Pre-engraftment syndrome: clinical significance and pathophysiology

Lee, Young-Ho; Rah, Wee-Jin

doi:10.5045/br.2016.51.3.152

Cited by 12 publications

(8 citation statements)

References 11 publications

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“…Overall, the dose level: 1.0 × 10 6 cells/kg was well-tolerated with no infusional toxicity or impact on engraftment. Specific presentation of high fevers associated with non-specific inflammatory rash and elevated IL-6 levels in the post-transplant period of patients receiving fucosylated UCB Tregs may be consistent with pre-engraftment syndrome [ 6 , 7 ]. It is unclear whether the short course of systemic steroids impacted efficacy of infused UCB Tregs, since all patients developed GVHD, however, it is important to consider that the infused donor T cells were significantly higher (12-356 times) than the infused Tregs.…”

Section: Discussionmentioning

confidence: 99%

Third party, umbilical cord blood derived regulatory T-cells for prevention of graft versus host disease in allogeneic hematopoietic stem cell transplantation: feasibility, safety and immune reconstitution

et al. 2018

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Incubation of umbilical cord blood (UCB) derived regulatory T-cells (Tregs) with fucosyltransferase enzyme improves their ability to home to the target tissue to prevent graft vs. host disease (GVHD). We report results of 5 patients (Double UCB Transplant, n=2; Peripheral Blood Matched Unrelated Donor Transplant, n=3) who received UCB-Tregs (Dose level = 1×106/kg), infused one day prior to the donor graft. All patients received their designated UCB-Treg dose without any infusion reaction. The ratio of conventional T-cells in donor graft was at least 10 times higher than infused UCB-Tregs (ratio range, 12-356). All patients engrafted at median of 13 days (range, 8-17 days). One patient died due to brain hemorrhage on day 45. A bi-modal increase of plasma IL-10 level occurred on day 7 and day 21 and notably, plasma IL-2 level dropped significantly in all patients at Day 7. All evaluable patients developed ≥grade II acute GVHD and at 1 year follow up, all were alive and without evidence of disease relapse. No increase in the chronic GVHD biomarkers (REG3a and Elafin) was observed at day 7. At the time of last follow up, all evaluable patients were off immune-suppression. Stage 2 of this clinical trial examining UCB-Treg at dose level= 1×107/kg is currently underway.

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Section: Discussionmentioning

confidence: 99%

Third party, umbilical cord blood derived regulatory T-cells for prevention of graft versus host disease in allogeneic hematopoietic stem cell transplantation: feasibility, safety and immune reconstitution

et al. 2018

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“… 103 , 104 Although a uniform definition is lacking, PES has overlapping features with hyperacute GVHD and engraftment syndrome (ES), which are commonly characterized by noninfectious fever, erythematous rash, diarrhea, jaundice, and capillary leak syndrome (CLS), including noncardiogenic fluid retention or pulmonary manifestations such as tachypnea, hypoxemia, and pulmonary edema, before neutrophil engraftment. 103 , 104 , 105 The pathogenesis and severity classification are still not clear; PES may be caused by cytokine storms associated with toxicities of the conditioning regimen, GVHD prophylaxis drugs, DMSO, G‐CSF, or mismatched antigens by donor T cells. However, heterogeneity of the conditioning regimens and specific GVHD prophylaxis strategies may account for the different ranges (20‐78%) of the reported incidences of PES.…”

Section: Major Strategies For Improvementmentioning

confidence: 99%

“…A randomized study is required to determine whether omitting ATG confers a survival advantage for patients undergoing UCBT.4.5 | Pre-engraftment syndromePre-engraftment syndrome (PES) was initially described as a preengraftment immune reaction (PIR) in 2005 and was first proposed by Professor Young-Ho Lee 103,104. Although a uniform definition is lacking, PES has overlapping features with hyperacute GVHD and engraftment syndrome (ES), which are commonly characterized by noninfectious fever, erythematous rash, diarrhea, jaundice, and capillary leak syndrome (CLS), including noncardiogenic fluid retention or pulmonary manifestations such as tachypnea, hypoxemia, and pulmonary edema, before neutrophil engraftment [103][104][105]. The pathogenesis and severity classification are still not clear; PES may be caused by cytokine storms associated with toxicities of the conditioning regimen, GVHD prophylaxis drugs, DMSO, G-CSF, or mismatched antigens by donor T cells.…”

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confidence: 99%

Umbilical Cord Blood Transplantation: Still Growing and Improving

Zhu

Tang

Sun

2021

Stem Cells Translational Medicine

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Umbilical cord blood transplantation (UCBT) has been performed in the clinic for over 30 years. The biological and immunological characteristics of umbilical cord blood (UCB) have been re-recognized in recent years. UCB, previously considered medical waste, is rich in hematopoietic stem cells (HSCs), which are naïve and more energetic and more easily expanded than other stem cells. UCB has been identified as a reliable source of HSCs for allogeneic hematopoietic stem cell transplantation (allo-HSCT). UCBT has several advantages over other methods, including no harm to mothers and donors, an off-the-shelf product for urgent use, less stringent HLA match, lower incidence and severity of chronic graft-vs-host disease (GVHD), and probably a stronger graft-vs-leukemia effect, especially for minimal residual disease-positive patients before transplant. Recent studies have shown that the outcome of UCBT has been improved and is comparable to other types of allo-HSCT. Currently, UCBT is widely used in malignant, nonmalignant, hematological, congenital and metabolic diseases. The number of UCB banks and transplantation procedures increased exponentially before 2013. However, the number of UCBTs increased steadily in Asia and China but decreased in the United States and Europe year-on-year from 2013 to 2019. In this review, we focus on the development of UCBT over the past 30 years, the challenges it faces and the strategies for future improvement, including increasing UCB numbers, cord blood unit selection, conditioning regimens and GVHD prophylaxis for UCBT, and management of complications of UCBT.

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“…Los factores de riesgo para su aparición y fisiopatología son poco claros; no obstante, la mayoría de los investigadores señala que es más común después de recibir el acondicionamiento mieloablativo, además de su relación con elevado riesgo de enfermedad injerto contra huésped aguda. 12 El diagnóstico de la enfermedad se establece por los hallazgos clínicos, mediante los criterios de Spitzer, incluso no debe haber recuperación en la cifra de neutrófilos al momento de la aparición de los síntomas. 13 Deben considerarse tres criterios mayores, o dos criterios mayores y uno o más de los criterios menores, sin características clínicas ni patológicas de síntomas y signos de enfermedad injerto contra huésped, infección y, en caso de afectación de la piel, farmacodermia.…”

Section: Gerardo López Hernándezunclassified

Lactante menor con leucemia congénita y enfermedad de injerto contra huésped postrasplante

et al. 2019

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Lactante de 6 meses de edad, enviada para valoración al servicio de Trasplante de células progenitoras hematopoyéticas del Instituto Nacional de Pediatría. Entre sus antecedentes personales: la madre de 24 años, primer embarazo, evolución normal, parto eutócico, peso al nacimiento 3 kg, talla 48 cm y Apgar 8/9. Desde el nacimiento se identificó dermatosis maculopapular generalizada, con nódulos subcutáneos infiltrativos violáceos en todo el cuerpo. (Figura 1) Se estableció el diagnóstico presuntivo de síndrome de neonato blueberry-muffin; además, se encontró hepatomegalia y esplenomegalia. La biometría hemática reportó hiperleucocitosis (215,900 leucocitos/mm3), a expensas de 75% de blastos, con inmunofenotipo de expresión: CD45+, MPO+, CD33+, CD13+ y CD14+, compatible con leucemia mieloblástica aguda.

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Pre-engraftment syndrome: clinical significance and pathophysiology

Cited by 12 publications

References 11 publications

Third party, umbilical cord blood derived regulatory T-cells for prevention of graft versus host disease in allogeneic hematopoietic stem cell transplantation: feasibility, safety and immune reconstitution

Third party, umbilical cord blood derived regulatory T-cells for prevention of graft versus host disease in allogeneic hematopoietic stem cell transplantation: feasibility, safety and immune reconstitution

Umbilical Cord Blood Transplantation: Still Growing and Improving

Lactante menor con leucemia congénita y enfermedad de injerto contra huésped postrasplante

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