RESUMEN
BACKGROUND: Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of the hemopoietic stem cells for which the only curative treatment is allogeneic hematopoietic stem cell transplantation. DESIGN AND METHODS: The aim of this retrospective study was to assess the long-term clinical and hematologic results in 26 paroxysmal nocturnal hemoglobinuria patients who received hematopoietic stem cell transplantation in Italy between 1988 and 2006. The patients were aged 22 to 60 years (median 32 years). Twenty-three donors were HLA-identical (22 siblings and one unrelated) and 3 were HLA-mismatched (2 related and one unrelated). RESULTS: Fifteen patients received a myeloablative conditioning consisting of busulfan and cyclophosphamide (in all cases from identical donor) and 11 were given a reduced intensity conditioning (8 from identical donor and 3 from mismatched donor). The cumulative incidence of graft failure was 8% (4% primary and 4% secondary graft failure). Transplant-related mortality for all patients was 42% (26% and 63% for patients transplanted following myeloablative or reduced intensity conditioning, respectively). As of October 31, 2009, 15 patients (11 in the myeloablative conditioning group and 4 in the reduced intensity conditioning group) are alive with complete hematologic recovery and no evidence of paroxysmal nocturnal hemoglobinuria following a median follow-up of 131 months (range 30-240). The 10-year Kaplan-Meier probability of disease-free survival was 57% for all patients: 65% for 23 patients transplanted from identical donor and 73% for 15 patients transplanted with myeloablative conditioning. No thromboembolic event nor recurrence of the disease were reported following transplant. CONCLUSIONS: The findings of this study confirm that most patients with paroxysmal nocturnal hemoglobinuria may be definitively cured with hematopoietic stem cell transplantation.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/tendencias , Hemoglobinuria Paroxística/cirugía , Acondicionamiento Pretrasplante/tendencias , Adulto , Supervivencia sin Enfermedad , Femenino , Hemoglobinuria Paroxística/mortalidad , Humanos , Italia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Human cytomegalovirus (HCMV) reactivation can cause a wide range of complications in hematopoietic stem cell transplant recipients, ranging from pneumonia to graft failure. Although reactivations are usually seen in the early post-transplant period, ongoing and untreated HCMV reactivation at the time of high-dose chemotherapy and autologous stem cell support is an exceedingly rare circumstance whose consequences remain largely unknown. This case report describes a patient who underwent high-dose melphalan and autologous transplantation with unknown active HCMV replication.
Asunto(s)
Antineoplásicos Alquilantes , Citomegalovirus/fisiología , Melfalán , Trasplante de Células Madre/efectos adversos , Trasplante Autólogo/efectos adversos , Activación Viral , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/uso terapéutico , Citomegalovirus/efectos de los fármacos , Infecciones por Citomegalovirus/virología , Resultado Fatal , Humanos , Masculino , Melfalán/administración & dosificación , Melfalán/uso terapéutico , Persona de Mediana EdadRESUMEN
We report on a 22-year-old female who developed aplastic anemia after administration of phenobarbital for 6 years. Being refractory to steroid and anti-lymphocyte serum, the patient received allogeneic stem cell transplantation, achieving complete remission. We discuss here the potential mechanisms by which phenobarbital and other anti-epileptic drugs can cause aplastic anemia and review the literature for previous case reports and epidemiological studies.
Asunto(s)
Anemia Aplásica/inducido químicamente , Anticonvulsivantes/efectos adversos , Fenobarbital/efectos adversos , Adulto , Anemia Aplásica/cirugía , Femenino , Humanos , Trasplante de Células MadreRESUMEN
The genomic profile of mantle cell lymphoma (MCL) has been reported to be significantly different from that of other indolent lymphoproliferative disorders, Topoisomerase IIalpha, glutathione-s-transferasepi (GSTpi) and ABCG2 (BCRP) chemoresistance genes being over-expressed in MCL. In our study, expression levels of the above mentioned genes plus MDR1 were tested on bone marrow samples from 20 patients treated with Rituximab plus hyper-CVAD regimen, in order to evaluate a possible impact of the chemoresistance phenomenon on this promising treatment regimen. All patients expressed ABCG2 and MDR1 genes; 85% of cases expressed GSTpi and topoisomerase IIalpha. Only ABCG2 were over-expressed in comparison both with marrow from healthy donors and tonsilar CD5+/CD20+ lymphocytes (adopted as normal counterpart of the neoplastic population). The overall response rate of the entire series was 87.5%, with 44% of complete responses. Fifty-seven percent of patients achieved the clearance of minimal residual disease. Levels of tested genes did not condition either quality of clinical response or PFS (76% at 24 months). Nevertheless, an ABCG2 higher expression appeared associated with a worse PFS and levels of this gene paralleled the status of minimal residual disease. A further evaluation of ABCG2 expression in larger series of MCL patients would be suitable.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Linfoma de Células del Manto/tratamiento farmacológico , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino , Antígenos de Neoplasias/genética , Estudios de Casos y Controles , Ciclofosfamida/uso terapéutico , ADN-Topoisomerasas de Tipo II/genética , Proteínas de Unión al ADN/genética , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Femenino , Gutatión-S-Transferasa pi/genética , Humanos , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/metabolismo , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Pronóstico , Rituximab , Tasa de Supervivencia , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
TCR gamma/delta profiles were analyzed in 13 multiple myeloma patients after allogeneic non-myeloablative transplantation. Results show that both aGVHD and minimal residual disease (MRD) eradication did significantly affect TCR gamma/delta profile. During follow-up, six patients developed an aGVHD episode; in five of them, this event fitted with a modification of the TCR profile. Eleven patients achieved PCR-negativity during follow-up. In the 90% of them, the appearance of a new predominant TCR peak was concomitant to the disappearance of the IgH clone. These results suggest that different T gamma/delta populations would sustain GVM and GVH effects after non-myeloablative allogeneic transplant.
Asunto(s)
Enfermedad Injerto contra Huésped/genética , Efecto Injerto vs Tumor/genética , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Neoplasia Residual/genética , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Adulto , Anciano , Células Clonales , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/terapia , Efecto Injerto vs Tumor/inmunología , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Neoplasia Residual/inmunología , Neoplasia Residual/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Trasplante Homólogo , Resultado del TratamientoRESUMEN
We report a rare case of a patient with bilateral uveal melanoma (the first eye surgically treated 6 years before the occurrence of melanoma in the contralateral eye), who developed an acute myeloid leukaemia.
Asunto(s)
Neoplasias del Ojo/complicaciones , Neoplasias del Ojo/diagnóstico , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/diagnóstico , Melanoma/complicaciones , Melanoma/diagnóstico , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias de la Úvea/complicaciones , Neoplasias de la Úvea/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Inducción de Remisión , Resultado del TratamientoRESUMEN
This study evaluates the prognostic value of molecular monitoring of minimal residual disease (MRD) in 20 patients with multiple myeloma (MM) following autologous (peripheral blood stem cell transplantation, PBSCT) and non-myeloablative allogeneic (NMT) transplant. All patients completed their program, with a treatment-related mortality (TRM) of 20% and a 2-year progression-free survival (PFS) of 51%. After PBSCT, only 3 patients (15%) achieved PCR-negativity, versus 12 (60%) after NMT. The eradication of MRD had a favorable impact on 2-year OS. In fact, 76% of patients with no detectable MRD was still alive versus 34% of persistently IgH-positive cases (p=0.03). PCR status did not correlate with chimerism percentage: Seventy-five percent of patients achieved full donor chimerism, which was more frequently observed in cases presenting cGHVD (p=0.01). These data sustain the relevant role of molecular monitoring in MM patients undergoing NMT. MRD monitoring would assist physicians in making additional therapeutic decisions to better control this hematological malignancy.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Neoplasia Residual/diagnóstico , Neoplasia Residual/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Adulto , Anciano , Electroforesis Capilar , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Reacción en Cadena de la Polimerasa , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Análisis de Supervivencia , Trasplante Autólogo , Trasplante HomólogoAsunto(s)
División Celular , Quimiocina CXCL12/antagonistas & inhibidores , Inhibidores de la Dipeptidil-Peptidasa IV , Rechazo de Injerto , Células Madre Hematopoyéticas/efectos de los fármacos , Leucemia Mieloide Aguda/cirugía , Inhibidores de Proteasas/farmacología , Pirazinas/farmacología , Triazoles/farmacología , Quimiocina CXCL12/metabolismo , Femenino , Células Madre Hematopoyéticas/citología , Humanos , Hidrólisis , Leucemia Mieloide Aguda/tratamiento farmacológico , Persona de Mediana Edad , Inhibidores de Proteasas/uso terapéutico , Pirazinas/uso terapéutico , Fosfato de Sitagliptina , Triazoles/uso terapéuticoAsunto(s)
Antígenos CD57/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Infecciones por Virus ADN/diagnóstico , Trasplante de Células Madre Hematopoyéticas , Torque teno virus , Viremia/diagnóstico , Proliferación Celular , Infecciones por Virus ADN/inmunología , Humanos , Melfalán/uso terapéutico , Mieloma Múltiple/cirugía , Agonistas Mieloablativos/uso terapéutico , Trasplante Autólogo , Carga Viral , Viremia/inmunologíaRESUMEN
Oral mucositis is an important side effect of hematopoietic stem cell transplantation (HCST), mainly due to toxicity of conditioning regimens. It produces significant pain and morbidity. The present study reports a prospective, randomized, non-blinded study testing the efficacy of a new mouthwash, called Baxidil Onco(®) (Sanitas Farmaceutici Srl, Tortona, Italy) in 60 hematologic patients undergoing HCST (28 autologous, 32 allogeneic). Baxidil Onco(®), used three times a day from Day -1 to Day +30, in addition to standard prophylactic schedules, was administered to 14 patients undergoing autologous and 14 patients undergoing allogeneic HCST. The remaining 32 patients (14 autologous and 18 HCST) were treated only with standard prophylactic schedules and served as control. In our study, the overall incidence of oral mucositis, measured according to the World Health Organization 0-4 scale, was 50% in the Baxidl Onco(®) group versus 82% in the control group (P=0.022). In addition, a significant reduction in scale 2-4 oral mucositis was observed in the Baxidil Onco(®) group (25% vs 56.2%; P=0.0029). The results obtained indicate that incidence, severity and duration of oral mucositis induced by conditioning regimens for HCST can be significantly reduced by oral rinsing with Baxidil Onco(®), in addition to the standard prophylaxis scheme. Since Camelia Sinensin extract, which is used to produce green tea, is the main agent in this mouthwash, we hypothesize that the anti-oxidative properties of polyphenolic compounds of tea might exert protective effects on oral mucosa.
Asunto(s)
Inmunoglobulina A/sangre , Paraproteinemias/complicaciones , Intercambio Plasmático , Talidomida/uso terapéutico , Vasculitis Leucocitoclástica Cutánea/complicaciones , Vasculitis Leucocitoclástica Cutánea/terapia , Anciano de 80 o más Años , Humanos , Inmunosupresores/uso terapéutico , Masculino , Paraproteinemias/sangre , Paraproteinemias/terapia , Plasmaféresis , Talidomida/sangre , Vasculitis Leucocitoclástica Cutánea/sangreRESUMEN
Hemorrhagic cystitis is a common complication in hematopoietic stem cell transplant recipients. We report here a case of severe BKV-associated hemorrhagic cystitis who did not respond to intravenous cidofovir. Overt hematuria successfully resolved after a few days on hyperbaric oxygen and intravesical instillations of cidofovir, while BK viruria dropped after a few weeks and remained low. We review the literature for therapeutic options in hemorrhagic cystitis and try to explain how hyperbaric oxygen stimulates mucosal repair in the urinary bladder.
Asunto(s)
Antivirales/administración & dosificación , Cistitis/terapia , Citosina/análogos & derivados , Oxigenoterapia Hiperbárica , Organofosfonatos/administración & dosificación , Administración Intravesical , Adulto , Antineoplásicos/efectos adversos , Virus BK , Cidofovir , Cistitis/etiología , Infecciones por Citomegalovirus/terapia , Citosina/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Hematuria/etiología , Hematuria/terapia , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/virología , Masculino , Infecciones por Polyomavirus/complicaciones , Infecciones por Polyomavirus/terapia , Infecciones por Polyomavirus/orina , Infecciones Tumorales por Virus/complicaciones , Infecciones Tumorales por Virus/terapia , Infecciones Tumorales por Virus/orinaRESUMEN
We report here a 50-years old female with multiple myeloma-associated chronic renal failure who underwent high-dose chemotherapy supported by autologous hematopoietic stem cell transplantation. She developed progressive encephalopathy on day 5 progressing to coma despite hemodialysis and no obvious organ failure. She finally recovered after a single 1-liter plasma exchange. The final diagnosis was metabolic encephalopathy due to hypercytokinemia, particularly high serum TNF levels. We discuss here the pathogenesis and raise an alert for monitoring cytokine levels in patients with renal failure undergoing high-dose chemotherapy.
Asunto(s)
Encefalopatías Metabólicas/terapia , Mieloma Múltiple/terapia , Intercambio Plasmático , Encefalopatías Metabólicas/sangre , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/etiología , Encefalopatías Metabólicas/fisiopatología , Coma , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Mieloma Múltiple/fisiopatología , Diálisis Renal , Insuficiencia Renal/prevención & control , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/efectos adversos , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Progressive multifocal leukoencephalopathy (PML) is a central nervous system (CNS) disease usually observed in immunodeficient patients, especially human immunodeficiency virus (HIV)-positive, caused by John Cunningham virus. This infectious complication has been described in many HIV-negative hematological patients, especially affected by lymphoproliferative diseases. PML has been observed after both chemotherapy and bone marrow transplantation and, recently, in association with rituximab. Diagnosis can be complicated, and often a CNS biopsy is required. Current treatment approaches are not effective in both HIV-positive and HIV-negative patients, and the outcome remain very poor in the majority of cases, even after combination therapies. We report three cases of PML in hematological patients, treated respectively with conventional chemotherapy and autologous and haploidentical transplantation, and review the literature on PML. All of them received rituximab, which has recently been in the focus of a Food and Drug Administration warning.
Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Inmunosupresores/efectos adversos , Leucoencefalopatía Multifocal Progresiva/inmunología , Linfoma Folicular/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino , Antivirales/uso terapéutico , Resultado Fatal , Femenino , Humanos , Huésped Inmunocomprometido , Virus JC/patogenicidad , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Linfoma Folicular/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , RituximabRESUMEN
Hematopoietic stem cell transplantation (HSCT) has been proposed for the treatment of severe multiple sclerosis (MS). In a phase 2 multicenter study we selected 19 non-primary progressive MS patients showing high disease activity on the basis of both brain magnetic resonance imaging (MRI) and sustained clinical deterioration despite conventional treatments. After stem cell mobilization with cyclophosphamide (CY) and filgrastim, patients were conditioned with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea), cytosine arabinoside, etoposide, and melphalan (BEAM) followed by antithymocyte globulin (ATG). Unmanipulated peripheral blood stem cells (PBSCs) were then infused. No maintenance treatment was administered with a median follow-up of 36 months (range, 12 to 72 months). All patients showed clinical stabilization or improvement; 3 subsequently deteriorated, 1 beyond the baseline. No MRI active lesions were detected after the HSCT except in 1 patient who showed a new lesion at 4.5 years. Infections were limited and restricted to 3 months after HSCT. Health-related quality of life was assessed through the 54-item MS quality of life (MSQOL-54) questionnaire, showing a statistically significant improvement in both composite scores and in most of the individual domains. HSCT is able to induce a prolonged clinical stabilization in severe progressive MS patients, resulting in both sustained treatment-free periods and quality of life improvement.