An essential component of allogeneic and autologous hematopoietic stem cell transplantation (HSCT) is the conditioning regimen administered before the hematopoietic cell infusion.
This post is about basic concepts of conditioning regimens in allogeneic HSCT.
Concept of conditioning has evolved over time from high dose myeloablative chemotherapy or radiotherapy to balanced myeloablation and immunosuppression which allows stem cell engraftment and disease eradication.
So, from the theoretic point of view, the conditioning consists of two components:
1. Myelo-depletion which targets the host stem cells
2. Lymphodepletion which targets the host lymphoid system, respectively.
Based on balance of above 2 factors 4 types of conditioning regimen exists.
[1] Myeloablative Conditioning (MAC)
[2] Myeloablative but Reduced Toxicity Conditioning (MAC-RTC)
[3] Reduced Intensity Conditioning (RIC)
[4] Nonmyeloablative Conditioning (NMA)
Myeloablative conditioning regimen: Is expected to produce “irreversible” pancytopenia and hence stem cell support is required to rescue marrow function and prevent aplasia-related death.
Non-myeloablative conditioning regimens produce minimal cytopaenias and doesn’t require stem cell support (means if stem cell support is not given autologous recovery is expected)
Reduced intensity conditioning regimens are those not fitting either of above definitions.
NMA & RIC “RELIES” on sufficient immunosuppression to allow engraftment.
NMA and RIC have been widely introduced over the past 20 years in an attempt to reduce organ toxicity and TRM allowing HSCT in elderly and medically infirm patients not eligible for standard MAC.
When a regimen is considered MAC?
If a regimen has following agents at doses, then its MAC
{a} TBI > 5Gy as a single fraction or >8Gy if fractionated
{b} Total BUSULPHAN > 8 mg/kg (IV) and BU > 9 mg/kg (PO)
{c} Total MELPHALAN >140 mg/m2
{d} Thiotepa >10 mg/kg
Examples of MAC regimen
[1] TBI Alone
[2] CY/TBI [TBI > 12Gy fractionated*+ Cyclophosphamide (CY) 120 mg/kg
[3] BU/CY (Total Dose BU – 16mg/kg PO or 13.2 mg/kg IV + CY 120-200 mg/kg)
*Typically used as 13.2 Gy in 8 fractions in < 18y and 14.4 Gy in 8 fractions >/= 18 y.
When a regimen is considered MAC but reduced TOXICITY (MAC-RTC)?
In an attempt to reduce regimen-related toxicity and reduced TRM, CY was replaced with FLUDARABINE (as in BU/FLU) and BU was replaced with Treosulphan (as in FLU/TREO)
These regimens are are also Myeloablative.
Treosulphan has better safety profile than busulphan and is myeloablative at doses of 30–42 g/m2. Hence it can be substituted for BU.
MAC-RTC regimens in use:
[1] BU/FLU [13.2 mg/kg IV + Fludarabine 200 mg/m2]
[2] TREO/FLU [Treosulfan 42 g/m2 + Fludarabine 150 mg/m2]
Which regimens are RIC?
These regimens have myeloablative agents at lower non myeloablative doses:
{a} TBI≤5Gy as a single fraction or≤8Gy if fractionated
{b} Total BUSULPHAN ≤ 8 mg/kg (IV) and BU ≤ 9 mg/kg (PO)
{c} Total MELPHALAN ≤140 mg/m2
{d} Thiotepa ≤ 10 mg/kg
Examples of RIC regimen
[1] BU/FLU [BU 6.6 mg/kg IV + Fludarabine 200 mg/m2]
[2] FLU/MEL [Melphalan 140 mg/m2 + Fludarabine 150 mg/m2]
What is non myeloablative regimen?
These regimens don’t have myeloablative chemotherapy agents. TBI if used is usually≤2Gy.
It is based on immunosupression only.
Examples:
TBI 2Gy
CY/ATG
FLU/CY/ATG
FLU/CY/TBI 2Gy
This post was to explain basic concept of conditioning protocols in allogeneic HSCT. and detailed disease specific protocol discussion can be sought elsewhere.
Intensity of conditioning regimen mostly depends on disease type and patients’ fitness.
This post has also been published as twitter thread
1/n: An essential component of allogeneic and autologous hematopoietic stem cell transplantation (HSCT) is the conditioning regimen administered before the hematopoietic cell infusion.
This thread is about basic concepts of conditioning regimens in allogeneic HSCT.
— thehematologist.org.in (@hematologist_in) May 4, 2023
Author
Dr Sujeet Kumar (@sujeethemat), Associate Professor, Dept of Medical Oncology (Hemat-oncology and BMT), HBCH & MPMMCC Varanasi