Clinical features, pathophysiology, and therapy of poor graft function post-allogeneic stem cell transplantation

Ashvind Prabahran, Rachel Koldej, Lynette Chee, David Ritchie, Ashvind Prabahran, Rachel Koldej, Lynette Chee, David Ritchie

Abstract

Poor graft function (PGF), defined by the presence of multilineage cytopenias in the presence of 100% donor chimerism, is a serious complication of allogeneic stem cell transplant (alloSCT). Inducers or potentiators of alloimmunity such as cytomegalovirus reactivation and graft-versus-host disease are associated with the development of PGF, however, more clinical studies are required to establish further risk factors and describe outcomes of PGF. The pathophysiology of PGF can be conceptualized as dysfunction related to the number or productivity of the stem cell compartment, defects in bone marrow microenvironment components such as mesenchymal stromal cells and endothelial cells, or immunological suppression of post-alloSCT hematopoiesis. Treatment strategies focused on improving stem cell number and function and microenvironment support of hematopoiesis have been attempted with variable success. There has been limited use of immune manipulation as a therapeutic strategy, but emerging therapies hold promise. This review details the current understanding of the causes of PGF and methods of treatment to provide a framework for clinicians managing this complex problem.

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Approach to engraftment syndromes post-alloSCT. A method of classifying engraftment syndromes post-alloSCT based on level of donor chimerism present.
Figure 2.
Figure 2.
Seed, soil, and climate model of PGF. Proposed pathophysiology of PGF based on the interplay of key components of the bone marrow. Seed (HSCs), soil (microenvironment), and climate (T cells and cytokines). T cells target and suppress microenvironment cells and actively suppress HSC function through inflammatory cytokines and loss of microenvironment trophic signals.

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