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3178 On the Children Side. Overview of 194 Outcomes from Gimema Registry of Conception/Pregnancy in Chronic Myeloid Leukemia (CML)

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
adult, Clinical Practice (Health Services and Quality), embryo/fetus, pediatric, neonatal, pregnant, young adult , Study Population, Human, Maternal Health
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Elisabetta Abruzzese, MD1, Elena Chiara, MD2*, Fausto Castagnetti, MD, PhD3, Mario Annunziata, MD4*, Carlo Gambacorti-Passerini, MD5, Luigiana Luciano, MD6, Antonella Russo Rossi, MD7*, Alessandra Iurlo, MD, PhD8*, Isabella Capodanno, MD9*, Valentina Giai, MD, PhD10*, Mariella D'Adda, MD11*, Fabio Stagno, MD, PhD12, Antonella Gozzini, MD13*, Mario Tiribelli, MD14*, Federica Sorà, MD15*, Sara Galimberti, MD, PhD16*, Monica Bocchia, MD17*, Germana Beltrami, MD18*, Carmen Fava, MD, PhD19*, Maria Cristina Miggiano, MD20*, Massimo Breccia21*, Marco Cerrano, MD22*, Anna Rita Scortechini, MD23*, Olga Mulas, MD24*, Clementina Caracciolo, MD25*, Stefana Impera, MD26*, Claudio Fozza, MD27*, Alessandra Malato, MD28*, Lucia Mastrullo, MD29*, Marzia Salvucci, MD30*, Monia Lunghi, MD, PhD31*, Filippo Gherlinzoni, MD32*, Paolo De Fabritiis, MD33*, Paola Fazi, MD34*, Sonia Maria Orlando35*, Alfonso Piciocchi, MS34* and Fabrizio Pane, MD36

1Hematology, S. Eugenio Hospital, Tor Vergata University, ASL Roma2, Rome, Italy
2IRCCS Fondazione Policlinico San Matteo, Pavia, Tennessee, ITA
3Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy
4Hematology, San Giuseppe Moscati Hospital, Aversa, Italy
5Department of Medicine and Surgery, University Milano-Bicocca, Monza, Italy
6Hematology Unit, Federico II University, Napoli, Italy
7hematology, University of Bari, Bari, ITA
8Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
9hematology, AUSL Reggio Emilia, Reggio Emilia, ITA
10Division of Hematology, Città della Salute e della Scienza, Turin, Italy
11ASST Spedali Civili Di Brescia, Brescia, ITA
12Division of Hematology and Bone Marrow Transplant, AOU Policlinico “Rodolico – San Marco”, Catania, Italy
13Hematology, AOU Careggi, University of Florence, Florence, Italy
14Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine, Italy
15Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy
16Department of Clinical and Experimental Medicine, Hematology, University of Pisa, Pisa, Italy
17UOC Ematologia, Azienda ospedaliero-universitaria Senese, Siena, Italy
18U.O. Ematologia e terapie cellulari, IRCCS Azienda Ospedaliera Universitaria San Martino, Genova, Italy
19Hematology, Mauriziano Hospital, Torino, Turin, Italy
20hematology, Vicenza, vicenza, Italy
21Department of Translational and Precision Medicine, Hematology-Sapienza University, Rome, Italy
22Division of Hematology, Department of Oncology, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy
23Division of Hematology, Department of Molecular and Clinical Sciences, Polytechnic University of Marche, Ancona, Italy
24Department of Medical Sciences and Public Health, University of Cagliari, Businco Hospital, Cagliari, Italy
25Hematology, AOU Policlinico P Giaccone, Palermo, Italy
26UOC Ematologia, ARNAS Garibaldi, Catania, Italy
27Hematology Unit – Azienda Ospedaliera Universitaria of Sassari, University of Sassari, Sassari, Italy
28Hematology Unit, Ospedale "V. Cervello", Palermo, Italy
29ASL Napoli 1 Presidio Ascalesi, NAPOLI, ITA
30Hematology, Ospedale S. Maria delle Croci, Ravenna, ITA
31Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
32Ospedale Ca' Foncello, Treviso, ITA
33University tor Vergata, Rome, ITA
34GIMEMA Foundation, Data Center and Health Outcomes Research Unit, Rome, Italy
35Gimema Foundation, Rome, ITA
36Dipartimento Medicina Clinica e Chirurgia, UOC Ematologia e Trapianti di Midollo, Azienda Ospedaliera Universita Federico II, Napoli, Italy

Pregnancy in patients with chronic myeloid leukemia (CML) is no longer precluded. The literature published to date has mainly evaluated the management of CML and pregnancy with little mention of follow-up of children. This work aims to focus on the effects of the disease and of the drugs taken before conception and/or during pregnancy on fertility, gestation, pre-natal development of the fetus, and the growth of the child.

GIMEMA has promoted an observational retrospective/prospective study to harvest and study detailed information on both pregnancies in female CML patients and pregnancies of partners of male patients followed at participating centers. The information requested addressed information on demographic, CML- related (CML therapy before/during/after pregnancy; transcript kinetics; outcome post delivery), pregnancy-related (type of conception; abortion rate; pregnancy progression, delivery, breastfeeding), and baby-related (birth, physical, intellectual, emotional, behavioral, social and sexual development)

Data from 83 male patients (109 pregnancies) and 74 female patients (84 pregnancies) were evaluated for a total of 193 pregnancies at term. Fourteen (7 female and 7 male) conceptions were medically assisted, all the others spontaneous. One hundred ninety-four children were born (a twin pregnancy), 15 abortions were registered, 12 spontaneous and 3 voluntary all within the first trimester, while one pregnancy is still in progress. Eleven patients (1 male, 10 female) were diagnosed as having CML during pregnancy. Three patients interrupted pregnancy (2 electives).

All male patients, with the exception of two (one undergoing assisted reproduction and one in TFR), conceived during treatment. TKI used were Imatinib (71%), Nilotinib (22%), Dasatinib (2%), Bosutinib (4%) and Ponatinib (1%). The pregnancies carried out by the partners of the male patients did not show any problems, neither pre-conception, nor during gestation, nor at birth. An initial speech delay in a child was reported, with recovery after speech therapy. Most pregnancies result in spontaneous delivery around the 39th week of gestation. Ninety-two/109 babies were breastfed (84%)

The last TKI used in the female CML group was imatinib (43%), nilotinib (33%), dasatinib (22%), and Ponatinib (2%). Most patients stopped TKI at the FPT "first pregnancy test" (3-5 weeks). Cesarean deliveries amounted to 41%, just above the national average of 30%, with a mean of 38 weeks of gestation. Of the 84 babies born to women diagnosed with CML, only 20 were breastfed (23%).

Three patients treated with IFN at the time of delivery breastfed for about a month, while one breastfed for 9 months and did not resume TKI as she was well-controlled by IFN and eager to start a new pregnancy. The lack of assimilation of IFN through breast milk orally does not contraindicate breastfeeding.

In female patients, out of 84 pregnancies, and 1 in progress, 15 required antileukemic therapy during pregnancy.

IFN was administered in 13 gestations, and also during organogenesis. In one case the patient introduced IFN at 7 weeks, then stopped due to poor disease control and started Nilotinib at 21 weeks, after placenta formation.

In 2 gestations (including the one mentioned above) the patients took nilotinib (starting at 21 and 23 week of gestation). One patient was treated with imatinib at 20 week.

The evaluation of the pediatric population under examination was divided into four age groups: 0-3 years for the evaluation of birth and psycho-physical development; 3-6 years for cognitive development; >6 years for socialization and interaction with the surrounding environment, including school performance; >12 years for sexual and hormonal development.

Five infants were small for date. Of those, only one was exposed to imatinib from the 20th week of gestation. (Table 1). All children presented a rapid recovery after birth and their development is comparable to that of children belonging to the same age group.

The oldest child is 15 years old, and was born at 39 weeks to a father on TFR after suspension of imatinib therapy; the youngest is a 15 days old girl, born at 38 week to a mother treated with IFN during pregnancy.

From the results obtained from the study, children born to parents diagnosed with CML do not appear to show any difference compared to their peers in the general population, even if exposed to therapy in the prenatal period.

Disclosures: Abruzzese: Takeda: Consultancy; Pfizer: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Castagnetti: Pfizer: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Iurlo: Novartis, Pfizer, Incyte, BMS, GSK, AOP Health: Honoraria. Giai: Alexion: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Stagno: Incyte, Novartis, Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Galimberti: Abbvie, Janssen, Novartis, Roche, Jazz, Astra Zeneca, Pfizer, Incyte: Speakers Bureau. Bocchia: Incyte: Honoraria; Novartis: Honoraria; BMS: Honoraria. Breccia: Pfizer: Honoraria; Novartis: Honoraria; Incyte: Honoraria; BMS: Honoraria; AOP: Honoraria; AbbVie: Honoraria. Cerrano: Insight Novartis Servier Abbvie Janssen Jazz Astellas Italfarmaco: Honoraria. Fozza: BMS: Research Funding; Amgen: Research Funding; Sanofi: Research Funding. Pane: Novartis: Research Funding, Speakers Bureau.

OffLabel Disclosure: some patients were treated during pregnancy with TKI inhibitors and interferons

*signifies non-member of ASH