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Acute lymphoblastic leukemia in children: correlation of musculoskeletal manifestations and immunophenotypes

  • Original Clinical Article
  • Published:
Journal of Children's Orthopaedics

Abstract

Purpose

Studies on musculoskeletal manifestations (MSM) of childhood acute lymphoblastic leukemia (ALL) have yielded variable findings with regard to their clinical impact. We investigated the significance for differential diagnosis, treatment and outcome of musculoskeletal complaints as presenting symptoms of ALL, and their correlation with leukemia immunophenotypes, for which data is lacking.

Methods

Data on 783 children in the national study for childhood ALL between 1984 and 2003 were reviewed retrospectively. Statistical analysis examined possible relationships between MSM at the time of diagnosis and demographic and clinical data, biological features of leukemia (peripheral blood counts, immunophenotype and main cytogenetic aberration), response to initial prednisone treatment, and outcome.

Results

Of 765 children with data on orthopaedic complaints, 240 presented with MSM (31.4%). Among these children, B cell precursor (BCP) was much more common (209/576, 36.3%) than T cell ALL (25/176, 14.2%). Patients with MSM had lower white blood cell counts (WBC) (median of 9 vs. 20 × 109/L, P < 0.001) and percentage of blast cells in the peripheral blood at diagnosis compared to those without (median of 27 vs. 53%, P < 0.001). Hepatomegaly and splenomegaly were less common in MSM group (67 vs. 53% <3 cm, P < 0.001, and 63 vs. 50% <3 cm, P < 0.001, respectively). Poor response to initial treatment with prednisone was recorded in 7.1% of patients with MSM versus 11.5% of those without (P = 0.086). The analysis revealed no independent effect of MSM on event-free survival (EFS), after correcting for differences in EFS related to immunophenotype or initial WBC.

Conclusions

MSM occur mostly in children with BCP ALL who present with less involvement of extramedullary organs, low peripheral blood blasts and white blood cells counts. These findings highlight the importance of including ALL in the differential diagnosis of MSM even in the presence of an apparently normal peripheral blood count. Our study also suggests that MSM are caused by leukemic cells with enhanced biological propensity to remain relatively confined within the intramedullary bone-marrow space.

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Acknowledgments

This study was partially funded by the Israel Cancer Association and The Goldberg Family Chair in Pediatric Surgery, Sackler Faculty of Medicine, Tel Aviv University—Incumbent: Prof. Shlomo Wientroub. The commitment of the principal investigators in The Israeli National Childhood ALL Study Group has been greatly appreciated: Dina Attias, M.D., Bnai Zion Medical Center, Haifa; Gali Avrahami, M.D., and Batia Stark, M.D., Schnieder Children’s Medical Center, Petah Tiqva; Ami Ballin, M.D., Edith Wolfson Medical Center, Holon; Bella Bielorai, M.D., and Shai Izraeli, M.D., Chaim Sheba Medical Center, Tel Hashomer; Yoav Burstein, M.D., Dana Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv; Ronit Elhasid, M.D., Rambam Medical Center, Haifa; Gabriel Herzel, M.D., Ha’Emek Medical Center, Afula; Yosef Kapelushnik, M.D., Soroka Medical Center, Beer Sheva; Hagit Miskin, M.D., Shaare Zedek Medical Center, Jerusalem; Dalia Sthoeger, M.D., Kaplan Medical Center, Rehovot; Michael Weintraub, M.D., Hadassah University Hospital, Jerusalem. We thank Galli Pen and Dina Kugel for maintaining the INS database, and Irina Opincariu for editing the manuscript.

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Authors and Affiliations

  1. Department of Pediatric Orthopaedics, Dana Children’s Hospital, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, Tel Aviv, 62439, Israel

    Eran Maman & Shlomo Wientroub

  2. Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel

    David M. Steinberg

  3. Pediatric Hematology Oncology Center, Schneider Children’s Medical Center, Petach-Tikva, Israel

    Batia Stark

  4. Pediatric Hemato-Oncology, Safra Children’s Hospital, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel

    Shai Izraeli

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  1. Eran Maman
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  2. David M. Steinberg
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  3. Batia Stark
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  5. Shlomo Wientroub
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Correspondence to Eran Maman.

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Maman, E., Steinberg, D.M., Stark, B. et al. Acute lymphoblastic leukemia in children: correlation of musculoskeletal manifestations and immunophenotypes. J Child Orthop 1, 63–68 (2007). https://doi.org/10.1007/s11832-007-0013-9

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  • DOI: https://doi.org/10.1007/s11832-007-0013-9

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