Hospital survival following pediatric HSCT: changes in complications, ICU therapies and outcomes over 10 years

IntroductionHematopoietic stem cell transplantation (HSCT) is an increasingly utilized therapy for malignant and non-malignant pediatric diseases. HSCT complications, including infection, organ dysfunction, and graft-versus-host-disease (GVHD) often require intensive care unit (ICU) therapies and are associated with mortality. Our aims were to identify the HSCT characteristics, complications and ICU therapies associated with (1) survival, and (2) survival changes over a ten-year period in a national dataset.MethodsA national sample from the Health Facts (Cerner Corporation, Kansas City, MO) database from 2009 to 2018 was utilized. Inclusion criteria were age 30 days to <22 years and HSCT procedure code. For patients with >1 HSCT, the first was analyzed. Data included demographics, hospital length of stay (LOS), hospital outcome, transplant type and indication. HSCT complications included GVHD and infections. ICU therapies were positive pressure ventilation (PPV), vasoactive infusion, and dialysis. Primary outcome was survival to discharge. Statistical methods included bivariate analyses and multivariate logistic regression.Results473 patients underwent HSCT with 93% survival. 62% were allogeneic (89% survival) and 38% were autologous (98% survival). GVHD occurred in 33% of allogeneic HSCT. Infections occurred in 26% of all HSCT. ICU therapies included PPV (11% of patients), vasoactive (25%), and dialysis (3%). Decreased survival was associated with allogeneic HSCT (p < 0.01), GVHD (p = 0.02), infection (p < 0.01), and ICU therapies (p < 0.01). Survival improved from 89% (2009–2013) to 96% (2014–2018) (p < 0.01). Allogeneic survival improved (82%–94%, p < 0.01) while autologous survival was unchanged. Survival improvement over time was associated with decreasing infections (33%–21%, p < 0.01) and increasing vasoactive infusions (20%–28%, p = 0.05). On multivariate analysis, later time period was associated with improved survival (p < 0.01, adjusted OR 4.28).DiscussionHospital survival for HSCT improved from 89% to 96% from 2009 to 2018. Factors associated with mortality included allogeneic HSCT, GVHD, infections and ICU therapies. Improving survival coincided with decreasing infections and increasing vasoactive use

Risk Factors for Symptomatic Pericardial Effusions Posthematopoietic Stem Cell Transplant

BACKGROUND: Pericardial effusions are a known complication posthematopoietic stem cell transplant (HSCT), causing significant morbidity. We aimed to evaluate the risk factors associated with the development of high-grade effusions requiring interventions. . A retrospective chart review of all HSCT patients over a period of 7 years (2013-2019) in a single institution in the Northeastern United States is conducted. All patients who developed an effusion requiring intervention were included. Patient\u27s clinical characteristics were compared with all others transplanted during the same time period. Echocardiogram findings of the affected patients were compared to a case-control cohort of unaffected patients with similar age and diagnosis. Chi-square and paired -tests were utilized to ascertain statistical differences between the groups. RESULTS: A total of 15 patients out of 201 (7.5%) transplanted at our institution developed a moderate or large pericardial effusion requiring pericardiocentesis or a pericardial window. Of this cohort, 13 (87%) underwent a myeloablative preparative regimen, 13 (87%) had cyclophosphamide as part of their regimen, 13 (87%) had recent treatment for viral reactivation, 6 (40%) had an underlying hemoglobinopathy diagnosis, and only 4 (27%) had an active diagnosis of GVHD. A myeloablative preparative regimen had a higher rate of effusion requiring intervention, although it was not statistically significant, and concurrent GVHD was not predictive of effusion development. However, exposure to cyclophosphamide, recent treatment for viral reactivation, and a diagnosis of transplant-associated thrombotic microangiopathy (Ta-TMA) were highly associated with effusions. The latter was associated with increased mortality. The duration of pericardial effusion correlated with the pretransplant echocardiogram left ventricle end diastolic diameter z-score and apical 4-chamber left ventricular peak average strain measurement. CONCLUSIONS: Potential risk factors for pericardial effusions post-HSCT include a diagnosis of Ta-TMA, active viral infection, exposure to cyclophosphamide, and a higher left ventricle end diastolic diameter -score. This information may help guide management for these patients, including identifying high-risk subjects, determining the frequency of echocardiograms, and determining specific echocardiogram measures to follow over time

Datasheet1_Hospital survival following pediatric HSCT: changes in complications, ICU therapies and outcomes over 10 years.pdf

IntroductionHematopoietic stem cell transplantation (HSCT) is an increasingly utilized therapy for malignant and non-malignant pediatric diseases. HSCT complications, including infection, organ dysfunction, and graft-versus-host-disease (GVHD) often require intensive care unit (ICU) therapies and are associated with mortality. Our aims were to identify the HSCT characteristics, complications and ICU therapies associated with (1) survival, and (2) survival changes over a ten-year period in a national dataset.MethodsA national sample from the Health Facts (Cerner Corporation, Kansas City, MO) database from 2009 to 2018 was utilized. Inclusion criteria were age 30 days to 1 HSCT, the first was analyzed. Data included demographics, hospital length of stay (LOS), hospital outcome, transplant type and indication. HSCT complications included GVHD and infections. ICU therapies were positive pressure ventilation (PPV), vasoactive infusion, and dialysis. Primary outcome was survival to discharge. Statistical methods included bivariate analyses and multivariate logistic regression.Results473 patients underwent HSCT with 93% survival. 62% were allogeneic (89% survival) and 38% were autologous (98% survival). GVHD occurred in 33% of allogeneic HSCT. Infections occurred in 26% of all HSCT. ICU therapies included PPV (11% of patients), vasoactive (25%), and dialysis (3%). Decreased survival was associated with allogeneic HSCT (p DiscussionHospital survival for HSCT improved from 89% to 96% from 2009 to 2018. Factors associated with mortality included allogeneic HSCT, GVHD, infections and ICU therapies. Improving survival coincided with decreasing infections and increasing vasoactive use.</p

Poor T-cell receptor β repertoire diversity early posttransplant for severe combined immunodeficiency predicts failure of immune reconstitution.

BackgroundDevelopment of a diverse T-cell receptor β (TRB) repertoire is associated with immune recovery following hematopoietic cell transplantation (HCT) for severe combined immunodeficiency (SCID). High-throughput sequencing of the TRB repertoire allows evaluation of clonotype dynamics during immune reconstitution.ObjectivesWe investigated whether longitudinal analysis of the TRB repertoire would accurately describe T-cell receptor diversity and illustrate the quality of T-cell reconstitution following HCT or gene therapy for SCID.MethodsWe used high-throughput sequencing to study composition and diversity of the TRB repertoire in 27 infants with SCID at 3, 6, and 12 months and yearly posttreatment(s). Total RNA from peripheral blood was used as template to amplify TRB rearrangements.ResultsTRB sequence analysis showed poor diversity at 3 months, followed by significant improvement by 6 months after cellular therapies. Kinetics of development of TRB diversity were similar in patients with a range of underlying gene defects. However, in patients with RAG and DCLRE1C defects, HCT with no conditioning or immune suppression only resulted in lower diversity than did HCT with conditioning. HCT from a matched donor correlated with higher diversity than did HCT from a mismatched donor. Naive CD4+ T-cell count at 6 months post-HCT correlated with higher TRB diversity. A&nbsp;Shannon index of diversity of 5.2 or lower 3 months after HCT predicted a need for a second intervention.ConclusionsTRB repertoire after hematopoietic cell therapies for SCID provides a quantitative and qualitative measure of diversity of T-cell reconstitution and permits early identification of patients who may require a second intervention

Poor T-cell receptor β Repertoire Diversity Early Post-transplant for Severe Combined Immunodeficiency Predicts Failure of Immune Reconstitution

Background: Development of a diverse T-cell receptor β (TRB) repertoire is associated with immune recovery following hematopoietic cell transplantation (HCT) for severe combined immunodeficiency (SCID). High-throughput sequencing of the TRB repertoire allows evaluation of clonotype dynamics during immune reconstitution. Objectives: We investigated whether longitudinal analysis of the TRB repertoire would accurately describe T-cell receptor diversity and illustrate the quality of T-cell reconstitution following HCT or gene therapy for SCID. Methods: We used high-throughput sequencing to study composition and diversity of the TRB repertoire in 27 infants with SCID at 3, 6, and 12 months and yearly posttreatment(s). Total RNA from peripheral blood was used as template to amplify TRB rearrangements. Results: TRB sequence analysis showed poor diversity at 3 months, followed by significant improvement by 6 months after cellular therapies. Kinetics of development of TRB diversity were similar in patients with a range of underlying gene defects. However, in patients with RAG and DCLRE1C defects, HCT with no conditioning or immune suppression only resulted in lower diversity than did HCT with conditioning. HCT from a matched donor correlated with higher diversity than did HCT from a mismatched donor. Naive CD4+ T-cell count at 6 months post-HCT correlated with higher TRB diversity. A Shannon index of diversity of 5.2 or lower 3 months after HCT predicted a need for a second intervention. Conclusions: TRB repertoire after hematopoietic cell therapies for SCID provides a quantitative and qualitative measure of diversity of T-cell reconstitution and permits early identification of patients who may require a second intervention.</p

Outcomes following posttransplant viral-specific T-cell therapy in patients with sickle cell disease

Hematopoietic stem cell transplantation (HSCT) is increasingly used as a curative approach for sickle cell disease (SCD). With the risk of graft-versus-host disease (GVHD), especially in the HLA-mismatched donors, intense immunosuppression is required leading to an increased risk of viral infection. Post-HSCT, adoptive transfer of virus-specific T cell (VSTs) therapies have not been well-studied in SCD patients. Here, we report the outcomes of patients with SCD at a single-center who received VSTs post-transplant to prevent or treat virus infections. Thirteen patients who received HSCT from HLA-matched (n=9) or mismatched (n=4) donors for SCD were treated with a total of 15 VST products for the treatment or prophylaxis of multiple viruses (cytomegalovirus, ebstein barr virus, adenovirus, BK virus, human herpes virus 6 +/- human parainfluenza virus 3). Of the patients evaluated, 46.2% (n=6)) received VSTs as treatment of virus infection. Eighty percent of patients with active viremia (n=4/5) achieved remission of at least 1 target virus. Seven additional patients (53.8%) received VSTs prophylactically and 6/7 (85.7%) remained virus-free post-infusion. No immediate infusion-related toxicities occurred, and severe de novo acute GVHD occurred in only 2 (15.4%) patients. Given the good safety profile, high-rate of clinical responses and sustained remissions when administered with standard anti-viral treatments, the routine use of VSTs post-HSCT as prophylaxis or treatment may improve the overall safety of transplant for patients with SCD