principal of conditioning regimen¸_ สุรเดช bmt.pdf · •pre transplant management...
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Principal of Conditioning Regimen
Suradej Hogneng,MD
Ramathibodi Hospital, Mahidol University
Bangkok, Thailand
Reasons for Conditioning Regimens
Opening the marrow space
Immunosuppressive effect
Antitumor effect
Opening the marrow space
Chemotherapy
Busulfan
Melphalan
TBI
Anti CD45
Immunosuppressive effect
TBI/TLI
ATG/Campath
ATG: time of giving ATG
Rituximab
CY, Thiotepa, Fludarabine
HSCT in Malignant Diseases
Decrease the tumor burden
Anti tumor effect from conditioning regimen
Chemotherapy: BEAM vs CVB in lymphoma
Bu Mel vs CEM in neuroblastoma
Thiotepa based in brain tumors
Mel in MM
Ara C in lymphoma/leukemia
TBI
Targeted therapy: rituximab in lymphoma
GVT effect
Graft vs Host (GVH) and Host vs Graft (HVG)
GvH HvGGvH HvG
Conditioning Regimen
HSCT in Genetic Diseases
Hemoglobinopathies
Storage diseases
Bone marrow failure syndromes (BMFS)
Primary immune deficiencies (PIDs)
Immune status and disease burden status
HvG or Graf Rejection
Contributing factors
Host immune: patient disease
Host disease burden: probably the younger the better
Conditioning regimen: myeloablative
nonmyeloabative
reduce toxicity
immunoablative
Hemoglobinopathies
Thalassemias
Sickle cell diseases
Hemoglobinopathies
Hyper immune or highly immunized
Ineffective erythropoiesis (thalassemia > sickle cell disease)
Myeloablative (MAC) vs Reduced Toxicity (RTC)
Conditioning Regimens
BBMT, 2014
Novel RTC Approach for High Risk Class 3 Patients
(Age > 10 and Hepatomegaly)
• Pre transplant management (6-12 months) to decrease
ineffective erythropoiesis
Hypertransfusion to keep Hb 9-10 gm/dL, iron chelation and
hydroxyurea (20 mg/kg/d)
• Pretransplant immunosuppression (PTIS)
Flu + Dex (2 cycles; 28 days/cycle)
• Conditioning regimen
Bu + Flu + ATG
Hemoglobinopathy/Genetic Diseases
MRD and MUD
0
20
40
60
80
100
120
140
1 2 3 4
Stim
ula
tio
n in
de
x
Time of testing
No.1
No.2
No.3
Decreased CD4 Cell Proliferation(PHA Stimulation)
8/5/2018 B.S. Andersson
Normal Organ
Toxicity
Fracti
on
of
Non
-En
graft
ed
Pati
ents
aGVHD
Systemic Drug Exposure
Leukemia Pats.
Immunosuppressed
Thalassemia- SCA- Pats.-
Immunocompetent
“Immuno-ablative Therapeutic Intervals”
“Safe Upper Limit”,
Syst.Exposure
SCIDs
Graft Patient subset HSCT features and challenges
Matched sibling SCID
Non-SCID
No conditioning needed, Poor B cell reconstitution
Myeloablation and Immunosuppression required, full chimerism might be needed, reduced intensity with mixed chimerism ?
Haplo with T cell depletion
SCID: B+NK-
SCID: B+/-NK+
Non-SCID
No conditioning: T cell engraftment achieved, poor B cell engraftmentMyeloablation: highly likelihood of T and B cell reconstitution, toxicity increased
No immunosuppression: risk of graft rejectionImmunosuppression: T cell but no B cell immunity restoredMyeloablation: higher likelihood of T and B reconstitution, toxicity increased
Myeloablation and immunosuppression required, higher TRM
Matched unrelated SCID
Non-SCID
Myeloablation: increased risk of TRM; searching process takes months
High resolution HLA matched donor required, myeloablation required
Unrelated cord blood
SCID
Non-SCID
Limited data, high dose chemotherapy conditioning needed
High dose chemotherapy conditioning needed, risk of graft rejection 10-15%
J Allergy Clin Immuno 2008
HSCT in Genetic Diseases
Hemoglobinopathies
AA Cy ATG + Flu
Storage diseases
Bone marrow failure syndromes (BMFS)
Primary immune deficiencies (PIDs)
Immune status and disease burden status