RESUMEN
Successful cytogenetic studies were performed on 69 biopsies from 64 patients with non-Hodgkin's lymphoma bearing a t(14;18)(q32;q21) translocation. This translocation appears to be a primary abnormality associated with the development of certain B-cell non-Hodgkin's lymphomas. We correlated the occurrence of secondary abnormalities, in addition to the t(14;18)(q32;q21), with histologic subtype to test the hypothesis that secondary abnormalities correlate with more aggressive histologic appearance. A large number of secondary abnormalities were identified, the most frequent being additional copies of chromosomes 7 (30%), 12 (22%), 18 (22%), 20 (16%), or 21 (14%), deletion of a portion of the long arm of chromosome 6 (17%), and either an additional chromosome 17 or an isochromosome for the long arm of chromosome 17 (13%). An extra chromosome 7 was highly associated with a diffuse histologic pattern; it was present in 52% of patients with a diffuse pattern and in only 15% of those with a follicular pattern (P = .002). A weaker association with a diffuse growth pattern was found for the addition of chromosome 17 or an i(17q); it was found in 24% of patients with a diffuse pattern and only 5% of those with a follicular pattern (P = .05). No other significant correlations between secondary chromosome abnormalities and histologic subtype were identified. Although the explanation for this association is not clear, it appears that patients with B-cell non-Hodgkin's lymphomas bearing the t(14;18)(q32;q21) translocation which also have an additional chromosome 7 are likely to exhibit a diffuse growth pattern.
Asunto(s)
Aberraciones Cromosómicas , Linfoma no Hodgkin/genética , Translocación Genética , Linfocitos B/ultraestructura , Humanos , Cariotipificación , Linfoma no Hodgkin/patología , Persona de Mediana Edad , FenotipoRESUMEN
PURPOSE: This study evaluated the results of high-dose therapy followed by autologous bone marrow or peripheral-blood stem-cell transplantation for patients with follicular low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: We performed a retrospective review of 100 patients undergoing autologous transplantation for follicular low-grade lymphoma between April 22, 1983 and December 31, 1993. RESULTS: Sixty-seven patients remained alive and 48 were failure-free. The median follow-up duration of surviving patients was 2.6 years (range, 1.0 to 11.7). There were eight (8%) deaths within 100 days of transplantation. Six additional patients died of nonrelapse causes up to 912 days after transplantation. Overall survival at 4 years was estimated to be 65% (95% confidence interval [CI], 54% to 75%) and failure-free survival was estimated to be 44% (95% CI, 33% to 55%). There was no definite evidence of a plateau in the failure-free survival curve. The only factor significantly associated with overall survival and failure-free survival was the number of chemotherapy regimen received before transplantation. No significant differences in outcome were observed between patients with follicular small cleaved-cell lymphoma and follicular mixed lymphoma, or between patients who received peripheral-blood stem-cell transplants and unpurged autologous bone marrow transplants. CONCLUSION: Prolonged failure-free survival is possible following high-dose therapy and autologous hematopoietic rescue for follicular low-grade lymphoma. It is unclear whether patients are cured with this therapy or if survival is prolonged.
Asunto(s)
Trasplante de Médula Ósea , Trasplante de Células Madre Hematopoyéticas , Linfoma Folicular/terapia , Linfoma no Hodgkin/terapia , Adulto , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Autólogo , Resultado del TratamientoRESUMEN
PURPOSE: A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period. RESULTS: The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test). CONCLUSION: High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/sangre , Trasplante de Médula Ósea , Carmustina/administración & dosificación , Carmustina/efectos adversos , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Infusiones Intravenosas , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Mucosa Bucal/efectos de los fármacos , Recurrencia , Inducción de Remisión , Factores de Riesgo , Estomatitis/inducido químicamente , Análisis de SupervivenciaRESUMEN
Patients with Hodgkin's disease who were previously untreated with chemotherapy received the chlorambucil, vinblastine, procarbazine, and prednisone (CHLVPP) regimen plus limited involved-field radiation therapy for treatment of Hodgkin's disease through the Nebraska Lymphoma Study Group. One hundred patients, 87 with newly diagnosed Hodgkin's disease and 13 who relapsed after receiving previous radiation therapy, were treated with this regimen between 1982 and 1989. Complete remissions (CRs) were obtained in 88 of 100 patients (88%), and there have been a total of eight relapses. The overall 3-year failure-free survival was 76%, with good-prognosis patients (ie, Karnofsky performance status greater than or equal to 80) having a 3-year failure-free survival of 87%. Toxicity with this regimen was minimal, with neutropenic fevers reported in 13% of the patient population, moderate alopecia in 5%, and mild to moderate nausea and vomiting in 11% of the patients. As primary induction therapy for Hodgkin's disease, CHLVPP is an effective regimen with a high patient acceptance profile.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorambucilo/administración & dosificación , Terapia Combinada , Esquema de Medicación , Femenino , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisolona/administración & dosificación , Procarbazina/administración & dosificación , Pronóstico , Modelos de Riesgos Proporcionales , Recurrencia , Inducción de Remisión , Tasa de Supervivencia , Vinblastina/administración & dosificaciónRESUMEN
Non-Hodgkin's lymphoma (NHL) is a malignancy that occurs frequently in the elderly with a median age greater than 60 years. However, most chemotherapy trials have included predominantly patients less than 60 years of age. We treated 157 patients with diffuse aggressive NHL between September 1982 and May 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), procarbazine, bleomycin, vincristine, and prednisone (CAP/BOP). There were no treatment exclusions for age. Patients in this study ranged in age from 15 to 91 years (median, 63) with 112 patients greater than or equal to 60 years of age. The overall complete remission (CR) rate was 65% with no significant difference for age less than 60 (76%) v age greater than or equal to 60 (61%) (P = .18). With a median 36-month follow-up (range, 22 to 65 months), the overall 5-year survival was 42%. The patients less than 60 years old had a 62% 5-year survival in contrast to a 34% 5-year survival in those patients greater than or equal to age 60 (P = .01). The deaths attributed to tumor or treatment-related toxicity were similar above and below age 60. The difference in survival was due to other causes of death not obviously related to the lymphoma or its therapy-occurring in 22% of patients greater than or equal to 60 years of age but only 2% of patients less than 60 years (P = .005). Our data supports the position that aggressive NHL in elderly patients is not significantly less responsive than in younger patients; however, the inclusion of older patients in clinical trials will decrease the overall survival secondary to deaths due to apparently unrelated causes.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Pronóstico , Vincristina/administración & dosificaciónRESUMEN
PURPOSE: To compare the use of intravenous (IV) hydration plus either continuous bladder irrigation or mesna for the prevention of hemorrhagic cystitis in the bone marrow transplant setting. PATIENTS AND METHODS: Two hundred patients were prospectively randomized to receive either continuous bladder irrigation with 200 mL/h of normal saline, or continuous infusion mesna at 100% of the cyclophosphamide dose. RESULTS: The overall incidence of hematuria of any grade was significantly higher in the bladder-irrigation group (76%) compared with the mesna group (53%) (P = .007). However, the incidence of grade III and IV hematuria was the same in both groups (18%; P = NS). Moderate or severe discomfort or bladder spasms were reported in 84% of the patients who received bladder irrigation, compared with 2% of the patients who received mesna prophylaxis (P < .0001). Urinary tract infections (UTIs) were documented in 27% of the patients in the bladder-irrigation group, compared with 14% of the patients in the mesna group (P = .03). CONCLUSION: Both continuous bladder irrigation and mesna were equally effective in preventing severe hemorrhagic cystitis associated with high-dose cyclophosphamide and bone marrow transplantation. However, the use of mesna was associated with significantly less discomfort and a lower incidence of UTIs.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Médula Ósea/efectos adversos , Cistitis/prevención & control , Hematuria/prevención & control , Mesna/uso terapéutico , Adulto , Terapia Combinada , Ciclofosfamida/efectos adversos , Cistitis/etiología , Femenino , Hematuria/etiología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Estudios Prospectivos , Irrigación Terapéutica/métodos , Vejiga UrinariaRESUMEN
PURPOSE: To evaluate clinical and tumor characteristics in patients receiving high-dose chemotherapy and autologous peripheral stem-cell transplantation (PSCT) or bone marrow transplantation (ABMT) for relapsed or primary refractory non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: One hundred fifty-eight patients with NHL received high-dose chemotherapy and ABMT or PSCT. A multivariate analysis of characteristics was performed for comparison of the long-term failure-free survival (FFS) rate. RESULTS: Using a multivariate analysis, a prognostic model was constructed with patients in the good-prognosis group being those without a mass > or = 10 cm at the time of transplant, and no more than one of the following characteristics: three or more prior chemotherapy regimens, lactate dehydrogenase (LDH) level above normal, and chemotherapy resistance. Patients in the poor-prognosis group had a mass > or = 10 cm, or two of the other characteristics noted. The poor-prognosis group had a 3-year FFS rate of 10%, compared with a 45% 3-year FFS in the good-prognosis group (P < .001). Within the prognostic groups, there was no difference in the 3-year FFS rate of the poor-prognosis patients who received ABMT versus PSCT (10% v 12%; not significant). However, in the good-prognosis group, patients who received ABMT had a 3-year FFS rate of 32%, compared with 70% for those who received PSCT (P < .008). CONCLUSION: This prognostic model can identify patients with good and poor prognoses following high-dose chemotherapy and ABMT or PSCT for aggressive NHL. In good-prognosis patients, those who received PSCT had a superior FFS rate.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/terapia , Adolescente , Adulto , Anciano , Trasplante de Médula Ósea , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Recurrencia , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the predictive value of computed tomography (CT) scanning and single-photon emission computed tomography (SPECT) gallium (Ga) scanning in the disease-free survival of patients receiving high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: One hundred forty-three patients undergoing transplant for NHL underwent CT scanning of chest, abdomen, and pelvis, and a SPECT Ga scan before transplantation and at day + 100 after transplant. The failure-free survival (FFS) by scan result was analyzed. RESULTS: In the diffuse aggressive lymphoma patients, the 1-year FFS for patients having a positive SPECT Ga scan at day + 100 was 15% compared with a 3-year FFS of 47% for those with a negative scan (P < .001). Patients with a positive CT scan at day + 100 had a 36% 3-year FFS, and those with a negative CT scan had a 39% 3-year FFS (P = not significant [NS]). An analysis of the combination of CT scan and SPECT Ga scan results at day + 100 posttransplant demonstrated a 3-year FFS of 14% if they were both abnormal; if the CT was positive and Ga was negative, the 3-year FFS was 68%; positive Ga with a negative CT was 25%; and both negative was 34% (P = .0015). For the patients with follicular NHL, those with a positive SPECT Ga at day + 100 had a 14% 1-year FFS compared with those with a negative scan, who had a 45% 3-year FFS (P < .001). In the follicular NHL patients, the 3-year FFS of those with a positive CT was 17% compared with a 64% 3-year FFS for patients with a negative CT scan (P < .001). CONCLUSION: The use of SPECT Ga scan at day + 100 posttransplant for evaluation of disease activity in patients with diffuse aggressive NHL was highly predictive of eventual outcome and was more predictive than the CT scan results. However, for patients with follicular NHL, the addition of SPECT Ga scanning to CT scanning did not add substantially to the evaluation of transplant outcome.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Radioisótopos de Galio , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/terapia , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma Folicular/diagnóstico por imagen , Linfoma Folicular/mortalidad , Linfoma Folicular/terapia , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Trasplante AutólogoRESUMEN
PURPOSE AND METHODS: High-dose therapy with autologous stem-cell support has become common treatment for relapsed or refractory lymphomas. We conducted a study of 178 patients with Hodgkin's disease and 149 patients with non-Hodgkin's lymphoma who received high-dose therapy with stem-cell support. We evaluated the following: (1) whether improvements in outcomes over time found for surgical procedures were also true for a new nonsurgical procedure, autologous bone marrow and peripheral stem-cell transplantation; and (2) whether such a relationship, if it existed, applied to both clinical and economic outcomes. RESULTS: Mortality rates for patients with Hodgkin's disease decreased from 20% in 1987 to 0% in 1991. For non-Hodgkin's lymphoma, the mortality rate decreased from 29% in 1987 to 4% in 1991. Multivariate analyses indicated that the number of previous transplants was the most important factor associated with survival and low-cost care. After controlling for differences in clinical factors, a logistic regression model predicted that patients with Hodgkin's disease had a 20% chance of dying after 30 cases and a 5% chance after 178 cases; patients with non-Hodgkin's disease had a 33% chance of dying after 14 cases and a 5% chance after 149 cases. For patients with Hodgkin's disease, the cost decreased at a rate of 10% per year from 1987 to 1991 (P = .001), while for patients with non-Hodgkin's lymphoma, the cost of transplants decreased at a rate of 8% per year. CONCLUSION: Survival rates improved and costs of care decreased over time for patients who received high-dose therapy with stem-cell support. These changes are most likely related to improvements in supportive care technologies, better patient selection, and experience of the transplant team.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Médula Ósea/economía , Costos de la Atención en Salud , Linfoma/economía , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/economía , Enfermedad de Hodgkin/terapia , Hospitalización/economía , Humanos , Tiempo de Internación , Modelos Logísticos , Linfoma/tratamiento farmacológico , Linfoma/mortalidad , Linfoma/terapia , Linfoma no Hodgkin/economía , Linfoma no Hodgkin/terapia , Análisis Multivariante , Pronóstico , Tasa de Supervivencia , Trasplante AutólogoRESUMEN
PURPOSE: We studied the effect of morphology and extent of bone marrow (BM) infiltrate on the survival of patients with diffuse aggressive B-cell non-Hodgkin's lymphoma (NHL), along with clinical features. PATIENTS AND METHODS: Sixty adult patients with diffuse aggressive B-cell NHL and BM involvement at the time of presentation were studied. All patients were uniformly staged and treated with a curative high-dose chemotherapy regimen. BM involvement was assessed according to the cytology, pattern of infiltration, and extent of involvement, and was correlated with overall survival (OS) and failure-free survival (FFS). RESULTS: Patients with BM involvement that consisted of > or = 50% large cells or BM involvement of > or = 70% had a poorer OS (P = .065 and P = .055, respectively). Those who presented with an infiltrate of less than 50% large cells and an international prognostic index (IPI) of < or = 3 had a significantly longer postrelapse survival time (P = .003). A diffuse or interstitial pattern of BM involvement was predictive of both poor OS and FFS (P = .008 and .009, respectively). Multivariate analysis indicated that only IPI (P = .0005) and pattern of BM infiltration (P = .009) were independent predictors of OS, and only the former was predictive of FFS (P = .03). CONCLUSION: The IPI is predictive of OS and FFS, while BM involvement with a diffuse or interstitial pattern is associated with significantly poorer OS. Patients with BM infiltration that involved > or = 70% of the marrow or contained > or = 50% large cells had poor OS, but more patients need to be studied to determine the significance. Two parameters, IPI < or = 3 and BM large cells less than 50%, identify a group of patients with long-term survival after relapse.
Asunto(s)
Enfermedades de la Médula Ósea/patología , Linfoma de Células B/patología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de la Médula Ósea/mortalidad , Femenino , Humanos , Linfoma de Células B/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Análisis de SupervivenciaRESUMEN
PURPOSE: A phase I/II study of PIXY321 following high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) was conducted to evaluate the safety and clinical potential of this agent. PATIENTS AND METHODS: Fifty patients with Hodgkin's disease or non-Hodgkin's lymphoma (NHL) undergoing HDT and ABMT received PIXY321 post-ABMT in doses that ranged from 50 to 1,000 micrograms/m2/d either as intravenous (i.v.) or subcutaneous (SC) dosing until engraftment was reached. RESULTS: If all doses are considered together, the median time to reach an absolute neutrophil count (ANC) > or = 500/microL was 18 days and the median time to platelet transfusion independence was 21 days. At the estimated optimum dose of 750 micrograms/m2/d by SC injection once daily, the median time to reach an ANC > or = 500/microL was 15 days and the median time to platelet transfusion independence was 16 days. Historical control patients who received granulocyte-macrophage colony-stimulating factor (GM-CSF) had a median time to an ANC > or = 500/microL of 19 days and a median time to platelet independence of 26 days. CONCLUSION: The administration of PIXY321 post-ABMT was generally well tolerated and resulted in prompt engraftment in the majority of patients who underwent HDT and ABMT for lymphoid malignancies. The optimum dose and route of administration of PIXY321 suggested by this trial was 750 micrograms/m2/d by once-daily SC injection. Compared with historical control patients who received 2-hour i.v. GM-CSF, patients who received PIXY321 at 750 micrograms/m2/d by SC injection once daily had an improvement in the median days to neutrophil and platelet engraftment by 4 and 10 days, respectively.
Asunto(s)
Trasplante de Médula Ósea , Refuerzo Inmunológico de Injertos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Enfermedad de Hodgkin/terapia , Interleucina-3/uso terapéutico , Linfoma no Hodgkin/terapia , Proteínas Recombinantes de Fusión/uso terapéutico , Adulto , Anciano , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Humanos , Interleucina-3/administración & dosificación , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/administración & dosificación , Trasplante AutólogoRESUMEN
PURPOSE: Our purpose was to describe the treatment outcome of patients with follicular large-cell lymphoma (FLCL) and to identify prognostic factors that affect the treatment outcome. PATIENTS AND METHODS: Between 1980 and 1991, 107 newly diagnosed, previously untreated patients with FLCL were prospectively treated using treatment plans of the Nebraska Lymphoma Study Group (NLSG). Most stage I/II patients received two to three cycles of one of four closely related six-drug combination chemotherapy regimens (cyclophosphamide, doxorubicin or mitoxantrone, and procarbazine, plus bleomycin, vincristine, and prednisone or dexamethasone [CAP/BOP I-IV]) plus involved-field radiotherapy; 10 patients received involved-field irradiation only. Stage III/IV patients received six to eight cycles of CAP/BOP. RESULTS: Forty-four percent of patients had stage I/II disease. Stage I/II patients were older and more often female than stage III/IV patients. Cytogenetic studies were available on 35 patients: seven were normal; the most common abnormality was a translocation involving 14q32. Abnormalities of 1p or 1q were also common, often secondary to a 14q32 abnormality. The median follow-up of surviving patients is 2 years. The complete response rates observed were stage I/II, 88%; stage III/IV, 49%. Complete response rates were affected by both age and tumor bulk. Failure-free survival (FFS; time to first occurrence of progression, relapse after response, or death from any cause) at 3 years was estimated to be 61% for stage I/II patients and 34% for stage III/IV patients. Survival at 3 years was estimated to be 76% and 61%, respectively. FFS of stage III/IV patients was poorer for stage IV patients and those with composite lymphomas. Significantly poorer survival was only seen in patients older than 70 years of age. CONCLUSION: A proportion of stage I/II FLCL patients may obtain long-term disease control with combination chemotherapy plus radiotherapy. Results for patients with stage III/IV FLCL are similar to those seen for other follicular lymphomas.
Asunto(s)
Linfoma Folicular/patología , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Linfoma Folicular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Análisis de SupervivenciaRESUMEN
PURPOSE: This study was undertaken to examine the feasibility of combining radiolabeled antibody therapy with high-dose chemotherapy followed by autologous bone marrow transplantation in patients with poor-prognosis Hodgkin's disease. PATIENTS AND METHODS: Patients were entered onto this protocol if they had chemotherapy-resistant disease, bulky disease, or extensive prior therapy. Patients received yttrium-labeled antiferritin on day -13, -12, or -11, followed by high-dose cyclophosphamide, carmustine, and etoposide (CBV) on days -6 to -3, and then bone marrow infusion on day 0. RESULTS: Twelve patients received both radiolabeled antibody and high-dose chemotherapy followed by autologous transplantation. Two additional patients started the study, but were unable to complete all therapy. Four of 12 patients experienced early transplant-related mortality. Four patients are alive more than 2 years following transplantation and three are free from disease progression at 24+, 25+, and 28+ months following transplantation. The progression-free survival rate at 1 year is estimated to be 21%. Considering the poor prognostic characteristics of these patients, toxicity on this protocol was not necessarily greater than that observed with high-dose chemotherapy alone. CONCLUSION: This report demonstrates the feasibility of combining radiolabeled antibody therapy with high-dose chemotherapy and autologous bone marrow transplantation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Enfermedad de Hodgkin/terapia , Radioinmunoterapia , Adolescente , Adulto , Carmustina/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Etopósido/administración & dosificación , Femenino , Ferritinas/inmunología , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Proteínas de Neoplasias/inmunología , Pronóstico , Tasa de Supervivencia , Radioisótopos de ItrioRESUMEN
PURPOSE: This study evaluated the outcomes of patients who received high-dose chemotherapy (HDC) and autologous hematopoietic stem-cell transplantation (ASCT) for large-cell non-Hodgkin's lymphoma (NHL) and the effect of a follicular versus a diffuse histology. PATIENTS AND METHODS: The prognostic factors in 289 patients who underwent HDC and ASCT for large-cell NHL between May 1983 and December 1996 were analyzed. RESULTS: With a median follow-up duration of 24 months for surviving patients (range, 3 to 131 months), 112 of 289 (39%) were alive and 82 of 289 (28%) were failure-free. In a multivariate analysis, the factors associated with a poorer failure-free survival (FFS) included a lactic dehydrogenase (LDH) level greater than normal (P < .0001), three or more prior chemotherapy regimens received (P < .01), a mass > or = 10 cm at transplant (P < .01), and diffuse histology at the time of transplant (P = .026). Patients who received HDC and ASCT for large-cell NHL in the good-prognosis category (normal LDH, < three prior chemotherapy regimens, no large mass, and not chemotherapy-resistant) had a 5-year survival rate of 45%. Within the good-prognosis group, patients with diffuse large-cell NHL had a 5-year survival rate of 42% compared with 58% for patients with follicular large-cell (FLC) lymphoma (P = .05). CONCLUSION: Good-prognosis patients with FLC histology who receive HDC and ASCT have an improved survival compared with good-prognosis patients with a diffuse large-cell histology.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso/terapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Femenino , Humanos , Linfoma Folicular/mortalidad , Linfoma Folicular/patología , Linfoma Folicular/terapia , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Trasplante AutólogoRESUMEN
PURPOSE: To analyze the risk of developing myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) following autologous bone marrow transplantation (ABMT) or peripheral stem-cell transplantation (PSCT) and to determine the impact on failure-free survival (FFS). PATIENTS AND METHODS: Patients underwent ABMT or PSCT for the treatment of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the University of Nebraska Medical Center. For those patients who went on to develop MDS/AML, controls were selected and a case-control-within-a-cohort study undertaken. RESULTS: Twelve patients developed MDS or AML a median of 44 months following ABMT/PSCT. The cumulative incidence (P = .42) and the conditional probability (P = .32) of MDS/AML were not statistically different between HD and NHL patients. Age greater than 40 years at the time of transplant (P = .05) and receipt of a total-body irradiation (TBI)-containing regimen (P = .06) were predictive for developing MDS/AML in patients with NHL. CONCLUSION: There is an increased risk of MDS/AML following ABMT/PSCT for lymphoid malignancies. NHL patients age > or = 40 years at the time of transplant and who received TBI are at greatest risk.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad de Hodgkin/terapia , Leucemia Mieloide Aguda/etiología , Linfoma no Hodgkin/terapia , Síndromes Mielodisplásicos/etiología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Casos y Controles , Estudios de Cohortes , Terapia Combinada , Femenino , Enfermedad de Hodgkin/mortalidad , Humanos , Incidencia , Leucemia Mieloide Aguda/epidemiología , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/epidemiología , Pronóstico , Dosificación Radioterapéutica , Factores de Riesgo , Tasa de Supervivencia , Irradiación Corporal TotalRESUMEN
Twenty patients (age range, 4 to 48 years; median age, 36 years) with de novo or drug-induced myelodysplastic syndromes or myeloproliferative disorders were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Four preparative regimens were used; three regimens consisted of combined total body irradiation (TBI) and chemotherapy and one of combination chemotherapy only. One patient received marrow from his identical twin brother, whereas the other 19 patients were grafted with marrow from histocompatible siblings. In 19 patients the abnormal clone was at least temporarily ablated, while in one patient the congenital myelodysplasia persisted. Eight patients are alive and well for +108 to +3,359 days post-transplantation. Nine patients died of transplant-related complications (six of interstitial pneumonia, two of gastrointestinal bleeding, and one of fungal sepsis) and three patients died with persisting or recurring disease. One patient with a late recurrence has undergone a second successful bone marrow transplant procedure. Outcome of BMT was not related to French-American-British (FAB) type, marrow fibrosis, cytogenetic abnormalities, or preparation regimen. Marrow transplantation as a means of providing long-term disease-free survival and possible cure should be considered in patients if a suitable donor is available.
Asunto(s)
Trasplante de Médula Ósea , Síndromes Mielodisplásicos/terapia , Trastornos Mieloproliferativos/terapia , Adolescente , Adulto , Niño , Preescolar , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/radioterapia , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/radioterapia , Recurrencia , Donantes de Tejidos , Irradiación Corporal TotalRESUMEN
PURPOSE: Mobilization of peripheral-blood cells (PBC) with cytokines alone results in rapid hematopoietic recovery and avoids the potential morbidity associated with mobilization by chemotherapy. PIXY321, a fusion protein that consists of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), has enhanced hematopoietic colony-forming activity as compared with individual or equimolar combinations of the two cytokines. A phase I trial of PIXY321 for mobilization of PBC in patients with malignant lymphoma was performed. PATIENTS AND METHODS: Thirteen patients with malignant lymphoma who were eligible for high-dose therapy (HDT) were enrolled onto the trial. All patients were ineligible for autologous bone marrow transplantation due to overt metastatic disease in the marrow or to severe marrow hypocellularity. PIXY321 was administered at three dose levels of 250, 500, and 750 micrograms/m2/d by continuous infusion until completion of PBC collections. Collections were initiated when the WBC count was greater than 10 x 10(9)/L or 4 days after the initiation of PIXY321, whichever came first. Collections were continued until a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg patient weight were obtained. RESULTS: PIXY321 was generally well tolerated. Side effects associated with PIXY321 administration did not exceed grade 2 and included fever (85%), chills/sweats (54%), myalgias (38%), fatigue (31%), nausea/vomiting (31%), headache (31%), edema (23%), and rhinorrhea (23%). The median numbers of colony-forming units-granulocyte/macrophage (CFU-GM) in the graft products for the three dose levels were 0.31, 2.94, and 2.88 x 10(4)/kg, respectively; the median numbers of burst-forming units-erythroid (BFU-e) were 0.20, 6.94, and 12.78 x 10(4)/kg, and the median numbers of CD34+ cells were 2.30, 0.74, and 0.39 x 10(6)/kg. Following transplantation, the median times to an absolute neutrophil count (ANC) > 0.5 x 10(9)/L were 12, 15, and 12 days, respectively, and the median times to platelet transfusion independence were 30, 19, and 15 days. CONCLUSION: PIXY321 can be safely administered and effectively mobilizes PBC in patients with bone marrow defects. PIXY321-mobilized PBC autotransplants result in rapid and sustained hematopoietic recovery.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Interleucina-3/administración & dosificación , Linfoma/terapia , Adulto , Antígenos CD34/análisis , Eliminación de Componentes Sanguíneos , Ensayo de Unidades Formadoras de Colonias , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Interleucina-3/efectos adversos , Linfoma/sangre , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversosRESUMEN
PURPOSE: To investigate whether primary mediastinal large B-cell lymphoma (PMLBL) is a distinct clinicopathologic entity with a more aggressive course than other diffuse large B-cell lymphomas (DLBL). MATERIALS AND METHODS: All patients with CD20-positive DLBL who presented with a mediastinal mass measuring at least 5.0 cm and were treated with curative intent were identified. A control group of 352 patients with nonmediastinal DLBL was selected for comparison. RESULTS: The 43 patients with PMLBL had a male to female ratio of 20:23 and a median age of 42 years. Stage I/II disease was present in 58% of the patients, with only 9% having bone marrow involvement. A complete remission was achieved in 63% of the patients, and the 5-year overall and failure-free survivals were 46% and 38%, respectively. Among the clinical variables, an elevated serum lactate dehydrogenase level, a low performance score, more than one extranodal site, and an intermediate or high International Prognostic Index score were predictive of poor survival. When compared with the DLBL group, a younger median age was the only clinical feature that was significantly different in the PMLBL group. CONCLUSION: The clinical features of PMLBL do not appear to be significantly different from those of nonmediastinal DLBL. Although the younger age of onset, slight female predominance, mediastinal location, and size of the mass may justify the recognition of PMLBL as a clinical syndrome, additional evidence is needed to define it as a distinct disease entity.
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Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/patología , Neoplasias del Mediastino/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma de Células B/terapia , Linfoma de Células B Grandes Difuso/terapia , Masculino , Neoplasias del Mediastino/terapia , Persona de Mediana Edad , Inducción de Remisión , Análisis de SupervivenciaRESUMEN
PURPOSE: To determine the treatment outcome and clinical factors that are of prognostic significance for children and adolescents with relapsed or refractory Hodgkin's disease (HD) who received treatment with high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS: Fifty-three consecutive children and adolescents 21 years of age or younger with relapsed or refractory HD underwent HSCT. RESULTS: At day 100 after transplantation, 29 patients (55%) were in a complete remission or maintained a continuous complete response, six (11%) had a partial response, and 11 (21%) failed to respond or had progressive disease. The failure-free survival (FFS) at 5 years was 31%, and overall survival was 43%. Twenty-one patients died of progressive HD, and nine died secondary to transplantation-related complications, including two secondary leukemias. Prognostic factors important for FFS were normal pretransplantation lactate dehydrogenase levels (5-year FFS = 42%), compared with patients with elevated LDH levels (5-year FFS = 0%) (P < .001), and disease sensitivity at the time of HSCT with FFS in untreated relapse, sensitive disease, and resistant disease 44%, 35%, and 9%, respectively (P = .06). There was no statistically significant difference in FFS or overall survival between age subgroups that were analyzed (< 13, 13 to 18, 19 to 21) or in comparison with an adult cohort. CONCLUSION: HSCT is an effective treatment modality that can result in long-term cures and should be considered for children and adolescents with relapsed HD.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/terapia , Adolescente , Adulto , Niño , Terapia Combinada , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Masculino , Pronóstico , Inducción de Remisión , Análisis de Supervivencia , Trasplante AutólogoRESUMEN
PURPOSE: The optimal dose of granulocyte colony-stimulating factor (G-CSF) for mobilization of allogeneic-blood stem cells (AlloBSC) has yet to be determined. As part of a prospective trial, 41 related human leukocyte antigen (HLA)-matched donors had blood cells mobilized with G-CSF at 5 micrograms/kg/d by subcutaneous administration. The purpose of this trial was to monitor adverse effects during G-CSF administration and stem-cell collection, to determine the optimal timing for stem-cell collection, and to determine the cellular composition of stem-cell products following G-CSF administration. PATIENTS AND METHODS: The median donor age was 42 years. Apheresis began on day 4 of G-CSF administration. At least three daily 12-L apheresis collections were performed on each donor. A minimum of 1.0 x 10(6) CD34+ cells/kg (recipient weight) and 8.0 x 10(8) mononuclear cells/kg were collected from each donor. All collections were cryopreserved in 5% dimethyl sulfoxide and 6% hydroxyethyl starch. RESULTS: Toxicities associated with G-CSF administration and the apheresis process included myalgias/arthralgias (83%), headache (44%), fever (27%), and chills (22%). The median baseline platelet count of 242 x 10(4)/ mL decreased to 221, 155, and 119 x 10(6)/mL on days 4, 5, and 6 of G-CSF administration, respectively. Median numbers of CD34+ cells in collections 1, 2, and 3 were 1.99, 2.52, and 3.13 x 10(6)/kg, respectively. The percentage and total number of CD4+, CD8+, and CD56+/CD3- cells remained relatively constant during the three collections. Median total numbers of cells were as follows: CD34+, 7.73 x 10(6)/kg; and lymphocytes, 6.93 x 10(8)/kg. CONCLUSION: Relatively low doses of G-CSF can mobilize sufficient numbers of AlloBSC safely and efficiently.