RESUMEN
Peri-engraftment respiratory distress syndrome (PERDS) is a kind of potentially life-threatening complication of autologous stem cell transplantation (ASCT). PERDS is characterized by fever, dyspnea, and hypoxemia during neutrophil engraftment. In order to identify the high-risk factors for PERDS, we retrospectively analyzed 260 patients with lymphoma undergoing ASCT in recent five years. The conditioning regimen was BuCyE (busulfan, cyclophosphamide, and etoposide). There were 16 patients (6.1%) diagnosed as PERDS. In multivariate analysis, prior anti-programmed death-1 (PD-1) therapy (hazard ratio [HR] = 8.852, 95% confidence interval [CI]: 2.954-26.527, P < 0.001) and history of pulmonary disease (HR = 3.718, 95% CI: 1.197-11.545, P = 0.023) were independent risk factors for PERDS. Patients with prior anti-PD-1 therapy (n = 31) had higher incidence of engraftment syndrome (77.4% vs. 33.4%, P < 0.001), PERDS (25.8% vs. 3.5%, P < 0.001), and transplant-related mortality (9.7% vs. 0.4%, P < 0.001), compared with those without prior anti-PD-1 therapy (n = 229). Subgroup analysis showed that sintilimab seemed to be associated with higher incidence of PERDS (42.9% vs. 11.8%, P = 0.06) compared with non-sintilimab group (pembrolizumab or toripalimab). C-reactive protein might be a feasible early predictor for PERDS. In conclusion, our study suggests that prior anti-PD-1 therapy may be a strong risk factor for life-threatening PERDS in patients with lymphoma undergoing ASCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Síndrome de Dificultad Respiratoria , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Busulfano , Ciclofosfamida , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Retrospectivos , Factores de Riesgo , Trasplante de Células Madre/efectos adversos , Acondicionamiento Pretrasplante/efectos adversos , Trasplante AutólogoRESUMEN
At present, autologous stem cell transplantation (ASCT) is considered as an optional consolidation therapy for natural killer/T-cell lymphoma (NKTCL). However, the high-risk patients undergoing ASCT are not clear enough. In this study, 56 patients with advanced staged or relapsed/refractory (R/R) NKTCL undergoing ASCT were reviewed. All patients achieved clinical complete response (CR) before ASCT. The median follow-up time was 36 months (range, 3-192 months). The three-year overall survival (OS) and three-year progression-free survival (PFS) were 70.2% and 56.5%, respectively. The independent prognostic factors for OS included prior testis involvement and pre-ASCT EBV-DNA. Patients without prior testis involvement and negative pre-ASCT EBV-DNA (group A) had better three-year OS (86.3% vs. 47.6%, p < .001) than the rest patients (group B). In conclusion, our study suggests that testis involvement and elevated EBV-DNA might be strong adverse prognostic factors for NKTCL. Patients without the above risk factors are more likely to benefit from ASCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Células Asesinas Naturales , Masculino , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Trasplante de Células Madre , Trasplante AutólogoRESUMEN
OBJECTIVE: To evaluate the safety and efficacy of rapid rituximab infusion (RRI) plus chemotherapy in patients with CD20(+) non-Hodgkin's lymphoma (NHL). RESEARCH DESIGN AND METHODS: A total of 177 patients received 4 - 6 cycles of rituximab-based chemotherapy. The first cycle was given with standard schedule. In the second and subsequent cycles, RRI was initiated. Rituximab was administered as 20% of the dose infused in the first 30 min and the remaining 80% was given over 60 min. Benadryl and dexamethasone were given before infusions. Vital signs were measured at baseline and during infusion. RESULTS: In the first cycle, 48 patients experienced grade I - II infusion reactions and two patients showed grade III - IV infusion reactions. Six patients experienced infusion reactions during RRI. Two patients showed grade III infusion reactions to RRI and dropped out of the study. With a median follow up of 37.5 months, the 3-year overall survival and progression-free survival rates of the whole cohort were 93.1 and 81.1%, respectively. CONCLUSIONS: Our preliminary observations suggested that RRI may be safe and feasible for patients with CD20(+) NHL.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/efectos adversos , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Antígenos CD20/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Pueblo Asiatico , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Linfoma no Hodgkin/inmunología , Masculino , Persona de Mediana Edad , Rituximab , Adulto JovenAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Células Asesinas Naturales/efectos de los fármacos , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Secuenciación Completa del Genoma/métodosRESUMEN
OBJECTIVE: Although cisplatin combined with 5-fluorouracil is a common first-line regimen for advanced nasopharyngeal carcinoma (NPC), there are no standard regimens for refractory or relapsed patients. A study of DXD regimen [cisplatin (D), capecitabine (X) and docetaxel (D)] was conducted to evaluate the efficacy and toxicity for patients with refractory or relapsed NPC. METHODS: The regimen was administered as follows: 50 mg/m(2) docetaxel and 50 mg/m(2) cisplatin on day 1 and 800 mg/m² capecitabine on days 1 - 14, repeated every 3 - 4 weeks. RESULTS: Thirty patients were enrolled. The overall response and complete remission rate was 46.4 and 21.4%. Median follow-up was 24 months; median overall survival (OS) and progression-free survival (PFS) were 14.0 and 8.0 months. Five-year OS and PFS rates were 14.8 and 13.3%, respectively. Four patients achieved long-term tumor-free survival (range, 53.8 - 125.3 months). Multivariate analysis demonstrated that Epstein-Barr virus DNA status (p = 0.003) and therapeutic effect (p < 0.001) were significant independent factors for OS and PFS. The main grade 3/4 toxicities included neutropenia (26.6%), anemia (13.3%) and thrombocytopenia (10.0%). There were no chemotherapy-related deaths. CONCLUSION: The DXD regimen appeared to be effective and well tolerated by patients with refractory or relapsed NPC. Further investigation is warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Herpesvirus Humano 4/aislamiento & purificación , Neoplasias Nasofaríngeas/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Carcinoma , Cisplatino/administración & dosificación , ADN Viral/aislamiento & purificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Docetaxel , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia , Inducción de Remisión , Tasa de Supervivencia , Taxoides/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
This study sought to investigate the efficacy and tolerability of the regimen of low-dose gemcitabine combined with carboplatin in chemo-naïve patients with non-small cell lung cancer (NSCLC). The study involved 37 chemo-naive patients with unresectable stage IIIB or stage IV NSCLC. The predominant histological type was squamous carcinoma (22/37), and the performance status (PS) was 2 in 23 patients (62%). All received gemcitabine, 250 mg/m(2) in 6-hour infusion on days 1 and 8 plus carboplatin area under the curve (AUC) â=â 5 on day 1, every 28 days. The overall response rate (ORR) was 62·2% and disease stabilization was achieved in 21·6% of the patients. After a median follow-up duration of 13 months, the median overall survival (OS) time was 14·0 months (95% CI 13·3-16·6 months), and the median progression-free survival (PFS) time was 7·0 months (95% CI 6·1-8·9 months). Hematological toxicities were well-tolerated with the development of grade 3/4 neutropenia and thrombocytopenia in 10·3 and 10·3% of patients respectively, and the gastrointestinal toxicities were mild.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Terapia Combinada , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , GemcitabinaRESUMEN
The role of temozolomide in untreated PCNSL patients has not yet been clearly defined. The purpose of this study was to compare the efficacy and toxicity of MT and MC chemotherapy in this population. A total of 41 consecutive patients were enrolled from March 2001 to July 2011. The ORR and CRR for MT vs. MC were 70% vs. 61.9% and 45% vs. 38.1% on ITT basis, (p = NS); 73.7% vs. 68.4% and 47.4% vs. 42.1% on PP basis, respectively (p = NS). Grade 3-4 hematological toxicities were more common in MC than in MT group (85.7% vs. 15%, p = 0.0001). One treatment-related death was observed in each group. The 5-year PFS and OS of MT (36% and 62.2%) were comparable to MC (32.6% and 46.7%), (p = NS). In summary, our preliminary results suggest that MT combination may be a simplified and effective regimen comparable to MC for newly diagnosed PCNSL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Nervioso Central/patología , Citarabina/administración & dosificación , Citarabina/efectos adversos , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Dacarbazina/análogos & derivados , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Linfoma/patología , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Neutropenia/inducido químicamente , Inducción de Remisión , Temozolomida , Trombocitopenia/inducido químicamente , Resultado del Tratamiento , Adulto JovenRESUMEN
The combination of gemcitabine (G), vinorelbine (V), and pegylated liposomal doxorubicin (D) has proved to be effective in relapsed Hodgkin's lymphoma (HL). Its efficacy in non-Hodgkin's lymphoma (NHL) remains to be discussed. We retrospectively evaluated the efficacy and toxicity of the dose-adjusted gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule in 35 heavily pretreated patients with relapsed and refractory aggressive NHL or HL. Treatment consisted of G: 800 mg/m(2) intravenous (i.v.) on day 1, V: 15 mg/m(2) i.v. on day 1; D: 20 mg/m(2) i.v. on day 1, repeated for 14 days. Patients responded to GVD proceeded to subsequent autologous stem cell transplantation. The objective response rate (ORR) was 48.6 %, with 31.4 % complete remission. A higher ORR was observed in patients with HL than in patients with NHL (80.0 vs. 36.0 %, P = 0.023). With a median follow-up of 26 months, the estimated median progression-free survival and overall survival were 5 (range 1-73 months) and 36 months (range 2-73 months), respectively. The estimated 5-year survival rate was 44.6 % (95 % confidence interval 28.1-61.1 %). Toxicities were mild (grade 3/4 neutropenia 34.3 %, thrombocytopenia 5.7 %). Our results suggest that the dose-adjusted GVD in 14-day schedule is effective and well tolerated in patients with refractory and relapsed HL and aggressive NHL. The potential long-term survival in NHL is promising.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Terapia Recuperativa/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Enfermedad de Hodgkin/mortalidad , Humanos , Estimación de Kaplan-Meier , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tiempo , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/análogos & derivados , Vinorelbina , GemcitabinaRESUMEN
The role of (18)Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in extranodal natural killer/T-cell lymphoma (ENKL) is not well established. This study aimed to investigate the prognostic role of the pretreatment maximum standardized uptake value (SUV(max)) on PET/CT in patients with newly diagnosed ENKL. Among 364 consecutive patients with newly diagnosed ENKL, 81 patients were included and reviewed. The impact of SUV(max) on survival and the relationship between SUV(max) and other clinicopathological parameters were analyzed. The median SUV(max) was 14.6 (range 2.0-45.4). The optimal cutoff value of SUV(max) to predict overall survival (OS) was 15. Patients with high SUV(max) (SUVmax >15) were associated with bulky disease (P < 0.001), local invasion (P = 0.030), high score of Korean Prognostic Index (KPI, P = 0.046), resistance to primary treatment (P = 0.014), poor OS (P < 0.001), and unfavorable progression-free survival (P < 0.001). With a median follow-up of 25.0 months, the median OS was 63.0 months (range 2.0-99.0 months). Multivariate analyses revealed the following independent prognostic factors for OS: age >60 years (P = 0.001), stage III-IV (P = 0.023), SUV(max) >15 (P = 0.020), and bulky disease (>5 cm) (P = 0.002). By using the SUV(max), patients in most subgroups stratified by the KPI or the International Prognostic Index (IPI) were further discriminated in OS with significant statistical difference. Our results suggest the pretreatment SUV(max) is predictive of prognosis in patients with newly diagnosed ENKL. The SUV(max) may provide additional prognostic information for IPI and KPI.
Asunto(s)
Linfoma Extranodal de Células NK-T/diagnóstico por imagen , Linfoma Extranodal de Células NK-T/mortalidad , Imagen Multimodal , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Área Bajo la Curva , Supervivencia sin Enfermedad , Femenino , Fluorodesoxiglucosa F18 , Humanos , Estimación de Kaplan-Meier , Linfoma Extranodal de Células NK-T/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Radiofármacos , Adulto JovenRESUMEN
Various studies on lymphoma microenvironment have demonstrated the prognostic impact of tumor-associated macrophages (TAMs) in patients with B-cell lymphoma. Little is known about the correlation between TAMs and treatment outcome in mature T- and natural killer (NK) cell lymphomas. We analyzed the prognostic relevance of CD68+ TAMs by immunohistochemical analysis in 64 Chinese patients with mature T- and NK-cell lymphomas. Higher number of infiltrated TAMs was significantly related to B symptoms and extranodal involvement (p < 0.05). The TAMs content did not differ significantly between pathological subtypes. Using the mean value of TAMs per high-power field (hpf) as the cutoff point (87/hpf), 36 cases (56.2 %) were categorized as low level of TAMs content and 28 cases (43.8%) as high level. Patients with high level of TAMs content had a worse 5-year overall survival compared to those with low level (28.1 vs. 44.3 %, p = 0.039). In multivariate analysis, TAMs content remained an independent biological variable for survival distinct from the International Prognostic Index (Cox multivariate model, p = 0.009). High TAMs content indicated an adverse overall outcome in mature T- and NK-cell lymphomas. Our results show that expression of stromal TAMs may become a useful marker for prognosis of mature T- and NK-cell lymphomas.
Asunto(s)
Linfoma Extranodal de Células NK-T/mortalidad , Linfoma Extranodal de Células NK-T/patología , Macrófagos/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Linfoma Extranodal de Células NK-T/inmunología , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is characterized by its clinical and biological heterogeneity. Although the International Prognostic Index (IPI) provides a clinical model for risk stratification of patients with DLBCL, notable variability in outcome is still observed within the same IPI category. Tumor-infiltrating macrophages (also called Tumor-associated macrophages) are the major component in the microenvironment of DLBCL. Their correlation with the prognosis of DLBCL remains controversial. Using a CD68 antibody in immunohistochemical analysis, we studied the expression of CD68 in 112 Chinese patients with DLBCL, with 65 patients (58%) categorized as low CD68 expression and 47 patients (42%) as high CD68 expression. The complete response (CR) rate of patients with low CD68 expression was higher than that with high CD68 expression (66.1% vs. 51.6%), but there was no statistical significance (P=0.060). The median survival time of patients with low CD68 expression was not achieved and that of high expression was 41 months (P=0.029). The results suggest that higher expression of CD68 tended to yield poor treatment outcome of DLBCL.
Asunto(s)
Linfoma de Células B Grandes Difuso/mortalidad , Macrófagos/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Femenino , Humanos , Linfoma de Células B Grandes Difuso/inmunología , Masculino , Persona de Mediana Edad , PronósticoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Ciclofosfamida/administración & dosificación , Epirrubicina/administración & dosificación , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Prednisolona , Rituximab , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND & OBJECTIVES: Though high dose chemo-therapy combined with autologous hematopoietic stem cell transplantation (AHSCT) has made great progress on the treatment of chemo-sensitive malignant tumors, the relapse rate remains high. Successful immune reconstitution after AHSCT may reduce recurrence; therefore this study was to explore the characteristics of immune reconstitution after AHSCT and assess its feasibility in clinical use. METHODS: Twenty four cases after AHSCT were enrolled in our study. There were 19 Non-hodgkin Lymphoma (NHL), 3 Hodgkin Lymphoma (HD) and 2 rhabdomyosarcoma. Nineteen cases had achieved complete remission (CR) while 5 partial remission (PR) before AHSCT. All cases were administered Interleukin (IL)-2 and Interferon (IFN)-alpha after AHSCT. Some patients were given thymus factor and/or CIK infusion. Phenotypes of peripheral blood T, B, NK subsets and immunological profile of TH1/TH2 by intracellular staining of cytokines after PMA/ionomycin stimulation were evaluated. RESULTS: 75% of the cases achieved CR while 4.17% were progression of disease (PD) and 16.67% were relapsed during the median follow-up time of 12 (2-60) months. The changes of immune parameters after AHSCT were as followed: (1) CD4+T cells (normal control 33.5+/-6.9%) started to decrease dramatically one month after AHSCT, which was 2.5-13% (median rate 5.6%)in the 2nd month; and then slowly increased to 10-20% in the 7th month, but did not return back to normal even after one year in all patients. In addition, reversed ratio of CD4/CD8 lasted for a long period of time. B cells also began to decrease 1 month after AHSCT, and recovered to normal in the 4th month. But B cells remained 0% in the 6th month and 1% in 12th month in patients treated by rituximab before receiving AHSCT. The ratio of NK cells was 10-20% (higher than normal controls) in the 2nd month, then returned to normal thereafter. (2) The cytokine secretion by T cell: there were 48.79% patients whose TH1 was lower than normal controls or at the lower limit of normal range. All the patients with normal TH1 were treated by IFN-alpha or CIK cell infusion. TH2 was much higher than normal level among 68.29% cases and this abnormality lasted at least for 1 year in some cases. TH2 at normal range was only observed in cases receiving IFN-alpha treatment. Furthermore, IFN-alpha could significantly decrease TH2 level. (3) Increasing tendency of CD4+CD25+/CD4+, CD4+CD69+/CD4+ ratio was observed in patients received additional thymus factor treatment compared to those did not. CONCLUSIONS: Administration of CIK cells, thymus factor, IL-2 and IFN-alpha after AHSCT could improve the immunologic function of patients, and TH1/TH2 ratio may virtually reflect the immune status of patients. However more information is required to make prognostic assessments of immune reconstruction and the long-term survival rate.