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Ankle osteonecrosis in fifty-one children and adolescent’s leukemia survivors: a prospective randomized study on percutaneous mesenchymal stem cells treatment

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Abstract

Purpose

Corticoid treatment associated with haematologic treatments can lead to ankle osteonecrosis in children’s survivors of acute leukemia (ALL). Based on the efficiency of mesenchymal stem cells (MSCs) in hip osteonecrosis, we performed an evaluation of this treatment in 51 children and adolescents who had symptomatic ankle osteonecrosis after therapy for haematologic cancer.

Material and methods

The 51 patients had a total of 79 osteonecrosis sites on MRI, with 29 talus sites, 18 metaphyseal tibia sites, 12 epiphyseal tibia sites, eight calcaneus sites, six fibula sites, four navicular sites, and two cuboid sites. In this prospective randomized trial, 37 ankles were addressed for cell therapy, 37 others for core decompression alone, and 20 were considered as a control group without treatment. We analyzed the outcome of this treatment osteonecrosis, the number and characteristics of bone marrow mesenchymal cells (MSCs) that could be transplanted, and the risks of tumorigenesis in these patients with haematologic cancers. The patients were operated on over a period of ten years from 2000 to 2010 and were monitored through December 31, 2019.

Results

Despite a normal systemic blood cells count, MSCs in the iliac crest (counted as CFU-F) were in low number (1021 MSCs/mL; range 314–3015) and were of host origin after even allogeneic bone marrow transplantation. Better clinical outcomes (pain, foot and ankle deformity) and osteonecrosis repair on MRI with absence of collapse were obtained in ankles that received cell therapy as compared with those with core decompression alone or those without initial surgery. No tumour was found on MRI at the sites of injection and this study found no increased risk of recurrence or of new cancer in this population after an average follow-up of 15 years.

Conclusions

These results suggest that autologous MSCs can improve the quality of life of leukemia survivors with ankle osteonecrosis.

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Data availability

Data are in Henri Mondor Hospital.

References

  1. Ribeiro RC, Fletcher BD, Kennedy W, Harrison PL, Neel MD, Kaste SC, Sandlund JT, Rubnitz JE, Razzouk BI, Relling MV, Pui CH (2001) 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 15(6):891–897

    Article  CAS  Google Scholar 

  2. Chollet CT, Britton L, Neel MD, Hudson MM, Kaste SC (2005) Childhood cancer survivors: an at-risk cohort for ankle osteonecrosis. ClinOrthop Relat Res 430:149–55

  3. Chollet CT, Britton L, Neel MD, Hudson MM, Kaste SC (2005) Childhood cancer survivors: an at-risk cohort for ankle osteonecrosis. ClinOrthop Relat Res 430:149–155

    Article  CAS  Google Scholar 

  4. Kitaoka HB, Patzer GL (1998) Arthrodesis for the treatment of arthrosis of the ankle and osteonecrosis of the talus. J Bone Joint Surg Am 80(3):370–9

    Article  CAS  Google Scholar 

  5. Manes HR, Alvarez E, Llevine LS (1977) Preliminary report of total ankle arthroplasty for osteonecrosis of the talus. Clin Orthop Relat Res 127:200–202

  6. Mody R, Li S, Dover DC, Sallan S, Leisenring W, Oeffinger KC, Yasui Y, Robison LL, Neglia JP (2008) Twenty-five-year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Blood 111(12):5515–23. https://doi.org/10.1182/blood-2007-10-117150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Coluzzi F, Rocco M, Green Gladden R, Persiani P, Thur LA, Milano F (2020) Pain management in childhood leukemia: diagnosis and available analgesic treatments. Cancers (Basel) 12(12):3671. https://doi.org/10.3390/cancers12123671

    Article  CAS  Google Scholar 

  8. Te Winkel ML, Pieters R, Wind EJ, Bessems JH, van den Heuvel-Eibrink MM (2014) Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia. Haematologica 99(3):430–436

    Article  Google Scholar 

  9. Hernigou P, Dubory A, FlouzatLachaniette CH, Khaled I, Chevallier N, Rouard H (2018) Stem cell therapy in early post-traumatic talus osteonecrosis. Int Orthop 42(12):2949–2956. https://doi.org/10.1007/s00264-017-3716-7

    Article  PubMed  Google Scholar 

  10. Flouzat-Lachaniette CH, Roubineau F, Heyberger C, Bouthors C, Hernigou P (2016) Multifocal osteonecrosis related to corticosteroid: ten years later, risk of progression and observation of subsequent new osteonecroses. Int Orthop 40(4):669–72. https://doi.org/10.1007/s00264-015-3060-8

    Article  PubMed  Google Scholar 

  11. Ippolito D, Masetto A, Franzesi CT et al (2016) Lower-limb MRI in the staging and re-staging of osteonecrosis in paediatric patients affected by acute lymphoblastic leukaemia after therapy. Skeletal Radiol 45(4):495–503

    Article  CAS  Google Scholar 

  12. Hernigou P, Flouzat-Lachaniette CH, Daltro G, Galacteros F (2016) Talar osteonecrosis related to adult sickle cell disease: natural evolution from early to late stages. J Bone Joint Surg Am 98(13):1113–21. https://doi.org/10.2106/JBJS.15.01074

    Article  PubMed  Google Scholar 

  13. Hernigou P (2020) Bone marrow in orthopaedics (part II): a three hundred and seventy million-year saga from the Devonian to the coronavirus disease 2019 pandemic-osteonecrosis; transplantation; “human chimera”; stem cells, bioreactors, and coronavirus disease. Int Orthop 44(12):2787–2805. https://doi.org/10.1007/s00264-020-04843-z

    Article  PubMed  Google Scholar 

  14. Cilloni D, Carlo-Stella C, Falzetti F et al (2000) Limited engraftment capacity of bone marrow-derived mesenchymal cells following T-cell-depleted hematopoietic stem cell transplantation. Blood 96:3637–3643

    Article  CAS  Google Scholar 

  15. Mazur JM, Schwartz E, Simon SR (1979) Ankle arthrodesis. Long-term follow-up with gait analysis. J Bone Joint Surg Am 61(7):964–75

    Article  CAS  Google Scholar 

  16. Hernigou P, Homma Y, Flouzat-Lachaniette CH, Poignard A, Chevallier N, Rouard H (2013) Cancer risk is not increased in patients treated for orthopaedic diseases with autologous bone marrow cell concentrate. J Bone Joint Surg Am 95(24):2215–21. https://doi.org/10.2106/JBJS.M.00261

    Article  PubMed  Google Scholar 

  17. Dixon SB, Chen Y, Yasui Y, Pui CH, Hunger SP, Silverman LB, Ness KK, Green DM, Howell RM, Leisenring WM, Kadan-Lottick NS, Krull KR, Oeffinger KC, Neglia JP, Mertens AC, Hudson MM, Robison LL, Armstrong GT, Nathan PC (2020) Reduced morbidity and mortality in survivors of childhood acute lymphoblastic leukemia: a report from the childhood cancer survivor study. J Clin Oncol. 38(29):3418–3429. https://doi.org/10.1200/JCO.20.00493

    Article  PubMed  Google Scholar 

  18. Mulrooney DA, Hyun G, Ness KK et al (2019) The changing burden of long-term health outcomes in survivors of childhood acute lymphoblastic leukaemia: a retrospective analysis of the St Jude Lifetime Cohort Study. Lancet Haematol 6:e306–e316

    Article  Google Scholar 

  19. Girard P, Auquier P, Barlogis V et al (2013) Symptomatic osteonecrosis in childhood leukemia survivors: prevalence, risk factors and impact on quality of life in adulthood. Haematologica 98(7):1089–1097

    Article  CAS  Google Scholar 

  20. te Winkel ML, Pieters R, Wind EJD, Gert Bessems JHJM, van den Heuvel- Eibrink MM (2014) Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia. Haematologica 99:430–436

    Article  Google Scholar 

  21. Hernigou P, Flouzat-Lachaniette CH, Delambre J, Poignard A, Allain J, Chevallier N, Rouard H (2015) Osteonecrosis repair with bone marrow cell therapies: state of the clinical art. Bone 70:102–9. https://doi.org/10.1016/j.bone.2014.04.034

    Article  PubMed  Google Scholar 

  22. Gómez-Barrena E, Padilla-Eguiluz NG, Rosset P, Hernigou P, Baldini N, Ciapetti G, Gonzalo-Daganzo RM, Avendaño-Solá C, Rouard H, Giordano R, Dominici M, Schrezenmeier H, Layrolle P, On Behalf Of The Reborne Consortium (2021) Osteonecrosis of the femoral head safely healed with autologous, expanded, bone marrow-derived mesenchymal stromal cells in a multicentric trial with minimum 5 years follow-up. J Clin Med 10(3):508–10.3390/jcm10030508

    Article  Google Scholar 

  23. Hernigou P, FlouzatLachaniette CH, Delambre J, Chevallier N, Rouard H (2014) Regenerative therapy with mesenchymal stem cells at the site of malignant primary bone tumour resection: what are the risks of early or late local recurrence? Int Orthop 38(9):1825–35. https://doi.org/10.1007/s00264-014-2384-0

    Article  PubMed  Google Scholar 

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Authors and Affiliations

Authors

Contributions

PH: surgery, data collection, and redaction; JC A: statistics; AD: surgery; CH FL: surgery; HR: cell therapy.

Corresponding author

Correspondence to Philippe Hernigou.

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All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Hernigou, P., Auregan, J.C., Dubory, A. et al. Ankle osteonecrosis in fifty-one children and adolescent’s leukemia survivors: a prospective randomized study on percutaneous mesenchymal stem cells treatment. International Orthopaedics (SICOT) 45, 2383–2393 (2021). https://doi.org/10.1007/s00264-021-05051-z

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