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Osteonekrosen – gravierende Therapiefolge bei akuter lymphoblastischer Leukämie

Osteonecrosis—severe side effect of treatment for acute lymphoblastic leukemia

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Zusammenfassung

Osteonekrosen treten als schwerwiegende Komplikation bei Kindern, Jugendlichen und Erwachsenen mit akuter lymphoblastischer Leukämie akut unter Therapie aber auch als Spätfolge auf. Diese gehen mit starken Schmerzen, Einschränkungen der Mobilität, Gelenkdestruktion und erheblicher Langzeitmorbidität einher. Die kumulative Inzidenz bei Jugendlichen und jungen Erwachsenen beträgt 11–20 %. Bei symptomatischen Patienten sind häufig multiple Gelenke betroffen, die multiple Gelenkbeteiligung ist ein Risikofaktor für einen schweren Verlauf. Leukämieassoziierte Osteonekrosen haben eine multifaktorielle Genese. Risikofaktoren umfassen v. a. die Gabe von Kortikosteroiden und Asparaginase. Diese verursachen eine Hypertriglyzeridämie, Hypercholesterolämie und arterielle Hypertonie, die die Blutzufuhr zum Knochen beeinträchtigen können. Weitere Risikofaktoren sind Bakteriämien, genetische Faktoren und eine Stammzelltransplantation. Die Therapie ist herausfordernd und bisher nicht evidenzbasiert, präventive Ansätze wurden bisher vor allem in präklinischen Modellen getestet.

Abstract

Osteonecrosis occurs as an acute and long-term serious side effect in children, adolescents, and adults with acute lymphoblastic leukemia. It is associated with severe pain and reduced mobility, ultimately leading to joint destruction and significant long-term morbidity. The cumulative incidence ranges from 11 to 20% in adolescents and young adults. In symptomatic patients, multiple joints are frequently affected, which in turns poses a risk factor for the development of severe osteonecrosis. The genesis of leukemia-associated osteonecrosis is multifactorial. Risk factors include the use of corticosteroids and asparaginase. These exert their effects on the blood supply to the bone through hypercholesterolemia, hypertriglyceridemia, and hypertension. Bacteriemia, genetic susceptibility, and stem cell transplantation pose additional risk factors. The treatment of osteonecrosis is challenging and not evidence based. Preventive measurements have as yet mainly been tested in preclinical models.

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Abbreviations

ALL:

Akute lymphoblastische Leukämie

BFM :

Berlin-Frankfurt-Münster-Studiengruppe

CCG :

Children’s Cancer Group

DFCI :

Dana-Farber Cancer Institute

ECOG :

Eastern Cooperative Oncology Group

NOPHO :

Nordic Society of Pediatric Hematology and Oncology

SNV :

Einzelnukleotid-Polymorphismen

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Förderung

Die OPAL-Studie wurde durch die Deutsche Kinderkrebsstiftung (DKS 2011.11) gefördert.

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Authors and Affiliations

  1. Schwäbisches Kinderkrebszentrum, Kinder- und Jugendmedizin, Medizinische Fakultät, Universität Augsburg, Stenglinstr. 2, 86156, Augsburg, Deutschland

    Michaela Kuhlen

  2. Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Universitätskinderklinik, Magdeburg, Deutschland

    Marina Kunstreich

  3. Medizinische Klinik II, Hämatologie/Onkologie, Universitätsklinikum Frankfurt/Main, Frankfurt/Main, Deutschland

    Nicola Gökbuget

  4. Klinik für Pädiatrische Hämatologie und Onkologie, Universitätskinderklinik Hamburg-Eppendorf, Hamburg, Deutschland

    Gabriele Escherich

Authors
  1. Michaela Kuhlen
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  2. Marina Kunstreich
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  3. Nicola Gökbuget
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  4. Gabriele Escherich
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Corresponding author

Correspondence to Michaela Kuhlen.

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Interessenkonflikt

M. Kuhlen, M. Kunstreich, N. Gökbuget und G. Escherich geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autorinnen durchgeführten Studien an Menschen oder Tieren. Die OPAL-Studie wurde durch die Ethikkommission der Medizinischen Fakultät der Heinrich-Heine-Universität Düsseldorf (Nr. 3707) und durch die zuständige Ethikkommission der Ludwig-Maximilians-Universität München (Nr. 20-140) positiv begutachtet.

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Kuhlen, M., Kunstreich, M., Gökbuget, N. et al. Osteonekrosen – gravierende Therapiefolge bei akuter lymphoblastischer Leukämie. Orthopädie 51, 792–799 (2022). https://doi.org/10.1007/s00132-022-04301-1

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