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Cytokine release syndrome after haploidentical hematopoietic cell transplantation: an international multicenter analysis
Abboud, R., Wan, F., Mariotti, J., Arango, M., Castagna, L., Romee, R., Hamadani, M., Chhabra, S.
Bone marrow transplantation. 2021
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Editor's Choice
Abstract
Haploidentical related donor transplantation (haplo-HCT) is associated with cytokine release syndrome (CRS). We conducted a multicenter retrospective study to analyze risk factors for CRS and outcomes after haplo-HCT. We included 451 patients from four academic centers receiving both peripheral blood and bone marrow grafts. Severe CRS was more common with PB vs. BM grafts (19.5% vs 4.9%, OR 2.9, p?=?0.05). Multivariable analysis identified recipient CMV sero-positivity, prior transplant, HCT-CI score and donor-recipient sex mismatch as risk factors for severe CRS. Outcomes were analyzed with no CRS as the comparison group. Overall survival (OS) was superior with mild CRS (HR 0.64, p?=?0.05) and worst with severe CRS (HR 2.12, p?=?0.0038). Relapse risk was significantly decreased in both mild CRS (HR 0.38, p?0.0001) and severe CRS (HR 0.17, p?0.0001) groups. The risk of non-relapse mortality was notably higher in severe CRS group (HR 8.0, p?0.0001), but not in mild CRS group. Acute GVHD was similar among groups. Chronic GVHD at 1 year was 18.5% for no CRS, 23% for mild CRS, and 4.3% for severe CRS (p?=?0.0023), with the competing risk of early mortality and short follow up of surviving patients contributing to the low chronic GVHD rates in the severe CRS group.
PICO Summary
Population
Patients receiving haploidentical bone marrow grafts in four academic centres in USA, South America and Europe (n=451)
Intervention
Retrospective study assessing the incidence and risk factors for cytokine release syndrome (CRS)
Comparison
Patients were grouped for analysis according to CRS grading, graft source and selected risk factors
Outcome
Severe CRS was more common with PB vs. BM grafts (19.5% vs 4.9%). Multivariable analysis identified recipient CMV sero-positivity, prior transplant, HCT-CI score and donor–recipient sex mismatch as risk factors for severe CRS. Outcomes were analysed with no CRS as the comparison group. Overall survival (OS) was superior with mild CRS (HR 0.64) and worst with severe CRS (HR 2.12). Relapse risk was significantly decreased in both mild CRS (HR 0.38) and severe CRS (HR 0.17) groups. The risk of non-relapse mortality was notably higher in severe CRS group (HR 8.0), but not in mild CRS group. Acute GVHD was similar among groups. Chronic GVHD at 1 year was 18.5% for no CRS, 23% for mild CRS, and 4.3% for severe CRS, with the competing risk of early mortality and short follow up of surviving patients contributing to the low chronic GVHD rates in the severe CRS group.
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Budesonide Prophylaxis Reduces the Risk of Engraftment Syndrome After Autologous Hematopoietic Cell Transplantation in Multiple Myeloma
Dhakal, B., Thapa, B., Dong, H., Tarima, S., Chhabra, S., D'Souza, A., Drobyski, W., Abid, M., Shah, N., Fenske, T., et al
Clinical lymphoma, myeloma & leukemia. 2021
Abstract
BACKGROUND Engraftment syndrome (ES) after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) encompasses a continuum of periengraftment complications characterized by noninfectious fever, rash, diarrhea, and capillary leak features. PATIENTS AND METHODS We analyzed the ES outcomes in 257 consecutive patients MM patients who underwent AHCT at our institution from 12/2017 to 11/2019 with budesonide prophylaxis (3 mg PO daily at day +5 post-AHCT till the time of discharge) (N = 109) and no prophylaxis (N = 148). RESULTS The rates of ES were significantly higher in the no prophylaxis group versus prophylaxis group [69 (46%) vs. 23 (21%); P< .001]. There was no significant difference in length of stay (LOS) [mean 15 (±3.2) vs. 16 (±2.8); P = .27] and 30-day readmission [9 (6%) vs. 8 (7%); P = .81] between the no prophylaxis and prophylaxis groups, respectively. On adjusted analysis, budesonide prophylaxis was associated with a significantly lower risk of developing ES [odds ratio (OR) 0.29 (95% confidence interval [CI], 0.16-0.51); P< .0001]. There was no difference in the 30-day readmission rates [OR 1.12 (95% CI, 0.41-3.03); P = .81], but a trend for shorter LOS in the prophylaxis group [7.3% reduction in LOS (95% CI, -14.4% to 0%); P = .06]. CONCLUSION Budesonide prophylaxis significantly reduces the risk of ES in MM patients undergoing AHCT. These promising results suggest the need for a randomized study investigate the role of budesonide for ES prophylaxis.
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Incidence and characteristics of engraftment syndrome after autologous hematopoietic cell transplantation in light chain amyloidosis
Badar, T., Khan, M. A., Szabo, A., Drobyski, W., Chhabra, S., Dhakal, B., Fenske, T. S., Hamadani, M., Hari, P., Jerkins, J. H., et al
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2019;:1-6
Abstract
Engraftment syndrome (ES), a complication of autologous hematopoietic cell transplantation (auto-HCT), can occur around the time of neutrophil recovery. We sought to identify the incidence of ES in light chain (AL) amyloidosis patients undergoing auto-HCT at our centre by evaluating 72 consecutive amyloidosis patients transplanted between 1999 and 2017. To assess trends in ES over time, patients were divided into two Eras (Era 1 = 1999-2008 and Era 2 = 2009-2017) based on year of auto-HCT. Twenty-two (31%) patients developed ES; three (16%) and 19 (36%) in Era 1 and 2, respectively (p = .1). Three (16%) and 51 (96%) patients in Era 1 and 2 received chemotherapy before auto-HCT (p = <.001). The most common symptoms observed with ES in addition to fever was diarrhoea (73%), rash (68%), weight gain (56%) and non-cardiogenic pulmonary oedema (23%). Day 100 post-auto-HCT haematological response (19.5% vs. 14%, p = .7) or post-transplant best organ response (23% vs. 36%, p = .2) were not significantly different in patients who did not or did develop ES, respectively. In this single centre series, we define the incidence and characteristics of ES in AL amyloidosis patients undergoing auto-HCT.
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Peripheral Blood Grafts for T-Cell Replete Haploidentical Transplantation Increase the Incidence and Severity of Cytokine Release Syndrome
Raj, R. V., Hamadani, M., Szabo, A., Pasquini, M. C., Shah, N. N., Drobyski, W. R., Shaw, B. E., Saber, W., Rizzo, J. D., Jerkins, J., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
T-cell replete post-transplant cyclophosphamide (PT-CY)-based protocols have led to increasing use of haploidentical allogeneic hematopoietic cell transplantation (haploHCT). With this approach, bidirectional alloreactivity causing non-engraftment or severe graft-versus-host disease (GVHD) are no longer major barriers to haploHCT. PT-CY eliminates alloreactive lymphocytes but spares CD34+ stem cells and regulatory T lymphocytes, resulting in reliable hematopoietic recovery with relatively low incidence of GVHD. The immediate post-haploHCT course, usually before PT-CY administration, is often complicated by cytokine release syndrome (CRS). The predictors of CRS and its effect on outcomes post-transplant have not been fully ascertained. We analyzed the outcomes of 66 patients who received haploHCT at our institution. Using published CRS criteria, we identified 48 patients who developed CRS. In multivariate analysis, peripheral blood grafts were significantly associated with grade ≥2 CRS, compared to bone marrow. Grade ≥2 CRS (compared to grade <2) was not associated with differences in overall survival or non-relapse mortality. Severe CRS was associated with a statistically non-significant trend toward higher incidence of grade III-IV acute GVHD, especially in the context of peripheral blood grafts. CRS is a common complication after T-cell replete peripheral blood haploHCT, but post-transplant survival outcomes may not be affected in those with severe CRS.