Use of neutropenic diet in the nutritional care of pediatric cancer patients with neutropenia: a scoping review.

OBJECTIVE: to carry out a scoping review with the purpose of mapping the scientific evidence on the use of the neutropenic diet in neutropenic pediatric cancer patients. SOURCE OF DATA: The scoping review protocol was prepared in accordance with the PRISMA-ScR and the checklist before the literature search was performed. Articles on nutritional management in adults or on the treatment of other diseases, and articles that were not in Portuguese or English and published before the year 2000, were excluded. Data were extracted based on the Cochrane Consumer and Communication Review Group form. SUMMARY OF THE FINDINGS: Three hundred and forty scientific articles were identified, with the final sample of this review consisting of nine studies. Although the neutropenic diet has been part of the nutritional management of pediatric cancer patients for more than 20 years, there is still great variation in the criteria for indicating use and starting and discontinuing it, as well as in the nutritional composition of the diet. Furthermore, there is no consensus on the impact of using a neutropenic diet on different clinical and nutritional outcomes. CONCLUSION: In the absence of guidelines that standardize the use of a neutropenic diet in pediatric patients with neutropenia, there are heterogeneous approaches reported in the literature, even within the same institution. The available literature presents an absence of evidence on the use, viability, and effectiveness of the neutropenic diet in oncological children with neutropenia. More studies are needed to identify the real impact of the neutropenic diet on clinical and nutritional outcomes.

Central Line-Associated Bloodstream Infection in Patients With Hematologic Malignancy Receiving Parenteral Nutrition.

PURPOSE: Parenteral nutrition (PN) has been shown to be a safe method of feeding in the intensive care unit with modern infection prevention practices, but similar analysis in the hematology-oncology setting is lacking. METHODS: A retrospective analysis of 1,617 patients with hematologic malignancies admitted and discharged from the Hospital of the University of Pennsylvania during 3,629 encounters from 2017 to 2019 was undertaken to evaluate the association of PN administration with risk of central line-associated bloodstream infection (CLABSI). Proportions of mucosal barrier injury (MBI)-CLABSI and non-MBI-CLABSI were also compared between groups. RESULTS: Risk of CLABSI was associated with cancer type and duration of neutropenia but not with PN administration (odds ratio, 1.015; 95% CI, 0.986 to 1.045; P = .305) in a multivariable analysis. MBI-CLABSI comprised 73% of CLABSI in patients exposed to and 70% in patients not exposed to PN, and there was no significant difference between groups (χ2 = 0.06, P = .800). CONCLUSION: PN was not associated with increased risk of CLABSI in a sample of patients with hematologic malignancy with central venous catheters when adjusting for cancer type, duration of neutropenia, and catheter days. The high proportion of MBI-CLABSI highlights the effect of gut permeability within this population.

Risk of infections associated with the use of bispecific antibodies in multiple myeloma: a pooled analysis.

The use of bispecific antibodies (BsAbs) in the treatment of relapsed/refractory multiple myeloma (MM) is showing early promising overall response rates in heavily pretreated patients. Infectious complications related to the use of BsAbs are not well described. We conducted a pooled analysis that included all single-agent BsAbs used in MM with no prior use of different BsAbs. A total of 1185 patients with MM were treated with a BsAb in the studied period (71.6% of the patients treated with an agent targeting B-cell maturation antigen (BCMA). Pooled median follow-up was short at 6.1 months (7.5 vs 5.2 months for BCMA vs non-BCMA BsAbs, respectively). Adverse events of interest included all grade neutropenia in 38.6%, all grade infections in 50% (n = 542/1083), all grade cytokine release syndrome in 59.6% (n = 706/1185), grade III/IV neutropenia in 34.8% (n = 372/1068), grade III/IV infections in 24.5% (n = 272/1110), grade III/IV pneumonia in 10% (n = 52.4/506), and grade III/IV coronavirus disease 2019 in 11.4% (n = 45.4/395) of the patients. Non-BCMA-targeted BsAbs were associated with lower grade III/IV neutropenia (25.3% vs 39.2%) and lower grade III/IV infections (11.9% vs 30%) when compared with BCMA-targeted BsAbs. Hypogammaglobulinemia was reported in 4 studies, with a prevalence of 75.3% (n = 256/340) of the patients, with IV immunoglobulin used in 48% (n = 123/256) of them. Death was reported in 110 patients, of which 28 (25.5%) were reported to be secondary to infections. Certain precautions should be used when using BsAbs to mitigate the risk and/or identify and treat infections promptly.

Impact of Granulocyte Colony-Stimulating Factor (G-CSF) on the Outcomes of Patients With Metastatic Pancreatic Adenocarcinoma (MPA) During First-Line Treatment With FOLFIRINOX: A Single-Center Retrospective Analysis.

INTRODUCTION: The role of primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) for patients with metastatic pancreatic adenocarcinoma (MPA) treated with FOLFIRINOX is unknown. We aimed to compare the frequencies of grades 3 or 4 neutropenia (G3/4N) and febrile neutropenia (FN) and survival outcomes according to the use of PP. METHODS: This is a retrospective study. We included patients with pathologically confirmed MPA treated with FOLFIRINOX in first-line. Patients who received primary prophylaxis (PP group) were compared to patients who received secondary or no G-CSF (no-PP group). Overall survival (OS) and progression-free survival (PFS) were evaluated using the standard Cox proportional hazard model. To account for potential biases, we performed sensitivity analyses excluding patients who received secondary prophilaxis and treating G-CSF as a time-dependent covariate in extended Cox proportional hazard models. RESULTS: The study population consisted of 123 patients. PP was used by 75 patients (61.0%). G3/4 N occurred more frequently among patients without PP (10.7 vs 41.7%; P < .001). There was no difference in the frequency of FN between groups (5.3 vs 8.3%; P = .710). In multivariate analysis, PP was associated with a trend toward improved OS (HR = .66; 95% confidence interval [95% CI] .41 - 1.07; P = .094). In the multivariate model excluding patients with secondary prophylaxis (HR = .54; 95% CI 0.32 - .91; P = .022) and in the time-dependent model (HR = .47; 95% CI 0.28 - .80; P = .005), PP was associated with statistically superior OS. CONCLUSIONS: Despite the reduction in the frequency of G3/4N, the risk of FN among patients treated with FOLFIRINOX without G-CSF is too low to justify its use in a routine basis. However, given the potential of G-CSF to improve survival in this setting, further studies are warranted to assess its role during treatment with FOLFIRINOX for patients with MPA.

Survival among children and adults treated with granulocyte transfusions: Twenty years' experience at a Brazilian blood center.

BACKGROUND: It remains controversial whether granulocyte transfusions as a supportive treatment improve survival in patients with febrile neutropenia or granulocyte dysfunctions. We describe survival rates subsequent to granulocyte transfusions in pediatric and adults patients treated at a major blood center in Brazil. MATERIAL AND METHODS: We retrospectively reviewed the clinical charts of pediatric and adult patients treated with granulocyte transfusions at our institution from January 2000 to October 2019. We assessed demographic characteristics, clinical features, indications for transfusion, units transfused, dose of granulocytes administered and survival rates 30 and 100 days after the initial transfusion. RESULTS: We identified 64 pediatric and 67 adult patients treated with 262 granulocyte transfusions. An optimal dose (> 0.6 × 109 granulocytes per kilogram per transfused unit) was available for transfusion in 80.4 % of pediatric patients but in only 19.6 % of adults (p = 0.017). Thirty days after their first granulocyte transfusion, 38 (59.4 %) pediatric and 61 (91 %) adult patients had died. Patients receiving the optimal dose of granulocytes had better survival outcomes, but even among this sub-group, adults were more likely to die than were children either at 30 days (OR = 8.67, 95 %CI 2.69-34.9) or 100 days (OR = 6.27, 95 %CI 1.86-25.9) after their initial granulocyte transfusion. CONCLUSION: Survival rates following granulocyte transfusion varied by the dose transfused and were higher in children than in adults.

Immunological repertoire linked to PSTPIP1-associated myeloid-related inflammatory (PAMI) syndrome.

BACKGROUND: Mutations along PSTPIP1 gene are associated to two specific conditions, PAPA syndrome and PAMI syndrome, both autoinflammatory disorders associated to disturbances in cytoskeleton formation. Immunological aspects of PAMI syndrome has not yet been reported neither the clinical impact on therapeutical decisions. METHODS: Clinical data of patients records were retrospectively accessed. Genomic DNA were extracted and sequenced following standard procedures. Peripheral lymphocytes were quantified in T, B e FOXP3 phenotypes. RESULTS: We describe two related patients with PAMI syndrome harboring the usual E250K mutation. Anti-IL1 therapy could partially control the disease in the index patient. A broad spectrum of immunological effects as well as an aberrant expression of FOXP3 could be observed. CONCLUSIONS: Here we report two related brazilian patients with PAMI syndromes harboring the E250K mutation in PSTPIP1, their immunological aspects and the therapeutical response to canakinumab.

Outcomes of second hematopoietic stem cell transplantation using reduced-intensity conditioning in an outpatient setting.

Relapse and graft failure after autologous (auto) or allogeneic (allo) hematopoietic stem cell transplantation (HSCT) are serious and frequently fatal events. A second HSCT can be a life-saving alternative, however, information on the results of such intervention in an outpatient setting is limited. Outpatient second hematoprogenitors transplant after reduced-intensity conditioning (RIC) at a single academic center was analyzed. Twenty-seven consecutive adults who received an allo-HSCT after an initial auto- or allo-HSCT from 2006 to 2019 were included. Data were compared using the χ2 -test. Survival analysis using Kaplan-Meier and Cox proportional hazard models was performed; cumulative incidence estimation of transplant-related mortality (TRM) was assessed. Hodgkin lymphoma was the most frequent diagnosis for the group with a first auto-HSCT with 5/12 (41.7%) cases, and acute myeloid leukemia for those with a first allo-HSCT with 6/15 (40%). One-year overall survival and disease-free survival (DFS) was 66.7% (95% CI 27.2-88.2) and 59% (95% CI 16-86) for 12 patients with a first auto-HSCT; and for 15 patients with a first allo-HSCT, it was 43.3% (95% CI 17.9-66.5) and 36% (95% CI 13.2-59.9), respectively. Eight (29.6%) patients died of TRM and the cumulative incidence of TRM at 1 year was 22% (95% CI 8.6-39.27). Chronic graft-versus-host disease and late (>10 months) second transplantation were protective factors for longer survival. Neutropenic fever was more common in the group with a first allo-HSCT (p = 0.01). In conclusion, outpatient second allo-HSCT using RIC after auto- or allografting failure or relapse is feasible and offers a reasonable alternative for patients with severe life-threatening hematological diseases.

[Sinus infection caused by Exserohilum rostratum in a pediatric patient with acute myeloid leukemia]. / Infección rino-sinusal por Exserohilum rostratum en un niño con leucemia mieloide aguda.

The episodes of febrile neutropenia are severe cases that require an exhaustive etiological study and a quick start of antimicrobial agents. Within the possible microorganisms, fungal origins are also found, and depending on its tissue invasion, they can reach a high mortality rate. A case of a pediatric patient who suffered from acute myeloid leukemia is reported, and after his induction chemotherapy, the patient showed an episode of febrile neutropenia, which matches a rhinosinusal infection caused by Exserohilum rostratum, a filamentous fungi that is uncommonly associated with pathological cases. An antifungal therapy and an early surgical treatment were started, which lead to a positive response, without complications to the patient. After the monitoring and receiving secondary prophylaxis during the episodes of neutropenia, the patient hasn't presented new injuries nor rhinosinusal damage.

Infección rino-sinusal por Exserohilum rostratum en un niño con leucemia mieloide aguda / Sinus infection caused by Exserohilum rostratum in a pediatric patient with acute myeloid leukemia

Resumen Los episodios de neutropenia febril son cuadros graves, que requieren un estudio etiológico exhaustivo y un inicio rápido de antimicrobianos. Dentro de los posibles microorganismos causales se encuentran los de origen fúngico, los que, dependiendo de su grado de invasión tisular, pueden llegar a presentar una alta mortalidad. Presentamos el caso de un niño con una leucemia mieloide aguda, que tras su quimioterapia de inducción, presentó un episodio de neutropenia febril, con una infección rino-sinusal por Exserohilum rostratum, hongo filamentoso que raramente se asocia a cuadros patológicos. Se inició rápidamente terapia antifúngica, lo cual, asociado a un aseo quirúrgico precoz, lograron una respuesta clínica favorable, sin complicaciones. Luego del seguimiento, y tras recibir profilaxis secundaria durante los episodios de neutropenia, no ha vuelto a presentar nuevas lesiones ni compromiso rino-sinusal.

Abstract The episodes of febrile neutropenia are severe cases that require an exhaustive etiological study and a quick start of antimicrobial agents. Within the possible microorganisms, fungal origins are also found, and depending on its tissue invasion, they can reach a high mortality rate. A case of a pediatric patient who suffered from acute myeloid leukemia is reported, and after his induction chemotherapy, the patient showed an episode of febrile neutropenia, which matches a rhinosinusal infection caused by Exserohilum rostratum, a filamentous fungi that is uncommonly associated with pathological cases. An antifungal therapy and an early surgical treatment were started, which lead to a positive response, without complications to the patient. After the monitoring and receiving secondary prophylaxis during the episodes of neutropenia, the patient hasn't presented new injuries nor rhinosinusal damage.

Impairment of G-CSF receptor on granulocytic progenitor cells causes neutropenia in protein malnutrition.

OBJECTIVE: It is well known that protein malnutrition (PM) states can affect hematopoiesis, leading to severe leukopenia and reduced number of granulocytes, which act as the first line of defense, and are important to the innate immune response. The aim of this study was to elucidate some of the mechanisms involved in the impairment of granulopoiesis in PM. METHODS: Male C57BL/6 mice were submitted to PM with a low-protein diet containing 2% protein. Control mice were fed a 12% protein-containing diet. Bone marrow histology and the percentage of granulocytic progenitors were evaluated after in vivo granulocyte-colony stimulating factor (G-CSF) stimulus. Cell proliferation, STAT3 signaling, and the expression of G-CSF receptor were evaluated in hematopoietic progenitor cells. RESULTS: Malnourished animals presented with leukopenia associated with reduced number of granulocytes and reduced percentage of granulocytic progenitors; however, no differences were observed in the regulatory granulopoietic cytokine G-CSF. Additionally, the malnourished group presented with impaired response to in vivo G-CSF stimulus compared with control animals. PM was implicated in decreased ability of c-Kit+ cells to differentiate into myeloid progenitor cells and downregulated STAT3 signaling. Furthermore, the malnourished group exhibited reduced expression of G-CSF receptor on granule-monocytic progenitors. This reduced expression was not completely reversible with G-CSF treatment. CONCLUSIONS: This study implies that PM promotes intrinsic alterations to hematopoietic precursors, which result in hematologic changes, mainly neutropenia, observed in peripheral blood in PM states.

How does preeclampsia affect neonates? Highlights in the disease's immunity.

INTRODUCTION: Preeclampsia (PE) is the primary obstetrical cause in one of the four perinatal deaths. Although the etiology and pathogenesis of preeclampsia is not fully known, a proinflammatory immune state prevails and can disrupt fetal hematopoiesis. Some of the effects on the newborn include neonatal thrombocytopenia, neutropenia, a reduction in T regulatory cells, and an increased cytotoxic natural killer cell profile. METHODS: Electronic databases were searched, and defined criteria were applied to select articles for review. The review covered literature on the effects on neonatal due to maternal preeclampsia, fetal outcomes, and new treatments in research aimed at reducing morbidity and mortality of the disease. DISCUSSION: The cytotoxic environment present in PE affects the development of fetal cell lineages. Neutropenia is observed in 50% of neonates and is correlated with mortality, although its treatment is not well-established. The enhancement in erythropoietin and the hypoxic setting present in the disease can also lead to thrombocytopenia. Per partum management includes platelet transfusion in order to avoid severe complications such as intraventricular hemorrhage. Regarding other cell lines, a cytotoxic profile is observed to be reflecting the milieu present in the mothers' bloodstream. This disruption alters the immune system response into a proinflammatory profile and can be correlated to neonatal necrotizing enterocolitis. An antiangiogenic environment is also part of the preeclampsia presentation and can be responsible for the enhancement of bronchopulmonary dysplasia observed in this population. Meanwhile, the reduction in angiogenic factors, such as vascular endothelial growth factor (VEGF), can be a protective mechanism for retinopathy of prematurity. Studies of the long-term effects of these observations are lacking, but lower neurodevelopmental scores and a higher cardiovascular risk are noted. New treatments in research propose a prevention of the disease during gestation in order to reduce the effects more efficiently in the fetus. Phosphodiesterase inhibitors, endothelin 1 receptor antagonists and manipulation of heme oxygenase-1 enzyme pathway are possible therapeutic alternatives. This review summarizes the current understanding of how preeclampsia affects neonates. As a conclusion, further studies are needed to build up a guideline to manage those effects. A research agenda is proposed.

[Epidemiology and risk factors for prolonged hospital length of stay in children with leukemia and bacteremia. Cohort study]. / Epidemiología y factores de riesgo de internación prolongada en niños con leucemia y bacteriemia. Estudio de cohorte.

INTRODUCTION: Bacteremia is a frequent complication in children with cancer, which is associated with greater severity, prolonged hospitalization and mortality. Prolonged hospitalization conditions greater morbidity and risk of acquisition of intranosocomial infections. AIM: To describe risk factors for prolonged hospital length of stay in children with leukemia and bacteremia. METHODS: Cohort study. Episodes of bacteremia in patients with leukemia at Garrahan Hospital from 1/1/2015 to 31/12/2016 were reviewed. We compared data from patients with a LOS of 14 days or more with those admitted for less than 14 days. Bivariate and logistic regression analysis was performed. We used Stata 13 statistical package. RESULTS: n = 121. Median age 59 months.81 patients (67%) had a diagnosis of acute lymphoblastic leukemia, followed by acute myeloid leukemia in 40 (33%). 96 patients (79%) had a central venous catheter (CVC), 94 patients (78%) were neutropenic. Blood cultures were positive for Enterobacteriaceae in 55 cases (45%), coagulase-negative staphylococci in 28 cases (23%), Group viridans Streptococcus in 19 (16%), Pseudomonas aeruginosa in 8 (7%). (9%). By the multivariate analysis, three factors remained significantly associated with length of stay of more than 14 days: CVC associated bacteremia (OR 21,73; CI95% 1.2-43.2; p 0.04), severe neutropenia (OR 1.75; CI95% 1.82-1.28; p 0.03) and coinfection (OR 27.4; CI95% 2.8-260.8; p 0.004). CONCLUSION: CVC associated bacteremia, severe neutropenia and viral coinfection were associated with hospital LOS of more than 14 days.

[Successful treatment of disseminated fusariosis in a febrile neutropenic patient with combined antifungal therapy of voriconazol plus amphotericin B deoxycholate]. / Tratamiento exitoso de una fusariosis diseminada en un paciente neutropénico febril con terapia antifúngica combinada de voriconazol más anfotericina B deoxicolato.

We report a case of a patient with acute lymphoblastic leukemia (ALL), who developed a disseminated infection by Fusarium verticillioides during chemotherapy-induced neutropenia. He was successfully treated only after combination therapy with voriconazole plus amphotericin B deoxycolate was used, but not when these compounds were used in an isolated form.

Disseminated fusariosis with cutaneous involvement in hematologic malignancies: report of six cases with high mortality rate

Abstract: Fusariosis is due to inhalation or direct contact with conidia. Clinical presentation depends on host's immunity and can be localized, focally invasive or disseminated. Given the severity of this infection and the possibility for the dermatologist to make an early diagnosis, we report six cases of patients with hematologic malignancies, who developed febrile neutropenia an skin lesions suggestive of cutaneous fusariosis. All patients had skin cultures showing growth of Fusarium solani complex, and they received amphotericin B and voriconazole. As this infection can quickly lead to death, dermatologists play a crucial role in diagnosing this disease.

Disseminated fusariosis with cutaneous involvement in hematologic malignancies: report of six cases with high mortality rate.

Fusariosis is due to inhalation or direct contact with conidia. Clinical presentation depends on host's immunity and can be localized, focally invasive or disseminated. Given the severity of this infection and the possibility for the dermatologist to make an early diagnosis, we report six cases of patients with hematologic malignancies, who developed febrile neutropenia an skin lesions suggestive of cutaneous fusariosis. All patients had skin cultures showing growth of Fusarium solani complex, and they received amphotericin B and voriconazole. As this infection can quickly lead to death, dermatologists play a crucial role in diagnosing this disease.

Tratamiento exitoso de una fusariosis diseminada en un paciente neutropénico febril con terapia antifúngica combinada de voriconazol más anfotericina B deoxicolato / Successful treatment of disseminated fusariosis in a febrile neutropenic patient with combined antifungal therapy of voriconazol plus amphotericin B deoxycholate

Resumen Presentamos el caso clínico de un paciente con una leucemia linfoblástica aguda (LLA) que desarrolló una fusariosis diseminada por Fusarium verticillioides durante un episodio prolongado de neutropenia febril post quimioterapia. Fue exitosamente tratado cuando se usó terapia combinada de voriconazol más anfotericina B deoxicolato.

We report a case of a patient with acute lymphoblastic leukemia (ALL), who developed a disseminated infection by Fusarium verticillioides during chemotherapy-induced neutropenia. He was successfully treated only after combination therapy with voriconazole plus amphotericin B deoxycolate was used, but not when these compounds were used in an isolated form.

National Trends in Hospitalization for Fever and Neutropenia in Children with Cancer, 2007-2014.

OBJECTIVE: To assess the trends of inpatient resource use and mortality in pediatric hospitalizations for fever with neutropenia in the US from 2007 to 2014. STUDY DESIGN: Using National (Nationwide) Inpatient Sample (NIS) and International Classification of Diseases, Ninth Revision, Clinical Modification codes, we studied pediatric cancer hospitalizations with fever with neutropenia between 2007 and 2014. Using appropriate weights for each NIS discharge, we created national estimates of median cost, length of stay, and in-hospital mortality rates. RESULTS: Between 2007 and 2014, there were 104 315 hospitalizations for pediatric fever with neutropenia. The number of weighted fever with neutropenia hospitalizations increased from 12.9 (2007) to 18.1 (2014) per 100 000 US population. A significant increase in fever with neutropenia hospitalizations trend was seen in the 5- to 14-year age group, male sex, all races, and in Midwest and Western US hospital regions. Overall mortality rate remained low at 0.75%, and the 15- to 19-year age group was at significantly greater risk of mortality (OR 2.23, 95% CI 1.36-3.68, P = .002). Sepsis, pneumonia, meningitis, and mycosis were the comorbidities with greater risk of mortality during fever with neutropenia hospitalizations. Median length of stay (2007: 4 days, 2014: 5 days, P < .001) and cost of hospitalization (2007: $8771, 2014: $11 202, P < .001) also significantly increased during the study period. CONCLUSIONS: Our study provides information regarding inpatient use associated with fever with neutropenia in pediatric hospitalizations. Continued research is needed to develop standardized risk stratification and cost-effective treatment strategies for fever with neutropenia hospitalizations considering increasing costs reported in our study. Future studies also are needed to address the greater observed mortality in adolescents with cancer.