Search

Zhengqin Tian,1,* Qihang Man,1,* Yixin Yang,1,* Xiaomei Zhang,2,* Hexian Guan,1 Wenjing Gu,2 Ying Wang,1 Dandan Song,2 Rongmu Luo,1,2 Jingbo Wang1 1Department of Hematology, Aerospace Center Hospital, Beijing, People’s Republic of China; 2Department of Hematology, China Aerospace Science & Industry Corporation 731 Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rongmu Luo; Jingbo Wang, Email luorongmu@163.com; wangjingbo721@126.comAbstract: Engraftment syndrome (ES) is an early complication of hematopoietic stem cell transplantation (HSCT) characterized by fever and additional clinical manifestations including rash, diarrhea, lung infiltrates, weight gain, and neurological symptoms. Steroid-resistant ES following HSCT significantly affects the efficacy of transplantation and may even result in patient mortality. As ES essentially represents a cytokine storm induced by engrafted donor cells with interferon-gamma (IFN-γ) playing a central role, we hypothesized that emapalumab (an anti-IFN-γ monoclonal antibody) may be an effective approach to treat steroid-resistant ES. Here, we present a case report of a 14-year-old female patient who received a second haploidentical HSCT due to a relapse of acute myeloid leukemia. Nine days after the transplantation, the patient developed a fever and exhibited a poor response to antimicrobials (ceftazidime/avibactam). A few days later, the patient presented with a new-onset rash, weight gain, and impaired liver function, leading to a diagnosis of ES. Initial immunosuppressive (tacrolimus and mycophenolate mofetil) treatment failed to control the disease. On day 16 post-transplantation, the patient received two infusions of 50 mg of emapalumab. Following the initiation of emapalumab treatment, the patient’s fever returned to normal and ES was effectively controlled. This case report demonstrated that emapalumab had a possible efficacy for steroid-resistant ES and provided a novel therapeutic strategy to treat this clinical complication.Keywords: haploidentical hematopoietic stem cell transplantation, engraftment syndrome, emapalumab, acute myeloid leukemia

PurposeTo describe a case of severe, bilateral periorbital edema after hematopoietic stem cell transplantation.ObservationsA three-year old girl with metastatic neuroblastoma underwent the second of two tandem autologous peripheral blood stem cell transplants, complicated by engraftment syndrome. On post-engraftment day 11, she developed acute onset of severe periorbital edema. She was soon thereafter diagnosed with transplant-associated thrombotic microangiopathy with significant volume overload requiring treatment with eculizumab and etanercept. Periorbital edema resolved after four days with concurrent treatment of her underlying condition.Conclusions and importanceWe report an ocular manifestation related to complications of hematopoietic stem cell transplantation. This highlights a non-infectious etiology of eyelid swelling in the post-transplant, immunocompromised population.

Endothelial dysfunction underlies many of the major complications following hematopoietic cell transplantation (HCT), including transplant-associated thrombotic microangiopathy (TA-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), and engraftment syndrome (ES). Emerging evidence similarly implicates endothelitis and microangiopathy in severe COVID-19-related multi-system organ dysfunction. Given the overlap in these two illness states, we hypothesize that prior COVID-19 infection may increase risk for HCT-related endotheliopathies. This retrospective, multicenter study included patients aged 0-25 years who underwent autologous or allogeneic HCT for any indication between January 1, 2020 and September 21, 2021, with close attention to those infected with COVID-19 in either the six months prior to transplant or twelve months following transplant. Incidences of TA-TMA, VOD/SOS, and ES were compared among patients with COVID-19 infection pre-HCT and post-HCT, as well as with historical controls who were never infected with SARS-CoV-2. Those who underwent HCT following COVID-19 infection displayed significantly increased rates of TA-TMA compared to those who were never infected. Additionally, our data suggests a similar trend for increased VOD/SOS and ES rates, although this did not reach statistical significance. Therefore, a history of COVID-19 infection prior to undergoing HCT may be a nonmodifiable risk factor for endothelial-related complications following HCT. Further studies are warranted to better clarify this relationship among larger cohorts and in the era of the Omicron SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Engraftment syndrome (ES) is a non-infectious complication seen both in autologous and allogeneic hematopoietic stem cell transplants and is characterized by the presence of non-infectious fever, diarrhea, skin rash, pulmonary infiltration, pulmonary edema, and deranged renal and liver function tests This review will be delineating the incidence of ES, important differential diagnoses to be considered and management options. The literature search was done through various databases like PubMed, Google scholar, Cochrane library, and EMBASE. The incidence of engraftment syndrome was ranging from 8 to 50% in patients undergoing Autologous stem cell transplantation while the incidence was 10-77% in patients undergoing Allogeneic stem cell transplantation. Fever was the most commonly observed symptom of ES in both Autologous and Allogeneic stem cell transplantation while the second most frequently reported symptom was non-infectious diarrhea in patients undergoing autologous stem cell transplantation and Skin rash in patients with Allogeneic stem cell transplantation. Pro-inflammatory cytokines and immune response dysregulation were highlighted as the mechanism behind ES development. The significant difference between ES and aGVHD was observed based on cytokines, with IL-12, IL-1β, IL-6, TNF-α, and IFN-γ levels in plasma being higher in patients with ES as compared to patients with aGVHD. Intravenous methylprednisolone was used as the treatment of choice in the majority of the studies. Overall the incidence of ES was high in patients undergoing allogeneic hematopoietic stem cells transplantation. The survival in patients developing ES was less compared to those who did not develop ES. Engraftment syndrome is one of the complications following hematopoietic stem cell transplantation that need early identification, differentiation from infectious complications, and aGVHD and timely initiation of corticosteroids therapy. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction underlies many of the major complications following hematopoietic cell transplantation (HCT), including transplant-associated thrombotic microangiopathy (TA-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), and engraftment syndrome (ES). Emerging evidence similarly implicates endothelitis and microangiopathy in severe COVID-19-related multi-system organ dysfunction. Given the overlap in these two illness states, we hypothesize that prior COVID-19 infection may increase risk for HCT-related endotheliopathies. This retrospective, multicenter study included patients aged 0-25 years who underwent autologous or allogeneic HCT for any indication between January 1, 2020 and September 21, 2021, with close attention to those infected with COVID-19 in either the six months prior to transplant or twelve months following transplant. Incidences of TA-TMA, VOD/SOS, and ES were compared among patients with COVID-19 infection pre-HCT and post-HCT, as well as with historical controls who were never infected with SARS-CoV-2. Those who underwent HCT following COVID-19 infection displayed significantly increased rates of TA-TMA compared to those who were never infected. Additionally, our data suggests a similar trend for increased VOD/SOS and ES rates, although this did not reach statistical significance. Therefore, a history of COVID-19 infection prior to undergoing HCT may be a nonmodifiable risk factor for endothelial-related complications following HCT. Further studies are warranted to better clarify this relationship among larger cohorts and in the era of the Omicron SARS-CoV-2 variants.

Objective To investigate the relationship between plasma interleukin-4 (IL-4) and IL-17 levels and implantation syndrome (ES) after allogeneic hematopoietic stem cell transplantation (HSCT), and to determine the diagnostic and predictive markers of ES. Methods The plasma samples were collected from38 patients who underwent allogeneic HSCT (the study group) from 2017 to 2020 and their plasma concentrations of 12 cytokines were detected by enzyme-linked immunosorbent assay (ELISA) before HSCT, ten days after HSCT, onset of ES and onset of acute graft-versus-host disease (aGVHD) . At the same time, they were compared with 20 healthy subjects (the control group), receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to assess the sensitivity and specificity of IL-4 and IL-17 biomarkers for the diagnosis of ES. Results In the study group of the 38 patients, a total of 9 patients developed ES after HSCT, a total of 13 patients developed aGVHD, and 16 patients did not develop ES or aGVHD. Compared with the aGVHD group, the no ES group and aGVHD group, the plasma levels of IL-4 and IL-17 in the ES group were significantly increased, and the differences were statistically significant (P <0.05) . After HSCT, the plasma levels of IL-4 and IL-17 in ES patients were significantly up-regulated compared with those before transplantation, and the expression levels were down-regulated after treatment compared with those in ES patients, and the differences were statistically significant (P<0.05), but there was no significant difference compared with the levels before HSCT (P>0.05). On the 10th day after HSCT, the levels of IL-4 and IL-17 in patients with ES were significantly higher than those in patients without ES, and the differences were statistically significant (P <0.05), and the increased expression levels preceded clinical diagnosis. At the detection time point, the AUC of IL-4 predicting ES was 0. 947 d±0.024, the specificity was 0.93% and the sensitivity was0. 72%;the AUC of IL-17 predicting ES was 0. 853 d±0. 056, the specificity was 0.83% and the sensitivity was 0.75 %;the AUC of IL-4+IL-17 predicting ES was 0. 896±0.031, the specificity was 0. 90% and the sensitivity was 0.73%. Conclusion IL-4 and IL-17 may serve as early biomarkers for the diagnosis and curative evaluation of ES after allogeneic HSCT. [ABSTRACT FROM AUTHOR]

Background: Engraftment syndrome (ES) is a clinical condition that may occur during neutrophil recovery after hematopoietic stem cell transplantation (HSCT). Diagnosis is challenging because of the varying diagnostic criteria and the controversial relationship between ES and graft-versus-host disease (GVHD)., Objective: To investigate the incidence of ES and its relationship with GVHD in patients undergoing allogeneic HSCT at our institution., Study Design: This retrospective cohort study included patients who underwent allogeneic HSCT (alloHSCT) at a Brazilian tertiary hospital between January 2015 and December 2016. ES was diagnosed based on the Spitzer or Maiolino criteria., Results: Of the 79 patients who underwent alloHSCT, three presented with graft failure and were excluded from the analysis. The incidence of ES, according to both Spitzer's and Maiolino's criteria, was 16.5 % and 9.8 % in patients older than 14 years and 28.6 % in children, respectively, with a significant correlation (P < 0.05, Pearson's chi-squared test). ES was associated with prolonged hospitalization (P = 0.01; Student's t-test). No correlation was observed between acute GVHD and ES. There was a positive correlation between the use of broad-spectrum antibiotics against multidrug-resistant bacteria and ES development (P < 0.05, Pearson's chi-squared test)., Conclusions: The general incidence of ES in this cohort was consistent with that reported in the literature. Remarkably, ES was associated with prolonged hospitalization (14 days longer than in patients without ES). Moreover, patients who used antibiotics against multidrug-resistant bacteria had a higher incidence of ES., Competing Interests: Declaration of competing interest The authors have no competing interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The paper aims to review current knowledge regarding the variable pathogenic mechanisms, as well as therapeutic options for ARDS in acute hematologic malignancy patients. Data collection: We provide an overview of ARDS in patients with acute hematologic malignancy, from an etiologic perspective. We searched databases such as PubMed or Google Scholar, including articles published until June 2022, using the following keywords: ARDS in hematologic malignancy, pneumonia in hematologic malignancy, drug-induced ARDS, leukostasis, pulmonary leukemic infiltration, pulmonary lysis syndrome, engraftment syndrome, diffuse alveolar hemorrhage, TRALI in hematologic malignancy, hematopoietic stem cell transplant ARDS, radiation pneumonitis. We included relevant research articles, case reports, and reviews published in the last 18 years. Results: The main causes of ARDS in acute hematologic malignancy are: pneumonia-associated ARDS, leukostasis, leukemic infiltration of the lung, pulmonary lysis syndrome, drug-induced ARDS, radiotherapy-induced ARDS, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, hematopoietic stem cell transplantation-related ARDS, transfusion-related acute lung injury. Conclusions: The short-term prognosis of ARDS in acute hematologic malignancy relies on prompt diagnosis and treatment. Due to its etiological heterogeneity, precision-based strategies should be used to improve overall survival. Future studies should focus on identifying the relevance of such etiologic-based diagnostic strategies in ARDS secondary to acute hematologic malignancy. [ABSTRACT FROM AUTHOR]

Purpose: To describe a case of severe, bilateral periorbital edema after hematopoietic stem cell transplantation. Observations: A three-year old girl with metastatic neuroblastoma underwent the second of two tandem autologous peripheral blood stem cell transplants, complicated by engraftment syndrome. On post-engraftment day 11, she developed acute onset of severe periorbital edema. She was soon thereafter diagnosed with transplant-associated thrombotic microangiopathy with significant volume overload requiring treatment with eculizumab and etanercept. Periorbital edema resolved after four days with concurrent treatment of her underlying condition. Conclusions and Importance: We report an ocular manifestation related to complications of hematopoietic stem cell transplantation. This highlights a non-infectious etiology of eyelid swelling in the post-transplant, immunocompromised population.

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. [ABSTRACT FROM AUTHOR]

Chemotherapy while revolutionizing cancer management by improving survival and quality of life; is also associated with several adverse effects. Lung is the most common organ affected in chemotherapy-related complications, due to either drug toxicity or more commonly due to infections caused by immunosuppression and less commonly due to immune-mediated injury. Radiology, when used in combination with clinical and lab data, can help reach the specific diagnosis or narrow down the differentials. The common radiological patterns of drug toxicity include pulmonary interstitial and airway infiltrates, diffuse alveolar damage, nonspecific interstitial pneumonia, eosinophilic pneumonia, cryptogenic organizing pneumonia, pulmonary hemorrhage, edema and hypertension. Cancer patients are immunosuppressed due to the underlying malignancy itself or due to therapy and are prone to a gamut of opportunistic infections including viral, bacterial, fungal and mycobacterial pathogens. Immune reconstitution inflammatory syndrome (IRIS), a well-known complication in HIV, is now being increasingly recognized in non-HIV patients with immunosuppression. Engraftment syndrome is specifically seen following hematopoietic stem cell transplant during neutrophil recovery phase. Pulmonary involvement is frequent, causing a radiological picture of noncardiogenic pulmonary edema. Thus, radiology in combination with clinical background and lab parameters helps in detecting and differentiating various causes of pulmonary complications. This approach can help alter potentially toxic treatment and initiate early treatment depending on the diagnosis.

Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective treatment for systemic sclerosis (SSc), but it also can cause immunological adverse events (iAEs). Therefore, we aimed to determine the frequency of iAEs [engraftment syndrome (ES) and secondary autoimmune disorder (sAD)] and to identify potential risk factors for their development in a retrospective analysis on 22 patients similarly transplanted due to SSc. While nine patients (41%) suffered from ESs, seven sADs occurred in six patients (27%). Patients who developed ES were older in our cohort (52.45 vs. 42.58 years, p =.0433, Cohen's d = 0.86), and cardiac involvement by SSc was associated with development of ES (OR = 40.11, p =.0017). Patients with manifestation of sAD had a higher modified Rodnan skin score (mRSS) reduction after aHSCT (90.50% vs. 60.00%, p =.0064, r =.65). Thus, IAEs are common after aHSCT for SSc and can occur in different stages during and after aHSCT with characteristic clinical manifestations. Good cutaneous response after aHSCT might be considered as a risk factor for sAD, and higher age at aHSCT and cardiac involvement might be considered as risk factors for the development of ES. [ABSTRACT FROM AUTHOR]

• Engraftment Syndrome and acute graft-versus-host disease are two major post-transplant complications. • ES was characterized by a significant increase in level of IL-5, IL-6, IL-8 and sIL-2R. • aGvHD was associated with a significant upregulation of IL-6, IL-5, IL-10 and sIL-2R. • Pronounced shift from naïve to memory cells was observed in ES patients. • Cytokine profiles can serve as potential indicators for distinguishing ES from aGvHD. The underlying biology of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) is not fully elucidated, and the extent of its overlap with acute graft-versus-host disease (aGvHD) remains unclear. In order to establish potential indicator to distinguish ES more accurately, we conducted a retrospective analysis of cytokine levels during HSCT. A total of 121 consecutive adult patients who underwent HSCT were enrolled in this study. Blood samples for interleukin (IL)-2, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-1β, IL-12p70, interferon (IFN)-γ, IFN-α, tumor necrosis factor alpha (TNF-α) and C-reactive protein CRP were regularly assessed after transplantation and during transplantation related adverse events. Additionally, the balance of naïve, central memory and effector memory of CD4+ and CD8+ was analyzed around 30 and 60 days after stem cell infusion, respectively. Thirty (24.79 %) and 33 (27.27 %) patients were diagnosed with ES and aGvHD, respectively. ES was characterized by a significant increase in level of IL-5, IL-6, IL-8 and sIL-2R, while aGvHD was associated with a significant upregulation of IL-6, IL-5, IL-10 and sIL-2R in the patients from grade I to grade IV. Notably, patients got much higher levels of IL-6, IL-5 and sIL-2R when developed to ES than to aGvHD. Moreover, a pronounced shift from naïve to memory cells, both in CD4+ and CD8+ subsets, was found in ES patients. These findings suggest that cytokine profiles could serve as potential indicators for detecting and differentiating ES and aGvHD, enabling timely clinical intervention. Prospective clinical trials involving larger, independent patient cohorts are required to validate these observations. [ABSTRACT FROM AUTHOR]

Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The paper aims to review current knowledge regarding the variable pathogenic mechanisms, as well as therapeutic options for ARDS in acute hematologic malignancy patients. Data collection: We provide an overview of ARDS in patients with acute hematologic malignancy, from an etiologic perspective. We searched databases such as PubMed or Google Scholar, including articles published until June 2022, using the following keywords: ARDS in hematologic malignancy, pneumonia in hematologic malignancy, drug-induced ARDS, leukostasis, pulmonary leukemic infiltration, pulmonary lysis syndrome, engraftment syndrome, diffuse alveolar hemorrhage, TRALI in hematologic malignancy, hematopoietic stem cell transplant ARDS, radiation pneumonitis. We included relevant research articles, case reports, and reviews published in the last 18 years. Results: The main causes of ARDS in acute hematologic malignancy are: pneumonia-associated ARDS, leukostasis, leukemic infiltration of the lung, pulmonary lysis syndrome, drug-induced ARDS, radiotherapy-induced ARDS, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, hematopoietic stem cell transplantation-related ARDS, transfusion-related acute lung injury. Conclusions: The short-term prognosis of ARDS in acute hematologic malignancy relies on prompt diagnosis and treatment. Due to its etiological heterogeneity, precision-based strategies should be used to improve overall survival. Future studies should focus on identifying the relevance of such etiologic-based diagnostic strategies in ARDS secondary to acute hematologic malignancy.

We have recently reported a new method for detecting T-cell-derived extracellular vesicles (EVs), CD3+CD4+EVs,CD3+CD8+EVs, and CD3+HLA-DR+EVs. In our previous study, CD3+HLA-DR+EVs were released profusely by CD8+T cells, only moderately by T helper1 (Th1) CD4+T cells, and very little from Th2 CD4+T cells in vitro. EVs were measured sequentially in patients undergoing hematopoietic stem cell transplantation (HSCT), and their relationship to GVHD was investigated in comparison with other conventional biomarkers. We analyzed peripheral blood samples from 20 patients (13 children and 7 adults) who underwent HSCT at Tokyo Medical and Dental University Hospital. CD3+CD4+EV and CD3+CD8+EV levels specifically correlated with the CD4+ and CD8+T lymphocyte counts, respectively. CD3+CD8+EVs and CD3+HLA-DR+EVs increased in GVHD and reflected the persistence of GVHD more specifically than soluble IL-2 receptor (sIL-2R). In engraftment syndrome, sIL-2R was markedly elevated, but CD3+HLA-DR+EVs were not. Furthermore, ferritin and sIL-2R markedly increased in hemophagocytic syndrome (HPS) that developed before engraftment; however, the change in CD3+HLA-DR+EVs was marginal. CD3+CD4+, CD3+CD8+, and CD3+HLA-DR+EVs efficiently reflect the cell-mediated immune response, and CD3+CD8+EVs and CD3+HLA-DR+EVs are more useful than other conventional biomarkers, such as sIL-2R, for monitoring and evaluation of acute GVHD. [ABSTRACT FROM AUTHOR]

Rationale: Acute respiratory distress syndrome (ARDS) is a common complication after hematopoietic stem cell transplantation (HCT) and is a major contributor to nonrelapse mortality. Objectives: To better understand pretransplant risk factors for developing ARDS after HCT. Methods: This is a single-center observational study comparing risk factors for ARDS development in 164 patients who went on to develop post-HCT ARDS compared with 492 patients who did not. The patients were matched 1 to 3 on age, sex, type of transplant (allogeneic vs. autologous), and underlying disease. Pertinent risk factors were analyzed separately in multivariable conditional logistic regression after adjustment for a priori variables known to be associated with ARDS development. Results: Patients with ARDS were more likely to have a lower pretransplant pulmonary function as measured by forced vital capacity (FVC) (odds ratio [OR], 0.54 [0.42-0.70] per liter increase in FVC; P < 0.001), forced expiratory volume in one second (FEV1) (OR, 0.52 [0.38-0.71] per liter increase in FEV1; P < 0.001) and diffusing capacity (OR, 0.92 [0.88-0.96] per ml/min/mm Hg increase in diffusing capacity; P < 0.001). Several laboratory indices were predictive of subsequent ARDS development including elevated AST (aspartate aminotransferase) (OR, 1.01 [1.00-1.01]; P < 0.008), lower serum albumin (OR, 0.44 [0.30-0.66]; P < 0.001), lower pretransplant hemoglobin (OR, 0.82 [0.73-0.92]; P = 0.001), and lower leukocyte count (OR, 0.88 [0.79-0.99]; P < 0.03). Patients who went on to develop ARDS were more likely to have been hospitalized in the year before the transplant (OR, 1.11 [1.04-1.20]; P = 0.003), and required invasive or noninvasive ventilation during that hospitalization. Lastly, patients with ARDS were significantly more likely to have received carboplatin, thalidomide, methotrexate, and cisplatin than the non-ARDS control subjects. Conclusions: Several risk factors for developing ARDS after HCT are identifiable at the time of transplantation, well before the development of critical illness and ARDS. The identification of risk factors long before ARDS develops is relatively unique to the HCT population. Further work is needed to develop usable risk prediction tools in this setting. [ABSTRACT FROM AUTHOR]

Engraftment syndrome (ES) following autologous stem cell transplantation (ASCT) at the time of neutrophil recovery may comprise fever, rash, pulmonary edema, or diarrhea. Usually, ES is easily manageable using corticosteroids but may prolong hospitalization. In two consecutive cohorts of subsequent patients with myeloma, lymphomas, and testicular/germ cell cancer, we assessed the benefit of corticosteroid use to prevent incidence and severity of ES following ASCT. Whereas Cohort A (82 patients) received no prophylactic corticosteroids, corticosteroids (4 mg dexamethasone oral daily) were started in Cohort B (60 patients) at day +9 until day +13 following ASCT. Steroid prophylaxis significantly reduced the incidence of ES (6/60; 10% vs. 33/82; 40%; p < 0.001). Hospitalization duration was longer in patients with ES than in patients without ES within both cohorts (in Cohort A: p = 0.007; and B: p = 0.011), but did not differ significantly between cohorts A and B. Finally, in Cohort A, there was a trend to an inferior 2‐year overall survival rate in patients without ES compared to patients with ES (p = 0.067), but definite conclusions are not yet allowed. Our results suggest that corticosteroid prophylaxis from days +9 to +13 following ASCT significantly reduces the risk of ES and shortens hospitalization duration. [ABSTRACT FROM AUTHOR]

Engraftment syndrome (ES) is one of the most common complications in the early phase after autologous hematopoietic stem cell transplantation (ASCT), and we aimed to evaluate the incidence and risk factors for ES patients receiving ASCT in the era of plerixafor-based mobilization. A total of 294 were enrolled, and 16.0% (n = 47) experienced ES after ASCT. The main clinical manifestations were fever (100%), diarrhea (78.7%), skin rash (23.4%), and hypoxemia/pulmonary edema (12.8%). Plerixafor-based mobilization was associated with higher counts of CD3 + cells, CD4 + cells, and CD8 + cells in grafts. In univariate analysis of the total cohort, age ≥60 years, receiving ASCT at complete remission (CR), higher number of mononuclear cell (MNC), CD3 + cell counts, CD4 + cells as well as CD8 + cells transfused and plerixafor-based mobilization were associated with ES after ASCT. Multivariate analysis showed that age ≥60 years ( P = .0014), receiving ASCT at CR ( P = .002), and higher number of MNC transfused ( P = .026) were associated with ES in total cohort. In plasma cell disease subgroup, age ≥60 years ( P = .013), plerixafor-based mobilization ( P = .036), and receiving ASCT at CR ( P = .002) were associated with ES. Patients with more risk factors had a higher risk of ES. The 1-year probabilities of relapse, non-relapse mortality, and survival were comparable between patients with and without ES. Thus, plerixafor-based mobilization may influence the composition of T lymphocytes in grafts and increase the risk of ES, particularly in patients with plasma cell disease., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the Chinese Medical Association (CMA) and Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College (IHCAMS).)

Introduction: Respiratory complications due to engraftment syndrome (ES) in the post-hematopoietic stem cell transplant (HSCT) setting can lead to acute respiratory failure (ARF). Outcomes of children developing ARF due to engraftment are unknown.Methods: We conducted a retrospective analysis of 1,527 pediatric HSCT recipients and identified children who developed ARF due to ES over a 17-year period. Thirty patients that developed ARF and required invasive mechanical ventilation (IMV) due to ES were included in this study.Results: The survival rate for our cohort was 80% [alive at intensive care unit (ICU) discharge]. The most common underlying primary disease was hematologic malignancy, and 67% of children underwent allogeneic HSCT. Further, 73% required vasopressor drips and 23% underwent dialysis. Survivors had a shorter median ICU length of stay than did non-survivors (15 vs. 40 days, respectively, p = 0.01). Survivors had a significantly lower median cumulative fluid overload % on days 4 and 5 after initiation of IMV than did non-survivors (2.8 vs. 14.0 ml/kg, p = 0.038 on day 4, and 1.8 vs. 14.9 ml/kg, p = 0.044 on day 5, respectively).Conclusion: Our results suggest that children who develop ARF during engraftment have better ICU survival rates than do those with other etiologies of ARF post-HSCT. Furthermore, fluid overload contributes to mortality in these children; therefore, strategies to prevent and address fluid overload should be considered.

Introduction: Respiratory complications due to engraftment syndrome (ES) in the post-hematopoietic stem cell transplant (HSCT) setting can lead to acute respiratory failure (ARF). Outcomes of children developing ARF due to engraftment are unknown. Methods: We conducted a retrospective analysis of 1,527 pediatric HSCT recipients and identified children who developed ARF due to ES over a 17-year period. Thirty patients that developed ARF and required invasive mechanical ventilation (IMV) due to ES were included in this study. Results: The survival rate for our cohort was 80% [alive at intensive care unit (ICU) discharge]. The most common underlying primary disease was hematologic malignancy, and 67% of children underwent allogeneic HSCT. Further, 73% required vasopressor drips and 23% underwent dialysis. Survivors had a shorter median ICU length of stay than did non-survivors (15 vs. 40 days, respectively, p = 0.01). Survivors had a significantly lower median cumulative fluid overload % on days 4 and 5 after initiation of IMV than did non-survivors (2.8 vs. 14.0 ml/kg, p = 0.038 on day 4, and 1.8 vs. 14.9 ml/kg, p = 0.044 on day 5, respectively). Conclusion: Our results suggest that children who develop ARF during engraftment have better ICU survival rates than do those with other etiologies of ARF post-HSCT. Furthermore, fluid overload contributes to mortality in these children; therefore, strategies to prevent and address fluid overload should be considered. [ABSTRACT FROM AUTHOR]

Engraftment syndrome (ES) is a poorly understood condition which continues to present a significant cause of morbidity following haematopoietic stem cell transplantation (HSCT). Yet a standard approach to diagnosis and treatment of ES remains elusive and has the potential to impact patient outcomes. A literature search was performed using the databases ProQuest Health, PubMed, Medline and Embase. Included studies were published in English from 2001‐2019 that reported on engraftment syndrome following HSCT. Articles were organized by study design, ES diagnostic criteria, symptom classification and treatment. The review consolidated an array of literature relating to all types of HSCT. Timing of ES onset, risk factors and outcomes were compared within the literature. Signs and symptoms of reported ES were collated to establish a concise set of diagnostic criteria that can provide rapid recognition. The use of a standard approach to ES diagnosis has the potential to improve patient outcomes and provide a uniform approach to future research. [ABSTRACT FROM AUTHOR]

Engraftment syndrome (ES) has been associated with the surge of neutrophils and cytokines, which is similar to the presumed underlying pathophysiology behind acute graft-versus-host disease (aGVHD). However, there has been no meta-analysis to evaluate the association; therefore, the team attempted to verify an association between ES and aGVHD through meta-analysis. The team searched for titles of articles in MEDLINE (PubMed), the Cochrane Library, and the EMBASE database up until December 2018 that evaluated the association between ES and aGVHD and conducted a random effect meta-analysis of 8 studies involving a total of 1,945 participants to report the pooled odds ratio (OR) for association of ES and aGVHD. The team found a significantly increased odds of developing aGVHD in patients with ES with the pooled OR of 2.76 (95% confidence interval [CI]: 1.64-4.63) and an I2 = 64.5%. In conclusion, patients with ES have significantly higher odds of developing aGVHD compared to patients without ES. [ABSTRACT FROM AUTHOR]

Postautologous stem cell transplantation (ASCT) engraftment syndrome (ES) is a well‐known clinical complication; however, many aspects remain largely controversial. In this retrospective study, we reviewed records of 156 ASCTs done over 2 years in our institution. Our results show that 45 (34 multiple myeloma/amyloidosis and 11 lymphoma) of 156 adult patients (29%) were diagnosed with ES. Patients with ES were significantly more likely to have fever, rash, and diarrhea upon engraftment. Risk factors for ES included shorter time from diagnosis to ASCT (P =.029), and lower number of pretransplant treatment regimens (0.012). Post‐ASCT, patients with ES had significantly lower absolute lymphocyte count on first engraftment day (P =.014). Most ES patients received treatment with steroids. Initial dose of prednisone/methylprednisolone was 2 mg/kg (n = 34), 1 mg/kg (n = 7), while four patients received 1000 mg IV with median length of therapy 7.5 days. One ES patient with inadequate steroid therapy died of ES complications, while another developed respiratory failure requiring intubation but had full recovery with steroids treatment. In conclusion, patients with shorter time from diagnosis to ASCT and with less prior therapy are more likely to develop ES. Overall survival of ES patients has improved with greater awareness of the diagnosis and earlier use of steroids. [ABSTRACT FROM AUTHOR]

Engraftment syndrome (ES) is a clinical syndrome that occurs in the early neutrophil recovery phase following hematopoietic stem cell transplant (HSCT). Although also described for allogenic HSCT, it is basically diagnosed in the context of autologous HSCT. We retrospectively reviewed 171 consecutive HSCTs performed between January 2013 and January 2015 in our Bone Marrow Transplant (BMT) unit and analyzed all cases of noninfectious fever and strong clinical features suggestive of ES in the peri-engraftment period for up to 7 days. We observed the incidence of ES to be 12.3% (16/130) in the autologous and 4.8% (2/41) in the allogeneic cohort. Among plasma cell disorders, which constitute 50% of our study population, the incidence of ES was 19.7%. Among the ES cases of autologous transplants, 81.2% (13/16) patients satisfied the Maiolino criteria (MC) and 87.5% (14/16) patients the Spitzer diagnostic criteria (SC). A total of 68.7% (11/16) patients satisfied both MC and SC, and two patients (12.5%) did not satisfy either (MC− SC−). There was no significant difference in days of hospitalization and usage of supportive care between ES and non-ES patients, and there was no mortality due to ES. On univariate analysis, female patients (p < 0.013) and those with diagnosis of a plasma cell disorder (p < 0.03) had higher risk of ES. In conclusion, the incidence of ES in our study population is consistent with that of many others, but severity evaluation needs exploration in larger cohorts with pragmatically modified diagnostic criteria.

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. [ABSTRACT FROM AUTHOR]

Engraftment syndrome (ES) is a known complication of autologous hematopoietic stem cell transplant during neutrophil recovery. There is a limited amount of data available comparing the incidence of ES with post-transplant granulocyte colony-stimulating factor versus granulocyte macrophage colony-stimulating factor (GM-CSF), specifically in patients with multiple myeloma. Our retrospective review of 156 patients at a single center showed that GM-CSF was associated with a higher incidence of ES compared with G-CSF (32% versus 8% of patients, P <.001) and that development of ES was associated with a 32.9% (P <.001) longer hospital stay. This suggests that the choice of growth factor could possibly contribute to the development of ES and the associated costs of increased medical care. [ABSTRACT FROM AUTHOR]

Engraftment Syndrome (ES) maybe observed in patients who undergo autologous stem cell transplant (SCT). To investigate clinical criteria for ES diagnosis and analyse the risk factors for this complication, we reviewed all auto-SCT cases (Lymphoma and Myeloma) performed during the past 9 years at two tertiary care centres. We analysed all patients with a non-infectious fever, developed within 7 days of engraftment (first day of ANC of 500 on two consecutive days) in 178 patients undergoing autologous stem cell transplant. A total of 46/178 (25.8%) patients developed non-infectious fever and one or more clinical signs of ES within 7 days of engraftment. In all, 29 (61%) fulfilled the Maiolino and 12 (26%) the Spitzer criteria. The incidence of engraftment syndrome using the Maiolino criteria in our study was 29 (15%), which compares well with Spanish study (13% using same criteria) and the original Maiolino study (20%). All patients with ES satisfactorily recovered and discharged with a median of 20 days from hospital. There was no significant difference in number of days of hospitalisation and days of antibiotics between the ES and non ES arms. All patients recovered without any morbidity and only 1 (2%) patient required readmission for fungal pneumonitis. 8 (17%) patients required ICU admission due to delay in initiation of steroids. None of the factors including number of chemotherapy cycles, conditioning regime, disease status, CD34 collection, growth factors and day of WBC engraftment except female (p = 0.064) were statistically significant (in univariate or multivariate analysis). Our study shows that engraftment syndrome is common in autologous transplant setting. Maiolino criteria to diagnose ES is more sensitive in our setting. If detected and treated early there is not much morbidity or mortality related to ES. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for many pediatric diseases. Cellular immunotherapy, such as the use of chimeric antigen receptor T cells, has emerged recently as a highly effective modality to treat refractory lymphoid malignancies. Although HSCT and cellular immunotherapy are now considered essential parts of the current therapeutic armamentarium, both are associated with a wide range of acute complications, many of which are unique to these treatment modalities. These acute complications are seen not only in hospitalized patients but also in patients in the ambulatory setting, including the emergency department. Emergency care providers will need to be able to recognize these complications and provide appropriate initial assessment and management. In this review, we describe the acute complications associated with HSCT and cellular immunotherapy, with the emphasis on their recognition, workup, and treatment. [ABSTRACT FROM AUTHOR]