Asunto(s)
Anemia , Trastornos Mentales , Anciano , Anemia/complicaciones , Anemia/diagnóstico , Femenino , HumanosRESUMEN
Novel therapeutics are needed for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). Everolimus is an mTOR pathway inhibitor with synergistic anti-tumor activity when combined with histone deacetylase inhibitors, such as panobinostat, in preclinical lymphoma models. In this Phase II study, we evaluated overall response rate to single and combination everolimus and panobinostat in R/R DLBCL. Fifteen patients were enrolled to single-agent and 18 to combination. One patient responded to everolimus, while none responded to panobinostat. Though 25% of patients responded to combination therapy, responses were not durable with significant toxicity. We demonstrated minimal single-agent activity and prohibitive toxicity with combination therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Everolimus/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Panobinostat/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Everolimus/administración & dosificación , Everolimus/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Panobinostat/administración & dosificación , Panobinostat/efectos adversos , Estudios Prospectivos , RecurrenciaRESUMEN
Allogeneic-HCT (allo-HCT), while potentially curative, can result in significant complications including graft versus host disease (GVHD). Prior studies suggest that metabolic syndrome may be one risk factor for GVHD. We hypothesized that hepatic steatosis on pre-HCT computed tomography (CT) scans may be a marker for development of GVHD and poor outcomes in allo-HCT. In this retrospective study, we reviewed the pre-HCT CT scans and transplant outcome data of patients who underwent allo-HCT at Duke University Medical Center from 2009 to 2017. The presence of steatosis was confirmed using CT attenuation measurements. We then assessed the association between pre-HCT hepatic steatosis and HCT-related outcomes including GVHD. 80 patients who had pre-HCT CT scans were included in the study. Pre-transplant hepatic steatosis was associated with the development of chronic GVHD (OR 4.2, p = 0.02), but was not associated with acute GVHD (OR 1.3, p = 0.7), non-relapse mortality (p = 0.81) or overall survival (p = 0.74). Based on this single center retrospective study, pre-transplant hepatic steatosis is associated with development of chronic GVHD. Further, prospective study with other imaging modalities including non-contrasted CT scans is needed to determine if this association is reproducible.
Asunto(s)
Hígado Graso/terapia , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Aguda , Adulto , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Tomografía Computarizada por Rayos X , Trasplante Homólogo/efectos adversosRESUMEN
Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical outcomes compared with chemotherapy alone. This is the first trial reporting on broad correlative studies to define immunologic mechanisms of action of MST in older AML patients. Older patients with newly diagnosed AML were eligible for enrollment, receiving induction chemotherapy with cytarabine (100 mg/m2) on days 1-7 and idarubicin (12 mg/m2) on days 1-3 (7 + 3). MST was administered 24 hours later. Patients with complete response (CR) were eligible for consolidation with high dose cytarabine (HiDAC) and a second cycle of MST. Responses were evaluated according to standard criteria per NCCN. Immune correlative studies were performed. Sixteen patients were enrolled and received 7 + 3 and MST (median age 73 years). Nine (56%) had high-risk and seven (44%) had standard-risk cytogenetics. Ten episodes of CRS were observed. No cases of GVHD or treatment-related mortality were reported. Event-free survival (EFS) was 50% at 6 months and 19% at 1 year. Overall survival (OS) was 63% at 6 months and 44% at 1 year. Donor microchimerism was not detected. Longitudinal changes were noted in NGS, TCR sequencing, and cytokine assays. Addition of MST to induction and consolidation chemotherapy was well tolerated in older AML patients. Inferior survival outcomes in our study may be attributed to a higher proportion of very elderly patients with high-risk features. Potential immunologic mechanisms of activity of MST include attenuation of inflammatory cytokines and emergence of tumor-specific T cell clones.
Asunto(s)
Citarabina/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Idarrubicina/administración & dosificación , Quimioterapia de Inducción , Leucemia Mieloide Aguda , Anciano , Aloinjertos , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Proyectos Piloto , Factores de RiesgoRESUMEN
PURPOSE: To evaluate the feasibility of reducing the dose of consolidation radiation therapy (RT) in diffuse large B-cell lymphoma. METHODS AND MATERIALS: This phase 2 study enrolled patients with diffuse large B-cell lymphoma, not otherwise specified and primary mediastinal (thymic) large B-cell lymphoma in complete response on positron emission tomography-computed tomography imaging after ≥4 cycles of a rituximab/anthracycline-containing combination chemotherapy regimen. Consolidation RT used a dose of 19.5 to 20 Gy. The primary endpoint was 5-year freedom from local recurrence. RESULTS: Sixty-two patients were enrolled between 2010 and 2016. Stage distribution was as follows: I to II (n = 49, 79%) and III to IV (n = 13, 21%). Bulky disease (defined as ≥7.5 cm or ≥10 cm) was present in 23 (40%) and 16 (28%) patients, respectively. Chemotherapy was R-CHOP (then list the drugs) in 58 (94%) and R-EPOCH (then list the drugs) in 4 (6%) with a median of 6 cycles. With a median follow-up of 51 months, 7 patients developed disease progression (6 outside the RT field, 1 within the RT field). Freedom from local recurrence at 5 years was 98% (90% lower confidence bound, 88%). Progression-free and overall survival at 5 years were 83% and 90%, respectively. CONCLUSIONS: With more effective systemic therapy (e.g., addition of rituximab) and more refined chemotherapy response assessment (e.g., positron emission tomography-computed tomography), the dose of RT in combined modality treatment programs may potentially be reduced to 20 Gy. This achieves excellent local control with the potential to decrease acute and long-term side effects.
Asunto(s)
Linfoma de Células B Grandes Difuso/radioterapia , Neoplasias del Mediastino/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Consolidación/métodos , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Estudios de Factibilidad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Masculino , Neoplasias del Mediastino/diagnóstico por imagen , Neoplasias del Mediastino/tratamiento farmacológico , Neoplasias del Mediastino/patología , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prednisona/administración & dosificación , Supervivencia sin Progresión , Estudios Prospectivos , Dosificación Radioterapéutica , Rituximab/administración & dosificación , Vincristina/administración & dosificaciónAsunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Neutropenia Febril/etiología , Neutropenia Febril/prevención & control , Fluoroquinolonas/uso terapéutico , Enfermedades Hematológicas/complicaciones , Sepsis/etiología , Sepsis/prevención & control , Adulto , Anciano , Comorbilidad , Cuidados Críticos , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/etiología , Infección Hospitalaria/prevención & control , Neutropenia Febril/diagnóstico , Femenino , Enfermedades Hematológicas/terapia , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Sepsis/diagnóstico , Resultado del TratamientoAsunto(s)
Quimioradioterapia , Inmunoterapia , Linfoma de Células B Grandes Difuso , Linfoma de Células del Manto , Rituximab/administración & dosificación , Adulto , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/terapia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: For patients with aggressive lymphomas who relapse after initial therapy, a durable response is rarely achieved with standard salvage therapies. Significant efforts have focused on the development of novel treatments with reduced toxicity. We conducted a phase I prospective single arm clinical trial of the novel combination of BuRP (bendamustine, rituximab, and pixantrone) in patients with relapsed/refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Eligible patients included adults with biopsy-proven R/R B-cell NHL who met the criteria for treatment. Patients received bendamustine 120 mg/m2, rituximab 375 mg/m2, and pixantrone, per cohort dose, on day 1 for up to 6 cycles. Dose escalation used a 3 + 3 design, from a starting dose level of pixantrone 55 mg/m2 to 115 mg/m at dose level 3. RESULTS: Twenty-two patients were enrolled onto the study with a median follow-up of 7.9 months. The maximum tolerated dose was not reached, but the highest dose level of pixantrone of 115 mg/m2 was well-tolerated. The most common grade 3/4 adverse events were neutropenia (27%) and thrombocytopenia (23%). The mean change in left ventricular ejection fraction was 2.5% (standard deviation, 5.51%; 95% confidence interval, 0.0%-4.9%). The overall response rate for the entire cohort was 37.5% (95% confidence interval, 15%-65%), but at the highest pixantrone dose, the overall response rate was 63%, with a complete response rate of 25%. CONCLUSION: The BuRP regimen was found to be safe in patients with R/R B-cell NHL. The favorable toxicity profile plus the encouraging response rates seen suggest that continued investigation of the highest dose level is warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Linfoma de Células B/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Terapia Recuperativa , Adulto , Anciano , Anciano de 80 o más Años , Clorhidrato de Bendamustina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Isoquinolinas/administración & dosificación , Linfoma de Células B/patología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos , Rituximab/administración & dosificación , Tasa de SupervivenciaRESUMEN
Peripheral T-cell lymphomas (PTCL), with the exception of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), have a very poor prognosis. Although current first line chemotherapy continues to be a CHOP-like (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen there is now data suggesting that the addition of etoposide in younger patients improves outcomes. Even for those patients who do have a response to therapy, the risk of relapse remains quite high. Although autologous transplant in first remission is often used, its role as consolidation therapy in first remission remains unclear and may preferentially benefit low-risk patients. In the relapsed setting, major advances have occurred with Food and Drug Administration (FDA) approval of 4 new agents (pralatrexate, romidepsin, belinostat, brentuximab vedotin) for relapsed/refractory PTCL since 2009. These 4 drugs represent the first agents ever approved specifically for this indication. Unfortunately, with the exception of ALCL for which brentuximab vedotin will likely substantially change our approach to treatment, there are still many patients for whom available drugs will not be effective, and it is for these patients that further advances are urgently needed.
Asunto(s)
Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Linfoma de Células T Periférico/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Supervivencia sin Enfermedad , Doxorrubicina , Aprobación de Drogas , Etopósido/uso terapéutico , Europa (Continente) , Humanos , Cooperación Internacional , Oncología Médica/métodos , Recurrencia Local de Neoplasia , Oligopéptidos/uso terapéutico , Prednisolona , Pronóstico , Recurrencia , Inducción de Remisión , Riesgo , Resultado del Tratamiento , Estados Unidos , United States Food and Drug Administration , VincristinaRESUMEN
PURPOSE: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. METHODS AND MATERIALS: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achieve a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. RESULTS: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤ 24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. CONCLUSIONS: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Terapia Combinada/métodos , Dacarbazina/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Hipotiroidismo/etiología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/etiología , Tomografía de Emisión de Positrones , Dosificación Radioterapéutica , Estudios Retrospectivos , Vinblastina/administración & dosificación , Adulto JovenRESUMEN
We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS > 3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorodesoxiglucosa F18/farmacocinética , Linfoma de Células B Grandes Difuso/patología , Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacocinética , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Dinamarca , Femenino , Finlandia , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Imagen Multimodal , Estadificación de Neoplasias , Noruega , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Suecia , Distribución Tisular , Estados Unidos , Adulto JovenRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Approximately half of patients will present with advanced (stage III/IV) disease. The cornerstone of treatment is a combination of chemotherapy and immunotherapy, most commonly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Efforts to improve upon R-CHOP-including more chemotherapy cycles, dose-dense chemotherapy, alternative drug combinations, high-dose chemotherapy with autologous stem cell transplant, and maintenance rituximab-have generally proved unsuccessful. There is a growing body of retrospective and prospective data, however, suggesting a benefit for consolidation radiation therapy (RT) in select patients with advanced DLBCL. Consolidation RT has been shown to improve outcomes for patients with advanced DLBCL generally, and in specific instances including initially bulky disease, bone involvement, or in the setting of a partial response to systemic therapy. In these settings consolidation RT is highly efficacious at achieving local disease control and improving overall outcomes.
Asunto(s)
Linfoma de Células B Grandes Difuso/radioterapia , Evaluación del Resultado de la Atención al Paciente , Radioterapia/estadística & datos numéricos , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Clínicos como Asunto , Terapia Combinada , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Tomografía de Emisión de Positrones , Prednisona/uso terapéutico , Rituximab , Tasa de Supervivencia , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
PURPOSE: Negative [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative predictive value would be even higher in patients responding rapidly enough to be PET negative after one cycle. This prospective study aimed to assess the prognostic value of PET after one cycle of chemotherapy in HL and to assess the dynamics of FDG uptake after one cycle (PET1) and after two cycles (PET2). PATIENTS AND METHODS: All PET scans were read by two blinded, independent reviewers in different countries, according to the Deauville five-point scale. The main end point was progression-free survival (PFS) after 2 years. RESULTS: A total of 126 patients were included, and all had PET1; 89 patients had both PET1 and PET2. The prognostic value of PET1 was statistically significant with respect to both PFS and overall survival. Two-year PFS for PET1-negative and PET1-positive patients was 94.1% and 40.8%, respectively. Among those with both PET1 and PET2, 2-year PFS was 98.3% and 38.5% for PET1-negative and PET1-positive patients and 90.2% and 23.1% for PET2-negative and PET2-positive patients, respectively. No PET1-negative patient was PET2 positive. CONCLUSION: PET after one cycle of chemotherapy is highly prognostic in HL. No other prognostic tool identifies a group of patients with HL with a more favorable outcome than those patients with a negative PET1. In the absence of precise pretherapeutic predictive markers, PET1 is the best method for response-adapted strategies designed to select patients for less intensive treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Dacarbazina/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Pronóstico , Estudios Prospectivos , Radiofármacos , Tasa de Supervivencia , Vinblastina/administración & dosificación , Adulto JovenRESUMEN
PTK787/ZK222584 (vatalanib), an orally active inhibitor of vascular endothelial growth factor receptors (VEGFRs), was evaluated in this phase II study of 20 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received once-daily PTK787/ZK222584 at a target dose of 1250 mg. Eighteen patients were evaluable for response: one patient had a complete response (CR), six patients had stable disease but subsequently progressed, 10 patients had progressive disease by three cycles and one subject withdrew before response evaluation. The patient who attained a CR underwent autologous stem cell transplant and remains disease-free 76 months after study completion. There were no grade 4 toxicities. Grade 3 thrombocytopenia occurred in 20% and grade 3 hypertension occurred in 10%. There were no episodes of grade 3 proteinuria. In conclusion, PTK787/ZK222584 was well tolerated in a heavily pretreated population of patients with DLBCL, although its therapeutic potential as a single agent in DLBCL appears limited.
Asunto(s)
Antineoplásicos/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Ftalazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ftalazinas/administración & dosificación , Ftalazinas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Piridinas/administración & dosificación , Piridinas/efectos adversos , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Recurrencia , Inducción de Remisión , Resultado del TratamientoRESUMEN
PURPOSE: This Phase I study assessed the feasibility of concomitant arsenic trioxide (ATO), ascorbic acid (AA), and bortezomib (Velcade™) (AAV) for patients with relapsed/refractory multiple myeloma. EXPERIMENTAL DESIGN: ATO (0.25 mg/kg) and AA (1 g) were given with an escalating dose of bortezomib (1 mg/m(2) or 1.3 mg/m(2) IV bolus on days 1 and 8 of a 21-day cycle). RESULTS: Ten patients (median age 62 years), with a median of 3 prior regimens, were enrolled. Four (40%) patients achieved clinical benefit, with one patient achieving a durable partial response. No formal DLTs were encountered. CONCLUSION: AAV combination was feasible and demonstrated some benefits in this heavily pretreated population.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trióxido de Arsénico , Arsenicales/administración & dosificación , Ácido Ascórbico/administración & dosificación , Ácidos Borónicos/administración & dosificación , Bortezomib , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxidos/administración & dosificación , Pirazinas/administración & dosificación , RecurrenciaRESUMEN
PURPOSE: The decision to re-induce patients with acute myeloid leukemia (AML) based on results of the day 14 bone marrow (BM) biopsy is variable and lacks evidence based data. The aim of our review was to evaluate the accuracy of a day 14 BM biopsy in determining the need for re-induction chemotherapy. METHODS: Seventy-four patients with newly diagnosed de novo AML treated with induction chemotherapy were retrospectively reviewed for the purpose of evaluating treatment decisions and outcomes based on their day 14 BM biopsy. Response to therapy in this analysis was based on morphology alone. RESULTS: Of the 74 patients undergoing standard induction, 45 patients (61%) had no evidence of leukemia on their day 14 BM biopsy. Eighteen patients (24%) had definitive residual disease (RD), and 11 patient's (15%) were classified as indeterminate response (IR). Fifteen patients with RD and one with IR underwent re-induction chemotherapy. However, thirteen patients (3 RD and 10 IR) were observed until count recovery without any re-induction therapy. Eleven of these 13 patients who were observed eventually attained a morphologic complete remission (CR), including two patients with RD. CONCLUSIONS: A day 14 BM biopsy may have suboptimal sensitivity for the detection of residual leukemia. Some patients with an IR on day 14 may not require re-induction chemotherapy, but instead, may benefit from careful observation until count recovery to avoid the mortality and morbidity associated with re-induction chemotherapy.
Asunto(s)
Médula Ósea/patología , Quimioterapia de Inducción , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Anciano , Biopsia , Humanos , Leucemia Mieloide Aguda/patología , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. METHODS AND MATERIALS: Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. RESULTS: Seventy-nine patients were identified. Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). CONCLUSIONS: Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.
Asunto(s)
Linfoma de Células B Grandes Difuso/radioterapia , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Quimioterapia de Inducción/métodos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Primarias Secundarias/diagnóstico , Tomografía de Emisión de Positrones , Prednisona/administración & dosificación , Dosificación Radioterapéutica , Estudios Retrospectivos , Rituximab , Tomografía Computarizada por Rayos X , Carga Tumoral , Vincristina/administración & dosificaciónRESUMEN
Patients with chronic lymphocytic leukemia (CLL) with deletion or mutation of TP53 have exceedingly poor clinical outcomes. Cenersen, an oligonucleotide targeting TP53, has been shown to abrogate the activity of TP53 gain-of-function mutants and to increase sensitivity of lymphoma cells to cytotoxic chemotherapy in vitro. We combined cenersen with fludarabine, cyclophosphamide and rituximab (FCR) as treatment for patients with high-risk CLL. The purpose of this phase II study was to determine the overall response rate, response duration and toxicity of cenersen administered in combination with FCR. Twenty patients with relapsed or high-risk CLL were evaluated. Nineteen patients were previously treated. The complete response rate was 18%; the overall response rate was 53%. Median progression-free and overall survival was 5.3 and 10.6 months, respectively. The most common serious adverse events were neutropenia and thrombocytopenia. In this single arm phase II study, cenersen combined with FCR yielded clinical responses with acceptable toxicity in patients with high-risk CLL.