RESUMEN
Genetic subgroups of diffuse large B-cell lymphoma (DLBCL) have been identified through comprehensive genomic analysis; however, it is unclear whether this can be applied in clinical practice. We assessed whether mutations detected by clinical laboratory mutation analysis (CLMA) were predictive of outcomes in patients with newly diagnosed DLBCL/high-grade B-cell lymphoma (HGBL). Patients diagnosed from 2018 to 2022 whose biopsy samples were subjected to CLMA and who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone or rituximab plus etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin were analyzed for overall/complete response rate (ORR/CRR) and estimated progression-free/overall survival (PFS/OS). CLMA was successfully performed in 117 of 122 patient samples (96%), with a median turnaround time of 17 days. Median duration of follow-up was 31.3 months. Of the mutations detected in ≥10% of the samples, only TP53 was associated with both progression and death at 2 years. TP53 mutations were detected in 36% of tumors, and patients with TP53 mutations experienced significantly lower ORR (71% vs 90%; P = .009), CRR (55% vs 77%; P = .01), 2-year PFS (57% vs 77%; P = .006), 2-year OS (70% vs 91%; P = .001), and median OS after relapse (6.1 months vs not yet reached; P = .001) as than those without TP53 mutations. Furthermore, patients with TP53 loss-of-function (LOF) mutations experienced lower rates of 2-year PFS/OS than those with non-LOF mutations and inferior or near-inferior 2-year PFS if harboring high-risk clinicopathologic features. TP53 mutations identified through CLMA can predict for inferior outcomes in patients with newly diagnosed DLBCL/HGBL. Results of CLMA can be used in real time to inform prognosis and/or identify candidates for clinical trials.
Asunto(s)
Linfoma de Células B Grandes Difuso , Recurrencia Local de Neoplasia , Humanos , Rituximab/uso terapéutico , Vincristina/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Mutación , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is increasingly used for frontline treatment of stage III/IV classical Hodgkin lymphoma (cHL). Peripheral neuropathy (PN) was the most common and treatment-limiting side effect seen in clinical trials but has not been studied in a nontrial setting, in which clinicians may have different strategies for managing it. We conducted a multisite retrospective study to characterize PN in patients who received BV + AVD for newly diagnosed cHL. One hundred fifty-three patients from 10 US institutions were eligible. Thirty-four patients (22%) had at least 1 ineligibility criteria for ECHELON-1, including stage, performance status, and comorbidities. PN was reported by 80% of patients during treatment; 39% experienced grade (G) 1, 31% G2, and 10% G3. In total, BV was modified in 44% of patients because of PN leading to BV discontinuation in 23%, dose reduction in 17%, and temporary hold in 4%. With a median follow-up of 24 months, PN resolution was documented in 36% and improvement in 33% at the last follow-up. Two-year progression-free survival (PFS) for the advanced-stage patients was 82.7% (95% confidence interval [CI], 0.76-0.90) and overall survival was 97.4% (95% CI, 0.94-1.00). Patients who discontinued BV because of PN did not have inferior PFS. In the nontrial setting, BV + AVD was associated with a high incidence of PN. In our cohort, which includes patients who would not have been eligible for the pivotal ECHELON-1 trial, BV discontinuation rates were higher than previously reported, but 2-year outcomes remain comparable.
Asunto(s)
Enfermedad de Hodgkin , Enfermedades del Sistema Nervioso Periférico , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Brentuximab Vedotina/uso terapéutico , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Incidencia , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Estudios RetrospectivosRESUMEN
PURPOSE: Patients weigh competing priorities when deciding whether to travel to a cellular therapy center for treatment. We conducted a choice-based conjoint analysis to determine the relative value they place on clinical factors, oncologist continuity, and travel time under different post-treatment follow-up arrangements. We also evaluated for differences in preferences by sociodemographic factors. METHODS: We administered a survey in which patients with diffuse large B-cell lymphoma selected treatment plans between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate. We determined importance weights (which represent attributes' value to participants) using generalized estimating equations. RESULTS: Three hundred and two patients (62%) responded. When all follow-up care was at the center providing treatment, plans requiring longer travel times were less attractive (v 30 minutes, importance weights [95% CI] of -0.54 [-0.80 to -0.27], -0.57 [-0.84 to -0.29], and -0.17 [-0.49 to 0.14] for 60, 90, and 120 minutes). However, the negative impact of travel on treatment plan choice was mitigated by offering shared follow-up (importance weights [95% CI] of 0.63 [0.33 to 0.93], 0.32 [0.08 to 0.57], and 0.26 [0.04 to 0.47] at 60, 90, and 120 minutes). Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, as indicated by lower value importance weights for longer travel times. CONCLUSION: Reducing travel burden through shared follow-up may increase patients' willingness to travel to receive cellular therapies, but additional measures are required to facilitate equitable access.
Asunto(s)
Cuidados Posteriores , Oncólogos , Humanos , Factores Sociodemográficos , Encuestas y Cuestionarios , ViajeRESUMEN
Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms (multicentric CD [MCD]). MCD includes human herpesvirus-8 (HHV-8)-associated MCD, POEMS-associated MCD, and HHV-8-/idiopathic MCD (iMCD). The first-ever diagnostic and treatment guidelines were recently developed for iMCD by an international expert consortium convened by the Castleman Disease Collaborative Network (CDCN). The focus of this report is to establish similar guidelines for the management of UCD. To this purpose, an international working group of 42 experts from 10 countries was convened to establish consensus recommendations based on review of treatment in published cases of UCD, the CDCN ACCELERATE registry, and expert opinion. Complete surgical resection is often curative and is therefore the preferred first-line therapy, if possible. The management of unresectable UCD is more challenging. Existing evidence supports that asymptomatic unresectable UCD may be observed. The anti-interleukin-6 monoclonal antibody siltuximab should be considered for unresectable UCD patients with an inflammatory syndrome. Unresectable UCD that is symptomatic as a result of compression of vital neighboring structures may be rendered amenable to resection by medical therapy (eg, rituximab, steroids), radiotherapy, or embolization. Further research is needed in UCD patients with persisting constitutional symptoms despite complete excision and normal laboratory markers. We hope that these guidelines will improve outcomes in UCD and help treating physicians decide the best therapeutic approach for their patients.
Asunto(s)
Antineoplásicos , Enfermedad de Castleman , Herpesvirus Humano 8 , Antineoplásicos/uso terapéutico , Enfermedad de Castleman/diagnóstico , Enfermedad de Castleman/tratamiento farmacológico , Consenso , Humanos , Rituximab/uso terapéuticoRESUMEN
PURPOSE: To describe long-term outcomes of anti-CD19 chimeric antigen receptor T (CART) cells in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). METHODS: Between January 2013 and June 2016, 42 patients with relapsed or refractory CLL were enrolled in this study and 38 were infused with anti-CD19 CART cells (CART-19). Of these, 28 patients were initially randomly assigned to receive a low (5 × 107) or high (5 × 108) dose of CART-19, and 24 were evaluable for response assessment. After an interim analysis, 10 additional patients received the selected (high) dose and of these, eight were evaluable for response. Patients were followed for a median 31.5 months (range, 2 to 75 months). RESULTS: At 4 weeks, the complete and overall responses for the 32 evaluable patients were 28% (90% CI, 16% to 44%) and 44% (90% CI, 29% to 60%), respectively. The median overall survival (OS) for all patients was 64 months; there was no statistically significant difference between low- and high-dose groups (P = .84). Regardless of dose, prolonged survival was observed in patients who achieved a CR versus those who did not (P = .035), with median OS not reached in patients with CR versus 64 months in those without CR. The median progression-free survival was 40.2 months in patients with CR and 1 month in those without a CR (P < .0001). Toxicity was comparable in both dose groups. CONCLUSION: In patients with advanced CLL, a 5 × 108 dose of CART-19 may be more effective than 5 × 107 CART-19 at inducing CR without excessive toxicity. Attainment of a CR after CART-19 infusion, regardless of cell dose, is associated with longer OS and progression-free survival in patients with relapsed CLL.
Asunto(s)
Inmunoterapia Adoptiva/métodos , Leucemia Linfocítica Crónica de Células B/terapia , Anciano , Antígenos CD19/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Relación Dosis-Respuesta Inmunológica , Femenino , Humanos , Inmunoterapia Adoptiva/efectos adversos , Leucemia Linfocítica Crónica de Células B/inmunología , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Receptores Quiméricos de Antígenos/inmunología , Recurrencia , Tasa de Supervivencia , Linfocitos T/inmunología , Linfocitos T/trasplanteRESUMEN
BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are generally aggressive non-Hodgkin lymphomas that portend poor prognosis with currently available therapies. Bexarotene, a retinoic acid derivative, has efficacy in cutaneous T-cell lymphomas, but its activity in PTCL is unknown. PATIENTS AND METHODS: We conducted a retrospective, single-institution, review of off-label bexarotene therapy in patients with PTCL between 2005 and 2016. RESULTS: Twelve patients were treated with bexarotene as monotherapy: 3 patients with PTCL, not otherwise specified, and 9 patients with angioimmunoblastic T-cell lymphoma. Bexarotene doses of 300 mg/m2 daily or 150 mg/m2 were used for all patients. The treatment was well-tolerated. The most common toxicities included hypothyroidism and hyperlipidemia, which were effectively managed. The overall response rate for all patients was 58% with a median duration of response of 11 months (95% confidence interval [CI], 1.3 months to not estimable). Among patients with angioimmunoblastic T-cell lymphoma, there was a 44% overall response rate. The median progression-free survival for all patients was 2.1 months (95% CI, 1.1 months to not estimable), and the median overall survival was 14.9 months (95% CI, 2.1-73.1 months). CONCLUSION: Bexarotene monotherapy is well-tolerated and has encouraging activity in PTCL that warrants further investigation in prospective clinical trials.
Asunto(s)
Antineoplásicos/uso terapéutico , Bexaroteno/uso terapéutico , Linfoma de Células T Periférico/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Bexaroteno/farmacología , Femenino , Humanos , Linfoma de Células T Periférico/patología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8-negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti-interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.
Asunto(s)
Corticoesteroides/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Enfermedad de Castleman/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad de Castleman/patología , Enfermedad de Castleman/terapia , Ensayos Clínicos como Asunto , Enfermedad Crítica/terapia , Manejo de la Enfermedad , Medicina Basada en la Evidencia , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
Chimeric antigen receptor (CAR)-modified T cells are being investigated in many settings, including classical Hodgkin lymphoma (cHL). The unique biology of cHL, characterized by scant Hodgkin and Reed-Sternberg (HRS) cells within an immunosuppressive tumor microenvironment (TME), may pose challenges for cellular therapies directly targeting antigens expressed on HRS cells. We hypothesized that eradicating CD19+ B cells within the TME and the putative circulating CD19+ HRS clonotypic cells using anti-CD19-directed CAR-modified T cells (CART19) may indirectly affect HRS cells, which do not express CD19. Here we describe our pilot trial using CART19 in patients with relapsed or refractory cHL. To limit potential toxicities, we used nonviral RNA CART19 cells, which are expected to express CAR protein for only a few days, as opposed to CART19 generated by viral vector transduction, which expand in vivo and retain CAR expression. All 5 enrolled patients underwent successful manufacturing of nonviral RNA CART19, and 4 were infused with protocol-specified cell dose. There were no severe toxicities. Responses were seen, but these were transient. To our knowledge, this is the first CART19 clinical trial to use nonviral RNA gene delivery. This trial was registered at www.clinicaltrials.gov as #NCT02277522 (adult) and #NCT02624258 (pediatric).
Asunto(s)
Técnicas de Transferencia de Gen , Enfermedad de Hodgkin/terapia , Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Linfocitos T/metabolismo , Microambiente Tumoral/inmunología , Adulto , Femenino , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/inmunología , Humanos , Masculino , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunologíaRESUMEN
Human herpesvirus-8 (HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare and life-threatening disorder involving systemic inflammatory symptoms, polyclonal lymphoproliferation, cytopenias, and multiple organ system dysfunction caused by a cytokine storm often including interleukin-6. iMCD accounts for one third to one half of all cases of MCD and can occur in individuals of any age. Accurate diagnosis is challenging, because no standard diagnostic criteria or diagnostic biomarkers currently exist, and there is significant overlap with malignant, autoimmune, and infectious disorders. An international working group comprising 34 pediatric and adult pathology and clinical experts in iMCD and related disorders from 8 countries, including 2 physicians that are also iMCD patients, was convened to establish iMCD diagnostic criteria. The working group reviewed data from 244 cases, met twice, and refined criteria over 15 months (June 2015 to September 2016). The proposed consensus criteria require both Major Criteria (characteristic lymph node histopathology and multicentric lymphadenopathy), at least 2 of 11 Minor Criteria with at least 1 laboratory abnormality, and exclusion of infectious, malignant, and autoimmune disorders that can mimic iMCD. Characteristic histopathologic features may include a constellation of regressed or hyperplastic germinal centers, follicular dendritic cell prominence, hypervascularization, and polytypic plasmacytosis. Laboratory and clinical Minor Criteria include elevated C-reactive protein or erythrocyte sedimentation rate, anemia, thrombocytopenia or thrombocytosis, hypoalbuminemia, renal dysfunction or proteinuria, polyclonal hypergammaglobulinemia, constitutional symptoms, hepatosplenomegaly, effusions or edema, eruptive cherry hemangiomatosis or violaceous papules, and lymphocytic interstitial pneumonitis. iMCD consensus diagnostic criteria will facilitate consistent diagnosis, appropriate treatment, and collaborative research.
Asunto(s)
Enfermedad de Castleman/diagnóstico , Enfermedad de Castleman/etiología , Herpesvirus Humano 8 , Consenso , Diagnóstico Diferencial , Humanos , Internacionalidad , Guías de Práctica Clínica como AsuntoRESUMEN
B-cell receptor kinase inhibitor (KI) therapy represents a paradigm shift in chronic lymphocytic leukemia (CLL) management, but data on practice patterns after KI discontinuation and optimal sequencing are limited. We conducted a multicenter, retrospective, comprehensive analysis on 178 patients with CLL (ibrutinib = 143; idelalisib = 35) who discontinued KI therapy. We examined responses, toxicity, post-KI therapies, and overall survival (OS). Patients had a median of 3 prior therapies (range 0-11); del17p (34%), p53 mutation (27%), del11q (33%), and complex karyotype (29%). Overall response rate (ORR) to first KI was 62% (complete response 14%). The most common reasons for KI discontinuation were toxicity (51%), CLL progression (29%), and Richter transformation (RT) (8%). Median progression-free survival (PFS) and OS from KI initiation were 10.5 and 29 months, respectively. Notably, initial KI choice did not impact PFS or OS; however, RT portended significantly inferior OS (P = .0007). One hundred fourteen patients received subsequent salvage therapy following KI discontinuation with an ORR to subsequent KI at 50% and a median PFS of 11.9 months. Median PFS in KI-intolerant patients treated with an alternate KI was not reached vs 7 months for patients with CLL progression. In summary, these data demonstrate that toxicity was the most common reason for KI discontinuation, that patients who discontinue KI due to toxicity can respond to an alternate KI, and that these responses may be durable. This trial was registered at www.clinicaltrials.gov as #NCT02717611 and #NCT02742090.
Asunto(s)
Antineoplásicos/administración & dosificación , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Purinas/administración & dosificación , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Quinazolinonas/administración & dosificación , Adenina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Estudios de Cohortes , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Piperidinas , Modelos de Riesgos Proporcionales , Purinas/efectos adversos , Pirazoles/efectos adversos , Pirimidinas/efectos adversos , Quinazolinonas/efectos adversos , Estudios Retrospectivos , Terapia Recuperativa/métodos , Terapia Recuperativa/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND: High-dose melphalan with autologous stem cell support improves survival for patients with myeloma. For selected patients, we have been using a protocol of short hospitalization, discharging patients to home with careful outpatient monitoring in the office, which we hypothesized would reduce complications and utilization of inpatient beds. METHODS: We reviewed 301 initial autologous transplants for myeloma, categorized as brief stay (≤ 4 days, 82 patients) or prolonged stay (≥ 5 days, 219 patients). Selection for a brief stay was determined by clinical characteristics, availability of caregivers at home, distance from our medical center, and patient preference. RESULTS: Within the brief stay population, 67% required readmission before day + 100, but this group still had fewer cumulative hospital days (9 vs. 18, P < .0001). There were fewer documented infections among brief stay patients (22% vs. 46% P < .001) and fewer admissions to intensive care units (0% vs. 5.9%, P = .02). The groups had similar rates of bleeding (1.2% vs. 1.4% P = 1.0) and thrombosis (3.7% vs. 4.6% P = 1.0). No patients in the brief stay group died within 100 days, compared with mortality of 1.8% (P = .6) in the prolonged stay group. CONCLUSION: Carefully selected patients receiving an autologous stem cell transplant for treatment of myeloma can be managed with a brief initial hospitalization and outpatient follow-up, with low morbidity and mortality.
Asunto(s)
Melfalán/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/cirugía , Adulto , Anciano , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Trasplante Autólogo/métodosRESUMEN
PURPOSE: To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies. PATIENTS AND METHODS: We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content. RESULTS: Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 10(8) CD8 cells per kilogram optimally segregated patients receiving CD8(hi) and CD8(lo) grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8(hi) graft, whereas approximately half of younger donors provided CD8(hi) grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8(lo) doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8(hi) doses (P = .03), but not for recipients of younger unrelated donor CD8(lo) grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors. CONCLUSION: Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT.
Asunto(s)
Linfocitos T CD8-positivos , Selección de Donante , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Femenino , Citometría de Flujo , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Donante no EmparentadoRESUMEN
BACKGROUND: Although intensive induction and autologous stem cell transplantation (ASCT) prolong survival in younger patients with mantle cell lymphoma (MCL), benefit in older patients remains uncertain because data supporting these approaches come almost exclusively from younger cohorts. PATIENTS AND METHODS: We reviewed outcomes for 38 patients with MCL aged ≥ 60 years who received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) (n = 19) or R-HyperCVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine) (n = 19) with or without ASCT. RESULTS: Median progression-free survival (PFS) of R-CHOP + ASCT (3.2 years) and R-HyperCVAD alone (4.0 years) was longer than that for R-CHOP alone (1.6 years; P = .013 and P = .009, respectively). R-CHOP + ASCT and R-HyperCVAD resulted in similar PFS (P = .66). R-HyperCVAD induction led to a higher incidence of toxicity, including therapy discontinuation and need for transfusions, compared with R-CHOP, although rates of adverse events were similar for R-HyperCVAD alone and R-CHOP + ASCT. CONCLUSION: R-CHOP alone is less effective therapy for fit older patients with MCL. Intensifying therapy with R-HyperCVAD induction or ASCT consolidation after R-CHOP is associated with prolonged PFS and similar rates of toxicity. Consideration should be given to individual preferences regarding the differing method of administration and relative timing of toxicity with each regimen.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células del Manto/terapia , Acondicionamiento Pretrasplante/métodos , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Estudios de Cohortes , Terapia Combinada , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células del Manto/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Rituximab , Trasplante Autólogo , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
OBJECTIVES: We evaluated whether staging with positron emission tomography (PET) or treatment with rituximab after involved-field radiation therapy (IFRT) results in an improved progression-free survival (PFS) for early-stage indolent non-Hodgkin lymphoma (NHL). METHODS: We identified 42 patients with stage I/II low-grade NHL treated with initial IFRT at our institution between 1992 and 2009, who had been staged with computed tomography (CT) or PET. A retrospective analysis was performed to evaluate PFS according to staging by CT or PET, and by receipt of rituximab after IFRT. RESULTS: Overall PFS was 68% and 61% at 5 and 10 years, respectively. There was no significant difference in PFS whether patients were staged by CT (n=17) or by PET (n=25), with 5-year PFS rates of 76% and 60%, respectively. Eleven patients received 4 weekly doses of rituximab after IFRT, with no improvement in 5-year PFS: 46% for rituximab-treated patients versus 72% for patients who were not given rituximab. However, more patients who were given rituximab were stage II. CONCLUSIONS: Patients with limited stage indolent NHL staged with either CT or PET and treated with IFRT have favorable PFS compared with historical controls. The administration of 4 weekly doses of rituximab after IFRT did not improve PFS in these patients. The use of rituximab in this setting should be evaluated in a randomized prospective study.