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