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BACKGROUND: Ankle Foot Orthoses (AFOs) are frequently prescribed to manage gait impairments in children with physical disability, and it is important that AFOs are prescribed and fitted appropriately to maximize potential benefits. AFO tuning, manipulation of the AFO footwear combination (AFO-FC) by means of video vector analysis, is routinely used to optimize AFO use. However, the incidence or types of changes that are implemented after this type of orthotic review are unknown. RESEARCH QUESTION: To investigate the impact of a multi-disciplinary video vector clinic on AFO provision in children with physical disability. METHODS: All children who attended a video vector clinic over a period of 10-years from the establishment of the clinic were included in the study. Outcomes of the clinic were grouped into 5 categories: (1) No change to AFO-FC; (2) Altered/tuned AFO-FC; (3) Discontinued AFO-FC; (4) Recast AFO; (5) Change in prescription. Data were summarised narratively. RESULTS: 141 independently ambulant children were included. The diagnoses were bilateral cerebral palsy (39â¯%, n=55), unilateral cerebral palsy (38â¯%, n=54), spina bifida (9â¯%, n=13), hereditary spastic paraparesis (2â¯%, n=3) and other (11â¯%, n=16). No changes were made in 52â¯% of cases (n=74), tuning in 22â¯% of cases (n=31), the AFO was recast in 13â¯% of cases (n=19) and discontinued in 10â¯% of cases (n=14). A prescription change was recommended in 3â¯% of cases (n=4). SIGNIFICANCE: Our findings suggest that the video vector clinic is a time efficient and effective means of assessing gait function in children with AFOs. Without assessment at the clinic, most of the children assessed would likely have been referred for a full and more time consuming 3-dimensional gait analysis. Video vector analysis at the initial AFO fitting may improve alignment and possibly reduce non-compliance at an earlier stage.
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BACKGROUND: Phosphoinositide 3-kinase (PI3K) inhibitors are a class of small-molecule inhibitors approved for the treatment of certain leukaemias and lymphomas. Their dermatological adverse event profile is poorly described. AIM: To characterize a rare cutaneous adverse event from PI3K inhibitors in order to help dermatologists and oncologists identify and effectively manage such eruptions. METHODS: This was a retrospective analysis of patients receiving PI3K inhibitors referred to the Skin Toxicities Program in The Center for Cutaneous Oncology. RESULTS: Three patients on PI3K inhibitors for treatment of malignancy developed diffuse erythroderma and keratoderma. Clinical and histopathological findings were consistent with pityriasis rubra pilaris (PRP)-like reactions. All patients improved with topical and oral corticosteroids, oral acitretin, and drug discontinuation. CONCLUSIONS: PRP-like cutaneous eruptions may develop secondary to PI3K inhibition. Early dermatological evaluation of cutaneous toxicities to PI3K inhibitors as well as rapid initiation of disease-specific treatments may help keep patients on life-prolonging anti-cancer therapies.
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Antineoplásicos/efectos adversos , Dermatitis Exfoliativa/inducido químicamente , Inhibidores de las Quinasa Fosfoinosítidos-3 , Pitiriasis Rubra Pilaris/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Anciano , Antineoplásicos/uso terapéutico , Dermatitis Exfoliativa/patología , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Oligodendroglioma/tratamiento farmacológico , Pitiriasis Rubra Pilaris/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Piel/patologíaRESUMEN
Chronic lymphocytic leukemia (CLL) remains incurable with chemoimmunotherapy, and allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential for cure. We assessed the outcomes of 108 CLL patients undergoing first allogeneic HSCTs, 76 with reduced-intensity (RIC) and 32 with myeloablative conditioning (MAC) between 1998 and 2009 at Dana-Farber Cancer Institute. With median follow-up of 5.9 years in surviving patients, the 5-year overall survival (OS) for the entire cohort is 63% for RIC regimens and 49% for MAC regimens (P=0.18). The risk of death declined significantly starting in 2004, and we found that 5-year OS for HSCT between 2004 and 2009 was 83% for RIC regimens compared with 47% for MAC regimens (P=0.003). For RIC transplantation, we developed a prognostic model based on predictors of progression-free survival (PFS), specifically remission status, lactate dehydrogenase, comorbidity score and lymphocyte count, and found 5-year PFS to be 83% for Score 0, 63% for Score 1, 24% for Score 2 and 6% for Score ≥3 (P<0.0001). We conclude that RIC HSCT for CLL in the current era is associated with excellent long-term PFS and OS, and, as potentially curative therapy, should be considered early in the disease course of relapsed high-risk CLL patients.
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Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Leucemia Linfocítica Crónica de Células B/terapia , Modelos Estadísticos , Recurrencia Local de Neoplasia/terapia , Adulto , Anciano , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Cariotipificación , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
Methylene blue has been used not only as a diagnostic agent, but also as an agent in the treatment of ifosfamide-induced encephalopathy (IIE) for several years. Recently, several cases of suspected serotonin syndrome have been reported in patients who received methylene blue in combination with serotonin active agents. Rodent models have revealed that methylene blue is a potent, reversible inhibitor of monoamine oxidase A. It is well known that serotonin active drugs, in combination with monoamine oxidase inhibitors can produce profound serotonin syndrome. To date, cases of serotonin syndrome, which resulted from concurrent methylene blue and serotonin active agents, have been published in the anesthesia literature. We report the first known case of serotonin syndrome in a patient receiving methylene blue for IIE.
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Encefalopatías/inducido químicamente , Encefalopatías/tratamiento farmacológico , Ifosfamida/efectos adversos , Azul de Metileno/efectos adversos , Síndrome de la Serotonina/inducido químicamente , Síndrome de la Serotonina/etiología , Humanos , Ifosfamida/uso terapéutico , Azul de Metileno/uso terapéuticoRESUMEN
BACKGROUND: The prognosis for patients with most forms of T-cell lymphoma is poor. Allogeneic hematopoietic stem-cell transplantation (HSCT) may improve the outcome. PATIENTS AND METHODS: This study examines the outcome of 52 patients who underwent ablative or nonablative allogeneic HSCT for peripheral T-cell lymphoma (PTCL) or advanced mycosis fungoides/Sezary syndrome over a 12-year period at a single institution. We divided the patients into those with predominantly nodal histologies: peripheral T-cell not otherwise specified (PTCL NOS), angioimmunoblastic (AITL), or anaplastic large cell lymphoma, T/null type (systemic) (ALCL), and predominantly extranodal histologies: natural killer (NK)/T cell, enteropathy type, hepatosplenic, subcutaneous panniculitic, mycosis fungoides, or T cell or NK cell other. RESULTS: Median follow-up of survivors is 49 months. Non-relapse mortality and relapse at 3 years was 27% and 43%, respectively. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 21%. The incidence of extensive chronic GVHD at 2 years was 27%. The 3-year progression-free survival was 30%: 45% in patients with predominantly nodal histologies (PTCL NOS, AITL, and ALCL) and 6% in patients with predominantly extranodal histologies (P = 0.016). Overall survival at 3 years was 41% for all patients. CONCLUSION: Allogeneic HSCT can produce long-term remissions in relapsed/refractory T-cell lymphoma, especially those with nodal histologies.
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Enfermedad Injerto contra Huésped/etiología , Linfoma de Células T Periférico/terapia , Micosis Fungoide/terapia , Síndrome de Sézary/terapia , Neoplasias Cutáneas/terapia , Trasplante de Células Madre , Adulto , Anciano , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/terapia , Humanos , Linfoma de Células T Periférico/complicaciones , Masculino , Persona de Mediana Edad , Micosis Fungoide/complicaciones , Síndrome de Sézary/complicaciones , Neoplasias Cutáneas/complicaciones , Tasa de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Reduced-intensity conditioning (RIC) hematopoietic SCT (HSCT) is a potentially curative therapeutic option for patients with advanced follicular lymphoma (FL), but disease relapse remains the most common cause of failure. Radioimmunoconjugates administered before RIC allo-HSCT may enhance cytoreduction and allow more time for GVL effect to develop without the associated toxicity of a myeloablative HSCT. We performed a retrospective study to describe the outcomes of patients with relapsed, refractory or transformed FL who received yttrium-90 ((90)Y)-ibritumomab tiuxetan followed by fludarabine and low-dose BU RIC allogeneic HSCT at the Dana-Farber Cancer Institute between 2006 and 2009, inclusively. Twelve patients were identified with a median age of 55 (40-66) years and a median number of lines of therapy of 5 (2-10). Two patients (17%) had transformed to a more aggressive histology and five (42%) had chemorefractory FL. Cumulative incidences of grade II-IV acute GVHD at 100 days were 17% (±11%) and chronic GVHD at 12 months were 63% (±19%). Two-year non-relapse mortality was 18% (±12%). Two-year OS and PFS were 83% (±11%) and 74% (±13%), respectively. This treatment is associated with favorable outcomes including acceptable rates of GVHD and relapse in advanced FL patients, and warrants prospective studies.
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Anticuerpos Monoclonales/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Linfoma Folicular/mortalidad , Linfoma Folicular/terapia , Acondicionamiento Pretrasplante , Adulto , Anciano , Enfermedad Crónica , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/terapia , Humanos , Incidencia , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante HomólogoRESUMEN
Epithelial-mesenchymal interactions guide tooth development through its early stages and establish the morphology of the dentin surface upon which enamel will be deposited. Starting with the onset of amelogenesis beneath the future cusp tips, the shape of the enamel layer covering the crown is determined by five growth parameters: the (1) appositional growth rate, (2) duration of appositional growth (at the cusp tip), (3) ameloblast extension rate, (4) duration of ameloblast extension, and (5) spreading rate of appositional termination. Appositional growth occurs at a mineralization front along the ameloblast distal membrane in which amorphous calcium phosphate (ACP) ribbons form and lengthen. The ACP ribbons convert into hydroxyapatite crystallites as the ribbons elongate. Appositional growth involves a secretory cycle that is reflected in a series of incremental lines. A potentially important function of enamel proteins is to ensure alignment of successive mineral increments on the tips of enamel ribbons deposited in the previous cycle, causing the crystallites to lengthen with each cycle. Enamel hardens in a maturation process that involves mineral deposition onto the sides of existing crystallites until they interlock with adjacent crystallites. Neutralization of acidity generated by hydroxyapatite formation is a key part of the mechanism. Here we review the growth parameters that determine the shape of the enamel crown as well as the mechanisms of enamel appositional growth and maturation.
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Amelogénesis/fisiología , Esmalte Dental/embriología , Ameloblastos/fisiología , Animales , Fosfatos de Calcio/metabolismo , Proteínas del Esmalte Dental/metabolismo , Durapatita/metabolismo , Órgano del Esmalte/fisiología , Humanos , Calcificación de Dientes/fisiología , Corona del Diente/embriologíaRESUMEN
BACKGROUND: The purpose of this study was to analyze response to palliative low-dose involved-field radiotherapy (LD-IF-RT) (two 2-Gy fractions), explore factors predicting for response, and determine the time course to subsequent treatment. PATIENTS AND METHODS: Thirty-three patients with advanced or recurrent indolent non-Hodgkin's lymphoma (NHL) received LD-IF-RT to 43 sites. Response was assessed by physical examination and radiographic studies. Median follow-up for individual sites was 14 months. Fisher's exact test was used to evaluate prognostic factors for response and in-field progression. RESULTS: Overall response was 95%. Thirty-six sites (84%) had a complete response (CR), five sites (12%) had a partial response, and two sites (5%) had progressive disease. The CR rate of head and neck sites was significantly higher than that of pelvic and/or inguinofemoral sites (95% versus 64%, P = 0.04). The CR rate was significantly higher for sites < or =40 mm than for sites >40 mm (90% versus 56%, P = 0.04). Ten sites (23%) had in-field progression diagnosed at a median of 9 months. Sixteen patients (48%) received systemic treatment at a median of 8 months. Fourteen patients (42%) did not require additional treatment. CONCLUSIONS: LD-IF-RT for selected NHL subtypes has excellent local CR and in-field control rates and may postpone the need for systemic therapy.
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Linfoma no Hodgkin/radioterapia , Cuidados Paliativos/métodos , Radioterapia/métodos , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: To prospectively study changes in lung function in Hodgkin's lymphoma (HL) patients and to explore predictors for these changes over time. METHODS: In all, 52 patients with HL receiving bleomycin-based chemotherapy with (n = 23) or without (n = 29) mediastinal radiotherapy were enrolled. Pretreatment pulmonary function tests were carried out. These were repeated at 1 month, 6 months, and 1 year after therapy. RESULTS: With chemotherapy alone, the median %DLCO declined significantly at 1 month but returned to baseline by 6 months. The median %DLCO did not further decrease with radiotherapy, but remained persistently reduced at 1 year. In patients who received radiotherapy, having >33% of lung volume receive 20 Gy (V20) and a mean lung dose (MLD) of >13 Gy significantly predicted for persistently reduced %DLCO at 6 months (P = 0.035). Smoking significantly predicted for a persistently reduced %DLCO at 1 year (P = 0.036). On multivariable analysis, significant predictors for decline in %DLCO at 1 year were higher baseline %DLCO (P = 0.01), higher MLD (P = 0.02), and a smoking history (P = 0.02). CONCLUSIONS: Several factors contribute to decline in %DLCO in HL patients who received bleomycin-based computed tomography. The identification of threshold radiation dosimetric parameters for reduced lung function may provide guidance in the radiation planning of these patients.
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Enfermedad de Hodgkin/fisiopatología , Enfermedades Pulmonares/etiología , Pulmón/fisiopatología , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Terapia Combinada , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Humanos , Pulmón/efectos de los fármacos , Pulmón/efectos de la radiación , Enfermedades Pulmonares/inducido químicamente , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Traumatismos por Radiación/etiologíaRESUMEN
BACKGROUND: To determine the long-term treatment outcome and late effects of mantle irradiation alone in selected patients with early-stage Hodgkin's disease. METHODS: Between 1988 and 2000, 87 patients with pathologic stage (Ann Arbor) I-IIA or clinical stage IA Hodgkin's disease were entered on to a prospective trial of mantle irradiation alone. Patients with B symptoms, large mediastinal adenopathy, or subcarinal or hilar involvement were excluded. The median doses to the mantle field and mediastinum were 36 Gy (range 30.3-40) and 38.6 Gy (range 30.6-44), respectively. The actuarial freedom from treatment failure (FFTF) and overall survival (OS) rates were calculated using the Kaplan-Meier technique. RESULTS: The median follow-up was 107 months (range 23-192). Thirteen of 87 patients (15%) relapsed at a median of 30 months (range 5-62). The 5- and 10-year actuarial FFTF rates were 86% and 84.7%, respectively. All 13 patients who relapsed are alive without evidence of disease at a median of 84 months (range 30-156) post-salvage therapy. Five patients developed a second malignancy at a median of 93 months (range 27-131). The 10-year actuarial risk of a second malignancy was 4.5%. There have been two deaths to date, both due to second malignancies. The 10-year OS rate was 98.2%. CONCLUSION: In selected patients with early-stage Hodgkin's disease, mantle irradiation alone has an excellent long-term survival rate, comparing favorably with the previous standard treatment of extended-field radiation therapy and the current standard of combined modality therapy.
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Enfermedad de Hodgkin/radioterapia , Adolescente , Adulto , Niño , Femenino , Enfermedad de Hodgkin/prevención & control , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Recurrencia , Terapia Recuperativa , Factores de Tiempo , Resultado del TratamientoRESUMEN
The diagnosis and treatment of cancer is often associated with high levels of psychosocial distress, yet exploration of these issues is rarely included in routine oncologic care. We conducted a pilot study to evaluate the feasibility of screening for psychosocial distress after autologous and allogeneic stem cell transplantation. A total of 80 adults were enrolled in Boston, MA, USA. Subjects completed self-administered assessments prior to hospital admission, at their first clinic visit after hospital discharge, and at 100 days post transplant. Assessments included validated instruments assessing psychosocial distress and quality of life (QOL). Elevated levels of anxiety and/or depression were detected in 55% of those providing pre-transplant assessments and were associated with compromised QOL. Post transplant screening was successfully performed in 69% of subjects and identified that 44% had symptoms of depression, anxiety or post traumatic stress disorder. Pre-transplant distress was associated with detection of distress after transplantation (81 vs 13%, P< 0.0001). In summary, we detected high levels of distress in transplant patients using self-administered tools. Pre-transplant distress appears to be highly predictive of distress post transplant and is a feasible marker to target screening and intervention programs.
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Trasplante de Células Madre Hematopoyéticas/métodos , Estrés Psicológico/diagnóstico , Adaptación Psicológica , Adulto , Ansiedad , Depresión , Emociones , Femenino , Humanos , Acontecimientos que Cambian la Vida , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Proyectos Piloto , Calidad de Vida , Rol del Enfermo , Trasplante de Células Madre/efectos adversos , Trasplante de Células Madre/psicología , Trastornos por Estrés Postraumático , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Prior studies suggest that depletion of CD8+ T cells from donor bone marrow or donor lymphocyte infusions can reduce graft-versus-host disease (GVHD) without compromising graft-versus-leukemia. We explored CD8 depletion in patients undergoing matched related donor (MRD, n=25) and unrelated donor (URD, n=16) peripheral blood stem cell transplantation following myeloablative conditioning with cyclophosphamide (60 mg/kg/day i.v. x 2) and total body irradiation (200 cGy x 7 fractions). Ex vivo incubation of mobilized donor peripheral blood cells with anti-CD8 antibody coated high-density microparticles removed 99% of CD8+ cells. The median number of CD8+ cells infused was 3.9 x 10(5) cells/kg (2.2 x 10(5) in MRD, and 8.1 x 10(5) in URD patients). Post transplant immune suppression included tacrolimus in the MRD cohort, and tacrolimus plus mini-methotrexate (5 mg/m2 days +1, 3, 6, 11) in the URD cohort. All 41 patients engrafted. Grade 2-4 acute GVHD incidence was 61% (44% MRD, 88% URD). Chronic GVHD incidence was 50% (48% MRD, 55% URD). Relapse incidence was 4.9%. Estimated event-free and overall survival rates were 65 and 63%, respectively, at 1 year and 56 and 57%, respectively, at 2 years. There was no correlation between CD8+ number and GVHD or survival. A 2-log depletion of CD8+ cells from PBSC is insufficient to prevent GVHD.
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Linfocitos T CD8-positivos , Enfermedad Injerto contra Huésped/prevención & control , Enfermedades Hematológicas/terapia , Depleción Linfocítica , Trasplante de Células Madre de Sangre Periférica , Acondicionamiento Pretrasplante , Adulto , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Depleción Linfocítica/métodos , Masculino , Persona de Mediana Edad , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Irradiación Corporal TotalRESUMEN
BACKGROUND: The aim of this study was to determine salvage outcome in patients with Hodgkin's disease who relapse after radiation therapy, and to compare the efficacy of mechlorethamine, Oncovin, procarbazine and prednisone (MOPP) versus Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) as salvage treatment. PATIENTS AND METHODS: One hundred patients with Hodgkin's disease (97 with stage I-II disease at presentation) who relapsed after radiation therapy alone were salvaged with either MOPP or ABVD. Freedom from second relapse (FFSR) and overall survival (OS) were determined, and prognostic factors for salvage outcome were evaluated. RESULTS: The median follow-up time since salvage therapy was 12 years. The 10-year FFSR and OS rates were 70% and 89%, respectively. Forty-one patients were salvaged with MOPP and 59 received ABVD. The type of salvage chemotherapy did not significantly influence FFSR or OS. Age >50 years at initial diagnosis was the only significant predictor for an inferior FFSR and OS on both univariate and multivariate analyses. CONCLUSIONS: The two salvage regimens of MOPP and ABVD had similar efficacy in this group of patients with predominantly early-stage disease at initial radiation therapy. The inferior salvage outcome in patients aged >50 years is a contributing factor to the overall poor prognosis of patients presenting with Hodgkin's disease at an older age.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Dacarbazina/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Enfermedad de Hodgkin/patología , Humanos , Masculino , Mecloretamina/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Pronóstico , Recurrencia , Terapia Recuperativa , Vinblastina/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
One limitation of ASCT is the potential reinfusion of tumor cells contaminating PBSC. The Eligix B cell SC system consists of high-density microparticles coated with anti-B cell antibodies. To determine if this system eliminates B cells and lymphoma cells from PBSC, immunocytochemistry and PCR of the bcl-2/IgH rearrangement were performed, and correlated with patient outcome after ASCT. Eligible patients (n=29) had relapsed or transformed follicular NHL with bone marrow involvement <20%, and all lymph nodes <5 cm. PBSCs were mobilized with cyclophosphamide/G-CSF (n=21), and patients were conditioned with cyclophosphamide, carmustine and etoposide. Using immunocytochemistry on PBSC, the median number of CD20+ cells pre-purge was 310/10(6) (range 0-16692) and post-purge was 0.75/10(6); the median log B cell depletion was 2.7 (range 1.4-3.9). B cell depletion correlated with PFS after ASCT (P=0.06). Of 17 available samples for PCR, only four had a detectable t(14;18) breakpoint. After purging, all four remained PCR+; two had a 1-3 log depletion of lymphoma cells. At median follow-up of 18 months, 10 patients, including five infused with PCR-negative PBSC, have had disease progression. The paucity of PCR-informative patients, possibly related to in vivo rituximab therapy, limited the utility of minimal residual disease as a surrogate marker of clinical outcome.
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Linfocitos B , Depleción Linfocítica/métodos , Linfoma Folicular/patología , Linfoma Folicular/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Adulto , Anciano , Antígenos CD20/análisis , Eliminación de Componentes Sanguíneos/normas , Separación Celular/métodos , Progresión de la Enfermedad , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Células Neoplásicas Circulantes/patología , Análisis de Supervivencia , Trasplante Autólogo , Resultado del TratamientoAsunto(s)
Neoplasias Óseas/patología , Fémur , Pierna , Linfoma de Células del Manto/patología , Neoplasias de los Tejidos Blandos/patología , Anciano , Neoplasias Óseas/diagnóstico por imagen , Femenino , Humanos , Linfoma de Células del Manto/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Waldenstrom's macroglobulinemia (WM, lymphoplasmacytic lymphoma) is a B-cell lymphoproliferative disorder in which CD20 is expressed on tumor cells from most patients. Several small studies have suggested a benefit from the anti-CD20 monoclonal antibody rituximab (Rituxan, MabThera) in patients with WM. In this retrospective study, we examined the outcome of 30 previously unreported patients with WM who received treatment with single-agent rituximab (median age 60; range 32-83 years old). The median number of prior treatments for these patients was 1 (range 0-6), and 14 patients (47%) received a nucleoside analogue before rituximab therapy. Patients received a median of 4.0 (1-11.3) infusions of rituximab (375 mg/m2). Three patients received steroids with their infusions for prophylaxis of rituximab-related infusion syndrome. Overall, treatment was well tolerated. Median immunoglobulin M (IgM) levels for all patients declined from 2,403 mg/dL (range 720-7639 mg/dL) to 1,525 mg/dL (range 177-5,063 mg/dL) after rituximab therapy (p = 0.001), with 8 of 30 (27%) and 18 of 30 (60%) patients demonstrating >50% and >25% decline in IgM, respectively. Median bone marrow lymphoplasmacytic (BM LPC) cell involvement declined from 60% (range 5-90%) to 15% (range 0-80%) for 17 patients for whom pre- and post-BM biopsies were performed (p < 0.001). Moreover, 19 of 30 (63%) and 15 of 30 (50%) patients had an increase in their hematocrit (HCT) and platelet (PLT) counts, respectively. Before rituximab therapy, 7 of 30 (23.3%) patients were either transfusion or erythropoietin dependent, whereas only 1/30 (3.3%) patients required transfusions (no erythropoietin) after rituximab. Overall responses after treatment with rituximab were as follows: 8 (27%) and 10 (33%) of the patients achieved a partial (PR) and a minor (MR) response, respectively, and an additional 9 (30%) of patients demonstrated stable disease (SD). No patients attained a complete response. The median time to treatment failure for responding (PR and MR) patients was 8.0 months (mean 8.4: range 3-20+ months), and 5.0 months (mean 6.1; range 3-12+ months) for patients with SD. These studies therefore demonstrate that rituximab is an active agent in WM. Marked increases in HCT and PLT counts were noted for most patients, including patients with WM who had MR or SD. A prospective clinical trial to more completely define the benefit of single-agent rituximab in patients with WM has been initiated by many of our centers.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos CD20/metabolismo , Macroglobulinemia de Waldenström/inmunología , Macroglobulinemia de Waldenström/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Médula Ósea/patología , Femenino , Humanos , Inmunoglobulina M/sangre , Inmunoterapia , Enfermedades Linfáticas/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab , Esplenomegalia/terapia , Macroglobulinemia de Waldenström/sangre , Macroglobulinemia de Waldenström/patologíaRESUMEN
PURPOSE: The role of donor marrow T-cell depletion (TCD) in preventing graft-versus-host disease (GVHD) after transplantation of unrelated allogeneic marrow remains undefined. Because different TCD methodologies differ in the degree and specificity with which T cells are removed, it is likely that transplant outcomes would depend on which technique is used. Herein, we report results in the first 48 recipients of unrelated marrow using CD6+ TCD as the sole form of GVHD prophylaxis. PATIENTS AND METHODS: Median age of patients was 46 years (20 to 58 years). Donors were matched at A/B HLA loci. Ablation consisted of cyclophosphamide and fractionated total-body irradiation (TBI; 14 Gy). To facilitate engraftment, patients also received 7.5 Gy (22 patients) [corrected] or 4.5 Gy (26 patients) [corrected] of total lymphoid irradiation (TLI) before admission. No additional immune suppressive prophylaxis was administered. Granulocyte colony-stimulating factor was administered daily from day +1 to engraftment. RESULTS: All 48 patients demonstrated neutrophil engraftment. An absolute neutrophil count of 500 x 10(6)/L was achieved at a median of 12 days (range, 9 to 23 days). There were no cases of late graft failure. The number of CD34+ cells infused/kg was associated with speed of platelet and neutrophil recovery. The dose of TLI did not influence engraftment. Grades 2-4 acute GVHD occurred in 42% of patients (95% confidence interval [CI], 0.28 to 0.57). Mortality at day 100 was 19%. There have been only five relapses. Estimated 2-year survival was 44% (95% CI, 0.28 to 0.59) for the entire group, 58% for patients less than 50 years of age. In multivariable analysis, age less than 50 years (P =.002), cytomegalovirus seronegative status (P =.04), and early disease status at bone marrow transplant (P =.05) were associated with superior survival. CONCLUSION: CD6+ TCD does not impede engraftment of unrelated bone marrow after low-dose TLI, cyclophosphamide, and TBI. CD6+ TCD as the sole form of GVHD prophylaxis results in an incidence of GVHD that compares favorably with many adult studies of unrelated transplantation using unmanipulated marrow and immune-suppressive medications, especially in light of the median age of our patients (46 years). Although event-free survival in patients less than 50 years of age is very encouraging, older patients experience frequent transplantation-related complications despite TCD.
Asunto(s)
Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , Depleción Linfocítica/métodos , Linfocitos T/inmunología , Adulto , Terapia Combinada , Femenino , Humanos , Leucemia/terapia , Subgrupos Linfocitarios , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To determine the efficacy of mantle radiation therapy alone in selected patients with early-stage Hodgkin's disease. PATIENTS AND METHODS: Between October 1988 and June 2000, 87 selected patients with pathologic stage (PS) IA to IIA or clinical stage (CS) IA Hodgkin's disease were entered onto a single-arm prospective trial of treatment with mantle irradiation alone. Eighty-three of 87 patients had > or = 1 year of follow-up after completion of mantle irradiation and were included for analysis in this study. Thirty-seven patients had PS IA, 40 had PS IIA, and six had CS IA disease. Histologic distribution was as follows: nodular sclerosis (n = 64), lymphocyte predominant (n = 15), mixed cellularity (n = 3), and unclassified (n = 1). Median follow-up time was 61 months. RESULTS: The 5-year actuarial rates of freedom from treatment failure (FFTF) and overall survival were 86% and 100%, respectively. Eleven of 83 patients relapsed at a median time of 27 months. Nine of the 11 relapses contained at least a component below the diaphragm. All 11 patients who developed recurrent disease were alive without evidence of Hodgkin's disease at the time of last follow-up. The 5-year FFTF in the 43 stage I patients was 92% compared with 78% in the 40 stage II patients (P =.04). Significant differences in FFTF were not seen by histology (P =.26) or by European Organization for Research and Treatment of Cancer H-5F eligibility (P =.25). CONCLUSION: Mantle irradiation alone in selected patients with early-stage Hodgkin's disease is associated with disease control rates comparable to those seen with extended field irradiation. The FFTF is especially favorable among stage I patients.