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Observational Study of Conception/Pregnancy in Adult Patients With Chronic Myeloid Leukemia (CML) Treated With Tyrosine Kinase Inhibitors

18 Years
Not Enrolling
Chronic Myeloid Leukemia, Pregnancy

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Trial Information

Observational Study of Conception/Pregnancy in Adult Patients With Chronic Myeloid Leukemia (CML) Treated With Tyrosine Kinase Inhibitors

The management of patients with chronic myeloid leukemia (CML) during pregnancy is a matter
of continued debate. The introduction of the TKIs in clinical practice has dramatically
changed the prognosis of CML. Patients diagnosed in chronic phase can reasonably expect many
years of excellent disease control and good quality of life. Thus, the need to address
issues related to fertility and pregnancy have arisen. Physicians are frequently being asked
for advice regarding the need for, and or the appropriateness of, stopping treatment in
order to conceive. The management of fertility begins at diagnosis. This means that
immediate and future treatments should be considered at the very beginning. Therefore, the
maintenance of fertility should be taken into account since diagnosis. Imatinib is not
genotoxic but might lead to a decrease in sperm counts. Nevertheless, Imatinib is
teratogenic in rats when given during organogenesis at doses higher than 100 mg/kg,
approximately equivalent to 800 mg/day in men. Until now, approximately 60 pregnancies were
reported in partners of men on Imatinib. No suggestions of any problems in conception,
pregnancy, delivery or any increase in congenital abnormalities were reported. Regarding
women, 204 patients were exposed to Imatinib, and 180 were reported in literature (76, 77).
Of 180 women exposed to imatinib during pregnancy, outcome data are available for 125 (69%).
Of those with known outcomes, 50% delivered normal infants and 28% underwent elective
terminations, 3 following the identification of abnormalities. There were a total of 12
infants in whom abnormalities were identified, 3 of which had strikingly similar complex
malformations that are clearly a cause for concern. It appears that although most
pregnancies exposed to imatinib are likely to have a successful outcome, there remains a
risk that exposure may result in serious fetal malformations. Although numbers are small
there has been a disturbing cluster of rare congenital malformations such that imatinib
cannot be safely recommended, particularly during the period of organogenesis. Last but not
least, it has recently been reported a poor outcome after reintroduction of Imatinib in
patients who interrupt therapy for pregnancy without having achieved an optimal response
(78), introducing another variable in the management of women pregnant while receiving
Imatinib. Only few data are available about the use of second generation TKIs, Nilotinib and
Dasatinib, during pregnancy. Dasatinib is not mutagenic in rats (in vitro and in vivo
tests), but is clastogenic in CHO cells. It does not seem to have such effect on fertility
of male and female rats. However, it gives skeletal alterations in rats and rabbits and has
embryolethality in rats if administered during pregnancies. Eleven pregnancies were reported
while in dasatinib: 5 patients delivered normal infants, while 3 elective termination and 2
spontaneous abortion were reported. On the other hand, 9 male patient conceived during
dasatinib: 8 normal infants were delivered, and 1 case was ongoing at the time of the
report. Nilotinib is not mutagenic in rats. It does not have any effect on fertility in male
and female rats. When administered during pregnancy, there is no evidence of teratogenicity
but it is embryo and foetotoxic in the rat and in the rabbit. Only sporadic cases of
patients who had been pregnant/had conceived during Nilotinib have been reported, and no
speculation should be made from these data. In summary, there are virtually no data
regarding II generation TKIs, that must be discontinued by women wishing to become pregnant.
Several questions still remains unanswered regarding the management of patients receiving
TKIs who want to conceive, or who have been exposed to TKI during pregnancy/conception.

Inclusion Criteria:

- Age > 18 years;

- Ph+/BCR-ABL+ CML in any phase of disease;

- Conception/pregnancy while diagnosed with CML

- Treatment with TKIs (before or after pregnancy);

- Signed written informed consent according to ICH/EU/GCP and national local laws.

Exclusion Criteria:

- Patient < 18 years

- Patients that suffer from any condition or illness that could prevent the patient to

Type of Study:


Study Design:

Observational Model: Case-Only, Time Perspective: Prospective

Outcome Measure:

Number of normal birth, elective termination and spontaneous abortion

Outcome Description:

Pregnancy outcome: it will be calculated in terms of normal birth, elective termination, spontaneous abortion

Outcome Time Frame:

At 3 years from study entry

Safety Issue:


Principal Investigator

Elisabetta Abruzzese

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hematology, S. Eugenio Hospital, Rome


Italy: Ethics Committee

Study ID:




Start Date:

January 2013

Completion Date:

December 2017

Related Keywords:

  • Chronic Myeloid Leukemia
  • Pregnancy
  • Chronic Myeloid Leukemia
  • CML
  • Pregnancy
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive