Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: considerations for evidence-based GVHD prophylaxis

Abstract

Development of reduced-intensity conditioning regimens (RIC) has enabled older or medically infirm patients with hematologic malignancies to be treated with allogeneic hematopoietic cell transplantation (HCT). This broader transplant eligibility has tripled the number of RIC-HCT procedures performed each year, with over 3000 in 2012. Currently about 50% of RIC-HCTs use unrelated donors, since many patients are older and do not have matched sibling donors. Naturally, this makes graft-versus-host disease (GVHD) prevention of particular importance. The ideal GVHD prophylaxis must balance tumor control/GVL with toxicity/GVHD. In this review, we discuss challenges in developing effective GVHD prophylaxis for RIC-HCT, various GVHD prophylactic regimens that are sometimes specific to the conditioning regimen, and the evidence to support their use.

Keywords::

• bortezomib
• cyclophosphamide
• cyclosporine
• graft-versus-host disease
• maraviroc
• methotrexate
• mycophenolate mofetil
• reduced intensity conditioning
• sirolimus
• tacrolimus
• vorinostat

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultations, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

The authors thank S Thomas for her critical reading of the manuscript.

Key issues

• Graft-versus-host disease (GVHD) prophylaxis remains a major issue in reduced-intensity conditioning-hematopoietic cell transplantation (HCT).

• The dynamics of allo-immune effects after reduced-intensity conditioning-HCT makes it very complex to develop optimal GVHD prophylaxis regimens.

• GVHD prophylaxis is often tied to a unique conditioning regimen, which makes it difficult to generalize and independently evaluate the efficacy of GVHD prophylaxis.

• Composite end points incorporating GVHD and relapse/survival are necessary for more relevant assessment of GVHD prophylaxis.

• Newer and promising strategies are being developed such as tacrolimus/sirolimus, post-HCT cyclophosphamide, maraviroc, vorinostat and bortezomib.

Notes