Non-relapse cytopenias following allogeneic stem cell transplantation, a case based review

Abstract

The development of non-relapse cytopenias (NRC) is a relatively common occurrence post allogeneic stem cell transplant (alloSCT). Whilst there have been attempts to classify post alloSCT cytopenias by transplantation groups, ambiguity of definitions in prior publications compounded by a lack of availability of high-quality evidence, provide challenges to clinicians attempting to manage these complex patients. In this review we describe 3 cases of NRC, (1) Graft Failure with graft rejection representing cytopenias with minimal donor chimerism (2) Poor Graft Function representing cytopenias with complete donor chimerism and (3) Cytopenias with mixed donor chimerism. This case-based review will evaluate the currently available evidence regarding the pathophysiology of each entity as well as the evidence for current therapies with the aim of providing guidance to clinicians managing these complex patients.

Prospects and Potential for Chimerism Analysis after Allogeneic Hematopoietic Stem Cell Transplantation

“…In such cases, no or minimal donor chimerism may be associated with graft rejection, whereas complete donor chimerism may mean poor graft function. In addition, there are cytopenic patients with mixed chimerism who may develop bone marrow failure, graft rejection, or resolution of their cytopenia [ 75 , 76 ]. Risk factors for graft failure include the use of RIC and/or CBT, the presence of HLA antibodies, low infused cell number, viral infection, and various other causes [ 62 ].…”

“…Most studies involving salvage second allo-HSCT for graft failure are retrospective and small with heterogeneity in conditioning regimens and graft selections as well as timing of onset; these studies presumably include primary and secondary graft failure. In general, OS after the second allo-HSCT for graft failure is poor due to high rates of treatment-related mortality associated with infections [ 76 ]. However, recent studies have shown acceptable OS after salvage second allo-HSCT, including CBT or allo-HSCT from haploidentical related donors [ 78 , 79 , 80 , 81 , 82 , 83 ].…”

“…However, recent studies have shown acceptable OS after salvage second allo-HSCT, including CBT or allo-HSCT from haploidentical related donors [ 78 , 79 , 80 , 81 , 82 , 83 ]. No treatments other than salvage second allo-HSCT are established for graft failure with graft rejection, although some investigational drugs, such as an interferon-gamma inhibitor, have been tried [ 76 ]. Interventions for graft failure without graft rejection are more variable than those with graft rejection and are based on specific situations [ 3 , 37 , 75 , 76 ].…”

“…No treatments other than salvage second allo-HSCT are established for graft failure with graft rejection, although some investigational drugs, such as an interferon-gamma inhibitor, have been tried [ 76 ]. Interventions for graft failure without graft rejection are more variable than those with graft rejection and are based on specific situations [ 3 , 37 , 75 , 76 ]. Cytopenias in the presence of dominant or complete donor chimerism associated with poor graft function, including donor-type aplasia, are well known [ 76 , 84 ].…”

Spatial proteomics identifies a spectrum of immune dysregulation in acquired bone marrow failure syndromes

“…Poor graft function is a syndrome of severe, life-threatening peripheral cytopenias despite >95% donor engraftment ( 8 ). Analysis of our transplant centre data (929 patients, alloSCT 2000–2016) has shown that PGF occurs in 13% of patients undergoing alloSCT, with a mortality rate of 60% in those without bone marrow (BM) recovery ( 9 ).…”