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, 22 (10), 1851-1860

Severe Cytokine-Release Syndrome After T Cell-Replete Peripheral Blood Haploidentical Donor Transplantation Is Associated With Poor Survival and Anti-IL-6 Therapy Is Safe and Well Tolerated

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Severe Cytokine-Release Syndrome After T Cell-Replete Peripheral Blood Haploidentical Donor Transplantation Is Associated With Poor Survival and Anti-IL-6 Therapy Is Safe and Well Tolerated

Ramzi Abboud et al. Biol Blood Marrow Transplant.

Abstract

Use of high-dose post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis has expanded the use of unmanipulated haploidentical hematopoietic cell transplantation. The immediate post-transplantation course in T cell-replete peripheral blood haploidentical hematopoietic cell transplantation (haplo-HCT) is often complicated by symptoms resembling cytokine-release syndrome (CRS), previously described in recipients of targeted cellular therapeutics. However, we know little about the incidence and impact of CRS on outcomes in these patients. To understand this syndrome in haplo-HCT patients, we reviewed data from 75 consecutive patients who received granulocyte colony-stimulating factor-mobilized T cell-replete peripheral blood haplo-HCT at a single center. Using CRS criteria described in recipients of chimeric antigen receptor T cell therapies, we found 65 of 75 (87%) met criteria for CRS, although most cases were only mild (grades 1 or 2). However, 9 patients (12%) experienced severe (grades 3 or 4) CRS. Median survival was 2.6 months (95% confidence interval [CI], .43 to 5.8) in patients with severe CRS, compared with 13.1 months (95% CI, 8.1 to not reached) in patients with mild CRS. Transplantation-related mortality was worse in the severe CRS cohort with a hazard ratio of 4.59 (95% CI, 1.43 to 14.67) compared with that in the mild CRS cohort. Severe CRS patients had a significant delay in median time for neutrophil engraftment. Serum IL-6 levels were measured in 10 haplo-HCT patients and were elevated in the early post-transplantation setting. Seven patients with CRS were treated with tocilizumab, resulting in a complete resolution of their CRS symptoms. Severe CRS represents a potential complication of peripheral blood haplo-HCT and is associated with worse outcomes. Anti-IL-6 receptor therapy is associated with rapid resolution of the CRS symptoms.

Keywords: Cytokine-release syndrome (CRS); Haploidentical; Tocilizumab; Transplantation-related mortality (TRM).

Conflict of interest statement

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Figures

Figure 1A
Figure 1A. Incidence of CRS by Severity in Haplo-HCT patients
Figure 1B
Figure 1B. Clinical Course of Patients with Severe CRS
Maximum daily temperature (left y-axis) and oxygen requirement (right y-axis) are graphed for all patients. The presence of other diagnostic criteria for CRS including AMS, pressor requirement, intubation and creatinine or LFT elevations are denoted by symbols. Clinical course until day +14 is shown for all patients except P04, who died on day +12.
Figure 2A
Figure 2A. Kaplan-Meier Curve of Overall Survival by Grade of Cytokine Release Syndrome
Figure 2B
Figure 2B. Cumulative Incidence of Transplant-Related Mortality by Grade of Cytokine Release Syndrome
Figure 3
Figure 3. Cumulative Incidence of Neutrophil Engraftment by Grade of Cytokine Release Syndrome
Figure 4
Figure 4. Interleukin 6 Levels after Haplo-SCT

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