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Special Clinical Scenarios: Extramedullary Disease

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Acute Myeloid Leukemia

Part of the book series: Hematologic Malignancies ((HEMATOLOGIC))

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Abstract

Extramedullary manifestation (EM) in patients with acute myeloid leukemia (AML) occurs frequently at diagnosis and more frequently at relapse in patients after allogeneic hematopoietic stem cell transplantation (HCT). While EM AML is clinically thought to represent a more aggressive form of AML, genetic analyses have shown that EM AML might harbor any AML-associated cytogenetic or genetic abnormalities that are observed in AML without EM. In this chapter also, the diagnostic approach to patients with EM AML is depicted and therapeutic scenarios are described discussing management options for patients with EM AML.

The difficulty in interpreting chloroma, in assigning to it its proper role within the categories of leukemia, arises from the fact that it belongs to that group of borderland cases which lies between genuine neoplasms and leukemias.

Heinrich Lehndorff, *1877 Vienna—†1965 New York

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References

  • Alakel N, Stolzel F, Mohr B, Kramer M, Oelschlagel U, Rollig C et al (2017) Symptomatic central nervous system involvement in adult patients with acute myeloid leukemia. Cancer Manag Res 9:97–102

    Article  PubMed  PubMed Central  Google Scholar 

  • Alvarez P, Navascues CA, Ordieres C, Pipa M, Vega IF, Granero P et al (2011) Granulocytic sarcoma of the small bowel, greater omentum and peritoneum associated with a CBFbeta/MYH11 fusion and inv(16) (p13q22): a case report. Int Arch Med 4(1):3

    Article  PubMed  PubMed Central  Google Scholar 

  • Ando T, Mitani N, Matsunaga K, Nakazora T, Gondo T, Yujiri T et al (2010) Gemtuzumab ozogamicin therapy for isolated extramedullary AML relapse after allogeneic hematopoietic stem-cell transplantation. Tohoku J Exp Med 220(2):121–126

    Article  CAS  PubMed  Google Scholar 

  • Ansari-Lari MA, Yang CF, Tinawi-Aljundi R, Cooper L, Long P, Allan RH et al (2004) FLT3 mutations in myeloid sarcoma. Br J Haematol 126(6):785–791

    Article  CAS  PubMed  Google Scholar 

  • Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405

    Article  CAS  PubMed  Google Scholar 

  • Arber DA, Borowitz MJ, Cessna M, Etzell J, Foucar K, Hasserjian RP et al (2017) Initial diagnostic workup of acute leukemia: guideline from the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med 141(10):1342–1393

    Article  PubMed  Google Scholar 

  • Avni B, Koren-Michowitz M (2011) Myeloid sarcoma: current approach and therapeutic options. Ther Adv Hematol 2(5):309–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bakst R, Yahalom J (2011) Radiation therapy for leukemia cutis. Pract Radiat Oncol 1(3):182–187

    Article  PubMed  Google Scholar 

  • Bakst RL, Tallman MS, Douer D, Yahalom J (2011) How I treat extramedullary acute myeloid leukemia. Blood 118(14):3785–3793

    Article  CAS  PubMed  Google Scholar 

  • Bakst R, Wolden S, Yahalom J (2012) Radiation therapy for chloroma (granulocytic sarcoma). Int J Radiat Oncol Biol Phys 82(5):1816–1822

    Article  PubMed  Google Scholar 

  • Byrd JC, Weiss RB (1994) Recurrent granulocytic sarcoma. An unusual variation of acute myelogenous leukemia associated with 8;21 chromosomal translocation and blast expression of the neural cell adhesion molecule. Cancer 73(8):2107–2112

    Article  CAS  PubMed  Google Scholar 

  • Byrd JC, Edenfield WJ, Shields DJ, Dawson NA (1995) Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review. J Clin Oncol 13(7):1800–1816

    Article  CAS  PubMed  Google Scholar 

  • Caraffini V, Perfler B, Berg JL, Uhl B, Schauer S, Kashofer K et al (2018) Loss of RKIP is a frequent event in myeloid sarcoma and promotes leukemic tissue infiltration. Blood 131(7):826–830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng CL, Li CC, Hou HA, Fang WQ, Chang CH, Lin CT et al (2015) Risk factors and clinical outcomes of acute myeloid leukaemia with central nervous system involvement in adults. BMC Cancer 15:344

    Article  PubMed  PubMed Central  Google Scholar 

  • Cohen PR, Talpaz M, Kurzrock R (1988) Malignancy-associated Sweet’s syndrome: review of the world literature. J Clin Oncol 6(12):1887–1897

    Article  CAS  PubMed  Google Scholar 

  • Cornelissen JJ, Gratwohl A, Schlenk RF, Sierra J, Bornhauser M, Juliusson G et al (2012) The European LeukemiaNet AML working party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol 9(10):579–590

    Article  CAS  PubMed  Google Scholar 

  • Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A et al (2016) Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med 375(2):143–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deeb G, Baer MR, Gaile DP, Sait SN, Barcos M, Wetzler M et al (2005) Genomic profiling of myeloid sarcoma by array comparative genomic hybridization. Genes Chromosomes Cancer 44(4):373–383

    Article  CAS  PubMed  Google Scholar 

  • Dohner K, Schlenk RF, Habdank M, Scholl C, Rucker FG, Corbacioglu A et al (2005) Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood 106(12):3740–3746

    Article  PubMed  CAS  Google Scholar 

  • Falini B, Lenze D, Hasserjian R, Coupland S, Jaehne D, Soupir C et al (2007) Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status of a significant fraction of myeloid sarcomas. Leukemia 21(7):1566–1570

    Article  CAS  PubMed  Google Scholar 

  • Fernandez HF, Sun Z, Litzow MR, Luger SM, Paietta E, Racevskis J et al (2019) Extramedullary acute myeloid leukemia presenting in young adults demonstrates sensitivity to high-dose anthracycline: a subset analysis from ECOG-ACRIN 1900. Haematologica 104(4):e147–ee50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganzel C, Manola J, Douer D, Rowe JM, Fernandez HF, Paietta EM 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(29):3544–3553

    Article  PubMed  PubMed Central  Google Scholar 

  • Ge L, Ye F, Mao X, Chen J, Sun A, Zhu X et al (2014) Extramedullary relapse of acute leukemia after allogeneic hematopoietic stem cell transplantation: different characteristics between acute myelogenous leukemia and acute lymphoblastic leukemia. Biol Blood Marrow Transplant 20(7):1040–1047

    Article  PubMed  Google Scholar 

  • Harris AC, Kitko CL, Couriel DR, Braun TM, Choi SW, Magenau J et al (2013) Extramedullary relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcomes. Haematologica 98(2):179–184

    Article  PubMed  PubMed Central  Google Scholar 

  • Karlin L, Itti E, Pautas C, Rachid M, Bories D, Cordonnier C et al (2006) PET-imaging as a useful tool for early detection of the relapse site in the management of primary myeloid sarcoma. Haematologica 91(12 Suppl):ECR54

    PubMed  Google Scholar 

  • Kashofer K, Gornicec M, Lind K, Caraffini V, Schauer S, Beham-Schmid C et al (2018) Detection of prognostically relevant mutations and translocations in myeloid sarcoma by next generation sequencing. Leuk Lymphoma 59(2):501–504

    Article  CAS  PubMed  Google Scholar 

  • King C (1934) A case of chloroma with orbital involvement locally benefited by X-ray therapy. Trans Am Ophthalmol Soc 32:340–353

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kuenzle K, Taverna C, Steinert HC (2002) Detection of extramedullary infiltrates in acute myelogenous leukemia with whole-body positron emission tomography and 2-deoxy-2-[18F]-fluoro-D-glucose. Mol Imaging Biol 4(2):179–183

    Article  PubMed  Google Scholar 

  • Larson SM, Graff KS, Tretner IH, Zager RF, Henderson EA, Johnston GS (1972) Positive gallium 677 photoscan in myeloblastoma. JAMA 222(3):321–323

    Article  CAS  PubMed  Google Scholar 

  • Lehndorff (1910) Ergebnisse der inneren Medizin und Kinderheilkunde, p 221

    Google Scholar 

  • Li Z, Stolzel F, Onel K, Sukhanova M, Mirza MK, Yap KL et al (2015) Next-generation sequencing reveals clinically actionable molecular markers in myeloid sarcoma. Leukemia 29(10):2113–2116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mantzarides M, Bonardel G, Fagot T, Gontier E, Soret M, Revel TD et al (2008) Granulocytic sarcomas evaluated with F-18-fluorodeoxyglucose PET. Clin Nucl Med 33(2):115–117

    Article  PubMed  Google Scholar 

  • Meis JM, Butler JJ, Osborne BM, Manning JT (1986) Granulocytic sarcoma in nonleukemic patients. Cancer 58(12):2697–2709

    Article  CAS  PubMed  Google Scholar 

  • Mirza MK, Sukhanova M, Stolzel F, Onel K, Larson RA, Stock W et al (2014) Genomic aberrations in myeloid sarcoma without blood or bone marrow involvement: characterization of formalin-fixed paraffin-embedded samples by chromosomal microarrays. Leuk Res 38(9):1091–1096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montesinos P, Diaz-Mediavilla J, Deben G, Prates V, Tormo M, Rubio V et al (2009) Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis. Haematologica 94(9):1242–1249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neumann M, Blau IW, Burmeister T, Tietze-Buerger C, Blau O, Gerbitz A et al (2011) Intrathecal application of donor lymphocytes in leukemic meningeosis after allogeneic stem cell transplantation. Ann Hematol 90(8):911–916

    Article  PubMed  Google Scholar 

  • O’Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA et al (2017) Acute myeloid leukemia, version 3.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 15(7):926–957

    Article  Google Scholar 

  • Ohanian M, Faderl S, Ravandi F, Pemmaraju N, Garcia-Manero G, Cortes J et al (2013) Is acute myeloid leukemia a liquid tumor? Int J Cancer 133(3):534–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Owonikoko T, Agha M, Balassanian R, Smith R, Raptis A (2007) Gemtuzumab therapy for isolated extramedullary AML relapse following allogeneic stem-cell transplant. Nat Clin Pract Oncol 4(8):491–495

    Article  CAS  PubMed  Google Scholar 

  • Piccaluga PP, Martinelli G, Rondoni M, Malagola M, Gaitani S, Isidori A et al (2004) Gemtuzumab ozogamicin for relapsed and refractory acute myeloid leukemia and myeloid sarcomas. Leuk Lymphoma 45(9):1791–1795

    Article  CAS  PubMed  Google Scholar 

  • Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M et al (2007) Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia 21(2):340–350

    Article  CAS  PubMed  Google Scholar 

  • Pui MH, Fletcher BD, Langston JW (1994) Granulocytic sarcoma in childhood leukemia: imaging features. Radiology 190(3):698–702

    Article  CAS  PubMed  Google Scholar 

  • Shem-Tov N, Saraceni F, Danylesko I, Shouval R, Yerushalmi R, Nagler A et al (2017) Isolated extramedullary relapse of acute leukemia after allogeneic stem cell transplantation: different kinetics and better prognosis than systemic relapse. Biol Blood Marrow Transplant 23(7):1087–1094

    Article  PubMed  Google Scholar 

  • Shihadeh F, Reed V, Faderl S, Medeiros LJ, Mazloom A, Hadziahmetovic M et al (2012) Cytogenetic profile of patients with acute myeloid leukemia and central nervous system disease. Cancer 118(1):112–117

    Article  CAS  PubMed  Google Scholar 

  • Shimizu H, Saitoh T, Hatsumi N, Takada S, Handa H, Jimbo T et al (2013) Prevalence of extramedullary relapses is higher after allogeneic stem cell transplantation than after chemotherapy in adult patients with acute myeloid leukemia. Leuk Res 37(11):1477–1481

    Article  CAS  PubMed  Google Scholar 

  • Solh M, DeFor TE, Weisdorf DJ, Kaufman DS (2012) Extramedullary relapse of acute myelogenous leukemia after allogeneic hematopoietic stem cell transplantation: better prognosis than systemic relapse. Biol Blood Marrow Transplant 18(1):106–112

    Article  PubMed  Google Scholar 

  • Solh M, Solomon S, Morris L, Holland K, Bashey A (2016) Extramedullary acute myelogenous leukemia. Blood Rev 30(5):333–339

    Article  PubMed  Google Scholar 

  • Stolzel F, Rollig C, Radke J, Mohr B, Platzbecker U, Bornhauser M et al (2011) (1)(8)F-FDG-PET/CT for detection of extramedullary acute myeloid leukemia. Haematologica 96(10):1552–1556

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stolzel F, Hackmann K, Kuithan F, Mohr B, Fussel M, Oelschlagel U et al (2012) Clonal evolution including partial loss of human leukocyte antigen genes favoring extramedullary acute myeloid leukemia relapse after matched related allogeneic hematopoietic stem cell transplantation. Transplantation 93(7):744–749

    Article  PubMed  CAS  Google Scholar 

  • Stolzel F, Luer T, Lock S, Parmentier S, Kuithan F, Kramer M et al (2020) The prevalence of extramedullary acute myeloid leukemia detected by 18FDG-PET/CT: final results from the prospective PETAML trial. Haematologica 105(6):1552–1558

    Article  PubMed  PubMed Central  Google Scholar 

  • Tsimberidou AM, Kantarjian HM, Wen S, Keating MJ, O’Brien S, Brandt M et al (2008) Myeloid sarcoma is associated with superior event-free survival and overall survival compared with acute myeloid leukemia. Cancer 113(6):1370–1378

    Article  PubMed  Google Scholar 

  • Ueda K, Ichikawa M, Takahashi M, Momose T, Ohtomo K, Kurokawa M (2010) FDG-PET is effective in the detection of granulocytic sarcoma in patients with myeloid malignancy. Leuk Res 34(9):1239–1241

    Article  PubMed  Google Scholar 

  • Vago L (2019) Clonal evolution and immune evasion in posttransplantation relapses. Hematology Am Soc Hematol Educ Program 2019(1):610–616

    Article  PubMed  PubMed Central  Google Scholar 

  • Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A 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(5):937–951

    Article  CAS  PubMed  Google Scholar 

  • Vega-Ruiz A, Faderl S, Estrov Z, Pierce S, Cortes J, Kantarjian H et al (2009) Incidence of extramedullary disease in patients with acute promyelocytic leukemia: a single-institution experience. Int J Hematol 89(4):489–496

    Article  PubMed  PubMed Central  Google Scholar 

  • von den Driesch P (1994) Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol 31(4):535–556; quiz 57–60

    Article  PubMed  Google Scholar 

  • Xavier SG, Fagundes EM, Hassan R, Bacchi C, Conchon M, Tabak DG et al (2003) Granulocytic sarcoma of the small intestine with CBFbeta/MYH11 fusion gene: report of an aleukaemic case and review of the literature. Leuk Res 27(11):1063–1066

    Article  CAS  PubMed  Google Scholar 

  • Yamauchi K, Yasuda M (2002) Comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature. Cancer 94(6):1739–1746

    Article  PubMed  Google Scholar 

  • Yoshihara S, Ando T, Ogawa H (2012) Extramedullary relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation: an easily overlooked but significant pattern of relapse. Biol Blood Marrow Transplant 18(12):1800–1807

    Article  PubMed  Google Scholar 

  • Zhang XH, Zhang R, Li Y (2010) Granulocytic sarcoma of abdomen in acute myeloid leukemia patient with inv(16) and t(6;17) abnormal chromosome: case report and review of literature. Leuk Res 34(7):958–961

    Article  PubMed  Google Scholar 

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  1. Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

    Friedrich Stölzel

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  1. Friedrich Stölzel
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Correspondence to Friedrich Stölzel .

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  1. Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus, Dresden, Germany

    Christoph Röllig

  2. Department of Haematology, Amsterdam University Medical Center location VUMC, Amsterdam, Noord-Holland, The Netherlands

    Gert J. Ossenkoppele

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Stölzel, F. (2021). Special Clinical Scenarios: Extramedullary Disease. In: Röllig, C., Ossenkoppele, G.J. (eds) Acute Myeloid Leukemia . Hematologic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-030-72676-8_15

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  • DOI: https://doi.org/10.1007/978-3-030-72676-8_15

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