RESUMO
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.
Assuntos
Transplante de Células-Tronco Hematopoéticas/tendências , Hemoglobinúria Paroxística/cirurgia , Condicionamento Pré-Transplante/tendências , Adulto , Intervalo Livre de Doença , Feminino , Hemoglobinúria Paroxística/mortalidade , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
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.
Assuntos
Antineoplásicos Alquilantes , Citomegalovirus/fisiologia , Melfalan , Transplante de Células-Tronco/efeitos adversos , Transplante Autólogo/efeitos adversos , Ativação Viral , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/virologia , Evolução Fatal , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Anemia Aplástica/induzido quimicamente , Anticonvulsivantes/efeitos adversos , Fenobarbital/efeitos adversos , Adulto , Anemia Aplástica/cirurgia , Feminino , Humanos , Transplante de Células-TroncoRESUMO
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.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Linfoma de Célula do Manto/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Anticorpos Monoclonais Murinos , Antígenos de Neoplasias/genética , Estudos de Casos e Controles , Ciclofosfamida/uso terapêutico , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/genética , Dexametasona/uso terapêutico , Doxorrubicina/uso terapêutico , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Glutationa S-Transferase pi/genética , Humanos , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Prognóstico , Rituximab , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
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.
Assuntos
Doença Enxerto-Hospedeiro/genética , Efeito Enxerto vs Tumor/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Neoplasia Residual/genética , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Receptores de Antígenos de Linfócitos T gama-delta/genética , Adulto , Idoso , Células Clonais , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/terapia , Efeito Enxerto vs Tumor/imunologia , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Neoplasia Residual/imunologia , Neoplasia Residual/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Receptores de Antígenos de Linfócitos T gama-delta/análise , Transplante Homólogo , Resultado do TratamentoRESUMO
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.
Assuntos
Neoplasias Oculares/complicações , Neoplasias Oculares/diagnóstico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Melanoma/complicações , Melanoma/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Neoplasias Uveais/complicações , Neoplasias Uveais/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Indução de Remissão , Resultado do TratamentoRESUMO
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.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Neoplasia Residual/diagnóstico , Neoplasia Residual/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Adulto , Idoso , Eletroforese Capilar , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Reação em Cadeia da Polimerase , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Análise de Sobrevida , Transplante Autólogo , Transplante HomólogoAssuntos
Divisão Celular , Quimiocina CXCL12/antagonistas & inibidores , Inibidores da Dipeptidil Peptidase IV , Rejeição de Enxerto , Células-Tronco Hematopoéticas/efeitos dos fármacos , Leucemia Mieloide Aguda/cirurgia , Inibidores de Proteases/farmacologia , Pirazinas/farmacologia , Triazóis/farmacologia , Quimiocina CXCL12/metabolismo , Feminino , Células-Tronco Hematopoéticas/citologia , Humanos , Hidrólise , Leucemia Mieloide Aguda/tratamento farmacológico , Pessoa de Meia-Idade , Inibidores de Proteases/uso terapêutico , Pirazinas/uso terapêutico , Fosfato de Sitagliptina , Triazóis/uso terapêuticoAssuntos
Antígenos CD57/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Infecções por Vírus de DNA/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Torque teno virus , Viremia/diagnóstico , Proliferação de Células , Infecções por Vírus de DNA/imunologia , Humanos , Melfalan/uso terapêutico , Mieloma Múltiplo/cirurgia , Agonistas Mieloablativos/uso terapêutico , Transplante Autólogo , Carga Viral , Viremia/imunologiaRESUMO
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.
Assuntos
Imunoglobulina A/sangue , Paraproteinemias/complicações , Troca Plasmática , Talidomida/uso terapêutico , Vasculite Leucocitoclástica Cutânea/complicações , Vasculite Leucocitoclástica Cutânea/terapia , Idoso de 80 Anos ou mais , Humanos , Imunossupressores/uso terapêutico , Masculino , Paraproteinemias/sangue , Paraproteinemias/terapia , Plasmaferese , Talidomida/sangue , Vasculite Leucocitoclástica Cutânea/sangueRESUMO
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.
Assuntos
Antivirais/administração & dosagem , Cistite/terapia , Citosina/análogos & derivados , Oxigenoterapia Hiperbárica , Organofosfonatos/administração & dosagem , Administração Intravesical , Adulto , Antineoplásicos/efeitos adversos , Vírus BK , Cidofovir , Cistite/etiologia , Infecções por Citomegalovirus/terapia , Citosina/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Hematúria/etiologia , Hematúria/terapia , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/virologia , Masculino , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/terapia , Infecções por Polyomavirus/urina , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/terapia , Infecções Tumorais por Vírus/urinaRESUMO
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.
Assuntos
Encefalopatias Metabólicas/terapia , Mieloma Múltiplo/terapia , Troca Plasmática , Encefalopatias Metabólicas/sangue , Encefalopatias Metabólicas/diagnóstico , Encefalopatias Metabólicas/etiologia , Encefalopatias Metabólicas/fisiopatologia , Coma , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/fisiopatologia , Diálise Renal , Insuficiência Renal/prevenção & controle , Resultado do Tratamento , Fator de Necrose Tumoral alfa/efeitos adversos , Fator de Necrose Tumoral alfa/sangueRESUMO
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.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Imunossupressores/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/imunologia , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Murinos , Antivirais/uso terapêutico , Evolução Fatal , Feminino , Humanos , Hospedeiro Imunocomprometido , Vírus JC/patogenicidade , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Linfoma Folicular/complicações , Linfoma Difuso de Grandes Células B/complicações , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , RituximabRESUMO
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.