AL-10. Clinical features of cytokine release syndrome in adult patients with acute leukemia after allogeneic stem cell transplantation: RM Gorbacheva Research Institute experience

Summary

Cytokine release syndrome (CRS) is a complex of symptoms that can occur during severe infections, as a side effect of immunotherapy and allogeneic stem cell transplantation (ASCT). CRS is usually characterized by fever, vasodilatation and in severe cases can cause macrophage activation syndrome (MAS), multiple organ failure and death. The number of studies describing the impact of CRS on the outcomes of ASCT are limited. The aim of current study is to describe clinical features and significance for prognosis of CRS in patients after ASCT.

Patients and methods

The data was collected retrospectively by analysis of medical histories. Chi-square test and Mann-Whiteney test were used to describe statistical differences between groups. Survival analysis was conducted using Kaplan-Meier method and log-rank test. To describe cumulative incidence of GVHD and relapse, we used competing risk analysis and Grey test. The study enrolled 386 adult patients with acute leukemia who underwent allogeneic stem cell transplantation from January 2015 till December 2021 including 65 cases (16.8%) from matched related donors (MRD); 242 (62.7%), from matched unrelated donors (MUD), and 79 (20.5%), from haploidentical donors. 202 ASCT recipients were diagnosed with AML (52.3%); 184 (47.7%), with ALL. GVHD prophylaxis proceeded with PTBe (n=22, 5.7%), PTCy (n=340, 88.1%). 12 patients (3.1%) underwent TCR ab depletion. The CRS was defined as a fever occurring over the first 3 days after the transplant transfusion, without any signs of infection.

Results

CRS occurred in 16.8% of cases (n=65), with 12.4% (n=48) of grade 1-2. CRS of 3-4^th grade was observed in 4.4% of cases (n=17). CRS was documented more frequently after HaploSCT in 62.0% (n=49); after MRD, in 2 cases (3.1%); after MUD SCT, in 5.79% (n=14) of the cases (p<0.001). CRS mostly presented after ASCT of peripheral blood stem cells (19.3%, n=61), than after bone marrow grafts (5.71%, n=4) (p<0.001). The following laboratory abnormalities were observed more frequently in CRS group vs controls: median ferritin level was 3354 (132-135000) vs 1145 (351-40120), p<0.001; AST, 53 (13-1498) vs 29 (7-1004), p<0.001; ALT, 64 (7-1300) vs 36 (4.6-925), p<0.001; CRP, 128.6 (10.3-509) vs 30.5 (0.5-636), p<0,001; LDH, 241.7 (114-2253) vs 206.8 (91-3597), p<0.001. The median value of H-score (probability of MAS) was higher in CRS group: 77 (42-195) vs 61 (42-175), p<0.001, however, with relatively low specificity scores. Age, gender and conditioning intensity were not associated with CRS incidence. One-year overall survival in the CRS group was 45% (CI95% 30-59%) being 76% in the control group (CI95% 69-79%). Graft failure was also associated with CRS: 12.3% (n=8) vs 4% (n=13), p=0.014. Cumulative incidence of grade II-IV aGVHD and grade III-IV GVHD by the day +125 in CRS group versus non-CRS patients was as follows: 37.1% (CI95% 25.4-48.8%) vs 12.1% (CI95% 8-16%), p<0.001; 26.4% (CI95% 16.3-37.6%) vs 6.3% (CI95% 4-9%), p<0.001; cGVHD incidence was 22% (CI95% 11-34%) vs 22.4% (CI95% 18-27%) p=0.77.

Conclusions

The study demonstrated that existing H-score at CRS scale has low specificity at early post-allograft terms. Significant elevation of ALT, AST, CRP, LDH and ferritin levels was documented in CRS patients. CRS negatively affects overall survival through high incidence of aGVHD and graft failure.

Keywords

Cytokine release syndrome, allogenic stem cell transplantation, acute graft-versus-host disease.