COVID-19 during Early Phase of Autologous Stem Cell Transplantation

We present one of few cases of COVID-19 occurrence during the early phase of autologous hematopoietic stem cell transplantation. We observed an interesting correlation between the patient’s rapid clinical deterioration and myeloid reconstitution that cannot be assigned to engraftment syndrome. Our report emphasizes the need to investigate whether timely steroid therapy upon neutrophil engraftment in the setting of COVID-19 could limit the extent of lung injury and prevent ARDS. Furthermore, we discuss a significant issue of possible prolonged incubation of the virus in heavily pretreated hematological patients.

Inflammatory monocytes promote pre-engraftment syndrome and tocilizumab can therapeutically limit pathology in patients

Unrelated cord blood transplantation (UCBT) is an effective treatment for hematopoietic disorders. However, this attractive approach is frequently accompanied by pre-engraftment syndrome (PES), severe cases of PES are associated with enhanced mortality and morbidity, but the pathogenesis of PES remains unclear. Here we show that GM-CSF produced by cord blood-derived inflammatory monocytes drives PES pathology, and that monocytes are the main source of IL-6 during PES. Further, we report the outcome of a single arm, single-center clinical study of tocilizumab in the treatment of steroid-refractory severe PES patients (www.chictr.org.cn ChiCTR1800015472). The study met the primary outcome measure since none of the patients was nonrelapse death during the 100 days follow-up. The study also met key secondary outcomes measures of neutrophil engraftment and hematopoiesis. These findings offer a therapeutic strategy with which to tackle PES and improve nonrelapse mortality.

Evaluating the incidence of engraftment syndrome with different melphalan formulations in adult multiple myeloma and immunoglobulin light chain amyloidosis patients undergoing autologous hematopoietic cell transplantation

Background Engraftment syndrome (ES) is a common complication of autologous hematopoietic cell transplantation (HCT). The difference in incidence of ES between melphalan formulations has not been widely reported throughout the literature and would allow for a more comprehensive understanding of the advantages and disadvantages of both melphalan formulations. Patients and methods This retrospective, single-center, observational study evaluated 83 adult multiple myeloma and immunoglobulin light chain amyloidosis patients who received either propylene glycol-containing (PG) or propylene glycol-free (PG-free) melphalan 140 mg/m2 as single-agent conditioning chemotherapy for autologous HCT from May 31, 2015 to May 31, 2019. The primary outcome was to assess the incidence of ES, as defined using the Maiolino criteria, with both melphalan formulations. Secondary outcomes included an analysis of potential risk factors for the development of ES, as well as an evaluation of overall length of stay (LOS). Results The incidence of ES for PG and PG-free melphalan did not differ significantly, 14/39 (35.9%) and 12/44 (27.3%) (P = 0.4), respectively. No potential risk factors for ES were identified on multivariate logistic regression analysis. A statistically significant difference in number of days to engraftment was identified for PG and PG-free melphalan, 15.56 vs. 13.82 days (P = 0.01), respectively; although, this did not translate to a decrease in LOS, 19.9 vs. 18.59 days (P = 0.14). Conclusions The incidence of ES did not differ significantly between melphalan formulations. Future research is needed to determine whether the faster time to engraftment seen with PG-free melphalan may translate to a decrease in LOS.

Budesonide Prophylaxis Reduces Engraftment Syndrome (ES) after Autologous Hematopoietic Cell Transplantation (autoHCT) in Multiple Myeloma (MM)

Introduction: ES after autoHCT encompasses a continuum of peri-engraftment complications characterized by non-infectious fever, rash, diarrhea, and capillary leak features. ES is an increasingly recognized complication after autoHCT in MM, with the varying incidence reported, based on the diagnostic criteria used. ES is typically mild and self-limited in most patients, while a subset can develop severe complications. In this study, we explored whether the use of budesonide prophylaxis reduces ES rates in MM patients undergoing autoHCT. Methods: All patients who underwent autoHCT for MM from 12/2017 to 11/2019 were included after IRB approval at our institution. Beginning on 12/15/2018, as a quality improvement institutional initiative to reduce ES, budesonide 3 mg orally three times a day was initiated at day +5 post autoHCT and continued until the time of discharge. In patients developing ES, systemic steroids were started, and budesonide was discontinued. The efficacy of the intervention was compared with patients who did not receive prophylaxis prior to the study period. ES was defined according to the previously published criteria [T R Spitzer BMT 50, 469-475(2015)]. Patient demographics, disease, and treatment outcomes between the 2 groups were compared using Mann-Whitney and Chi-squared tests when appropriate. The primary outcome was the ES rates between the 2 groups. Multiple logistic regression was used to model ES rates with other predictors, including budesonide prophylaxis as the main effect. Length of stay (LOS) and 30-day readmission were the secondary endpoints. Results: Table 1 shows the patient-, disease- and treatment characteristics between no prophylaxis (N=148) and prophylaxis (N=109) groups. The two groups were well matched overall except for induction therapy and Karnofsky performance status (KPS). The rates of ES were significantly higher in the no prophylaxis group vs. prophylaxis group [69 (75%) vs. 23 (25%); p<0.001]. All patients in both groups were able to achieve neutrophil and platelet engraftment at day 28 and day 100, respectively. There was no significant difference in LOS [mean 15 (±3.2) vs. 16 (±2.8); p=0.27] and 30-day readmission [9 (6%) vs. 8 (7%); p=0.81] between the no prophylaxis and prophylaxis groups, respectively. On adjusted analysis, budesonide prophylaxis was associated with a significantly lower risk of developing ES compared to no prophylaxis groups [Odds ratio, OR 0.30 (95%CI: 0.17-0.53); p<0.0001]. No other significant predictors were identified for the development of ES. There was no difference in the 30-day readmission rates [OR 1.12 (95%CI: 0.41-3.03); p= 0.75], but a trend for shorter LOS in the prophylaxis group [7.3% reduction in LOS (95%CI: 14.4%- 0%); p=0.052] (Table 2). Conclusion: Our study concludes that the use of budesonide prophylaxis significantly reduces the risk of ES in MM patients undergoing autoHCT. Future large-scale randomized studies are needed to confirm these findings in patients undergoing autoHCT for MM and other diseases. Disclosures Dhakal: Celgene: Consultancy, Honoraria; Takeda: Consultancy, Other: Advisory Board; Sanofi: Research Funding; Amgen: Consultancy, Other: AdvIsory Board, Research Funding; Janssen: Consultancy, Other: Advisory Board, Research Funding; GSK: Consultancy, Research Funding, Speakers Bureau.