ESSENTIAL THROMBOCYTHEMIA AND PREGNANCY PRELIMINARY REPORT OF THE PREGNANCY COMMITTEE OF THE

REGISTRO ITALIANO TROMBOCITEMIE (RIT)L Melillo1, A Tieghi 2, A.Candoni 3, R Ciancia4, V Martinelli4, R Latagliata5, G Specchia6, PR Scalzulli1, R Fanci7, G Comitini2, N Cascavilla1 and L Gugliotta 2 on behalf of the Registro Italiano Trombocitemie (RIT )1Hematology Unit S. Giovanni Rotondo, 2Hematology Unit Reggio Emilia, 3Hematology Unit Udine, 4Hematology University of Napoli, 5Hematology University of Roma1, 6Hematology University of Bari, 7Hematology University of Firenze, Italy.This study is supported by a Ministero Istruzione, Università e Ricerca grant ( Grant RC0606EM71)

Background

• Essential Thrombocythemia (ET) is diagnosed in the childbearing age in about 20% of patients.

• Fertility reduction and adverse outcome of pregnancy due to thrombotic or hemorragic complications are a matter of concern

• Pregnancies in women affected by ET can be complicated by recurrent abortion, fetal growth restriction, stillbirth and placental abruction.

• Present therapeutic approaches vary from no treatment to treatment with platelet reductive agents and/or ASA.

Methods

We evaluated the outcome of pregnancy in a series of ET patients observed in 7 Italian Hematological Centres.

• Study population: Sixty pregnancies occurring in 48 women with ET

• Study Period: January 1998 - May 2006• Age, median 33 (range 21-45) years• Diagnosis: WHO criteria• Concomitant thrombophilic abnormalities: none• High-risk patients: previous pregnancy complications

or platelet count >1,000 x109 /L • Management: no specific treatment in 7 pregnancies,

ASA 100 mg die in 47/60 pregnancies. LMWH for 6 weeks post-partum. Interferon alpha in 13 high-risk patients.

Outcome of the 24 pregnancies observed in 22 women who conceived during treatment for ET

67%

21%

8% 4%

Live birth Foetal losses Voluntary abortion Ongoing

Outcome of the 60 pregnancies in 48 patients with ET

11%

10%

3%

8%

5%

48%

2%

13%

62%

1st trim loss 2nd trim loss

Still Birth Voluntary abortion

Ongoing Live birth FT

IUGR Premature live birth

Outcome of the 17 pregnancies treated with alphaIFN

6%

12%

47%

35%

82%

Ongoing Foetal loss Full Term Delivery Live birth premature delivery

Legend – GA gestational age; SA spontaneous abortion; VA voluntary abortion; A&W alive and healthy; SB still birth; FT term; IUD intrauterine death; IUGR intrauterine growth retard§ Pregnancy occurred before ET diagnosis * Pregnancy started during ET treatment

Patients characteristics

Conclusions

•These data confirm that fetal morbidity and mortality is not negligible in ET•Cytoreductive therapy with AlphaIFN seems potentially able to protect against fetal losses•Although normal pregnancies have been observed in patients who conceived during cytotoxic treatment, effective forms of contraception throughout treatment is still strongly recommended•Optimal management of pregnancy in ET patients is still poorly defined, and there are no established protocols. Recommendations for ET in pregnancy, based on current knowledge of ET and the management of inherited thrombophilia and the Antiphospholipid Syndrome in pregnancy, have been proposed ( Harrison,BJH 2005)•The epidemiological, clinical and biological data on pregnancy in ET obtained by the partecipating Centres are now object of a prospective study by the RIT, a GIMEMA projects which records the ET patients diagnosed in Italy since January 2004.

Patient Age at

Pregnancy ET

Treatment Noof

Pregnancy Antiaggregant

Drug Treatment Outcome And GA

MG 29 ANA 1* ASA VA 6w

DC 34 ANA 1* ASA FT

MM 35 ANA 1* ASA FT

FP 22 ANA 1* ASA alphaIFN FT

SL 24,29 ANA 2 (1§, 1*) ASA alphaIFN FT

GM 33 ANA 1* ASA alphaIFN FT

ZO 40 ANA 1* ASA alphaIFN FT

AL 25 ANA 1* ASA alphaIFN ongoing

IN 45 BUS 1* ASA FT

MC 32,37 HU 2 ( 1*) No SA 9w, A&W 32 w

ME 34 HU 1* ASA SA 7w

CA 36 HU 1* ASA SA 13w

DG 35 HU 1* ASA FT

CH 38 HU 1* No FT

AL 35 IFN 1* ASA SA 14 w

VI 29,31 IFN 2* ASA SA 20 w, FT

OR 30 IFN 1* ASA VA 10w

FL 39 IFN 1* ASA FT

DC 32 IFN 1* ASA FT

MI 38 IFN 1* ASA FT

CL 28 IFN 1 ASA FT

RR 30 IFN 1* No ongoing

AA 35 IFN 1 No alphaIFN A&W 34w

DS 29 IFN 1 No alphaIFN A&W 35w

TS 24,28 IFN 2* No alphaIFN FT,FT

MO 33 IFN 1 ASA alphaIFN FT

MD 33 NO 1§(FIVET) ASA SA 11w

MA 33 NO 1 No SA 9w

CE 26 NO 1 ASA VA 16w

CI 28 NO 1 ASA VA 8w

FS 36 NO 1 ASA VA 10w

LA 29,31 NO 2 ASA SA 16w,SA 13w

PU 26,27,27 NO 3 ASA SA 8w,SA 11w, FT

ES 22 NO 1 ASA A&W 36w

TO 32 NO 1 ASA FT

SA 35 NO 1§ ASA ongoing

BB 38 NO 1 ASA FT

TS 28,36 NO 2 ASA alphaIFN FT, FT

SO 21 NO 1 No FT

BA 36 NO 1 No FT

MU 21 NO 1 ASA FT

CA 38 NO 1 ASA FT

CA 38 NO 1 No FT

BE 28,3 NO 2 ASA FT,FT

GG 25,26,30,32 NO 4 No alphaIFN A&W 36w,A&W34w,SA8w,SB26w

EF 30,35 NO 2 ASA alphaIFN IUD 28w,FT

DFA 22 NO 1 No alphaIFN IUGR 34w