Blood Reviews
Volume 22, Issue 5 , Pages 247-259 , September 2008

How I treat acute and chronic leukemia in pregnancy

  • Tal Shapira

      Affiliations

    • Department of Internal Medicine A, Meir Hospital, Sapir Medical Center, Kfar-Sava, Israel
    • ,
  • David Pereg

      Affiliations

    • Department of Internal Medicine A, Meir Hospital, Sapir Medical Center, Kfar-Sava, Israel
    • Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
    • ,
  • Michael Lishner

      Affiliations

    • Department of Internal Medicine A, Meir Hospital, Sapir Medical Center, Kfar-Sava, Israel
    • Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
    • Corresponding Author InformationCorresponding author. Tel.: +972 9 7472534; fax: +972 9 7460781.

References 

  1. Pentheroudakis G, Pavlidis N. Cancer and pregnancy: poema magna, not anymore. Eur J Cancer. 2006;42:126–140
  2. Koren G, Lishner M, Santiago S. The Motherisk Guide to Cancer in Pregnancy and Lactation. 2nd ed.. Toronto: Motherisk program; 2005;
  3. Pavlidis NA. Coexistence of pregnancy and malignancy. Oncologist. 2002;7:279–287
  4. Peleg D, Ben-Ami M. Lymphoma and leukemia complicating pregnancy. Obstet Gynecol Clin North Am. 1998;25:365–383
  5. Caligiuri MA, Mayer RJ. Pregnancy and leukemia. Semin Oncol. 1989;16:388–396
  6. Chrisomalis L, Baxi LV, Heller D. Chronic lymphocytic leukemia in pregnancy. Am J Obstet Gynecol. 1996;175:1381–1382
  7. Weisz B, Meirow D, Schiff E, Lishner M. Impact and treatment of cancer during pregnancy. Exper Rev Anticancer Ther. 2004;4:889–902
  8. Pacifici GM, Nottoli R. Placental transfer of drugs administered to the mother. Clin Pharmacokinet. 1995;28:235–269
  9. Cardonick E, Iacobucci A. Use of chemotherapy during human pregnancy. Lancet Oncol. 2004;5:283–291
  10. Leslie KK, Koil C, Rayburn WF. Chemotherapeutic drugs in pregnancy. Obstet Gynecol Clin North Am. 2005;32:627–640
  11. Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Sutcliffe SB, Koren G. Fetal outcome after in utero exposure to cancer chemotherapy. Arch Intern Med. 1992;152:573–576
  12. Doll DC, Ringenberg QS, Yarbro JW. Management of cancer during pregnancy. Arch Intern Med. 1998;148:2058–2064
  13. Randall T. National registry seeks scarce data on pregnancy outcomes during chemotherapy. JAMA. 1993;269:323
  14. Asker C, Wikner B, Kallen B. Use of antiemetic drugs during pregnancy in Sweden. Eur J Clin Pharmacol. 2005;61:899–906
  15. Einarson A, Maltepe C, Navioz Y, Kennedy D, Tan MP, Koren G. The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study. BJOG. 2004;111:940–943
  16. Lynch CM, Sinnott JT, Holt DA, Herold AH. Use of antibiotics during pregnancy. Am Fam Physician. 1991;43:1365–1368
  17. Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. The teratogenic risk of trimethoprim-sulfonamides: a population based case-control study. Reprod Toxicol. 2001;15:637–646
  18. King CT, Rogers PD, Cleary JD, Chapman SW. Antifungal therapy during pregnancy. Clin Infect Dis. 1998;27:1151–1160
  19. Sobel JD. Use of antifungal drugs in pregnancy: a focus on safety. Drug Saf. 2000;23:77–85
  20. Aviles A, Neri N. Hematological malignancies and pregnancy: a final report of 84 children who received chemotherapy in utero. Clin Lymphoma. 2001;2:173–177
  21. Nulman I, Laslo D, Fried S, Uleryk E, Lishner M, Koren G. Neurodevelopment of children exposed in utero to treatment of maternal malignancy. Br J Cancer. 2001;85:1611–1618
  22. Kawamura S, Yoshike M, Shimoyama T, et al. Management of acute leukemia during pregnancy: From the results of a nationwide questionnaire survey and literature survey. Tohoku J. Exp. Med. 1994;174:167–175
  23. Greenlund LIS, Letendre L, Tefferi A. Acute leukemia during pregnancy: A single institution experience with 17 cases. Leuk Lymph. 2001;41:571–577
  24. http://www.utdol.com/utd/content/topic.do?topicKey=drug_a_k/69863&drug=true.
  25. Hahn KM, Johnson PH, Gordon N, et al. Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Cancer. 2006;107:1219–1226
  26. Aviles A, Neri N, Nambo MJ. Long term evaluation of cardiac function in children who received anthracyclines during pregnancy. Ann Oncol. 2006;17:286–288
  27. Lishner M, Zemlickis D, Degendorfer P, Panzarella T, Sutcliffe SB, Koren G. Maternal and fetal outcome following Hodgkin’s disease in pregnancy. Br J Cancer. 1992;65:114–117
  28. Pereg D, Koren G, Lishner M. The treatment of Hodgkin’s and non-Hodgkin’s lymphoma in pregnancy. Haematologica. 2007;92:1230–1237
  29. Germann N, Goffiner F, Godwasser F. Anthracyclines during pregnancy: embryo-fetal outcome in 160 patients. Ann Oncol. 2004;15:146–150
  30. 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
  31. Siu BL, Alonzo MR, Vargo TA, Fenrich AL. Transient dilated cardiomyopathy in a newborn exposed to idarubicin and all-trans-retinoic acid (ATRA) early in the second trimester of pregnancy. Int J Gynecol Cancer. 2002;12:399–402
  32. 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
  33. Delgado-Lamas JL, Garcés-Ruiz OM. Acute promyelocytic leukemia in late pregnancy. Successful treatment with All-Trans-Retinoic Acid (ATRA) and Chemotherapy. Hematology. 2000;4:415–418
  34. Harrison P, Chipping P, Fothergill GA. Successful use of all-trans retinoic acid in acute promyelocytic leukaemia presenting during the second trimester of pregnancy. Br J Haematol. 1994;86:681–682
  35. 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
  36. Stentoft J, Nielsen JL, Hvidman LE. All-trans retinoic acid in acute promyelocytic leukemia in late pregnancy. Leukemia. 1994;8:1585–1588
  37. Molkenboer JF, Vos AH, Schouten HC, Vos MC. Acute lymphoblastic leukaemia in pregnancy. Neth J Med. 2005;63:361–363
  38. Chelghoum Y, Vey N, Raffoux E, et al. Acute leukemia during pregnancy: a report on 37 patients and a review of the literature. Cancer. 2005;104:110–117
  39. Hansen WF, Fretz P, Hunter SK, Yankowitz J. Leukemia in pregnancy and fetal response to multiagent chemotherapy. Obstet Gynecol. 2001;97:809–812
  40. Bergstrom SK, Altman AJ. Pregnancy during therapy for childhood acute lymphoblastic leukemia: two case reports and a review of the literature. J Pediatr Hematol Oncol. 1998;20:154–159
  41. Milunsky A, Graef JW, Gaynor MF. Methotrexate-induced congenital malformations. J Pediatr. 1968;72:790–795
  42. Powell HR, Ekert H. Methotrexate-induced congenital malformations. Med J Aust. 1971;2:1076–1077
  43. Diniz EM, Corradini HB, Ramos JL, Brock R. Effect on the fetus of methotrexate (amethopterin) administered to the mother. Presentation of a case. Rev Hosp Clin Fac Med Sao Paulo. 1978;33:286–290
  44. Dara P, Slater LM, Armentrout SA. Successful pregnancy during chemotherapy for acute leukemia. Cancer. 1981;47:845–846
  45. Feliu J, Juarez S, Ordonez A, Garcia-Paredes ML, Gonzalez-Baron M, Montero JM. Acute leukemia and pregnancy. Cancer. 1988;61:580–584
  46. Kozlowski RD, Steinbrunner JV, MacKenzie AH, Clough JD, Wilke WS, Segal AM. Outcome of first-trimester exposure to low-dose methotrexate in eight patients with rheumatic disease. Am J Med. 1990;88:589–592
  47. Buckley LM, Bullaboy CA, Leichtman L, Marquez M. Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother. Arthritis Rheum. 1997;40:971–973
  48. Bawle EV, Conard JV, Weiss L. Adult and two children with fetal methotrexate syndrome. Teratology. 1998;7:51–55
  49. Addar MH. Methotrexate embryopathy in a surviving intrauterine fetus after presumed diagnosis of ectopic pregnancy: case report. J Obstet Gynaecol Can. 2004;26:1001–1003
  50. In:  De Vita VT,  Hellman S,  Rosenberg SA editor. 7th ed.. Cancer, principles and practice of oncology. Philadelphia: Lippincot Williams & Wilkins; 2001;p. 2121
  51. Mesquita MM, Pestana A, Mota A. Succesful pregnancy occurring with interferon-alpha therapy in chronic myelod leukemia. Acta Obste Gynecol Scand. 2005;84:300–301
  52. Goldman JM. How I treat chronic myeloid leukemia in the imatinib era. Blood. 2007;110:2828–2837
  53. Cohen MH, Johnson JR, Pazdur R. US Food and Drug Administration drug approval summary: Conversion of imatinib mesylate tablets from accelerated approval to full approval. Clin Can Res. 2005;11:12–19
  54. Russell MA, Carpenter MW, Akhtar MS, Lagattuta TF, Gorin MJ. Imatinb mesylate and metabolite concentrations in maternal blood, umbilical cord blood, placnta and breast milk. Journal of Perinatol. 2007;27:241–243
  55. Garderet L, Santacruz R, Barbu V, van den Akker J, Carbonne B, Gorin NC. Two successful pregnancies in chronic myeloid leukemia patient treated with imatinib. Haematologica. 2007;92:ECR05
  56. Choundhary DR, Mishra P, Kumar R, Mahapatra M, Choundary VP. Pregnancy on imatinib: fatal outcome with meningocele. Ann Oncol. 2006;17:178–179
  57. Ault P, Kantarjian H, O’Brien S, et al. Pregnancy among patients with CML treated with Imatinib. JCO. 2006;24:1204–1208
  58. Suppiah R, Kalaycio M. Successful outcome of pregnancy in a patient with chronic myelogenous leukemia exposed to imatinib during the first trimester. Leuk Lymphoma. 2006;47:1149–1150
  59. Alkindi S, Dennison D, Pathare A. Imatinib in pregnancy. Eur J haematol. 2005;74:535–537
  60. Prabash K, Sastry PSRK, Biswas G, et al. Pregnancy outcome of two patients treated with imatnib. Ann Oncol. 2005;16:1983–1984
  61. Ali R, Ozkalemkas F, Ozcelik T, et al. Pregnancy under treatment of imatinib and successful labor in patient with chronic myelogenous leukemia. Outcome of discontinuation of imatinib therapy after achieving a molecular remission. Leuk Res. 2005;29:971–973
  62. Heartin E, Walkinshow S, Clarck RE. Successful outcome of pregnancy in chronic myeloid leukaemia treated with imatinib. Leuk Lymphoma. 2004;45:1307–1308
  63. Mauro MJ, Druker BJ, Maziarz RT. Divergent clinical outcome in two CML patients who discontinued imatinib therapy after achieving a molecular remission. Leuk Res. 2004;28S1:S71–S73
  64. Cortes J, O’Brien S, Kantarjian H. Discontinuation of imatinib therapy after achieving a molecular response. Blood. 2004;104:2204–2205
  65. Roth MS, Foon KA. Alpha interferon in the treatment of hematologic malignancies. Am J Med. 1986;81:871–882
  66. Mubarak AAS, Kakil IR, Awidi A, et al. Normal outcome of pregnancy in chronic myeloid leukemia treated with interferon-α in 1st trimester: report of 3 cases and review of the literature. Am J Hematol. 2002;69:115–118
  67. Hiratsuka M, Minakami H, Koshizuka S, Sato I. Administration of interferon-α during pregnancy: effect on fetus. J Perinat Med. 2000;28:372–376
  68. Vantroyen B, Vanstraelen D. Management of essential thrombocythemia during pregnancy with aspirin, interferon alpha 2a and no treatment. A comprehensive analysis of the literature. Acta Hematol. 2002;107:158–169
  69. Regierer AC, Schulz CO, Kuehnhardt D, Flath B, Possinger K. Interferon α – therapy for chronic myeloid leukemia during pregnancy. Am J Hematol. 2006;81:149–156
  70. Al Bahar S, Pandita R, Nath SV. Pregnancy in chronic myeloid leukemia patients treated with alpha interferon. Int J Gynecol Obstet. 2004;85:281–282
  71. Kuroiwa M, Gondo H, Ashida K, et al. Interferon alpha therapy for chronic myeloid leukemia during pregnancy. Am J Hematol. 1998;59:101–102
  72. Haggstrom J, Adrinsson M, Hybbinette T, Harnby E, Thornbert G. Two cases of CML treated with alpha-Interferon during second and third trimester of pregnancy with analysis of the drug in the newborn immediately postpartum. Eur J Haematol. 1996;57:101–102
  73. http://www.utdol.com/utd/content/topic.do?topicKey=leukemia/15171&type=A&selectedTitle=3~33.
  74. Fadila SAW, Ahmad-Zaliani H, Soon-Keng C, Norlaila M. Successful treatment of chronic myeloid leukemia during pregnancy with hydroxyurea. Leukemia. 2002;16:1202–1203
  75. Celiloglu M, Altunyurt S, Undar B. Hydroxyurea treatment for CML during pregnancy. Acta Obstet Gynecol Scand. 2000;79:803–804
  76. Jackson N, Shukri A, Kamaruzan A. Hydroxyurea treatment for CML during pregnancy. Br J Haematol. 1993;85:203–204
  77. Delmer A, Rio B, Bauduer F, Ajehenbaum F, Marie JP, Zittoun R. Pregnancy during myelosuppressive treatment for CML. Br J Haematol. 1992;82:783–784
  78. Tertian G, Tchernia G, Papiernik E, Elefant E. Hydroxyurea and pregnancy. Am J Obstet Gynecol. 1992;18:68–74
  79. Patel M, Dukes IAF, Hull JC. Use of hydroxyurea in CML during pregnancy: a case report. Am J Obstet Gynecol. 1991;165:565–566
  80. Thauvin Robinet C, Maingueneau C, Robert E, et al. Exposure to hydroxyurea during pregnancy: a case series. Leukemia. 2001;15:1309–1311
  81. Ali R, Ozkalemkaş F, Ozkocaman V, et al. Successful pregnancy and delivery in patient with CML and management of CML with leukapheresis during pregnancy. Jpn J Clin Oncol. 2004;34:215–217
  82. Klaasen R, de-Jong P, Wijermans PW. Successful management of chronic myeloid leukemia with leucapheresis during a twin pregnancy. Neth J Med. 2007;65:147–149
  83. Robak T. Current treatment options in hairy cell leukemia and hairy cell leukemia variant. Cancer Treat Rev. 2006;32:365–376
  84. Stiles GM, Stanco LM, Saven A, Hoffmann KD. Splenecomy for hairy cell leukemia during pregnancy. J Perinatol. 1998;18:200–201
  85. Alothman A, Sparling TG. Managing hairy cell leukemia in pregnancy. Ann Intern Med. 1994;120:1048–1049
  86. Baer MR, Ozer H, Foon KA. Interferon alpha therapy during pregnancy in chronic myelogenous leukemia and hairy cell leukemia. Br J Hematol. 1992;81:167–169
  87. Williams JK. Hairy cell leukemia in pregnancy: a case report. Am J Obstet Gynecol. 1987;156:210–211
  88. Patsner B, Penney RW, Walsh CM. Recurrent hairy cell leukemia during pregnancy: a case report. Am J Obstet Gynecol. 1994;170:1380–1381
  89. http://www.cancer.gov/cancertopics/pdq/treatment/CLL/healthprofessional/.
  90. Gurman G. Pregnancy and successful labor in the course of chronic lymphocytic leukemia. Am J Hematol. 2002;71:208–210
  91. Welsh TM, Thompson J, Lim S. Chronic lymphocytic leukemia in pregnancy. Leukemia. 2000;14:1155
  92. Chrisomalis L, Baxi LV, Heller D. Chronic lymphocytic leukemia in pregnancy. Am J Obstet Gynecol. 1996;175:1381–1382
  93. Padmanabhan R, Samad PA. Chlorambucil-induced postclosure exencephaly and axial skeletal abnormalities in rat fetuses. Reprod Toxicol. 1999;13:189–201
  94. Salder TW, Kochhar DM. Teratogenic effects of chlorambucil on in vivo and in vitro organogenesis in mice. Teratology. 1975;12:71–78
  95. Kavlock RJ, Rhenberg BF, Rogerts EH. Chlorambucil induced congenital renal hypoplasia: effects on basal renal function in developing rat. Toxicology. 1986;40:247–258
  96. Nicholson HO. Cytotoxic drugs in pregnancy. Review of reported cases. J Obstet Gynaecol Br Commonw. 1968;75:307–312
  97. Jacobs C, Donaldson SS, Rosenberg SA, Kaplan HS. Management of the pregnant patient with Hodgkin’s disease. Ann Intern Med. 1981;95:669–675
  98. Ba-Thike K, Oo N. Non-Hodgkin’s lymphoma in pregnancy. Asia Oceania J Obstet Gynaecol. 1990;16:229–232
  99. Shoton D, Monie IW. Possible teratogenic effect of chlorambucil on a human fetus. JAMA. 1963;186:180–181
  100. Steege JF, Caldwell DS. Renal agenesis after first trimester exposure to chlorambucil. South Med J. 1980;73:1414–1415
  101. Blanford A, Murphy BP. In vitro metabolism of prednisolone, dexamethsone, betamethasone and cortisol by the human placenta. Am J Obstet Gynecol. 1977;27:264–267
  102. In:  Hardman JG,  Limbird LE editor. Goodman and Gilman’s the pharmacological basis of therapeutics. 10th ed.. New York: McGrow-Hill; 2001;p. 1668
  103. van Runnard Heimel PJ, Franx A, Schobben AFAM, Huisjes AJM, Derks JB, Bruinse HW. Corticosteroids, pregnancy, and HELLP syndrome: A review. Obstet gynecol surv. 2005;60:57–70
  104. American College of Rheumatology Ad Hoc committee on clinical guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996;39:723-31.
  105. Janssen NM, Genta MS. The effect of immunosuppressive and anti-inflammatory medications on fertility, pregnancy and lactation. Arch Int Med. 2000;160:610–619
  106. Matalon ST, Ornoy A, Lishner M. The effect of 6-mercaptopurine on early human placental explants. Hum Reprod. 2005;20:1390–1397
  107. DeLoia JA, Stewart-Akers AM, Creinin MD. Effects of methotrexate on trophoblast proliferation and local immune responses. Hum Reprod. 1998;13:1063–1069
  108. Matalon ST, Ornoy A, Lishner M. Review of the potential effects of three commonly used antineoplastic and immunosuppressive drugs (cyclophosphamide, azathioprine, doxorubicin) on the embryo and placenta. Reprod Toxicol. 2004;18:219–230
  109. Kraemer J, Klein J, Lubetsky A, Koren G. Perfusion studies of glyburide transfer across the human placenta: implications for fetal safety. Am J Obstet Gynecol. 2006;195:270–274
  110. Hnat M, Bawdon RE. Transfer of meropenem in the ex vivo human placenta perfusion model. Infect Dis Obstet Gynecol. 2005;13:223–227
  111. Polachek H, Holcberg G, Sapir G, et al. Transfer of ciprofloxacin, ofloxacin and levofloxacin across the perfused human placenta in vitro. Eur J Obstet Gynecol Reprod Biol. 2005;122:61–65

PII: S0268-960X(08)00025-8

doi: 10.1016/j.blre.2008.03.006

Blood Reviews
Volume 22, Issue 5 , Pages 247-259 , September 2008

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