Abstract
Cytokine release syndrome (CRS) represents a life‐threatening side effect after haploidentical stem cell transplantation (Haplo‐SCT) with posttransplant cyclophosphamide (PT‐Cy). Factors predictive of CRS development is still a matter of debate. We retrospectively analyzed 102 consecutive patients receiving a bone marrow (BM) (n = 42) or peripheral blood stem cells (PBSC) (n = 60) Haplo‐SCT with PT‐Cy. The two cohorts were similar in main patients’ characteristics besides disease type (P = .02). Cumulative incidence of grades 1, 2, and ≥3 CRS was 80%, 52%, and 15% at a median of 2, 4, and 7 days, respectively. Moderate/High‐grade fever (39°‐41°), grade 1 and grade ≥3 CRS occurred more frequently after PBSC relative to BM grafts (68% vs 33%, P = .0005; 87% vs 71%, P = .009; 20% vs 7%, P = .07). Only patients experiencing grade ≥3 CRS had a worse outcome in terms of 1‐year overall survival (OS) and nonrelapse mortality (NRM): 39% vs 80% (P = .002) and 40% vs 8% (P = .005), respectively. By univariate analysis the only factors associated with the increased risk of ≥3 CRS were pretransplant disease status (8% for complete remission, 11% for partial remission, and 38% for active disease, P = .002), HLA‐DRB1 mismatching (57% vs 14%, P = .007), and PBSC graft (P = .07). By multivariable analysis, only pretransplant disease status (hazard ratio, HR: 6.84, P = .005) and HLA‐DRB1 mismatching (HR: 17.19, P = .003) remained independent predictors of grade ≥3 CRS. Only grade ≥3 CRS is clinically relevant for the final outcome of patients receiving Haplo‐SCT with PT‐Cy, is more frequent after a PBSC graft and is associated with pretransplant active disease and HLA‐DRB1 mismatching.
Highlights
Cumulative incidence of grades 1 and 3 Cytokine release syndrome (CRS) was higher after peripheral blood stem cells (PBSC) relative to Bone marrow (BM) grafts recipients (87% vs 71%, P = .009 and 20% vs 7%, P = .07), while there was no difference in terms of grade 2 CRS between the two stem cell sources (58% vs 43%, P = .15) (Figure 1B, D, and F)
In this report we have confirmed that grade ≥3 CRS is associated with a worse outcome in patients receiving Haplo‐SCT with posttransplant cyclophosphamide (PT‐Cy) both in terms of overall survival (OS) and nonrelapse mortality (NRM)
Our results extends previous observations on risk factors for the development of life‐threatening CRS since we have identified that disease burden, HLA‐DRB1 mismatching, and graft type (PBSC vs BM) were significantly associated with a higher incidence of grade ≥3 CRS
Summary
T‐cell‐replete haploidentical stem cell transplantation (Haplo‐SCT) with high‐dose posttransplant cyclophosphamide (PT‐Cy) represents an emerging alternative option for patients with hematologic malignancies when a HLA identical sibling or a matched related donor is not available.[1,2] Bone marrow (BM) stem cells represented the first type of graft used for Haplo‐SCT,[3] but peripheral blood stem cells (PBSC) are more often employed because of the ease and convenience of collection.[2]. We analyze whether other variables, including HLA mismatching, may correlate with an increased risk of CRS This is a retrospective study comprising 102 consecutive patients with hematologic malignancies receiving T‐cell‐replete Haplo‐SCT with PT‐Cy at a single institution between January 2014 and December 2017. Symptoms occurring before day +14 were included as in the manuscript by Abboud et al[7] and Raj et al.[8] The detailed clinical data from posttransplantation days 0‐14 were collected and used to grade CRS. These data included fever curves, vital signs, renal and hepatic function tests, CRP levels, the development of vasopressor dependence, oxygen requirement, and the need for mechanical ventilation.
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