.....................THALASEMMIA

1. Treatment is getting
“trendy”
Dr Sunil Bhat
Director and Clinical Lead
Paediatric Haematology, Oncology and Bone Marrow Transplantation
SRCC NH Children’s Hospital Mumbai
Mazumdar Shaw Cancer Centre and Narayana Multispecialty Hospitals, Bangalore
Ex Chair Stem Cell Working Group, INPOG, PHO Chapter, IAP
Secretary Karnataka Hematology Oncology Society
Secretary Pediatric Hematology Oncology Chapter, IAP
Editor: International Journal of Medical Pediatrics and Oncology

3. Comprehensive care
• Confirmation of diagnosis.
• Correction of anaemia-packed cell transfusions.
• Removal of excess iron-Chelation therapy.
• Management of complications-endocrine and cardiac.
• Pharmacological methods to increase gamma chain synthesis.
• Curative treatment- stem cell transplantation.
• Future treatment- gene replacement therapy.
• Prevention of disease by antenatal diagnosis and genetic counselling.

5. • RECOMMENDED TRANSFUSION: pretransfusion Hb level
is around 9-10.5 gm% and mean Hb is maintained is
>12gm%
• HYPERTRANSFUSION: pretransfusion Hb is around
>10gm% and mean Hb maintained is >12gm%
• SUPERTRANSFUSION: pretransfusion Hb level is around
>12gm% and mean Hb maintained is >14gm%

6. Methods for leukodepletion
• Centrifugation-packed red cell transfusions-can remove 70% of
leukocytes from 1 unit of blood.
• Saline-cell washing (triple saline washed) or deglycerolised-red
cells can remove 90-95% of contaminated white cells.
• Third generation leucocyte filters-
 remove 99.9% of white cells but not cytokines.
 These are highly expensive, meant for single use
only, are disposable and are not affordable.
• Irradiated blood cells
given to patients who have received BMT or
candidates waiting for BMT.

7. Advances in transfusion therapy
• Minimise blood transmitted infections by NAT
testing
• Phenotypically matched
• “Donor pool”

8. • Iron overload is the one of the most common
problem encountered in the management of
thalassemia.
• Most of the complications of thalassemia is
attributed to iron overload
• Excess iron is toxic to heart ,liver and endocrine
organs
IRON OVERLOAD

9. Drugs used in chelation
therapy
• Desferrioxamine
• Deferiprone
• Deferasirox
• Other newer agents
Oleptis/Jadenu: Better tolerability/convenience

10. Combination therapy
Shuttle hypothesis :
• Bidentate chelator (L1)- mobilizes tissue iron into blood
stream
• Hexadentate (DFO) = binds irreversibly and excretes iron

11. • Many studies have shown the effectiveness of the
combination therapy with DFO and DEFRIPRONE.
• Other combinations exhibiting shuttle mechanism
are DEFRESIROX and DFO

12. Serum markers: Ferritin
 Serum ferritin
 Most widely used and the least expensive parameter
 Positive correlation exists between serum ferritin
concentration and iron stores, but
 Independent conditions may falsely elevate ferritin levels (cancer,
hepatitis, inflammation, haemolysis, vitamin C deficiency)
 Accuracy diminishes at high ferritin values
 Serial assessments are recommended

14. MRI assessment
• Heart
• Liver
• Pancreas
• Pituitary

15. Newer Medications
• Luspatercept
• Sotatercept
• Hypomethylating agents : Decitabine
• HDAC Inhibitors: Butyrates
• Amlodipine for cardiac iron

16. Monitoring
• Better understanding of the “complications”
• Access and guidelines for monitoring especially
endocrine and bone health
• Bisphosphonates, hormone replacement
therapies
• DEXA, Fibroscans etc
• Concept of “Comprehensive Thalassemia Care
Centers”
• Psychological counseling

17. Gene Therapy

18. PREVENTION OF THALASSEMIA
• Pre-implantation genetic diagnosis
• Fetal cells in maternal circulation
• Fetal DNA in maternal plasma

20. Bloodyfast App

21. Case Scenarios
• 12 year old boy
• Stunting/oragnomegaly
• LIC 2017 Jan: 12mg/g
• Chelation optimised
• LIC 2018 Feb: 14.5 mg/g
• ??? Compliance

22. Case 2
• 5 year old girl
• Pre transfusion HB in range of 6-6.5 gm
• Huge spleen
• Ferritin 4200 ng/ml
• ?? Waiting for Gene therapy

23. Summary
• Remember : Basics are very important
• Thal care has of course become trendy
• Newer advances have made care better
resulting in better quality of life
• They are definitely complimentary
• Advised to be judicious