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1.
Blood ; 142(16): 1387-1398, 2023 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-37856089

RESUMEN

The correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children as well. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S ribosomal RNA amplicon sequencing to profile the gut microbiota and estimate diversity with the Shannon index. A global-to-local networking approach was used to characterize the ecological structure of the gut microbiota. Patients were stratified into higher- and lower-diversity groups at 2 time points: before transplantation and at neutrophil engraftment. The higher-diversity group before transplantation exhibited a higher probability of overall survival (88.9% ± 5.7% standard error [SE] vs 62.7% ± 8.2% SE; P = .011) and lower incidence of grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD). No significant difference in relapse-free survival was observed between the 2 groups (80.0% ± 6.0% SE vs 55.4% ± 10.8% SE; P = .091). The higher-diversity group was characterized by higher relative abundances of potentially health-related microbial families, such as Ruminococcaceae and Oscillospiraceae. In contrast, the lower-diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae. Network analysis detected short-chain fatty acid producers, such as Blautia, Faecalibacterium, Roseburia, and Bacteroides, as keystones in the higher-diversity group. Enterococcus, Escherichia-Shigella, and Enterobacter were instead the keystones detected in the lower-diversity group. These results indicate that gut microbiota diversity and composition before transplantation correlate with survival and with the likelihood of developing aGVHD.


Asunto(s)
Microbioma Gastrointestinal , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Humanos , Niño , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante Homólogo , Enfermedad Injerto contra Huésped/microbiología , Probabilidad
2.
J Infect Dis ; 229(4): 1050-1058, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37962869

RESUMEN

OBJECTIVE: The objective of this study was to assess the clinical impact and outcome of the SARS-CoV-2 infection on children with cancer or those who received a hematopoietic stem cell transplantation. METHODS: AIEOP (Italian Association of Pediatric Hematology and Oncology) performed a nationwide multicenter observational cohort study, including consecutive patients between April 2020 and November 2022. RESULTS: Twenty-five Italian centers participated and 455 patients were enrolled. We reported a significant increasing trend of symptomatic cases over the years, while the number of nonmild infections remained stable. Early infection after oncologic diagnosis (<60 days) and severe neutropenia were identified as independent risk factors for developing moderate, severe, or critical infections. The percentage of patients who were asymptomatic and mildly symptomatic and who stopped chemotherapy reduced over the years of the pandemic. Nine patients died, but no death was attributed to SARS-CoV-2 infection. CONCLUSIONS: SARS-CoV-2 infection presented a self-limiting benign course in the Italian pediatric oncohematology population during the pandemic, and its main consequence has been the discontinuation of cancer-directed therapies. The rate of patients who were asymptomatic and stopped chemotherapy reduced over the years, suggesting that the continuation of chemotherapy is a feasible option.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Niño , Humanos , SARS-CoV-2 , Neoplasias/complicaciones , Neoplasias/terapia , Neoplasias/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos
3.
Br J Haematol ; 204(1): 292-305, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37876306

RESUMEN

Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency and skeletal abnormalities. SDS bone marrow haematopoietic progenitors show increased apoptosis and impairment in granulocytic differentiation. Loss of Shwachman-Bodian-Diamond syndrome (SBDS) expression results in reduced eukaryotic 80S ribosome maturation. Biallelic mutations in the SBDS gene are found in ~90% of SDS patients, ~55% of whom carry the c.183-184TA>CT nonsense mutation. Several translational readthrough-inducing drugs aimed at suppressing nonsense mutations have been developed. One of these, ataluren, has received approval in Europe for the treatment of Duchenne muscular dystrophy. We previously showed that ataluren can restore full-length SBDS protein synthesis in SDS-derived bone marrow cells. Here, we extend our preclinical study to assess the functional restoration of SBDS capabilities in vitro and ex vivo. Ataluren improved 80S ribosome assembly and total protein synthesis in SDS-derived cells, restored myelopoiesis in myeloid progenitors, improved neutrophil chemotaxis in vitro and reduced neutrophil dysplastic markers ex vivo. Ataluren also restored full-length SBDS synthesis in primary osteoblasts, suggesting that its beneficial role may go beyond the myeloid compartment. Altogether, our results strengthened the rationale for a Phase I/II clinical trial of ataluren in SDS patients who harbour the nonsense mutation.


Asunto(s)
Enfermedades de la Médula Ósea , Insuficiencia Pancreática Exocrina , Lipomatosis , Humanos , Síndrome de Shwachman-Diamond , Proteína p53 Supresora de Tumor/genética , Lipomatosis/genética , Codón sin Sentido , Mielopoyesis , Neutrófilos/metabolismo , Quimiotaxis , Enfermedades de la Médula Ósea/genética , Enfermedades de la Médula Ósea/terapia , Insuficiencia Pancreática Exocrina/genética , Ribosomas/metabolismo
4.
Haematologica ; 109(8): 2515-2524, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-38385274

RESUMEN

Primary hemophagocytic lymphohistiocytosis (pHLH) is a severe, life-threatening hyperinflammatory syndrome caused by defects in genes of the granule-dependent cytotoxic pathway. Here we investigated the clinical presentation and outcome in a large cohort of 143 patients with pHLH diagnosed in the last 15 years and enrolled in the Italian registry. The median age at diagnosis was 12 months (interquartile range, 2-81), and 92 patients (64%) fulfilled the HLH-2004 criteria. Of 111 patients who received first-line combined therapy (HLH-94, HLH-2004, Euro-HIT protocols), 65 (59%) achieved complete response and 21 (19%) partial response. Thereafter, 33 patients (30%) reactivated, and 92 (64%) received hematopoietic stem cell transplantation, 78 of whom (85%) survived and were alive at a median follow-up from diagnosis of 67 months. Thirty-six patients (25%) died before hematopoietic stem cell transplantation and 14 (10%) after. Overall, 93 patients (65%) were alive after a median follow-up of 30 months. Unadjusted predictors of non-response were age <6 months and high ferritin and bilirubin levels, while predictors of pre-transplant and overall mortality were high ferritin and bilirubin levels. At multivariable analysis, high levels of ferritin predicted non-response, while high levels of bilirubin predicted pre-transplant and overall mortality. Despite recent advances in therapeutic management, pHLH remains a life-threatening condition with significant early mortality. Liver dysfunction is the main predictor of poor prognosis.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfohistiocitosis Hemofagocítica , Sistema de Registros , Humanos , Linfohistiocitosis Hemofagocítica/mortalidad , Linfohistiocitosis Hemofagocítica/terapia , Linfohistiocitosis Hemofagocítica/diagnóstico , Italia/epidemiología , Masculino , Femenino , Lactante , Preescolar , Niño , Resultado del Tratamiento , Adolescente , Pronóstico , Terapia Combinada , Estudios de Seguimiento
5.
Am J Hematol ; 99(6): 1066-1076, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38497679

RESUMEN

Haploidentical stem cell transplantation (haplo-SCT) represents the main alternative for children with inherited bone marrow failure syndrome (I-BMF) lacking a matched donor. This retrospective study, conducted on behalf of the EBMT SAAWP and PDWP, aims to report the current outcomes of haplo-SCT in I-BMFs, comparing the different in vivo and ex vivo T-cell depletion approaches. One hundred and sixty-two I-BMF patients who underwent haplo-SCT (median age 7.4 years) have been registered. Fanconi Anemia was the most represented diagnosis (70.1%). Based on different T-cell depletion (TCD) approaches, four categories were identified: (1) TCRαß+/CD19+-depletion (43.8%); (2) T-repleted with post-transplant Cyclophosphamide (PTCy, 34.0%); (3) In-vivo T-depletion with ATG/alemtuzumab (14.8%); (4) CD34+ positive selection (7.4%). The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 76% respectively, while that of primary and secondary graft failure was 10% and 8% respectively. The 100-day CI of acute GvHD grade III-IV(95% CI) was 13%, while the 24-month CI of extensive chronic GvHD was 4%. After a median follow-up of 43.4 months, the 2-year overall survival(OS) and GvHD/Rejection-free Survival (GRFS) probabilities are 67% and 53%, respectively. The TCR CD3+αß+/CD19+ depletion group showed a significantly lower incidence of both acute and chronic GvHD and higher OS (79%; p0.013) and GRFS (71%; p < .001), while no significant differences in outcomes have been observed by different diagnosis and conditioning regimens. This large retrospective study supports the safety and feasibility of haplo-SCT in I-BMF patients. TCRαß+/CD19+ depletion offers higher chances of patients' survival, with a significantly lower risk of severe a- and c-GvHD in I-BMFs compared to other platforms.


Asunto(s)
Anemia Aplásica , Humanos , Niño , Estudios Retrospectivos , Masculino , Femenino , Preescolar , Adolescente , Anemia Aplásica/terapia , Lactante , Trasplante de Células Madre Hematopoyéticas , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trastornos de Fallo de la Médula Ósea , Trasplante Haploidéntico , Depleción Linfocítica , Acondicionamiento Pretrasplante/métodos , Hemoglobinuria Paroxística/terapia , Anemia de Fanconi/terapia , Anemia de Fanconi/mortalidad , Enfermedades de la Médula Ósea/terapia , Antígenos HLA/genética , Antígenos HLA/inmunología
6.
Pediatr Blood Cancer ; 71(7): e30990, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38605511

RESUMEN

BACKGROUND: Central venous catheter (CVC)-related complications remain a significant cause of morbidity in pediatric hematology-oncology. We prospectively surveyed the incidence of CVC-related complications in children with hematologic-oncologic diseases. PROCEDURE: Five-hundred-eighty-one CVCs were inserted in 421 patients from January 2010 to June 2022 (153,731 CVC days observation; follow-up data up to December 31, 2022). RESULTS: Overall, 671 complications were recorded (4.365/1000 CVC days): 49.7% malfunctions (1.88/1000 CVC days, 4.8% of CVC early removals), 23.9% bacteremia (0.90/1000, 15.1%), 19.6% mechanical complications (0.74/1000, 70.2%), 20.1% localized infections (0.76/1000, 17.1%), 0.5% thrombosis (0.02/1000, 33.3%). At multivariate analysis, risk factors for malfunction were Broviac-Hickman type of CVC (hazard ratio [HR] 2.5) or Port-a-cath (HR 3.4) or Proline (HR 4.3), p < .0001; for bacteremia double-lumen CVC (HR 3.2, p < .0001); for mechanical complications age at CVC insertion under median (HR 4.5, p < .0001) and Broviac-Hickman (HR 1.6) or Proline (HR 2.7), p = .01; finally for localized infections Broviac-Hickman (HR 2.9) or Proline (HR 4.4), p = .0001. The 2-year cumulative incidence of premature removal was 23.5%, and risk factors were age at CVC insertion under median (HR 2.4, p < .0001), Broviac-Hickman (HR 2.3) or Proline (HR 4.2), p < .0001. CONCLUSIONS: Premature removal occurs in approximately 20%-25% of long-term CVCs. A surveillance program has a fundamental role in identifying the risk factors for CVC complications and the areas of intervention to improve CVC management.


Asunto(s)
Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Catéteres Venosos Centrales , Neoplasias Hematológicas , Humanos , Femenino , Niño , Masculino , Estudios Prospectivos , Preescolar , Catéteres Venosos Centrales/efectos adversos , Adolescente , Lactante , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/etiología , Cateterismo Venoso Central/efectos adversos , Neoplasias Hematológicas/terapia , Estudios de Seguimiento , Factores de Riesgo , Bacteriemia/etiología , Bacteriemia/epidemiología , Incidencia , Pronóstico
7.
N Engl J Med ; 382(19): 1811-1822, 2020 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-32374962

RESUMEN

BACKGROUND: Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality. METHODS: We investigated the efficacy and safety of emapalumab (a human anti-interferon-γ antibody), administered with dexamethasone, in an open-label, single-group, phase 2-3 study involving patients who had received conventional therapy before enrollment (previously treated patients) and previously untreated patients who were 18 years of age or younger and had primary hemophagocytic lymphohistiocytosis. The patients could enter a long-term follow-up study until 1 year after allogeneic hematopoietic stem-cell transplantation or until 1 year after the last dose of emapalumab, if transplantation was not performed. The planned 8-week treatment period could be shortened or extended if needed according to the timing of transplantation. The primary efficacy end point was the overall response, which was assessed in the previously treated patients according to objective clinical and laboratory criteria. RESULTS: At the cutoff date of July 20, 2017, a total of 34 patients (27 previously treated patients and 7 previously untreated patients) had received emapalumab; 26 patients completed the study. A total of 63% of the previously treated patients and 65% of the patients who received an emapalumab infusion had a response; these percentages were significantly higher than the prespecified null hypothesis of 40% (P = 0.02 and P = 0.005, respectively). In the previously treated group, 70% of the patients were able to proceed to transplantation, as were 65% of the patients who received emapalumab. At the last observation, 74% of the previously treated patients and 71% of the patients who received emapalumab were alive. Emapalumab was not associated with any organ toxicity. Severe infections developed in 10 patients during emapalumab treatment. Emapalumab was discontinued in 1 patient because of disseminated histoplasmosis. CONCLUSIONS: Emapalumab was an efficacious targeted therapy for patients with primary hemophagocytic lymphohistiocytosis. (Funded by NovImmune and the European Commission; NI-0501-04 and NI-0501-05 ClinicalTrials.gov numbers, NCT01818492 and NCT02069899.).


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Neutralizantes/administración & dosificación , Interferón gamma/antagonistas & inhibidores , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Adolescente , Edad de Inicio , Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Neutralizantes/efectos adversos , Quimiocina CXCL9/sangre , Niño , Preescolar , Dexametasona/administración & dosificación , Quimioterapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Infecciones/etiología , Estimación de Kaplan-Meier , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/mortalidad , Linfohistiocitosis Hemofagocítica/terapia , Masculino , Resultado del Tratamiento
8.
Transpl Infect Dis ; 25 Suppl 1: e14173, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37846850

RESUMEN

Adenovirus (AdV) infection occurs in 0-20% of patients in the first 3-4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than in adult patients. About 50% of AdV infections involve the blood, which in turn, correlates with an increased risk developing AdV diseases, end-organ damage, and 6-month overall mortality. The main risk factors for AdV infection are T-cell depletion of the graft by ex vivo selection procedures or in vivo use of alemtuzumab or antithymocyte serum, development of graft versus host disease (GVHD) grade III-IV, donor type (haploidentical or human leucocyte antigen mismatched related donor > cord blood> unrelated matched donor) and severe lymphopenia (<0.2 × 109 /L). The prevention of AdV disease relies on early diagnosis of increasing viral replication in blood or stool and the pre-emptive start of cidofovir as viral load exceeds the threshold of ≥102-3 copies/mL in blood and/or 106 copies/g stool in the stool. Cidofovir (CDV), a cytosine monophosphate nucleotide analog, is currently the only antiviral recommended for AdV infection despite limited efficacy and moderate risk of nephrotoxicity. Brincidofovir, a lipid derivative of CDV with more favorable pharmacokinetics properties and superior efficacy, is not available and currently is being investigated for other viral infections. The enhancement of virus-specific T-cell immunity in the first few months post-HCT by the administration of donor-derived or third-party-donor-derived virus-specific T-cells represents an innovative and promising modality of intervention and data of efficacy and safety of the ongoing prospective randomized studies are eagerly awaited.


Asunto(s)
Infecciones por Adenoviridae , Trasplante de Células Madre Hematopoyéticas , Adulto , Humanos , Niño , Cidofovir , Estudios Prospectivos , Infecciones por Adenoviridae/tratamiento farmacológico , Infecciones por Adenoviridae/epidemiología , Factores de Riesgo , Factores Inmunológicos , Trasplante de Células Madre Hematopoyéticas/efectos adversos
9.
Eur J Pediatr ; 182(2): 689-696, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36446889

RESUMEN

Music therapy (MT) is a complementary therapy offered to children, young adults, and their families in pediatric oncology and palliative care. We performed a survey to collect information about MT in pediatric oncology in Italy. The outbreak of COVID-19 unavoidably changed the scenario of MT, suggesting some considerations presented in this survey. 27/32 (84.4%) centers belonging to the Infections and Supportive Therapy Working Group of Association of Pediatric Hematology and Oncology (AEIOP) completed in 2 different time points (T1 and T2) an online survey on MT, before and after COVID-19 pandemia. Different kinds of music approach were used taking care of patients in 21/27 centers, while in 14/21 (66%), a specific project of MT conducted by a music therapist was present. In 6/14 centers, MT activities were delivered for < 3 h/week, in 3 centers for > 3 and < 10 h/week, and in the remaining 5 for > 3 h/week. MT sessions were in different areas, day hospital, or ward (patient rooms, operating rooms, waiting rooms), on an individual basis or by groups. Patients were invited to MT by psychologists, caring physician, or nurse, or on equipé decision. MT was evaluated with tools self-made by music therapist in 11/14 centers. After COVID-19, MT has been withdrawn in 3 centers, sessions in the waiting rooms were reduced, individual sessions were preferred, and enrollment by multidisciplinary teams increased. CONCLUSION: This survey represents the starting platform to compare and discuss different experience of MT in AIEOP centers, to implement MT in pediatric oncology for a more qualified assistance to patients, and to improve quality of care. WHAT IS KNOWN: • Music therapy in pediatric oncology and palliative care can be used for the management and prevention of various somatic and psychological symptoms of patients and often is provided to children together with their families. • In Italy the application of Music therapy in the AIEOP pediatric oncology centers is constantly increasing, but due to the outbreak of Covid-19 Pandemic, Italian pediatric oncology departments were obliged to adopt restrictive measures. WHAT IS NEW: • Although the majority of Centres did not abrogate MT interventions, judgment about limitation should be carefully taken since MT helps children and even more adolescents in their fight against cancer. • The best practice of Music therapy in pediatric oncology requires communication and collaboration among qualified music therapists and multidisciplinary care team, using a model of family-centered care that actively involves parents/ caregivers in assessment, treatment planning, and care delivery.


Asunto(s)
COVID-19 , Musicoterapia , Neoplasias , Niño , Adolescente , Adulto Joven , Humanos , Pandemias , COVID-19/terapia , COVID-19/epidemiología , Neoplasias/epidemiología , Italia/epidemiología
10.
Mycoses ; 66(1): 35-46, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36064299

RESUMEN

BACKGROUND: Our multicentre study aims to identify baseline factors and provide guidance for therapeutic decisions regarding Magnusiomyces-associated infections, an emerging threat in patients with haematological malignancies. METHODS: HM patients with proven (Magnusiomyces capitatus) M. capitatus or (Magnusiomyces clavatus) M. clavatus (formerly Saprochaete capitata and Saprochaete clavata) infection diagnosed between January 2010 and December 2020 were recorded from the SEIFEM (Sorveglianza Epidemiologica Infezioni nelle Emopatie) group and FungiScope (Global Emerging Fungal Infection Registry). Cases of Magnusiomyces fungemia were compared with candidemia. RESULTS: Among 90 Magnusiomyces cases (60 [66%] M. capitatus and 30 (34%) M. clavatus), median age was 50 years (range 2-78), 46 patients (51%) were female and 67 (74%) had acute leukaemia. Thirty-six (40%) of Magnusiomyces-associated infections occurred during antifungal prophylaxis, mainly with posaconazole (n = 13, 36%) and echinocandins (n = 12, 34%). Instead, the candidemia rarely occurred during prophylaxis (p < .0001). First-line antifungal therapy with azoles, alone or in combination, was associated with improved response compared to other antifungals (p = .001). Overall day-30 mortality rate was 43%. Factors associated with higher mortality rates were septic shock (HR 2.696, 95% CI 1.396-5.204, p = .003), corticosteroid treatment longer than 14 days (HR 2.245, 95% CI 1.151-4.376, p = .018) and lack of neutrophil recovery (HR 3.997, 95% CI 2.102-7.601, p < .001). The latter was independently associated with poor outcome (HR 2.495, 95% CI 1.192-5.222, p = .015). CONCLUSIONS: Magnusiomyces-associated infections are often breakthrough infections. Effective treatment regimens of these infections remain to be determined, but neutrophil recovery appears to play an important role in the favourable outcome.


Asunto(s)
Candidemia , Hematología , Humanos , Femenino , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Masculino , Antifúngicos/uso terapéutico , Candidemia/tratamiento farmacológico , Pronóstico , Equinocandinas/uso terapéutico
11.
J Antimicrob Chemother ; 77(10): 2850-2858, 2022 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-35929089

RESUMEN

BACKGROUND: Trichoderma spp. are filamentous fungi causing invasive fungal diseases in patients with haematological malignancies and in peritoneal dialysis patients. OBJECTIVES: To analyse clinical presentation, predisposing factors, treatment and outcome of Trichoderma infections. METHODS: A systematic literature review was conducted for published cases of invasive Trichoderma infection in PubMed until December 2021 and by reviewing the included studies' references. Cases from the FungiScope® registry were added to a combined analysis. RESULTS: We identified 50 invasive infections due to Trichoderma species, including 11 in the FungiScope® registry. The main underlying conditions were haematological malignancies in 19 and continuous ambulatory peritoneal dialysis (CAPD) in 10 cases. The most prevalent infection sites were lung (42%) and peritoneum (22%). Systemic antifungal therapy was administered in 42 cases (84%), mostly amphotericin B (n = 27, lipid-based formulation 13/27) and voriconazole in 15 cases (30%). Surgical interventions were performed in 13 cases (26%). Overall mortality was 48% (n = 24) and highest for allogeneic HSCT and solid organ transplantation (SOT) recipients [80% (4/5) and 77% (7/9), respectively]. In patients treated with amphotericin B, voriconazole and caspofungin, mortality was 55% (15/27), 46% (7/15) and 28% (2/7), respectively. Three out of four patients treated with a combination therapy of voriconazole and caspofungin survived. CONCLUSIONS: Despite treatment with antifungal therapies and surgery, invasive Trichoderma infections are life-threatening complications in immunocompromised patients, especially after HSCT and SOT. In addition, Trichoderma spp. mainly affect the lungs in patients with haematological malignancies and the peritoneum in CAPD patients.


Asunto(s)
Neoplasias Hematológicas , Trichoderma , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Caspofungina , Neoplasias Hematológicas/complicaciones , Humanos , Sistema de Registros , Voriconazol/uso terapéutico
12.
Ann Hematol ; 101(8): 1843-1851, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35726104

RESUMEN

COVID-19 has a mild clinical course with low mortality rate in general pediatric population, while variable outcomes have been described in children with cancer. Infectious diseases working party of the AIEOP collected data on the clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric oncology/hematology patients from April 2020 to May 2021, including the second and the third waves of the pandemic in Italy. Factors potentially associated with moderate, severe, or critical COVID-19 were analyzed. Of the 153 SARS-Cov2 infections recorded, 100 were asymptomatic and 53 symptomatic. The course of COVID-19 was mild in 41, moderate in 2, severe in 5, and critical in 5 children. A total of 40.5% of patients were hospitalized, ten requiring oxygen support and 5 admitted to the intensive care unit. Antibiotics and steroids were the most used therapies. No patient died due to SARS-CoV-2 infection. Infections occurring early (< 60 days) after the diagnosis of the underlying disease or after SCT were associated to moderate, severe, and critical disease compared to infections occurring late (> 60 days) or during maintenance therapy. In the patients on active chemotherapy, 59% withdrew the treatment for a median of 15 days. SARS-CoV-2 presented a favorable outcome in children with cancer in Italy during the pandemic. Modification of therapy represents a major concern in this population. Our findings suggest considering regular chemotherapy continuation, particularly in patients on maintenance therapy or infected late after the diagnosis.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Hematología , Neoplasias , COVID-19/epidemiología , Niño , Enfermedades Transmisibles/epidemiología , Humanos , Italia/epidemiología , Neoplasias/epidemiología , Pandemias , ARN Viral , SARS-CoV-2
13.
Pediatr Blood Cancer ; 69(10): e29801, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35656841

RESUMEN

BACKGROUND: Brentuximab vedotin (BV) is an antibody drug-conjugated anti-CD30 approved for the treatment of adult classical Hodgkin's lymphoma (HL), whereas it is considered as off-label indication in paediatrics. The aim of the study was to evaluate the safety and efficacy of BV to treat patients aged less than 18 years with refractory/relapsed HL. MATERIALS AND METHODS: In this multicentre, retrospective study, 68 paediatric patients who received at least one dose of BV between November 2011 and August 2020 were enrolled. A median of nine doses of BV were administered as monotherapy (n = 31) or combined with other therapies (n = 37). BV was administrated alone as consolidation therapy after stem cell transplantation (SCT) in 12 patients, before SCT in 18 patients, whereas in 15 patients it was used before and after SCT as consolidation therapy. Median follow-up was 2.8 years (range: 0.6-8.9 years). RESULTS: The best response was observed in the 86% of patients; the overall response rate was 66%. The 3-year progression-free survival was 58%, whereas the overall survival was 75%. No statistically significant differences between patients treated with BV monotherapy or combination were highlighted. In multivariate analysis, patients with non-nodular sclerosis HL and not transplanted had an increased risk of failure. Overall, 46% of patients had grade 3-4 adverse events that led to BV discontinuation in five of them. CONCLUSION: In conclusion, our study confirms that BV was a safe and effective drug, able to induce complete remission, either as monotherapy or in association with standard therapy.


Asunto(s)
Enfermedad de Hodgkin , Inmunoconjugados , Adulto , Brentuximab Vedotina , Niño , Enfermedad de Hodgkin/terapia , Humanos , Inmunoconjugados/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento
14.
Transpl Infect Dis ; 24(2): e13773, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34918856

RESUMEN

The objective of the study was to assess the current clinical practice and the attitude toward deferral of HCT/chemotherapy in patients with hematological diseases in cases of asymptomatic patients with a positive assay for SARS-CoV-2. In August 2021, we performed a survey among EBMT centers regarding their attitude toward deferral of HCT/chemotherapy in patients with a positive PCR result. Centers were willing to defer the planned cellular therapy for patients with asymptomatic SARS-CoV-2 infection without previous COVID-19 disease, and patients who became asymptomatic after a previous COVID19 disease but persistently shed the virus, respectively, in case of high-risk allo-HCT (90.2%/76.9%), low-risk allo-HCT for malignant diseases (88.2%/83.7%), allo-HCT for nonmalignant diseases (91.0%/91.0%), auto-HCT (88.0%/79.8%), and CAR-T therapy (83.1%/81.4%). The respective rates toward deferral of noncellular therapy patients was lower for both groups of patients, and varied with the primary diagnosis and anti-malignant treatment. There is a relatively high rate of willingness to defer treatment in asymptomatic patients being positive for SARS-CoV-2, planned for cellular therapy, regardless of previous history of vaccination or COVID-19. The same approach is presented for most of patients before noncellular therapy. Nevertheless, each patient should be considered individually weighting risks and benefits.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Infecciones Asintomáticas , Humanos , Inmunoterapia Adoptiva , SARS-CoV-2
15.
Lancet Oncol ; 22(6): e254-e269, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33811813

RESUMEN

Paediatric patients with cancer and those undergoing allogeneic haematopoietic cell transplantation have an increased susceptibility to invasive fungal diseases. In addition to differences in underlying conditions and comorbidities relative to adults, invasive fungal diseases in infants, children, and adolescents are unique in terms of their epidemiology, the validity of current diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of phase 3 clinical trials to provide data to guide evidence-based interventions. To re-examine the state of knowledge and to further improve invasive fungal disease diagnosis, prevention, and management, the 8th European Conference on Infections in Leukaemia (ECIL-8) reconvened a Paediatric Group to review the literature and to formulate updated recommendations according to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) grading system, which are summarised in this Review.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia/terapia , Micosis/terapia , Antifúngicos/uso terapéutico , Congresos como Asunto , Guías como Asunto , Humanos , Leucemia/complicaciones , Leucemia/epidemiología , Leucemia/microbiología , Micosis/complicaciones , Micosis/epidemiología , Micosis/microbiología , Pediatría/tendencias
16.
Lancet Oncol ; 22(6): e270-e280, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33811814

RESUMEN

Paediatric patients with cancer and those undergoing haematopoietic cell transplantation are at high risk of bacterial infections. The 8th European Conference on Infections in Leukaemia (ECIL-8) convened a Paediatric Group to review the literature and to formulate recommendations for the use of antibiotics according to the European Society of Clinical Microbiology and Infectious Diseases grading system. The evaluation of antibacterial prophylaxis included mortality, bloodstream infection, febrile neutropenia, emergence of resistance, and adverse effects as endpoints. Initial antibacterial therapy and antibiotic de-escalation or discontinuation focused on patients with a clinically stable condition and without previous infection or colonisation by resistant bacteria, and on patients with a clinically unstable condition or with previous infection or colonisation by resistant bacteria. The final considerations and recommendations of the ECIL-8 Paediatric Group on antibacterial prophylaxis, initial therapy, and de-escalation strategies are summarised in this Policy Review.


Asunto(s)
Antibacterianos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia/terapia , Micosis/terapia , Congresos como Asunto , Guías como Asunto , Humanos , Leucemia/complicaciones , Leucemia/epidemiología , Leucemia/microbiología , Micosis/complicaciones , Micosis/epidemiología , Micosis/microbiología , Pediatría/tendencias
17.
J Clin Immunol ; 41(7): 1633-1647, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34324127

RESUMEN

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. METHODS: We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). RESULTS: Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. CONCLUSION: HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. CLINICAL IMPLICATIONS: HCT is a definitive cure for DADA2 with > 95% survival.


Asunto(s)
Agammaglobulinemia/terapia , Trastornos de Fallo de la Médula Ósea/terapia , Trasplante de Células Madre Hematopoyéticas , Inmunodeficiencia Combinada Grave/terapia , Adenosina Desaminasa/deficiencia , Adolescente , Adulto , Agammaglobulinemia/enzimología , Agammaglobulinemia/genética , Agammaglobulinemia/mortalidad , Trastornos de Fallo de la Médula Ósea/enzimología , Trastornos de Fallo de la Médula Ósea/genética , Trastornos de Fallo de la Médula Ósea/mortalidad , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Péptidos y Proteínas de Señalización Intercelular/deficiencia , Estimación de Kaplan-Meier , Masculino , Estudios Retrospectivos , Inmunodeficiencia Combinada Grave/enzimología , Inmunodeficiencia Combinada Grave/genética , Inmunodeficiencia Combinada Grave/mortalidad , Resultado del Tratamiento , Adulto Joven
18.
Pediatr Blood Cancer ; 68(4): e28880, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33522705

RESUMEN

BACKGROUND: Extra-appendicular neuroendocrine tumors (NETs) are very rare tumors. While diagnostic and therapeutic guidelines are well established for adults, data on children and adolescents are lacking. PATIENTS AND METHODS: Patients with a diagnosis of extra-appendicular NET registered on the Tumori Rari in Età Pediatrica - Rare Tumors in Pediatric Age (TREP) from 2000 to 2020 were analyzed. Clinical characteristics including patients' presentation, tumor features, treatment, and outcome were reviewed. RESULTS: Twenty-seven patients with extra-appendicular NET registered on TREP with a median age of 173 months. The primary site was the pancreas (12) or bronchi (10) in the majority of cases. Other primary sites included the thymus, Meckel's diverticulum, and liver. Thirteen (48%) of tumors extended beyond the organ of origin: four invaded neighboring organs and/or regional nodes and nine involved distant metastases. The 3-year event-free survival (EFS) for those with localized disease was superior to those with metastatic disease (66.6% 95% CI 5-95% vs 33% 95% CI 5-68%, respectively; P = .005). A complete resection was feasible in 17 patients. The 3-year EFS in these patients was superior to those with no or incomplete resection (R0 vs R1/R2, respectively; P = .007). Overall, 16 children had no evidence of disease at follow-up, and one is alive with disease; five died, and five were lost to follow-up. CONCLUSIONS: Data from our experience demonstrated a wide heterogeneity of presentation and outcome of these tumors. Localized disease and complete surgical resection were the main prognostic factors of good outcome. Other therapies may have a role in prolonging survival in metastatic disease.


Asunto(s)
Neoplasias de los Bronquios/diagnóstico , Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adolescente , Neoplasias de los Bronquios/epidemiología , Neoplasias de los Bronquios/terapia , Niño , Manejo de la Enfermedad , Femenino , Humanos , Neoplasias Intestinales/diagnóstico , Neoplasias Intestinales/epidemiología , Neoplasias Intestinales/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/terapia , Masculino , Tumores Neuroendocrinos/epidemiología , Tumores Neuroendocrinos/terapia , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/terapia , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/epidemiología , Neoplasias del Timo/terapia
19.
Int J Mol Sci ; 22(24)2021 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-34948128

RESUMEN

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, caused by loss-of-function mutations in the SBDS gene, a factor involved in ribosome biogenesis. By analyzing osteoblasts from SDS patients (SDS-OBs), we show that SDS-OBs displayed reduced SBDS gene expression and reduced/undetectable SBDS protein compared to osteoblasts from healthy subjects (H-OBs). SDS-OBs cultured in an osteogenic medium displayed a lower mineralization capacity compared to H-OBs. Whole transcriptome analysis showed significant differences in the gene expression of SDS-OBs vs. H-OBs, particularly in the ossification pathway. SDS-OBs expressed lower levels of the main genes responsible for osteoblastogenesis. Of all downregulated genes, Western blot analyses confirmed lower levels of alkaline phosphatase and collagen type I in SDS-OBs than in H-OBs. Interestingly, SDS-OBs showed higher protein levels of p53, an inhibitor of osteogenesis, compared to H-OBs. Silencing of Tp53 was associated with higher collagen type I and alkaline phosphatase protein levels and an increase in SDS-OB mineralization capacity. In conclusion, our results show that the reduced capacity of SDS-OBs to mineralize is mediated, at least in part, by the high levels of p53 and highlight an important role of SBDS in osteoblast functions.


Asunto(s)
Calcificación Fisiológica , Osteoblastos/metabolismo , Síndrome de Shwachman-Diamond/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Células Cultivadas , Femenino , Humanos , Masculino , Osteoblastos/patología , Proteínas/genética , Proteínas/metabolismo , Síndrome de Shwachman-Diamond/genética , Síndrome de Shwachman-Diamond/patología , Proteína p53 Supresora de Tumor/genética
20.
Br J Haematol ; 190(1): 93-104, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32080838

RESUMEN

Diamond-Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry's future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.


Asunto(s)
Anemia de Diamond-Blackfan/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Sistema de Registros , Factores de Tiempo , Adulto Joven
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