Symptoms of Survivors of Pediatric Hematopoietic Stem Cell Transplant by Age, Sex, and Transplant Type

Purpose: The purpose of this study was to describe symptoms experienced by survivors of pediatric hematopoietic stem cell transplant (HSCT), and demographic and treatment-factors associated with ongoing symptomology. Methods: Fifty pediatric survivors completed a cross-sectional pilot study. Questionnaires were administered online via REDCap to assess symptoms experienced in the last week. Survivors also consented to a medical record chart review. Results: Survivors were on average 5.4 years post-HSCT (range 1.1 to 9 years), male (58%), and Caucasian (80%) who received an allogeneic HSCT (92%). The most commonly reported symptoms were difficulty concentrating (42.5%), pain (38%), worry (38%), nervousness (37.5%), and lack of energy/fatigue (34%). Survivors reported up to 14 symptoms, with 90% of the sample experiencing at least one symptom in the previous week. Average number of symptoms varied by age group between 2.1 (8–9 years) and 6.8 (18 and older). Age and female gender were associated with higher levels of fatigue. Conclusions: The majority of survivors experienced at least one symptom in the previous week. Neuropsychological symptoms and pain endure well into survivorship that can influence outcomes such as function and health-related quality of life (HRQOL). Research is needed on biological mechanisms of ongoing symptomology, effective interventions to prevent or mitigate symptoms, and the impact of symptoms on patient outcomes including daily functioning and HRQOL. Implications Survivors of pediatric HSCT continued to experience symptoms for up to nine years. Survivors should be frequently screened for symptoms, as symptoms may affect function, learning/employment outcomes, and HRQOL.

Management of Invasive Fungal Infections in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: The Turin Experience

BackgroundAllogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are exposed to an increased risk of invasive fungal infections (IFIs) due to neutropenia, immunosuppressive treatments, graft-versus-host disease (GvHD) and incomplete immune reconstitution. Although clinical benefit from antifungal prophylaxis has been demonstrated, IFIs remain a leading cause of morbidity and mortality in these patients. In the last decades, attention has also been focused on potential risk factors for IFI to tailor an antifungal prevention strategy based on risk stratification.Aim of the StudyThis retrospective single-center study aimed to assess the epidemiology and the prognostic factors of IFI in a large cohort of allo-HSCT patients.MethodsBetween January 2004 and December 2020, 563 patients with hematological malignancies received an allo-HSCT at the Stem Cell Transplant Unit in Turin: 191 patients (34%) received grafts from a matched sibling donor, 284 (50.5%) from a matched unrelated donor, and 87 (15.5%) from an haploidentical family member. The graft source was peripheral blood in 81.5% of the patients. Our policy for antifungal prophylaxis included fluconazole in matched related and unrelated donors, while micafungin was administered in patients receiving haploidentical transplant. According to this practice, fluconazole was administered in 441 patients (79.6%) and micafungin in 62 (11.2%), while only 9 patients received mold-active prophylaxis. Galactomannan testing was routinely performed twice a week; patients with persisting fever unresponsive to broad spectrum antibiotics were evaluated with lung high-resolution computed tomography (HRCT) scan. In case of imaging suggestive of IFI, bronchoalveolar lavage (BAL) was performed whenever feasible.Statistical AnalysisOnly probable/proven IFI (PP-IFI) occurring during the first 12 months after transplant have been evaluated. IFIs were classified as probable or proven according to the new revised European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) consensus criteria. Multivariate competing risk regression, binary logistic, and proportional hazard models were performed to identify risk factors for PP-IFI.ResultsA total of 58 PP-IFIs (n = 47 probable; n = 11 proven) occurred in our patients resulting in a cumulative incidence of 4.1%, 8.1%, and 9.6% at 30, 180, and 365 days, respectively. Molds were the predominant agents (n = 50 Aspergillus; n = 1 Mucor), followed by invasive candidemia (n = 5 non-albicans Candida; n = 1 Candida albicans; n = 1 Trichosporon). Lung was the most frequent site involved in patients with mold infections (47/51, 92.2%). Median time from HSCT to IFI was 98.44 days (0–365 days). Only 34.5% of patients with IFI were neutropenic at the time of infection. The presence of IFI had a significant impact on overall survival at 1 year (IFI, 32.8% vs. non-IFI, 54.6%; p < 0.001). IFI-related mortality rate was 20.7% in the overall population, 17% in patients with probable IFI, and 36% in patients with proven IFI. Multivariate competing risk regression revealed that donor type was the factor significantly associated to the risk of IFI [subdistribution hazard ratio (SDHR), 1.91, IC 1.13–3.20; p = 0.015]. BAL was informative in a consistent number of cases (36/57, 63.2%) leading to the identification of fungal (21), bacterial (4), viral (3), and polymicrobial (8) infections. Overall, 79 patients (14%) received a diagnostic-driven treatment, and 63 patients (11.2%) received a fever-driven treatment. Liposomal amphoteric B was the drug used in the majority of patients receiving diagnostic-driven therapy (30/79, 38%), while caspofungin was administered more frequently in patients who received a fever-driven strategy (27/63, 42.9%).ConclusionAccording to our experience, a non-mold active prophylaxis in patients undergoing allo-HSCT is feasible when combined with an intensive diagnostic work-up including CT scan and BAL. BAL performed at the onset of the disease may provide informative results in most patients. A diagnostic-driven treatment strategy may contribute to limit the use of costly antifungal therapies.

Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia

Allogeneic stem cell transplantation still represents the best curative option for most patients with acute myeloid leukemia, but relapse is still dramatically high. Due to their immunologic activity and safety profile, hypomethylating agents (HMAs) represent an interesting backbone for combination therapies. This review reports mechanism of action, safety, and efficacy data on combination strategies based on HMAs in the setting of post-allogeneic stem cell transplant relapse. Several studies highlighted how HMAs and donor lymphocyte infusion (DLI) combination may be advantageous. The combination strategy of HMA with venetoclax, possibly in association with DLI, is showing excellent results in terms of response rate, including molecular responses. Lenalidomide, despite its well-known high rates of severe graft-versus-host disease in post-transplant settings, is showing an acceptable safety profile in association with HMAs with a competitive response rate. Regarding FLT3 internal tandem duplication (ITD) mutant AML, tyrosine kinase inhibitors and particularly sorafenib have promising results as monotherapy and in combination with HMAs. Conversely, combination strategies with gemtuzumab ozogamicin or immune checkpoint inhibitors did not show competitive response rates and seem to be currently less attractive strategies. Associations with histone deacetylase inhibitors and isocitrate dehydrogenase 1 and 2 (IDH1/2) inhibitors represent new possible strategies that need to be better investigated.

Lenalidomide, Bortezomib, and Dexamethasone as Induction Therapy Before Autologous Stem Cell Transplant for Multiple Myeloma

One relevant systematic review and network meta-analysis (which included 1 relevant randomized controlled trial), 4 non-randomized studies, and 6 evidence-based guideline reports, representing 5 evidence-based guidelines were identified in this report. The clinical effectiveness regarding response, relapse, progression-free survival, and overall survival broadly favoured bortezomib-lenalidomide-dexamethasone (RVd) over bortezomib-cyclophosphamide-dexamethasone (CyBorD), although the magnitude and direction of association was not always consistent, and few estimates were statistically significant. Limited evidence on the safety of RVd relative to CyBorD was found. No evidence on the cost-effectiveness of RVd as induction therapy before autologous stem cell transplant for multiple myeloma was found. Among the 5 included guidelines, 3 specifically recommend RVd as a first option for induction therapy among transplant-eligible newly diagnosed multiple myeloma patients, and 2 recommend more broadly defined 3-drug induction regimens that include RVd.

Evaluation of healthcare-associated infection rates in patients with hematologic malignancies and stem cell transplantation during the coronavirus disease 2019 (COVID-19) pandemic

Objective: To evaluate whether rates of healthcare-associated infections (HAIs) changed during the coronavirus disease 2019 (COVID-19) pandemic in malignant hematology and stem cell transplant patients. Design: A retrospective, cohort study. Patients: The study included malignant hematology and stem cell transplant patients admitted between March 1, 2019, through July 31, 2019, and March 1, 2020, through July 31, 2020. Methods: Rates of catheter-associated urinary tract infections (CAUTIs), central-line–associated bloodstream infections (CLABSIs), central-line–associated mucosal barrier injury infections (CLAMBIs), and Clostridioides difficile infections (CDIs) during the pandemic were compared to those in a control cohort. Secondary outcomes included the rate of non–COVID-19 respiratory viruses. Results: The rate of CAUTIs per 1,000 hospital days was 0.435 before the pandemic and 0.532 during the pandemic (incidence rate ratio [IRR], 1.224; 95% confidence interval [CI], 0.0314–47.72; P = .899). The rate of CLABSIs was 0.435 before the pandemic and 1.064 during the pandemic (IRR, 2.447; 95% CI, 0.186–72.18; P = .516). The rate of CLAMBIs was 2.61 before the pandemic and 1.064 during the pandemic (IRR 0.408, 95% CI 0.057–1.927; P = .284). The rate of CDIs was 2.61 before the pandemic and 1.579 during the pandemic (IRR, 0.612; 95% CI, 0.125–2.457; P = .512). Non–COVID-19 respiratory virus cases decreased significantly from 12 (30.8%) to 2 cases (8.3%) (P = 0.014). Conclusions: There was no significant difference in HAIs among inpatient malignant hematology and stem cell transplant patients during the COVID-19 pandemic compared to those of a control cohort. Rates of infection were low among both cohorts. Rates of community-acquired respiratory viruses decreased significantly during the pandemic among this population.