NextGen 2024: Bone Marrow Transplantation (BMT) Session Part 4

    NextGen 2024: Bone Marrow Transplantation (BMT) Session Part 4

    S
    @SJIA_Foundation
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    7 months ago 324

    AIAI Summary

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    Key Insights

    Long Term outcomes of Allogeneic 
HSCT for severe, refractory Juvenile 
Idiopathic Arthritis
Juliana Silva
Bone marrow Transplant Consultant
Great Ormond Street Hospital
 London, UK
    1/14
    Allo-HSCT for JIA
• Most common cancer in children & most common cause of death 
< 20 years of age;
• 16 patients underwent allo HSCT from 5 different centres
• Median FU was 2y 5m 
• 4 MSD, 8 MUD and 4 mMUD
• 10 Flu/Mel/Alemtuzumab and 6 Flu/Treo/ Alemtuzumab 
Blood Advances, 2018
    2/14
    Results
• 12/16 (75%) patients achieved 
CR;
• 2/16 patients died of transplant 
related toxicity.
• 9/15 FULL donor chimerism
– 1 relapse, 1 PR
• 5/15 MIXED chimerism
– 1 PR
• 1/15 AUTOLOGOUS 
reconstitution
– CR
    3/14
    LTFU UPDATED COHORT
N. centers 9
N. patients 31
Period 2007 - 2022
Type of JIA
• Polyarthritis
• sJIA
7
24
Median lines of IS 5
Median age at transplant (years) 9.5 (2-18)
Complications associated with sJIA
• MAS
• ILD
19
5
Median follow-up (years) 6 (1-15)
    4/14
    HSCT CHARACTERISTICS
HLA matching
10/10 MSD 6/31 (19%)
10/10 MUD 18/31 (58%)
9/10 MMUD 5/31 (16%)
 PTCy Haploidentical 2/31 (6%)
Source of Stem Cell
PBSCT 14
BM 17
Conditioning
Flu/Mel/Alemtuzumab 10/31
Flu/Treo/Alemtuzumab 13/31
Other 8/31
    5/14
    LONG TERM RESULTS
N=31 
24/26
CR
1/26
PR
5/31
Died 
14/31
CR
1/2
Relapsed
/
Active 
disease
1 patient – 
M: 0%, T <10%, B: 0%, 
CR 7 y post HSCT
5/1
2
CR
6/12
Active
disea
se
11/31
Relapse
    6/14
    CAUSES OF DEATH
 1 Fungal chest infection D+85
 
 1 RSV pneumonitis D+28
 2 Thrombotic microangiopathy both 6/8 m post HSCT
 1 Sepsis post-surgery for hips replacement 1.5 y, CR
    7/14
    RELAPSE/REMISSION
Patient JIA
subtype
Time to 
relapse
Type of 
relapse
Chimerism 
at relapse
Treatment at 
relapse
Status at 
last FU
Last FU
Pt 1
Poly-JIA 1.6 y MAS WB:86%,
M:92%, 
T: 56%, 
B: 76% 
Steroids Well, off IS 8.5 y
Pt 14 sJIA
+ MAS
2.9 y Arthritis 100% MTX (for 6m) Well, off IS 8 y
Pt 21 sJIA
+ MAS
2 m MAS 100% CsA Well, off IS 5 y
Pt 22 sJIA
+ MAS
5 m MAS T: 75%
 M:83%
CSA/steroids Well, off IS 4.8 y 
Pt 23 sJIA
+ MAS
1 m/1.5y MAS/
Arthritis
T:96%
M:99% / 
T:98%
M:96%
Infliximab/
IVIG/steroids/
ia steroids
Well, off IS 8.7 y
Pt 24 Poly-JIA
+ MAS
6 m MAS WB:15% 2nd graft,
CR
Well, off IS 2.4 y
    8/14
    RELAPSE/ ACTIVE DISEASE
Patient JIA
subtype
Time to 
relapse
Type of relapse Chimerism at 
relapse
Treatment at 
relapse
Last FU
Pt 2 sJIA
+ MAS
10 y Arthritis WB:85% 
T: 100% M:82% 
MTX 15 y
Pt 6 Poly – JIA 6 y Polyarthritis and 
then uveitis
100% Toc,
Steroid injections,
MMF,
Certolizumab
9 y 
Pt 8 sJIA 3 y Polyarthritis T 67%
B 30%
M 10%
Toc, Adalimumab, 
Abatacept, 
Tofacitinib
8 y
Pt 9 sJIA 3 y Polyarthritis T 88% B 94% M
94%
Etanercept, MTX,
Golimumab
6 y
Pt 10 sJIA 6 m Polyarthritis then 
MAS 
T 75%
M 87%
MTX, steroids,
Adalimumab,
Anakinra, Toc,
Ruxolitinib,
Joint injections
6.5 y
Pt 15 sJIA
+ MAS
6 m Arthritis 100% Tofacitinib and 
prednisolone
1 y
Pt 17 Poly – JIA 8 y Arthritis 100% Pred, siro, MTX, 
Canakinumab
8 y
    9/14
    Survival Outcomes
6y OS: 84% 
• Deaths within first 18 m
CR: 19/26 (61%) at last FU
PR: 1/26 (4%)
O(S
Relapse: 42% (11/26)
• Achieved further CR: 5/11 (45%) 
• Active disease: 6/11 (54%)
Deaths: 4x transplant related
 1x complication post 
surgery, in CR
No JIA related deaths
    10/14
    In summary
•Allogeneic HSCT is an alternative option for patients with 
refractory and/or complicated sJIA;
•Promising results for ILD;
•Indications and Timing for transplant;
    11/14
    Future perspectives 
• Consensus Statement on indications and timing for transplant
• Prospective study 
• Standardised transplant recommendations;
• Consolidate response with biologics;
• Biomarkers analysis to assess disease response
• Short and LTFU including joint/quality of life assessments;
• CAR T cells
    12/14
    Acknowledgements
Teaching Hospital 
Motol, Prague
Petr Sedlacek 
Renata Formankova
GOSH
Persis Amrolia
Kanchan Rao
Robert Chiesa 
Giovanna Lucchini
Khushnuma 
Mullafironze
Harini Rao
Archana Rauthan
Rheumatology 
Team GOSH
Great North Children’s Hospital
Andrew Gennery 
Mary Slatter
Sophie Hambleton
Terence Flood
Zohreh Nademi
Mario Abinun
Andrew Cant 
Mark Friswell
UCLH
Rachael Hough 
Ben Carpenter
Vicky Grandage
Cincinnati Children’s 
Hospital
Rebecca Marsh
Sharat Chandra
University of 
Children’s Hospital, 
Zurich, Switzerland
Tayfun Güngör
Ulrike Zeilhofer
Necker Enfants 
Malades, University 
Hospital Paris, 
France
Bénédicte Neven
Despina Moshous
Benjamin Fournier 
Dana-Farber/Boston 
Children's Cancer and Blood 
Disorders Center, Boston, 
USA
Susan Prockop
    13/14
    Thank you!
    14/14

    NextGen 2024: Bone Marrow Transplantation (BMT) Session Part 4

    • 1. Long Term outcomes of Allogeneic HSCT for severe, refractory Juvenile Idiopathic Arthritis Juliana Silva Bone marrow Transplant Consultant Great Ormond Street Hospital London, UK
    • 2. Allo-HSCT for JIA • Most common cancer in children & most common cause of death < 20 years of age; • 16 patients underwent allo HSCT from 5 different centres • Median FU was 2y 5m • 4 MSD, 8 MUD and 4 mMUD • 10 Flu/Mel/Alemtuzumab and 6 Flu/Treo/ Alemtuzumab Blood Advances, 2018
    • 3. Results • 12/16 (75%) patients achieved CR; • 2/16 patients died of transplant related toxicity. • 9/15 FULL donor chimerism – 1 relapse, 1 PR • 5/15 MIXED chimerism – 1 PR • 1/15 AUTOLOGOUS reconstitution – CR
    • 4. LTFU UPDATED COHORT N. centers 9 N. patients 31 Period 2007 - 2022 Type of JIA • Polyarthritis • sJIA 7 24 Median lines of IS 5 Median age at transplant (years) 9.5 (2-18) Complications associated with sJIA • MAS • ILD 19 5 Median follow-up (years) 6 (1-15)
    • 5. HSCT CHARACTERISTICS HLA matching 10/10 MSD 6/31 (19%) 10/10 MUD 18/31 (58%) 9/10 MMUD 5/31 (16%) PTCy Haploidentical 2/31 (6%) Source of Stem Cell PBSCT 14 BM 17 Conditioning Flu/Mel/Alemtuzumab 10/31 Flu/Treo/Alemtuzumab 13/31 Other 8/31
    • 6. LONG TERM RESULTS N=31 24/26 CR 1/26 PR 5/31 Died 14/31 CR 1/2 Relapsed / Active disease 1 patient – M: 0%, T <10%, B: 0%, CR 7 y post HSCT 5/1 2 CR 6/12 Active disea se 11/31 Relapse
    • 7. CAUSES OF DEATH 1 Fungal chest infection D+85 1 RSV pneumonitis D+28 2 Thrombotic microangiopathy both 6/8 m post HSCT 1 Sepsis post-surgery for hips replacement 1.5 y, CR
    • 8. RELAPSE/REMISSION Patient JIA subtype Time to relapse Type of relapse Chimerism at relapse Treatment at relapse Status at last FU Last FU Pt 1 Poly-JIA 1.6 y MAS WB:86%, M:92%, T: 56%, B: 76% Steroids Well, off IS 8.5 y Pt 14 sJIA + MAS 2.9 y Arthritis 100% MTX (for 6m) Well, off IS 8 y Pt 21 sJIA + MAS 2 m MAS 100% CsA Well, off IS 5 y Pt 22 sJIA + MAS 5 m MAS T: 75% M:83% CSA/steroids Well, off IS 4.8 y Pt 23 sJIA + MAS 1 m/1.5y MAS/ Arthritis T:96% M:99% / T:98% M:96% Infliximab/ IVIG/steroids/ ia steroids Well, off IS 8.7 y Pt 24 Poly-JIA + MAS 6 m MAS WB:15% 2nd graft, CR Well, off IS 2.4 y
    • 9. RELAPSE/ ACTIVE DISEASE Patient JIA subtype Time to relapse Type of relapse Chimerism at relapse Treatment at relapse Last FU Pt 2 sJIA + MAS 10 y Arthritis WB:85% T: 100% M:82% MTX 15 y Pt 6 Poly – JIA 6 y Polyarthritis and then uveitis 100% Toc, Steroid injections, MMF, Certolizumab 9 y Pt 8 sJIA 3 y Polyarthritis T 67% B 30% M 10% Toc, Adalimumab, Abatacept, Tofacitinib 8 y Pt 9 sJIA 3 y Polyarthritis T 88% B 94% M 94% Etanercept, MTX, Golimumab 6 y Pt 10 sJIA 6 m Polyarthritis then MAS T 75% M 87% MTX, steroids, Adalimumab, Anakinra, Toc, Ruxolitinib, Joint injections 6.5 y Pt 15 sJIA + MAS 6 m Arthritis 100% Tofacitinib and prednisolone 1 y Pt 17 Poly – JIA 8 y Arthritis 100% Pred, siro, MTX, Canakinumab 8 y
    • 10. Survival Outcomes 6y OS: 84% • Deaths within first 18 m CR: 19/26 (61%) at last FU PR: 1/26 (4%) O(S Relapse: 42% (11/26) • Achieved further CR: 5/11 (45%) • Active disease: 6/11 (54%) Deaths: 4x transplant related 1x complication post surgery, in CR No JIA related deaths
    • 11. In summary •Allogeneic HSCT is an alternative option for patients with refractory and/or complicated sJIA; •Promising results for ILD; •Indications and Timing for transplant;
    • 12. Future perspectives • Consensus Statement on indications and timing for transplant • Prospective study • Standardised transplant recommendations; • Consolidate response with biologics; • Biomarkers analysis to assess disease response • Short and LTFU including joint/quality of life assessments; • CAR T cells
    • 13. Acknowledgements Teaching Hospital Motol, Prague Petr Sedlacek Renata Formankova GOSH Persis Amrolia Kanchan Rao Robert Chiesa Giovanna Lucchini Khushnuma Mullafironze Harini Rao Archana Rauthan Rheumatology Team GOSH Great North Children’s Hospital Andrew Gennery Mary Slatter Sophie Hambleton Terence Flood Zohreh Nademi Mario Abinun Andrew Cant Mark Friswell UCLH Rachael Hough Ben Carpenter Vicky Grandage Cincinnati Children’s Hospital Rebecca Marsh Sharat Chandra University of Children’s Hospital, Zurich, Switzerland Tayfun Güngör Ulrike Zeilhofer Necker Enfants Malades, University Hospital Paris, France Bénédicte Neven Despina Moshous Benjamin Fournier Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, USA Susan Prockop
    • 14. Thank you!


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