Advertisement

International Journal of Hematology

, Volume 79, Issue 1, pp 31–36 | Cite as

Acute Promyelocytic Leukemia during Pregnancy: Report of 3 Cases

  • Ugo Consoli
  • Amalia Figuera
  • Giuseppe Milone
  • Carmela Rita Meli
  • Giulia Guido
  • Francesco Indelicato
  • Gaetano Moschetti
  • Salvatore Leotta
  • Antonella Tornello
  • Massimo Poidomani
  • Pamela Murgano
  • Valeria Pinto
  • Rosario Giustolisi
Case Report

Abstract

Acute promyelocytic leukemia (APL) is characterized by onset at a young age and a life-threatening hemorrhagic diathesis, which is attributed to a disseminated intravascular coagulation (DIC)-like coagulopathy. The discovery of all-trans-retinoic acid has changed the course of APL treatment by reducing the onset of DIC and inducing a complete and durable remission in more than 90% of patients. The occurrence of APL during pregnancy is not a frequent event, but the management of these patients raises many therapeutic and ethical dilemmas and requires a careful clinical case evaluation of fetal and maternal risk, coagulation status, the parents’ wishes, and therapeutic options. Here we describe 3 patients with APL diagnosed during pregnancy. Clinical data and the therapeutic approaches are presented. In the discussion, we analyze clinical decisions and therapeutic options and compare our cases with those found in the literature. Int J Hematol. 2004;79:31-36.

Key words

APL ATRA Pregnancy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Warrell RP, de The H, Wang ZY, Degos L. Acute promyelocytic leukemia.N Engl J Med. 1993;329:177–189.CrossRefPubMedGoogle Scholar
  2. 2.
    Tallman MS, Kwaan HC. Reassessing the hemostatic disorder associated with acute promyelocytic leukemia.Blood. 1992;79:543–553.PubMedGoogle Scholar
  3. 3.
    Speiser W, Pabinger-Fasching I, Kyrle PA, et al. Hemostatic and fibrinolytic parameters in patients with acute myeloid leukemia: activation of blood coagulation, fibrinolysis and unspecific proteolysis.Blut. 1990;61:298–302.CrossRefPubMedGoogle Scholar
  4. 4.
    Degos L, Dombret H, Chomienne C, et al. All-trans-retinoic acid as a differentiating agent in the treatment of acute promyelocytic leukemia.Blood. 1995;85:2643–2653.PubMedGoogle Scholar
  5. 5.
    Warrell RP Jr, Frankel SR, Miller WH Jr, et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin(all-trans- retinoic acid).N Engl J Med. 1991;324:1385–1893.CrossRefPubMedGoogle Scholar
  6. 6.
    Fenaux P, Chomienne C, Degos L.All-trans retinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia.Semin Hematol. 2001;38:13–25.CrossRefPubMedGoogle Scholar
  7. 7.
    Zuazu J, Julia A, Sierra J, et al. Pregnancy outcome in hematological malignancies.Cancer. 1991;67:703–709.CrossRefPubMedGoogle Scholar
  8. 8.
    Huang ME, Ye YC, Chen SR, et al. Use ofall-trans retinoic acid in the treatment of acute promyelocytic leukemia.Blood. 1988;72:567–572.PubMedGoogle Scholar
  9. 9.
    Frankel SR, Eardley A, Lauwers G, Weiss M, Warrel RP. The “retinoic acid syndrome” in acute promyelocytic leukemia.Ann Intern Med. 1992;117:292–296.CrossRefPubMedGoogle Scholar
  10. 10.
    Lipovsky MM, Biesma DH, Christiaens GCML, Petersen EJ. Successful treatment of acute promyelocytic leukemia withall-trans- retinoic-acid during late pregnancy.Br J Haematol. 1996;94:699–701.CrossRefPubMedGoogle Scholar
  11. 11.
    Giagounidis AA, Beckmann MW, Giagounidis AS, et al. Acute promyelocytic leukemia and pregnancy.Eur J Haematol. 2000;64:267–271.CrossRefPubMedGoogle Scholar
  12. 12.
    Incerpi MH, Miller DA, Posen R, Byrne JD.All-trans retinoic acid for the treatment of acute promyelocytic leukemia in pregnancy.Obstet Gynecol. 1997;89:826–828.CrossRefPubMedGoogle Scholar
  13. 13.
    Fadilah SA, Hatta AZ, Keng CS, Jamil MA, Singh S. Successful treatment of acute promyelocytic leukemia in pregnancy with all-trans retinoic acid.Leukemia. 2001;15:1665–1666.CrossRefPubMedGoogle Scholar
  14. 14.
    Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy.N Engl J Med. 1985;313:837–841.CrossRefPubMedGoogle Scholar
  15. 15.
    Lynchberg MC, Khoury MJ, Lammer EJ, Waller KO, Cordero JF, Erickson JD. Sensitivity, specificity, and positive predictive value of multiple malformations in isotretinoin embryopathy surveillance.Teratology. 1990;42:513–519.CrossRefGoogle Scholar
  16. 16.
    Stern R. When a uniquely effective drug is teratogenic: the case of isotretinoin.N Engl J Med. 1989;320:1007–1009.CrossRefPubMedGoogle Scholar
  17. 17.
    Chalmers RJ. Retinoid therapy: a real hazard for the developing embryo.Br J Obstet Gynaecol. 1992;99:276–278.CrossRefPubMedGoogle Scholar
  18. 18.
    Caligiuri MA. Leukemia and pregnancy: treatment and outcome.Adv Oncol. 1992;8:10–17.Google Scholar
  19. 19.
    Doll DC, Ringerberg S, Yarbro JW. Antineoplastic agent and pregnancy.Semin Oncol. 1989;16:337–346.PubMedGoogle Scholar
  20. 20.
    Caligiuri MA, Mayer RY. Pregnancy and leukemia.Semin Oncol. 1989;16:388–396.PubMedGoogle Scholar
  21. 21.
    Harrison P, Chipping P, Fothergill GA. Successful use ofall-trans retinoic acid in acute promyelocytic leukemia presenting during the second trimester of pregnancy.Br J Haematol. 1994;86:681–682.CrossRefPubMedGoogle Scholar
  22. 22.
    Stentoft J, Nielsen LJ, Hvidman LE.All-trans retinoic acid in acute promyelocytic leukemia in late pregnancy.Leukemia. 1994;8:1585–1588.PubMedGoogle Scholar
  23. 23.
    Watanabe R, Okamoto S, Moriki T, Kizaki M, Kawai Y, Ikeda Y. Treatment of acute promyelocytic leukemia withall-trans retinoic acid during the third trimester of pregnancy.Am J Hematol. 1995;48:210–211.CrossRefPubMedGoogle Scholar
  24. 24.
    Bhoopathi B, Ostapowicz F, Bazley W. Acute promyelocytic leukemia in pregnancy.Obstet Gynecol. 1973;41:275–278.PubMedGoogle Scholar
  25. 25.
    Ewing PA, Whittaker JA. Acute leukemia in pregnancy.Obstet Gynecol. 1973;42:245–251.PubMedGoogle Scholar
  26. 26.
    Beller FK, Wagner H, Buchner T. Peripheral microthrombotic purpura associated with acute promyelocytic leukemia in pregnancy: a light and electron microscopic study [in German].Klin Wochen- schr. 1978;56:593–599.CrossRefGoogle Scholar
  27. 27.
    Coser P, Prinoth O, Fabris P, Colombetti V, Mengarda G, Delucca A. Successful pregnancy in acute promyelocytic leukaemia.Haematologica. 1979;64:356–361.PubMedGoogle Scholar
  28. 28.
    Gstöttner M, Frisch H, Dienstl F. Delivery of a normal child after chemotherapy of acute promyelocytic leukaemia during pregnancy [in German].Blut. 1978;36:171–174.CrossRefPubMedGoogle Scholar
  29. 29.
    Alegre A, Chunchurreta R, Rodriguez-Alarcon J, Cruz E, Prada M. Successful pregnancy in promyelocytic leukemia.Cancer. 1982;49:152–153.CrossRefPubMedGoogle Scholar
  30. 30.
    Pralle H, Amberg R, Granbuer M, Loffler H. Treatment results for acute leukemias in the 22nd and 36th week of pregnancy.Blut. 1982;45:190–191.Google Scholar
  31. 31.
    Sanz MA, Rafecas FJ. Successful pregnancy during chemotherapy for acute promyelocytic leukemia.N Engl J Med. 1982;306:939.CrossRefPubMedGoogle Scholar
  32. 32.
    Katagiri S, Tsubakio T, Minami G, et al. Successful embolization for uterine hemorrhage in a patient with acute promyelocytic leukemia.Acta Haematol. 1983;70:119–121.CrossRefPubMedGoogle Scholar
  33. 33.
    Catanzarite VA, Ferguson JE 2nd. Acute leukemia and pregnancy: a review of management and outcome, 1972-1982.Obstet Gynecol Surv. 1984;39:663–678.CrossRefPubMedGoogle Scholar
  34. 34.
    Fassas A, Kartalis G, Klearchou N, Tsatalas K, Sinacos Z, Mantalenakis S. Chemotherapy for acute leukemia during pregnancy: five case reports.Nouv Rev Fr Hematol. 1984;26:19–24.Google Scholar
  35. 35.
    Tono A, Shimokawa H, Uchino H, et al. Pregnancy complicated with acute promyelocytic leukemia: case report [in Japanese].Nippon Sanka Fujinka Gakkai Zasshi. 1986;38:131–134.Google Scholar
  36. 36.
    Bartsch HH, Meyer D, Teichmann AT, Speer CP. Treatment of promyelocytic leukemia during pregnancy: a case report and review of the literature.Blut. 1988;57:51–54.CrossRefGoogle Scholar
  37. 37.
    D'Emilio A, Dragone P, De Negri G, Montaldi A, Stella M, Battista R. Acute myelogenous leukemia in pregnancy.Haematologica. 1989;74:601–604.Google Scholar
  38. 38.
    Wallace PJ. Complete remission in acute promyelocytic leukemia despite the persistence of the 15;17 translocation.Am J Hematol. 1989;31:266–268.CrossRefGoogle Scholar
  39. 39.
    Takatsuki H, Abe Y, Goto T, et al. Two cases of acute promyelocytic leukemia in pregnancy and the effect of anthracyclines on fetal development [in Japanese].Rinsho Ketsueki. 1992;33:1736–1740.Google Scholar
  40. 40.
    Celo JS, Kim HC, Houlihan C, Canavan BF, Manzullo GP, Saidi P. Acute promyelocytic leukemia in pregnancy:all-trans retinoic acid as a newer therapeutic option.Obstet Gynecol. 1994;83:808–811.PubMedGoogle Scholar
  41. 41.
    Tsuda H, Doi H, Inada T, Shirono K. Successful treatment of acute promyelocytic leukemia in a pregnant woman by usingall-trans retinoic acid [in Japanese].Rinsho Ketsueki. 1994;35:717–719.PubMedGoogle Scholar
  42. 42.
    Morton J, Taylor K, Wright S, et al. Successful maternal and fetal outcome following the use of ATRA for the induction of APML late in the first trimester [abstract].Blood. 1995;86:772a.Google Scholar
  43. 43.
    Aragona M, Asmundo A. Two fatal cases of acute myeloid leukemia (M3, M4) during pregnancy [in Italian].Pathologica. 1995;87:125–134.PubMedGoogle Scholar
  44. 44.
    Simone MD, Stasi R, Venditti A, et al.All-trans retinoic acid (ATRA) administration during pregnancy in relapsed acute promyelocytic leukemia.Leukemia. 1995;9:1412–1413.PubMedGoogle Scholar
  45. 45.
    Nakamura K, Dan K, Iwakiri R, Gomi S, Nomura T. Successful treatment of acute promyelocytic leukemia in pregnancy with all-trans retinoic acid.Ann Hematol. 1995;71:263–264.CrossRefPubMedGoogle Scholar
  46. 46.
    Hoffman MA, Wiernik PH, Kleiner GJ. Acute promyelocytic leukemia and pregnancy: a case report.Cancer. 1995;76:2237–2241.CrossRefPubMedGoogle Scholar
  47. 47.
    Lin CP, Huang MJ, Liu HJ, Chang IY, Tsai CH. Successful treatment of acute promyelocytic leukemia in a pregnant Jehovah's Witness withall-trans retinoic acid, rhG-CSF, and erythropoietin.Am J Hematol. 1996;51:251–252.CrossRefPubMedGoogle Scholar
  48. 48.
    Sham RL.All-trans retinoic acid-induced labor in a pregnant patient with acute promyelocytic leukemia [letter].Am J Hematol. 1996;53:145.CrossRefPubMedGoogle Scholar
  49. 49.
    Terada Y, Shindo T, Endoh A, Watanabe M, Fukaya T, Yajima A. Fetal arrhythmia during treatment of pregnancy-associated acute promyelocytic leukemia withall-trans retinoic acid and favorable outcome.Leukemia. 1997;11:454–455.CrossRefPubMedGoogle Scholar
  50. 50.
    Maeda M, Tyugu H, Okubo T, Yamamoto M, Nakamura K, Dan K. A neonate born to a mother with acute promyelocytic leukemia treated byall-trans retinoic acid [in Japanese].Rinsho Ketsueki. 1997;38:770–775.PubMedGoogle Scholar
  51. 51.
    Breccia M, Cimino G, Alimena G, De Carolis S, Lo Coco F, Mandelli F. AIDA treatment for high-risk acute promyelocytic leukemia in a pregnant woman at 21 weeks of gestation.Haematologica. 2002;87:ELT12.Google Scholar
  52. 52.
    Carradice D, Austin N, Bayston K, Ganly PS. Successful treatment of acute promyelocytic leukaemia during pregnancy.Clin Lab Haematol. 2002;24:307–311.CrossRefPubMedGoogle Scholar
  53. 53.
    Siu BL, Alonzo MR, Vargo TA, Fenrich AL. Transient dilated cardiomy opathy in a newborn exposed to idarubicin and all-transretinoic acid (ATRA) early in the second trimester of pregnancy.Int J Gynecol Cancer. 2002;12:399–402.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Ugo Consoli
    • 1
  • Amalia Figuera
    • 1
  • Giuseppe Milone
    • 1
  • Carmela Rita Meli
    • 1
  • Giulia Guido
    • 1
  • Francesco Indelicato
    • 1
  • Gaetano Moschetti
    • 1
  • Salvatore Leotta
    • 1
  • Antonella Tornello
    • 1
  • Massimo Poidomani
    • 1
  • Pamela Murgano
    • 1
  • Valeria Pinto
    • 1
  • Rosario Giustolisi
    • 1
  1. 1.Chair and Division of Haematology with Bone Marrow Transplantation UnitUniversity of CataniaCataniaItaly

Personalised recommendations