pre-engraftment syndrome

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a global pandemic that upended existing protocols and practices, including those for allogeneic hematopoietic stem cell transplantation (HCT). Here we describe the successful clinical course and multiple key interventions administered to an acute lymphoblastic leukemia patient, who tested SARS-CoV-2 positive by RT-PCR on day -1 of matched unrelated donor (SARS-CoV-2 IgG negative) T-cell-replete HCT...

Granulocyte colony-stimulating factor (G-CSF) used after hematopoietic stem cell transplantation (HSCT) can enhance neutrophil recovery in patients rendered neutropenic by the preparative regimen. G-CSF is contraindicated in patients with sickle cell disease (SCD), because life-threatening complications can ensue in the presence of sickle vasculopathy. The safety profile of G-CSF after HSCT for SCD has not been described, however. We report clinical outcomes in the first 100 days post-HSCT in 62 patients supported with G-CSF until neutrophil recovery on a clinical trial of reduced- intensity conditioning HSCT for SCD...

Patient-derived xenograft (PDX) models have emerged as versatile pre-clinical platforms for investigation of functional pathomechanisms in Myelodysplastic Syndromes (MDS) and other myeloid neoplasms. However, despite increasingly improved methodology, engraftment efficiencies frequently remain low. Humanized 3D scaffold models (ossicle xenotransplantation models) in immunocompromised mice have recently been shown to enable improved engraftment rates of healthy and malignant human hematopoiesis. We therefore interrogated the feasibility of 4 different 3D ossicle-based PDX models for application with primary MDS samples...

PURPOSE: Treosulfan and fludarabine (Treo/Flu) were successfully introduced into toxicity-reduced conditioning for SCT. However, the risk of post-SCT relapse remains a matter of concern. We report the results of a novel individual treatment approach with Treo/Flu and cytarabine (Treo/Flu/AraC) conditioning prior to allogeneic SCT in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative neoplasms (MPN). METHODS: Seventy-seven patients (median age 54 years) at high risk of disease relapse due to unfavorable cytogenetics or failure to achieve complete remission prior to SCT were included...

BACKGROUND: Haematopoietic stem cell transplantation (HSCT) is used worldwide in various malignant and nonmalignant childhood diseases, including haematologic, genetic, autoimmune and metabolic disorders, and is the only curative treatment for many of these illnesses. The survival rates of many childhood diseases have been increased due to HSCT treatment. However, associated complications are still important for management. Central nervous system (CNS) complications in paediatric HSCT recipients can be associated with high morbidity and significantly contribute to mortality...

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...

Allogeneic bone marrow transplant (alloBMT) with continuous antiretroviral therapy alone has not been shown to completely eradicate HIV, possibly due to HIV persistence in rare residual host cells or infection of donor cells. Within a trial of alloBMT in individuals with hematological malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay. We sequenced the reverse transcriptase region of pol for replication-competent virus and performed maximum-likelihood phylogenetic reconstruction...

Marrow fibrosis (MF) is usually accompanied with primary myelodysplastic syndromes (MDS) and no consensus has been reached on the relationship between MF and prognosis. We retrospectively analyzed 239 MDS and MDS derived acute myeloid leukemia patients with known grade of MF who received allogeneic stem cell transplantation (allo-HSCT). Of these, it included 121 (50.6%) without fibrosis (MF-0), 81 (33.9%) with mild fibrosis (MF-1), 37 (15.5%) with moderate to severe fibrosis (MF-2/3). MF-2/3 was associated with more pronounced dysmegakaryopoiesis (P = 0...

Severe acute respiratory syndrome coronavirus 2 can lead to life-threatening coronavirus disease 2019 (COVID-19) infections in patients with hematologic malignancies, particularly among hematopoietic cell transplant (HCT) recipients. We describe two patients with COVID-19 during the pre-engraftment period after HCT and review previous reports of COVID-19 in HCT recipients. Because of significant mortality from COVID-19, primarily after allogeneic HCT, early, preemptive, and optimal directed therapy may improve outcomes and reduce the mortality rate but still needs to be established in clinical trials...

In this work we present the case of SARS-CoV-2 infection in a 1.5-year-old boy affected by severe Wiskott-Aldrich Syndrome with previous history of autoinflammatory disease, occurring 5 months after treatment with gene therapy. Before SARS-CoV-2 infection, the patient had obtained engraftment of gene corrected cells, resulting in WASP expression restoration and early immune reconstitution. The patient produced specific immunoglobulins to SARS-CoV-2 at high titer with neutralizing capacity and experienced a mild course of infection, with limited inflammatory complications, despite pre-gene therapy clinical phenotype...

Rationale: The periengraftment respiratory distress syndrome (PERDS) is an early important cause of morbidity following autologous hematopoietic cell transplantation (HCT). There are few contemporary data describing PERDS. Objectives: To determine prevalence, risk factors, and outcomes of PERDS after autologous HCT. Methods: This was a historical cohort study of adults undergoing autologous HCT at Mayo Clinic, Rochester, Minnesota, between 2005 and 2016. PERDS was defined as 1 ) respiratory failure requiring supplemental oxygen within 5 days on either side of the neutrophil engraftment date, 2 ) new pulmonary opacities on chest imaging, and 3 ) exclusion of an infectious or cardiac etiology to explain the clinical presentation...

Objectives: Humanised mice have emerged as valuable models for pre-clinical testing of the safety and efficacy of immunotherapies. Given the variety of models available, selection of the most appropriate humanised mouse model is critical in study design. Here, we aimed to develop a model for predicting cytokine release syndrome (CRS) while minimising graft- versus -host disease (GvHD). Methods: To overcome donor-induced variation, we directly compared the in vitro and in vivo immune phenotype of immunodeficient NSG mice reconstituted with human bone marrow (BM) CD34+ haematopoietic stem cells (HSCs), peripheral blood mononuclear cells (PBMCs) or spleen mononuclear cells (SPMCs) from the same human donors...

Tacrolimus (TAC) is essential for prophylaxis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HSCT). We have sometimes observed large fluctuations in TAC concentration. However, links between the variability in the concentration or the concentration/dose (C/D) ratio of TAC and clinical complications remain ambiguous. To clarify relationships between various parameters of TAC and early complications such as pre-engraftment immune reactions/engraftment syndrome, aGVHD, and transplant-associated thrombotic microangiopathy (TA-TMA), a total of 146 patients who underwent allo-HSCT were included...

BACKGROUND: Mesenchymal stem cells (MSCs) may be used to treat steroid-refractory graft versus host disease (GVHD). However, the effects of MSCs in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) have not been confirmed in randomized studies. METHODS: We conducted a randomized clinical study to investigate the effects of pre-infusion (1 × 106 cells/kg) MSCs on hematopoietic recovery, Epstein-Barr and cytomegalovirus infection, GVHD, and relapse in patients undergoing haplo-PBSCT...

BACKGROUND: Infectious complications are significant causes of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). They occur variably over different periods, with scant data reported from Lebanon and neighboring countries. In this study, we described the pre-engraftment neutropenic phase, febrile episodes, and peri-transplant medical complications in patients undergoing allo-HCT at a tertiary-care hospital. METHODS: This is a retrospective chart review of patients who underwent allo-HCT between 2007 and 2016 at Makassed General Hospital in Beirut, Lebanon...

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 = ...

OBJECTIVE: We investigated the role of anti-thymocyte globulin (ATG; Thymoglobulin) in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) after reduced intensity conditioning (RIC) in myelodysplastic syndrome (MDS). METHODS: Forty-seven patients with 10 mg/kg ATG (ATG group; median age 53 years) and 33 without ATG (no-ATG group; median age 43, P < .0001) were compared. RESULTS: Median time to engraftment was similar...

Fecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has been used to treat inflammatory bowel disease (IBD) for almost a decade. Here, we report an interventional prospective cohort study performed to elucidate the extent of and processes underlying microbiota engraftment in IBD patients after FMT treatment. The cohort included two categories of patients: (a) patients with moderate to severe Crohn's disease (CD) (Harvey-Bradshaw Index ≥ 7, n = 11) and (b) patients with ulcerative colitis (UC) (Montreal classification S2 and S3, n = 4)...

90% of relapse/refractory B cell acute lymphatic leukemia (R/R B-ALL) patients can achieve complete remission (CR) after CD19-targeting chimeric antigen receptor T (CAR-T) cell therapy. However, around 50% of them relapse in one year. Persistent CAR-T cell engraftment is considered as the key to remain durable remission. Here we initiated a Phase I study to treat ten pediatric B-ALL patients using a CD19 targeted 2nd generation CAR with a 4-1BB intracellular costimulatory domain. All patients received a standard fludarabine and cyclophosphamide (FC) preconditioning regiment, followed by a CAR-T infusion with a median number of 0...

Ruxolitinib (Rux), a Jak1/2 inhibitor, results in reduced spleen size and improvement in constitutional symptoms in the majority of patients with myelofibrosis (MF). Therefore Rux, when given prior to hematopoietic cell transplantation (HCT) in patients with MF was hypothesized to improve engraftment, decrease incidence and severity of graft-versus-host disease, and lower non-relapse mortality (NRM). We conducted a phase II prospective trial to assess the effects of pre-HCT Rux on post-HCT outcomes in patients with MF...