Gimema Registry of Conception/Pregnancy in Adult Patients Diagnosed with Chronic Myeloid Leukemia (CML) Treated with Tyrosine Kinase Inhibitors (TKIs)
Authors: Abruzzese Elisabetta , Scortechini Anna Rita , Gugliotta Gabriele , Pierri Ivana , Musolino Caterina , Iurlo Alessandra , Mastrullo Lucia , Caracciolo Clementina , Orlandi Ester , Galimberti Sara , Salvucci Marzia , Avanzini Paolo , Sica Simona , Alimena Giuliana , Bocchia Monica , Pregno Patrizia , D'Emilio Anna , Gambacorti-Passerini Carlo , Stagno Fabio , Santorsola Domenico , Castagnetti Fausto , Perrotti Alessio Pio , de Fabritiis Paolo , Baccarani Michele 
Published: October 2019

Abstract
The management of patients with chronic myeloid leukemia (CML) during pregnancy is a matter of continuous debate. The introduction of the tyrosin kinase inhibitors (TKIs) in clinical practice has dramatically changed the prognosis of CML patients. Patients diagnosed in chronic phase can expect an excellent disease control and a normal lifespan. Issues relating to fertility and pregnancy must be introduced at diagnosis. Different reports were published in patients conceving/getting pregnant during Imatinib treatment, while there are only sporadic data about other TKIs. The GIMEMA CML working party has started a retrospective and prospective study to describe all female pregnancies/male conception outcome in the CML population from January 2013 until 2015.
Inclusion criteria were age>18, CML in any phase of the disease, conception/pregnancy while diagnosed with CML, treatment with TKIs (before, during or after pregnancy), and signed written informed consent IRB approved.
Sixty-three patients have been enrolled so far in the study. Male to female ratio was 43/20, mother age at pregnancy (female patients or female partners of male patients) varies from 22 to 37 years. CML was diagnosed when patients were aged between 17 and 55 years old, all patients were in chronic phase at time of conception, but one. This patient was a male patient with accelerated phase aged 31 treated with Nilotinib whose conception outcome was unremarkable. Data on 71 pregnancies have been harvested. The majority of pregnancies were spontaneous, with 3 PMA (pregnancy medically assisted). All pregnancies were carried on, 2 are ongoing, and 6 ended up in an abortion within the 3rdmonth, 2 of which non induced (miscarriages). At pregnancy/conception 8 patients were treated with Nilotinib, 4 with Dasatinib, 3 with Bosutinib, the remaining patients were treated with Imatinib or were at onset with no treatment. All carried pregnancies were unremarkable, except two placental detachment, one at 5 months and one at 12 weeks pregnancy, 1 abortion threat requiring rest, 1 gestational diabetes with intra-uterine growth retard, 1 oligohydramnios, 1 congenital hip dysplasia, and 1 speech retard in a 36 months old baby girl.
Data on female patients population, regarding the status of CML at pregnancy, the CML therapy since conception and throughout pregnancy, particularly regarding the organogenesis period (between 5-12 weeks), the status of the illness during pregnancy (any MR4.5, MR4 and major molecular response, complete cytogenetic response, hematologic response losses, and progressions), the outcome of pregnancy, breast feeding, baby growth and development (walk, speech, behaviour), will be detailed. The same will be for female partners of male patients treated with TKIs other than Imatinib.
Acquiring detailed information about how a pregnancy/conception is managed will increase our knowledge in order to establish a consensus on patients with CML receiving TKIs who wants to father a child or become/are pregnant.

Disclosures
Abruzzese: novartis, bristol myers squibb, ariad, pfizer, takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Gugliotta:Novartis: Consultancy; Bristol-Myers-Squibb: Consultancy. Castagnetti:Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Baccarani:Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau.