Survivorship After Allogeneic Stem Cell Transplantation: Monitoring, Management and Quality of Life

Transcription

1 1 Survivorship After Allogeneic Stem Cell Transplantation: Monitoring, Management and Quality of Life Stephanie J. Lee, MD, MPH Fred Hutchinson Cancer Research Center April 16, 2016 (40 min) Hematopoietic cell transplantation One millionth transplant performed Dec 2012 # transplant survivors doubling every 10 years Success limited by: disease recurrence high cost, lack of optimal donor availability treatment-related complications early less intensive conditioning, better supportive care late not as much progress Autologous and allogeneic transplant survivors have higher mortality and morbidity

2 2 Increased mortality rates persist Martin et al. JCO 2010; 28: x increased mortality rates in 5 year survivors Age and sex matched general population Among 2 year DFS, subsequent survival: Autologous 80% at 10 years Allogeneic 85% at 10 years 80% at 15 years Bhatia et al, Blood 2007 Majhail et al, BJH 2009 Martin et al, JCO 2010 Wingard et al, JCO 2011 Atsuta et al, Tandem 2013 Late deaths (5 year DFS) N=1,625 allogeneic recipients (13% died, n=219) N=342 autologous recipients (19% died, n=65) Martin et al. JCO 2010; 28: 2011 Syrjala et al. JCO 2012; 30: 3746

3 3 Chronic health conditions N=564 allos, 458 autos Median FU 7.3 yrs Grade 3-4: 3x rate in siblings Sun CL et al, Blood 2010 Survivorship After Allogeneic Stem Cell Transplantation: Monitoring, Management and Quality of Life

4 guidelines, 7 transplant societies BBMT 2012; 18: 348; BMT 2012; 47: 337 Screening and Preventive Guidelines Immunity/Infections Ocular Oral Lung Cardiovascular Liver Renal/GU Skeletal Muscle/Connective Tissue Nervous system Endocrine Secondary cancers Psychosocial/Sexual General health

5 5 Concise summaries Provider and patient versions FHCRC adult vaccination schedule P Carpenter, 2015

6 6 Highest priority late effects monitoring Assumes: routine visits (vital signs, ROS, physical), basic laboratory monitoring (CBC, glucose, creatinine, liver function), infectious prophylaxis, vaccinations Excludes: disease monitoring, chronic GVHD management Based on disease burden, available treatment options Thyroid function test (annual) Mammogram/PAP smear; skin, oral & thyroid exam (annual) DEXA scan (if steroids) Lipid profile (q3-5 years) Dental exam (q 6mos) (Psychosocial assessment) (Healthy lifestyle counseling exercise, weight, smoking, sun)

7 7 Who gets less preventive care? Study population N=1549 (50% response rate) Median current age: 54.5 years Median time since transplant: 11 years 95% White, 51% Male Khera N, et al. BBMT 2011; 17: Who gets less preventive care? Men Autologous transplant survivors Allos without chronic GVHD > 15 years since transplant Non-white Low physical functioning Concerned about medical costs Self-reported lack of knowledge about recommendations Khera N, et al. BBMT 2011; 17:

8 8 Second cancers (7-28% deaths) Most reports in allos 1.5-3x general population risk, inc. with time Excess O/E 5 yr TBI 10 yr TBI BuCY Oral X X X Thyroid X X Melanoma X X Connective tissue X X Brain X X Liver X X Bone Breast Esophagus Lung X X X X Rizzo et al, Blood 2009 Majhail et al, Blood 2011 Second cancers (7-28% deaths) Most reports in allos 1.5-3x general population risk, inc. with time Excess O/E 5 yr TBI 10 yr TBI BuCY Oral X X X Thyroid X X Melanoma X X Connective tissue X X Brain X X Liver X X Bone Breast Esophagus Lung X X X X Rizzo et al, Blood 2009 Majhail et al, Blood 2011

9 9 Counseling patients about monitoring The rate of chronic medical conditions is 2-4x higher after a transplant compared to the general population You will need close medical follow-up for the rest of your life Prevention, monitoring, and appropriate management are KEY to minimizing any adverse impact of late effects on your life Survivorship After Allogeneic Stem Cell Transplantation: Monitoring, Management and Quality of Life

10 10 Survivorship care models Transplant Survivor -Disease surveillance -Late effects monitoring and management -General preventive care -Cancer screening (new cancers) -Other screening and prevention (diabetes, thyroid) -Co-morbidity management -Education Survivorship care models Transplant Physician/Nurse Transplant Survivor -Disease surveillance -Late effects monitoring and management -General preventive care -Cancer screening (new cancers) -Other screening and prevention (diabetes, thyroid) -Co-morbidity management -Education

11 11 Survivorship care models Transplant Physician/Nurse Hematologist/ Oncologist Physician/Nurse Transplant Survivor -Disease surveillance -Late effects monitoring and management -General preventive care -Cancer screening (new cancers) -Other screening and prevention (diabetes, thyroid) -Co-morbidity management -Education Survivorship care models Transplant Physician/Nurse Hematologist/ Oncologist Physician/Nurse Primary Care Physician/Nurse Transplant Survivor -Disease surveillance -Late effects monitoring and management -General preventive care -Cancer screening (new cancers) -Other screening and prevention (diabetes, thyroid) -Co-morbidity management -Education

12 12 Survivorship care models Transplant Physician/Nurse Hematologist/ Oncologist Physician/Nurse Primary Care Physician/Nurse Transplant Survivor Survivorship or LTFU clinic -Medical subspecialists -Psychosocial support -Physical therapy -Nutrition -Disease surveillance -Late effects monitoring and management -General preventive care -Cancer screening (new cancers) -Other screening and prevention (diabetes, thyroid) -Co-morbidity management -Education Cardiovascular Hypertension (20-30%) treat if > 140/90 on 2 visits at least 1 week apart Hyperlipidemia (10-40%) ATP III guidelines: ACC/AHA guidelines Diabetes (7-13%) Obesity (16%) BP on each visit, at least q 2 yrs Fasting lipid panel q 5 yrs, starting age 20 DM screening q 3 yrs, if HTN, chol, > 45 y/o

13 13 Cardiovascular hospitalizations and mortality N=1,491 HCT 2 year survivors matched with WA state residents Chow et al. Ann Int Med 2011; 155: Attributable risk percent (AR%) associated with risk factors (x-axis) for (A) serious cardiovascular outcomes and (B) related conditions among exposed hematopoietic cell transplantation survivors. Eric J. Chow et al. JCO 2014;32: by American Society of Clinical Oncology

14 14 Psychosocial distress Depression (20%) Over the past 2 weeks Have you felt down, depressed, or hopeless? Have you felt little interest or pleasure in doing things? Sexual dysfunction (45% women) Do you have any concerns about your sex life? Screen for depression and sexual dysfunction every 6-12 mos Depression and Fatigue p=.01 p=.005 p=.04 PHQ-8 FSI Severity FSI Disruptiveness N=1869 Allo: Auto Mod-severe depression 14% 15% Mod-severe fatigue 31% 31% General population: Major depressive episode: 6.6% Fatigue: % Allo - related (n=663) Allo - unrelated (n=525) Auto (n=666) Jim H et al. Cancer 2016; 122: 1290

15 15 Focus of medical care Non-HCT related Co-morbidities Transplant long-term effects Getting older concerns Relapse Transplant late effects Day 0 Rest of your life Surviving the cure Survivorship care limited by lack of: Time Money Interest Knowledge Majhail & Rizzo, BMT 2013

16 16 Research questions in survivorship care If the goal is to decrease morbidity and mortality from late effects: What testing is necessary? Reasonable? A luxury? Incidence and severity of the problem Availability and effectiveness of treatments Should treatment thresholds or management approaches be adjusted in HCT survivors? What care model works best for survivors? Treating physician vs. centralized survivorship clinic How do you engage survivors in health maintenance? Given limited funding and time for survivorship care, where is that money best spent? Survivorship After Allogeneic Stem Cell Transplantation: Monitoring, Management and Quality of Life

17 17 Global QOL PHYSICAL* fatigue pain FUNCTIONAL* work sleep EMOTIONAL anxiety enthusiasm SOCIAL family friends Multidimensional Individual Surrogates inaccurate Subjective Framing Response Shift Summary of QOL findings High global QOL, many specific problems: fatigue, cognitive deficits, sleep, sexual functioning 20-30% do not return to work 5-20% have sig functional deficits or poor QOL recovery is a 3-5 year process Some positive effects: greater appreciation for life, health, loved ones

18 18 Summary of QOL findings Factors associated with better QOL: higher pre-hct functioning, education, income younger age, male good risk disease longer time since HCT, no chronic GVHD auto or chemo vs. allo not NMA/RIC vs. myeloablative Number of late adverse effects Lower PF, KPS Limitations in normal activities Less likely to work Poor functioning: joint replacement, diabetes, adrenal insufficiency, pulmonary disease Khera et al, JCO 2011

19 19 Clinical Implications Make patients aware of potential deficits self-monitor for problems provide reassurance about common experiences discordance between expectations and reality is a major source of post transplant distress Improve survivorship care risk stratification for more intensive monitoring interventions to address deficits Consider QOL in treatment decisions QOL before allogeneic HCT BMT CTN 0902 N=310 allos Median FU 23 mos TRM: p=0.047 OS: p=0.001 P<0.001 Similar or better predictive ability as HCT-Comorbidity Index and Disease Risk Index for 6 and 12 month survival Physical functioning; general health Wood et al, Cancer 2015; 122: 91

20 20 BM or PB for URD HCT BMT CTN 0201 was a RCT of unrelated donor bone marrow (BM) vs. peripheral blood (PB) transplantation for hematologic malignancies MA/RIC conditioning, Tac/Csa+methotrexate 2 year results showed similar survival, DFS, TRM BM had a higher rate of graft failure (9% vs. 3%, p=0.002) PB had a higher rate of chronic GVHD (53% vs. 41%, p=0.01) PB still >80% of URD HCT Anasetti et al. NEJM 2012; 367: 1487 Five year results of BM vs. PB QOL scale Bone marrow (n=102) FACT-BMT TOI ( better) Mean +/- SE /- 1.6 (n=79) MHI Psychological wellbeing ( better) Mean +/- SE MHI-Psychological Distress ( better) Mean +/- SE Chronic GVHD symptoms ( better) Mean +/- SE /- 1.7 (n=80) /- 1.3 (n=80) Peripheral blood (n=93) /- 1.9 (n=69) /- 1.9 (n=72) /- 1.5 (n=71) P value Clinically significant difference 1 Difference between BM and PB (95% CI) ( ) ( ) (-6.8,0.9) /- 1.5 (n=80) /- 1.6 (n=72) (-10.5, -2.0) FACT-BMT TOI, Functional Assessment of Cancer Therapy, Bone Marrow Transplant Trial Outcome Index; MHI, Mental Health Inventory; GVHD, Graft-versus-Host Disease; SE, standard error x STD 2 Adjusted for enrollment values and missing data using inverse probability weighting using significant clinical characteristics 40

21 21 Additional results chronic GVHD Chronic GVHD skin (0-100, better) Mean +/- SE /- 1.8 (n=80) Chronic GVHD eyes (0-100, better) Mean +/- SE /- 3.0 (n=80) Chronic GVHD mouth (0-100, better) Mean +/- SE 6.7 +/- 2.1 (n=80) Chronic GVHD lung (0-100, better) Mean +/- SE 3.8 +/- 0.9 (n=80) Chronic GVHD nutrition (0-100, better) Mean +/- SE 3.3 +/- 0.8 (n=80) Chronic GVHD energy (0-100, better) Mean +/- SE /- 2.7 (n=80) Chronic GVHD psych (0-100, better) Mean +/- SE /- 3.0 (n=80) BM PB P-value /- 2.3 (n=72) /- 4.1 (n=72) 9.2 +/- 1.7 (n=72) 9.2 +/- 1.7 (n=72) 5.3 +/- 1.2 (n=72) /- 3.1 (n=72) /- 2.8 (n=72) 0.06 < Additional 5 yr results reported by centers Chronic GVHD, n (%) No cgvhd Mild Moderate Severe Missing BM (n=102) PB (n=93) P-value 72 (71) 17 (17) 9 (9) 4 (4) 0 46 (49) 21 (23) 16 (17) 8 (9) 2 (2) Skin sclerosis, n (%) 8 (8) 17 (18) 0.03 Eye involvement, n (%) 15 (15) 31 (33) Musculoskeletal involvement, n (%) 3 (3) 14 (15) Avascular necrosis, n (%) 5 (5) 14 (15) 0.02 No differences in: - mouth, lung or GI involvement - diabetes, dialysis, hypothyroidism, cardiac

22 22 Return to work Likelihood of return to full or part time work outside the home was higher for BM 52% vs. 40%, OR 1.5, 95% CI , p=0.002 Adjusted for work status before transplant Missing data imputed based on graft source, disease risk, and age 43 Overall Survival 100 Probability, % Median FU 73 months P=0.84 Bone marrow Peripheral Blood Stem Cells Years 44

23 23 Summary HCT survivors are at higher risks of morbidity (2-4x) and mortality (2-9x). The number of survivors is growing Long-term follow-up of HCT survivors involves prevention, screening, appropriate interventions and patient education Data supporting specific models of care are lacking; efficacy likely depends on clinician interest and resources Late effects are associated with worse quality of life Survivorship is a good problem to have