Unique Challenges in MPNs 2012 Bay Area MPN Patient Symposium Laura C. Michaelis, MD Loyola University Medical Center 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 Cancer: Sex-based differences Breast Ovarian Cervical Testicular Prostate Cancer: Gender-based differences Gender and Cancer Does the disease occur more frequently in one sex vs. the other? Does the disease behave differently in one sex vs the other? Diagnostic bias? Due to exposure? Due to genetic predisposition? 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? Sex Ratio Hematologic diseases Disease Male:Female Ratio AML 1:1 ALL 1.3:1.0 HD 1.3:1.0 Multiple Myeloma 1.4:1 CLL 2:1 CML 3:2 ET Female Predominance PV 1.2:1.0 MF 1:1 25-29 30-50 Over 50 years Sex Ratio: MPN More women diagnosed than men All MPNs Essential Thrombocythemia More men diagnosed than women Cartwright et al. British Journal of Hematology 2002, 118 1071-1077 Clinical Trial Inclusion Trial Total Patients HU in High-Risk ET NEJM 1995 114 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%) Male Female 37 (32%) 77 (68%) 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 Challenges: Clotting ET – most common MPN in fertile women Hormonal contraception + ET = hypercoaguable state Pregnancy + ET = hypercoaguable state Thrombosis -- #1 cause of maternal death Challenges: Fertility Contraception Combination hormones >progesterone only OCPs General population have a 3–6fold 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 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? Preconception Counseling Risk Assessment Prior VTE or arterial clot Prior hemorrhage Prior pregnancy complication Diabetes or Hypertension requiring treatment Platelet count of >1500 X 109 before or during pregnancy Preconception Counseling Multidisciplinary approach Discussion of teratogenic drugs Therapeutic options Aspirin LMWH Cytoreductive therapy Delivery and post-partum plan Breastfeeding information Pregnancy: Low-Risk Patients Antiplatelet agents reduce risk of VTE in ET patients Generally Keep HCT under 45% Consider venesection if necessary Pregnancy is thrombotic Aspirin is likely safe in pregnancy (APLA pts) Continue low-dose aspirin Monitor platelet or Hct Increased plasma volume of pregnancy means no set targets Pregnancy: High-risk patients Remove possible teratogeneic drugs Cytoreduction Taper off hydrea or anagrilide 3-6 months prior to conception Hydrea likely contraindicated, men and women Anagrilide crosses the placenta Interferon-alpha -- Case reports indicating likely safe Prevent Clotting LMWH Prophylactic or, in some cases, therapeutic doses Challenges: Bleeding More common when platelets are elevated 1,000-1,500 X 109 Often related to acquired Von Willebrands Disease Occurs in both men And women 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 Outcomes: Venous, Arterial Events like stroke, heart attack, VTE, bleeding Exercise HTN control MPN Smoking lipids DM Healthy Weight Conclusions Get involved in your care Ask questions Participate in clinical trials Control what you can Any questions?