Paediatric Patients with Acute Lymphoblastic Leukaemia Treated on Co-ALL-07-03 Trial: a Single Centre Analysis

M. Kuhlen; A. Moldovan; K. Krull; R. Meisel; A. Borkhardt

doi:10.1055/s-0033-1358723

Klin Padiatr 2014; 226(03): 154-160
DOI: 10.1055/s-0033-1358723

Original Article

Osteonecrosis in Paediatric Patients with Acute Lymphoblastic Leukaemia Treated on Co-ALL-07-03 Trial: a Single Centre Analysis

Osteonekrosen bei pädiatrischen Patienten mit akuter lymphoblastischer Leukämie behandelt gemäß der CoALL 07-03-Studie: Eine monozentrische Analyse

M. Kuhlen

¹Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Centre for Child and Adolescent Health, Medical Faculty, Heinrich-Heine-University, Duesseldorf

,

A. Moldovan

²St. Rochus-Hospital, Clinic for Gynaecology and Obstetrics, Castrop-Rauxel, Germany

,

K. Krull

¹Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Centre for Child and Adolescent Health, Medical Faculty, Heinrich-Heine-University, Duesseldorf

,

R. Meisel

¹Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Centre for Child and Adolescent Health, Medical Faculty, Heinrich-Heine-University, Duesseldorf

,

A. Borkhardt

¹Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Centre for Child and Adolescent Health, Medical Faculty, Heinrich-Heine-University, Duesseldorf

› Institutsangaben

Abstract

Background: Osteonecroses (ON) are a serious problem after anti-leukaemic treatment in childhood and critically depend on treatment intensity. We analysed ON incidence, risk factors and outcome in patients (pts) from our institution treated according to the CoALL 07-03 trial.

Methods: Between 01.09.2003 and 31.12.2009, 124 children aged 1–18 years were treated, 22 pts with ON (ARCO I–IV) were assessed by retrospective chart review. Follow-up data were collected as of March 2013.

Results: 5-year cumulative incidence of ON grade I–IV was 25%. Median age at ALL diagnosis with vs. without ON was 11 years vs. 4.4 years. In logistic multivariate regression analysis, age was the only independent risk factor for ON (p<0.01). 90.9% of the pts with ON presented with ≥2 bilaterally affected joints, most frequent the weight-bearing joints (95.5%). 77.2% developed ON ≥°III acc. to ARCO. 36.4% underwent core decompression, one patient bilateral total hip arthroplasty. As of March 2013, 12 pts still presented with ON-induced symptoms.

Discussion: Our data suggest an overall high incidence of ON in pts treated according to trial CoALL 07-03. Cumulative steroid dose in trial CoALL 07-03 was small, thus, the high CI might be triggered by other treatment-related and study population based risk factors.

Conclusion: ON are a serious problem concerning long-term sequelae with major impact on activities of daily living. Further prospective evaluation is urgently needed to develop risk-adapted diagnostic strategies and preventive and interventional approaches for high-risk pts.

Zusammenfassung

Hintergrund: Osteonekrosen (ON) sind ein schwerwiegendes Problem nach antileukämischer Therapie im Kindesalter und sind wesentlich mit der Therapieintensität assoziiert. Wir haben Inzidenzen, Risikofaktoren und Verlauf von ON bei Patienten, die in unserer Klinik gemäß CoALL-07-03 Protokoll behandelt wurden, untersucht.

Methode: Zwischen 01.09.2003 und 31.12.2009 wurden 124 Patienten zwischen 1–18 Jahren behandelt. 22 Patienten mit nachgewiesenen ON (ARCO I–IV) wurden mittels retrospektiver Aktenrecherche analysiert. ON-Verlauf und -Folgen wurden bis Stand März 2013 erhoben.

Ergebnisse: Die kumulative 5-Jahres Inzidenz für ON betrug 25%. Das mediane Alter mit und ohne ON betrug 11 vs. 4,4 Jahre. Das Alter wurde als einziger unabhängiger Risikofaktor für das Auftreten von ON identifiziert (p<0,01). 90,9% der Patienten präsentierten sich mit ≥2, bilateral betroffenen Gelenken, vor allem der gewichtstragenden Gelenke (95,5%). 77,2% entwickelten ON ≥°III. 36,4% mussten sich einer Anbohrung mit oder ohne autologer Zellgabe unterziehen, eine Patientin erhielt beidseits Hüftendoprothesen. Stand März 2013 zeigten 12 anhaltende ON-assoziierte Symptome.

Diskussion: Unsere Daten zeigen eine hohe ON-Inzidenz bei nach CoALL 07-03 Protokoll behandelten Patienten. Die kumulativen Steroiddosen waren niedrig, sodass für die hohe CI insbesondere bei jungen Patienten andere behandlungsassoziierte und Studien populationsbasierte Risikofaktoren zu diskutieren sind.

Schlussfolgerung: ON sind ein schwerwiegendes Spätfolgenproblem mit erheblichen Auswirkungen auf das tägliche Leben. Prospektive Untersuchungen zur Entwicklung von risikoadaptierten Diagnostikstrategien sowie präventive und interventionelle Ansätze zur Behandlung dieser Hochrisikopatienten werden dringend benötigt.

Key words

osteonecrosis - children - acute lymphoblastic leukaemia - incidence

Schlüsselwörter

Osteonekrose - Kinder - akute lymphoblastische Leukämie - Inzidenz

Volltext

Referenzen

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