Histocompatibility & Immunogenetics

A collection of brief revision notes

Role of Reduced Intensity Conditioning (RIC)

Myeloablative or high dose conditioning regimens are defined as regimes where alkylating agents +/- total body irradiation (TBI) are used at doses which do not allow autologous hematologic recovery. Examples of Myeloablative regimens include:

  • Busulfan (high-dose 16 mg/kg), Cyclophosphamide (120 mg/kg) and high dose TBI (>800cGy)
  • Busulfan (high-dose 16 mg/kg) and high dose TBI (>800cGy)
  • Cyclophosphamide (120 mg/kg) ) and high dose TBI (>800cGy)
  • Busulfan (high-dose 16 mg/kg) and Cyclophosphamide (120 mg/kg) +/- ATG
  • Busulfan (high-dose 16 mg/kg) and Melphalan (140mg/m2)

These does can be toxic in older patients and have historically limited the availability of HSCT in older patients until the emergence of Reduced Intensity Regimes (RICs).

Reduced Intensity conditioning (RIC) regimes fall in between myeloablative and non-myeloablative regimens. RIC regimens differ from non-myeloablative regimens in that they cause cytopenia which may be prolonged and they do require stem cell support. RIC regimens differ from myeloablative regimens in the dose of alkylating agents or TBI. These are typically reduced by at least 30%. The introduction of reduced intensity conditioning has expanded the recipient pool for HSCT, which has importantly made transplant an option for the more commonly affected older age groups. RIC is used mainly in the care of older patients and those with medical comorbidities and for patients with immune deficiencies and bone marrow failure syndromes.

Most RIC regimens combine fludarabine with an alkylating agent at reduced doses. Examples of include:

  • Fludarabine, Cyclophosphamide and Melphalan
  • Fludarabine, Melphalan and Alemtuzumab
  • Fludarabine and Melphalan
  • Fludarabine and Busulfan (low-dose 16 mg/kg)
  • Fludarabine and TBI

Non-myeloablative regimens are defined as those which cause minimal cytopenia and do not require stem cell support. Examples of non-myeloablative regimens include reduced doses of:

  • Fludarabine, Cyclophosphamide and Anti-Thymocyte Globulin (FLU + CY + ATG)
  • Fludarabine, Cytarabine also known as Cytosine Arabinoside (Ara-C) and Idarubicin (FLU + CY + Ida)
  • Cladribine and Cytarabine also known as Cytosine Arabinoside (Ara-C) (Cladribine + Ara-C)
  • Total lymphoid irradiation + ATG
  • Low dose TBI (<2 Gy) +/- purine analog

Transplant related mortality (TRM) after myeloablative regimens increases with increasing age and especially in patients over 50. Non-myeloablative conditioning regimens have reduced toxicity, thus making transplantation available in the older patient population. Non-myeloablative regimens also require a large number of donor T lymphocytes and donor CD34+ cells to facilitate donor engraftment, which also contributes to the GvL effect.