Lab Med Online.  2011 Oct;1(4):227-231. 10.3343/lmo.2011.1.4.9.

A Case of Therapy-related Myeloid Neoplasm after Successful Treatment of Acute Promyelocytic Leukemia

• Kwon A
• Park JY
• Kwon JH
• Song HH
• Shin KS
• Lee YK
• Cho HC

• KMID: 1993641
• DOI: http://doi.org/10.3343/lmo.2011.1.4.9

Abstract

Acute promyelocytic leukemia (APL) is considered as a curative disease after combined chemotherapy based on all-trans retinoic acid (ATRA) and anthracycline. However, as long-term survivors continue to increase, reports on sporadic cases of therapy-related myeloid neoplasm (t-MN) after successful APL treatment are also increasing. Recently, we have experienced one patient who developed t-MN 7 yr after APL diagnosis. Even though he had not been exposed to alkylating agents at all, he showed alkylating agents-associated features such as long latency period (>5 yr), first presentation as myelodysplatic phase (multilineage dysplasia with increased blasts), and complex karyotype including monosomy 5 and 7. He received only supportive care and expired 3 months after the diagnosis of t-MN (6 months of survival after the onset of cytopenias). t-MN after complete remission of APL is a rare but fatal complication, and patients with complex karyotypes show ominous prognosis in particular. For the early diagnosis of t-MN, long-term and close monitoring of the patient is needed. One should suspect this late complication whenever any unknown cytopenia develops, and should perform bone marrow biopsy and cytogenetic analysis.

Keyword

Therapy-related myeloid neoplasm; Acute promyelocytic leukemia; Alkylating agents

MeSH Terms

Alkylating Agents
Biopsy
Bone Marrow
Cytogenetic Analysis
Early Diagnosis
Humans
Karyotype
Latency Period (Psychology)
Leukemia, Promyelocytic, Acute
Monosomy
Prognosis
Survivors
Tretinoin
Alkylating Agents
Tretinoin

Figure

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  Fig. 1 Bone marrow aspirate smear showing blasts (A to C) and dyserythropoiesis (D to F) at the diagnosis of therapy-related myeloid neoplasm (Wright-Giemsa stain, ×1,000).

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  Fig. 2 Giemsa-banded karyotype of bone marrow cells showing 42,XY, -3,-5,-7,-12,der(17)t(11;17)(p10;q10) at the diagnosis of therapy-related myeloid neoplasm (arrows).

Reference

1. Warrell RP Jr, de Thé H, Wang ZY, Degos L. Acute promyelocytic leukemia. N Engl J Med. 1993. 329:177–189.

2. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008. 111:2505–2515.

3. Leone G, Fianchi L, Pagano L, Voso MT. Incidence and susceptibility to therapy-related myeloid neoplasms. Chem Biol Interact. 2010. 184:39–45.

4. Park TS, Choi JR, Yoon SH, Song J, Kim J, Kim SJ, et al. Acute promyelocytic leukemia relapsing as secondary acute myelogenous leukemia with translocation t(3;21)(q26;q22) and RUNX1-MDS1-EVI1 fusion transcript. Cancer Genet Cytogenet. 2008. 187:61–73.

5. Jubashi T, Nagai K, Miyazaki Y, Nakamura H, Matsuo T, Kuriyama K, et al. A unique case of t(15;17) acute promyelocytic leukemia (M3) developing into acute myeloblastic leukemia (M1) with t(7;21) at relapse. Br J Haematol. 1993. 83:665–668.

6. Miyazaki H, Ino T, Sobue R, Kojima H, Wakita M, Nomura T, et al. Translocation (3;21)(q26;q22) in treatment-related acute leukemia secondary to acute promyelocytic leukemia. Cancer Genet Cytogenet. 1994. 74:84–86.

7. Hatzis T, Standen GR, Howell RT, Savill C, Wagstaff M, Scott GL. Acute promyelocytic leukemia (M3): relapse with acute myeloblastic leukaemia (M2) and dic(5;17)(q11;p11). Am J Hematol. 1995. 48:40–44.

8. Felice MS, Rossi J, Gallego M, Zubizarreta PA, Cygler AM, Alfaro E, et al. Acute trilineage leukemia with monosomy of chromosome 7 following an acute promyelocytic leukemia. Leuk Lymphoma. 1999. 34:409–413.

9. Sawada H, Morimoto H, Wake A, Yamasaki Y, Izumi Y. Therapy-related acute myeloid leukemia with t(10;11)(q23;p15) following successful chemotherapy for acute promyelocytic leukemia with t(15;17)(q22;q21). Int J Hematol. 1999. 69:270–271.

10. Stavroyianni N, Yataganas X, Abazis D, Pangalos C, Meletis J. Acute promyelocytic leukemia relapsing into FAB-M2 acute myeloid leukemia with trisomy 8. Cancer Genet Cytogenet. 2000. 117:82–83.

11. Zompi S, Legrand O, Bouscary D, Blanc CM, Picard F, Casadevall N, et al. Therapy-related acute myeloid leukaemia after successful therapy for acute promyelocytic leukaemia with t(15;17): a report of two cases and a review of the literature. Br J Haematol. 2000. 110:610–613.

12. Au WY, Lam CC, Ma ES, Man C, Wan T, Kwong YL. Therapy-related myelodysplastic syndrome after eradication of acute promyelocytic leukemia: cytogenetic and molecular features. Hum Pathol. 2001. 32:126–129.

13. Pecci A, Invernizzi R. A therapy-related myelodysplastic syndrome with unusual features in a patient treated for acute promyelocytic leukemia. Haematologica. 2001. 86:102–103.

14. Athanasiadou A, Saloum R, Zorbas I, Tsompanakou A, Batsis I, Fassas A, et al. Therapy-related myelodysplastic syndrome with monosomy 5 and 7 following successful therapy for acute promyelocytic leukemia with anthracyclines. Leuk Lymphoma. 2002. 43:2409–2411.

15. Garcia-Manero G, Kantarjian HM, Kornblau S, Estey E. Therapy-related myelodysplastic syndrome or acute myelogenous leukemia in patients with acute promyelocytic leukemia (APL). Leukemia. 2002. 16:1888.

16. Latagliata R, Petti MC, Fenu S, Mancini M, Spiriti MA, Breccia M, et al. Therapy-related myelodysplastic syndrome-acute myelogenous leukemia in patients treated for acute promyelocytic leukemia: an emerging problem. Blood. 2002. 99:822–824.

17. Drake M, Humphreys MW, Alexander HD, Morris TC. Early second leukaemia in a patient with successfully treated acute promyelocytic leukaemia. Leuk Lymphoma. 2003. 44:895–896.

18. Lobe I, Rigal-Huguet F, Vekhoff A, Desablens B, Bordessoule D, Mounier C, et al. Myelodysplastic syndrome after acute promyelocytic leukemia: the European APL group experience. Leukemia. 2003. 17:1600–1604.

19. Panizo C, Patiño A, Lecumberri R, Calasanz MJ, Odero MD, Bendandi M, et al. Secondary myelodysplastic syndrome after treatment for promyelocytic leukemia: clinical and genetic features of two cases. Cancer Genet Cytogenet. 2003. 143:178–181.

20. Lee GY, Christina S, Tien SL, Ghafar AB, Hwang W, Lim LC, et al. Acute promyelocytic leukemia with PML-RARA fusion on i(17q) and therapy-related acute myeloid leukemia. Cancer Genet Cytogenet. 2005. 159:129–136.

21. Pawarode A, Finlay E, Sait SN, Barcos M, Baer MR. Isochromosome 1q in a myelodysplastic syndrome after treatment for acute promyelocytic leukemia. Cancer Genet Cytogenet. 2006. 167:155–160.

22. Gündüz E, Akay OM, Durak B, Gülbaş Z. Therapy-related myelodysplastic syndrome following acute promyelocytic leukemia and biphenotypic acute leukemia following stem cell transplantation in the same patient. Turk J Hematol. 2007. 24:85–87.

23. Snijder S, Mellink CH, van der Lelie H. Translocation (2;11)(q37;q23) in therapy-related myelodysplastic syndrome after treatment for acute promyelocytic leukemia. Cancer Genet Cytogenet. 2008. 180:149–152.

24. Bao L, Lu X, Lai Y, Zhang X, Zhu H, Liu Y, et al. Therapy-related acute myeloid leukemia after successful therapy for acute promyelocytic leukemia with t(15;17): A case report and literature review. Leuk Res. 2009. 33:e64–e68.

25. Batzios C, Hayes LA, He SZ, Quach H, McQuilten ZK, Wall M, et al. Secondary clonal cytogenetic abnormalities following successful treatment of acute promyelocytic leukemia. Am J Hematol. 2009. 84:715–719.

26. Imagawa J, Harada Y, Shimomura T, Tanaka H, Okikawa Y, Hyodo H, et al. Clinical and genetic features of therapy-related myeloid neoplasms after chemotherapy for acute promyelocytic leukemia. Blood. 2010. 116:6018–6022.

27. Montesinos P, González JD, González J, Rayón C, de Lisa E, Amigo ML, et al. Therapy-related myeloid neoplasms in patients with acute promyelocytic leukemia treated with all-trans-retinoic acid and anthracycline-based chemotherapy. J Clin Oncol. 2010. 28:3872–3879.

28. Vardiman JW, Arber DA, et al. Swerdlow SH, Campo E, editors. Therapy-related myeloid neoplasms. WHO classification of tumours of haematopoietic and lymphoid tissues. 2008. 4th ed. Lyon: IARC;127–129.

29. Lo Coco F, Latagliata R, Diverio D, Breccia M, Chiusolo P, Mandelli F. Independent clonal origin of therapy-related MDS-AML developing after treatment of acute promyelocytic leukemia. Blood. 2002. 100:1929.

30. Andersen MK, Pedersen-Bjergaard J. Therapy-related MDS and AML in acute promyelocytic leukemia. Blood. 2002. 100:1928–1929.