Diagnosis of Chronic Myeloid Leukemia Early in Pregnancy

doi:10.4236/ojbd.2011.11001

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Open Journal of Bloo d Di seases, 2011, 1, 1-2

doi:10.4236/ojbd.2011.11001 Published Online September 2011 (http://www.SciRP.org/journal/ojbd)

Diagnosis of Chronic Myeloid Leukemia Early in

Pregnancy

Fabio Stagno*, Paolo Vigneri*, Massimo Poidomani, Stefania Stella, Alessandra Cupri,

Michele Massimino, Livia Manzella, Francesco Di Raimondo

Department of Clinical and Molecular Bio-Medicine, Sections of Hematology, Oncology and Clinical Pathology, University of

Catania, Catania, Italy.

Email: [email protected]

Received July 28th, 2011; revised August 28th, 2011; accepted September 6th, 2011.

ABSTRACT

Imatinib therapy has revolutionized the clinical course of Chronic Myeloid Leukemia. The unexpected prolonged sur-

vival raised several issues on the quality of life and on the possibility to parent childs.

Keywords: Chronic Myeloid Leukemia, Pregnancy, Therapy, BCR-ABL

1. Introduction

The introduc tion of the tyrosine kinase inhibitor Imatinib

Mesylate (IM) for the treatment of Chronic Myeloid

Leukemia (CML) in chronic phase (CP) resulted in high

rates of hematologic, cytogenetic and molecular responses

[1]. Furthermore, clinical long term follow up has shown

an estimated 8-year overall survival of 85% for patients

receiving IM on an intention to treat basis [2]. These

spectacular results led CML patients not only to a pro-

longed survival but also to drive relatively normal lives.

In this view, several issues on the quality of life and,

among them, on fertility and pregn ancy have b een raised .

Here we report the case of a female patient who was in-

cidentally diagnosed with CML while early in pregnancy

and who wanted to get gestation to term.

2. Case Report

A 41 year-old female was referred to our Institution be-

cause of severe leukocytosis. She was at the 10th week of

gestation and at physical examination presented only a

mild splenomegaly (1 cm below costal margin) without

any lymph nodes enlargement. Laboratory exams re-

vealed a white blood cell (WBC) cou nt of 146.3 × 109/L,

a platelet cell count of 820.0 × 109/L, a hemoglobin con-

centration of 10.1 g/dL and lactic acid dehydrogenase of

1440 UI/L. The differential WBC showed the presence of

immature myeloid circulating cells (metamyelocytes

11%, myelocytes 13%, promyelocites 3% and blasts 2%),

while bone marrow cytogenetic showed the presence of

the Philadelphia (Ph)-positive chromosome in all the ex-

amined methaphases with no further abnormalities. The

patient was then diagnosed as having CP-CML, interme-

diate Sokal risk with a e13a2 BCR-ABL-transcript and a

BCR-ABL/ABL % ratio of 107.62 on the International

Standardized Scale (IS). Since the patient wanted to carry

pregnancy to term, she started cytoreduction, with five

weekly leukapheresis, and thrombosis prophylaxis with

low dose low molecular weight heparin (Clivarin 1750 U)

every 12 hours. From the 23 rd week of gestation she begu n

α-interferon-treatment (α-IFN; 5MUI daily), obtaining

soon a complete hemato logical remission (CHR). α-IFN-

therapy was interrupted at the 37th week of gestation

since a cesarean delivery was scheduled at the 38th week,

when the patient gave birth to a healthy baby. After fif-

teen days from delivery and while still in CHR, she

started conventional IM-therapy (400 mg daily). BCR-

ABL/ABL transcript levels were 46.52IS at that time and

decreased to 10.26IS at the third month of therapy. She is

presently alive and well on standard IM treatment.

3. Conclusions

The radical improvements in the long-term survival of

CML patients now pose novel medical challenges.

Treating physicians will have to manage IM long-term

side effects [3] as well as simultaneous chronic illnesses

in an aging CML population. Moreover, the higher rates

of molecular remission coupled with a relatively normal

quality of life raised in some CML patients the issue on

the ability to parent children. On this address a recent

cumulative experience has been published on CML pa-

*The indicated authors e

uall

contributed to this wor

Diagnosis of Chronic Myeloid Leukemia Early in Pregnancy

tients conceiving while taking IM [4]. Nevertheless the

CML management during pregnancy remains still a

clinical challenge and no systematic clinical studies are

described. Here we report a pregnant woman whose

CP-CML disease was incidentally diagnosed while early

in gestation and who wanted to carry her pregnancy to

term. A similar clinical case has been reported by Cole S.

and collegues [5] whereas Bjorkholm M. et al. described

a CML patient presenting late in pregnancy [6]. However

our patient had an intermediate Sokal risk, a high

BCR-ABL/ABL transcript at diagnosis (both representa-

tive of aggressive leukemic burden) and an increasing

WBC-count: these two relevant clinical events prompted

us to consider a proper therapeutical intervention.

Since the use of both hydroxyurea and IM is not rec-

ommended during gestation, we started cytoreduction

with leukapheresis and introduced α-IFN therapy, which

reduced BCR-ABL/ABL transcript levels from 107.62IS to

46.52IS Therefore, on th e basis o f our clinical experience,

we believe that α-IFN-treatment might be a useful tool in

the management of early pregnancy during CML. How-

ever, when a CML female patient wants to conceive, the

best choice could be to start IM-therapy, to achieve a

major molecular response, or better a complete molecular

response, and then to stop treatment attempting to con-

ceive.

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