Less intense conditioning regimens are being used more frequently today that retain the desirable effects of standard high-dose conditioning regimens, but with significantly lower transplant-related mortality (TRM).
The adoption of less toxic conditioning regimens has expanded the number of patients eligible to receive transplants -- patients who may have previously been excluded due to older age or existing co-morbidities. Today, patients to their 70s are receiving transplants. For more information, see Trends in Allogeneic Transplants.
Reduced-intensity or non-myeloablative regimens use lower doses of pre-transplant chemotherapy drugs and/or radiation than the traditional high-dose, myeloablative regimens that have been in use for more than 40 years.
These regimens do not necessarily completely eliminate malignant cells prior to transplant, but instead rely upon a graft-versus-malignancy effect mediated by donor-origin lymphoid cells, mostly T cells. Clinical studies of reduced-intensity transplantation have shown that the graft-versus-malignancy effect is particularly pronounced in:
- Chronic myelogenous leukemia
- Chronic lymphocytic leukemia
- Low-grade, indolent lymphomas 
Reduced-intensity regimens typically use combinations of chemotherapy drugs such as fludarabine, busulfan, and melphalan, with or without low-dose radiation. Due to the reduced toxicity of these regimens, TRM can be lower, and may result in improved outcomes. Recent studies comparing reduced-intensity transplants to fully myeloablative transplants have also shown:
- Survival in older patients after reduced-intensity transplants is comparable to survival in younger transplant patients. [2,3]
- No significant difference in non-relapse mortality and overall survival between patients older than 55 years and those younger than 55. 
- Significantly lower 1-year infection-related mortality after reduced-intensity transplantation than after myeloablative transplantation. 
Some transplant centers are also performing autologous transplants followed by reduced-intensity allogeneic transplantation. This strategy combines the tumor cytoreduction of a high-dose autologous transplant with the lowered TRM of a reduced-intensity conditioning regimen. This technique has been particularly promising in treating patients with multiple myeloma. [6,7]
Despite the growth in the use of reduced-intensity conditioning regimens, fully myeloablative regimens are still used for a large percentage of patients undergoing hematopoietic cell transplantation. High-dose regimens are particularly useful in conditioning patients with aggressive malignancies, where there is a need for a strong anti-leukemia or anti-tumor effect.
Cyclophosphamide plus total body irradiation (TBI) and busulfan and cyclophosphamide are typical approaches for fully myeloablative regimens, but combining busulfan with fludarabine is being increasingly used. [8,9,10]
- Antin JH. Stem cell transplantation -- harnessing of graft-versus-malignancy. Curr Opin Hematol. 2003; 10(6):440-444.
- Couriel DR, Saliba RM, Giralt S, et al. Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant. 2004; 10(3):178-185.
- Hegenbart U, Niederwieser D, Sandmaier BM, et al. Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors. J Clin Oncol. 2005; 24(3):444-453.
- Corradini P, Zallio F, Mariotti J, et al. Effect of age and previous autologous transplantation on nonrelapse mortality and survival in patients treated with reduced-intensity conditioning and allografting for advanced hematologic malignancies. J Clin Oncol. 2005; 23(27): 6690-6698.
- Bachanova V, Brunstein CG, Burns LJ, et al. Fewer infections and lower infection-related mortality following non-myeloablative versus myeloablative conditioning for allotransplantation of patients with lymphoma. Bone Marrow Transplant. 2009; 43(3): 237-244.
- Maloney DG, Molina AJ, Sahebi F, et al. Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood. 2003; 102(9):3447-3454.
- Bruno B, Rotta M, Patriarca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007; 356(11):1110-1120.
- Kroger N, Zabelina T, Kruger W, et al. Comparison of total body irradiation vs busulfan in combination with cyclophosphamide as conditioning for unrelated stem cell transplantation in CML patients. Bone Marrow Transplant. 2001; 27(4):349-354.
- De Lima M, Couriel D, Thall PF, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004; 104(3):857-864.
- Chae YS, Sohn SK, Kim JG, et al. New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2. Bone Marrow Transplant. 2007; 40(6):541-547.