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The current study includes all consecutive patients (N = 484) who received a reduced-intensity conditioning regimen (RIC) allogeneic hematopoietic stem cell transplantation in our center from 1999 to 2020. Conditioning regimens were based on fludarabine with melphalan or busulfan, with low-dose thiotepa and pharmacological GVHD prophylaxis consisted of cyclosporine A (CsA)-methotrexate (MTX)/mofetil (MMF) (n = 271), tacrolimus-sirolimus (n = 145), and post-transplantation cyclophosphamide (PTCy)-tacrolimus (n = 68). The median time of overall follow-up in survivors was 8 years (1-22 years) and was at least 3 years in all three GVHD prophylaxis groups. Thirty-three percent had a high or very high disease risk index, 56% ≥ 4 European bone marrow transplantation risk, and 65% ≥ 3 hematopoietic stem cell transplantation comorbidity index score-age score. Neutrophil and platelet engraftment was longer for PTCy-tacro (p 0.0001). Cumulative incidence of grade III-IV aGVHD was 17% at 200 days, and that of moderate-severe cGvHD was 36% at 8 years. GVHD prophylaxis was the only prognostic factor in the multivariable analyses for the development of aGVHD and moderate-severe cGVHD (p 0.0001). NRM and relapse incidences were 29% and 30% at 8 years, while OS and PFS rates were 43% and 39% at 8 years. At 3 years, OS was highest in the PTCy-tacro group (68%) than in the tacro-siro (61%) and CsA-MTX/MMF (49%) cohorts (p < 0.01). In the three groups, respectively, the 200-day incidence of grade III-IV aGvHD (6% vs. 12% vs. 23%) and 3-year moderate-severe cGVHD (8% vs. 40% vs. 38%) were lower in the PTCy cohort. These better outcomes were confirmed in multivariable analyses. Based on our recent results, the PTCy could be considered as a real GvHD prophylaxis in the RIC setting due to improve best 3-year GvHD and survival outcomes.
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Doença Enxerto-Hospedeiro , Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/métodos , Metotrexato/uso terapêutico , Tacrolimo/uso terapêutico , Condicionamento Pré-Transplante/métodosRESUMO
OBJECTIVE: This retrospective single center study aims to describe changes in the severity and organ-specific distribution of GvHD, by comparing the outcomes of 3 distinct GvHD prophylaxis approaches. METHODS: Between January 2012 and June 2022, 226 patients underwent allogeneic hematopoietic stem cell transplantation from HLA-matched or 1-allele mismatched related or unrelated donors. Fifty-eight (26%) received prophylaxis with calcineurin inhibitor in combination with mycophenolate mofetil or a short course of methotrexate (Cohort-1), 87 (38%) tacrolimus plus sirolimus (Cohort-2), and 81 (36%) post-transplant cyclophosphamide (PTCy) plus tacrolimus (Cohort-3). RESULTS: The incidence of grade II-IV aGvHD was 69% vs. 41.4% vs. 27.2%; p < .01. The most significant reduction with PTCy was observed in both stage 3-4 skin and lower gastrointestinal (GI) involvement (p < .01). The incidence of moderate-to-severe cGvHD at 12 months was 34.5% vs. 34.5% vs. 6.2%; p < .01. Moderate-to-severe skin and GI cGvHD was less common after PTCy (p < .01). The 1-year GvHD-free/relapse-free survival was higher with PTCy (p < .01). CONCLUSIONS: Our study indicates that PTCy-based GvHD prophylaxis reduces the frequency and severity of both acute and chronic GvHD, with a notable decrease in severe GI and cutaneous manifestations. The higher GRFS may result in lower GvHD-related mortality, leading to an improved quality of life among survivors.
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OBJECTIVES: High-dose total body irradiation (TBI) is considered a cornerstone of myeloablative conditioning for allogeneic stem cell transplantation (allo-SCT). We retrospectively compared the main outcomes of an HLA matched or 1-allele mismatched related or unrelated allo-SCT in adult patients affected by acute leukemia (AL) or myelodysplastic syndromes (MDS). METHODS: Fifty-nine patients received cyclophosphamide (Cy)-TBI (13.5 Gy) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin-inhibitor plus methrotrexate (CyTBI group) and 28 patients received fludarabine-TBI (8.8-13.5 Gy) and GVHD prophylaxis with PTCy and tacrolimus (FluTBI-PTCy group). RESULTS: Median follow-up for survivors was 82 and 22 months. The 12-month probability of overall survival and progression-free survival were similar (p = .18, p = .7). The incidence of Grades 2-4 and 3-4 acute GVHD, and the incidence of moderate-to-severe chronic GVHD were higher in the CyTBI group (p = .02, p < .01and p = .03). Nonrelapse mortality (NRM) at 12 months posttransplant was higher in the CyTBI group (p = 0.05), while the incidence of relapse was similar in both groups (p = 0.7). The number of GVHD-free and relapse-free patients without systemic immunosuppression (GRFS) at 1-year posttransplant was higher in the FluTBI-PTCy group (p = 0.01). CONCLUSIONS: The study confirms the safety and efficacy of a novel FluTBI-PTCy platform with reduced incidence of severe acute and chronic GVHD, and early improvement of NRM.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Estudos Retrospectivos , Irradiação Corporal Total , Ciclofosfamida/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva , Condicionamento Pré-TransplanteRESUMO
Haploidentical related (Haplo) and umbilical cord blood (UCB) donors are the main "alternative donor" options for allogeneic hematopoietic stem cell transplantation (HCT) for patients without identical donor. At our institution, UCB was the main alternative donor type until 2013, when HaploHCT was introduced as the preferred procedure. A common myeloablative conditioning regimen was used, based on thiotepa, busulfan, and fludarabine. We analyze the outcomes of 47 patients (61%) who received a single UCB transplantation (UCBT) and 30 patients (39%) who received a HaploHCT with post-transplant cyclophosphamide. No differences were found in the rate of neutrophil engraftment, whereas platelet recovery was earlier with HaploHCT. NRM was higher after UCBT at 3 months and 3 years (13% and 13% vs. 23% and 45% in HaploHCT and UCBT, respectively; p < 0.001 for both time points). The 3-year relapse incidence was 35% after HaploHCT vs. 17% after UCBT, respectively (p = 0.13). The 100-day incidence of grade 3-4 acute GVHD (3% vs. 11%) and the 3-year moderate-to-severe chronic GVHD (4% vs. 15%) did not differ between HaploHCT and UCBT, respectively (p > 0.2). There was a trend for higher overall survival at 1 and 3 years in HaploHCT recipients (69% vs. 45% and 64% vs. 38%, respectively; p = 0.055 for both time points). Despite the small sample sizes, multivariate analysis adjusted for patient age and disease status at transplant showed a better 3-year OS in HaploHCT recipients, mostly due to a lower NRM (p < 0.001). Our results support the use of HaploHCT when feasible when an identical donor is not available.
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Bussulfano/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Antígenos HLA , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico , Tiotepa/administração & dosagem , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Adulto , Idoso , Aloenxertos , Feminino , Neoplasias Hematológicas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vidarabina/administração & dosagemRESUMO
We analyze the impact of cyclosporine (CsA) levels in the development of acute graft-versus-host disease (aGVHD) after reduced intensity conditioning allogeneic hematopoietic transplantation (allo-RIC). We retrospectively evaluated 156 consecutive patients who underwent HLA-identical sibling allo-RIC at our institution. CsA median blood levels in the 1st, 2nd, 3rd and 4th weeks after allo-RIC were 134 (range: 10-444), 219 (54-656), 253 (53-910) and 224 (30-699) ng/mL; 60%, 16%, 11% and 17% of the patients had median CsA blood levels below 150 ng/mL during these weeks. 53 patients developed grade 2-4 aGVHD for a cumulative incidence of 45% (95% CI 34-50%) at a median of 42 days. Low CsA levels on the 3rd week and sex-mismatch were associated with the development of GVHD. Risk factors for 1-year NRM and OS were advanced disease status (HR: 2.2, P = 0.02) and development of grade 2-4 aGVHD (HR: 2.5, P < 0.01), while there was a trend for higher NRM in patients with a low median CsA concentration on the 3rd week (P = 0.06). These results emphasize the relevance of sustaining adequate levels of blood CsA by close monitoring and dose adjustments, particularly when engraftment becomes evident. CsA adequate management will impact on long-term outcomes in the allo-RIC setting.
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Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Idoso , Alelos , Feminino , Antígenos HLA/química , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Transplante de Células-Tronco/métodos , Fatores de Tempo , Transplante Homólogo/métodos , Adulto JovemRESUMO
Objectives: Gastric involvement in patients with early systemic sclerosis (SSc) has not been previously investigated. We aim to evaluate the association of gastric dysrhythmias with gastrointestinal (GI) symptoms and nailfold video capillaroscopy (NVC). Methods: Cross-sectional study. Patients with early SSc, completed the UCLA GIT 2.0 questionnaire, performed an NVC, and a surface Electrogastrography (EGG). Descriptive statistics was used for demographic and clinical characteristics and Fisher and Kendall Tau tests were used for association analysis. Results: 75 patients were screened, 30 patients were consecutively enrolled, 29 performed the EGG and 1 patient had a non-interpretable NVC. 29/30 were female with a mean age of 48.7 years (25-72). The mean disease duration from the first non-RP symptom was 22.6 +/-10.8 months and most of the patients had limited disease (76.6%). Total GIT 2.0 score symptoms were moderate-severe in 63% of the participants and 28/29 had an abnormal EGG. Bradygastria was the most common pattern present in 70% of the participants. NVC patterns: 17% early, 34% active, 28% scleroderma-like, 14% non-specific, and 2 patients had a normal NVC. There was no association between severe GI symptoms or NVC patterns and severely abnormal EGG, but the presence of bradygastria was associated with severe impairment in the social functioning area (p 0.018). Conclusions: Gastric dysmotility is common in early SSc and there is a lack of correlation between GI symptoms and NVC scleroderma patterns. EGG is a sensitive, cheap, and non-invasive exam, that may be an alternative to early diagnosis of GI involvement.
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Refractory acute graft-versus-host disease (aGVHD) remains an important cause of mortality after allogeneic stem cell transplantation. No standard therapy exists once steroids fail to obtain a good response. In 2006, our group published a series of patients who received inolimomab, an anti-interleukin-2 receptor monoclonal antibody, as salvage therapy with initial encouraging results. In this update, we analyzed a larger group of patients with prolonged follow-up. Ninety-two consecutive patients were treated with inolimomab at our center between April 1999 and December 2011. Overall response rate was 42% (complete response in 14%) on day +30. Predictors of failure to respond in the multivariate analysis were overall aGVHD grade IV, instauration of inolimomab before day 15 of aGVHD diagnosis, and severe lymphopenia. Patients without gastrointestinal involvement appeared to do better, with a 70% response rate compared with 39% in patients with gastrointestinal involvement (P = .06). However, the 2-year overall survival rate was of 18% for the entire cohort (95% confidence interval, 10% to 26%) and 33% for day 30 responders (95% confidence interval, 25% to 40%) and Acute GVHD was the main cause of death (49%) followed by opportunistic infections (27%). Results of this update show that although inolimomab is a well-tolerated drug with a moderate number of short-term responses, it is associated with long-term survival in only one-third of responding patients. These data highlight the need to investigate new rescue treatments with sustained effect and the importance of reporting long-term outcomes in GVHD studies.
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Anticorpos Monoclonais/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Doença Aguda , Adolescente , Corticosteroides/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais/farmacologia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Humanos , Imunossupressores/farmacologia , Interleucina-2/antagonistas & inibidores , Interleucina-2/imunologia , Linfopenia/imunologia , Linfopenia/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
INTRODUCTION: the indigenous population is vulnerable and there is limited understanding of their somatometric indicators and APGAR score at birth. AIM: the objective of the study was to explore the association of the condition of indigenous newborn (INB) on somatometric parameters and APGAR score at birth. METHODS: this study employed an exploratory cross-sectional design, utilizing the registry of newborns (NB) from a private clinic. The APGAR score at one minute after birth, as well as nutritional indicators derived from measurements of weight, height, and perimeters, were taken into consideration. The statistical analysis involved the use of logistic regressions. RESULTS: the analysis included 7413 NB (1.8 % INB), 52 % were male and 8.1 % were born preterm (gestational age < 37 weeks). In comparison to non-indigenous NB, the INB group showed a higher risk of malnutrition (8 % vs. 6.3 %; p < 0.001), a greater prevalence of excess weight (7.3 % vs. 1.8 %; p < 0.001), smaller head circumference (33.6 cm vs. 34.1 cm; p = 0.017), smaller abdominal circumference (30.9 cm vs. 31.5 cm; p = 0.011), and a higher occurrence of low APGAR scores (< 7) (8.7 % vs. 1.2 %; p < 0.001). Furthermore, the indigenous condition was independently associated with low birth weight (< 2.500 g) (OR, 0.4; 95 % CI, 0.2; 0.9), excess head circumference (OR, 2.7; 95 % CI, 1.5; 4.7), and APGAR score < 7 points (OR, 8.3; 95 % CI, 4.2; 16.5). CONCLUSIONS: the indigenous condition was associated with factors that have adverse effects on the health of NB, including reduced head circumference and suboptimal performance on the APGAR scale. These results emphasize the importance of improving access to and quality of prenatal healthcare services for indigenous communities.
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Engraftment and nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT) depend greatly on the transplantation platform in patients with myelofibrosis (MF). We report outcomes of 14 consecutive MF patients who received reduced doses of post-transplantation cyclophosphamide (PTCy; 60 mg/kg total dose) and tacrolimus as graft-versus-host disease (GVHD) prophylaxis as part of a new standardized allo-HCT protocol. The median patient age at allo-HCT was 59 years (range, 41 to 67 years), and the median interval from diagnosis to HCT was 19 months (range, 2 to 114 months). All patients received ruxolitinib before HCT, and 71% had no response. Most patients (78%) had symptomatic splenomegaly at HCT. Eighty-six percent received reduced-intensity conditioning, and 64% underwent allo-HCT from an unrelated donor. There were no graft failures, and neutrophil and platelet recovery occurred at a median of 21 days and 31 days, respectively. The cumulative incidence of grade II-IV acute GVHD was 28.6%, and that of grade III-IV acute GVHD was 7%. The 2-year incidence of overall and moderate-severe chronic GVHD was 36% and 14%, respectively. Only 1 patient relapsed after transplantation, and NRM was 7% at 100 days and 14% at 2 years. The GVHD-free/relapse-free and immunosuppression-free incidence at 1 year was 41%. With a median follow-up for survivors of 28 months (range, 8 to 55 months), the 2-year overall survival and progression-free survival were 86% and 69%, respectively. Reduced doses of PTCy as GVHD prophylaxis for high-risk MF patients showed promising results by reducing the incidence of GVHD without any cases of graft failure.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doadores não RelacionadosRESUMO
Treatment of chronic lymphocytic leukemia (CLL) has dramatically evolved over the last decades thanks to the introduction of targeted therapies. We aimed to describe retrospectively the evolution in the frontline prescription in the CLL patients from our institution. As a secondary objective, the impact of frontline therapy on the time-to-next-treatment (TTNT) and overall survival (OS). After a median of 6.4 years (0.1-36.4) of follow-up from diagnosis, 323 of 780 CLL patients (41.4%) required therapy. Alkylating agents in monotherapy (chlorambucil) were the most used until 2012, and from then, chemoimmunotherapy. Since 2018, targeted therapies were the most common therapeutic strategy (74.1%). Patients who received targeted therapies had significantly longer TTNT compared to other regimens. In the multivariable analyses, mutated IGHV genes targeted therapies and chemoimmunotherapy regimens were related to longer TTNT, and sex female, age younger than 65, and mutated IGHV genes were associated with better OS.
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Leucemia Linfocítica Crônica de Células B , Humanos , Feminino , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Clorambucila , ImunoterapiaRESUMO
The comorbidity burden is an important risk factor for overall survival (OS) in several hematological malignancies. This observational prospective study was conducted to evaluate the impact of individual comorbidities on survival in a multicenter series of 668 patients with primary myelofibrosis (PMF) or MF secondary to polycythemia vera (PPV-MF) or essential thrombocythemia (PET-MF). Hypertension (hazard ratio (HR) = 4.96, p < 0.001), smoking (HR = 5.08, p < 0.001), dyslipidemia (HR = 4.65, p < 0.001) and hepatitis C virus (HCV) (HR = 4.26, p = 0.015) were most adversely associated with OS. Diabetes (HR = 3.01, p < 0.001), pulmonary disease (HR = 3.13, p < 0.001) and renal dysfunction (HR = 1.82, p = 0.037) were also associated with an increased risk of death. Multivariate analysis showed that pulmonary disease (HR = 2.69, p = 0.001), smoking (HR = 3.34, p < 0.001), renal dysfunction (HR = 2.08, p = 0.043) and HCV (HR = 11.49, p = 0.001) had a negative impact on OS. When ruxolitinib exposure was included in the model, the effect of each comorbidity on survival was modified. Therefore, individual comorbidities should be taken into account in determining the survival prognosis for patients with MF.
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Clinical studies focused on outcomes of umbilical cord blood transplantation (UCBT) for patients with chronic myelogenous leukemia (CML) in need of allogeneic stem cell transplantation and lacking an HLA-matched adult donor are limited. We analyzed the outcome of 26 adults with CML receiving single-unit UCBT from unrelated donors after myeloablative conditioning at a single institution. Conditioning regimens were based on combinations of thiotepa, busulfan, cyclophospamide or fludarabine, and antithymocyte globulin. At the time of transplantation, 7 patients (27%) were in first chronic phase (CP), 11 (42%) were in second CP, 2 (8%) were in accelerated phase (AP), and 6 (23%) were in blast crisis (BC). The cumulative incidence (CI) of myeloid engraftment was 88% at a median time of 22 days and was significantly better for patients receiving higher doses of CD34(+) cells. The CI of acute graft-versus-host disease (GVHD) grade II-IV was 61%, that of acute GVHD grade III-IV was 39%, and that of chronic extensive GVHD was 60%. Treatment-related mortality (TRM) was 41% for patients undergoing UCBT while in first or second CP and 100% for patients in AP or BC (P < .01). After a median follow-up of 8 years, none of the patients relapsed, giving an overall disease-free survival (DFS) at 8 years of 41%. The DFS for patients undergoing UCBT while in any CP was 59%. These results demonstrate that UCBT from unrelated donors can be a curative treatment for a substantial number of patients with CML. Advances in supportive care and better selection of cord blood units and patients are needed to improve TRM.
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Doadores de Sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Adulto , Causas de Morte , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Intervalo Livre de Doença , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Histocompatibilidade , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Contagem de Plaquetas , Recidiva , Estudos Retrospectivos , Quimeras de Transplante , Resultado do Tratamento , Adulto JovemRESUMO
Clinical studies focused on disease-specific outcomes of cord blood transplant (CBT) from unrelated donors are limited. We analyzed the outcome and prognostic factors of 49 adults with high-risk acute myelogenous leukemia (AML) receiving single-unit CBT from unrelated donors after myeloablative (MA) conditioning at a single institution. Conditioning regimens were based on the combination of thiotepa, busulfan (Bu), cyclophospamide (Cy), or fludarabine (Flu), and antithymocyte globulin (ATG). Cumulative incidence of myeloid and platelet engraftment was 96% and 73% at a median time of 20 and 62 days, respectively. Engraftment was significantly faster for patients receiving higher doses of CD34(+) cells. Confidence Interval of graft-versus-host disease (GVHD), acute GVHD (aGVHD) grade II-IV, III-IV, and extensive chronic GVHD (cGVHD) were 26%, 15%, and 30%, respectively. Leukemia-free survival (LFS), nonrelapse mortality (NRM), and relapse at 2 years were 42%, 39%, and 19%, respectively. Low number of total nucleated cells (TNC) had a negative impact on NRM and LFS. Patients transplanted in first complete remission (CR1) receiving TNC above 2 x 10(7)/kg had a 4-year LFS of 75%. These results show that CBT from unrelated donors is a curative treatment for a substantial number of patients with high-risk AML, particularly if transplant is performed with highly cellular units in patients in first CR.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Antígenos CD34/análise , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Estatística como Assunto , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Only proven pathogenic mutations associated with myeloid neoplasms are key to establish the clonal nature of the bone marrow fibrosis. In cases with genetic variants of uncertain meaning, the clinical picture may be required to rule out secondary causes.
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In classical reduced-intensity conditioning (RIC) regimens, including the fludarabine and busulphan (BF) combination, sirolimus and tacrolimus (SIR-TAC) as graft vs host disease (GVHD) prophylaxis has shown acceptable results. The outcomes of SIR-TAC in a more intense RIC regimen as Thiotepa-fludarabine-busulfan (TBF) have been hardly investigated. This retrospective study included all consecutive patients receiving an allogeneic hematopoietic stem cell transplantation for myeloid malignancies (January 2009-2017) conditioned with either TBF or BF and receiving SIR-TAC. Patients receiving TBF presented higher non-relapse mortality (31.6 vs 12.3%, p = .01), along with shorter overall survival (51.8% vs 77.8%, p < .01) at 2 years than patients treated with BF. There were no significant differences in the cumulative incidence of grade II-IV acute GVHD or moderate-severe chronic GVHD or relapse between both groups. These results suggest that TBF does not seem to improve the traditional RIC BF regimen, at least when associated with SIR-TAC prophylaxis.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Bussulfano , Estudos de Viabilidade , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Sirolimo , Tacrolimo , Tiotepa , Condicionamento Pré-Transplante , Vidarabina/análogos & derivadosRESUMO
There is no information on the efficacy and safety of anticytomegalovirus (CMV) prophylaxis with intravenous ganciclovir or oral valganciclovir after unrelated cord-blood transplantation (UCBT). This issue was addressed in 151 adults (117 CMV-seropositive) undergoing UCBT at a single institution. The first 38 CMV-seropositive recipients were assigned to receive prophylactic ganciclovir, and the next 79 were given valganciclovir after engraftment. The cumulative incidence (CI) of CMV infection and disease was similar in patients receiving valganciclovir or ganciclovir (59% versus 55%, P = .59; and 9% versus 18%, P = .33, respectively). The toxicity profile and CI of nonrelapse mortality (CMV) and infection-related mortality did not differ between drugs. Patients receiving valganciclovir required fewer visits to the day hospital (P = .04). The CI of CMV infection and disease in 34 CMV-seronegative recipients was 12% and 6%, indicating that tight CMV monitoring is mandatory in this subset. The recipient's CMV serostatus, acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were the main risk factors for CMV infection, and aGVHD for CMV disease. This study suggests that prophylaxis with oral valganciclovir is as safe and effective as intravenous ganciclovir for preventing CMV infection and disease after UCBT, but valganciclovir reduces the use of hospital resources.
Assuntos
Antivirais/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Citomegalovirus/epidemiologia , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Administração Oral , Adolescente , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Estudos de Coortes , Infecções por Citomegalovirus/prevenção & controle , Esquema de Medicação , Feminino , Seguimentos , Ganciclovir/administração & dosagem , Ganciclovir/efeitos adversos , Doença Enxerto-Hospedeiro/epidemiologia , Recursos em Saúde/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Humanos , Incidência , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Pré-Medicação , Prognóstico , Fatores de Risco , Condicionamento Pré-Transplante , Resultado do Tratamento , Valganciclovir , Adulto JovemRESUMO
BACKGROUND: To determine whether in patients with chronic lymphocytic leukemia (CLL), the clinical stage maintains prognostic significance over time and can be considered as a surrogate for the response to therapy. PATIENTS AND METHODS: The data from 229 CLL patients were retrospectively evaluated. The main aims of the study were to describe the changes in clinical stage during the course of CLL as a result of the response to treatment and to determine the time to next therapy (TTNT) and overall survival (OS) according to those changes, in particular, among the heterogeneous International Workshop on CLL (IWCLL) partial response (PR) category. RESULTS: Among the patients in the IWCLL PR category, differences were found in TTNT and OS according to the clinical stage at the response evaluation. With a median follow-up period of 91 months (range, 2-390 months), patients with a PR- Binet A at the response evaluation had significantly longer TTNT and OS compared with those with PR-Binet B/C (median TTNT, 26 vs. 11 months; P = .00; median OS, 63 vs. 43 months; P = .047). CONCLUSION: The results of the present study have shown that for patients with CLL, the Binet clinical stages are good outcome predictors throughout the disease course and also suggest that changes in Binet clinical stage could be useful as response surrogates and to divide the IWCLL PR category into different prognostic subgroups.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Tempo para o TratamentoRESUMO
In normal B-cells, B-cell antigen receptor (BCR) signaling can be negatively regulated by the low-affinity receptor FcγRIIb (CD32b). To better understand the role of FcγRIIb in chronic lymphocytic leukemia (CLL), we correlated its expression on 155 samples from newly-diagnosed Binet A patients with clinical characteristics and outcome. FcγRIIb expression was similar in normal B-cells and leukemic cells, this being heterogenous among patients and within CLL clones. FcγRIIb expression did not correlate with well known prognostic markers [disease stage, serum beta-2 microglobulin (B2M), IGHV mutational status, expression of ZAP-70 and CD38, and cytogenetics] except for a weak concordance with CD49d. Moreover, patients with low FcγRIIb expression (69/155, 44.5%) required therapy earlier than those with high FcγRIIb expression (86/155, 55.5%) (median 151.4 months vs. not reached; p=.071). These results encourage further investigation on the role of FcγRIIb in CLL biology and prognostic significance in larger series of patients.