1. Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part I. Biology of Relapse after Transplantation 
Ronald E. Gress, Jeffrey S. Miller, Minoo Battiwalla, Michael R. Bishop, Sergio A. Giralt, Nancy M. Hardy, Nicolaus Kröger, Alan S. Wayne, Dan A. Landau, Catherine J. Wu 
Biology of Blood and Marrow Transplantation 
Volume 19, Issue 11, Pages (November 2013)
DOI: /j.bbmt
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2. Figure 1
Diagrammatic representation of the timeline of immune reconstitution in a 40-year-old CMV-seropositive adult. After cytoreductive therapy, the peripheral CD4 and CD8 T cell populations are severely depleted. The thymus is reduced to a small remnant (shown at 1.5 months post-transplant). CD4 and CD8 T cells immediately undergo a marked expansion in response to homeostatic cytokines and endogenous antigens, generating a population that is mainly composed of memory (green) and effector (orange) T cells, with few naïve (blue) or T cell receptor excision circle (TREC)–bearing cells (also represented at 1.5 months post-transplant). The CD4/CD8 ratio becomes inverted by the more rapid expansion of CD8+ T cells, demonstrated by the peak of (orange) effector CD8 cells as compared with the smaller (green) peak of CD4+ cells at 1.5 months. TCR repertoire diversity that has been lost by lymphodepletion is further skewed by oligoclonal expansion of the limited number of remaining cells. The expanded population of CD8 T cells persists and may continue to dominate the CD8 TCR repertoire as shown in subsequent months by the large effector (orange) CD8 population. Renewed thymopoiesis begins within the first 6 months, but the full contribution of naïve, TREC-bearing T cells with a diverse TCR repertoire may require 1 to 2 years to be evident.
(Reprinted from Williams KM, Hakim FT, Gress RE. T cell immune reconstitution following lymphodepletion. Semin Immunol 2007;19: , Copyright (2007), with permission from Elsevier.)
Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt )
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3. Figure 2
NK cells express a number of inhibitory and activating receptors that determine function. Some of these interactions are definitively established with known signaling pathways, whereas others are less clear. Most receptors interact with cellular targets, but CD16 delivers a potent signal by binding the Fc portion of immunoglobulin-coated targets. The ability of NK cells to kill a target is determined by the net balance of these inhibitory, activating, antibody-dependent, and adhesion interactions.
(Reprinted from Murphy WJ, Parham P, Miller JS. NK cells—from bench to clinic. Biol Blood Marrow Transplant 2012;18:S2-S7. Copyright (2012), with permission from Elsevier.)
Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt )
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4. Figure 3
Potential treatment effects on clonal heterogeneity and disease behavior. Interclonal equilibrium can remain remarkably stable for years (top). However, when an aggressive minor clone arises (bottom), clonal evolution begins and can be potentially accelerated by therapy. This may be due to differential resistance of subpopulations to treatment. Additionally, a mass extinction event, such as chemotherapy, may accelerate evolution by removing the strong incumbent and allowing the fitter rising subclone to repopulate the compartment more efficiently, as sometimes seen with bottlenecks in population genetics.
(Adapted from Landau DA, et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 2013;152: )
Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt )
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