RESUMEN
Dasatinib and nilotinib are tyrosine kinase inhibitors (TKIs) developed to overcome imatinib resistance in Philadelphia-positive leukemias. To assess how Bcr-Abl kinase domain mutation status evolves during sequential therapy with these TKIs and which mutations may further develop and impair their efficacy, we monitored the mutation status of 95 imatinib-resistant patients before and during treatment with dasatinib and/or nilotinib as second or third TKI. We found that 83% of cases of relapse after an initial response are associated with emergence of newly acquired mutations. However, the spectra of mutants conferring resistance to dasatinib or nilotinib are small and nonoverlapping, except for T315I. Patients already harboring mutations had higher likelihood of relapse associated with development of further mutations compared with patients who did not harbor mutations (23 of 51 vs 8 of 44, respectively, for patients who relapsed on second TKI; 13 of 20 vs 1 of 6, respectively, for patients who relapsed on third TKI).
Asunto(s)
Resistencia a Antineoplásicos/genética , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Mutación/efectos de los fármacos , Piperazinas/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inhibidores de Proteínas Quinasas/administración & dosificación , Proteínas Tirosina Quinasas/genética , Pirimidinas/administración & dosificación , Tiazoles/administración & dosificación , Adolescente , Adulto , Anciano , Benzamidas , Dasatinib , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/enzimología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , RecurrenciaRESUMEN
Hemorrhagic cystitis is characterized by hematuria due to inflammation of the bladder. In bone marrow transplants, this disease is linked to the infection by human polyomavirus BK, whereas the role of the human polyomavirus JC is unclear. The transcriptional control regions of both viruses contain important cellular transcription factor binding sites that undergo rearrangement process generating suitable variants that could be more active for viral replication and for the onset of hemorrhagic cystitis. In this study urine obtained from seven patients with bone marrow transplant were examined. Polyomavirus genomes were quantified by PCR and viral loads were compared. The transcriptional regions of both viruses were amplified and sequenced to determine the presence of variants. Subtypes of polyomaviruses were determined by amplification and sequencing of the viral protein 1 region. The results showed that four of seven patients were positive for BK DNA, two of seven patients had BK and JC DNA and one of seven had JC DNA. Positive samples were amplified and sequenced successively for transcriptional regions. The viral archetype was always found in both viruses. Finally, typing showed that BK virus subtype I infected patients with BK, whereas JC virus genotype IA and genotype 1B were found in patients infected with JC. The data suggest that new and different approaches are required to improve the morbidity and mortality caused by polyoma-associated hemorrhagic cystitis, since it known that BK virus is involved in the onset of hemorrhagic cystitis, whereas the role of JC virus should be investigated further.
Asunto(s)
Virus BK/aislamiento & purificación , Trasplante de Médula Ósea/efectos adversos , Cistitis/virología , ADN Viral/orina , Hemorragia/virología , Virus JC/aislamiento & purificación , Adulto , Virus BK/clasificación , Virus BK/genética , Femenino , Humanos , Italia , Virus JC/clasificación , Virus JC/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Infecciones por Polyomavirus/virología , Infecciones Tumorales por Virus/virología , Carga Viral , Adulto JovenRESUMEN
The acronym POEMS refers to polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes. This disease is progressive and weakening for patients and lead to death generally for neurological problem without therapy. We treated four patients affected by POEMS syndrome with front-line chemotherapy and autologous peripheral blood stem cell transplantation (aPBSCT). After a median follow-up of 40.5 months (range 12-52), all patients are alive with slow but progressive improvement in neurological disease, skin changes, performance status and without evidence of clonal plasmacytosis and organomegaly. In conclusion early diagnosis is crucial to obtain best response and improve clinical outcome.
Asunto(s)
Síndrome POEMS/terapia , Trasplante de Células Madre de Sangre Periférica , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Diagnóstico Precoz , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante AutólogoRESUMEN
Granulocyte colony-stimulating factor (G-CSF) can be administered after a peripheral blood stem cell transplantation with the aim of accelerating neutrophil recovery. In a randomized, single-blind study we studied a new administration schedule of G-CSF in this context.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Antígenos CD34/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Esquema de Medicación , Femenino , Supervivencia de Injerto/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/cirugía , Humanos , Lenograstim , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Método Simple Ciego , Trasplante Autólogo , Resultado del TratamientoRESUMEN
To evaluate the normalization of lymphocyte subsets several years after autologous peripheral blood stem cell transplantation (aPBSCT) and to detect any differences based on the underlying lymphoproliferative diseases, we analyzed the immunological recovery of 149 patients with Non Hodgkin's Lymphoma (NHL), Hodgkin's Disease (HD), Multiple Myeloma (MM). Lymphocyte recovery was assessed before the transplant, on days 15, 30, 60, 90, 120 and on years 1, 2, 4, 6. Analysis of a total of 709 lymphocytes, including total lymphocyte count, CD3 +, CD4 +, CD8 +, CD4 +/CD8 + ratio, CD19 +, CD3 + HLA-DR +, CD16 + 56 +, was performed. The normalization of total lymphocyte counts was achieved between days 14 to 22 following PBSCT. CD3 + cells count showed a normalization after 2 years in the HD and NHL groups and after 4 years in MM group. CD4 + subset achieved normalization during the sixth year in the 3 groups. The CD8 + and CD19 + lymphocytes subsets achieved normal values in the 3 groups at day 60 and at day 120 respectively. CD16 + 56 + and CD3 +/HLA-DR + lymphocytes showed median values above the normal range starting from day 30. Immunological recovery was similar in all 3 groups. Moreover, the recovery of all subsets evaluated was similarly demonstrated within 6 years after aPBSCT.
Asunto(s)
Sistema Inmunológico/citología , Subgrupos Linfocitarios/fisiología , Trastornos Linfoproliferativos/terapia , Trasplante de Células Madre de Sangre Periférica , Regeneración , Adolescente , Adulto , Células Sanguíneas/citología , Femenino , Citometría de Flujo , Enfermedad de Hodgkin/terapia , Humanos , Sistema Inmunológico/fisiología , Inmunofenotipificación , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Estudios Retrospectivos , Tiempo , Acondicionamiento Pretrasplante/métodos , Trasplante AutólogoAsunto(s)
Leucemia/diagnóstico , Leucocitosis/diagnóstico , Leucostasis/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Leucemia/sangre , Leucemia/patología , Leucocitosis/sangre , Leucocitosis/patología , Leucostasis/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To evaluate HRT compliance and efficacy in the treatment of symptomatic ovarian failure in pre-menopausal women after stem cell transplantation (SCT) for malignancies. METHODS: Thirty-one females were selected and prospectively followed in a university bone marrow transplantation unit and gynecologic outpatient clinic in a university teaching hospital. The patients received regular gynecological examinations, hormonal assessment every 6 months including plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), 17-beta estradiol (E2), and transvaginal pelvic ultrasonography, mammography, and computerized bone mineralometry every 12 months. Self-assessment form of menopausal symptoms perception was filled in by all patients before HRT and during the observation period. RESULTS: All patients developed gonadal failure after SCT. The menopausal symptoms more frequently reported were: vasomotor (90%), muscleskeletal symptoms (61%), vulvo-vaginal atrophy (54%), and mood changes (54%). Fifteen premenopausal women out of 31 (51.6%) received systemic HRT on the basis of age (<45 years), absence of medical contraindication or subjective refusal, and complete remission of underlying malignancies post-SCT. The remaining patients (48.4%) did not receive HRT mainly for patient's refusal (29%), relapse of malignancy (13%) or liver toxicity (9.6%). HRT was effective in HRT treated patients promptly relieving unpleasant symptoms of gonadal failure. HRT was tolerated without minimal complications or serious side effects. CONCLUSIONS: Dramatic improvement in menopausal symptoms was observed in women on HRT although treatment was feasible only in nearly half of the patients. HRT alleviates unnecessary discomfort and improves the well-being of female patients post-transplant also by preventing menopause related complications. Feasibility and patients' compliance of HRT should be carefully evaluated in long-term survivors after stem cell transplantation.
Asunto(s)
Terapia de Reemplazo de Estrógeno , Cooperación del Paciente , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Trasplante de Células Madre/efectos adversos , Adulto , Estradiol/administración & dosificación , Femenino , Humanos , Italia , Leucemia/terapia , Persona de Mediana Edad , Noretindrona/administración & dosificación , Insuficiencia Ovárica Primaria/etiología , Insuficiencia Ovárica Primaria/patología , Estudios Prospectivos , Encuestas y CuestionariosAsunto(s)
Neoplasias Hematológicas/cirugía , Células Madre Hematopoyéticas/citología , Trasplante de Células Madre de Sangre Periférica/métodos , Adolescente , Adulto , Anciano , Antígenos CD34/sangre , Femenino , Citometría de Flujo , Neoplasias Hematológicas/sangre , Células Madre Hematopoyéticas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Trasplante Autólogo , Adulto JovenAsunto(s)
Antineoplásicos/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Pirimidinas/uso terapéutico , Inducción de Remisión , Adulto , Benzamidas , Femenino , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Embarazo , Resultado del EmbarazoRESUMEN
BACKGROUND AND OBJECTIVES: Glutamine (gln), a non-essential amino acid, has recently received increasing attention because it becomes essential during stress and catabolic states: glutamine seems to modulate immune function and to promote faster intestinal healing after chemotherapy. We designed two consecutive randomized clinical trials to evaluate the role of glutamine-enriched parenteral nutrition (GEPN) in patients with hematologic malignancies submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation (aPBSCT) or immunoselected CD34+ aPBSCT. DESIGN AND METHODS: In study1, the Gln group (12 patients) received total parenteral nutrition (TPN) enriched with glutamine 20 g from day +1 after aPBSCT, while the placebo group (15 patients) received TPN lacking in glutamine (placebo). In study2, the Gln group (10 patients) received TPN enriched with glutamine 13.46 g from day +1, while the placebo group (11 patients) received a placebo. RESULTS: In the first study, a lymphocyte count >0.5 109/L was achieved on day 16.5 in the Gln group and on day 29 in the placebo group (p=0.005); in the second study, the lymphocyte count >0.5 109/L was achieved on day 18 in the Gln group and on day 29 in the placebo group (p=0.009). Lymphocyte subset analysis showed an increase of CD3+ and CD4+ and normalization of the CD16+CD56+ subset. Furthermore patients receiving GEPN showed a decrease in the mucositis severity peak calculated by the DMS (daily mucositis score: sum of the daily score of signs and symptoms) (p=0.047). INTERPRETATION AND CONCLUSIONS: GEPN is safe and effective and improves lymphocyte recovery after aPBSCT; further studies are needed to assess the clinical benefits of such an approach in order to justify its economic impact.