PERFORMANCE AFTER HSCT Mutlu arat, md ıstanbul bilim un., dept. hematology ıstanbul, turkey

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1 PERFORMANCE AFTER HSCT Mutlu arat, md ıstanbul bilim un., dept. hematology ıstanbul, turkey Joint Educational Meeting of the EBMT Severe Aplastic Anaemia, Late Effects and Autoimmune Diseases Working Parties 3rd - 6th November 2011, Barcelona, Spain

2 Flow Components of QoL Health related QoL Performance after Allo HSCT (BMT-SS) Children Performance after AutoHSCT Intervention? Possible How to run a study? Take home messages, future, general summary

3 Components of QoL Global QoL Physical (Fatigue, Pain) Emotional (Anxiety, Depression) Social (Family, friends) Functional (Work, sleep) Spiritual (religion, meaning) in HSCT, SJ Lee, QoL issues post tx.,

4 HRQoL: rısk factors changes according tıme Bevans, ASH Ed. Book, 2010

5 performance after allo hsct

6 Impact of different post-remission strategies on QoL in patients with AML German AML-Intergroup, survey on QoL with a RFS> 5 years after 1st Tr 419 of 818 patients (51.2%) median age: 42 years, and the med. f/u: 8 years EORTC QoL C allohct, 49 autohct in CR1; 249 CCT Haematologica 2008; 93:

7 Impact of different post-remission strategies on QoL in patients with AML German AML-Intergroup, survey on QoL with a RFS> 5 years after 1st Tr 419 of 818 patients (51.2%) median age: 42 years, and the med. f/u: 8 years EORTC QoL C allohct, 49 autohct in CR1; 249 CCT Haematologica 2008; 93:

8 Impact of different post-remission strategies on QoL in patients with AML Haematologica 2008; 93:

9 Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease Bone Marrow Transplant. 2010; 45:

10 Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease N=100, allo HSCT. Utility of three instruments recommended by the NIH; SF-36, the distance walked in 2 min, Lee chronic GVHD symptom bother scale. Results: Functional performance, measured by the SF-36 physical component summary score, was substantially lower (mean = 36.8±10.7) than the US population norm of 50 (P<0.001). The most severe decrements were in physical function (mean = 38.8±10.9) and physical role function (mean= 37.88±11.88) Bone Marrow Transplant. 2010; 45:

11 Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease Bone Marrow Transplant. 2010; 45:

12 bone marrow transplant survivor study (bmt-ss) A collaboration between City of Hope Cancer Center (and the University of Minnesota, established in 2000 Aim: To evaluate outcomes in a cohort of individuals with a diagnosis of cancer or other life-threatening illness Eligibility criteria: 1. HCT for hematologic and non-hematologic malignancies and other life-threatening disorders; 2. Date of transplantation between 01/ / Survival of 2 years or longer after HCT regardless of disease and SCT PIs: S. Bathia, D. Weisdorf Publications: 17 papers, since 2004

13 Impact of cgvhd on the health status of hematopoietic cell transplantation survivors: a report from the BMT-SS N=584 Blood. 2006;108:

14 Impact of cgvhd on the health status survivors: a report from the BMT-SS

15 functional status of long-term survivors: BMT-SS N=1479, >2 years post allohct. Med. age: 25.9 y Median f/u: 9.5 y. HCT survivors difficulty in holding jobs ([OR] 13.9) in obtaining health (OR: 7.1) or life (OR: 9.9) insurance compared with siblings (N=319) Blood. 2007;110:

16 Letter: very long-term survivors after HSCT Basel Group N=44, paired controls. f/u: 17.5 y physical health status can be impaired, while mental health preserved Blood. 2008;111:1740

17 Functional status limitations among survivors, overall and by diagnosis, compared to siblings: BMT-SS N= 401 (AML/ALL), siblings of participants (n=319) are controls Med age: 36.5 yr survivors/ 44yr siblings. Med. f/u: 8.4 yr. Conditioning included TBI in 86% of AML and 100% of ALL subjects. Compared to siblings, survivors had a higher frequency of exercise induced shortness of breath (DOI), neurosensory impairments, and problems with balance, tremor or weakness. M-V analysis, the risk did not differ by diagnosis. Abnormal sense of touch (OR 2.6, p=0.02) and to report their overall health as fair or poor (OR 2.2, p=0.03). (OP x3, DM x4) Conclusion: Ongoing surveillance for LEs and appropriate interventions are required to improve the health Leukemia. 2010; 24:

18 functional status limitations among survivors, overall and by diagnosis, compared to siblings: BMT-SS Leukemia. 2010; 24:

19 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS Blood. 2011;118:

20 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS N=1065 (69%) 56% Allo HCT Blood. 2011;118:

21 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS Blood. 2011;118:

22 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS Blood. 2011;118:

23 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS Blood. 2011;118:

24 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS Blood. 2011;118:

25 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS Blood. 2011;118:

26 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS Blood. 2011;118:

27 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS Blood. 2011;118:

28 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS Blood. 2011;118:

29 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS presence of active chronic GVHD were associated with a 2-fold increased risk for somatic distress. 7% of the HCT survivors expressed suicidal ideation; patients with higher scores on depression subscale were most vulnerable Somatic distress is the biggest challenge Blood. 2011;118:

30 Adverse psychological outcomes in long-term survivors of HCT: BMT-SS presence of active chronic GVHD were associated with a 2-fold increased risk for somatic distress. 7% of the HCT survivors expressed suicidal ideation; patients with higher scores on depression subscale were most vulnerable Somatic distress is the biggest challenge Blood. 2011;118:

31 Chıldren

32 Performance Limitations and Participation Restrictions Among Childhood Cancer Survivors Treated With HCT

33 Performance Limitations and Participation Restrictions Among Childhood Cancer Survivors Treated With HCT N=235 age<21, alive >2 years, BMT-SS Arch Pediatr Adolesc Med. 2005;159:

34 performance after Auto HSCT&HDCT

35 Quality of life and rehabilitation in social and professional life after AHSCT&HDCT C-S, n=391, 12 y.s, 78% ASCT: significant, unfavourable impact on QoL (reintegration into social and professional life). Most symptoms and scores returned to N 3-6 years. Employment status and QoL were similar in patients who participated or not Annals of Oncology 13: , 2002

36 ıs Intervention possıble?

37 A randomized trial on the effect of a multimodal intervention on physical capacity, functional performance and QoL in adult patients undergoing allosct Randomized controlled trial Aim: investigate the effect of a 4- to 6-week multimodal program of exercise, relaxation and psychoeducation Physical capacity, Functional performance and QoL in allo-hsct N=42, adult pat.s 1st end point: aerobic capacity measured in VO2 max. 2nd end points: muscle strength, functional performance, physical activity level, QoL, fatigue, psychological wellbeing and clinical outcomes. Bone Marrow Transplantation (2009) 43,

38 A randomized trial on the effect of a multimodal intervention on physical capacity, functional performance and quality of life in adult patients Table 1 Multimodal intervention: exercise, progressive relaxation and psychoeducation Mode Frequency Intensity Duration Progression Stationary cycling 5 days/week Low to moderate: 50 75% HR max, RPE 10 13, MET min/session rest intervals as needed Dynamic and 5 days/week Dynamic: 1 2 sets, reps min/session stretching exercises Static: 1 set, hold for s MET 3.5 Resistance training 3 days/week Low to moderate: 1 2 sets of reps, min/session RPE 10 13, MET 3 Progressive relaxation 2 days/week Low: RPE 6 9, MET min/session Psychoeducation Ongoing Increased intensity and duration ¼ ¼ ¼ ¼ Bone Marrow Transplantation (2009) 43,

39 Intervention: possıble! Multimodal Intervention with aerobic, resistance and active exercises, progressive relaxation and psychoeducation; sustained 1- aerobic fitness, 2- muscle strength and 3- minimized loss of functional performance, favored the intervention group, but did not reach statistical significance. no untoward events sustained aerobic capacity and muscle strenght reduced loss of functional performance Bone Marrow Transplantation (2009) 43,

40 AIM: Effectiveness of an individualized high intensity strength and interval training program with respect to physiological and psychological health status PATs: MM & NHL, ASCT&HDCT, N=120, incl.period 2 y. METHODs: Multicenter, prospective, single blind randomized controlled trial will be performed. (1) intervention plus usual care; or (2) usual care. The intervention consists of an18-week individualized supervised high-intensity exercise program and counselling. The primary outcomes: cardiorespiratory fitness, muscle strength and fatigue) and secondary outcomes are assessed at BL, completion of the intervention and at 12 mo.s BMC Cancer 2010, 10:671

41 How to run a study?

42 Function, Adjustment, Quality of Life and Symptoms (FAQS) in Allo HSCT Survivors: A Study Protocol Aim: 1. explore the patterns of change in these health outcomes during the survivorship phase 2. characterize subgroups of survivors experiencing adverse outcomes 3. Examine relationships among outcomes and demographic 4. clinical factors (such as age, graft-versus-host disease (GVHD), and disease relapse) Health and Quality of Life Outcomes 2011, 9:24

43 Function, Adjustment, Quality of Life and Symptoms (FAQS) in Allo HSCT Survivors: A Study Protocol Methodology: Longitudinal observational study, adults, who >3 y post Allo HSCT, Qs annually. Demographic and clinical data with a series of patient-reported outcome measures, specifically: 1) Medical Outcomes Study SF- 36; 2) Functional Assessment of Chronic Illness Therapy (FACIT) - General 3) FACIT-Fatigue; 4) FACIT- Spiritual; 5) Psychosocial Adjustment to Illness Scale; 6) Rotterdam Symptom Checklist-Revised 7) Pittsburgh Sleep Quality Index. Health and Quality of Life Outcomes 2011, 9:24

44 Sample: fact-g /vrs. 4)

45 Current status conclusıon future prospects last words

46 Chronic Health Condıtıons

47 Health Care Utilization by Adult Long-term Survivors of HCT : BMT-SS Report HCU: general contact with health care system, general physical examination, and cancer/hct related visit N=845, f/u: 6 ys. Conclusion: need for increased awareness of the LT f/u needs of the HCT survivors by the health care providers Cancer Epidemiol Biomarkers Prev 2007;16: 834 9

48 Health Care Utilization by Adult Long-term Survivors of HCT : BMT-SS Report HCU: general contact with health care system, general physical examination, and cancer/hct related visit N=845, f/u: 6 ys. Conclusion: need for increased awareness of the LT f/u needs of the HCT survivors by the health care providers Cancer Epidemiol Biomarkers Prev 2007;16: 834 9

49 Current STATUS on QoL related performance Bevans, ASH Ed. Book, 2010

50 take home message for clinicians-i

51 take home message for clinicians-i Allogeneic HCT is an arduous treatment with curative potential that risks serious complications!!!

52 take home message for clinicians-i Allogeneic HCT is an arduous treatment with curative potential that risks serious complications!!! 1- Patients should be counseled: disease-specific and treatment-specific risks for TR morbidity and mortality, acute and cgvhd, infectious complications, primary disease relapse, and late complications of transplantation.

53 take home message for clinicians-i Allogeneic HCT is an arduous treatment with curative potential that risks serious complications!!! 1- Patients should be counseled: disease-specific and treatment-specific risks for TR morbidity and mortality, acute and cgvhd, infectious complications, primary disease relapse, and late complications of transplantation. Information: Complications can result in worsened QoL.

54 take home message for clinicians-i Allogeneic HCT is an arduous treatment with curative potential that risks serious complications!!! 1- Patients should be counseled: disease-specific and treatment-specific risks for TR morbidity and mortality, acute and cgvhd, infectious complications, primary disease relapse, and late complications of transplantation. Information: Complications can result in worsened QoL. 2- GOOD NEWS: greater than 60% of transplant survivors report their QOL as good to excellent and greater than 60% have no major functional limitations.

55 take home message for clinicians-i Allogeneic HCT is an arduous treatment with curative potential that risks serious complications!!! 1- Patients should be counseled: disease-specific and treatment-specific risks for TR morbidity and mortality, acute and cgvhd, infectious complications, primary disease relapse, and late complications of transplantation. Information: Complications can result in worsened QoL. 2- GOOD NEWS: greater than 60% of transplant survivors report their QOL as good to excellent and greater than 60% have no major functional limitations. 3- BAD NEWS: following adverse outcomes: >25% of survivors will have ongoing significant medical problems and >25% experience emotional distress and impaired life satisfaction. Stated differently, at least 25% of survivors have ongoing bothersome symptoms.

56 take home message for clinicians-ii Blood. 2009;114:7-19

57 take home message for clinicians-ii Transplant physicians should consider performance as secondary to the curative potential of HCT, not underestimate patients symptoms, and overestimate their QoL and HR performance. Blood. 2009;114:7-19

58 take home message for clinicians-ii Transplant physicians should consider performance as secondary to the curative potential of HCT, not underestimate patients symptoms, and overestimate their QoL and HR performance. Increased awareness is needed regarding the impact of HCT on performance and the importance of QoL to patients. Blood. 2009;114:7-19

59 take home message for clinicians-ii Transplant physicians should consider performance as secondary to the curative potential of HCT, not underestimate patients symptoms, and overestimate their QoL and HR performance. Increased awareness is needed regarding the impact of HCT on performance and the importance of QoL to patients. Use update literature to help your patients to make informed decisions. Blood. 2009;114:7-19

60 Future Prospects

61 Future Prospects Long-term impact of resolved cgvhd

62 Future Prospects Long-term impact of resolved cgvhd Interventions to improve physical HS

63 Future Prospects Long-term impact of resolved cgvhd Interventions to improve physical HS Impact of RIC regimens,

64 Future Prospects Long-term impact of resolved cgvhd Interventions to improve physical HS Impact of RIC regimens, Predictors of Functional health status after HCT

65 Future Prospects Long-term impact of resolved cgvhd Interventions to improve physical HS Impact of RIC regimens, Predictors of Functional health status after HCT Establish a Cohort with collaboration of interested centers within EBMT

66 Future Prospects Long-term impact of resolved cgvhd Interventions to improve physical HS Impact of RIC regimens, Predictors of Functional health status after HCT Establish a Cohort with collaboration of interested centers within EBMT Performance of the team, physician???

67 KEY ISSUES To understand the contribution of pre-hsct exposures, HSCTrelated exposures and comorbidities in the development of adverse events. It is necessary to identify those at highest risk of complications. There is a need to develop intervention strategies. Long-term follow-up guidelines need to be disseminated and refined. Expert Rev. Hematol. 2011; 4:

68 KEY ISSUES To understand the contribution of pre-hsct exposures, HSCTrelated exposures and comorbidities in the development of adverse events. It is necessary to identify those at highest risk of complications. There is a need to develop intervention strategies. Long-term follow-up guidelines need to be disseminated and refined. Expert Rev. Hematol. 2011; 4: