DEFINING THE INTENSITY OF CONDITIONING REGIMENS : working definitions

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• The intensity of the conditioning regimen can vary significantly. The conventional conditioning for most young patients with leukemia/lymphoma is either cyclophosphamide (CY) 120 mg/kg and total body irradiation (TBI) (10–15 Gy) (referred to as CY-TBI) (3) or busulfan (BU) 16 mg/kg p.o. and CY 120 mg/kg, (referred to as BU-CY)

• Several attempts have been made in the past 30 years to limit early transplant toxicity, by reducing the intensity of the conditioning regimen: John Hobbs used half the dose of BU (8 mg/kg) in children with inborn errors

• Peter Tutchka reduced the dose of CY from 200 to 120 in the classic BU-CY regimen

• and Guido Lucarelli reduced the dose of busulfan from 16 mg/kg to 14 mg/kg for his thalassemia conditioning regimen

• In contrast some regimens were intensified with the aim of reducing leukemia relapse: the Seattle team delivered 15.75 Gy rather than 12 Gy in patients with leukemia

• Other investigators introduced the use of etoposide in combination with TBI

• Very few regimens have been prospectively compared head to head, with the exception of the Seattle TBI regimens

• and we have no evidence that intensified conditioning improves survival: the reason being that any decrease of leukemia recurrence with a higher dose of TBI is achieved at the expense of increased toxicity

• Within the past 15 years two changes have occurred in the conditioning regimens: the introduction of fludarabine (10–13) and further dose reduction of the alkylating agents (14–16) or TBI (17

• These regimens, were specifically designed for patients ineligible for conventional conditioning, either because of age (usually above 50 years) or because of the presence of co-morbidities

• By reducing the intensity of the conditioning regimen, the benefit of allogeneic transplantation would come from a graft-versus-malignancy effect, rather than from the upfront cyto-reductive effect of the conditioning regimen

• These modified regimens have rapidly become popular, such that by 2001 almost 30% of transplants were performed with reduced intensity regimens

• Regimens using fludarabine and/or reduced doses of chemo/radiotherapy have been referred to as non myeloablative stem cell transplants (NMA), reduced intensity conditioning transplants (RIC) or mini transplants

• In the present report we will discuss three categories of conditioning regimens: myeloablative, reduced intensity and non myeloablative