{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:37:19Z","timestamp":1791301039468,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The overwhelming success of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML) patients has opened a discussion among medical practitioners and the lay public on the real possibility of pregnancy and conception in females and males with CML. In the past 10 years this subject has acquired growing interest in the scientific community and specific knowledge has been obtained \u201cfrom bench to bedside\u201d. Embryological, pharmacological, and pathophysiological studies have merged with worldwide patient databases to provide a roadmap to a successful pregnancy and birth in CML patients. Male conception does not seem to be affected by TKI therapy, since this class of drugs is neither genotoxic nor mutagenic, however, caution should be used specially with newer drugs for which little or no data are available. In contrast, female patients should avoid TKI therapy specifically during the embryonic stage of organogenesis (5\u201312 weeks) because TKIs can be teratogenic. In the last 15 years, 41 pregnancies have been followed in our center. A total of 11 male conceptions and 30 female pregnancies are described. TKI treatment was generally terminated as soon as the pregnancy was discovered (3\u20135 weeks), to avoid exposure during embryonic period and to reduce the risk of needing treatment in the first trimester. Eleven pregnancies were treated with interferon, imatinib or nilotinib during gestation. Nilotinib plasma levels in cord blood and maternal blood at delivery were studied in 2 patients and reduced or absent placental crossing of nilotinib was observed. All of the patients were managed by a multidisciplinary team of physicians with obligatory hematological and obgyn consultations. This work provides an update on the state of the art and detailed description of pregnancy management and outcomes in CML patients.<\/jats:p>","DOI":"10.3390\/jcm11071801","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:27:51Z","timestamp":1648416471000},"page":"1801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Chronic Myeloid Leukemia and Pregnancy: When Dreams Meet Reality. State of the Art, Management and Outcome of 41 Cases, Nilotinib Placental Transfer"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-6491","authenticated-orcid":false,"given":"Elisabetta","family":"Abruzzese","sequence":"first","affiliation":[{"name":"Hematology, Sant\u2019Eugenio Hospital, ASL Roma 2, Tor Vergata University, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Aureli","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Sant\u2019Eugenio Hospital, ASL Roma 2, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Bondanini","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Sant\u2019Eugenio Hospital, ASL Roma 2, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariavita","family":"Ciccarone","sequence":"additional","affiliation":[{"name":"\u201cDormant Buds\u201d Association, Obstetrics and Gynecology, San Carlo di Nancy Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Cortis","sequence":"additional","affiliation":[{"name":"Pediatrics, Sant\u2019Eugenio Hospital, ASL Roma 2, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2661-6183","authenticated-orcid":false,"given":"Antonello","family":"Di Paolo","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7525-2550","authenticated-orcid":false,"given":"Cristina","family":"Fabiani","sequence":"additional","affiliation":[{"name":"Reproduction Pathophisiology and Andrology, Sandro Pertini Hospital, ASL Roma 2, 00157 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-5966","authenticated-orcid":false,"given":"Sara","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Malagola","sequence":"additional","affiliation":[{"name":"Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Malato","sequence":"additional","affiliation":[{"name":"Division of Hematology, Ospedali Riuniti Villa Sofia-Cervello, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Martino","sequence":"additional","affiliation":[{"name":"Hematology Unit, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89124 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata Monika","family":"Trawinska","sequence":"additional","affiliation":[{"name":"Hematology, Sant\u2019Eugenio Hospital, ASL Roma 2, Tor Vergata University, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Russo","sequence":"additional","affiliation":[{"name":"Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"de Fabritiis","sequence":"additional","affiliation":[{"name":"Hematology, Sant\u2019Eugenio Hospital, ASL Roma 2, Tor Vergata University, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4554","DOI":"10.1182\/blood-2011-04-347575","article-title":"Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population","volume":"118","author":"Efficace","year":"2011","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/jnci\/djr060","article-title":"Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib","volume":"103","author":"Antolini","year":"2011","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/ejh.13192","article-title":"Back to the future: Treatment-free remission and pregnancy in chronic myeloid leukemia","volume":"102","author":"Abruzzese","year":"2018","journal-title":"Eur. J. Haematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s00277-015-2326-y","article-title":"The interferon-alpha revival in CML","volume":"94","author":"Talpaz","year":"2015","journal-title":"Ann. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Russo, D., Garcia-Gutierrez, J.V., Soverini, S., and Baccarani, M. (2020). Chronic myeloid leukemia prognosis and therapy: Criticisms and perspectives. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061709"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/ajh.23593","article-title":"Long term outcome of Ph + CML patients achieving complete cytogenetic remission with interferon based therapy moving from interferon to imatinib era","volume":"89","author":"Malagola","year":"2013","journal-title":"Am. J. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1089\/jir.1997.17.543","article-title":"Hypothalamic-pituitary axis remains intact after interferon-\u03b1 treatment in hematologic diseases","volume":"17","author":"Kauppila","year":"1997","journal-title":"J. Interf. Cytokine Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1442-2042.1997.tb00317.x","article-title":"Effects of? -Interferon on sperm production, concentration, and motility in the rat","volume":"4","author":"Hibi","year":"1997","journal-title":"Int. J. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.reprotox.2011.11.003","article-title":"A systematic review of the fetal safety of interferon alpha","volume":"33","author":"Brojeni","year":"2012","journal-title":"Reprod. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hehlmann, R. (2021). Managing pregnancy in chronic myeloid leukemia. Chronic Myeloid Leukemia, Springer. [2nd ed.].","DOI":"10.1007\/978-3-030-71913-5"},{"key":"ref_11","unstructured":"(2021, July 01). Bosulif (Bosutinib) [Prescribing Information], Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/203341s020lbl.pdf."},{"key":"ref_12","unstructured":"(2021, July 01). Iclusig (Ponatinib) [Prescribing Information], Available online: https:\/\/www.iclusig.com\/pdf\/ICLUSIG-Prescribing-Information.pdf."},{"key":"ref_13","unstructured":"(2021, July 01). Sprycel (Dasatinib) [Prescribing Information], Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2010\/021986s7s8lbl.pdf."},{"key":"ref_14","unstructured":"(2021, July 01). Tasigna (Nilotinib) [Prescribing Information], Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2007\/022068lbl.pdf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1182\/blood-2018-99-118908","article-title":"Gimema registry of conception\/pregnancy in adult italian patients diagnosed with chronic myeloid leukemia (cml): Report on 166 outcomes","volume":"132","author":"Abruzzese","year":"2018","journal-title":"Blood"},{"key":"ref_16","unstructured":"(2021, July 01). Gleevec (Imatinib) [Prescribing Information], Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2001\/21335lbl.pdf."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Szak\u00e1cs, Z., Hegyi, P.J., Farkas, N., Balask\u00f3, M., Er\u0151s, A., Szuj\u00f3, S., Pammer, J., Mosd\u00f3si, B., Simon, M., and Nagy, A. (2020). Pregnancy outcomes of women whom spouse fathered children after tyrosine kinase inhibitor therapy for chronic myeloid leukemia: A systematic review. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0243045"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/bdra.10012","article-title":"Guidelines for case classification for the national birth defects prevention study","volume":"67","author":"Rasmussen","year":"2003","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1007\/s10815-021-02181-6","article-title":"Fertility considerations in targeted biologic therapy with tyrosine kinase inhibitors: A review","volume":"38","author":"Rambhatla","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.6004\/jnccn.2009.0069","article-title":"Issues of Imatinib and Pregnancy Outcome","volume":"7","author":"Apperley","year":"2009","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/sj.jp.7211665","article-title":"Imatinib mesylate and metabolite concentrations in maternal blood, umbilical cord blood, placenta and breast milk","volume":"27","author":"Russell","year":"2007","journal-title":"J. Perinatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1080\/10428194.2017.1347929","article-title":"Placental transfer of tyrosine kinase inhibitors used for chronic myeloid leukemia treatment","volume":"59","author":"Chelysheva","year":"2017","journal-title":"Leuk. Lymphoma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1002\/ajh.24186","article-title":"The impact of dasatinib on pregnancy outcomes","volume":"90","author":"Cortes","year":"2015","journal-title":"Am. J. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"IJH26","DOI":"10.2217\/ijh-2020-0004","article-title":"Pregnancy outcomes in patients treated with bosutinib","volume":"9","author":"Cortes","year":"2020","journal-title":"Int. J. Hematol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S153","DOI":"10.1016\/S2152-2650(21)01245-3","article-title":"Chronic myeloid leukemia and pregnancy: \u201cPer Aspera Ad Astra\u201d","volume":"21","author":"Abruzzese","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1182\/blood-2019-124430","article-title":"Pregnancy management in cml patients: To treat or not to treat? report of 224 outcomes of the european leukemia net (eln) database","volume":"134","author":"Abruzzese","year":"2019","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1080\/17474086.2018.1506325","article-title":"Contemporary management of patients with BCR-ABL1-negative myeloproliferative neoplasms during pregnancy","volume":"9","author":"Griesshammer","year":"2018","journal-title":"Expert Rev Hematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fmolb.2020.00016","article-title":"Pregnancy in Thalassemia and Sickle Cell Disease: The Experience of an Italian Thalassemia Center","volume":"7","author":"Sorrentino","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2015020","DOI":"10.4084\/mjhid.2015.020","article-title":"Successful management of pregnancy and hepatic toxicity in a cml female patient treated with nilotinib: A case report and a review","volume":"7","author":"Santorsola","year":"2015","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1016\/j.clinthera.2019.10.009","article-title":"Utility of therapeutic drug monitoring of imatinib, nilotinib, and dasatinib in chronic myeloid leukemia: A systematic review and meta-analysis","volume":"41","author":"Wojnicz","year":"2019","journal-title":"Clin. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/cpt.787","article-title":"Practical recommendations for therapeutic drug monitoring of kinase inhibitors in oncology","volume":"102","author":"Verheijen","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_32","first-page":"441","article-title":"Therapeutic drug monitoring of oral targeted antineoplastic drugs","volume":"77","author":"Groenland","year":"2020","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"22811","DOI":"10.3390\/ijms160922811","article-title":"Pharmacogenetics of BCR\/ABL inhibitors in chronic myeloid leukemia","volume":"16","author":"Polillo","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"88021","DOI":"10.18632\/oncotarget.21406","article-title":"The hOCT1 and ABCB1 polymorphisms do not influence the pharmacodynamics of nilotinib in chronic myeloid leukemia","volume":"8","author":"Galimberti","year":"2017","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"736","DOI":"10.3109\/1061186X.2012.716847","article-title":"Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug transport across the placenta and fetal drug exposure","volume":"20","author":"Staud","year":"2012","journal-title":"J. Drug Target."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"645555","DOI":"10.3389\/fgene.2021.645555","article-title":"Genetic susceptibility to drug teratogenicity: A systematic literature review","volume":"12","author":"Gomes","year":"2021","journal-title":"Front. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1055\/s-0035-1556745","article-title":"Identifying human teratogens: An update","volume":"4","author":"Chambers","year":"2015","journal-title":"J. Pediatr. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1093\/bjaceaccp\/mku013","article-title":"Placental structure, function and drug transfer","volume":"15","author":"Griffiths","year":"2014","journal-title":"Contin. Educ. Anaesth. Crit. Care Pain"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1124\/dmd.108.022764","article-title":"Lacteal secretion, fetal and maternal tissue distribution of dasatinib in rats","volume":"36","author":"He","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.leukres.2005.01.009","article-title":"Pregnancy under treatment of imatinib and successful labor in a patient with chronic myelogenous leukemia (CML): Outcome of discontinuation of imatinib therapy after achieving a molecular remission","volume":"29","author":"Ali","year":"2005","journal-title":"Leuk. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5505","DOI":"10.1182\/blood-2007-10-114900","article-title":"The effects of imatinib on pregnancy outcome","volume":"111","author":"Pye","year":"2008","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1080\/10428194.2020.1849672","article-title":"Management of chronic myeloid leukemia during pregnancy among patients treated with a tyrosine kinase inhibitor: A single-Center experience","volume":"62","author":"Assi","year":"2020","journal-title":"Leuk. Lymphoma"},{"key":"ref_43","first-page":"1","article-title":"Pregnancy outcomes in chronic myeloid leukemia: A single center experience","volume":"5","author":"Madabhavi","year":"2019","journal-title":"J. Glob. Oncol."},{"key":"ref_44","first-page":"e182","article-title":"Pegylated interferon alpha-2a for essential thrombocythemia during pregnancy: Outcome and safety","volume":"101","author":"Beauverd","year":"2016","journal-title":"A Case Series. Haematol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000506590","article-title":"Outcome of pregnancy in the era of pegylated interferon-\u03b12a in females with chronic myeloid leukemia: An experience from qatar","volume":"13","author":"Kassem","year":"2020","journal-title":"Case Rep. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2040620720966120","DOI":"10.1177\/2040620720966120","article-title":"Tyrosine kinase inhibitors and pregnancy in chronic myeloid leukemia: Opinion, evidence, and recommendations","volume":"11","author":"Abruzzese","year":"2020","journal-title":"Ther. Adv. Hematol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/7\/1801\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:42:35Z","timestamp":1760136155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/7\/1801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,24]]},"references-count":46,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["jcm11071801"],"URL":"https:\/\/doi.org\/10.3390\/jcm11071801","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,24]]}}}