Smita Bhatia, M.D., M.P.H.


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Health-related outcomes after pediatric cancer: Price of cure

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  • Improvements in diagnosis and management of childhood cancer have resulted in survival rates approaching 80%. Currently in the US, there are over 250,000 childhood cancer survivors, such that 1 in 1000 individuals is a survivor of childhood cancer. Moreover, among individuals between the ages of 18 and 45 years, 1 in 640 individuals is a childhood cancer survivor.
  • Cancer and its treatment during childhood can result in a variety of long-term sequelae, ranging from impairment in growth and development to vital organ dysfunction, to issues related to fertility and reproduction and finally, the development of subsequent neoplasms, all of which can potentially have an adverse effect on the overall quality of life of the survivor.
  • In fact, follow-up of a multi-national cohort of children with HD has demonstrated that HD survivors are at a 55-fold increased risk of breast cancer when compared with the general population. All breast cancers in this cohort developed within the radiation field and, among girls treated with mantle radiation, the cumulative incidence of developing breast cancer approached 20% by the time the cohort was 45 years of age.
  • Although there have been several studies describing toxicities associated with therapeutic exposures and late mortality, little is know of the overall morbidity within this population.
  • This study demonstrates quite conclusively, that the implications of cure are not trivial, and that indeed the burden of morbidity carried by childhood cancer survivors is quite substantial.
  • The fact that, one third of the survivors suffer from life-threatening illness by 30 years from diagnosis And the survivors are four times more likely to report chronic disease when compared with healthy siblings. These data support a critical need for continuing follow-up of childhood cancer survivors into adult life, and, more importantly identification and provision of resources to do so. Furthermore, survivors and their healthcare providers need to be aware of the “at risk” populations in order to institute appropriate surveillance and early prevention strategies.
  • Healthcare utilization by long-term cancer survivors revealed that while 87% reported general medical contact within the past two years, and 72% reported a general physical examination, only 42% reported a cancer-related visit, and, only 19% reported a cancer center visit. Furthermore, cancer-related visits and cancer-center medical visits declined with time since diagnosis, placing the burden on the general practitioner for providing ongoing care of these survivors. Factors associated with no medical care No health insurance, male sex, lack of concern about future health
  • Thus, knowledge deficits exist among adult survivors of childhood cancer regarding basic aspects of diagnosis and treatment. The survivors are unaware of their risks, thus impairing their ability to seek and receive appropriate long-term follow-up care. Provision of risk-based care decreases with time Primary care providers are responsible for healthcare for most of the survivors Primary care providers should educate patients about future health risks and recommend appropriate evidence-based screening.
  • Dr. Oeffinger has shown very effectively, that indeed childhood cancer survivors carry a significant burden of morbidity, necessitating comprehensive follow-up of cancer survivors, which would begin at the end of therapy, with a documented summarization of therapeutic expsoures, with follow-up guided by these exposures per the long-term follow-up guidelines utilizing a standardized protocol for follow-up of cancer survivors.
  • Hematopoietic cell transplantation is now an established curative option for a variety of hematological malignancies. Over the years, the number of both allogeneic and autologous transplants have continued to increase, as a result of the wide utilization of this treatment and its extension to recipients older than age 60.
  • More than 40’000 transplants are performed worldwide each year
  • More than 40’000 transplants are performed worldwide each year
  • Good Morning, my name is Liton Francisco and I am presenting today is on Psychological Outcomes in Adult Long-Term survivors of HCT. This report comes from the Bone Marrow Transplant Survivor Study, a collaborative effort between the City of Hope and the University of Minnesota.
  • The next several slides provide data on the comparisons of the percents of medical late effects associated with the metabolic syndrome in the graphs and the odds ratios for these comparisons in the table below. The first of these, shows the comparison between transplant survivors vs. the sibling controls. Cases were 3 times more likely to have developed diabetes and 1.6 times more likely to have been diagnosed with HTN. There was no difference in the likelihood of developing any of the cardiovascular outcomes, and interestingly, survivors were less likely to be obese than were sibling controls.
  • For the comparison of TBI in the preparative regimen vs. no radiation, radiation exposure was associated with a 3 fold higher risk of diabetes but did not increase the risk for HTN, any of the cardiovascular outcomes or for obesity.
  • Good Morning, my name is Liton Francisco and I am presenting today is on Psychological Outcomes in Adult Long-Term survivors of HCT. This report comes from the Bone Marrow Transplant Survivor Study, a collaborative effort between the City of Hope and the University of Minnesota.
  • Good Morning, my name is Liton Francisco and I am presenting today is on Psychological Outcomes in Adult Long-Term survivors of HCT. This report comes from the Bone Marrow Transplant Survivor Study, a collaborative effort between the City of Hope and the University of Minnesota.
  • One such late complication of HCT is chronic kidney disease, characterized by the presence of sustained abnormalities of renal function, resulting from a variety of causes of renal injury. It may lead to progressive loss of renal function and may terminate in end-stage renal disease. Reported risk factors for post-transplant chronic kidney disease have included presence of chronic Graft versus Host Disease, and exposure to nephrotoxic agents, including conditioning with high-dose chemotherapy and total body irradiation, and exposure to calcineurin inhibitors for GVHD prophylaxis and treatment; exposure to antibiotics (particularly vancomycin and aminoglycosides), and antifungal agents.
  • Risk factors for development of delayed CKD after allogeneic HCT included older age at HCT, exposure to Cyclosporine and Tacrolimus, and a primary diagnosis of multiple myeloma.
  • The percent of people returning to work at 6m was about 24% which increased to almost 58% at 3y after transplant.
  • cGVHD also delayed return to full time work.
  • And the 10 year cumulative incidence of a severe or life-threatening condition reached 51% in survivors but only 14% in siblings.
  • However, there is a lack of information regarding burden of morbidity and psychological health among HCT recipients who have survived for an extended length of time, such as those who have survived 10 or more years. Furthermore, there is a paucity of information with regards to the healthcare utilization by these long-term survivors.
  • As you can see from this slide, survivors were more likely to report have a chronic health condition compared to siblings. The difference was especially prominent for grade 3 or 4 conditions.
  • As for the reltive risk, survivors were 2 times more likely to report any health condition, but were 5.6 times more likely to report life-threatening/disabling conditions.
  • The cumulative incidence of any grade condition in survivors reached 71% at 15 years post HCT, and 40% for grade 3-5 conditions
  • With respect to psychological outcomes, survivors were not different from siblings in terms of reporting anxiety, depression, and global distress. However, even after 10 years, survivors were significantly more likely to report somatic distress compared with sibling.
  • On multivariate analysis, survivors were 2.7 times more likely to report somatic distress.
  • 90% of survivors did report that they had health insurance coverage. 100% of the survivors reported making medical contact within the past 2 years; 78% had received a general physical and nearly two thirds were returning to the cancer center for ongoing care.
  • Smita Bhatia, M.D., M.P.H.

    1. 1. Health-related Outcomes after Pediatric Cancer Price of CureSmita Bhatia, M.D., M.P.H.Director, Center for Cancer Survivorship
    2. 2. Childhood Cancer Survivors Currently in the US…. • Over 300,000 childhood cancer survivors • 1 in 1,000 is a childhood cancer survivor • 1 in 540 is a childhood cancer survivor (18-45 yr.)
    3. 3. Distribution of Childhood Cancer Survivors
    4. 4. Landmarks in Pediatric Oncology by Decade1970s • Recognition that cure was possible • Proliferation of clinical trials • Effective multi-modality protocols1980s • Tailoring therapy to risk factors • Defining late effects • Reducing radiation dose • Substituting effective drugs for radiation1990s • Understanding relationship of dose to late effects • Initiating efforts to track and educate survivors
    5. 5. Long-term Sequelae in Childhood Cancer Survivors Growth and development Vital Organ Function linear growth Cardiac skeletal maturation Pulmonary intellectual function Renal emotional/social maturation Endocrine Health-related Quality of Life sexual development Gastrointestinal Vision/Hearing Fertility and Reproduction Second Neoplasms Fertility Benign Health of Offspring Malignant
    6. 6. Cognitive Dysfunction
    7. 7. Cognitive Dysfunction1 to 2 yrs following radiation• progressiveAcademic difficulties• reading, language, mathematics• significant drops in IQ scoresRisk Factors• Leukemia, brain tumors• Radiation to the brain• Intrathecal chemotherapy• Young age – less than 5 years• Female gender
    8. 8. Cardiac Complications Can occur years after completion of treatment Spontaneous or coincide with exertion or pregnancy • Chemotherapy (anthracyclines) • Chest radiation • Females • Younger age
    9. 9. Lung Complications Causes • Radiation • Chemotherapy Symptoms • Chronic cough • Shortness of breath Prevention • Caution about smoking • Frequent checks
    10. 10. Growth Retardation • Brain tumors (30% to 35%) • Leukemia (10% to 15%) • Whole-brain irradiation • Younger age at treatment • Females
    11. 11. Second Primary CancersRadiationChemotherapySmokingDietExerciseGenetic susceptibility
    12. 12. Breast Cancer after Hodgkin disease in girls receiving radiation 0.30 SIR=55Cumulative incidence 0.20 0.10 20% 0.0 15.0 25.0 35.0 45.0 Age in years
    13. 13. Burden of Morbidity in Survivors ofChildhood Cancer?
    14. 14. Growth Impairment After Radiation
    15. 15. R
    16. 16. Cardiac ComplicationsPulmonary Dysfunction
    17. 17. The implications of cure are not trivial Burden of morbidity in survivors of childhood cancer is substantial
    18. 18. Chronic Diseases in Childhood Cancer Survivors 1.0 0.8 Grade 1-5Cumulative Incidence 0.6 Grade 3-5 0.4 0.2 0.0 N Engl J Med, 2006 0 10 20 30
    19. 19. Burden of Morbidity in Childhood Cancer SurvivorsNeed for continuing follow-up of childhood cancer survivors into adult life Survivors and healthcare providers need to be aware of the “at risk” populationsOnly 35% of survivors understand that serious health problems could result from past treatmentImpairs survivors’ ability to seek and receive appropriate long- term follow-up care
    20. 20. Health Care Utilization by Young Adult Survivors Ann Fam Med 2004;2:61-70ov vr uS t necr e P Years since Diagnosis i
    21. 21. ConclusionsPrimary care providers are unfamiliar with the problems faced by childhood cancer survivors
    22. 22. Survivorship IssuesExtended and standardized follow-up of survivorsWho provides the follow-up?• Primary oncologist• Primary health care provider• BothIssues related to transitioning of care• From pediatrics to adult-centered care• From oncology to primary careIssues related to lack of insuranceIssues related to lack of awareness regarding potential late effects• Survivors• Health care providers
    23. 23. Care of Childhood Cancer Survivors Long-term survival is an expected outcome for most children with cancer Infrastructure for long-term specialized care for survivors
    24. 24. City of HopeChildhood Cancer Survivorship Program • Diagnosis of cancer at age 21 or younger • In remission and off-therapy for 2 yr • Consent to participate in IRB-approved protocol • No upper age limit
    25. 25. Childhood Cancer Survivorship Clinic:Therapeutic Summary
    26. 26. Childhood Cancer Survivorship Clinic:Recommendations for Follow-Up
    27. 27. Childhood Cancer Survivorship Clinic:Health Links
    28. 28. Childhood Cancer Survivorship Clinic:Lay Recommendations
    29. 29. Follow-Up – Patient Report
    30. 30. Follow-Up (PCP Report)
    31. 31. Comprehensive Follow-up of Cancer Survivors Summarization of Long-term Follow-up Guidelines therapy exposures End of therapy
    32. 32. Cancer Survivors
    33. 33. Surviving Hematopoietic Cell Transplantation
    34. 34. Hematopoietic cell transplantation activity worldwide >60,000 HCTs/ year • Improved efficacy in many diseases 35,000 • Increased options of stem cell source 30,000Number of HCTs 25,000 Autologous HCT 20,000 15,000 Allogeneic HCT 10,000 5,000 Growing number of HCT survivors • Increasing focus on long-term health 0 80 81 8283 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 Year of HCT (1980 to 2009)
    35. 35. Post-transplantation ComplicationsNon-malignant late effects  New tumors • Ocular • Benign • Orodental • Malignant • Pulmonary • Gastrointestinal • Cognitive dysfunction  Psychosocial outcomes • Musculoskeletal • Renal dysfunction • Fatigue • Cardiac • Sexual functioning • Social integration • Metabolic syndrome • Quality of life
    36. 36. Post-transplantation late effects Non-malignant late effects Malignant late effects Psychosocial well being Chronic Graft versus Host disease
    37. 37. Diabetes, hypertension, and cardiovascular events in HCTsurvivors Blood, 2007;109:1765-72
    38. 38. Increased risk of DM in HCT survivors•Prolonged exposure to steroids•Exposure to TBIIncreased risk of hypertension in HCT survivors•Prolonged exposure to steroids, cyclosporine•Exposure to other immunosuppressive agents Increased risk for cardiovascular disease
    39. 39. Diabetes, Hypertension, Cardiovascular diseaseComparison with siblings Blood, 2007;109:1765-72 % Diabetes HTN Arterial MI Stroke BMI 30+ Disease OR 3.0* 1.6* 0.8 0.9 6.4 0.7* CI 1.6-5.6 1.1-2.1 0.3-1.8 0.2-4.0 0.8-49.6 0.5-0.9 Adjusted for current age, age at HCT, and sex *p <0.05
    40. 40. Diabetes, Hypertension, Cardiovascular diseaseRole of TBI Blood, 2007;109:1765-72 % Diabetes HTN Arterial MI Stroke BMI 30+ Disease OR 3.1* 1.2 1.1 1.2 2.7 0.8 CI 1.5-6.3 0.8-1.6 0.4-3.6 0.2-5.9 0.6-12.5 0.5-1.1 Adjusted for age, age at HCT, and sex *P<0.05
    41. 41. Osteonecrosis in HCT survivors Cancer. 2009;115:4127-35
    42. 42. Late osteonecrosis after HCT 15% 1+ year survivors of HCT N=1346 10% 6% at 10 years 5%ne d c n ev t a u m C i I i l u 0% 0 1825 3650 5475 7300 9125 10950 DAYSCancer. 2009;115:4127-35
    43. 43. Late osteonecrosis by stem cell donor type 15 % Unrelated donor HCT (15% at 10 years) 10 % Allogeneic related HCT (6% at 10 years) 5 % e d c n ev t a u m C Autologous HCT u P<0.001 4% at 10 years i I i l 0% 0 182 365 547 730 912 1095 5 0 5 0 5 0 DAYSCancer. 2009;115:4127-35
    44. 44. OsteonecrosisRisk factors in allogeneic HCT recipientsDiagnosis of Hodgkin lymphoma or multiple myeloma • RR=11.7 (2.3-60.01)Exposure to cyclosporine, tacrolimus, prednisone, mycophenolate mofetil • RR=6.8 (1.5-30.9)Presence of chronic GvHD • RR=2.2 (1.0-4.8)Cancer. 2009;115:4127-35
    45. 45. Chronic Kidney Disease in HCT survivors Cancer, 2008, 113(7):1580-7
    46. 46. Chronic Kidney DiseaseSustained compromise of renal function • Variety of causes of renal injury • May lead to progressive loss of renal function • terminate in end-stage renal diseaseImportant to understand the populations at risk • Institute appropriate monitoring • Judicious use of potentially nephrotoxic drugs
    47. 47. Late Chronic Kidney Disease after HCT 14% 12% 10% 8% 5.7% at 10 years 6% ec ne d c n ev t a u m C 4% u 2% i I i l 0% 0 5 10 15 20 25 30 Years post-HCTCancer, 2008, 113:1580-7
    48. 48. Who is at highest risk for chronic kidney disease after Allogeneic transplant RR 95% CI Age at HCT Increments of 5 years 1.3 1.3-1.34 Drug combinations for prophylaxis/ treatment of GvHD None/ methotrexate alone 1.0 __ Cyclosporine without tacrolimus 1.8 0.6-5.20 Cyclosporine with tacrolimus 4.3 1.3-14.9 Primary diagnosis Primary diagnosis other than 1.0 __ myeloma Multiple myeloma 5.4 1.8-16.2Cancer, 2008, 113:1580-7
    49. 49. Risk of Chronic Kidney Disease after transplant 25% Exposure to Calcineurin Inhibitors; Age at HCT > 45 years 20% 15% P< 0.01 10% No Exposure to Calcineurin Inhibitors;% ec ne d c n ev t a u m C Age at HCT < 45 years u 5% i I i l 0% 0 5 10 15 20 25 30 Year s Cancer, 2008, 113:1580-7(
    50. 50. Solid tumors after Hematopoietic CellTransplantation J Clin Oncol, 2001;19:464-71
    51. 51. Solid cancers after transplantation . 40 Age at HCT < 34 years . 30 RR=4.8, p<0.05 .20 Total Body Irradiation RR=2.7, p<0.05 . 10 c ne d c n ev t a u m C u 0 i I i l 0 3 6 9 1 1 1 2 5 8 Time (Years)J Clin Oncol, 2001;19:464-71
    52. 52. Excess Risk of Solid Cancersezi dr a dnat SJ Clin Oncol, 2001;19:464-71
    53. 53. Therapy-related leukemia after autologoustransplantation for lymphoma Blood, 2000;95:1588-93
    54. 54. Therapy-related leukemia after autologoustransplantation .30 .20 8.6% at 6 years .10 ec ne d c n ev t a u m C u .0 0 2 4 6 8 10 i I i l Time in Years from aHCT Blood, 2000;95:1588-93
    55. 55. Who is at risk for therapy-related leukemia? Risk Factors Total Cohort HD NHL Priming with VP-16 6.1* 5.9* 6.7* PSC 2.8* 1.7 4.9* Primary Dx (HD) 1.6 __ __ Gender (females) 1.8 2.4 1.3 Age at BMT (> 40 yr) 0.8 1.2 0.9Blood, 2000;95:1588-93
    56. 56. Longitudinal Trajectory of Fatigue and Vigorafter HCT J Clin Oncol, 2008
    57. 57. Fatigue and Vigor• Describe longitudinal trends in fatigue, vigor and quality of life• Identify predictors of fatigue, vigor and QOL• Understand the impact of fatigue and vigor on return to work after HCT
    58. 58. Methods• Profile of Mood States • standardized self-report instrument measuring fatigue, vigor• City of Hope HCT-QOL Questionnaire HCT Pre-HCT 6 months 1 year 2 years 3 years
    59. 59. Longitudinal trends in FatigueFatigue decreased across time after transplantation•Maximum effect observed at the 2 and 3 year points
    60. 60. Longitudinal trends in Vigor scoresVigor increased across time after transplantation•Improvement observed across all time points
    61. 61. Longitudinal trends in Physical well-being by Fatigue Physical well being scores were significantly lower among patients with higher levels of fatigue Low fatigue High fatigue
    62. 62. Longitudinal trends in Psychological well-being byFatigue Psychological well being scores were significantly lower among patients with higher levels of fatigue
    63. 63. Longitudinal trends in Psychological well-being byVigor Psychological well being scores were significantly lower among patients with lower levels of vigor High vigor Low vigor
    64. 64. Longitudinal trends in Spiritual well-being byVigor Spiritual well being scores were significantly lower among patients with low levels of vigor High vigor Low vigor
    65. 65. Longitudinal trends in Social well-being byVigor Social well being scores were significantly lower among patients with low levels of vigor High vigor Low vigor
    66. 66. Percent Returning to Full-time Work 100 90 p<.0001, df=3 80 70 60 57.6% Percent 50 50.0% 42.5% 40 30 23.7% 20 10 0 Pre 6m 1y 2y 3y Time after HCTBlood, 2010;115:2508-19
    67. 67. Variables associated with successful return tofull time work 1.2 Upper 95% CI Lower 95% CI 1.0 Blood, 2010;115:2508-19 0.8 Relative Risk 0.6 RR=.56 RR=.56 0.4 RR=.40 RR=.25 0.2 0.0 Income cGVHD BMI Avg Fatigue < 20K With <Obese Worst 40% vs vs vs vs > 20K Without >Obese Least 60%
    68. 68. Cumulative incidence of return to workby baseline vigor scores 1 High vigor 0.9 0.8 Cumulative incidence 0.7 0.6 Low vigor 0.5 0.4 P = .02* 0.3 High vigor (75th percentile) 0.2 Low vigor (25th percentile) 0.1 0 0 6 12 18 24 30 36 Months after HCT
    69. 69. Sexual functioning after hematopoietic celltransplantation Blood. 2008;112: 743a
    70. 70. Sexual Functioning after HCT 10 HCT 0 90 8 Pre- 6 mo. 1 year 2 years 3 years 0 HCT 7 0 Men 6 0 er oc Sl at oT T RS- FS D 5 I 0 Women 4 0 P<.0001 3 0 0 6 1 1 24 30 36 2 8 Months since HCTBlood. 2008;112: 743a
    71. 71. Sexual Functioning – age effect Men 9 0 <40y 8 0 7 40-60y 0 6 0 >40y 5 60y er oc Sl at oT RS- FSI D 0 4 P=.002 0 0 6 1 1 24 30 36 2 8 Months since HCTBlood. 2008;112: 743a
    72. 72. Sexual Functioning – age effect Women 10 0 9 0 P=.006 8 0 7 <30y 0 6 0 er oc Sl at oT RS- FS D 5 >30y I 0 4 0 6 1 1 24 30 36 2 8 Months since HCTBlood. 2008;112: 743a
    73. 73. Impact of total body irradiation 10 Men 0 9 0 8 0 No TBI 7 0 6 er oc Sl a oT RS F S D 0 TBI - I 5 0 4 0 t P=.006 3 0 0 6 1 1 24 30 36 2 8 Blood. 2008;112: 743a Months since HCT
    74. 74. Neuropsychological outcomes after transplantation Blood. 2009a
    75. 75. COH Neurocognitive Function Study  Study design  5-year longitudinal study  Standardized 2-hour battery of neurocognitive tests HCT Pre 6m 1y 2y 3y 5yPatients Healthy Controls
    76. 76. Processing SpeedThe rate at which mental activities are performedWechsler Adult Intelligence Scale – Digital Symbol Coding•Measures visual-motor coordination; motor/ mental speed“Copy the symbols corresponding to the numbers into the emptyboxes as fast as you can.”
    77. 77. Processing Speed Wechsler Adult Intelligence Scale – Symbol Search • Measures speed of visual perception “Does the shape on the left match any of the shapes in the group on the right? Answer as many as you can before time runs out.”
    78. 78. Working MemoryMemory for, or information processing of, material or eventsin a temporary mental workspace •On-line information processing and manipulation system •Related to attention and concentrationWechsler Adult Intelligence Scale •Digit Span •Arithmetic •Letter-Number Sequencing
    79. 79. Working MemoryDigit SpanTo assess attention, concentration, mental controlItems range from easy (2 digits) to difficult (9 digits) “Repeat these numbers: 2-4-3-8-1.” “Repeat these numbers, but in reverse sequence: 9-2-1-5-4.”Arithmetic Measures concentration while manipulating mental math problems Items range from very easy to very difficult "How many 45-cent stamps can you buy for 5 dollars?"Letter-Number Sequencing To measure attention and working memory Items range from very short to very long “Repeat the sequence Q-8-B-3-J-2, but place the numbers in numerical order and then the letters in alphabetical order.”
    80. 80. Auditory MemoryThe ability to store, retain, and recall information after it is orallypresentedWechsler Memory Scale•Logical Memory “I will read a short story aloud. When I’m done, repeat thewhole story to me.”
    81. 81. Visual MemoryThe ability to store, retain, and recall information after it isvisually presentedWechsler Memory Scale•Family Pictures • Examiner shows participant pictures of characters doing things, then participant must recall the scenes “Remember as much as you can about this picture. I’m going to ask you about it later.”
    82. 82. Visual Memory“Where was the mother? What was she doing?”
    83. 83. Verbal SpeedAssesses the speed at which an examinee can name/read high-frequency, repeating stimuli/wordsDelis-Kaplan Executive Function System•Color Naming•Word Reading
    84. 84. Verbal SpeedColor Naming: “Name the colors. Go as fast as you can.”Word Reading: “Read the words. Go as fast as you can.” GREEN BLACK RED PURPLE BLUE GREEN BLACK RED BLUE
    85. 85. Executive FunctionProcesses that guide, direct, and manage cognitive, emotional andbehavioral functions, esp. during active, novel, problem solving •Delis-Kaplan Executive Function System • Color-Word Interference: Inhibition: Assesses verbal inhibition “Name the colors of the words. Do NOT read the words. Go as fast as you can.”
    86. 86. Verbal Fluency Assesses fluent productivity in the verbal domain Delis-Kaplan Executive Function System •Letter Fluency •Category Fluency “Say as many words as possible from a category before time runs out.” •Letter Fluency: Words that start with the letter P •Category Fluency: Animals •Switch between two categories (animal, tool, animal, tool, etc.)
    87. 87. Fine Motor DexterityCoordination of small musclemovements which occur e.g., in thefingers, usually in coordination with theeyes•Grooved Pegboard–Measures motor speed and dexterityParticipants insert a peg into a boardcontaining holes angled in differentdirections.–Each peg has a ridge along one side,requiring rotation for correct insertion into “Put the pegs into the board asthe hole fast as you can, using only your dominant hand.”
    88. 88. Intelligence“Global capacity of the individual to act purposefully, to thinkrationally, and to deal effectively with the environment”Wide Range Achievement Test: Word Reading•To assess single word reading ability • Established as a reliable estimate of IQ • Word reading is an over-learned ability – Relatively resistant to cognitive impairment and can be used as a predictor of pre-morbid intelligence•Words range from very easy to very difficult“Read the following words aloud." DOG LICORICE PRESTIGIOUS
    89. 89. Fine Motor DexterityPercent Impaired
    90. 90. Executive FunctionPercent Impaired
    91. 91. Percent Impaired Auditory Memory
    92. 92. Percent Impaired Visual Memory
    93. 93. Processing SpeedPercent Impaired
    94. 94. Working Memory (Letter Number Sequencing)Percent Impaired
    95. 95. Verbal Speed (Word Reading Score)Percent Impaired
    96. 96. Verbal Fluency (Letter Fluency)Percent Impaired
    97. 97. Trajectory of Cognitive ImpairmentSignificant increase in prevalence of impaired individualsfrom pre-HCT to 1 years• Allogeneic HCT recipients • Fine Motor Dexterity, Auditory Memory, Visual Memory, Processing Speed, Working Memory•Autologous HCT recipients • Fine Motor Dexterity, Visual Memory, Working memory, Verbal Fluency
    98. 98. Trajectory of Cognitive ImpairmentSignificant decrease in prevalence of impaired individualsfrom pre-HCT to 1 year•Allogeneic HCT recipients • none•Autologous HCT recipients • Processing Speed, Verbal Speed
    99. 99. Trajectory of Cognitive ImpairmentStable prevalence rates from pre-HCT to 1 year post-HCT•Allogeneic HCT recipients • Executive Function, Verbal Speed, Verbal Fluency•Autologous HCT recipients • Executive Function, Auditory Memory
    100. 100. Burden of Morbidity Blood, 2010;116:3129-39
    101. 101. Chronic Health Conditions – Survivors vs. Siblings Severe or life-threatening Conditions 51% (10 yr) Survivors RR=5.0 (95% CI:3.4-7.4 ) 14% (10 yr) SiblingsBlood, 2010;116:3129-39
    102. 102. Survivorship issues in 10+Year Survivors of HCT• Chemotherapy/ radiation• cGVHD and its sequelae• Prolonged immune suppression Chronic Health Conditions Adverse Psychological outcome Unknown for 10+ year survivors Healthcare utilization Burden of Long-term Morbidity Psychological Health Status
    103. 103. Prevalence of chronic health conditionsSurvivors compared to siblings P<0.001BBMT, 2012, in press
    104. 104. Risk of Chronic Health Conditions Survivors compared to siblings Adjusted for age at questionnaire, sex, race/ethnicity, education, income andRelative Risk insurance status BBMT, 2012, in press
    105. 105. Cumulative Incidence of Chronic Health ConditionsAmong 10+ year Survivors Any chronic health 71% (15 yr) condition Severe/ life-threatening condition or death 40% (15 yr)BBMT, 2012, in press
    106. 106. Prevalence of Adverse Psychological Outcomes P<0.001 P=0.1 P=0.11 P=0.55Blood, 2011;118:4723-31
    107. 107. Are survivors at a higher risk of psychologicalproblems when compared with siblings? Adjusted for age at questionnaire, sex, marital status, race/ethnicity, education, income, insurance status, health status, and chronic health conditions. Odds Ratio P=0.03 P=0.2 P=0.9 P=0.52 Blood, 2011;118:4723-31
    108. 108. Healthcare utilization among long-term survivors 90% of the survivors carried health insurance BBMT, 2013, in press
    109. 109. Health-related Outcomes after HCT Long-term sequelae Impact of long- term sequelae on HRQL is unknown Quality of Life
    110. 110. Impact of Chronic Health Conditions on Health-related Quality of Life Blood, 2006;108: 73a
    111. 111.  demographics  medication use  education  medical conditions  income  Graft vs. host diseaseBMT-SS  employment  surgical proceduresQuestionnaire  insurance  recurrent cancer  marital status  new neoplasms  health habits  offspring/pregnancy history  family history  utilization of medical care Physical Physical Psychological Psychological Psychological Well Being Well Being Well Being Well Being HCT-QOL Overall QOL Social Social Spiritual Spiritual Well Being Well Being Well Being Well Being
    112. 112. Physical Well Being Blood, 2006;108: 73aML det s u d A S j Adjusted for inability to return to work, cGVHD, pain or anxiety, inability to exercise, age at HCT
    113. 113. Social Well Being Blood, 2006;108: 73aMSL de s u d A t j Adjusted for inability to return to work, cGVHD, pain or anxiety, marital status
    114. 114. Aims of hematopoietic cell transplantation Sustained remission/ cure of primary disease Complete recovery of health status Normal physical and psychological functioning Normal and orderly social integration
    115. 115. Long-term consequences of hematopoietic celltransplantation• Substantial burden of chronic morbidity• Challenges in social integration• Need for life-long follow-up of HCT survivors
    116. 116. Recommendations
    117. 117. Intervention Strategies Modification ofPrimary Cancer Therapeutic Protocols Genetic Predisposition Therapeutic Lifestyle Exposures Exposures Viral infections Identification and Screening of Late Effects “High Risk” Populations