RESUMEN
PURPOSE: Orbital rhabdomyosarcoma is a rare soft tissue sarcoma in childhood but with a good prognosis. Treatment usually includes surgery, chemotherapy, and radiotherapy. This study aimed to evaluate long-term alterations in teeth and cranial bones in children, adolescents, and young adults after oncologic treatment for childhood orbital rhabdomyosarcoma. METHOD: This was a cross-sectional study that evaluated patients treated for orbital rhabdomyosarcoma between 1988 and 2011. Demographic, clinical, and treatment data were collected during the study period; also, panoramic radiographs, cephalometric study, and photographs of the face were taken. RESULTS: Eight long-term survivors were studied. Of those, 50% were male, 75% had less than 5 years of treatment, and 88% had only one of the orbits affected by the tumor. Regarding treatment, 50% received 50.4 Gy of radiotherapy in the orbit; the chemotherapy included vincristine, actinomycin D, and cyclophosphamide in 75% of the cases and also ifosfamide and etoposide in 25%. The children presented craniofacial alterations, mainly when radiotherapy occurred between 0 and 5 years old (p = 0.01). The mandibles also showed dental alterations, probably due to chemotherapy. CONCLUSION: In conclusion, orbital RMS patients treated with chemoradiotherapy, important dental, and facial bone alterations were found. The most significant were in the maxilla and close to the irradiation field. Dental and mandibular bone alterations were also found, indicating the probable chemotherapy action, as this region was not included in the irradiation field.
Asunto(s)
Neoplasias Orbitales , Rabdomiosarcoma , Humanos , Masculino , Femenino , Estudios Transversales , Rabdomiosarcoma/terapia , Adolescente , Neoplasias Orbitales/terapia , Niño , Preescolar , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia/métodos , Quimioradioterapia/efectos adversos , Lactante , Supervivientes de Cáncer/estadística & datos numéricos , Ciclofosfamida/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Colonic lymphoma is a rare malignant gastrointestinal tumor that can be revealed by an exceptional and serious complication: intestinal obstruction. Treatment is based on surgery and chemotherapy. We here report a case of diffuse colonic large B-cell lymphoma revealed by occlusion and diagnosed based on the examination of surgical specimen in a 64-year-old man who was in complete remission after six courses of R-CHOP.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Colon , Ciclofosfamida , Doxorrubicina , Obstrucción Intestinal , Linfoma de Células B Grandes Difuso , Prednisona , Rituximab , Vincristina , Humanos , Masculino , Persona de Mediana Edad , Obstrucción Intestinal/etiología , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/cirugía , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/complicaciones , Neoplasias del Colon/patología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/patología , Ciclofosfamida/administración & dosificación , Vincristina/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Prednisona/administración & dosificación , Doxorrubicina/administración & dosificación , Rituximab/administración & dosificación , Inducción de RemisiónRESUMEN
This case report describes a 40-year-old male patient with severe cardiac failure due to eosinophilic granulomatosis with polyangiitis (EGPA) and myocarditis. The fast diagnostic approach with cardiac MRI (CMR) and immunosuppressive treatment with glucocorticoid and cyclophosphamide near-normalized the patient's cardiac function. Myocarditis due to EGPA is rare, however life-threatening, so a systematic approach and early CMR should be considered in patients with known asthma presenting with eosinophilia and cardiac involvement.
Asunto(s)
Granulomatosis con Poliangitis , Miocarditis , Humanos , Masculino , Adulto , Miocarditis/tratamiento farmacológico , Miocarditis/etiología , Miocarditis/diagnóstico por imagen , Miocarditis/diagnóstico , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/patología , Imagen por Resonancia Magnética , Síndrome de Churg-Strauss/complicaciones , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/diagnóstico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéuticoRESUMEN
Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease with multi-system involvement. It involves the upper respiratory tract, lungs and kidneys. A 36-year-old female patient presented to a tertiary care referral hospital in Central India in 2023 with complaints of low-grade fever, dry cough and loss of appetite initially followed by dyspnoea, purpuric skin lesions, right lower limb swelling with pain and redness. Her chest radiograph revealed right upper lobe cavitary lesion with consolidation in the right lower lobe. Mycobacterium tuberculosis was detected in sputum and broncho alveolar lavage via cartridge based nucleic acid amplification assay. Later, computed tomography pulmonary angiography revealed bilateral pulmonary artery thromboembolism. Furthermore, her cytoplasmic-antineutrophil cytoplasmic antibody test was positive, serum creatinine was rising, urine microscopy had red cell casts and lower limb venous doppler revealed deep venous thrombosis. Histopathological examination of the skin lesion revealed vasculitis. Based on these findings, the patient was diagnosed with GPA. The patient improved with pulse steroids, cyclophosphamide, anticoagulants and anti-tuberculous therapy.
Asunto(s)
Granulomatosis con Poliangitis , Embolia Pulmonar , Tuberculosis Pulmonar , Humanos , Femenino , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiología , Embolia Pulmonar/complicaciones , Adulto , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico , India , Ciclofosfamida/uso terapéuticoRESUMEN
Background: Angioimmunoblastic T-cell lymphoma (AITL) is known for its unfavorable survival prognosis. Chidamide has shown efficacy in relapsed/refractory AITL, but its efficacy in newly diagnosed AITL is uncertain. Objective: This retrospective research aimed to evaluate the effectiveness and safety of chidamide when used with doxorubicin, cyclophosphamide, prednisone, and vincristine (CHOP) in comparison to CHOP by itself for individuals newly diagnosed with AITL, and to examine the impact of transplantation. Method: This was an analysis that compared outcomes among patients who received chidamide + CHOP on a clinical trial vs. historical controls who received CHOP alone, enrolling a total of sixty-six treatment-naive AITL patients between April 2014 and November 2022. Among them, thirty-three received chidamide in addition to CHOP (chidamide group), while thirty-three received CHOP alone (control group). The clinical characteristics were balanced between the two groups. All patients were scheduled to undergo up to six courses of treatment before transplantation. Results: The chidamide group had a significantly longer median overall survival (OS) compared to the control group, with a median OS that was not reached, as opposed to 20 months in the control group (p = 0.002). In the control group, the median progression-free survival (PFS) was 11 months, while in the chidamide group, it was 22 months (p = 0.080). In the high-risk group (IPI ≥ 3), the chidamide group demonstrated notably superior complete response (CR) and overall response rate (ORR) compared to the control cohort (p = 0.002, p = 0.034). The PFS and OS in the chidamide group were not reached, and there were significant differences compared to the control group (p = 0.007, p = 0.003). The median OS of the transplanted group was longer than the non-transplanted group (p = 0.004). On multivariate analysis, chidamide group reduced the hazards of death in the total cohort. Conclusion: As the study was non-random and retrospective, Chidamide combined with chemotherapy should be tested in randomized trials given its potential to improve prognosis in treatment-naive AITL patients. Furthermore, autologous hematopoietic stem cell transplantation (auto-HSCT) has demonstrated enhanced overall survival in individuals with AITL. Clinical trial registration: https://clinicaltrials.gov/, NCT03268889.
Asunto(s)
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aminopiridinas/uso terapéutico , Aminopiridinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzamidas/uso terapéutico , Benzamidas/administración & dosificación , Benzamidas/efectos adversos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Linfoma de Células T/mortalidad , Linfoma de Células T/terapia , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/diagnóstico , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Estudios Retrospectivos , Resultado del Tratamiento , Vincristina/uso terapéutico , Vincristina/administración & dosificaciónRESUMEN
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a severe autoimmune disease that often involves the upper and lower respiratory tracts. In recent years, numerous studies have found a significant increase in the incidence of cancer among AAV patients, but the association between lung cancer and AAV remains inconclusive, with relatively low clinical attention. This review summarizes the current literature on the risk of lung cancer in patients with ANCA-associated vasculitis (AAV), detailing the potential mechanisms by which AAV may contribute to lung cancer, and further elucidates the inherent carcinogenic risks of immunosuppressants.There is a correlation between AAV and lung cancer, which is related to T cell senescence and damage, as well as the abnormal expression of cytokines such as IL-6 and IL-10. In AAV patients, the use of cyclophosphamide and azathioprine (AZA) alone has a clear carcinogenic risk, with frequent use of CYC potentially posing a high risk for lung cancer. Although TNF inhibitors (TNFi) combined with CYC have carcinogenic risks, there is insufficient evidence to link them directly to an increased risk of lung cancer. For patients at high risk for lung cancer, the judicious use of immunosuppressants, timely computed tomography (CT), and lung cancer screening can reduce the risk of lung cancer in AAV patients.
Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Inmunosupresores , Neoplasias Pulmonares , Humanos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Azatioprina/uso terapéutico , Azatioprina/efectos adversosRESUMEN
BACKGROUND: F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). METHODS: This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. RESULTS: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 - 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. CONCLUSIONS: A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04174599, on 22/11/2019.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Factor Estimulante de Colonias de Granulocitos , Neutropenia , Humanos , Femenino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Filgrastim/administración & dosificación , Filgrastim/efectos adversos , Filgrastim/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/administración & dosificación , Epirrubicina/efectos adversos , Epirrubicina/administración & dosificación , Esquema de MedicaciónRESUMEN
First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014-2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72-1.09) and OS (HR = 0.93; 95% CI, 0.73-1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, -0.4%-34.1% and OS = 12.1%; 95% CI, -5.4-29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Linfoma de Células B Grandes Difuso , Prednisona , Rituximab , Vincristina , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Adulto , Anciano de 80 o más Años , Estadificación de Neoplasias , Resultado del Tratamiento , Países Bajos/epidemiologíaRESUMEN
In patients with relapsed or refractory neuroblastoma (NB), the limited efficacy of conventional chemotherapies necessitates the exploration of new treatment options. Previous studies have highlighted the anti-tumor properties of arsenic trioxide (ATO) in high-risk NB (HR-NB). This study aims to assess the effectiveness and safety of ATO combined with salvage chemotherapy regimens, featuring cyclophosphamide and topotecan, as a foundational treatment for children with relapsed or refractory NB. Eleven patients (four relapsed, seven refractory NB) were retrospectively analyzed for efficacy and treatment relevance. Salvage treatments, incorporating ATO (0.18 mg/kg daily for 8 h intravenously on days 1 to 10), were administered upon disease progression or relapse, with assessments conducted every two cycles. Treatments had 63.6% efficacy, with six cases of partial response, one case of stable disease, and four cases of disease progression. The overall response rate was 54.5%, and the disease control rate was 63.6%. Importantly, the systemic toxicity experienced by patients following salvage chemotherapy with ATO was mild. Salvage chemotherapy regimens featuring ATO demonstrated potential for prolonging disease stabilization for relapsed or refractory HR-NB patients, exhibiting both favorable efficacy and safety profiles. This suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.
Point 1. The inadequate effectiveness of traditional chemotherapy in individuals with recurrent or resistant neuroblastoma (NB) necessitates the investigation of novel therapeutic approaches. Point 2. Arsenic trioxide (ATO)-based salvage treatments are both effective and less toxic in relapsed or refractory NB. Point 3. Salvage chemotherapy regimens incorporating ATO have shown promise in extending disease stabilization in relapsed or refractory high-risk NB patients, with favorable efficacy and safety profiles, which suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Trióxido de Arsénico , Recurrencia Local de Neoplasia , Neuroblastoma , Terapia Recuperativa , Humanos , Trióxido de Arsénico/administración & dosificación , Trióxido de Arsénico/uso terapéutico , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/patología , Femenino , Masculino , Preescolar , Niño , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Topotecan/administración & dosificación , Topotecan/uso terapéutico , Topotecan/efectos adversos , Lactante , Resultado del Tratamiento , Adolescente , Resistencia a Antineoplásicos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversosRESUMEN
INTRODUCTION: There is a scarcity of research comparing the efficacy of cyclophosphamide and mycophenolate mofetil in childhood nephrotic syndrome. The aim was to evaluate the efficacy and safety of oral cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in children with steroid-sensitive nephrotic syndrome in terms of the proportion of children who have been off steroids for at least 6 months without proteinuria (responders). METHODS: This open-label retrospective-prospective comparative study was conducted in a pediatric nephrology clinic of a referral center for children between 1 and 18 years of age with FR/SD nephrotic syndrome. Group A consisted of patients who received oral cyclophosphamide (100, 25% female) at a dose of 2-2.5 mg/kg once daily for a period of 8-12 weeks. Group B consisted of patients who received oral mycophenolate mofetil (n = 61, 18% female) (dose: 800-1200 mg/m2) for at least 12 months. Responders were defined as children who were off steroids for at least 6 months along with absence of proteinuria. RESULTS: In the CYC group, 50% of the patients were responders, whereas 54% of the patients in the MMF group were responders (p = 0.614). The time to first relapse with CYC was 7 months (IQR 5.25-11) compared to 7 months (IQR 3.5-12) with MMF (p = 0.092). The relapse rate in the CYC group was 1.77 relapses per patient-year compared to 1.295 relapses per patient-year in the MMF group. The difference in relapse rate was significant (-0.474; 95% CI, 0.09 to 0.86 relapses/person-year) (p value = 0.009). Multivariate analysis revealed that an age of less than 5 years at the start of treatment was a significant factor for a better response to MMF (p value = 0.039, OR = 2.988, CI -1.055-8.468). CONCLUSIONS: The efficacy of MMF was similar to that of CYC in terms of response (6 months without steroids) in children with FR/SD nephrotic syndrome. MMF showed a favorable response in terms of the frequency of relapse and treatment failure. REGISTRATION OF THE STUDY WITH CLINICAL TRIALS REGISTRY OF INDIA: ( http://ctri.nic.in ;CTRI/2021/06/034421) (Dt: 28/06/2021).
Asunto(s)
Ciclofosfamida , Inmunosupresores , Ácido Micofenólico , Síndrome Nefrótico , Humanos , Ácido Micofenólico/uso terapéutico , Ácido Micofenólico/administración & dosificación , Síndrome Nefrótico/tratamiento farmacológico , Femenino , Niño , Masculino , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Preescolar , Adolescente , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Administración Oral , Lactante , Resultado del Tratamiento , Estudios Retrospectivos , Estudios ProspectivosRESUMEN
Ovarian insufficiency is one of the common reproductive disorders affecting women with limited therapeutic aids. Mesenchymal stem cells have been investigated in such disorders before yet, the exact mechanism of MSCs in ovarian regeneration regarding their epigenetic regulation remains elusive. The current study is to investigate the role of the bone marrow-derived mesenchymal stem cells (BM-MSCs) lncRNA (Neat-1 and Hotair1) and miRNA (mir-21-5p, mir-144-5p, and mir-664-5p) in mitigating ovarian granulosa cell apoptosis as well as searching BM-MSCs in altering the expression of ovarian and hypothalamic IGF-1 - kisspeptin system in connection to HPG axis in a cyclophosphamide-induced ovarian failure rat model. Sixty mature female Sprague Dawley rats were divided into 3 equal groups; control group, premature ovarian insufficiency (POI) group, and POI + BM-MSCs. POI female rat model was established with cyclophosphamide. The result revealed that BM-MSCs and their conditioned media displayed a significant expression level of Neat-1, Hotair-1, mir-21-5p, mir-144-5p, and mir-664-5p. Moreover, BM-MSCs transplantation in POI rats improves; the ovarian and hypothalamic IGF-1 - kisspeptin, HPG axis, ovarian granulosa cell apoptosis, steroidogenesis, angiogenesis, energy balance, and oxidative stress. BM-MSCs expressed higher levels of antiapoptotic lncRNAs and microRNAs that mitigate ovarian insufficiency.
Asunto(s)
Apoptosis , Ciclofosfamida , Factor I del Crecimiento Similar a la Insulina , Células Madre Mesenquimatosas , MicroARNs , Insuficiencia Ovárica Primaria , ARN Largo no Codificante , Ratas Sprague-Dawley , Animales , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ciclofosfamida/efectos adversos , Ratas , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Insuficiencia Ovárica Primaria/metabolismo , Insuficiencia Ovárica Primaria/genética , Insuficiencia Ovárica Primaria/inducido químicamente , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , Ovario/metabolismo , Células de la Médula Ósea/metabolismo , AngiogénesisAsunto(s)
Linfadenopatía Inmunoblástica , Ganglios Linfáticos , Linfoma de Células T , Células Plasmáticas , Humanos , Femenino , Persona de Mediana Edad , Anciano , Células Plasmáticas/patología , Ganglios Linfáticos/patología , Linfadenopatía Inmunoblástica/patología , Linfadenopatía Inmunoblástica/genética , Linfoma de Células T/patología , Linfoma de Células T/genética , Inmunofenotipificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Vincristina/uso terapéutico , Prednisona/uso terapéutico , Ciclofosfamida , DoxorrubicinaRESUMEN
INTRODUCTION: The diffuse large B-cell lymphoma (Dlbcl) is the most common non-Hodgkin lymphoma and at highest incidence among the elderly. Despite the improved outcomes of patients treated with the first-line (1L) standard of care until the end of 2022, composed by rituximab and polychemotherapy (R-Chop), during the last 20 years, the rate of relapsed and refractory Dlbcl (rrDlbcl) remains elevated. This study has identified and analyzed patients newly diagnosed with Dlbcl and treated with 1L, from the perspective of the Italian National Health Service (Ssn). METHODS: From the administrative database of Fondazione Ricerca e Salute (ReS) including ~5.5 million inhabitants/year in Italy, adults with a new in-hospital Dlbcl diagnosis (index date) and treated with 1L in 2018, 2019, 2020 and 2021 were identified and characterized in terms of demographics and comorbidities during a period (from 4 to 8 years) preceding index date. From 1 to 4 years following index date (follow-up), overall survival (Kaplan-Meier curves), percentage distribution of patients by line of therapy including dispensation/administration of chemo-immunotherapy, hemopoietic stem cell transplantation (Hsct), and direct healthcare costs charge to the Ssn, were evaluated. RESULTS: Overall, from the ReS database, 206 patients newly diagnosed with Dlbcl and treated with 1L from 2018 to 2021 in Italy (incidence from 0.9 to 1.7 x100,000 adult inhabitants) were identified. They were mainly older (median age 68 [56; 75] years), males (56%) and affected by ≥2 comorbidities (52%), mostly cardiometabolic. During 4 years of follow-up, 56% of cases in 2018 survived. During the first follow-up year: 73%, 80%, 100% and 35% of cases in 2018, 2019, 2020 and 2021, respectively, received a 2L; 42% and 64% of cases in 2018 and 2020, respectively, received a 3L. At least one Hsct was found as a 2L among cases in 2018, 2020 and 2021. On average, each patient newly diagnosed with Dlbcl and treated with 1L from 2018 to 2021 caused a total expenditure directly charged to the Ssn ranging from 20,000 to 30,000 during the first follow-up year (chemo-immunotherapy accounted for 40-53%), which reduced with time in favor of other drugs and Hsct. CONCLUSIONS: This analysis confirms the high rate of rrDlbcl and the high economic impact charged to the SSN to support first the chemo-immunotherapy, then the chronic care and the absence of standardized further lines of therapy for patients with rrDlbcl.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bases de Datos Factuales , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/epidemiología , Italia , Masculino , Anciano , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Anciano de 80 o más Años , Adulto , Rituximab/administración & dosificación , Estimación de Kaplan-Meier , Trasplante de Células Madre Hematopoyéticas , Costos de la Atención en Salud/estadística & datos numéricos , Vincristina/administración & dosificación , Estudios de Seguimiento , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Doxorrubicina/administración & dosificación , Prednisona/administración & dosificación , Prednisona/uso terapéuticoRESUMEN
The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.
Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Inmunosupresores , Recurrencia , Humanos , Anemia Aplásica/terapia , Anemia Aplásica/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Adolescente , Adulto , Enfermedad Injerto contra Huésped/etiología , Niño , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Adulto Joven , Preescolar , Persona de Mediana Edad , Resultado del Tratamiento , Suero Antilinfocítico/uso terapéutico , Suero Antilinfocítico/administración & dosificación , Trasplante Homólogo , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Terapia de Inmunosupresión/métodos , Estudios Retrospectivos , Ciclosporina/uso terapéutico , Ciclosporina/administración & dosificaciónRESUMEN
The anti-inflammatory effects of plant polysaccharides are well known. However, the stimulatory effects of polysaccharides under immunosuppressive conditions and their link with the polysaccharide structure is underexplored. In this work, the immune modulatory effects of a garlic polysaccharide (GP) are investigated via in vitro and vivo methods. It is observed that GP enhance the immune response of macrophages (RAW264.7) as indicated by the elevated levels of nitric oxide, TNF-α and IL-6. The observation that GP are able to stimulate the immune response in vitro was then explored with the use of an immunosuppressed mouse model. Surprisingly, GP exhibited dose-dependent up-regulatory impacts on the cyclophosphamide (CTX) suppressed levels of cytokines such as IFN-γ and IL-6 and immunoglobulins (e.g. IgA and IgG). The GP intervention reversed histopathological damage to the small intestine and spleen and increased fecal short-chain fatty acid levels. Moreover, GP modulates the gut microbiota dysbiosis by increasing the abundance of immunogenic bacteria such as g__norank_f__Erysipelotrichaceae, while inhibiting the over-abundance of g_Bacteroides. Functional predictions indicated that gut biomarkers of GP possessed the functions of glycoside hydrolase family 32 (GH32) and ß-fructofuranosidase. It is concluded that GP is a promising immunostimulant for immune-compromised individuals.
Asunto(s)
Ajo , Macrófagos , Polisacáridos , Animales , Ratones , Ajo/química , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Polisacáridos/farmacología , Polisacáridos/química , Fructanos/farmacología , Fructanos/química , Ciclofosfamida/farmacología , Inmunosupresores/farmacología , Inmunosupresores/química , Citocinas/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Óxido Nítrico/metabolismo , Ratones Endogámicos BALB C , Regulación hacia Arriba/efectos de los fármacosRESUMEN
This study aimed to estimate the medical costs associated with febrile neutropenia (FN) prophylaxis with pegfilgrastim and evaluate its impact on survival outcomes in daily practice in Japan. In this single-center retrospective study, we obtained data from 296 Japanese patients with breast cancer receiving fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 chemotherapy; the patients were divided into the pegfilgrastim and non-pegfilgrastim groups. We analyzed the median costs of chemotherapy, drugs for all adverse events (AEs) and FN, and hospitalization due to FN. We also assessed the survival outcomes. The pegfilgrastim group showed a significantly higher median total cost (JPY 872320.0 vs. JPY 466715.0, p<0.001). This difference was associated with the prophylactic use of pegfilgrastim. The median costs of the drugs for all AE treatments were JPY 9030.4 and JPY 24690.6, with the non-pegfilgrastim group showing a significantly higher cost (p<0.001). In 11 patients hospitalized for FN management, no significant difference in hospitalization cost was observed between the pegfilgrastim and non-pegfilgrastim groups (JPY 512390.0 vs. JPY 307555.0, p=0.102). No significant difference in the 3-year overall survival was observed between the pegfilgrastim and non-pegfilgrastim groups (79.9% vs. 88.3%, p=0.672). In this study, although the total medical cost in daily practice increased because of primary prophylaxis with pegfilgrastim, the 3-year overall survival was not impacted by the use of pegfilgrastim. Our study data suggested that the primary prophylaxis pegfilgrastim should be used during FEC-100 chemotherapy based on the patient-related FN risk factors, instead of routine use.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Neutropenia Febril Inducida por Quimioterapia , Filgrastim , Polietilenglicoles , Humanos , Filgrastim/economía , Filgrastim/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Estudios Retrospectivos , Polietilenglicoles/economía , Polietilenglicoles/administración & dosificación , Japón/epidemiología , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Anciano , Neutropenia Febril Inducida por Quimioterapia/etiología , Neutropenia Febril Inducida por Quimioterapia/prevención & control , Neutropenia Febril Inducida por Quimioterapia/economía , Fluorouracilo/efectos adversos , Fluorouracilo/administración & dosificación , Adulto , Ciclofosfamida/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/economía , Epirrubicina/efectos adversos , Epirrubicina/administración & dosificación , Hospitalización/economía , Costos de los Medicamentos , Atención Perioperativa/economía , Neutropenia Febril/prevención & control , Neutropenia Febril/inducido químicamenteRESUMEN
Richter transformation (RT) is an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia. Here we investigated the anti-CD3/anti-CD19 T-cell-engager blinatumomab after R-CHOP (i.e. rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with untreated RT of diffuse large B-cell lymphoma histology (NCT03931642). In this multicentre phase 2 study, patients without complete response (CR) after two cycles of R-CHOP were eligible to receive an 8-week blinatumomab induction via continuous vein infusion with stepwise dosing until 112 µg/day. The primary endpoint was the CR rate after blinatumomab induction and secondary endpoint included safety, response duration, progression-free and overall survival. Thirty-nine patients started the first cycle of R-CHOP, 25 of whom received blinatumomab. After blinatumomab induction, five (20%) patients achieved CR, four (16%) achieved partial response, and six (24%) were stable. Considering the entire strategy, the overall response rate in the full-analysis-set was 46% (n = 18), with CR in 14 (36%) patients. The most common treatment-emergent adverse events of all grades in the blinatumomab-safety-set included fever (36%), anaemia (24%), and lymphopaenia (24%). Cytokine release syndrome (grade 1/2) was observed in 16% and neurotoxicity in 20% of patients. Blinatumomab demonstrated encouraging anti-tumour activity (the trial met its primary endpoint) and acceptable toxicity in patients with RT.
Asunto(s)
Anticuerpos Biespecíficos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Linfoma de Células B Grandes Difuso , Prednisona , Rituximab , Vincristina , Humanos , Masculino , Femenino , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/efectos adversos , Anticuerpos Biespecíficos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Persona de Mediana Edad , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Rituximab/efectos adversos , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Anciano , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Prednisona/efectos adversos , Vincristina/uso terapéutico , Vincristina/efectos adversos , Vincristina/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano de 80 o más Años , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Resultado del TratamientoRESUMEN
OBJECTIVES: Rheumatic diseases were previously associated with increased incidence of monoclonal gammopathy (MG) and its malignant transformation. The present study aimed to investigate the prevalence, malignant transformation risk, clinical correlates and prognostic impact of MG in SLE. METHODS: A retrospective cohort study based on the medical records of n=1039 patients with SLE fulfilling the 1997 American College of Rheumatology (ACR), the 2019 European Alliance of Associations for Rheumatology (EULAR)/ACR and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria managed at two tertiary care departments of the University Hospital (Krakow, Poland) from January 2012 until November 2019. RESULTS: SLE+MG cases were older at SLE diagnosis compared with non-MG SLE controls (53±15 years vs 37±15 years, respectively, p<0.01), had higher rates of lymphopenia, anaemia, haemolysis, serous effusions and interstitial lung disease (all p<0.05), and were more frequently treated with cyclophosphamide (57% vs 28%, p<0.01) or rituximab (13% vs 3%, p<0.01). Most MG cases were detected within a year after SLE diagnosis (Q25, Q75: 0, 12 years). With the median follow-up of 11 years (Q25, Q75: 6, 19 years), 34.8% (8 cases) of the SLE+MG cohort were diagnosed with malignancy, compared with 8.1% (82 cases) among the SLE controls (p<0.001). MG was associated with the relative hazard of death of HR 2.99 (95% CI 1.26 to 7.06, p<0.05) and a median survival time from SLE diagnosis to death of 5 years (Q25, Q75: 1, 14; range 0-41) for SLE+MG cases, as compared with 12 years (Q25, Q75: 6, 19; range 0-62) for the controls. The effect was non-independent on antimalarial medication use. CONCLUSIONS: Our study emphasises heightened malignancy and mortality rates in SLE+MG cases. The association between immunosuppression, MG incidence and progression warrants further research.
Asunto(s)
Lupus Eritematoso Sistémico , Neoplasias , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/mortalidad , Lupus Eritematoso Sistémico/tratamiento farmacológico , Estudios Retrospectivos , Persona de Mediana Edad , Femenino , Masculino , Adulto , Anciano , Neoplasias/mortalidad , Neoplasias/complicaciones , Neoplasias/epidemiología , Paraproteinemias/complicaciones , Paraproteinemias/mortalidad , Paraproteinemias/epidemiología , Polonia/epidemiología , Ciclofosfamida/uso terapéutico , Pronóstico , PrevalenciaRESUMEN
Metronomic chemotherapy with cyclophosphamide (Cpp) has shown promising results in cancer protocols. These lower and prolonged doses have antiangiogenic, pro-cytotoxic, and moderate secondary effects. Molecular iodine (I2) reduces the viability of cancer cells and, with chemotherapeutic agents, activates the antitumoral immune response and diminishes side effects. The present work evaluates the adjuvant of oral I2 with Cpp using a murine model of mammary cancer. Female Sprague Dawley rats with 7,12-dimethylbenzantracene-induced tumors received Cpp intraperitoneal (50 and 70 mg/kg two times/week, iCpp50 and iCpp70) and oral (0.03%; 50 mg/Kg; oCpp50) doses. I2 (0.05%, 50 mg/100 mL) and oCpp50 were offered in drinking water for three weeks. iCpp70 was the most efficient antitumoral dose but generated severe body weight loss and hemorrhagic cystitis (HC). I2 prevented body weight loss, exhibited adjuvant actions with Cpp, decreasing tumor growth, and canceled HC mechanisms, including decreases in vascular endothelial growth factor (VEGF) and Survivin expression. oCpp50 + I2 diminished angiogenic signals (CD34, vessel-length, and VEGF content) and proinflammatory cytokines (interleukin-10 and tumor necrosis factor-alpha) and increased cytotoxic (lymphocytic infiltration, CD8+ cells, Tbet, and interferon-gamma) and antioxidant markers (nuclear erythroid factor-2 and glutathione peroxidase). I2 enhances the effectiveness of oCpp, making it a compelling candidate for a clinical protocol.