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Etiology of acute myeloid leukemia following intensive therapy for AML – relapse, secondary disease or bad luck?

Leukemia volume 16, pages 2459–2462 (2002)Cite this article

A young woman (age 28) was diagnosed with acute myeloid leukemia in March 1998 (FAB subtype M2) with a trisomy 13 as the sole cytogenetic abnormality. Following double induction chemotherapy comprising cytosine arabinoside, daunorubicine and mitoxantrone (TAD-HAM) a complete remission was achieved. Consolidation therapy comprised another cycle of TAD and an autologous peripheral blood stem cell transplantation (PBSCT). Analyses for trisomy 13 as a marker for residual disease of her AML by fluorescence in-situ hybridization (FISH) were negative. A relapse in November 1998 was associated with reappearance of the original clone with trisomy 13 (no further chromosomal aberrations) which remained refractory to reinduction treatment. Following conditioning therapy (total body irradiation (2 Gy), anti-thymocyte globuline, cyclophosphamide) and peripheral blood stem cell transplantation from a female HLA-identical unrelated donor a complete remission was achieved. Analyses of short-tandem repeats (STRs) as highly specific individual genetic markers demonstrated the presence of hematopoiesis of donor origin. Moreover, FISH analysis for trisomy 13 was equally negative for 4 months confirming the absence of trisomy 13 containing blasts. In October 1998 – ie 5 months after BMT and 1½ years after the initial diagnosis – myeloid blasts were again detected. However, this time cytogenetic analyses demonstrated complete absence of the initially observed trisomy 13, instead a translocation (1;5) and a monosomy 7 were observed in the AML blasts. STR analysis proved the recipient origin of the AML blasts. Cytoreductive therapy was initiated to facilitate planned adoptive immunotherapy as the sole remaining therapeutic option. The patient was transplanted with peripheral blood stem cells from the original donor with no further conditioning therapy. Granulocyte–macrophage colony-stimulating factor (GM-CSF) was applied to induce the formation of antigen-presenting cells (APCs) followed by transplantation of donor T cells and stimulation by interleukin 2. Severe acute graft-versus-host disease of the skin occurred but the leukemia was only insufficiently controlled. Three months later the diseased progressed and with no further treatment available the patient died 26 months after the initial diagnosis.

The tragic clinical course of this patient with AML is – in our opinion – very instructive for two reasons: (1) The crescendo of treatment imposed on this patient is a paradigm of current intensive multimodal antileukemic chemo- and immunotherapy featuring its potential and its shortcomings. (2) It illustrates that – when AML follows AML – the underlying pathogenesis might be considerably more complex than ‘classical relapse’, requiring appropriate diagnostic and therapeutic consequences. These two aspects will be further discussed.

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References

  1. Buchner T, Hiddemann W, Wormann B, Loffler H, Gassmann W, Haferlach T, Fonatsch C, Haase D, Schoch C, Hossfeld D, Lengfelder E, Aul C, Heyll A, Maschmeyer G, Ludwig WD, Sauerland MC, Heinecke A . Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group Blood 1999 93: 4116–4124

    CAS  PubMed  Google Scholar 

  2. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, Ljungman P, Ferrant A, Verdonck L, Niederwieser D et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia Blood 1995 86: 2041–2050

    CAS  PubMed  Google Scholar 

  3. Heath WR, Carbone FR . Cross-presentation, dendritic cells, tolerance and immunity Annu Rev Immunol 2001 19: 47–64

    Article  CAS  PubMed  Google Scholar 

  4. Stark B, Jeison M, Gobuzov R, Finkelshtein S, Ash S, Avrahami G, Cohen IJ, Stein J, Yaniv I, Zaizov R, Bar-Am I . Apparently unrelated clones shown by spectral karyotyping to represent clonal evolution of cryptic t(10;11)(p13;q23) in a patient with acute monoblastic leukemia Cancer Genet Cytogenet 2000 120: 105–110

    Article  CAS  PubMed  Google Scholar 

  5. Pedersen-Bjergaard J, Andersen MK, Christiansen DH . Therapy-related acute myeloid leukemia and myelodysplasia after high-dose chemotherapy and autologous stem cell transplantation Blood 2000 95: 3273–3279

    CAS  PubMed  Google Scholar 

  6. Andersen MK, Christiansen DH, Kirchhoff M, Pedersen-Bjergaard J . Duplication or amplification of chromosome band 11q23, including the unrearranged MLL gene, is a recurrent abnormality in therapy-related MDS and AML, and is closely related to mutation of the TP53 gene and to previous therapy with alkylating agents Genes Chromosomes Cancer 2001 31: 33–41

    Article  CAS  PubMed  Google Scholar 

  7. Blanco JG, Dervieux T, Edick MJ, Mehta PK, Rubnitz JE, Shurtleff S, Raimondi SC, Behm FG, Pui CH, Relling MV . Molecular emergence of acute myeloid leukemia during treatment for acute lymphoblastic leukemia Proc Natl Acad Sci USA 2001 98: 10338–10343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Braess J, Jahns-Streubel G, Schoch C, Haase D, Haferlach T, Fiegl M, Voss S, Kern W, Schleyer E, Hiddemann W . Proliferative activity of leukaemic blasts and cytosine arabinoside pharmacodynamics are associated with cytogenetically defined prognostic subgroups in acute myeloid leukaemia Br J Haematol 2001 113: 975–982

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Medicine III, Forschungslabor A, Klinikum Grosshadern, Germany

    J Braess, C Schoch, M Fiegl, C Schmid, W Hiddemann & H-J Kolb

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  2. C Schoch
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Braess, J., Schoch, C., Fiegl, M. et al. Etiology of acute myeloid leukemia following intensive therapy for AML – relapse, secondary disease or bad luck?. Leukemia 16, 2459–2462 (2002). https://doi.org/10.1038/sj.leu.2402772

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