Acute Promyelocytic Leukemia Differential Diagnoses

  • Author: Sandy D Kotiah, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Aug 2, 2011
 
 

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Sandy D Kotiah, MD  Fellow in Hematology Oncology, Thomas Jefferson University Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Specialty Editor Board

Clarence Sarkodee-Adoo, MD  Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Disclosure: Takeda Millenium Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Ronald A Sacher, MB, BCh, MD, FRCPC  Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgments

I would like to acknowledge Dr. Emmanuel Besa for allowing me the opportunity to write this article.

References

  1. Bernard J. History of promyelocytic leukaemia. Leukemia. 1994;8 suppl 2:S1-5. [Medline].

  2. Vahdat L, Maslak P, Miller WH Jr, et al. Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid. Blood. Dec 1 1994;84(11):3843-9. [Medline]. [Full Text].

  3. Jurcic JG, Soignet SL, Maslak AP. Diagnosis and treatment of acute promyelocytic leukemia. Curr Oncol Rep. Sep 2007;9(5):337-44. [Medline].

  4. Ribeiro RC, Rego E. Management of APL in developing countries: epidemiology, challenges and opportunities for international collaboration. Hematology Am Soc Hematol Educ Program. 2006;162-8. [Medline]. [Full Text].

  5. Devita VT, Hellman S, Rosenberg SA. Acute leukemias. In: DeVita VT, Rosenberg SA, Lawrence TS, eds. DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology. Vol. 2. 8th ed. Philadelphia, Pa: Lippincott, Williams and Wilkins; 2008:2240-1.

  6. Menell JS, Cesarman GM, Jacovina AT, et al. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med. Apr 1 1999;340(13):994-1004. [Medline]. [Full Text].

  7. Sainty D, Liso V, Cantu-Rajnoldi A, et al for the Group Francais de Cytogenetique Hematologique, UK Cancer Cytogenetics Group and BIOMED 1 European Community-Concerted Acion "Molecular Cytogenetic Diagnosis in Haematological Malignancies. A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements. Blood. Aug 15 2000;96(4):1287-96. [Medline]. [Full Text].

  8. Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. Feb 26 2009;113(9):1875-91. [Medline]. [Full Text].

  9. Tallman MS, Andersen JW, Schiffer CA, et al. All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood. Dec 15 2002;100(13):4298-302. [Medline]. [Full Text].

  10. Sanz MA, Martin G, Gonzalez M, et al, for the Programa de Estudio y Traitmiento de las Hemopatias Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. Feb 15 2004;103(4):1237-43. [Medline]. [Full Text].

  11. Fenaux P, Chastang C, Chevret S, et al, for the The European APL Group. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. Blood. Aug 15 1999;94(4):1192-200. [Medline]. [Full Text].

  12. Sanz MA, Lo Coco F, Martin G, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. Aug 15 2000;96(4):1247-53. [Medline]. [Full Text].

  13. Ades L, Sanz MA, Chevret S, et al. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. Feb 1 2008;111(3):1078-84. [Medline]. [Full Text].

  14. de la Serna J, Montesinos P, Vellenga E, et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood. Apr 1 2008;111(7):3395-402. [Medline]. [Full Text].

  15. Montesinos P, Gonzalez JD, Gonzalez J, 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. Aug 20 2010;28(24):3872-9. [Medline].

  16. Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, et al. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. Nov 11 2010;116(19):3751-7. [Medline]. [Full Text].

  17. Grimwade D, Howe K, Langabeer S, et al. Minimal residual disease detection in acute promyelocytic leukemia by reverse-transcriptase PCR: evaluation of PML-RAR alpha and RAR alpha-PML assessment in patients who ultimately relapse. Leukemia. Jan 1996;10(1):61-6. [Medline].

  18. Avvisati G, Lo-Coco F, Paoloni FP, et al. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. May 5 2011;117(18):4716-25. [Medline].

  19. Shigeno K, Naito K, Sahara N, et al. Arsenic trioxide therapy in relapsed or refractory Japanese patients with acute promyelocytic leukemia: updated outcomes of the phase II study and postremission therapies. Int J Hematol. Oct 2005;82(3):224-9. [Medline].

  20. Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, et al. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. Apr 13 2004;101(15):5328-35. [Medline]. [Full Text].

  21. Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. Sep 15 2001;19(18):3852-60. [Medline]. [Full Text].

  22. Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. Aug 20 2010;28(24):3866-71. [Medline].

  23. Lo Coco F, Ammatuna E, Noguera N. Treatment of acute promyelocytic leukemia with gemtuzumab ozogamicin. Clin Adv Hematol Oncol. Jan 2006;4(1):57-62, 76-7. [Medline].

  24. Lo-Coco F, Cimino G, Breccia M, et al. Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood. Oct 1 2004;104(7):1995-9. [Medline]. [Full Text].

  25. Estey EH, Giles FJ, Beran M, et al. Experience with gemtuzumab ozogamycin ("Mylotarg") and all-trans retinoic acid in untreated acute promyelocytic leukemia. Blood. Jun 1 2002;99(11):4222-4. [Medline]. [Full Text].

  26. de Botton S, Fawaz A, Chevret S, et al. Autologous and allogeneic stem-cell transplantation as salvage treatment of acute promyelocytic leukemia initially treated with all-trans-retinoic acid: a retrospective analysis of the European Acute Promyelocytic Leukemia Group. J Clin Oncol. Jan 1 2005;23(1):120-6. [Medline]. [Full Text].

  27. Fenaux P, Chastang C, Chevret S, et al, for the European APL Group. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. Blood. Aug 15 1999;94(4):1192-200. [Medline]. [Full Text].

  28. Sanz MA, Vellenga E, Rayon C, et al. All-trans retinoic acid and anthracycline monochemotherapy for the treatment of elderly patients with acute promyelocytic leukemia. Blood. Dec 1 2004;104(12):3490-3. [Medline]. [Full Text].

  29. [Best Evidence] 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. Aug 20 2010;28(24):3872-9. [Medline].

  30. Montesinos P, Rayon C, Vellenga E, et al. Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens. Blood. Dec 8 2010;[Medline].

  31. Tallman MS, Kim HT, Montesinos P, et al. Does microgranular variant morphology of acute promyelocytic leukemia independently predict a less favorable outcome compared with classical M3 APL? A joint study of the North American Intergroup and the PETHEMA Group. Blood. Dec 16 2010;116(25):5650-9. [Medline].

  32. [Best Evidence] Bhojwani D, Kang H, Menezes RX, et al, for the Children's Oncology Group Study. Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: a Children's Oncology Group study [corrected]. J Clin Oncol. Sep 20 2008;26(27):4376-84. [Medline].

  33. de Botton S, Dombret H, Sanz M, et al, for the European APL Group. Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. Blood. Oct 15 1998;92(8):2712-8. [Medline]. [Full Text].

  34. de Botton S, Sanz MA, Chevret S, et al for the European APL Group and PETHEMA Group. Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Leukemia. Jan 2006;20(1):35-41. [Medline].

  35. Douer D. The epidemiology of acute promyelocytic leukaemia. Best Pract Res Clin Haematol. Sep 2003;16(3):357-67. [Medline].

  36. Ferrara F, Morabito F, Martino B, et al. CD56 expression is an indicator of poor clinical outcome in patients with acute promyelocytic leukemia treated with simultaneous all-trans-retinoic acid and chemotherapy. J Clin Oncol. Mar 2000;18(6):1295-300. [Medline]. [Full Text].

  37. Ghavamzadeh A, Alimoghaddam K, Ghaffari SH, et al. Treatment of acute promyelocytic leukemia with arsenic trioxide without ATRA and/or chemotherapy. Ann Oncol. Jan 2006;17(1):131-4. [Medline]. [Full Text].

  38. Ikeda K, Sasaki K, Tasaka T, et al. Reverse transcription-polymerase chain reaction for PML-RAR alpha fusion transcripts in acute promyelocytic leukemia and its application to minimal residual leukemia detection. Leukemia. Apr 1993;7(4):544-8. [Medline].

  39. Kharfan-Dabaja MA, Abou Mourad YR, Fernandez HF, Pasquini MC, Santos ES. Hematopoietic cell transplantation in acute promyelocytic leukemia: a comprehensive review. Biol Blood Marrow Transplant. Sep 2007;13(9):997-1004. [Medline].

  40. Matasar MJ, Ritchie EK, Consedine N, Magai C, Neugut AI. Incidence rates of acute promyelocytic leukemia among Hispanics, blacks, Asians, and non-Hispanic whites in the United States. Eur J Cancer Prev. Aug 2006;15(4):367-70. [Medline].

  41. Rego EM, Wang ZG, Peruzzi D, et al. Role of promyelocytic leukemia (PML) protein in tumor suppression. J Exp Med. Feb 19 2001;193(4):521-29. [Medline]. [Full Text].

  42. Shimokawa T, Kojima Y. [Gemtuzumab ozogamicin successfully induced molecular remission in relapsed therapy-related acute promyelocytic leukemia] [Japanese]. Rinsho Ketsueki. Apr 2008;49(4):270-2. [Medline].

  43. Slack JL, Arthur DC, Lawrence D, et al. Secondary cytogenetic changes in acute promyelocytic leukemia--prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: a Cancer and Leukemia Group B study. J Clin Oncol. May 1997;15(5):1786-95. [Medline].

  44. Stasi R, Evangelista ML, Buccisano F, Venditti A, Amadori S. Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. Cancer Treat Rev. Feb 2008;34(1):49-60. [Medline].

  45. Tallman MS, Nabhan C, Feusner JH, Rowe JM. Acute promyelocytic leukemia: evolving therapeutic strategies. Blood. Feb 1 2002;99(3):759-67. [Medline]. [Full Text].

  46. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. Mar 1 2008;111(5):2505-15. [Medline]. [Full Text].

 
Previous
Next
 
Bone marrow aspirate hybridized with the RARA dual color break-apart probe set (Abbott-Vysis). The cell to the left shows a normal cell with 2 fusion signals, as the 5'RARA probe (orange) and the 3'RARA probe (green) are not separated. The cell on the right shows split signals for one RARA gene, indicating a chromosomal rearrangement disrupting the RARA gene. Image courtesy of Dr. Tina Edmonston from the Department of Pathology at Thomas Jefferson University Hospital.
Bone marrow aspirate hybridized with PML/RARA dual color translocation probe set (Abbott-Vysis). The cell to the right shows a normal cell with 2 separate PML (orange) and RARA (green) signals each. The cell to the left shows an abnormal cell characterized by a single fusion signal juxtaposing the PML and RARA signals, suggestive of a translocation of the 2 genes. Images courtesy of Dr. Tina Edmonston from the Department of Pathology at Thomas Jefferson University Hospital.
Hypogranular subtype of acute promyelocytic leukemia. Image courtesy of Dr. William Kocher.
Regularly hypergranular subtype of acute promyelocytic leukemia. Image courtesy of Dr. William Kocher.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.