ELISABETTA ABRUZZESE (ROME)
PREGNANCY AND TKI
Elisabetta Abruzzese and Paolo de Fabritiis
Hematology, S. Eugenio Hospital, Tor vergata University, ASL ROMA2, Rome, Italy
The introduction of tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid
leukemia (CML) changed the whole approach to the illness very quickly.
In the past twenty years, expectations of patients receiving the diagnosis of chronic myeloid
leukemia (CML) moved from needing to accept an invariably fatal disease fraught with
treatment related side effects with interferon based therapy and allogeneic transplant being
the only curative approach 1, to an illness treated at home with a targeted drug, able to
restore a normal hematopoiesis but requiring uninterrupted lifelong therapy 2, to a
condition whose survival might be comparable to the non-CML age matched population, with
multiple targeted drugs available, each able to induce deep molecular response that could
allow, in a significant minority, discontinuation of treatment 3. For this category of patients,
in both men and women, conception and pregnancy are justifiable and can be planned and
successfully accomplished.
With worldwide access to TKI, a considerable proportion of patients with CML is of
childbearing age and many of them want to have children. Although the median age at
diagnosis for patients with CML in industrialized countries is around 60 years and “only” 40-
50% are fertile, in developing countries with the greatest population growth, this is 10-15
years younger 4, thus physicians are frequently asked for advice on this subject.
Current conclusions regarding fertility, conception and delivery of female partners of male
patients are that there is no significant effect, even if for newer TKIs, very few data are
available 5. In stark contrast, female patients should not be exposed to TKIs during
pregnancy, as it is well known both from in vitro and in vivo (animal model) preclinical studies
that TKIs are not genotoxic but could be teratogenic, resulting in bone, vascular and organ
defects when administered during pregnancy 6. This has been confirmed in pregnant
women treated with TKIs, mainly with imatinib, and exposed during the 1st trimester or
beyond, since in approximately 20% of cases defects described in animal model could be found
in the product of conception 7.
The management of fertility begins at diagnosis: the patient of reproductive age should be
informed of the risk of unplanned pregnancies in terms of fetal problems and/or the risk of
uncontrolled disease in the case of need to stop therapy, but also of the possibility that a
controlled pregnancy can be carried out potentially at later points during treatment,
particularly with optimal response and long observed deep remission.
Recently recommendations regarding the best approach to manage cases of pregnancy have
been published 8. Different situations can occur and will be specifically discussed:
CML diagnosed during pregnancy
pregnancy inadvertently discovered during TKI treatment for CML
planned pregnancy after establishment of optimal CML response.
In the first two cases the approach should be individualized, taking into consideration two
principal variables: the patient (her willingness to continue, the parity, the week of gestation,
the TKI exposure relative to the age of gestation) and the CML (chronic phase versus more
advanced stage, TKI used, and in particular, remission status). Leukemic burden plays an
SCIENTIFIC PROGRAMME
SESSION I
OPTIMIZING
CYTOREDUCTION
SESSION II
MANAGEMENT OF CML
WITH TKI
SESSION III
MPN RISK
STRATIFICATION
INCLUDING VASCULAR
EVENTS
DEBATE 1
INTERFERON ALPHA
SHOULD BE FRONT LINE
THERAPY IN ALL ET/PV
PATIENTS
ROUNDTABLE 1
INFECTIONS IN
MYELOPROLIFERATIVE
DISORDERS, INCLUDING
CML
ROUNDTABLE 2
PREGNANCY AND
PARENTING
DEBATE 2
ALLOGENEIC STEM CELL
TRANSPLANTATION
SHOULD BE CONSIDERED
THIRD LINE OPTION IN
CHRONIC PHASE CML
SESSION IV
EVOLVING THERAPIES
IN MYELOFIBROSIS
SESSION V
MANAGEMENT OF
ADVANCED AND UNUSUAL
DISEASE (MPN AND CML)
SESSION VI
TREATMENT FREE
REMISSION IN CML
KEYNOTE LECTURE
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FO R A POSTER
PRESENTATION
DISCLOSURES