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1.
Clin Lymphoma Myeloma Leuk ; 22(12): e1059-e1066, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36117041

RESUMO

INTRODUCTION: Prognosis of patients with myelodysplastic syndrome (MDS), particularly the group with lower-risk disease (LR-MDS) is very heterogeneous. Several studies have described the prognostic value of recurrent somatic mutations in MDS including all risk categories. Recently, the incorporation of genomic data to clinical parameters defined the new Molecular International Prognostic Scoring System (IPSS-M). MATERIALS AND METHODS: In this study, we evaluated the impact of molecular profile in a series of 181 patients with LR-MDS and non-proliferative chronic myelomonocytic leukemia. RESULTS: Epigenetic regulators (TET2, ASXL1) and splicing (SF3B1) were the most recurrent mutated pathways. In univariate analysis, RUNX1 or TP53 mutations correlated with lower median overall survival (OS). In contrast, SF3B1 mutation was associated with prolonged median OS [95 months (95% IC, 32-157) vs. 33 months (95% CI, 19-46) in unmutated patients (P < 0.01)]. In a multivariate Cox regression model, RUNX1 mutations independently associated with shorter OS, while SF3B1 mutation retained its favorable impact on outcome (HR: 0.24, 95% CI, 0.1-0.5; P = 0.001). In addition, TP53 or RUNX1 mutations were identified as predictive covariates for the probability of leukemic progression (P < 0.001). CONCLUSION: Incorporation of molecular testing in LR-MDS identified a subset of patients with expected poorer outcome, either due to lower survival or probability of leukemic progression.


Assuntos
Leucemia Mielomonocítica Crônica , Síndromes Mielodisplásicas , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Síndromes Mielodisplásicas/genética , Mutação , Prognóstico , Proteína Supressora de Tumor p53/genética , Fatores de Processamento de RNA/genética , Fosfoproteínas/genética
2.
Bone Marrow Transplant ; 55(3): 641-648, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31700138

RESUMO

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Doença Crônica , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Nitrilas , Pirazóis/uso terapêutico , Pirimidinas , Estudos Retrospectivos
3.
Eur J Haematol ; 104(3): 181-189, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31737951

RESUMO

OBJECTIVES: The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma-reduced intensity conditioning (RIC), non-myeloablative (NMA), myeloablative conditioning (MAC) or Auto-AlloHCT-on outcomes in patients who had had a prior autologous transplant. METHODS: A retrospective analysis of the EBMT database (1991-2012) was performed. RESULTS: A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto-Allo transplants. At a median follow-up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%-47%), 45% (95% CI 32%-57%), 19% (95% CI 6%-32%) and 34% (95% CI 17%-51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276). CONCLUSION: From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , História do Século XX , História do Século XXI , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/história , Mieloma Múltiplo/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Retratamento , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
4.
Clin Cancer Res ; 25(15): 4616-4623, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043390

RESUMO

PURPOSE: The biologically active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (vit D), has immunoregulatory properties via binding vitamin D receptor (VDR). In a prospective trial, we previously reported a reduction in the incidence of chronic GvHD (cGvHD) among patients who received vit D after allogeneic stem cell transplantation (allo-HSCT; Clinical Trials.gov: NCT02600988). Here we analyze the role of patients and donors' VDR SNPs on the immunomodulatory effect of vit D. PATIENTS AND METHODS: Patients undergoing allo-HSCT were included in a prospective phase I/II clinical trial (Alovita) in three consecutive cohorts: control (without vit D), low-dose (1,000 IU/day), and high-dose (5,000 IU/day) groups. Vit D was given from day -5 until +100 after transplant. Genotyping of four SNPs of the VDR gene, FokI, BsmI, ApaI, and TaqI, were performed using TaqMan SNP genotyping assays. RESULTS: We observed a decrease in the incidence of overall cGvHD at 1 year after allo-HSCT depending on the use or not of vit D among patients with FokI CT genotype (22.5% vs 80%, P = 0.0004) and among those patients without BsmI/ApaI/TaqI ATC haplotype (22.2% vs 68.8%, P = 0.0005). In a multivariate analysis, FokI CT genotype significantly influenced the risk of cGvHD in patients treated with vit D as compared with the control group (HR 0.143, P interaction < 0.001). CONCLUSIONS: Our results show that the immunomodulatory effect of vit D depends on the VDR SNPs, and patients carrying the FokI CT genotype display the highest benefit from receiving vit D after allo-HSCT.


Assuntos
Colecalciferol/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/epidemiologia , Haplótipos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Estudos de Casos e Controles , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Incidência , Estudos Prospectivos , Espanha/epidemiologia , Resultado do Tratamento , Vitaminas/uso terapêutico
5.
Clin Lymphoma Myeloma Leuk ; 18(7): 469-474.e1, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29807802

RESUMO

BACKGROUND: The prognosis of patients with lower-risk myelodysplastic syndrome (LR-MDS) is very heterogeneous. In addition to survival estimates, identification of factors related to the probability of leukemic progression might help prognosis assessment. PATIENTS AND METHODS: The present study is a retrospective analysis of 409 patients with primary LR-MDS. The probability of leukemic progression was estimated in the competing risk framework by the cumulative incidence method considering death without acute myeloid leukemia (AML) as a competing event. RESULTS: Sixty-six patients (16.1%) progressed to AML. The following covariates influenced the probability of leukemic progression in a multivariate competing risk regression model: intermediate karyotype versus diploid or chromosome 5 deletion, 5% to 9% bone marrow blast percentage, platelet count <50 × 10e9/L and age younger than 75 years. CONCLUSION: According to these, a predictive model is proposed, which categorizes patients with different probability of leukemic progression (P < .001). Validation of these results might help prognostic refinement of patients with LR-MDS.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/etiologia , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Incidência , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Síndromes Mielodisplásicas/terapia , Probabilidade , Prognóstico , Medição de Risco , Fatores de Risco
6.
Biol Blood Marrow Transplant ; 24(5): 964-972, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29305194

RESUMO

Reduced-intensity conditioning (RIC) and T cell depletion (TCD) through CD34+ cell selection without the use of post-transplantation immunosuppression are 2 strategies used to reduce nonrelapse mortality (NRM) in older patients after allogeneic hematopoietic cell transplantation (allo-HCT). To compare the efficacy of the RIC and TCD approaches, we evaluated the outcomes of patients age >50 years with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) who underwent allo-HCT from an HLA-matched donor with one of these strategies. Baseline characteristics were comparable in the patients receiving TCD (n = 204) and those receiving RIC (n = 151), except for a higher proportion of unrelated donors (68% versus 40%; P < .001) and a higher comorbidity burden (Hematopoietic Cell Transplantation Comorbidity Index [HCT-CI] ≥3: 51% versus 38%; P < .001) in the TCD cohort. Analysis of outcomes at 3 years showed a higher chronic graft-versus-host disease (GVHD)/relapse-free survival (CRFS) (51% versus 7%; P < .001), lower incidences of grade II-IV acute GVHD (18% versus 46% at day +180) and chronic GVHD (6% versus 55% at 3 years; P < .001), and a lower incidence of relapse (19% versus 33% at 3 years; P = .001) in the TCD group compared with the RIC group. Relapse-free survival (RFS), overall survival (OS), and NRM were similar in the 2 groups. Combining transplantation approach (RIC versus TCD) and comorbidity burden (HCT-CI 0-2 versus ≥3), patients with an HCT-CI score of 0-2 seemed to benefit from the TCD approach. In conclusion, in this retrospective study, the use of a CD34+ cell-selected graft and a myeloablative conditioning regimen was associated with higher CRFS and similar RFS and OS compared with unmodified allo-RIC in patients age >50 years with AML and MDS.


Assuntos
Antígenos CD34/sangue , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Leucemia Mieloide Aguda/mortalidade , Depleção Linfocítica/métodos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Síndromes Mielodisplásicas/mortalidade , Recidiva , Estudos Retrospectivos , Transplante Homólogo/métodos
7.
Leuk Lymphoma ; 58(8): 1893-1902, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27951729

RESUMO

Chronic medical diseases, evaluated by several comorbidities indexes have been reported to influence on overall survival in patients with myelodysplastic syndrome (MDS). However, these studies included patients with lower and higher-risk disease by IPSS. This study retrospectively evaluates the role of comorbidities (evaluated by the MDS comorbidity index; MDS-CI) together with clinical parameters in a series of 232 patients with LR-MDS (defined as either an IPSS score of low/intermediate-1 and favorable cytogenetic categories by IPSS-R). In multivariate analysis, together with age >75 years, diabetes requiring therapy and hemoglobin <10 g/dL; the incorporation of comorbidities by the MDS-CI (HR = 2.5; p< 0.0001) were independently associated to the probability of nonleukemic death (NLD). The combination of these variables allowed development of a model, which categorizes patients in three different groups with significantly different probability of NLD overtime (p< 0.001). This integrated score confirms the importance of comorbidities at diagnosis of patients with LR-MDS.


Assuntos
Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Medula Óssea/patologia , Causas de Morte , Comorbidade , Feminino , Humanos , Incidência , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Prevalência , Prognóstico , Estudos Retrospectivos , Risco , Análise de Sobrevida , Avaliação de Sintomas
8.
Clin Cancer Res ; 22(23): 5673-5681, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27358490

RESUMO

PURPOSE: We describe the results of a prospective multicenter phase I/II trial evaluating the impact of the use of vitamin D (VitD) from day -5 to +100 on the outcome of patients undergoing allogeneic transplantation (EudraCT: 2010-023279-25; ClinicalTrials.gov: NCT02600988). EXPERIMENTAL DESIGN: A total of 150 patients were included in three consecutive cohorts of 50 patients each group: control group (CG, not receive VitD); low-dose group (LdD, received 1,000 IU VitD daily); and high-dose group (HdD, 5,000 IU VitD daily). We measured levels of VitD, cytokines, and immune subpopulations after transplantation. RESULTS: No significant differences were observed in terms of cumulative incidence of overall and grades 2-4 acute GVHD in terms of relapse, nonrelapse mortality, and overall survival. However, a significantly lower cumulative incidence of both overall and moderate plus severe chronic GVHD (cGVHD) at 1 year was observed in LdD (37.5% and 19.5%, respectively) and HdD (42.4% and 27%, respectively) as compared with CG (67.5% and 44.7%, respectively; P < 0.05). In multivariable analysis, treatment with VitD significantly decreased the risk of both overall (for LdD: HR = 0.31, P = 0.002; for HdD: HR = 0.36, P = 0.006) and moderate plus severe cGVHD (for LdD: HR = 0.22, P = 0.001; for HdD: HR = 0.33, P = 0.01). VitD modified the immune response, decreasing the number of B cells and naïve CD8 T cells, with a lower expression of CD40L. CONCLUSIONS: This is the first prospective trial that analyzes the effect of VitD postransplant. We observed a significantly lower incidence of cGVHD among patients receiving VitD. Interestingly, VitD modified the immune response after allo-SCT. Clin Cancer Res; 22(23); 5673-81. ©2016 AACR.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Fatores Imunológicos/imunologia , Vitamina D/imunologia , Adolescente , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo/métodos , Adulto Jovem
9.
Biol Blood Marrow Transplant ; 22(10): 1808-1815, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27470290

RESUMO

There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P < .0001). The cumulative incidence of relapse at 1 year was 29% with FluBu and 10% with FluMel (P = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel (P = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel (P = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Condicionamento Pré-Transplante/mortalidade , Condicionamento Pré-Transplante/métodos , Adulto , Bussulfano/uso terapêutico , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfoma/mortalidade , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Taxa de Sobrevida , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
10.
Leuk Res ; 39(1): 52-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25487012

RESUMO

Scoring systems for lower-risk myelodysplastic syndrome (LR-MDS) recognize patients with a poorer than expected outcome. This study retrospectively analyzes the role of azacitidine in LR-MDS with adverse risk score and compared to an historical cohort treated with best supportive care or erythropoiesis-stimulating agents. Overall response to AZA was 40%. One and 2-year probabilities of survival were 62% and 45% for AZA vs. 25% and 11% (P=10(-4)). In a multivariable time-dependent analysis, response to AZA (CR/PR/HI) was associated with an improved survival (HR=0.234, 95% CI, 0.063-0.0863; P=0.029). Thrombocytopenia (<50 × 10(9)L(-1)) is confirmed as an adverse parameter in LR-MDS (HR=1.649, 95% CI, 1.012-2.687; P=0.045).


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Azacitidina/administração & dosagem , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
11.
Clin Lymphoma Myeloma Leuk ; 15(4): 236-44, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25487600

RESUMO

BACKGROUND: The prognosis of myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) is very heterogeneous. PATIENTS AND METHODS: We analyzed the prognostic value of several genes in a cohort of 85 MDS and AML patients. RESULTS: Overexpression of glycogen synthase 1 and macrophage migration inhibitory factor genes had an adverse outcome in multivariate analysis (P = .003 and P < .001, respectively). Furthermore, the higher expression of myelocytomatosis oncogene was associated with a lower response to azacitidine (P = .03). CONCLUSION: In the current study we identified a specific gene expression profile as prognostic factors for response to azacitidine and survival in MDS and AML.


Assuntos
Expressão Gênica , Genes myc , Glicogênio Sintase/genética , Oxirredutases Intramoleculares/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Fatores Inibidores da Migração de Macrófagos/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Perfilação da Expressão Gênica , Humanos , Hipóxia/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento
12.
Clin Lymphoma Myeloma Leuk ; 14(1): 80-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24220615

RESUMO

Incidence, etiology, and outcome of infectious episodes in patients with myeloid neoplasms receiving azacitidine are uncertain, with no prospective data available in this group of patients. The aim of the current study was to analyze the incidence and factors related to the probability of infection in a cohort of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with azacitidine who did not receive any type of antimicrobial prophylaxis. Significantly, the group of patients who received prior intensive chemotherapy had more infectious episodes (P = 10(-4)), and particularly, invasive aspergillosis (P = .015), than patients who received frontline azacitidine. Primary antifungal prophylaxis might be recommended in MDS and AML patients receiving azacitidine as salvage therapy after intensive regimens.


Assuntos
Antifúngicos/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/microbiologia , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação/métodos
13.
Eur J Haematol ; 91(5): 448-55, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23710624

RESUMO

BACKGROUND: The standard practice in allogeneic stem cell transplant (alloSCT) is to infuse peripheral blood stem cells (PBSC) the same day or the day after collection once the patient has received conditioning regimen. To obtain and freeze PBSC prior to SCT would be desirable to get a better logistic and to confirm the quality of the product. Unfortunately, studies comparing both approaches are lacking. AIM: In this retrospective study, we analyze the impact of using fresh (N: 107) or previously frozen PBSC (N: 224) on overall outcomes among patients consecutively undergoing alloPBSCT from a matched related donor. RESULTS: Granulocyte engraftment (>500/mcl × 3 days) was faster in the frozen group (14 vs. 16 days, respectively; P = 0.001), while no significant differences on platelet recovery were observed. Patients receiving frozen PBSC had a higher incidence of global acute graft-versus-host disease (aGVHD) (63 vs. 44%, P < 0.001) mostly involving skin and had an earlier onset (13 vs. 30 days, P < 0.001). Response to first-line treatment with corticoids was similar in both groups. No statistically significant differences were found regarding overall chronic GVHD (58 vs. 66%) nor global survival (44 vs 48%), disease-free survival (39 vs. 33%), non-relapse mortality (24 vs. 16% at 1 year), and relapse rates in the frozen vs. fresh group, respectively. CONCLUSIONS: Infusion of previously frozen stem cells may achieve similar overall outcomes compared to fresh infusion, allowing to program donor apheresis and transplantation. However, cryopreservation might influence on the different pattern of aGVHD, issue that deserves further studies.


Assuntos
Criopreservação , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante , Doença Aguda , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Antígenos HLA/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento
14.
Haematologica ; 98(4): 526-32, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23065527

RESUMO

Different types of graft-versus-host disease prophylaxis have been proposed in the setting of reduced intensity and non-myeloablative allogeneic stem cell transplantation. An alternative combination with sirolimus and tacrolimus has recently been tested although comparative studies against the classical combination of a calcineurin inhibitor and mycophenolate mofetil or methotrexate are lacking. We describe the results of a prospective, multicenter trial using sirolimus + tacrolimus as immunoprophylaxis, and compare this approach with our previous experience using cyclosporine + mycophenolate in the setting of unrelated donor transplantation setting after reduced-intensity conditioning. Forty-five patients received cyclosporine + mycophenolate between 2002 and mid-2007, while the subsequent 50 patients, who were transplanted from late 2007, were given sirolimus + tacrolimus. No significant differences were observed in terms of hematopoietic recovery or acute graft-versus-host disease overall, although gastrointestinal acute graft-versus-host disease grade ≥ 2 was more common in the cyclosporine + mycophenolate group (55% versus 21%, respectively, P=0.003). The 1-year cumulative incidence of chronic graft-versus-host disease was 50% versus 90% for the patients treated with the sirolimus- versus cyclosporine-based regimen, respectively (P<0.001), while the incidence of extensive chronic disease was 27% versus 49%, respectively (P=0.043). The 2-year non-relapse mortality rate was 18% versus 38% for patients receiving the sirolimus- versus the cyclosporine-based regimen, respectively (P=0.02). The event-free survival and overall survival at 2 years were 53% versus 29% (P=0.028) and 70% versus 45% (P=0.018) among patients receiving the sirolimus- versus the cyclosporine-based regimen, respectively. In conclusion, in the setting of reduced intensity transplantation from an unrelated donor, promising results can be achieved with the combination of sirolimus + tacrolimus, due to a lower risk of chronic graft-versus-host disease and non-relapse mortality, which translates into better event-free and overall survival rates, in comparison with those achieved with cyclosporine + mycophenolate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Intervalo Livre de Doença , Feminino , Gastroenteropatias/induzido quimicamente , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infecções/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/análogos & derivados , Estudos Prospectivos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Taxa de Sobrevida , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Fatores de Tempo , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
15.
Clin Lymphoma Myeloma Leuk ; 13(2): 144-52, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23137720

RESUMO

UNLABELLED: Prognosis of myelodysplastic syndromes (MDS) is an area of ongoing interest. Identification of patients with poor outcome in the categories of lower risk disease is critical. In this study, we classify a cohort of 332 lower risk MDS into 3 groups with differences in survival and risk for leukemic progression that could drive treatment approaches to improve prognosis in a fraction of these patients. BACKGROUND: Prognosis of MDS and particularly in patients categorized as lower risk (< 10% blasts or low and intermediate-1 International Prognostic Scoring System [IPSS]) is very heterogeneous and includes patients with very different outcomes with current scoring systems. Recently, a new cytogenetic classification has been proposed for the revised IPSS in predicting the outcome for MDS. PATIENTS AND METHODS: To evaluate the prognostic significance of multiple variables for survival and risk of progression to acute myeloid leukemia, we analyzed baseline characteristics of 332 lower risk MDS patients within the lower risk cytogenetic categories by IPSS and the recent proposal for the new cytogenetic classification. RESULTS: In multivariate analysis, severity of cytopenias, age > 60 years, bone marrow blasts (5%-9%) and transfusion dependency significantly influenced outcome. The combination of these variables allowed development of a model which categorizes patients in 3 different groups with median survival of 95, 44, and 13 months for groups 1, 2, and 3, respectively (P < .001). In addition, this score also stratified patients for their risk for leukemic progression, estimated at 2 years in 3.1%, 7.6%, and 21.3% for each group (P = .024). CONCLUSION: Although karyotype remains the main prognostic factor in MDS, the current study identifies clinical parameters predicting outcome among patients with the better cytogenetic profile. Degree of cytopenias, blasts 5%-9% and transfusion dependence might identify a subset of patients within the nonadverse karyotype, in which early or more aggressive approaches could possibly be required to improve survival or prevent disease progression.


Assuntos
Células da Medula Óssea/patologia , Aberrações Cromossômicas , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/mortalidade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
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