Outcome of Pregnancy in Rare Case of Chronic Myeloid Leukemia Diagnosed at 24 Weeks of Gestation

Abstract

The management of chronic myelogenous leukemia during pregnancy requires balancing the health of both mother and fetus. We report a case of a 22-year-old female who was diagnosed with chronic myelogenous leukemia (CML) at 24 weeks gestation and who had an atypical chromosome t(9;22;11) (q34;q11.2;q13) translocation. She was managed with PEG-IFNa through the remainder of the pregnancy and the disease remained stable; she delivered a normal male child. Treatment with dasatinib was initiated 1 week after delivery on patient's request and she went into complete hematologic remission after 1 month of therapy. We discuss the course of the disease and various treatment modalities available for CML during pregnancy.

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Volume 8, Issue 4, April – 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
IJISRT23APR495 www.ijisrt.com 193
Outcome of Pregnancy in Rare Case of
Chronic Myeloid Leukemia Diagnosed at 24
Weeks of Gestation
1. Dr Vishnu Sharma
Department of General Medicine
SMS Medical College
Jaipur, India
2. Vansh Bagrodia
Final MBBS Student
SMS Medical College
Jaipur, India
Abstract:- The management of chronic myelogenous
leukemia during pregnancy requires balancing the health
of both mother and fetus. We report a case of a 22-year-
old female who was diagnosed with chronic myelogenous
leukemia (CML) at 24 weeks gestation and who had an
atypical chromosome t(9;22;11) (q34;q11.2;q13)
translocation. She was managed with PEG-IFNa through
the remainder of the pregnancy and the disease remained
stable; she delivered a normal male child. Treatment with
dasatinib was initiated 1 week after delivery on patient’s
request and she went into complete hematologic remission
after 1 month of therapy. We discuss the course of the
disease and various treatment modalities available for
CML during pregnancy.
I. INTRODUCTION
Chronic myelogenous leukemia (CML) is a chronic
myeloproliferative disorder defined by the presence of a
chimeric gene, BCR::ABL. CML accounts for 7% to 15% of
all cases of leukemia in adults. In western countries the
median age of CML patients is about 57 years. In Asia the
median age at diagnosis is <50 years, reflecting in part the
lower median age of the population.1 There is slight male
predominance. There is no association with geographic
distribution or race. The etiology of CML is unknown. High-
dose radiation exposure is a well-established environmental
risk factor. No genetic predisposition is thought to play any
role in pathogenesis of CML. BCR::ABL is created by a
reciprocal translocation of genetic material between the long
arm of chromosome 9 (containing the proto-oncogene c-abl)
and the long arm of chromosome 22 (containing the bcr gene).
This is the Philadelphia chromosome, and it is correctly
annotated t(9;22) (q34.1;q11.21). The translocation results in
constitutive upregulation of tyrosine kinase activity of abl,
which triggers downstream transduction pathways of a
signaling cascade of oncogenic events.
Patients usually present in the initial chronic phase,
exhibiting a cluster of specific clinical and laboratory features.
More than half of patients with CML diagnosed in the chronic
phase are asymptomatic. The median time to the development
of terminal blast phase is 3 to 6 years. The disease typically
progresses through slow evolution into an accelerated phase
and then blast phase, but it can transform rapidly directly into
the blast phase.
The therapeutic landscape of chronic myeloid leukemia
(CML) has profoundly changed over the past few years. Most
patients with chronic phase (CP) now have a normal life
expectancy. Another goal is achieving a stable deep molecular
response (DMR) and discontinuing medication for treatment-
free remission (TFR). First-line treatment is a tyrosine kinase
inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib,
and bosutinib are available first-line). Allogeneic
transplantation continues to be a therapeutic option
particularly for advanced phase CML. Treatment
discontinuation may be considered in patients with durable
DMR with the goal of achieving TFR.1 The occurrence of
CML during pregnancy poses a unique clinical challenge for
physicians treating these patients and requires balancing
concerns between maternal survival and fetal health in both
the short- and long-term. Interferon-alpha is a safe option due
to its safety profile while TKI’s are not given because of their
teratogenic potential.2
II. CASE
We report the case of a 20 year female G1P0 in 2nd
trimester (at 24 weeks of gestation) presented
withleukocytosis, left shift, thrombocytosis and splenomegaly
on her regular pregnancy checkup. She was suspected for
CML and was investigated for it, the findings of which are
seen in table 1.
Hemoglobin
9.5 %
Total leukocyte count
46300/Cumm
Platelet count
12.14 Lakh/Cu mm
Neutrophil
66%
Lymphocyte
05%
Eosinophil
02%
Monocyte
05%

Volume 8, Issue 4, April – 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
IJISRT23APR495 www.ijisrt.com 194
Basophils
07%
Myelocytes +
Metamyelocytes
14%
Blast
1%
Spleen
5cm BCM
Blasts on Bone Marrow
Biopsy
2.3%
BCR-ABL (P210)
51.964% IS
Sokal
1.04 (intermediate risk)
ELTS
0.8053 (low risk)
Table 1 : Pre-treatment initiation investigations for suspected
CML
Patient was diagnosed with Chronic Myeloid Leukemia
in Chronic Phase and put on Interferon-alpha 2b 3 mu/day 3
times/week to be taken until delivery.
Patient took interferon-alpha 2b for 13 weeks and had a
normal full term delivery. Baby was healthy, weighed 2.6 kg
and no malformations were seen. Investigations to assess the
status of her CML were done after delivery and seen in table
2.
Hemoglobin
9.9 %
Total leukocyte count
26900/Cumm
Platelet count
17.68 Lakh/Cu mm
Neutrophil
60%
Lymphocyte
05%
Eosinophil
04%
Monocyte
04%
Basophils
07%
Myelocytes +
Metamyelocytes
20%
Blast
0%
Spleen
5 cm BCM
Sokal
1.59 (high risk)
ELTS
0.6393 (low risk)
Table 2 : Post-delivery investigations to assess CML status
Patient was counselled to continue Interferon-alpha 2b
even after pregnancy to facilitate exclusive breast feeding to
infant but she asked to be put on standard therapy for CML
and was thus given Dasatinib 100mg/day OD and achieved
complete hematologic remission after one month of therapy.
III. DISCUSSION
CML in pregnancy is a rare condition, with an annual
incidence of 1 per 100,000 pregnancies. The disease during
pregnancy has been traditionally managed conservatively by
leukapheresis, hydroxyurea and interferonbecause it has an
initial chronic phase that may not require an immediate
therapy and pregnancy per se does not affect CML. The
therapeutic management of CML in pregnant women with
TKIs often poses substantial challenges to both patients and
their physicians.3
Our patient was not put on TKI therapy due to its
teratogenic potential. This is supported by various studies.
Like in Pye et al’s. study, 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.4
Our patient was given interferon-alpha 2b for CML
during the course of her pregnancy. The results of a study by
Brojeni et al suggested that IFN-alphaα does not significantly
increase the risk of major malformation, miscarriage, stillbirth
or preterm delivery above general population rates.5
Leukapheresis in pregnant CML patients is generally
used in cases with severe hyperleukocytosis which was not
observed in our patient at any instance and was thus not
considered anytime during the course of her pregnancy.
Hydroxyurea was also not used due to its teratogenic profile
and no need for any other therapy was noticed since the
patient was relatively well controlled on interferon therapy.
Our patient was observed to have controlled CML after
pregnancy and was thus suggested and counseled to continue
Interferon-alpha 2b even after pregnancy to facilitate exclusive
breast feeding to infant since TKIs are secreted in breast milk
thus it is not advisable to give an actively feeding mother TKIs
such as Dasatinib. But the patient wasn't much comfortable
with continuing IFN-alpha due to its flu-like side effects and
also wanted to take the best therapy possible for her, for the
CML. So she asked to be put on standard therapy for CML
and was started on Dasatinib 100mg/day OD whilst the patient
was simultaneously referred to the Pediatrics department for
the proper nursing of her newborn.
Dasatinib is a multi-targeted kinase inhibitor
of bcr/abl and Src kinases that has 100- to 300-fold higher
activity than imatinib.6
Our patient was observed to have complete hematologic
remission after 1 month of dasatinib therapy.
IV. CONCLUSION
CML occurrence during pregnancy is noted to be a rare
phenomenon and warrants careful therapeutic planning due to
the relative risk of embryotoxicity of TKIs, which is
considered as first-line therapy in CML on one hand, but the
good efficacy and treatment success rates of the same on the
other hand. Interferon-alpha 2b 3 mu/day 3 times/week is
noted to be a safe option in pregnant CML patients managed
without TKIs. Our study supports this fact with its observed
positive outcome of both the pregnancy and fetus.
Conflicts of Interest -

Volume 8, Issue 4, April – 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
IJISRT23APR495 www.ijisrt.com 195
No conflicts of interest declared.
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