Re: article about pregnancy during gleevec-Giora & Zavie

[Guest guest]

Giora & Zavie,

Here is an abstract that will be presented this year at ASH on this

subject. I keep a watch out for things like this as there are

several members of our group who would like to become pregnant

eventually - but this does sound like it is rather encouraging news!

[1104] Conception and Pregnancy in Patients (pts) with Chronic

Myeloid Leukemia (CML) Receiving Therapy with Imatinib Mesylate (IM).

Session Type: Poster Session 262-I

Pat Ault, Hagop Kantarjian, O'Brien, Koller, Stefan

Faderl, Emil J. Freireich, Beth Rios, Cortes Leukemia,

University of Texas M.D. Cancer Center, Houston, TX, USA

Although pts with CML receiving IM therapy are required to practice

contraception while on therapy, there are isolated case reports of

conception and pregnancy while on therapy. Here we present our

experience with 18 pts who conceived while on IM therapy: 10 females

and 8 males. All 10 females received IM for chronic phase (CP) CML.

At the time of conception 1 had a complete cytogenetic (CG) response

(CG CR), 3 a partial CG response (CG PR), 2 a minor CG response (CG

MR), 2 complete hematologic response (CHR), and 2 no response. All

pts stopped therapy immediately when pregnancy was recognized. Pts

were managed with hydroxyurea (n=3), leukapheresis (n=1), interferon

(n=1) or observation. Two pts had a spontaneous and 1 an elective

abortion; 7 pregnancies continued uneventfully until delivery (median

duration of pregnancy 36 weeks). Eight babies have been born (1 pair

of twins): one had hypospadias, 7 were normal. The median age of the

children is now 14 months (mo) and all are developing normally. At

the time of delivery/abortion, 5 pts were 100% Ph-positive, 3 had

still a CG MR and 1 a CG PR [i.e. 5 of 7 evaluable had increased Ph

off therapy (1 not tested yet, 2 results pending) (median off therapy

9 months, range 4 to 22 months).] Pts re-started therapy after

delivery and again after a median of 18 months after delivery (range

5 to 48 months), 3 have a CG CR, 2 CG PR, 1 CG MR, 2 CHR and 1

unknown. Among 8 males (6 CP, 2 AP) who impregnated their partners

while on IM, 9 pregnancies resulted in the birth of 8 healthy babies

and 1 spontaneous abortion. One baby had a mild rotation of the small

intestine that resolved surgically. There were no complications of

the other 7 babies. With a median age of 37 mo (range, 5 to 50),

there are no known growth or development problems for any of the

babies. This small experience suggests that conception while

receiving IM is most frequently associated with a normal pregnancy

and healthy babies, provided IM is immediately discontinued. Still,

the recommendation to practice effective contraception while on IM

should be enforced.

Abstract #1104 appears in Blood, Volume 106, issue 11, November 16,

2005

>

> here is a case story of 1 indian patient. it only strengthen the

caution that should be exercised if a woman wants to become pregnant

on gleevec

> shalom

> gior

> ls of Oncology letter to the editor

>

> Pregnancy on imatinib: fatal

>

> outcome with meningocele

>

> We read with interest a recent letter by Prabhash et al. [1]

>

> showing a successful outcome of pregnancy in two patients on

>

> imatinib. There have also been a few other recent reports where

>

> no adverse effects have been reported [2–4]. However, we

>

> would suggest extreme caution, based on our experience in

>

> a patient who conceived while on imatinib with an adverse

>

> outcome.

>

> A 25-year-old female was diagnosed as having chronic

>

> myeloid leukemia in chronic phase in July 2004. She had no

>

> significant past medical history and was nulliparous.

>

> Examination revealed spleen palpable 10 cm below costal

>

> margin. Hematological parameters (hemoglobin 7.8 g/dl, white

>

> blood cell count 23.4 · 109/l and platelet count 383 · 109/l) and

>

> RT–PCR revealed positive BCR-ABL translocation. Her

>

> biochemical parameters, including liver, renal functions and

>

> uric acid, were within normal limits. Therapy was started with

>

> imatinib (Glivec; Novartis, Basel, Switzerland) 400 mg/day as

>

> part of a research project where the drug was provided free. She

>

> was counseled to avoid pregnancy. Complete hematological

>

> remission was achieved at the end of 1 month and molecular

>

> remission after 3 months. Imatinib was continued at the same

>

> dosage. The patient reported to the clinic with history of

>

> amenorrhea of one and half months' duration in January 2005

>

> and a pregnancy test was positive. After counseling, she

>

> declined termination of pregnancy, but imatinib was stopped.

>

> No drug was administered until completion of the first

>

> trimester. As the patient could not afford interferon,

>

> hydroxyurea was administered to control the blood counts and

>

> symptoms. At 30 weeks, ultrasound abdomen revealed the

>

> presence of a meningocele. She delivered a dead fetus with the

>

> meningocele at the 34th week of pregnancy. She was restarted

>

> on imatinib with further advice for strict contraception and to

>

> stop the drug before any planned pregnancy.

>

> The limited published literature suggests that imatinib is

>

> safe in pregnancy [1–4]. However, animal experiments suggest

>

> it is unsafe. Imatinib, an inhibitor of abl-tyrosine kinase, is

>

> teratogenic in mouse and rats when administered during

>

> organogenesis at doses of >100 mg/kg, causing exencephaly or

>

> encephalocele, and absent or reduced frontal and absent

>

> parietal bones [5]. The most critical period for teratogenicity is

>

> the first trimester as this period correlates with active

>

> organogenesis. Our patient had been exposed to imatinib

>

> during conception and for 6 weeks thereafter with development

>

> of a meningocele and a fatal outcome. The few reports of

>

> delivery of a normal fetus, even with intake of imitanib during

>

> pregnancy, should not suggest that the drug is safe. Our case

>

> clearly highlights that the drug is potentially teratogenic. To the

>

> best of our knowledge this is the first such complication

>

> reported in humans. We strongly recommend effective

>

> contraception for all patients who are on imatinib.

>

> D. R. Choudhary, P. Mishra, R. Kumar*, M. Mahapatra &

>

> V. P. Choudhry

>

> All India Institute of Medical Sciences, Department of Hematology,

>

> AIIMS, 110029 New Delhi, India

>

> (*E-mail: rajatkr@h... or rajat1954@g...)

>

> references

>

> 1. Prabhash K, Sastry PS, Biswas G et al. Pregnancy outcome of two

patients

>

> treated with imatinib. Ann Oncol 2005; doi:10.1093/annonc/mdi398.

>

> 2. Ali R, Ozkalemkas F, Ozcelik T et al. Pregnancy under treatment

of imatinib

>

> and successful labor in a patient with chronic myelogenous leukemia

(CML).

>

> Outcome of discontinuation of imatinib therapy after achieving a

molecular

>

> remission. Leuk Res 2005; 29: 971–973.

>

> 3. AlKindi S, Dennison D, Pathare A. Imatinib in pregnancy. Eur J

Haematol 2005;

>

> 74: 535–537.

>

> 4. Heartin E, Walkinshaw S, RE. Successful outcome of

pregnancy in

>

> chronic myeloid leukaemia treated with imatinib. Leuk Lymphoma

2004; 45:

>

> 1307–1308.

>

> 5. Hensley ML, Ford JM. Imatinib treatment: specific issues related

to safety, fertility,

>

> and pregnancy. Semin Hematol 2003; 40: 21–25.

>

> doi:10.1093/annonc/mdj065

>

> letter to

>

> the editor

>

> ª 2005 European Society for Medical Oncology

>

> ls of Oncology Advance Access published November 15, 2005

>

> a

>

>