Abstract
ObjectivesInfections are a major cause of mortality after allogeneic haemopoietic stem cell transplantation (alloHSCT), and immune recovery is necessary for prevention. Novel transplant procedures have changed the epidemiology of infections but contemporary data on functional immune recovery are limited. In this pilot study, we aimed to measure immune recovery in the current era of alloHSCT.MethodsTwenty, 13, 11, 9 and 9 alloHSCT recipients had blood collected at baseline (time of conditioning) and 3‐, 6‐, 9‐, and 12‐months post‐alloHSCT, respectively. Clinical data were collected, and immune recovery was measured using immunophenotyping, lymphocyte proliferation, cytokine analysis and antibody isotyping.ResultsMedian absolute T‐ and B‐cell counts were below normal from baseline until 9‐ to 12‐months post‐alloHSCT. Median absolute CD4+ T‐cell counts recovered at 12‐months post‐alloHSCT. Positive proliferative responses to Aspergillus, cytomegalovirus (CMV), Epstein‐Barr virus (EBV), influenza and tetanus antigens were detected from 9 months. IL‐6 was the most abundant cytokine in cell cultures. In cultures stimulated with CMV, EBV, influenza and tetanus peptides, the CD4+ T‐cell count correlated with IL‐1β (P = 0.045) and CD8+ T‐cell count with IFNγ (P = 0.013) and IL‐1β (P = 0.012). The NK‐cell count correlated with IL‐1β (P = 0.02) and IL‐17a (P = 0.03). Median serum levels of IgG1, IgG2 and IgG3 were normal while IgG4 and IgA were below normal range throughout follow‐up.ConclusionsThis pilot study demonstrates that immune recovery can be measured using CD4+ T‐cell counts, in vitro antigen stimulation and selected cytokines (IFNγ, IL‐1β, IL‐4, IL‐6, IL‐17, IL‐21, IL‐31) in alloHSCT recipients. While larger studies are required, monitoring immune recovery may have utility in predicting infection risk post‐alloHSCT.
Highlights
Allogeneic haemopoietic stem cell transplantation is routinely used to cure a wide variety of haematological malignancies
CMV, cytomegalovirus; IQR, interquartile range; n, number. aT-cell lymphoma (1), B-lymphoblastic leukaemia/lymphoma (1), Follicular non-Hodgkin lymphoma (2), chronic myelo-monocytic leukaemia (1). bNonmyeloablative. cDefined as an absolute neutrophil count > 0.5 9 109 LÀ1 sustained over 3 days
We report that recovery of functional CD4+ T-cell pathogen responses occurs 9- to 12 months post-alloHSCT and, based on antigenspecific in vitro responses, identify a panel of cytokines (IFN-c, IL-1b, IL-4, IL-6, IL-17, IL-21 and IL-31), with potential for immune-profiling and infection risk prediction
Summary
Allogeneic haemopoietic stem cell transplantation (alloHSCT) is routinely used to cure a wide variety of haematological malignancies. Risk stratification models are used to guide the timing and duration of antimicrobial prophylaxis.[7] These are based on clinical factors such as age at time of alloHSCT, underlying disease, prior therapy, conditioning regimen, donor type, degree of matching, stem cell source and presence of GVHD. Such clinically based models only give a qualitative measure of immune function and lack precision. A strategy which quantifies immune function is urgently needed to more accurately predict risk and guide antimicrobial prophylaxis . Immune-based strategies for cytomegalovirus (CMV) have been examined and appear promising for guiding CMV prophylaxis;[8] more broad-based immune function strategies incorporating other important opportunistic pathogens, such as Aspergillus still need to be developed
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