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Acute Leukemias

High incidence of avascular necrosis in adolescents with acute lymphoblastic leukaemia: a UKALL XII analysis

Leukemia volume 22, pages 308–312 (2008)Cite this article

Abstract

Avascular necrosis (AVN) is a serious complication of acute lymphoblastic leukaemia (ALL) therapy. Little is known of the scope and magnitude of this problem among adults with ALL. We analysed the incidence and risk factors for AVN in 1053 patients on the UKALLXII/ECOG2993 study. AVN affected 99 joints in 42 patients at a median of 2.2 years post-diagnosis, giving a crude incidence rate of 4.0%. Statistically significant risk factors for the development of AVN were age and treatment with chemotherapy. Patients receiving prolonged chemotherapy without stem cell transplant were at significantly greater risk of developing AVN than stem cell transplant recipients (P<0.00005). The actuarial incidence of AVN was 29% at 10 years in patients <20 years old compared to 8% at 10 years in those >20 years old; P=0.0004; odds ratio 0.28 (95% CI=0.14–0.56).

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References

  1. Mattano Jr LA, Sather HN, Trigg ME, Nachman JB . Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children's Cancer Group. J Clin Oncol 2000; 18: 3262–3272.

    Article  Google Scholar 

  2. Bomelburg T, von Lengerke HJ, Ritter J . Aseptic osteonecroses in the treatment of childhood acute leukaemias. Eur J Pediatr 1989; 149: 20–23.

    Article  CAS  Google Scholar 

  3. Strauss AJ, Su JT, Dalton VM, Gelber RD, Sallan SE, Silverman LB . Bony morbidity in children treated for acute lymphoblastic leukemia. J Clin Oncol 2001; 19: 3066–3072.

    Article  CAS  Google Scholar 

  4. Gaynon PS, Lustig RH . The use of glucocorticoids in acute lymphoblastic leukemia of childhood. Molecular, cellular, and clinical considerations. J Pediatr Hematol Oncol 1995; 17: 1–12.

    Article  CAS  Google Scholar 

  5. Murphy RG, Greenberg ML . Osteonecrosis in pediatric patients with acute lymphoblastic leukemia. Cancer 1990; 65: 1717–1721.

    Article  CAS  Google Scholar 

  6. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 2005; 106: 3760–3767.

    Article  CAS  Google Scholar 

  7. Lackner H, Benesch M, Moser A, Smolle-Juttner F, Linhart W, Raith J et al. Aseptic osteonecrosis in children and adolescents treated for hemato-oncologic diseases: a 13-year longitudinal observational study. J Pediatr Hematol Oncol 2005; 27: 259–263.

    Article  Google Scholar 

  8. Kenzora JE, Glimcher MJ . Accumulative cell stress: the multifactorial etiology of idiopathic osteonecrosis. Orthop Clin North Am 1985; 16: 669–679.

    CAS  Google Scholar 

  9. Wang CJ, Wang FS, Huang CC, Yang KD, Weng LH, Huang HY . Treatment for osteonecrosis of the femoral head: comparison of extracorporeal shock waves with core decompression and bone-grafting. J Bone Joint Surg Am 2005; 87: 2380–2387.

    Article  Google Scholar 

  10. Ficat RP . Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment. J Bone Joint Surg Br 1985; 67: 3–9.

    Article  CAS  Google Scholar 

  11. Drescher W, Schneider T, Becker C, Hobolth J, Ruther W, Hansen ES et al. Selective reduction of bone blood flow by short-term treatment with high-dose methylprednisolone. An experimental study in pigs. J Bone Joint Surg Br 2001; 83: 274–277.

    Article  CAS  Google Scholar 

  12. Weinstein RS, Nicholas RW, Manolagas SC . Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J Clin Endocrinol Metab 2000; 85: 2907–2912.

    CAS  Google Scholar 

  13. Ruderman RJ, Poehling GG, Gray R, Nardone M, Goodman W, Seigler HF . Orthopedic complications of renal transplantation in children. Transplant Proc 1979; 11: 104–106.

    CAS  Google Scholar 

  14. Haajanen J, Saarinen O, Laasonen L, Kuhlback B, Edgren J, Slatis P . Steroid treatment and aseptic necrosis of the femoral head in renal transplant recipients. Transplant Proc 1984; 16: 1316–1319.

    CAS  Google Scholar 

  15. de Bont JM, Holt B, Dekker AW, van der Does-van den Berg A, Sonneveld P, Pieters R . Significant difference in outcome for adolescents with acute lymphoblastic leukemia treated on pediatric vs adult protocols in the Netherlands. Leukemia 2004; 18: 2032–2035.

    Article  CAS  Google Scholar 

  16. Sather HN, Dodge RK, Bloomfield CD, Larson RA, Nachman J, Stock W . Outcome of adolescents and young adults with ALL: a comparison of Childrens Cancer Group (CCG) and Cancer and Leukaemia Group B (CALGB) regimens. Blood 2007; 96; (Abstract 467a).

  17. Boissel N, Auclerc MF, Lheritier V, Perel Y, Thomas X, Leblanc T et al. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol 2003; 21: 774–780.

    Article  Google Scholar 

  18. Ramanujachar R, Richards S, Hann I, Goldstone A, Mitchell C, Vora A et al. Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer 2007; 48: 254–261.

    Article  Google Scholar 

  19. Ribeiro RC, Fletcher BD, Kennedy W, Harrison PL, Neel MD, Kaste SC et al. Magnetic resonance imaging detection of avascular necrosis of the bone in children receiving intensive prednisone therapy for acute lymphoblastic leukemia or non-Hodgkin lymphoma. Leukemia 2001; 15: 891–897.

    Article  CAS  Google Scholar 

  20. Ribeiro RC, Fletcher BD, Kennedy W, Harrison PL, Neel MD, Kaste SC et al. Magnetic resonance imaging detection of avascular necrosis of the bone in children receiving intensive prednisone therapy for acute lymphoblastic leukemia or non-Hodgkin lymphoma. Leukemia 2001; 15: 891–897.

    Article  CAS  Google Scholar 

  21. Lafforgue P, Dahan E, Chagnaud C, Schiano A, Kasbarian M, Acquaviva PC . Early-stage avascular necrosis of the femoral head: MR imaging for prognosis in 31 cases with at least 2 years of follow-up. Radiology 1993; 187: 199–204.

    Article  CAS  Google Scholar 

  22. Steinberg ME, Bands RE, Parry S, Hoffman E, Chan T, Hartman KM . Does lesion size affect the outcome in avascular necrosis? Clin Orthop Relat Res 1999; 367: 262–271.

    Article  Google Scholar 

  23. Wang GJ, Rawles JG, Hubbard SL, Stamp WG . Steroid-induced femoral head pressure changes and their response to lipid-clearing agents. Clin Orthop Relat Res 1983; 174: 298–302.

    CAS  Google Scholar 

  24. Reis ND, Schwartz O, Militianu D, Ramon Y, Levin D, Norman D et al. Hyperbaric oxygen therapy as a treatment for stage-I avascular necrosis of the femoral head. J Bone Joint Surg Br 2003; 85: 371–375.

    Article  CAS  Google Scholar 

  25. Tauchmanova L, De Rosa G, Serio B, Fazioli F, Mainolfi C, Lombardi G et al. Avascular necrosis in long-term survivors after allogeneic or autologous stem cell transplantation: a single center experience and a review. Cancer 2003; 97: 2453–2461.

    Article  Google Scholar 

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Acknowledgements

AKF is supported by the Leukaemia Research Fund (UK).

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Authors and Affiliations

  1. Department of Haematology, Royal Free and University College Medical School, London, UK

    B Patel & A K Fielding

  2. Clinical Trial Service Unit, Oxford, UK

    S M Richards

  3. Department of Hematology, Rambam Medical Center, Haifa, Israel

    J M Rowe

  4. Technion, Haifa, Israel

    J M Rowe

  5. North London Cancer Network, UCL Hospitals, London, UK

    A H Goldstone

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  1. B Patel
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  2. S M Richards
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  3. J M Rowe
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  4. A H Goldstone
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  5. A K Fielding
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Correspondence to A K Fielding.

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Patel, B., Richards, S., Rowe, J. et al. High incidence of avascular necrosis in adolescents with acute lymphoblastic leukaemia: a UKALL XII analysis. Leukemia 22, 308–312 (2008). https://doi.org/10.1038/sj.leu.2405032

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