A Critical Care and Transplantation-Based Approach to Acute Respiratory Failure after Hematopoietic Stem Cell Transplantation in Children.
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ABSTRACT:
SUBMITTER: Elbahlawan L
PROVIDER: S-EPMC5033513 | biostudies-literature | 2016 Apr
REPOSITORIES: biostudies-literature
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A Critical Care and Transplantation-Based Approach to Acute Respiratory Failure after Hematopoietic Stem Cell Transplantation in Children.
Elbahlawan Lama L Srinivasan Ashok A Morrison R Ray RR
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20150925 4
Acute respiratory failure contributes significantly to nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Although there is a trend of improved survival over time, mortality remains unacceptably high. An understanding of the pathophysiology of early respiratory failure, opportunities for targeted therapy, assessment of the patient at risk, optimal use of noninvasive positive pressure ventilation, strategies to improve alveolar recruitment, appropriate fluid management ...[more]
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Project description:BackgroundNon-invasive ventilation (NIV) was one of the first-line ventilation supports for hematopoietic stem-cell transplantation (HSCT) patients with acute respiratory distress syndrome (ARDS). Successful NIV may avoid need for intubation. However, the influence NIV failure had on patients' outcome and its risk factors were hardly known.MethodsIn this retrospective observational study, we reported risk factors and incidence of NIV failure in HSCT patients who were admitted to the Intensive Care Unit (ICU) with a diagnosis of ARDS and supported with mechanical ventilation, in a 5-year period. Patient outcomes, such as ventilator-free days, ICU-free days, and ICU mortality were also reported.ResultsOf all the 94 patients included, 70 patients were initially supported with NIV. NIV failure occurred in 44 (63%) patients. Male sex, elevated serum galactomannan (GM) test, (1-3)-β-D-glucan (BG) assay, or elevated serum creatinine level were risk factors for NIV failure. When compared with the NIV success group, failure of NIV was associated with much fewer ICU-free days (22 versus 0, p < 0.001, Cohen's d = 0.62) and higher ICU mortality (9.5% versus 75.5%, p < 0.001, Pearson's r = 0.75). There was no difference in ICU-free days, ventilator-free days and ICU mortality between NIV failure and initial invasive mechanical ventilation (IMV) groups. Patients who failed in NIV support had a higher ICU mortality (75.5%) than those who succeeded (9.5%).ConclusionIn a small cohort of HSCT patients with mainly moderate severity of ARDS, male patients with elevated serum GM/BG test or serum creatinine level had a higher risk of NIV failure. Both NIV failure and initial IMV groups were characterized by high mortality rate and extremely low ICU-free days and ventilator-free days; failure of NIV support may further aggravate patient prognosis. The reviews of this paper are available via the supplemental material section.
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Project description:Patients with acute leukemia refractory to induction or reinduction chemotherapy have poor prognoses if they do not undergo hematopoietic stem-cell transplantation (HSCT). However, HSCT when a patient is not in complete remission (CR) is of uncertain benefit. We hypothesized that pretransplantation variables may define subgroups that have a better prognosis.Overall, 2,255 patients who underwent transplantation for acute leukemia in relapse or with primary induction failure after myeloablative conditioning regimen between 1995 and 2004 were reported to the Center for International Blood and Marrow Transplant Research. The median follow-up of survivors was 61 months. We performed multivariate analysis of pretransplantation variables and developed a predictive scoring system for survival.The 3-year overall survival (OS) rates were 19% for acute myeloid leukemia (AML) and 16% for acute lymphoblastic leukemia (ALL). For AML, five adverse pretransplantation variables significantly influenced survival: first CR duration less than 6 months, circulating blasts, donor other than HLA-identical sibling, Karnofsky or Lansky score less than 90, and poor-risk cytogenetics. For ALL, survival was worse with the following: first refractory or second or greater relapse, > or = 25% marrow blasts, cytomegalovirus-seropositive donor, and age of 10 years or older. Patients with AML who had a predictive score of 0 had 42% OS at 3 years, whereas OS was 6% for a score > or = 3. Patients with ALL who had a score of 0 or 1 had 46% 3-year OS but only 10% OS rate for a score > or = 3.Pretransplantation variables delineate subgroups with different outcomes. HSCT during relapse can achieve long-term survival in selected patients with acute leukemia.
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Project description:IntroductionHematopoietic stem cell transplantation (HSCT) is the essential and often the only curative therapeutic option in high risk and relapsed pediatric acute lymphoblastic leukemia (ALL).MethodsThe objective of the study was to investigate whole-genome expression in children with high risk or relapsed ALL referred for HSCT. Gene expression was assessed in 18 children with ALL referred for HSCT (10 high risk, 8 relapsed; median age of 9.4 years) and in a control group of 38 obese children (median age of 14.1 years). Whole-genome expression was assessed in leukocytes using GeneChip® HumanGene 1.0 ST microarray.ResultsThe analysis of genomic profiles revealed a significantly lower expression of 21 genes with a defined function, involved in immunoglobulin production, lymphocyte function, or regulation of DNA processing in ALL patients referred for HSCT compared with the control group.ConclusionGenome expression of patients with ALL in remission referred to HSCT revealed deep immunosuppression of both B-cell and T-cell lineages, which may increase the probability of donor cell engraftment.
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Project description:ObjectivesGraft-versus-host disease (GVHD) commonly affects the gastrointestinal (GI) tract among children who undergo hematopoietic stem cell transplantation (HSCT). Studies concerning GI-acute GVHD (aGVHD) in developing countries are limited. Therefore, our aims were (1) to demonstrate clinical characteristics, endoscopic and histopathological findings in children with GI-aGVHD post-HSCT and (2) to compare features, risk factors, and clinical outcomes of children with GI-aGVHD versus non GI-aGVHD.MethodsA retrospective single-center study was conducted on patients receiving the first successful HSCT aged <20 years old between January 2011 and December 2020. The patients were divided into groups with GI-aGVHD (clinically or endoscopy-histopathologically diagnosed) and without GI-aGVHD. Various aforementioned data were recorded to compare the risk factors and clinical outcomes of children with and without GI-aGVHD.ResultsAmong 246 children post-HSCT, we identified 42 cases (17%) with GI-aGVHD (32 cases with the clinical diagnosis and 10 cases with endoscopy-histopathology confirmed diagnosis) and 204 patients without GI-aGVHD. When compared with children without GI-aGVHD, the GI-aGVHD group had higher rates of hypovolemic shock, renal failure, more extended hospital stays, and deaths (all p < 0.05). The GI-aGVHD group also had a higher proportion of cases with nonhematologic malignancy (odds ratio [OR] = 2.34, 95% confidence interval [CI] = 1.01-5.41, p = 0.047) and cytomegalovirus (CMV) reactivation before the GI-aGVHD episode (OR = 2.22, 95% CI = 1.09-4.51, p = 0.027).ConclusionsGI-aGVHD after HSCT leads to increased morbidity and death. Underlying nonhematologic malignancy and history of CMV reactivation are associated with GI-aGVHD. Direct links between the aforementioned factors and the development of GI-aGVHD merit future studies.
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Project description:Acute respiratory failure (ARF) is the main reason for ICU admission following allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal CO2 removal (ECCO2 R) can be used as an adjunct to mechanical ventilation in patients with severe hypercapnia but has not been assessed in HSCT recipients. Retrospective analysis of all allogeneic HSCT recipients ≥18 years treated with ECCO2 R at two HSCT centers. 11 patients (m:f = 4:7, median age: 45 [IQR: 32-58] years) were analyzed. Acute leukemia was the underlying hematologic malignancy in all patients. The time from HSCT to ICU admission was 37 [8-79] months, and 9/11 (82%) suffered from chronic graft-versus-host disease (GVHD) with lung involvement. Pneumonia was the most frequent reason for ventilatory decompensation (n = 9). ECCO2 R was initiated for severe hypercapnia (Pa CO2 : 96 [84-115] mm Hg; pH: 7.13 [7.09-7.27]) despite aggressive mechanical ventilation (invasive, n = 9; non-invasive, n = 2). ECCO2 R effectively resolved blood gas disturbances in all patients, but only 2/11 (18%) could be weaned off ventilatory support, and one (9%) patient survived hospital discharge. Progressive respiratory and multiorgan dysfunction were the main reasons for treatment failure. ECCO2 R was technically feasible but resulted in a low survival rate in our cohort. A better understanding of the prognosis of ARF in patients with chronic GVHD and lung involvement is necessary before its use can be reconsidered in this setting.
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Project description:Ruxolitinib, a selective inhibitor of Janus kinases 1 and 2, is increasingly being used in allogeneic hematopoietic cell transplantation (HCT) recipients following its approval by the U.S. Food and Drug Administration for the treatment of steroid-refractory acute graft-versus-host disease. Although there is extensive experience using ruxolitinib for patients with myeloproliferative neoplasms, the biologic effects and clinical implications of its dosing, tapering, and discontinuation for allogeneic HCT recipients are incompletely characterized. We describe three allogeneic HCT recipients who developed acute hypoxemic respiratory failure within 3 months of ruxolitinib discontinuation. Radiographic findings included marked bilateral ground-glass opacities. Systemic corticosteroids and reinitiation of ruxolitinib resulted in rapid clinical improvement in all three patients. All three patients achieved a significant clinical response, with decrease in oxygen requirement and improvement in radiographic changes. Given the increasing use of ruxolitinib in allogeneic HCT recipients, there is significant impetus to characterize the biologic and clinical effects resulting from discontinuation of ruxolitinib, to better tailor treatment plans and prevent potential adverse effects.
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Project description:ObjectivesTo present the recommendations and supporting literature for RBC transfusions in critically ill children with bleeding developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.DesignConsensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children.MethodsThe panel of 38 experts developed evidence-based and, when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The respiratory subgroup included six experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method.ResultsTransfusion and Anemia Expertise Initiative experts developed seven recommendations focused on children with acute respiratory failure. All recommendations reached agreement (> 80%). Transfusion of RBCs in children with respiratory failure with an hemoglobin level less than 5 g/dL was strongly recommended. It was strongly recommended that RBCs not be systematically administered to children with respiratory failure who are hemodynamically stable and who have a hemoglobin level greater than or equal to 7 g/dL. Experts could not make a recommendation for children with hemodynamic instability, with severe hypoxemia and/or with an hemoglobin level between 5 and 7 g/dL. Specific RBC transfusion strategies using physiologic-based metrics and biomarkers could not be elaborated.ConclusionsThe Transfusion and Anemia Expertise Initiative Consensus Conference developed specific recommendations regarding RBC transfusion management in critically ill children with respiratory failure, as well as recommendations to guide future research. Clinical recommendations emphasize relevant hemoglobin thresholds. Research recommendations emphasize the need to identify appropriate physiologic thresholds, suggest a better understanding of alternatives to RBC transfusion, and identify the need for better evidence on hemoglobin thresholds that might be used in specific subpopulations of critically ill children.
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