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Erschienen in: memo - Magazine of European Medical Oncology 2/2015

01.06.2015 | case report

Potential impact of the hypomethylating agent 5-azacitidine on chronic lymphocytic leukemia with del(17)(p)/del(p53) and subsequent therapy-related acute myeloid leukemia without these aberrations: a case report

verfasst von: MD, MBA Prof. Michael Pfeilstöcker, MD Rainer Weichselbaum, Helmut Mühlberger, MD Elisabeth Menschel, MD Felix Keil

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 2/2015

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Abstract

The patient presented here had a very poor prognosis due to previous chronic lymphocytic leukemia with unfavourable cytogenetics (deleted 17p and p53), therapy-related acute myeloid leukemia (intact 17p/p53), multiple pre-treatments (fludarabine, rituximab-CHOP, rituximab-bendamustine), advanced age (71 years) and several comorbidities—circumstances that usually do not allow high-dose chemotherapy or stem cell transplantation. Due to this unfavourable condition and reportedly poorer outcome of therapy-related acute myeloid leukemia relative to de novo acute myeloid leukemia with chemotherapy, treatment with the hypomethylating agent 5-azacitidine (Vidaza®), 75 mg/m2/day, subcutaneously for 7 days of 28-day cycles was started. Therapy was well tolerated and yielded a good response not only by eradicating the therapy-related acute myeloid leukemia but also by keeping the chronic lymphocytic leukemia under control for a rather long period of time. The simultaneous suppression and re-appearance of both the therapy-related acute myeloid leukemia with intact p53 and the chronic lymphocytic leukemia with deleted p53 suggests that hypomethylation by azacitidine attains tumour control by a mechanism that (i) is similar in the different tumours and (ii) acts independently of the p53 status. This case may serve as a model for disease progression mirrored in molecular and cytogenetic findings which are factored into treatment decisions.
Literatur
1.
Zurück zum Zitat Hallek M. Chronic lymphocytic leukemia: 2013 update on diagnosis, risk stratification and treatment. Am J Hematol. 2013;88(9):803–16. PubMedCrossRef Hallek M. Chronic lymphocytic leukemia: 2013 update on diagnosis, risk stratification and treatment. Am J Hematol. 2013;88(9):803–16. PubMedCrossRef
2.
Zurück zum Zitat Zenz T, Mertens D, Döhner H, Stilgenbauer S. Importance of genetics in chronic lymphocytic leukemia. Blood Rev. 2011;25(3):131–7. PubMedCrossRef Zenz T, Mertens D, Döhner H, Stilgenbauer S. Importance of genetics in chronic lymphocytic leukemia. Blood Rev. 2011;25(3):131–7. PubMedCrossRef
3.
Zurück zum Zitat Zenz T, Benner A, Döhner H, Stilgenbauer S. Chronic lymphocytic leukemia and treatment resistance in cancer: the role of the p53 pathway. Cell Cycle. 2008;7(24):3810–4. PubMedCrossRef Zenz T, Benner A, Döhner H, Stilgenbauer S. Chronic lymphocytic leukemia and treatment resistance in cancer: the role of the p53 pathway. Cell Cycle. 2008;7(24):3810–4. PubMedCrossRef
4.
Zurück zum Zitat Doubek M, Mayer J, Obrtlíková P, et al. Modern and conventional prognostic markers of chronic lymphocytic leukaemia in the everyday haematological practice. Eur J Haematol. 2011;87(2):130–7. PubMedCrossRef Doubek M, Mayer J, Obrtlíková P, et al. Modern and conventional prognostic markers of chronic lymphocytic leukaemia in the everyday haematological practice. Eur J Haematol. 2011;87(2):130–7. PubMedCrossRef
5.
6.
Zurück zum Zitat Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997–1007. PubMedCentralPubMedCrossRef Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997–1007. PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat Ricci F, Tedeschi A, Montillo M, Morra E. Therapy-related myeloid neoplasms in chronic lymphocytic leukemia and Waldenstrom’s macroglobulinemia. Mediterr J Hematol Infect Dis. 2011;3:e2011031. doi:10.4084/MJHID.2011.031. PubMedCentralPubMedCrossRef Ricci F, Tedeschi A, Montillo M, Morra E. Therapy-related myeloid neoplasms in chronic lymphocytic leukemia and Waldenstrom’s macroglobulinemia. Mediterr J Hematol Infect Dis. 2011;3:e2011031. doi:10.4084/MJHID.2011.031. PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat Stoddart A, McNerney ME, Bartom E, et al. Genetic pathways leading to therapy-related myeloid neoplasms. Mediterr J Hematol Infect Dis. 2011;3:e2011019. doi:10.4084/MJHID.2011.019. PubMedCentralPubMedCrossRef Stoddart A, McNerney ME, Bartom E, et al. Genetic pathways leading to therapy-related myeloid neoplasms. Mediterr J Hematol Infect Dis. 2011;3:e2011019. doi:10.4084/MJHID.2011.019. PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Azacitidine (vidaza) Injection [EU prescribing information]. Switzerland: Celgene International; 2014. Azacitidine (vidaza) Injection [EU prescribing information]. Switzerland: Celgene International; 2014.
10.
Zurück zum Zitat Eltrombopag (revolade) Tablet [EU prescribing information]. United Kingdom: Glaxo Operations UK Ltd; 2010. Eltrombopag (revolade) Tablet [EU prescribing information]. United Kingdom: Glaxo Operations UK Ltd; 2010.
11.
Zurück zum Zitat Colović M, Suvajdžić N, Janković G, et al. Therapy-related myelodysplastic syndrome and acute myeloid leukemia in patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide. Biomed Pharmacother. 2011;65(5):319–21. PubMedCrossRef Colović M, Suvajdžić N, Janković G, et al. Therapy-related myelodysplastic syndrome and acute myeloid leukemia in patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide. Biomed Pharmacother. 2011;65(5):319–21. PubMedCrossRef
13.
Zurück zum Zitat Decitabine (dacogen) Powder [EU prescribing information]. Belgium: Janssen-Cilag Corporation; 2014. Decitabine (dacogen) Powder [EU prescribing information]. Belgium: Janssen-Cilag Corporation; 2014.
14.
15.
Zurück zum Zitat Duong VH, Lancet JE, Alrawi E, et al. Outcome of azacitidine treatment in patients with therapy-related myeloid neoplasms with assessment of prognostic risk stratification models. Leuk Res. 2013;37(5):510–5. PubMedCrossRef Duong VH, Lancet JE, Alrawi E, et al. Outcome of azacitidine treatment in patients with therapy-related myeloid neoplasms with assessment of prognostic risk stratification models. Leuk Res. 2013;37(5):510–5. PubMedCrossRef
16.
Zurück zum Zitat Bally C, Thépot S, Quesnel B, et al. Azacitidine in the treatment of therapy related myelodysplastic syndrome and acute myeloid leukemia (tMDS/AML): a report on 54 patients by the Groupe Francophone Des Myelodysplasies (GFM). Leuk Res. 2013;37(6):637–40. PubMedCrossRef Bally C, Thépot S, Quesnel B, et al. Azacitidine in the treatment of therapy related myelodysplastic syndrome and acute myeloid leukemia (tMDS/AML): a report on 54 patients by the Groupe Francophone Des Myelodysplasies (GFM). Leuk Res. 2013;37(6):637–40. PubMedCrossRef
17.
Zurück zum Zitat Malik A, Shoukier M, Garcia-Manero G, et al. Azacitidine in fludarabine-refractory chronic lymphocytic leukemia: a phase II study. Clin Lymphoma Myeloma Leuk. 2013;13(3):292–5. PubMedCrossRef Malik A, Shoukier M, Garcia-Manero G, et al. Azacitidine in fludarabine-refractory chronic lymphocytic leukemia: a phase II study. Clin Lymphoma Myeloma Leuk. 2013;13(3):292–5. PubMedCrossRef
18.
Zurück zum Zitat Fenaux P, Gattermann N, Seymour JF, et al. Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: azacitidine compared with low dose ara-C. Br J Haematol. 2010;149(2):244–9. PubMedCentralPubMedCrossRef Fenaux P, Gattermann N, Seymour JF, et al. Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: azacitidine compared with low dose ara-C. Br J Haematol. 2010;149(2):244–9. PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat Fenaux P, Mufti GJ, Hellström-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010;28(4):562–9. PubMedCrossRef Fenaux P, Mufti GJ, Hellström-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010;28(4):562–9. PubMedCrossRef
20.
Zurück zum Zitat Bally C, Ades L, Renneville A, et al. Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine. Leuk Res. 2014;38(7):751–5. PubMedCrossRef Bally C, Ades L, Renneville A, et al. Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine. Leuk Res. 2014;38(7):751–5. PubMedCrossRef
21.
Zurück zum Zitat Kulasekararaj AG, Smith AE, Mian SA, et al. TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis. Br J Haematol. 2013;160(5):660–72. PubMedCrossRef Kulasekararaj AG, Smith AE, Mian SA, et al. TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis. Br J Haematol. 2013;160(5):660–72. PubMedCrossRef
22.
Zurück zum Zitat Platzbecker U, Braulke F, Kündgen A, et al. Sequential combination of azacitidine and lenalidomide in del(5q) higher-risk myelodysplastic syndromes or acute myeloid leukemia: a phase I study. Leukemia. 2013;27(6):1403–7. PubMedCentralPubMedCrossRef Platzbecker U, Braulke F, Kündgen A, et al. Sequential combination of azacitidine and lenalidomide in del(5q) higher-risk myelodysplastic syndromes or acute myeloid leukemia: a phase I study. Leukemia. 2013;27(6):1403–7. PubMedCentralPubMedCrossRef
Metadaten
Titel
Potential impact of the hypomethylating agent 5-azacitidine on chronic lymphocytic leukemia with del(17)(p)/del(p53) and subsequent therapy-related acute myeloid leukemia without these aberrations: a case report
verfasst von
MD, MBA Prof. Michael Pfeilstöcker
MD Rainer Weichselbaum
Helmut Mühlberger
MD Elisabeth Menschel
MD Felix Keil
Publikationsdatum
01.06.2015
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 2/2015
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-015-0201-0