1. Unique Challenges in MPNs 2012 Bay Area MPN Patient Symposium Laura C. Michaelis, MD Loyola University Medical Center

2. Topics to Discuss  Overview: Gender and Cancer  Gender and MPNs  Special issues facing females with MPNs  Clotting  Pregnancy  Bleeding  Modifiable risk factors – both genders  Conclusions

3. Cancer: Sex-based differences Breast Ovarian Cervical Testicular Prostate

4. Cancer: Gender-based differences

5. Gender and Cancer  Does the disease occur more frequently in one sex vs. the other?  Diagnostic bias?  Due to exposure?  Due to genetic predisposition?  Does the disease behave differently in one sex vs the other?  Modulated hormones? Gender-based lifestyle differences?  Interactions that we don’t understand?  Are there different consequences to the disease or treatment that depend on gender?

6. Sex Ratio Hematologic diseases DiseaseMale:Female Ratio AML1:1 ALL1.3:1.0 HD1.3:1.0 Multiple Myeloma1.4:1 CLL2:1 CML3:2 ETFemale Predominance PV1.2:1.0 MF1:1

7. Cartwright et al. British Journal of Hematology 2002, 118 1071-1077 More women diagnosed than men More men diagnosed than women

8. Clinical Trial Inclusion Trial Total Patients MaleFemale HU in High-Risk ET NEJM 1995 11437 (32%)77 (68%) ASA in PV NEJM 2004 518 308 (59%) 210 (41%) HU vs Anagrilide in high-risk ET NEJM 2005 809 342 (42%) 467 (58%) Ruxolitinib in MF (US Study) NEJM 2012 309 167 (54%) 142 (46%)

9. Topics to Discuss  Overview: Gender and Cancer  Gender and MPNs  Special issues facing females with MPNs  Clotting  Pregnancy  Bleeding  Modifiable risk factors – both genders  Conclusions

10. Challenges: Clotting  ET – most common MPN in fertile women  Hormonal contraception + ET = hypercoaguable state  Pregnancy + ET = hypercoaguable state  Thrombosis -- #1 cause of maternal death

11. Challenges: Fertility  Contraception  Combination hormones >progesterone only OCPs  General population have a 3–6- fold increased risk of venous thrombosis with OCPs  One retrospective study of >300 patients. Subset on OCPs  ET + OCPs = 23% VTE  ET no OCPs = 7% VTE

13. Challenges: Pregnancy  Pregnancy outcomes likely impacted  Live birth rate 50-70%  First trimester loss 10-20%  Late pregnancy loss 10%  Increased rates of placental abruption, intrauterine growth restriction  Can we change those outcomes?

14. Preconception Counseling  Risk Assessment  Prior VTE or arterial clot  Prior hemorrhage  Prior pregnancy complication  Diabetes or Hypertension requiring treatment  Platelet count of >1500 X 10 9 before or during pregnancy

15. Preconception Counseling  Multidisciplinary approach  Discussion of teratogenic drugs  Therapeutic options  Aspirin  LMWH  Cytoreductive therapy  Delivery and post-partum plan  Breastfeeding information

16. Pregnancy: Low-Risk Patients  Generally  Continue low-dose aspirin  Monitor platelet or Hct  Keep HCT under 45%  Consider venesection if necessary  Increased plasma volume of pregnancy means no set targets Antiplatelet agents  reduce risk of VTE in ET patients Pregnancy is thrombotic Aspirin is likely safe in pregnancy (APLA pts)

17. Pregnancy: High-risk patients  Remove possible teratogeneic drugs  Taper off hydrea or anagrilide 3-6 months prior to conception  Hydrea likely contraindicated, men and women  Anagrilide crosses the placenta  Cytoreduction  Interferon-alpha -- Case reports indicating likely safe  Prevent Clotting  LMWH  Prophylactic or, in some cases, therapeutic doses

18. Challenges: Bleeding  More common when platelets are elevated  1,000-1,500 X 10 9  Often related to acquired Von Willebrands Disease  Occurs in both men And women

19. Topics to Discuss  Overview: Gender and Cancer  Gender and MPNs  Special issues facing females with MPNs  Pregnancy  Clotting  Bleeding  Modifiable risk factors – both genders  Conclusions

20. Outcomes: Venous, Arterial Events like stroke, heart attack, VTE, bleeding MPN Smoking lipids Exercise Healthy Weight DM HTN control

21. Conclusions  Get involved in your care  Ask questions  Participate in clinical trials  Control what you can  Any questions?