Is there a risk of early relapse in patients with acute lymphoblastic leukemia presenting with bone-associated symptoms?

Children with bone pain



leukemia, childhood, bone involvement


Background/Aim: Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. Patients usually present with fatigue, pallor, weight loss, and joint and/or bone findings. However, the effects of bone-associated symptoms on prognosis remains controversial. We aimed to demonstrate whether bone-associated symptoms affect prognosis in children with ALL.

Methods: This retrospective cohort study included the data from 268 patients with ALL who were diagnosed and treated between January 2011 and December 2020. The patients were divided into two groups as those with and without bone-associated symptoms. We compared the groups in terms of age, gender, immunophenotyping, day 8 prednisolone response, and risk groups, in addition to minimal residual disease (MRD), relapse, and survival rates.

Results: Eighty-five out of 268 (32%) children had bone-associated symptoms at the time of diagnosis, whereas others (n=183) had none of these symptoms. The relapse rate in children with bone-associated symptoms was found to be higher than the others (17.6% versus 12%), but the difference was not significant (P=0.24). However, children with bone findings developed earlier relapse when compared with the others (18.6 versus 28.6 months; P<0.001).

Conclusion: Therefore, we suggest that bone-associated symptoms at the time of diagnosis could be considered a warning sign for earlier relapse, and these children should be carefully followed.


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Stanulla M, Schrappe M. Treatment of childhood acute lymphoblastic leukemia. In: Seminars in hematology. Elsevier; 2009. p. 52–63. DOI:

Pui CH. Childhood leukemias. 3rd. 2012. DOI:

Zombori L, Kovacs G, Csoka M, Derfalvi B. Rheumatic symptoms in childhood leukaemia and lymphoma-a ten-year retrospective study. Pediatric Rheumatology. 2013;11:1–5. DOI:

Kang S, Im HJ, Bae K, Park S-S. Influence of musculoskeletal manifestations as the only presenting symptom in B-cell acute lymphoblastic leukemia. The Journal of Pediatrics. 2017;182:290–5. DOI:

Sinigaglia R, Gigante C, Bisinella G, Varotto S, Zanesco L, Turra S. Musculoskeletal manifestations in pediatric acute leukemia. J Pediatr Orthop. 2008;28:20–8. DOI:

Apak A, Celkan T, Yıldız I, Zeybek C, Özkan A, Yüksel L, et al. Akut lenfoblastik lösemide iyi prognoz göstergesi; kemik tutulumu. Cocuk Sagligi Hast Derg. 2003;46:275–80.

Maman E, Steinberg DM, Stark B, Izraeli S, Wientroub S. Acute lymphoblastic leukemia in children: correlation of musculoskeletal manifestations and immunophenotypes. Journal of Children’s Orthopaedics. 2007;1:63–8. DOI:

Robazzi TCMV, Barreto JH, Silva LR, Santiago MB, Mendonça N. Osteoarticular manifestations as initial presentation of acute leukemias in children and adolescents in Bahia, Brazil. Journal of pediatric hematology/oncology. 2007;29:622–6. DOI:

Clarke RT, Van den Bruel A, Bankhead C, Mitchell CD, Phillips B, Thompson MJ. Clinical presentation of childhood leukaemia: a systematic review and meta-analysis. Archives of Disease in Childhood. 2016;101:894–901. DOI:

Louvigné M, Rakotonjanahary J, Goumy L, Tavenard A, Brasme J-F, Rialland F, et al. Persistent osteoarticular pain in children: early clinical and laboratory findings suggestive of acute lymphoblastic leukemia (a multicenter case-control study of 147 patients). Pediatric Rheumatology. 2020;18:1–8. DOI:

Révész T, Kardos G, Kajtár P, Schuler D. The adverse effect of prolonged prednisolone pretreatment in children with acute lymphoblastic leukemia. Cancer. 1985;55:1637–40. DOI:<1637::AID-CNCR2820550804>3.0.CO;2-H

Zhou F, Zhang M, Han J, Hao J, Xiao Y, Liu Q, et al. Skeletal abnormalities detected by SPECT is associated with increased relapse risk in pediatric acute lymphoblastic leukemia. Oncotarget. 2017;8:79347. DOI:

Müller HL, Horwitz AE, Kühl J. Acute lymphoblastic leukemia with severe skeletal involvement: a subset of childhood leukemia with a good prognosis. Pediatric Hematology and Oncology. 1998;15:121–33. DOI:

Halton JM, Atkinson SA, Fraher L, Webber CE, Cockshott WP, Tam C, et al. Mineral homeostasis and bone mass at diagnosis in children with acute lymphoblastic leukemia. The Journal of Pediatrics. 1995;126:557–64. DOI:

Tragiannidis A, Vasileiou E, Papageorgiou M, Damianidou L, Hatzipantelis E, Gombakis N, et al. Bone involvement at diagnosis as a predictive factor in children with acute lymphoblastic leukemia. Hippokratia. 2016;20:227.

BK AR, Singh KA, Shah H. Orthopedic manifestation as the presenting symptom of acute lymphoblastic leukemia. Journal of Orthopaedics. 2020;22:326–30. DOI:

Radu L-E, Colita A, Pasca S, Tomuleasa C, Popa C, Serban C, et al. Day 15 and day 33 minimal residual disease assessment for acute lymphoblastic leukemia patients treated according to the BFM ALL IC 2009 protocol: Single-center experience of 133 cases. Frontiers in oncology. 2020;10:923. DOI:






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Temuroğlu A, Güler S, Aksoy GR, Evim MS, Güneş AM. Is there a risk of early relapse in patients with acute lymphoblastic leukemia presenting with bone-associated symptoms? Children with bone pain. J Surg Med [Internet]. 2023 Jan. 17 [cited 2024 May 25];7(1):40-3. Available from: