Blum, Sabine

Bornhäuser, Martin

Ehninger, Gerhard

Gattermann, Norbert

Kronenberger, Roland

Schleyer, Eberhard

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LETTER TO THE EDITORImatinib in breast milkRoland Kronenberger & Eberhard Schleyer &Martin Bornhäuser & Gerhard Ehninger &Norbert Gattermann & Sabine BlumReceived: 20 March 2009 /Accepted: 5 May 2009 /Published online: 22 May 2009# Springer-Verlag 2009Dear Editor,To our knowledge, not much is known about imatinib (IM)treatment and pregnancy, child birth, and breast feeding.Pye and colleagues recently investigated the treatment,pregnancy, and fetal outcomes of 180 women exposed toimatinib during pregnancy. There were a total of 12 infantsin whom abnormalities were identified. It appeared that,although most pregnancies exposed to imatinib are likely tohave a successful outcome, an element of risk remains forexposure to result in serious fetal malformations [1]. Weshould like to share the results of measuring imatinib levelsin the breast milk of a woman treated with imatinib, eventhough our findings are related to neonatal rather than fetaldrug exposure.A 34-year-old woman was diagnosed with chronicmyeloid leukemia (CML) in chronic phase in 2001 andstarted on interferon (IFN) alpha of three million units perday at a regional hospital. IFN was well tolerated and thepatient achieved complete hematological remission but nomajor cytogenetic response. In February 2004, the patientwas referred to our institution because Bcr-Abl wasdetectable in 75% of peripheral blood cells by fluorescencein situ hybridization analysis. The patient was started onimatinib of 400 mg/day. Between February and May 2004,molecular monitoring yielded a 1-log decrease in Bcr-Ablmessenger RNA (mRNA). In June 2004, the patientreported that she was pregnant. Imatinib was discontinued.As the molecular monitoring in July showed a further 1-logdecrease in Bcr-Abl mRNA, no further CML treatment wasgiven during pregnancy. Bcr-Abl transcripts increased up tothe May 2004 level only towards the end of pregnancy. Ahealthy child was born at term. No malformations weredetectable. After delivery, imatinib was immediatelyrestarted at 400mg/day. The infant received bottle feedingfrom the start. However, we asked the mother to deferablactation until 171 h of imatinib treatment in order toobtain measurements of IM and its active metabolite N-desmethyl-imatinib (N-DesM-IM, CGP74588) in plasmaand breast milk. Drug levels were measured repeatedly (seeTable 1). We found that the level of imatinib in breast milkwas about half the plasma level. The active metabolite N-DesM-IM accumulated about threefold in breast milk ascompared to plasma levels. A pseudo-steady-state level wasreached in the breast milk after about 2 days of imatinibAnn Hematol (2009) 88:1265–1266DOI 10.1007/s00277-009-0754-2R. Kronenberger : E. SchleyerInternal Medicine II, Division of Hematology and Oncology,Carl-von-Basedow Hospital Merseburg,06217 Merseburg, GermanyE. Schleyer :M. Bornhäuser :G. EhningerInternal Medicine I, Division of Hematology and Oncology,Carl Gustav Carus University,01307 Dresden, GermanyN. GattermannDepartment of Hematology, Oncology, and Clinical Immunology,Heinrich-Heine-University,Moorenstr.5,40225 Düsseldorf, GermanyS. Blum (*)Department of Hematology,Centre Hospitalier Universitaire Vaudois,Rue du Bugnon 46,1011 Lausanne, Switzerlande-mail: sabine.blum@chuv.chtreatment. According to our results, breastfeeding cannot berecommended during treatment with imatinib.Acknowledgements We thank the CML patient who voluntarilygave blood and breast milk samples.References1. Pye SM, Cortes J, Ault P, Hatfield A, Kantarjian H, Pilot R et al(2008) The effects of imatinib on pregnancy outcome. Blood111:5505–5508Table 1 Drug level measureTime aftertherapy start(h)IM plasmaconcentration(ng/ml)N-DesM-IMplasmaconcentration(ng/ml)Plasma ratio N-DesM-IM/IM(%)IM breast milkconcentration(ng/ml)N-DesM-IM breastmilk concentration(ng/ml)Breast milk ratio N-DesM-IM/IM (%)0 0 0 0 0 0 03 1,301 177 14 751 409 5427 2,482 334 13 1,057 791 7551 2,010 284 14 1,153 1,024 89171 2,003 301 15 797 1,052 1321266 Ann Hematol (2009) 88:1265–1266

Imatinib in breast milk

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Imatinib in breast milk

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