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Symptoms and Special Circumstance in MPNs

Symptoms and Special Circumstance in MPNs. 2014 Florida Patient Symposium Laura C. Michaelis, MD Medical College of Wisconsin, Milwaukee. Spectrum of Symptoms.

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Symptoms and Special Circumstance in MPNs

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  1. Symptoms and Special Circumstance in MPNs 2014 Florida Patient Symposium Laura C. Michaelis, MD Medical College of Wisconsin, Milwaukee

  2. Spectrum of Symptoms • “clinical conditions with high relevance for the duration and quality of the patient’s life, but with limited evidence to support sound diagnostic and therapeutic recommendations…” • TizianoBarbui. 2010

  3. Spectrum of Symptoms • Day-to-Day • Fatigue, Itching, Night sweats, Bone Pain, Fevers, Bleeding, Erythromelagia • Life-Threatening • Arterial and Venous Clots, Bleeding • Medication Associated • Side Effects, Anxieties, Financial • Special Circumstances • Surgery, Contraception and Pregnancy

  4. Heterogeneous Presentations: Symptoms Mesa, Cancer 2007

  5. Risks and Benefits TX Sx of Disease SX of Disease Tox

  6. Case #1: Denise • 46 yo woman with newly diagnosed PV • History of a blood clot in the left leg following her last pregnancy, 8 years ago • She has had 5 phlebotomies since diagnosis and her CBC demonstrates good control of her blood counts • She has been allergic to aspirin since childhood • She tells you: I’m still having a lot of itching after showering

  7. Aquagenic pruritus • Often occurs with PV • Stinging, itching – often after contact with water • Majority of patients experience it • Recent German study demonstrated 68% of PV patients reported about pruritus • Can be relentless and may not always respond to treatment for the disease

  8. Treatment options for Pruritis • Symptom-Oriented • Antihistamines • Paroxetine • Light therapy • Aprepitant • Disease-Oriented • Cytoreduction: HU or IFN • Jak-Stat Pathway therapy • Aspirin

  9. Case #2: Carla • 64 yo woman with ET • Diagnosed after a stroke at the age of 55 • Blood numbers are under good control • Taking HU to control platelet count • But “I’m so tired at night – especially after eating.”

  10. Managing MPN Fatigue • Symptom-Oriented • Exercise (low-intensity as good as high intensity) • Healthy Lifestyle and Diet • Correction of Iron Deficiency When Possible • Stimulants: Ritalin/Provigil/ Nuvigil • Disease Treatment • JAK2 Inhibitors

  11. Severity Spleen-Related Symptoms: N=1433 Prevalence Scherber Blood 2011

  12. COMFORT-1: Symptoms Verstovsek S et al. NEJM 2012; 366; 799-807

  13. Case #3: Jessica • 42 yo mother • Essential Thrombocythemia • Diagnosed on routineblood testing at GYN office • No risk factors • WBC 12.3; Hgn 13; Plts 560 • 1.5 years after diagnosis, reports “foot pain.” • Occurs when walking or standing on her feet • Burning, painful, reddish

  14. Case #3 Jessica • Erythromelalgia • Neurovascular pain disorder • Can occur secondary to ET • Characterized by severe burning pain and redness • Can be debilitating • Treatment • Aspirin, Cytoreduction • Gabapentin

  15. Spectrum of Symptoms • Day-to-Day • Fatigue, Itching, Night sweats, Bone Pain, Fevers, Bleeding, Erythromelagia • Life-Threatening • Arterial and Venous Clots, Bleeding • Medication Associated • Side Effects, Anxieties, Financial • Special Circumstances • Surgery, Contraception and Pregnancy

  16. Case #4: Gerald • Gerald S. • 56 yo man with newly diagnosed Polycythemia Vera • Hgn 19.3 gm/dL • Hct 58% • WBC 12.4 k/uL • Plts 338 k/uL • I recommend phlebotomy and starting a low-dose aspirin. He asks – how many treatments will I need and what’s our goal?

  17. PV: What is the optimal hematocrit? January 2013

  18. Target Hematocrit Hct <45% Which group developed more arterial and venous clots? Which group experiences more bleeding episode? Which group develops fibrosis or leukemia more readily? 365 Hct 45-50%

  19. Case #4: Gerald • So – answers? • Phlebotomy goal should be a hematocrit of less than 45% • In women, generally aim for even lower than that, 42-43% • Frequency varies – but as often as needed • Sometimes medication also needed, but you have to give phlebotomy a chance

  20. Case #5: Kyle • 57 yo man with Essential Thrombocythemia • Incidentally discovered two years ago • No symptoms, no history of blood clots • Platelet count of 1,380 k/uL • Now with found to occult + stools • Colonscopy normal, but stomach ulcers noted on endoscopy

  21. Bleeding vs. Clotting • Not as common as clotting problems • Often manifest with • Nosebleeds • Gum bleeding • Menorrhagia • Less likely to be deep tissue bleeding • Rarely can be life threatening • Risk increases with Platelets>1,000,000/uL

  22. Acquired VWD Normal Blood Vessel Increase in platelets

  23. Case #5: Kyle • What can we do about his nose bleeds? • Normalization of platelet count • Medication vigilance  combos in particular • Anagrilide + Aspirin • Plavix or Aspirin + heparin products • Predictable bleeding • i.e. interventions to prevent menorrhagia • Special care in individuals with gastric ulcers or esophageal varices

  24. Case #6: Bonnie • Surgery and VTE • Increased risk for patients with MPN • Likely due to differences in the • Blood vessels • Platelets • Clotting factors? • 67 years old with PV • TIA in her late 50s • Treatment: HU and aspirin • Recently diagnosed with small left-sided breast cancer, has opted for mastectomy • What are my surgical risks?

  25. Modifying Surgical Risk

  26. Spectrum of Symptoms • Day-to-Day • Fatigue, Itching, Night sweats, Bone Pain, Fevers, Bleeding, Erythromelagia • Life-Threatening • Arterial and Venous Clots, Bleeding • Medication Associated • Side Effects, Anxieties, Financial • Special Circumstances • Surgery, Contraception and Pregnancy

  27. Gender-based differences • Differences between the disease incidence in men and women • Problems specifically faced by women • Contraception • Pregnancy/Fertility

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

  29. Cancer: Gender-based differences

  30. 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?

  31. Sex RatioHematologic diseases

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

  33. Clinical Trial Inclusion

  34. Case #7: Jennifer • 37 yo woman with a history of thrombosis in her right calf while on birth control • Found to have JAK2 mutation and a slightly elevated platelet count • She asks you: did the birth control or ET cause the blood clot? Can she take birth control again? Can she try and get pregnant?

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

  36. 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

  37. 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?

  38. 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

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

  40. 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)

  41. Pregnancy: High-risk patients • Remove possible teratogeneic drugs • Taper off hydrea or anagrilide 3-6 months prior to conception • Hydrealikely 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

  42. Summary and Conclusions • Some symptoms can be addressed with a palliative approach • Some require that the disease be treated • Target Hgn, PV • Preventing Bleeding • Undergoing Surgery • Gender-specific issues: Contraception, Fertility and Pregnancy • Modifying risk – lifelong effort for all patients • Cholesterol, Blood pressure, SMOKING

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

  44. Conclusions • Get involved in your care • Partner with your physician • Educate other physicians, care-providers • Ask questions • Participate in clinical trials • Control what you can • Any questions?

  45. Thank yous to All the patients Ann Brazeau MPN Research Foundation The Chicago MPN Roundtable JamileShammo ToyosiOdenike Brady Stein DamianoRondelli My mentors Wendy Stock Richard Larsen Patrick Stiff SuchaNand Mary Horowitz Ruben Mesa

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