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To evaluate safety and therapeutic effect along 12 months of allogenic adipose tissue-derived stromal/stem cells (ASCs) transplantation with cholecalciferol (VITD) in patients with recent-onset type 1 diabetes (T1D). Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1xKgx106 cells) and VITD 2000UI/day for 12 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide area under the curve (CPAUC), insulin dose, HbA1c and frequency of FoxP3+ in CD4+ or CD8+ T-cells(flow cytometry) were evaluated at baseline(T0), after 3(T3), 6(T6) and 12 months(T12). Eleven patients completed follow up (7:group 1;4:group 2). Group 1 had lower insulin requirement at T3(0.24±0.18vs0.53±0.23UI/kg,p=0.04), T6(0.24±0.15vs0.66±0.33 UI/kg,p=0.04) and T12(0.39±0.15vs0.74±0.29 UI/Kg,p=0.04).HbA1c was lower at T6 (50.57±8.56vs72.25±10.34 mmol/mol,p=0.01), without differences at T12 (57.14±11.98 in group 1 vs. 73.5±14.57 mmol/min in group 2, p=0.16). CPAUC was not significantly different between groups at T0(p=0.07), higher in group 1 at T3(p=0.04) and T6(p=0.006), but similar at T12(p=0.23). IDAA1c was significantly lower in group 1 than group 2 at T3,T6 and T12 (p=0.006, 0.006 and 0.042, respectively). IDDA1c was inversely correlated to FoxP3 expression in CD4 and CD8+ T cells at T6 (p<0.001 and p=0.01, respectively). In group 1, one patient had recurrence of a benign teratoma that was surgically removed, not associated to the intervention. ASCs with VITD without immunosuppression were safe and associated lower insulin requirements, better glycemic control, and transient better pancreatic function in recent onset T1D, but the potential benefits were not sustained.
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Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/terapia , Colecalciferol/uso terapêutico , Hemoglobinas Glicadas , Projetos Piloto , Estudos Prospectivos , Seguimentos , Insulina/metabolismo , Tecido Adiposo/metabolismo , Suplementos Nutricionais , Células-Tronco/metabolismo , Fatores de Transcrição ForkheadRESUMO
This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.
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Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Terapia de Salvação , Humanos , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologiaRESUMO
In previous observational studies, we have separately characterized patients with multiple myeloma (MM) both from Latin America (LA) and from Asia. Here, we analyze these two datasets jointly, in order to assess the overall survival (OS) in these two world regions. Data were available from 3664 patients (1968 from LA and 1696 from Asia); all of whom diagnosed between 1998 and 2007. Approximately, 26% of patients in both world regions underwent transplantation. OS (from diagnosis of MM) was explored with Kaplan-Meier analyses and Cox proportional hazards models. Patients from LA were significantly younger and had hypercalcemia more often than Asian patients, who in turn had higher proportions of anemia and International Staging System (ISS) stage III disease. The median OS was 56 months in LA, and 47 months in Asia (hazard ratio [HR] = 0.83; 95% confidence interval [CI], 0.76 to 0.91; P < 0.001). In multivariable analysis, age, ISS stage III, anemia, hypercalcemia, and world region remained significantly associated with OS (P < 0.001 for all covariates). These results were largely driven by patients not undergoing transplantation, as no difference in OS emerged between the two world regions in univariable or multivariable analysis for transplanted patients. Despite adverse prognostic features differentially favoring each region, and adjusting for such differences, we found an OS advantage for patients from LA, in comparison with contemporaneous patients from Asia. Whether this is due to different biological features, differences in access to novel agents (especially thalidomide in earlier periods of the study), unmeasured confounders, or the play of chance, remain unknown.
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Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Sistema de Registros , Idoso , Ásia/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de SobrevidaRESUMO
Bortezomib (V), lenalidomide (R), cyclophosphamide (C), and dexamethasone (D) are components of the most commonly used modern doublet (RD, VD) or triplet (VRD, CVD) initial induction regimens before autologous hematopoietic cell transplantation (AHCT) for multiple myeloma (MM) in the United States. In this study we evaluated 693 patients receiving "upfront" AHCT after initial induction therapy with modern doublet or triplet regimens using data reported to the Center for International Blood and Marrow Transplant Research from 2008 to 2013. Analysis was limited to those receiving a single AHCT after 1 line of induction therapy within 12 months from treatment initiation for MM. In multivariate analysis, progression-free survival (PFS) and overall survival were similar irrespective of induction regimen. However, high-risk cytogenetics and nonreceipt of post-transplant maintenance/consolidation therapy were associated with higher risk of relapse. Patients receiving post-transplant therapy had significantly improved 3-year PFS versus no post-transplant therapy (55% versus 39%, P = .0001). This benefit was most evident in patients not achieving at least a complete response post-AHCT (P = .005). In patients receiving upfront AHCT, the choice of induction regimen (doublet or triplet therapies) appears to be of lower impact than use of post-transplant therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Causas de Morte , Terapia Combinada , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Segunda Neoplasia Primária/mortalidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Inibidores de Proteassoma/administração & dosagem , Indução de Remissão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
Relatively little is known about the outcomes of multiple myeloma in Latin America, a world region where incorporation of novel agents is generally slow. In the current retrospective-prospective study, we aimed to describe the patterns of care and treatment results in five Latin American countries. Between April 2007 and October 2009, patients who had been diagnosed from January 2005 to December 2007 were registered at 23 institutions from Argentina, Brazil, Chile, Mexico, and Peru. We divided patients into two cohorts, according to transplantation eligibility, and analyzed them with regard to first-line treatment and overall survival (OS). We analyzed a total of 852 patients, 46.9 % of whom were female. The median follow-up was 62 months. Among transplantation-ineligible patients (N = 461), the mean age was 67.4 years, approximately one third of patients received a thalidomide-based treatment in the first line, and the median OS was 43.0 months. Transplantation-eligible patients (N = 391) had a mean age of 54.7 years and a median OS of 73.6 months. Autologous transplantation was performed in 58.6 % of the patients for whom this procedure was initially planned and in only 26.9 % of the overall patients. Our long-term results reflect the contemporary literature for patients with multiple myeloma treated with autologous transplantation and thalidomide-based regimens in clinical trials and observational studies. However, further efforts are needed to approve and incorporate novel agents in Latin American countries, as well as to increase access to transplantation, in order to achieve the expected improvements in patient outcomes.
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Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos RetrospectivosAssuntos
Citometria de Fluxo , Imunofenotipagem , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/metabolismo , Células Neoplásicas Circulantes/metabolismo , Plasmócitos/metabolismo , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem/métodos , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Células Neoplásicas Circulantes/patologia , Plasmócitos/patologia , PrognósticoRESUMO
BACKGROUND: Risk factors for invasive fusariosis (IF) have not been characterized. We attempted to identify risk factors for IF in a prospective cohort of hematologic patients treated in 8 centers in Brazil. METHODS: Patients with (cases) and without (controls) proven or probable IF diagnosed in a cohort of patients with acute myeloid leukemia (AML) or myelodysplasia (MDS), and in allogeneic hematopoietic cell transplant (HCT) recipients (early, until day 40; late, after day 40 posttransplant) were compared by univariate Cox regression analysis. RESULTS: Among 237 induction remission courses of AML/MDS and 663 HCTs (345 allogeneic and 318 autologous), 25 cases of IF were diagnosed. In the AML/MDS cohort, active smoking (hazard ratio [HR], 9.11 [95% confidence interval {CI}, 2.04-40.71]) was associated with IF. Variables associated with IF in the early phase of allogeneic HCT were receipt of antithymocyte globulin (HR, 22.77 [95% CI, 4.85-101.34]), hyperglycemia (HR, 5.17 [95% CI, 1.40-19.11]), center 7 (HR, 5.15 [95% CI, 1.66-15.97]), and AML (HR, 4.38 [95% CI, 1.39-13.81]), and in the late phase were nonmyeloablative conditioning regimen (HR, 35.08 [95% CI, 3.90-315.27]), grade III/IV graft-vs-host disease (HR, 16.50 [95% CI, 2.67-102.28]), and previous invasive mold disease (HR, 10.65 [95% CI, 1.19-95.39]). CONCLUSIONS: Attempts to reduce the risk of IF may include smoking cessation, aggressive control of hyperglycemia, and the use of a mold-active agent as prophylaxis in patients receiving nonmyeloablative HCT or ATG in the conditioning regimen. Future research should further explore smoking and other prehospital variables as risks for IF.
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Fusariose/etiologia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/complicações , Transplantados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Soro Antilinfocitário/uso terapêutico , Brasil , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fusariose/diagnóstico , Doença Enxerto-Hospedeiro , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Estudos Prospectivos , Indução de Remissão , Fatores de Risco , Fumar , Condicionamento Pré-Transplante , Adulto JovemRESUMO
We compared the safety and efficacy of siltuximab (S), an anti-interleukin-6 chimeric monoclonal antibody, plus bortezomib (B) with placebo (plc) + B in patients with relapsed/refractory multiple myeloma in a randomized phase 2 study. Siltuximab was given by 6 mg/kg IV every 2 weeks. On progression, B was discontinued and high-dose dexamethasone could be added to S/plc. Response and progression-free survival (PFS) were analyzed pre-dexamethasone by European Group for Blood and Marrow Transplantation (EBMT) criteria. For the 281 randomized patients, median PFS for S + B and plc + B was 8.0 and 7.6 months (HR 0.869, P = 0.345), overall response rate was 55 versus 47% (P = 0.213), complete response rate was 11 versus 7%, and median overall survival (OS) was 30.8 versus 36.8 months (HR 1.353, P = 0.103). Sustained suppression of C-reactive protein, a marker reflective of inhibition of interleukin-6 activity, was seen with S + B. Siltuximab did not affect B pharmacokinetics. Siltuximab/placebo discontinuation (75 versus 66%), grade ≥3 neutropenia (49 versus 29%), thrombocytopenia (48 versus 34%), and all-grade infections (62 versus 49%) occurred more frequently with S + B. The addition of siltuximab to bortezomib did not appear to improve PFS or OS despite a numerical increase in response rate in patients with relapsed or refractory multiple myeloma.
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Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/uso terapêutico , Interleucina-6/imunologia , Mieloma Múltiplo/tratamento farmacológico , Pirazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Bortezomib , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/mortalidade , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , RecidivaRESUMO
Patients who undergo allogeneic stem cell transplantation frequently develop an immunologic disease caused by the reactivation of the graft to the host tissues. This disease is called graft-versus-host disease (GVHD) and it is usually a systemic disorder. In a large proportion of cases, oral disorders that are related to a chronic phase of GVHD (cGVHD) occur, and their treatment involves the use of topical immunosuppressive drugs. Several medications have been studied for this purpose, but only a small number of clinical trials have been published. The present study is a randomized, double-blind clinical trial that compares topical clobetasol and dexamethasone for the treatment of symptomatic oral cGVHD. Patients were randomly assigned to treatment with clobetasol propionate .05% or dexamethasone .1 mg/mL for 28 days. In both arms, nystatin 100,000 IU/mL was administered with the corticosteroid. Oral lesions were evaluated by the modified oral mucositis rating scale (mOMRS) and symptoms were registered using a visual analogue scale. Thirty-five patients were recruited, and 32 patients were randomized into the study groups: 18 patients (56.3%) to the dexamethasone group and 14 patients (43.8%) to the clobetasol group. The use of clobetasol resulted in a significant reduction in mOMRS total score (P = .04) and in the score for ulcers (P = .03). In both groups, there was significant symptomatic improvement but the response was significantly greater in the clobetasol group (P = .02). In conclusion, clobetasol was significantly more effective than dexamethasone for the amelioration of symptoms and clinical aspects of oral lesions in cGVHD.
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Anti-Inflamatórios/uso terapêutico , Clobetasol/uso terapêutico , Dexametasona/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/métodos , Doenças da Boca/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Administração Tópica , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Autologous hematopoietic cell transplantation (AHCT) for plasma cell myeloma is performed less often in people >70 years old than in people ≤70 years old. We analyzed 11,430 AHCT recipients for plasma cell myeloma prospectively reported to the Center for International Blood and Marrow Transplant Research between 2008 and 2011, representing the majority of US AHCT activity during this period. Survival (OS) was compared in 3 cohorts: ages 18 to 59 years (n = 5818), 60 to 69 years (n = 4666), and >70 years (n = 946). Median OS was not reached for any cohort. In multivariate analysis, increasing age was associated with mortality (P = .0006). Myeloma-specific mortality was similar among cohorts at 12%, indicating an age-related effect on nonmyeloma mortality. Analyses were performed in a representative subgroup comparing relapse rate, progression-free survival (PFS), and nonrelapse mortality (NRM). One-year NRM was 0% for age >70 years and 2% for other ages (P = not significant). The three-year relapse rate was 56% in age 18 to 59 years, 61% in age 60 to 69 years, and 63% age >70 (P = not significant). Three-year PFS was similar at 42% in age 18 to 59 years, 38% in age 60 to 69 years, and 33% in age >70 years (P = not significant). Postrelapse survival was significantly worse for the older cohort (P = .03). Older subjects selected for AHCT derived similar antimyeloma benefit without worse NRM, relapse rate, or PFS.
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Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adolescente , Adulto , Fatores Etários , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Oral infection may be a source of bacteremia in patients undergoing hematopoietic stem cell transplant (HSCT). The aim of this study was to evaluate the relationship between patients with poor periodontal status and complications after HSCT. METHODS: A cohort of patients with hematological malignancies candidates for autologous HSCT was observed before and during the neutropenic phase of HSCT. A primary evaluation was performed before the HSCT procedure, including medical and socio-demographic data and physical examination (number of teeth and decayed, missing and filled teeth index (DMFT), oral mucosa, and full mouth periodontal assessment). During the neutropenic phase, data regarding the development of febrile neutropenia, bacteremia, and mucositis were also prospectively obtained. RESULTS: Forty-eight patients were included. The most common baseline disease was multiple myeloma (70 %). In the primary evaluations, the median DMFT was 13 (ranging 0-27), and periodontitis and gingivitis were present in 29 and 60 % of the patients, respectively. During the neutropenic phase of HSCT, fever occurred in 96 % of patients, and bacteremia was documented in 29 %. Coagulase-negative Staphylococcus was the most common isolated bacteria. Patients who developed bacteremia had a higher frequency of oral disorders compared with those without bacteremia, but it was not statistically significant. Oral mucositis affected 89.6 % of the patients, and patients with gingivitis or periodontal disorders had a high frequency of mucositis. CONCLUSIONS: The prevalence of oral pathologic conditions previous to HSCT procedures was very high in the studied population. A possible association was noted between previous gingivitis and the development of mucositis during the neutropenia of HSCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças da Boca/diagnóstico , Estomatite/etiologia , Adolescente , Adulto , Idoso , Bacteriemia/sangue , Bacteriemia/microbiologia , Estudos de Coortes , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Boca/microbiologia , Mucosa Bucal/patologia , Mieloma Múltiplo/sangue , Mieloma Múltiplo/cirurgia , Neutropenia/etiologia , Neutropenia/microbiologia , Higiene Bucal , Estudos Prospectivos , Estomatite/sangue , Estomatite/diagnóstico , Estomatite/microbiologiaRESUMO
BACKGROUND: Mesenchymal stem cell infusion and vitamin D supplementation may have immunomodulatory actions that could prolong the preservation of residual insulin secretion in patients with type 1 diabetes (T1D). Intervention with these agents after onset of T1D could favor the development of a remission phase, with potential clinical impact. We aimed to compare the presence of clinical remission (CR), glycemic control and daily insulin requirement at 6, 12, 18, 24 and 36 months after the diagnosis of T1D using IDAA1c in patients who received therapy with adipose tissue-derived mesenchymal stem cell (ASC) infusion and vitamin D supplementation and a control group. METHODS: This retrospective cohort study analyzed data from the medical records of patients with T1D diagnosed between 15 and 40 years. Partial CR was defined as an IDAA1c index < 9. Patients in the intervention group received an infusion of adipose tissued-derived mesenchymal stem cells (ASCs) within 3 months after diagnosis and supplementation with 2000 IU of cholecalciferol for 1 year, started on the day following the infusion. Partial CR was also determined using the ISPAD criteria, to assess its agreement with IDAA1c. RESULTS: A total of 28 patients were evaluated: 7 in the intervention group (group 1) and 21 in the control group (group 2). All patients in group 1 evolved with partial CR while only 46.7% of patients in group 2 had this outcome. Group 1 had a higher frequency of CR when evaluated with IDAA1c and ISPAD criteria. The mean duration of CR varied between the two criteria. Although HbA1c was similar between groups during follow-up, group 1 had a lower total daily insulin requirement (p < 0.005) at all time points. At 36 months, group 1 used 49% of the total daily insulin dose used by group 2 with similar glycemic control. CONCLUSION: The intervention with infusion of ASC + vitamin D supplementation was associated with partial CR at 6 months. Although there were no differences in CR established by the IDAA1c and ISPAD criteria after three years of follow-up, patients who underwent intervention had nearly the half insulin requirement of controls with conventional treatment, with similar glycemic control. TRIAL REGISTRATION: 37001514.0.0000.5257.
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Patients with focal segmental glomerulosclerosis (FSGS) who are refractory to drug treatment may present progressive loss of kidney function, leading to chronic kidney disease stage 5 under dialysis treatment. The safety of systemic administration of bone marrow-derived mononuclear cells (BMDMCs) has been shown in different preclinical models of kidney diseases. However, to date, no study has evaluated the safety and biodistribution of BMDMCs after infusion in renal arteries in patients with FSGS. We used a prospective, non-randomized, single-center longitudinal design to investigate this approach. Five patients with refractory FSGS and an estimated glomerular filtration rate (eGFR) between 20 and 40 ml/min/1.73 m2 underwent bone marrow aspiration and received an arterial infusion of autologous BMDMCs (5 × 107) for each kidney. In addition, BMDMCs labeled with technetium-99m (99mTc-BMDMCs) were used to assess the biodistribution by scintigraphy. All patients completed the 270-day follow-up protocol with no serious adverse events. A transient increase in creatinine was observed after the cell therapy, with improvement on day 30. 99mTc-BMDMCs were detected in both kidneys and counts were higher after 2 hr compared with 24 hr. The arterial infusion of BMDMCs in both kidneys of patients with FSGS was considered safe with stable eGFR at the end of follow-up. This trial is registered with NCT02693366.
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Autologous hematopoietic cell transplantation (AHCT) as initial therapy of patients with multiple myeloma (MM) improves survival. However, data to support this approach for relapsed/progressive disease after initial AHCT (AHCT1) are limited. Using Center for International Blood and Marrow Transplant Research data, we report the outcomes of 187 patients who underwent a second AHCT (AHCT2) for the treatment of relapsed/progressive MM. Planned tandem AHCT was excluded. Median age at AHCT2 was 59 years (range, 28 to 72), and median patient follow-up was 47 months (range, 3 to 97). Nonrelapse mortality after AHCT2 was 2% at 1 year and 4% at 3 years. Median interval from AHCT1 to relapse/progression was 18 months, and median interval between transplantations was 32 months. After AHCT2, the incidence of relapse/progression at 1 and 3 years was 51% and 82%, respectively. At 3 years after AHCT2, progression-free survival was 13%, and overall survival was 46%. In multivariate analyses, those relapsing ≥36 months after AHCT1 had superior progression-free (P = .045) and overall survival (P = .019). Patients who underwent AHCT2 after 2004 had superior survival (P = .026). AHCT2 is safe and feasible for disease progression after AHCT1. In this retrospective study, individuals relapsing ≥36 months from AHCT1 derived greater benefit from AHCT2 compared with those with a shorter disease-free interval. Storage of an adequate graft before AHCT1 will ensure that the option of a second autologous transplantation is retained for patients with relapsed/progressive MM.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/cirurgia , Terapia de Salvação/métodos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do TratamentoRESUMO
Allogeneic hematopoietic cell transplantation in multiple myeloma is limited by prior reports of high treatment-related mortality. We analyzed outcomes after allogeneic hematopoietic cell transplantation for multiple myeloma in 1207 recipients in 3 cohorts based on the year of transplantation: 1989-1994 (n = 343), 1995-2000 (n = 376), and 2001-2005 (n = 488). The most recent cohort was significantly older (53% > 50 years) and had more recipients after prior autotransplantation. Use of unrelated donors, reduced-intensity conditioning and the blood cell grafts increased over time. Rates of acute graft-versus-host (GVHD) were similar, but chronic GVHD rates were highest in the most recent cohort. Overall survival (OS) at 1-year increased over time, reflecting a decrease in treatment-related mortality, but 5-year relapse rates increased from 39% (95% confidence interval [CI], 33%-44%) in 1989-1994 to 58% (95% CI, 51%-64%; P < .001) in the 2001-2005 cohort. Projected 5-year progression-free survival and OS are 14% (95% CI, 9%-20%) and 29% (95% CI, 23%-35%), respectively, in the latest cohort. Increasing age, longer interval from diagnosis to transplantation, and unrelated donor grafts adversely affected OS in multivariate analysis. Survival at 5 years for subjects with none, 1, 2, or 3 of these risk factors were 41% (range, 36%-47%), 32% (range, 27%-37%), 25% (range, 19%-31%), and 3% (range, 0%-11%), respectively (P < .0001).
Assuntos
Mieloma Múltiplo/cirurgia , Mieloma Múltiplo/terapia , Transplante de Células-Tronco/tendências , Transplante Homólogo/tendências , Adulto , Idoso , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco/efeitos adversos , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8(+) T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes favoring both immune cytotoxicity and recovery of B-cell production and homing, suggesting improved immune surveillance.
Assuntos
Citometria de Fluxo/tendências , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Feminino , Citometria de Fluxo/métodos , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/patologia , Masculino , Pessoa de Meia-Idade , Plasmócitos/imunologia , Plasmócitos/patologia , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: The use of quinolone prophylaxis in high-risk neutropenic patients is considered standard of care but the development of resistance is a concern. Previous studies have focused mainly on quinolone resistance among patients receiving prophylaxis, with very few data reporting its impact on the hospital microbial epidemiology. METHODS: We analyzed a cohort of 329 episodes of chemotherapy-induced neutropenia in adults, and compared two periods: 2005 (period 1, no prophylaxis, n=110) and 2006-2008 (period 2, ciprofloxacin prophylaxis, n=219). Outcomes analyzed were the frequency of febrile neutropenia, bacteremia, duration of antibiotic therapy and hospitalization, and antimicrobial resistance to ciprofloxacin and extended-spectrum beta-lactamase [ESBL] production. We analyzed resistance rates (by patients-day) in the cohort, as well as in other patients (neutropenic and non-neutropenic, 11,975 patients-day) admitted to the hematology unit in the same period, taking into consideration the general resistance patterns in the hospital. RESULTS: Quinolone prophylaxis (period 2) resulted in fewer episodes of febrile neutropenia (159/219 [73%] vs. 102/110 [93%], Chi-square 18.09, p = 0.00002), and bacteremia (49/219 [22] vs. 36/110 [33%], Chi-square 4.10, p = 0.04), shorter duration of antibiotic therapy (p = 0.0002) and hospitalization (p = 0.002), but more frequent use of carbapenems (79/219 [36%] vs. 15/110 [14%], Chi-square 18.06, p = 0.0002). In addition, period 2 was associated with higher rates of quinolone resistance (6.77 vs. 3.02 per 1,000 patients-day, p = 0.03). The rate of ESBL-producing enterobacteria in the two periods was slightly higher in patients receiving quinolone prophylaxis (1.27 vs. 0.38 per 1,000 patients-day, p = 0.26) as well as in the hematology unit overall (1.59 vs. 0.53 per 1,000 patients-day, p = 0.08), but remained stable in the whole hospital (0.53 vs. 0.56 per 1,000 patients-day, p = 0.74). CONCLUSIONS: Ciprofloxacin prophylaxis was beneficial in high risk neutropenic patients, but important modifications in the prescription of carbapenems and on antimicrobial resistance patterns of isolates were observed. The importance of hospital or ward ecology must be taken into account when deciding for quinolone prophylaxis in high-risk neutropenic patients.
Assuntos
Anti-Infecciosos/uso terapêutico , Antibioticoprofilaxia , Ciprofloxacina/uso terapêutico , Neutropenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/complicações , Bacteriemia/prevenção & controle , Estudos de Coortes , Farmacorresistência Bacteriana , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/complicações , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success. METHODS: A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions. RESULTS: This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers. CONCLUSION: We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil.
RESUMO
BACKGROUND AND OBJECTIVES: Three different scores were addressed as predictors of outcomes in autologous stem cell transplant (Auto SCT): one was calculated by pretransplant characteristics (European Society for Blood and Marrow Transplantation [EBMT] risk score), and two were calculated at the onset of febrile neutropenia (Multinational Association for Supportive Care in Cancer [MASCC] and Quick Sequential Organ Failure Assessment [qSOFA]). We considered bloodstream infection (BSI), carbapenem prescription, admission to the intensive care unit (ICU), and mortality as outcomes. PATIENTS: A total of 309 patients with a median age of 54 years were enrolled. RESULTS: Patients with EBMT score ≥4 (EBMT 4+) had higher ICU rates (14% vs. 4%; p < 0.01) and more carbapenem prescriptions (61% vs. 38%; p < 0.001) than those with EBMT score <4. MASCC <21 points (MASCC HR) was associated with carbapenem prescription (59% vs. 44%; p = 0.013), ICU (19% vs. 3%; p < 0.01), and death (4% vs. 0; p = 0.014). Patients with at least two points by qSOFA (qSOFA 2+) had more frequent BSI (55% vs. 22%; p = 0.03), ICU admissions (73% vs. 7; p < 0.01), and death (18% vs. 0.7, p = 0.02). EBMT 4+ and MASCC HR achieved the best sensitivities for ICU. For death, the best sensitivity was obtained with MASCC. CONCLUSION: In conclusion, risk scores for Auto SCT showed an association with outcomes and had different performances when combined or used alone. Therefore, risk scores for Auto SCT are useful in supportive care and clinical surveillance in stem cell transplant recipients.