International Journal of Hematology

, Volume 106, Issue 2, pp 299–303 | Cite as

Successful treatment of histiocytic sarcoma with cladribine and high-dose cytosine arabinoside in a child

  • Haruko Iwabuchi
  • Hiroyuki Kawashima
  • Hajime Umezu
  • Takayuki Takachi
  • Masaru Imamura
  • Akihiko Saitoh
  • Akira Ogose
  • Chihaya ImaiEmail author
Case Report


Histiocytic sarcoma, a rare hematopoietic neoplasm with evidence of histiocytic differentiation, is often refractory to conventional chemotherapy and radiotherapy, and its prognosis is generally dismal. The optimal management of this malignancy has not been established. We report a case of 8-year-old girl with histiocytic sarcoma involving the left femur. The tumor rapidly responded to a combination of cladribine and high-dose cytosine arabinoside, an aggressive salvage regimen for refractory Langerhans cell histiocytosis, and became impalpable during the first cycle. The patient has remained in complete remission more than 7 years from diagnosis.


Histiocytic sarcoma Cladribine Cytosine arabinoside 



We acknowledge the patient and her parents for giving us a written informed consent to the off-label use of the anticancer drugs and publication of this case report. We also acknowledge Drs. Ryosuke Hosokai, Sakiko Yoshida, and Junko Sakurada for patient care.

Compliance with ethical standards

Conflict of interest

CI received patent royalty from Juno Therapeutics. Other authors declare no conflict of interest.


  1. 1.
    Takahashi E, Nakamura S. Histiocytic sarcoma: an updated literature review based on the 2008 WHO classification. J Clin Exp Hematopathol. 2013;53:1–8.CrossRefGoogle Scholar
  2. 2.
    Pileri SA, Grogan TM, Harris NL, Banks P, Campo E, Chan J, et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology. 2002;41:1–29.CrossRefPubMedGoogle Scholar
  3. 3.
    Shukla N, Kobos R, Renaud T, Teruya-Feldstein J, Price A, McAllister-Lucas L, et al. Successful treatment of refractory metastatic histiocytic sarcoma with alemtuzumab. Cancer. 2012;118:3719–24.CrossRefPubMedGoogle Scholar
  4. 4.
    Abidi MH, Tove I, Ibrahim RB, Maria D, Peres E. Thalidomide for the treatment of histiocytic sarcoma after hematopoietic stem cell transplant. Am J Hematol. 2007;82:932–3.CrossRefPubMedGoogle Scholar
  5. 5.
    Gergis U, Dax H, Ritchie E, Marcus R, Wissa U, Orazi A. Autologous hematopoietic stem-cell transplantation in combination with thalidomide as treatment for histiocytic sarcoma: a case report and review of the literature. J Clin Oncol. 2011;29:e251–3.CrossRefPubMedGoogle Scholar
  6. 6.
    Van Dongen JJ, Langerak AW, Brüggemann M, Evans PA, Hummel M, Lavender FL, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17:2257–317.CrossRefPubMedGoogle Scholar
  7. 7.
    Choi SW, Bangaru BS, Wu CD, Finlay JL. Gastrointestinal involvement in disseminated Langerhans cell histiocytosis (LCH) with durable complete response to 2-chlorodeoxyadenosine and high-dose cytarabine. J Pediatr Hematol Oncol. 2003;25:503–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, et al. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015;126:1415–23.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Nguyen TT, Schwartz EJ, West RB, Warnke RA, Arber DA, Natkunam Y. Expression of CD163 (hemoglobin scavenger receptor) in normal tissues, lymphomas, carcinomas, and sarcomas is largely restricted to the monocyte/macrophage lineage. Am J Surg Pathol. 2005;29:617–24.CrossRefPubMedGoogle Scholar
  10. 10.
    Vos JA, Abbondanzo SL, Barekman CL, Andriko JW, Miettinen M, Aguilera NS. Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163. Mod Pathol. 2005;18:693–704.CrossRefPubMedGoogle Scholar
  11. 11.
    Grogan TM, Pileri SA, Chan JKC, Weiss LM, Fletcher CDM. Histiocytic sarcoma. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer Press; 2008. p. 356–7.Google Scholar
  12. 12.
    Carrera CJ, Terai C, Lotz M, Curd JG, Piro LD, Beutler E, et al. Potent toxicity of 2-chlorodeoxyadenosine toward human monocytes in vitro and in vivo. A novel approach to immunosuppressive therapy. J Clin Invest. 1990;86:1480–8.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Carson DA, Wasson DB, Taetle R, Yu A. Specific toxicity of 2-chlorodeoxyadenosine toward resting and proliferating human lymphocytes. Blood. 1983;62:737–43.PubMedGoogle Scholar
  14. 14.
    Saven A, Foon KA, Piro LD. 2-Chlorodeoxyadenosine-induced complete remissions in Langerhans-cell histiocytosis. Ann Intern Med. 1994;121:430–2.CrossRefPubMedGoogle Scholar
  15. 15.
    Morimoto A, Shioda Y, Imamura T, Kudo K, Kawaguchi H, Sakashita K, et al. Intensified and prolonged therapy comprising cytarabine, vincristine and prednisolone improves outcome in patients with multisystem Langerhans cell histiocytosis: results of the Japan Langerhans Cell Histiocytosis Study Group-02 Protocol Study. Int J Hematol. 2016;104:99–109.CrossRefPubMedGoogle Scholar
  16. 16.
    Gandhi V, Estey E, Keating MJ, Chucrallah A, Plunkett W. Chlorodeoxyadenosine and arabinosylcytosine in patients with acute myelogenous leukemia: pharmacokinetic, pharmacodynamic, and molecular interactions. Blood. 1996;87:256–64.PubMedGoogle Scholar
  17. 17.
    Freund A, Boos J, Harkin S, Schultze-Mosgau M, Veerman G, Peters GJ, et al. Augmentation of 1-beta-d-arabinofuranosylcytosine (Ara-C) cytotoxicity in leukaemia cells by co-administration with antisignalling drugs. Eur J Cancer. 1998;34:895–901.CrossRefPubMedGoogle Scholar
  18. 18.
    Buonocore S, Valente AL, Nightingale D, Bogart J, Souid AK. Histiocytic sarcoma in a 3-year-old male: a case report. Pediatrics. 2005;116:e322–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Tomlin J, Orosco RK, Boles S, Tipps A, Wang HY, Husseman J, et al. Successful treatment of multifocal histiocytic sarcoma occurring after renal transplantation with cladribine, high-dose cytarabine, G-CSF, and mitoxantrone (CLAG-M) followed by allogeneic hematopoietic stem cell transplantation. Case Rep Hematol. 2015;2015:728260.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Heath JL, Burgett SE, Gaca AM, Jaffe R, Wechsler DS. Successful treatment of pediatric histiocytic sarcoma using abbreviated high-risk leukemia chemotherapy. Pediatr Blood Cancer. 2014;61:1874–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Hornick JL, Jaffe ES, Fletcher CD. Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy. Am J Surg Pathol. 2004;28:1133–44.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  1. 1.Department of PediatricsNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  2. 2.Department of Orthopedic SurgeryNiigata University Graduate School Medical and Dental SciencesNiigataJapan
  3. 3.Department of PathologyNiigata University Graduate School Medical and Dental SciencesNiigataJapan

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