Strahlentherapie und Onkologie

, Volume 194, Issue 2, pp 164–173 | Cite as

Radiotherapy for extramedullary leukaemic manifestation (Chloroma)

  • Michael Oertel
  • Khaled Elsayad
  • Uwe Haverkamp
  • Matthias Stelljes
  • Hans Theodor Eich
Original Article



Extramedullary leukaemic disease (EMD, synonym chloroma) is a rare solid manifestation of myeloid leukaemia for which the value of radiotherapy (RT) as a treatment strategy remains controversial. The aim of this study is to analyse the effectiveness of various RT doses for EMD in the modern treatment era.

Materials and methods

Between January 2000 and June 2016, 20 patients with total of 45 lesions underwent RT for EMD at our institution.


With a median radiation dose of 26 Gy (range 4–42 Gy), local remission could be achieved in 91% of patients (complete remission rate: 71%). The median duration of local control (DOLC) was 17 months (95% confidence interval [CI] 0.5–33) and the median overall survival (OS) after chloroma onset was 24 months (95% CI 11–38). No noticeable difference between high- and low-dose regimens has been observed (74% versus 68%; P = 0.5). In the multivariate analysis, only Eastern Cooperative Oncology Group (ECOG) score and bone marrow state during RT have proven to be determinant for durable local control and OS.


Low-dose RT (≤26 Gy) achieves good local control compared to high-dose regimes. Bone marrow state during RT and ECOG score during RT may play a crucial role, influencing both DOLC and OS.


Chloroma Leukemia Intensity-modulated radiotherapy Hematologic diseases Survival 

Strahlentherapie bei extramedullärer leukämischer Manifestation (Chlorom)



Extramedulläre leukämische Infiltrate (EMD) sind seltene Manifestationen myeloischer Leukämien, in deren Behandlungskonzepten der Stellenwert der Radiotherapie (RT) unklar ist. Das Ziel der vorgelegten Studie ist es, die Wirksamkeit verschiedener Strahlentherapiedosen für EMD in der modernen Behandlungsära zu untersuchen.

Material und Methoden

Zwischen Januar 2000 und Juni 2016 durchliefen 20 Patienten mit insgesamt 45 Läsionen eine RT für EMD in unserer Klinik.


Mit einer mittleren RT-Dosis von 26 Gy (Spanne 4–42 Gy) konnte eine lokale Remission bei 91 % der Patienten erzielt werden (komplette Remissionsrate, CRR: 71 %). Die mittlere Dauer der Lokalkontrolle (DOLC) betrug 17 Monate (95 %-KI 0,5–33) und das mediane Gesamtüberleben (OS) nach Chloromadiagnose war 24 Monate (95 %-KI 11–38). Es fand sich kein wesentlicher Unterschied zwischen Niedrig- und Hochdosis-RT (74 % versus 68 %; P = 0,5). Läsionen mit einer günstigen Prognose nach zytogenetischen und molekulargenetischen Faktoren sowie Läsionen, die mit einer modernen Strahlentherapietechnik wie intensitätsmodulierter Radiotherapie (IMRT) behandelt wurden, erreichten eine CRR von 100 % (P = 0,05 bzw. P = 0,008). In der multivariaten Analyse zeigten sich der ECOG-Score (Eastern Cooperative Oncology Group) und eine Remission im Knochenmark als entscheidend für die lokale Kontrolle, während der ECOG-Score, die Bestrahlungstechnik und das Ansprechen auf die RT das OS beeinflussten.


Niedrigdosis-RT (≤26 Gy) erzielt eine ebenso gute lokale Kontrolle wie Behandlungskonzepte mit höherer Dosis. Der ECOG-Score vor der RT scheint eine zentrale Rolle für OS und DOLC zu spielen.


Chlorome Leukämien Intensitätsmodulierte Strahlentherapie Hämatologische Erkrankungen Überleben 


Compliance with ethical guidelines

Conflict of interest

M. Oertel, K. Elsayad, U. Haverkamp, M. Stelljes and H.T. Eich declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants 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.

Supplementary material

66_2017_1236_MOESM1_ESM.docx (19 kb)
Supplementary Material 1: Published large series of chloroma treated with radiation therapy
66_2017_1236_MOESM2_ESM.jpg (43 kb)
Supplementary Figure 1: Kaplan–Meier estimates of overall survival according to skin involvement


  1. 1.
    Vardiman JW, Thiele J, Arber DA et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951. CrossRefPubMedGoogle Scholar
  2. 2.
    Agis H, Weltermann A, Fonatsch C et al (2002) A comparative study on demographic, hematological, and cytogenetic findings and prognosis in acute myeloid leukemia with and without leukemia cutis. Ann Hematol 81:90–95. CrossRefPubMedGoogle Scholar
  3. 3.
    Ganzel C, Manola J, Douer D et al (2016) Extramedullary disease in adult acute myeloid leukemia is common but lacks independent significance: analysis of patients in ECOG-ACRIN Cancer Research Group Trials, 1980-2008. J Clin Oncol 34:3544–3553. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Movassaghian M, Brunner AM, Blonquist TM et al (2015) Presentation and outcomes among patients with isolated myeloid sarcoma: a surveillance, epidemiology, and end results database analysis. Leuk Lymphoma 56:1698–1703. CrossRefPubMedGoogle Scholar
  5. 5.
    King A (1853) A case of chloroma. Monthly J Med 17:97Google Scholar
  6. 6.
    Bakst R, Wolden S, Yahalom J (2012) Radiation therapy for Chloroma (Granulocytic Sarcoma). Int J Radiat Oncol Biol Phys 82:1816–1822. CrossRefPubMedGoogle Scholar
  7. 7.
    Chak LY, Sapozink MD, Cox RS (1983) Extramedullary lesions in non-lymphocytic leukemia: results of radiation therapy. Int J Radiat Oncol Biol Phys 9:1173–1176CrossRefPubMedGoogle Scholar
  8. 8.
    Kawamoto K, Miyoshi H, Yoshida N et al (2016) Clinicopathological, cytogenetic, and prognostic analysis of 131 myeloid sarcoma patients. Am J Surg Pathol 40:1473–1483. CrossRefPubMedGoogle Scholar
  9. 9.
    Meis JM, Butler JJ, Osborne BM, Manning JT (1986) Granulocytic sarcoma in nonleukemic patients. Cancer 58:2697–2709CrossRefPubMedGoogle Scholar
  10. 10.
    Cantone E, Cavaliere M, Di Lullo A et al (2016) Immunohistochemical patterns in the differential diagnosis of rhinopharyngeal granulocytic sarcoma. Oncol Lett. PubMedPubMedCentralGoogle Scholar
  11. 11.
    Hall MD, Chen Y‑J, Schultheiss TE et al (2014) Treatment outcomes for patients with chloroma receiving radiation therapy: radiation therapy for chloroma. J Med Imaging Radiat Oncol. PubMedGoogle Scholar
  12. 12.
    Walker GV, Shihadeh F, Kantarjian H et al (2014) Comprehensive craniospinal radiation for controlling central nervous system leukemia. Int J Radiat Oncol Biol Phys 90:1119–1125. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Byrd JC, Edenfield WJ, Shields DJ, Dawson NA (1995) Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review. J Clin Oncol 13:1800–1816. CrossRefPubMedGoogle Scholar
  14. 14.
    Schlenk RF, Döhner K, Krauter J et al (2008) Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 358:1909–1918. CrossRefPubMedGoogle Scholar
  15. 15.
    Döhner H, Estey E, Grimwade D et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129:424–447. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Dabaja B (2017) Renaissance of low-dose radiotherapy concepts for cutaneous lymphomas. Oncol Res Treat. PubMedGoogle Scholar
  17. 17.
    Elsayad K, Kriz J, Moustakis C et al (2015) Total skin electron beam for primary cutaneous T‑cell lymphoma. Int J Radiat Oncol Biol Phys 93:1077–1086. CrossRefPubMedGoogle Scholar
  18. 18.
    Elsayad K, Oertel M, Haverkamp U, Eich HT (2017) The effectiveness of radiotherapy for leukemia cutis. J Cancer Res Clin Oncol. PubMedGoogle Scholar
  19. 19.
    Chen W‑Y, Wang C‑W, Chang C‑H et al (2013) Clinicopathologic features and responses to radiotherapy of myeloid sarcoma. Radiat Oncol 8:245. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Bastianutto C, Mian A, Symes J et al (2007) Local radiotherapy induces homing of hematopoietic stem cells to the irradiated bone marrow. Cancer Res 67:10112–10116. CrossRefPubMedGoogle Scholar
  21. 21.
    Collis SJ, Neutzel S, Thompson TL et al (2004) Hematopoietic progenitor stem cell homing in mice lethally irradiated with ionizing radiation at differing dose rates. Radiat Res 162:48–55CrossRefPubMedGoogle Scholar
  22. 22.
    Plett PA, Frankovitz SM, Orschell-Traycoff CM (2002) In vivo trafficking, cell cycle activity, and engraftment potential of phenotypically defined primitive hematopoietic cells after transplantation into irradiated or nonirradiated recipients. Blood 100:3545–3552. CrossRefPubMedGoogle Scholar
  23. 23.
    Sauer MG (2015) Cognitive deficits following hematopoietic stem cell transplantation in childhood. Strahlenther Onkol 191:456–457CrossRefPubMedGoogle Scholar
  24. 24.
    Fleckenstein J, Kremp K, Kremp S et al (2016) IMRT and 3D conformal radiotherapy with or without elective nodal irradiation in locally advanced NSCLC: a direct comparison of PET-based treatment planning. Strahlenther Onkol 192:75–82. CrossRefPubMedGoogle Scholar
  25. 25.
    Jöst V, Kretschmer M, Sabatino M et al (2015) Heart dose reduction in breast cancer treatment with simultaneous integrated boost: comparison of treatment planning and dosimetry for a novel hybrid technique and 3D-CRT. Strahlenther Onkol 191:734–741. CrossRefPubMedGoogle Scholar
  26. 26.
    Moon SH, Cho KH, Lee C‑G et al (2016) IMRT vs. 2D-radiotherapy or 3D-conformal radiotherapy of nasopharyngeal carcinoma : survival outcome in a Korean multi-institutional retrospective study (KROG 11-06). Strahlenther Onkol 192:377–385. CrossRefPubMedGoogle Scholar
  27. 27.
    Bullinger L, Döhner K, Döhner H (2017) Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol 35:934–946. CrossRefPubMedGoogle Scholar
  28. 28.
    Port M, Böttcher M, Thol F et al (2014) Prognostic significance of FLT3 internal tandem duplication, nucleophosmin 1, and CEBPA gene mutations for acute myeloid leukemia patients with normal karyotype and younger than 60 years: a systematic review and meta-analysis. Ann Hematol 93:1279–1286. CrossRefPubMedGoogle Scholar
  29. 29.
    Carow CE, Levenstein M, Kaufmann SH et al (1996) Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias. Blood 87:1089–1096PubMedGoogle Scholar
  30. 30.
    Rosnet O, Bühring HJ, Marchetto S et al (1996) Human FLT3/FLK2 receptor tyrosine kinase is expressed at the surface of normal and malignant hematopoietic cells. Leukemia 10:238–248PubMedGoogle Scholar
  31. 31.
    Ansari-Lari MA, Yang C‑F, Tinawi-Aljundi R et al (2004) FLT3 mutations in myeloid sarcoma. Br J Haematol 126:785–791. CrossRefPubMedGoogle Scholar
  32. 32.
    Mead AJ, Linch DC, Hills RK et al (2007) FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. Blood 110:1262–1270. CrossRefPubMedGoogle Scholar
  33. 33.
    Yanada M, Matsuo K, Suzuki T et al (2005) Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia 19:1345–1349. CrossRefPubMedGoogle Scholar
  34. 34.
    Cribe A‑SWI, Steenhof M, Marcher CW et al (2013) Extramedullary disease in patients with acute myeloid leukemia assessed by (18)F-FDG PET. Eur J Haematol 90:273–278. CrossRefPubMedGoogle Scholar
  35. 35.
    Reinartz G, Haverkamp U, Wullenkord R et al (2016) 4D-Listmode-PET-CT and 4D-CT for optimizing PTV margins in gastric lymphoma: determination of intra- and interfractional gastric motion. Strahlenther Onkol 192:322–332. CrossRefPubMedGoogle Scholar
  36. 36.
    Kai T, Kimura H, Shiga Y et al (2006) Recurrent extramedullary relapse of acute promyelocytic leukemia after allogeneic stem cell transplantation: successful treatment by arsenic trioxide in combination with local radiotherapy. Int J Hematol 83:337–340. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Deutschland 2017

Authors and Affiliations

  1. 1.Department of Radiation OncologyUniversity Hospital of MuensterMuensterGermany
  2. 2.Department of Internal MedicineUniversity Hospital of MuensterMuensterGermany

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