Late effects and quality of life after haematological stem cell transplantation

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1 Late effects and quality of life after haematological stem cell transplantation Prof. dr hab. Ewa Gorczyńska Zofia Lutrowicz Department of Pediatric Hematology Oncology and Bone Marrow Transplantation, Wrocław.

2 Allogeneic hematopoietic stem cell transplantation (allo-hsct) is an effectiveand curativetherapy for various malignant and non-malignant diseases.

3 Allogeneic hematopoietic stem cell transplantation (allo-hsct) is an effectiveand curativetherapy for various malignant and non-malignant diseases. Advances in hematopoietic cell transplantation technology and supportive care techniques have led to improvements in long-term survival after HCT. Over 1 year survival 75% 65% 55% 45% 6 74% 35% 25%

4 Allogeneic hematopoietic stem cell transplantation (allo-hsct) is an effectiveand curativetherapy for various malignant and non-malignant diseases. Advances in hematopoietic cell transplantation technology and supportive care techniques have led to improvements in long-term survival after HCT. These survivors are at risk for developing late complications secondary to pre-, peri- and posttransplant exposures and risk-factors.

5 Who pays the price?

6 AIM OF STUDY

7 MATERIALS AND METHODS 343 medical records of children who survived longer than one year after HSCT proceeded in Paediatrics Hematology and Oncology Clinic UM Wrocław during years The follow-up period was from 13 months to 17.3 years; median 6.1 years. DISEASE n= 247 n= 343 NON- DISEASE n= AGE <5 yr 5-10 yr yr >15 yr AGE NON NON- TBI 70 0 MSD MUD MMD Busulfan based Treosulfan based CY/ATG 0 12 Fludarabine based 0 22 Other

8 Cutaneous complications 59,5% cgvhd 42, Ocular complications 38% Respiratory disorders 38% Endocrine dysfunction 33% Bones disorders 24% Cardiovascular complications 19% Nervous system complications 1 Renal complications 10,5% Late systemic infections 8% Second neoplasms 2,5%

9 CUTANEOUS COMPLICATIONS 63% 49% NON- 45% 4 41% 37,5% 37% 35% 3 25% % 17% 24% 8% 32% 28% 3 2 5% 2% Sclerodermia Dryness Discoloration Flakiness Rush Hair regrowth disorder Other COMBINED NON-

10 CUTANEOUS COMPLICATIONS 63% 49% NON- 45% 4 41% p<<0,05 37,5% 37% p<<0,05 35% 3 25% % 17% 24% 8% 32% 28% 3 2 5% 2% Sclerodermia Dryness Discoloration Flakiness Rush Hair regrowth disorder Other COMBINED NON-

11 CUTANEOUS COMPLICATIONS 63% 49% NON- 45% 4 41% p<<0,05 37,5% 37% p<<0,05 35% 3 25% % 17% 24% 8% 32% 28% 3 2 5% 2% Sclerodermia Dryness Discoloration Flakiness Rush Hair regrowth disorder Other COMBINED NON-

12 OCULAR COMPLICATIONS 43% 24% NON- 25% 2 20,5% 19% 14,5% 13% 11% 1 5% 5,5 6,5% 6,5% 4% 3% 2,5% 5% 3% Lacrimation Abnormal Schrimmer test Glaucoma Cataracta Cornea damage Reduced visual acuity Strabismus Conjunctivitis Other COMBINED NON-

13 OCULAR COMPLICATIONS 43% 24% NON- p= 0, % 2 20,5% 19% 14,5% 13% 11% 1 5% 5,5 6,5% 6,5% 4% 3% 2,5% 5% 3% Lacrimation Abnormal Schrimmer test Glaucoma Cataracta Cornea damage Reduced visual acuity Strabismus Conjunctivitis Other COMBINED NON-

14 OCULAR COMPLICATIONS 43% 24% NON- p= 0, % 2 20,5% 19% 14,5% 13% 11% 1 5% 5,5 6,5% 6,5% 4% 3% 2,5% 5% 3% Lacrimation Abnormal Schrimmer test Glaucoma Cataracta Cornea damage Reduced visual acuity Strabismus Conjunctivitis Other COMBINED NON-

15 OCULAR COMPLICATIONS 43% 24% NON- p= 0, % 2 20,5% 19% 14,5% 13% 11% 1 5% 5,5 6,5% 6,5% 4% 3% 2,5% 5% 3% Lacrimation Abnormal Schrimmer test Glaucoma Cataracta Cornea damage Reduced visual acuity Strabismus Conjunctivitis Other COMBINED NON-

16 RESPIRATORY SYSTEM DISORDERS 4 32% NON- 35% 35% 3 27% 25% 2 1 5% 7,5% 4% 5% 2% 1% Infections Mycoses Obturatie disorders BOS NON-

17 RESPIRATORY SYSTEM DISORDERS 4 32% NON- 35% 35% 3 27% 25% 2 1 5% 7,5% 4% 5% 2% 1% Infections Mycoses Obturatie disorders BOS NON-

18 RESPIRATORY SYSTEM DISORDERS 4 32% NON- 35% 35% 3 27% 25% 2 1 5% 7,5% 4% 5% 2% 1% Infections Mycoses Obturatie disorders BOS NON-

19 ENDOCRINE DISORDERS 49% 4 NON- 18% 1 17% 1 14% 12% 12% 1 9,5% 8,5% 1 8% 8% 8% 4% 2% 1% 4% 3% 4% 5% 2% 2% 1,5 3% Growth inhibition Hypothyroidism Hypogonadism Amenorhea Puberty retardation Sex hormones deficiency Glucose intolerance Adrenals disfunction COMBINED NON-

20 ENDOCRINE DISORDERS 49% 4 NON- 18% 1 17% 1 14% 12% 12% 1 9,5% 8,5% 1 8% 8% 8% 4% 2% 1% 4% 3% 4% 5% 2% 2% 1,5 3% Growth inhibition Hypothyroidism Hypogonadism Amenorhea Puberty retardation Sex hormones deficiency Glucose intolerance Adrenals disfunction COMBINED NON-

21 ENDOCRINE DISORDERS 49% 4 NON- 18% 1 17% 1 14% 12% 12% 1 9,5% 8,5% 1 8% 8% 8% 4% 2% 1% 4% 3% 4% 5% 2% 2% 1,5 3% Growth inhibition Hypothyroidism Hypogonadism Amenorhea Puberty retardation Sex hormones deficiency Glucose intolerance Adrenals disfunction COMBINED NON-

22 SKELETAL COMPLICATIONS 28% 13,5% NON- 18% 1 14% 12% 1 8% 4% 2% 17% 7% 8% Osteoporosis Avascular necrosis 3% 3% 2% Infections 3,5% 3,5% 1% 1,5% Fractures Body posture disorders NON- Limbs asymmetry COOMBINED

23 SKELETAL COMPLICATIONS 28% 13,5% NON- 18% 1 14% 12% 1 8% 4% 2% p= 0, % 7% 8% Osteoporosis Avascular necrosis 3% 3% 2% Infections 3,5% 3,5% 1% 1,5% Fractures Body posture disorders NON- Limbs asymmetry COOMBINED

24 CARDIAC AND VASCULAR COMPLICATIONS 2 1 NON- 12% 11% 10,5% 1 1 8% 7% 4% 2% 1,5% 1,5% 1,5% 1% Hypertensia Arythmia Pericarditis Cardiovascular failure Thrombosis NON-

25 CENTRAL AND PERIPHERAL NERVOUS SYSTEM COMPLICATIONS 16,5% 14,5% NON- 9% 8% 7% 5% 4% 3% 2% 1% 9% 9% 7% 3,5% 2,5% 2% 1% 1% Epilepsy Headaches Neuropathy Paresis Impaired consciousness NON- 3% Other

26 RENAL COMPLICATIONS 1 11% NON- 5, 5% 4% 3% 2% 2% 1% 2,5% 2% 3,5% 1,5% 2% 1% 1% 3% 1% Lithasis Nephropathy Reccurent infections Proteinuria Renal failure Tubulopathy NON-

27 LATE SYSTEMIC INFECTIONS HBV HCV CMV Systemic mycoses Tuberculosis 2 NON- 2 1 NON- 0 4 NON NON- 5 5 NON- 2

28 LATE SYSTEMIC INFECTIONS HBV HCV CMV Systemic mycoses Tuberculosis 2 NON- 2 1 NON- 0 4 NON NON- 5 5 NON- 2

29 SECOND NEOPLASM 3% NON- 1,04% Osteosarcoma Astrocytoama NHL pre-b MDS Melanoma EBV-LPD Squamous cells carcinoma EBV-LPD

30 Statistic structure of combined multiple organ disorders. NON- 17% 11% ,5% 14,5% 27% 2 4 >=5 16,5% 19%

31 Statistic structure of combined multiple organ disorders. p<<0,05 NON- 17% 11% ,5% 14,5% 27% 2 4 >=5 16,5% 19%

32 Statistic structure of combined multiple organ disorders. p<<0,05 NON- 17% 11% ,5% 14,5% 27% 2 4 >=5 16,5% 19%

33 Who is the silent villain? % 11% >=5

34 Who is the silent villain? cgvhd-coexistance p=0, % 11% % 19% 21% 12% 17% 2,5% >=5

35 6 INCIDENCE OF CHRONIC GRAFT VERSUS HOST DISEASE 5 Who is the silent 4 villain? 48% % 27% NON- 11% 2,5% 21% % 19% 12% 17% % 17% 52% 11% 13% >=5 NON- cgvhd-free limited cgvhd extensive cgvhd

36 CAUSE-OF-DEATH STRUCTURE 81,5% 18,5% n=45 DISORDERS NON- DISORDERS n=1 1,04% 98,9 Relapse/progression 19 Haemorrhage 1 DEAD ALIVE Infections 12 cgvhd 7 Secondary neoplasm 2 n= 247 n= 96 Treatment-related toxicity Pulmonary artery thrombosis Haemorrhage 1 Suicide DEAD ALIVE

37 CAUSE-OF-DEATH STRUCTURE 81,5% 18,5% n=45 DISORDERS NON- DISORDERS n=1 1,04% 98,9 Relapse/progression 19 Haemorrhage 1 DEAD ALIVE Infections 12 cgvhd 7 Secondary neoplasm 2 n= 247 n= 96 Treatment-related toxicity Pulmonary artery thrombosis Haemorrhage 1 Suicide DEAD ALIVE LATE TRANSPLANT RELATED MORTALITY 10,5%

38 OVERALL SURVIVAL AFTER 1 YEAR n=343

39 OVERALL SURVIVAL AFTER 1 YEAR- COMPARISON

40 OVERALL SURVIVAL AFTER 1 YEAR- cgvhd COEXISTANCE

41 CONCLUSIONS 1. Majority of survivors after allo-hpct develop late sequelaewhich influence their quality oflife. 2. Patients transplanted due to malignant disease are at higher risk of developing late complications, mainly skin, ocular, endocrine and bone disorders. 5. cgvhd have a strong impact on frequency of occurence of combined, multiorgan disfunctions. 6. Specific screening recomendations and protocols are needed.

42 CONCLUSIONS Haematological stem cell transplant survivors require carefull, multidisciplinary, long-term monitoring. Don t let them pay that price

43 THANK YOU FOR YOUR ATTENTION!