Assuntos
Neoplasias Hematológicas/cirurgia , Células-Tronco Hematopoéticas/citologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Adolescente , Adulto , Idoso , Antígenos CD34/sangue , Feminino , Citometria de Fluxo , Neoplasias Hematológicas/sangue , Células-Tronco Hematopoéticas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Transplante Autólogo , Adulto JovemRESUMO
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.
Assuntos
Vírus BK/isolamento & purificação , Transplante de Medula Óssea/efeitos adversos , Cistite/virologia , DNA Viral/urina , Hemorragia/virologia , Vírus JC/isolamento & purificação , Adulto , Vírus BK/classificação , Vírus BK/genética , Feminino , Humanos , Itália , Vírus JC/classificação , Vírus JC/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/virologia , Carga Viral , Adulto JovemRESUMO
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).
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação/efeitos dos fármacos , Piperazinas/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Tirosina Quinases/genética , Pirimidinas/administração & dosagem , Tiazóis/administração & dosagem , Adolescente , Adulto , Idoso , Benzamidas , Dasatinibe , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Proteínas Tirosina Quinases/antagonistas & inibidores , RecidivaAssuntos
Leucemia/diagnóstico , Leucocitose/diagnóstico , Leucostasia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Leucemia/sangue , Leucemia/patologia , Leucocitose/sangue , Leucocitose/patologia , Leucostasia/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemAssuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Pirimidinas/uso terapêutico , Indução de Remissão , Adulto , Benzamidas , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Gravidez , Resultado da GravidezRESUMO
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.
Assuntos
Síndrome POEMS/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Precoce , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante AutólogoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Soropositividade para HIV/tratamento farmacológico , HIV-1 , Leucemia Promielocítica Aguda/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Feminino , Soropositividade para HIV/sangue , Soropositividade para HIV/complicações , Humanos , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/virologia , Pessoa de Meia-IdadeAssuntos
Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Dacarbazina/análogos & derivados , Leucemia Mielogênica Crônica BCR-ABL Positiva/induzido quimicamente , Adulto , Antineoplásicos/administração & dosagem , Benzamidas , Dacarbazina/efeitos adversos , Feminino , Humanos , Mesilato de Imatinib , Masculino , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , TemozolomidaAssuntos
Sistema ABO de Grupos Sanguíneos , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Aplasia Pura de Série Vermelha/tratamento farmacológico , Anticorpos Monoclonais Murinos , Feminino , Humanos , Pessoa de Meia-Idade , Aplasia Pura de Série Vermelha/etiologia , RituximabRESUMO
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.
Assuntos
Terapia de Reposição de Estrogênios , Cooperação do Paciente , Insuficiência Ovariana Primária/tratamento farmacológico , Transplante de Células-Tronco/efeitos adversos , Adulto , Estradiol/administração & dosagem , Feminino , Humanos , Itália , Leucemia/terapia , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Insuficiência Ovariana Primária/etiologia , Insuficiência Ovariana Primária/patologia , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
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.
Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Antígenos CD34/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Esquema de Medicação , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/cirurgia , Humanos , Lenograstim , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Método Simples-Cego , Transplante Autólogo , Resultado do TratamentoRESUMO
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.
Assuntos
Sistema Imunitário/citologia , Subpopulações de Linfócitos/fisiologia , Transtornos Linfoproliferativos/terapia , Transplante de Células-Tronco de Sangue Periférico , Regeneração , Adolescente , Adulto , Células Sanguíneas/citologia , Feminino , Citometria de Fluxo , Doença de Hodgkin/terapia , Humanos , Sistema Imunitário/fisiologia , Imunofenotipagem , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Estudos Retrospectivos , Tempo , Condicionamento Pré-Transplante/métodos , Transplante AutólogoRESUMO
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.