Conditioning regimens for hematopoietic cell transplantation: one size does not fit all

Abstract

An essential component of allogeneic and autologous hematopoietic cell transplantation (HCT) is the conditioning regimen administered before the hematopoietic cell infusion. Early regimens relied on dose intensity, assuming that high-dose chemoradiotherapy would eliminate malignant disease and reinfusion of the graft would then restore hematopoiesis. However, as the contribution of graft-versus-tumor effects to the success of allogeneic HCT was recognized over time, in an effort to exploit these, many investigators lowered the dose of radiation and chemotherapeutic agents in the preparative regimen. This resulted in a major paradigm shift, and consequently, the pool of eligible patients underwent a remarkable expansion. In this article, we provide a review of the definition of high-dose, reduced-intensity, and nonmyeloablative conditioning regimens, the most commonly used agents and combinations, and the evolution of some early regimens. We also provide a brief review of the toxicities associated with these regimens.

Figure 1

Selected conditioning regimens of different dose intensities. AraC, cytosine arabinoside; ATG, antithymocyte globulin (or thymoglobulin); ¹³¹I, anti-CD45 antibody conjugated to ¹³¹I. BU, busulfan; CY, cyclophosphamide; Flu, fludarabine (various dosing schedules). *High-dose TBI (800-1320 cGy). ^†Low-dose TBI (200-400 cGy). Reproduced from Deeg and Sandmaier.

Figure 2

Trends in transplant by type and recipient age, 2002 to 2006 and 2007 to 2011, CIBMTR data. Transplants are for AML, ALL, NHL, Hodgkin’s lymphoma, and multiple myeloma. Figure originally presented as slide 6 of Pasquini and Wang.

Figure 3

Allogeneic transplants registered with the CIBMTR, 2001 to 2011, by conditioning regimen intensity and age. CIBMTR data. Figure originally presented as slide 21 of Pasquini and Wang.

Figure 4

Percentage of RIC allo-HCTs, registered with CIBMTR, 1998 to 2011, by year of transplant and disease. CIBMTR data. Figure originally presented as slide 23 of Pasquini and Wang.