RESUMO
BACKGROUND: This study aimed to assess the impact that the quality of primary and subsequent surgeries has on the survival of patients with para-testicular rhabdomyosarcoma (PTRMS). METHODS: Patients with localized (IRS I-III) and metastatic (IRS IV) PTRMS were enrolled in the two Cooperative Weichteilsarkom Studiengruppe (CWS) trials (CWS-96, CWS-2002P) and the Soft Tissue Sarcoma Registry (SoTiSaR). RESULTS: Among 196 patients (median age, 8.4 years), 106 (54.1%) had primary complete resection. Image-defined lymph node (LN) disease was detected in 21 (11.5%) patients in the localized cohort and 12 (92.3%) patients in the metastatic cohort. The 5-year event-free survival (EFS) and overall survival (OS) were respectively 87.3% and 94.0% for the patients with localized PTRMS and 46.2% and 42.2% for the patients with metastatic PTRMS. Protocol violations during the primary surgery (PV-PS) were observed in 70 (42%) of the IRS I-III patients. This resulted in higher rates of R1/R2 resections (n = 53 [76%] vs n = 20 [21%]; p < 0.001) with a need for pretreatment re-excision (PRE) (n = 50 [83%] vs n = 10 [17%]; p < 0.001) compared with the patients undergoing correct primary surgery. Protocol violations during PRE occurred for 13 (20%) patients. Although PV-PS did not influence the 5-year EFS or OS in the localized PTRMS cohort, the unadjusted log-rank test showed that R status after PRE is a prognostic factor for 5-year OS (R1 vs R0 [81.8% vs 97.6%]; p = 0.02). CONCLUSIONS: The quality of surgical local control in PTRMS is unsatisfactory. Emphasis should be placed on evaluating the resection status after PRE in further clinical trials.
Assuntos
Sistema de Registros , Rabdomiossarcoma , Neoplasias Testiculares , Humanos , Masculino , Criança , Taxa de Sobrevida , Rabdomiossarcoma/cirurgia , Rabdomiossarcoma/patologia , Rabdomiossarcoma/mortalidade , Adolescente , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/mortalidade , Pré-Escolar , Seguimentos , Sarcoma/cirurgia , Sarcoma/patologia , Adulto Jovem , Adulto , Lactente , Prognóstico , Metástase Linfática , Pessoa de Meia-IdadeRESUMO
Therapy-resistant viral reactivations contribute significantly to mortality after hematopoietic stem cell transplantation. Adoptive cellular therapy with virus-specific T cells (VST) has shown efficacy in various single-center trials. However, the scalability of this therapy is hampered by laborious production methods. In this study we describe the in-house production of VST in a closed system (CliniMACS Prodigy® system, Miltenyi Biotec). In addition, we report the efficacy in 26 patients with viral disease following hematopoietic stem cell transplantation in a retrospective analysis (adenovirus, n=7; cytomegalovirus, n=8; Epstein-Barr virus, n=4; multi-viral, n=7). The production of VST was successful in 100% of cases. The safety profile of VST therapy was favorable (n=2 grade 3 and n=1 grade 4 adverse events; all three were reversible). A response was seen in 20 of 26 patients (77%). Responding patients had a significantly better overall survival than patients who did not respond (P<0.001). Virus-specific symptoms were reduced or resolved in 47% of patients. The overall survival of the whole cohort was 28% after 6 months. This study shows the feasibility of automated VST production and safety of application. The scalability of the CliniMACS Prodigy® device increases the accessibility of VST treatment.
Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Viroses , Humanos , Linfócitos T , Infecções por Vírus Epstein-Barr/terapia , Estudos Retrospectivos , Herpesvirus Humano 4 , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Viroses/etiologia , Viroses/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-TroncoRESUMO
BACKGROUND: Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance. METHODS: Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low- (LR), standard- (SR), and high-risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline-based regimen in the very high-risk (VHR) group. Data of patients with relapse (n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018) were retrospectively analyzed. RESULTS: Patients of initial LR (n = 2), SR (n = 16), HR (n = 41), and VHR (n = 9) group relapsed. sCHT consisted of ACCTTIVE (n = 36), TECC (n = 12), or other (n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection (p = .17). The 5-year event-free survival (EFS) and overall survival (OS) were 26% (±12%) and 31% (±14%). The 5-year OS of patients with relapse of SR, HR, and VHR groups was 80% (±21%), 20% (±16%), and 13% (±23%, p = .008), respectively. CONCLUSION: Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups.
Assuntos
Policetídeos , Rabdomiossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Criança , Etoposídeo , Carboplatina , Estudos Retrospectivos , Topotecan , Ciclofosfamida , Doença Crônica , Antraciclinas , Recidiva , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
Objective: Hypotonic fluids are commonly used in pediatric oncology despite evidence that these fluids can lead to hospital-acquired hyponatremia. This practice is most likely due to lack of data evaluating risks and benefits of isotonic fluids in pediatric oncology. To address this issue, our study investigates the effects of exchanging hypotonic fluids with isotonic fluids in a large pediatric oncology unit. Study Design: Prevalence of laboratory disorders before and after the change to balanced, isotonic fluids for all patients are compared in this retrospective analysis. Disturbances in electrolyte levels, fluid-, acid-base balance and kidney function were examined. Results: The rate of hyponatremia was reduced using isotonic fluids. There were no hypernatremic events. Volume overload might increase the use of furosemide when using isotonic fluids. Potassium and bivalent cation levels increased. The risk of acidosis is greatly reduced, whereas alkalosis was more frequent due to furosemide use. The rate of acute kidney injury did not increase. Conclusion: Using isotonic fluids for hyper-hydration in pediatric oncology lead to a modest reduction of hospital-acquired hyponatremia without causing hypernatremia, but the effects on fluid balance need further investigation. The additional intake of bivalent cations and buffering anions in balanced fluids has measurable effects.
Assuntos
Hipernatremia , Hiponatremia , Criança , Hidratação/efeitos adversos , Furosemida , Humanos , Hipernatremia/etiologia , Hiponatremia/complicações , Soluções Hipotônicas/efeitos adversos , Infusões Intravenosas , Soluções Isotônicas , Estudos RetrospectivosRESUMO
OBJECTIVE: Pediatric patients with relapsed or refractory acute lymphoblastic leukemia have a poor prognosis. We here assess the response rates, adverse events, and long-term follow-up of pediatric patients with relapsed/refractory acute lymphoblastic leukemia receiving blinatumomab. METHODS: Retrospective analysis of a single-center experience with blinatumomab in 38 patients over a period of 10 years. RESULTS: The median age at onset of therapy was 10 years (1-21 years). Seventy-one percent of patients had undergone at least one hematopoietic stem cell transplantation (HSCT) prior to treatment with blinatumomab. We observed a response to blinatumomab in 13/38 patients (34%). The predominant side effect was febrile reactions, nearly half of the patients developed a cytokine release syndrome. Eight events of neurotoxicity were registered over the 78 cycles (15%). To date, nine patients (24%) are alive and in complete molecular remission. All survivors underwent haploidentical HSCT after treatment with blinatumomab. CONCLUSIONS: Despite heavy pretreatment of most of our patients, severe adverse events were rare and response rates encouraging. Blinatumomab is a valuable bridging salvage therapy for relapsed or refractory patients to a second or even third HSCT.
Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Adolescente , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Criança , Pré-Escolar , Terapia Combinada , Gerenciamento Clínico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Prognóstico , Recidiva , Retratamento , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The etiology of pediatric acute lymphatic leukemia (ALL) is still unclear. Whole-metagenome shotgun sequencing of bone marrow samples in patients with treatment-naïve ALL (n=6) was performed for untargeted investigation of bacterial and viral DNA. The control group consisted of healthy children (n=4) and children with non-oncologic diseases (n=2) undergoing bone marrow sampling. Peripheral blood of all participants was investigated at the same time. After bioinformatical elimination of potential contaminants by comparison with the employed controls, no significant amounts of microbial or viral DNA were identified.