Strategies to improve posttransplant immunity - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 121

ch 6

Strategies to improve post-
transplant immunity

Miguel-Angel Perales, Alan M Hanash
Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA
Jarrod A Dudakov
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA and Monash Immunology and
Stem Cell Laboratories (MISCL), Monash University, Melbourne, Australia
Marcel RM van den Brink
Department of Medicine and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York,
Department of Immunology and Microbial Pathogenesis and Department of Medicine, Weill Cornell Medical College,
New York, NY, USA

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Introduction

In this chapter we will discuss current and future strategies to enhance post-
transplant immune deficiency. We will briefly discuss the well-known causes
for this deficiency and then direct our attention toward the considerable
progress in the development of strategies to enhance immune cell recov-
ery after hematopoietic stem cell transplantation (HSCT). We will focus on
three strategies that are currently in clinical trials (Interleukin-7 (IL-7), kera-
tinocyte growth factor 1 (KGF) and sex steroid blockade) and a few selected
strategies which have shown promise in preclinical studies (Figure 6.1).

Post-transplant immune deficiency

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a well-
established curative approach for a variety of malignant and nonmalignant
hematologic disorders [1] . Progression or recurrence of primary disease,
graft-versus-host disease (GVHD), infection, and regimen-related toxic-
ity remain the primary causes of transplant failure. The timing and quality
of immune reconstitution significantly influence morbidity and mortality
following allo-HSCT. Adult recipients of an allo-HSCT experience deficien-
cies in their B- and T-cell reconstitution, which can persist for more than a
year, and are associated with an increased risk of infections [2-5] , relapse of
malignancy [6] and the development of secondary malignancies [7] . Despite
more stringent matching of patient and potential unrelated donors through
molecular typing of HLA alleles [8-12] , and the systematic prophylaxis and
treatment of invasive viral, fungal and parasitic infections, opportunistic
infections represent a major cause of death in most unrelated transplant
series, regardless of whether the stem cell source is bone marrow, peripheral