RESUMO
BACKGROUND: Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. METHODS: We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. RESULTS: The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P = .01). CONCLUSIONS: Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. CLINICAL TRIALS REGISTRATION: NCT02088840.
Assuntos
Bacteriemia/epidemiologia , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Bacteriemia/etiologia , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Criança , Pré-Escolar , Farmacorresistência Bacteriana Múltipla , Escherichia coli/isolamento & purificação , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Incidência , Lactente , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Transplante Autólogo , Transplante Homólogo , Adulto JovemRESUMO
Seventy-four patients who relapsed after allogeneic stem cell transplantation were enrolled in a phase IIA study and treated with the sequential infusion of donor lymphocyte infusion (DLI) followed by cytokine-induced killer (CIK) cells. Seventy-three patients were available for the intention to treat analysis. At least 1 infusion of CIK cells was given to 59 patients, whereas 43 patients received the complete cell therapy planned (58%). Overall, 12 patients (16%) developed acute graft-versus-host disease (aGVHD) of grades I to II in 7 cases and grades III to IV in 5). In 8 of 12 cases, aGVHD developed during DLI treatment, leading to interruption of the cellular program in 3 patients, whereas in the remaining 5 cases aGVHD was controlled by steroids treatment, thus allowing the subsequent planned administration of CIK cells. Chronic GVHD (cGVHD) was observed in 11 patients (15%). A complete response was observed in 19 (26%), partial response in 3 (4%), stable disease in 8 (11%), early death in 2 (3%), and disease progression in 41 (56%). At 1 and 3 years, rates of progression-free survival were 31% and 29%, whereas rates of overall survival were 51% and 40%, respectively. By multivariate analysis, the type of relapse, the presence of cGVHD, and a short (<6 months) time from allogeneic hematopoietic stem cell transplantation to relapse were the significant predictors of survival. In conclusion, a low incidence of GVHD is observed after the sequential administration of DLI and CIK cells, and disease control can be achieved mostly after a cytogenetic or molecular relapse.
Assuntos
Células Matadoras Induzidas por Citocinas/transplante , Transplante de Células-Tronco Hematopoéticas/métodos , Transfusão de Linfócitos/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Transfusão de Linfócitos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Indução de Remissão , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
This phase I multicenter study was aimed at assessing the feasibility and safety of intravenous administration of third party bone marrow-derived mesenchymal stromal cells (MSC) expanded in platelet lysate in 40 patients (15 children and 25 adults), experiencing steroid-resistant grade II to IV graft-versus-host disease (GVHD). Patients received a median of 3 MSC infusions after having failed conventional immunosuppressive therapy. A median cell dose of 1.5 × 10(6)/kg per infusion was administered. No acute toxicity was reported. Overall, 86 adverse events and serious adverse events were reported in the study, most of which (72.1%) were of infectious nature. Overall response rate, measured at 28 days after the last MSC injection, was 67.5%, with 27.5% complete response. The latter was significantly more frequent in patients exhibiting grade II GVHD as compared with higher grades (61.5% versus 11.1%, P = .002) and was borderline significant in children as compared with adults (46.7 versus 16.0%, P = .065). Overall survival at 1 and 2 years from the first MSC administration was 50.0% and 38.6%, with a median survival time of 1.1 years. In conclusion, MSC can be safely administered on top of conventional immunosuppression for steroid resistant GVHD treatment. Eudract Number 2008-007869-23, NCT01764100.
Assuntos
Antineoplásicos/uso terapêutico , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Mesenquimais , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Resistencia a Medicamentos Antineoplásicos , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Humanos , Imunossupressores/uso terapêutico , Lactente , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Esteroides/uso terapêutico , Análise de Sobrevida , Transplante HomólogoRESUMO
Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs.
Assuntos
Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Micoses/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Lactente , Itália/epidemiologia , Pessoa de Meia-Idade , Micoses/etiologia , Estudos Prospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
ABO-group major incompatibility hematopoietic stem cell transplantation (HSCT) increases the risk of delayed red cell engraftment and other immunological complications. In this study, we evaluated the efficacy of pre-transplant infusion of rituximab in patients with ABO-incompatibility in improving red blood cell engraftment after HSCT, measured by time to reach transfusion independence. We performed a retrospective, single-center study including 131 consecutive patients transplanted with major or bidirectional ABO-incompatible grafts between 1st January 2013 and 31st December 2019. Fifty-one patients received an infusion of rituximab during the conditioning regimen, while 80 patients did not receive any additional preventive treatment. Time to transfusion independence was significantly reduced for patients treated with rituximab (1 month, 95% CI, 0.5-2) compared with the control group (3.2 months, 95% CI 1.5-3.2, p = 0.02). By multivariable analysis, rituximab use was associated with a faster red blood cell (RBC) engraftment (RR 1.88, 95% CI 1.17-3.03, p = 0.009), while a pre-transplant anti-donor isohemagglutinins titer >1:128 was associated with delayed transfusion independence (RR 0.61, 95% CI 0.37-0.99, p = 0.05). Although limited by the retrospective nature of the study, the results of this analysis suggest that rituximab added to conditioning regimens is feasible, safe, and able to improve post-transplant red blood cell engraftment.
Assuntos
Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Transplante de Células-Tronco Hematopoéticas , Rituximab , Condicionamento Pré-Transplante , Humanos , Rituximab/uso terapêutico , Rituximab/farmacologia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , IdosoRESUMO
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option for patients with Myelodysplastic syndromes (MDS). For many years, the selection of patients to allogeneic HSCT has been largely based on use of the International Prognostic Scoring System-Revised (IPSS-R). However, the recent broader application of next generation sequencing in clinical practice provided an abundance of molecular data and led to the introduction of molecular prognostic scores as IPSS-Molecular (IPSS-M). In this paper, we retrospectively analyzed the outcomes of 57 consecutive MDS patients treated with allogeneic HSCT in our center. Re-stratification from IPSS-R to IPSS-M occurred in almost half of patients. The application of IPSS-M to our cohort demonstrated a stronger prognostic separation compared to IPSS-R and improved the C-index. Very high-risk IPSS-M patients showed worse outcomes following HSCT compared to high-risk patients. This study provides data supporting the need of integrating molecular information in the transplant decision making of patients with MDS. This allows an earlier and better identification of patients to whom the transplant should be advised.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Síndromes Mielodisplásicas/terapia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/diagnóstico , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Tomada de Decisão Clínica , Transplante Homólogo , Sequenciamento de Nucleotídeos em Larga Escala , Adulto JovemRESUMO
Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication following hematopoietic stem cell transplantation (HSCT). No approved treatments are currently available. This study presents real-world data obtained with narsoplimab, a human immunoglobulin G4 monoclonal antibody that inhibits MASP-2, the effector enzyme of the lectin pathway of the complement system. Between January 2018 and August 2023, 20 (13 adult and 7 pediatric) patients diagnosed with TA-TMA received narsoplimab under an ongoing compassionate use program. The diagnosis was based on internationally defined criteria for pediatric and adult patients. Fifteen patients fulfilled the criteria recently established by an international consensus on TA-TMA. Nineteen patients exhibited high-risk characteristics. Thirteen patients (65%) responded to narsoplimab, achieving transfusion independence and significant clinical improvement. The one-hundred-day Overall Survival (OS) post-TA-TMA diagnosis was 70%, and 100% for responders. Narsoplimab proved to be effective and safe in the treatment of high-risk TA-TMA, with no increased infectious complications or other safety signals of concern across all age groups. The high response rates and the encouraging survival outcomes underscore the potential of narsoplimab as a valuable therapeutic option, particularly for high-risk cases.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Humanos , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/terapia , Adulto , Masculino , Feminino , Criança , Adolescente , Pessoa de Meia-Idade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pré-Escolar , Adulto Jovem , Idoso , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
Myeloablative single-unit umbilical cord blood transplantation (sUCBT) using busulfan, thiotepa, fludarabine, and antithymocyte globulin (Grupo Español de Trasplante Hematopoyético [GETH]-2005 protocol) resulted in high rates of engraftment and high antitumor activity. We designed a new graft-versus-host disease prophylaxis, substituting long-term steroids with mycophenolate mofetil together with a slight reduction of antithymocyte globulin (GETH/Gruppo Italiano Trapianto Midollo Osseo [GITMO]-2008 protocol). The results in 145 consecutive patients were compared with those obtained in 88 patients from the previous GETH-2005 trial. The cumulative incidence (CI) of myeloid engraftment at 60 days for patients in the GETH-2005 and GETH/GITMO-2008 trials was 94% and 88%, respectively, at a median time to neutrophil recovery of 19 and 23 days, respectively (P < .0001). In the multivariable analyses, platelet engraftment, acute and chronic graft-versus-host disease, nonrelapse mortality, relapse, and event-free survival were not significantly different. The 3-year event-free survival rate in the GETH/GITMO-2008 trial was 66%, 31%, and 25% for patients transplanted in early, intermediate, and advanced stages of the disease, respectively (P < .0001). This study confirms that myeloablative sUCBT using busulfan-based conditioning is a valuable strategy for patients with hematological malignancies. The use of mycophenolate mofetil apparently had an adverse effect on myeloid engraftment, and therefore a cautious use of this agent is warranted in the UCBT setting.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Condicionamento Pré-Transplante/métodos , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Fatores de Risco , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Invasive fungal infections (IFIs) are considered a major problem among patients undergoing acute leukaemia (AL) induction treatment. PROphylaxis of Fungal invasive Infections in Leukaemia-Caspofungin (PROFIL-C) is a multicentre study aiming to assess the comparative yield of using caspofungin versus standard policy (SP) regimens and the overall impact of IFI in routine clinical care conditions. METHODS: All AL patients receiving IFI prophylaxis according to local SP were prospectively included in the study by Northern Italy Leukaemia Group (NILG) centres. To allow the comparison of caspofungin versus SP regimens as prophylaxis strategies, caspofungin treatment was assigned via a centralized randomized procedure. The study was registered at http://www.clinicaltrial.gov (NCT00501098). RESULTS: Over a 2 year period, 175 patients were included. The overall incidence of IFI was 32/175 (18.3%) [10/175 (5.7%) probable/proven and 22/175 (12.6%) possible], with no statistically significant differences between caspofungin-based versus SP-based regimens [overall: 15/93 (16.1%) versus 17/82 (20.7%), relative risk (RR) 0.78, 95% confidence interval (CI) 0.42-1.46; probable/proven: 7/93 (7.5%) versus 3/82 (3.7%), RR 2.06, 95% CI 0.55-7.7; possible: 8/93 (8.6%) versus 14/82 (17.1%), RR 0.5, 95% CI 0.22-1.14]. Only one IFI-related death was recorded (10%). CONCLUSIONS: The incidence and mortality of IFI were lower than expected in this strictly sequential cohort representative of the routine care in the NILG network. The efficacy and safety of caspofungin were similar to other prophylactic regimens.
Assuntos
Antifúngicos/uso terapêutico , Antineoplásicos/efeitos adversos , Equinocandinas/uso terapêutico , Leucemia/complicações , Leucemia/tratamento farmacológico , Aspergilose Pulmonar/prevenção & controle , Adolescente , Adulto , Idoso , Antifúngicos/efeitos adversos , Antineoplásicos/uso terapêutico , Caspofungina , Estudos de Coortes , Equinocandinas/efeitos adversos , Feminino , Seguimentos , Humanos , Leucemia Mieloide/complicações , Leucemia Mieloide/tratamento farmacológico , Lipopeptídeos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Aspergilose Pulmonar/etiologia , Tamanho da Amostra , Resultado do Tratamento , Adulto JovemRESUMO
Five patients with aggressive acute leukemias who had relapsed after cord blood transplantation were treated with cord blood derived cytokine-induced killer (CIK) cells. These were obtained by ex vivo expansion, using as starting material the washouts of the cord blood units, left over at the end of the transplant. We did not observe any acute or delayed adverse event, and observed 1 partial response in 1 patient concomitantly with the development of acute grade III graft-versus-host disease (GVHD). These observations show the relatively low toxicity of cord blood-derived CIK cells and, more importantly, the feasibility of this immunotherapy program for patients who could not otherwise benefit from donor lymphocyte infusions.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Células Matadoras Induzidas por Citocinas/transplante , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Leucemia/terapia , Adolescente , Adulto , Células Matadoras Induzidas por Citocinas/citologia , Células Matadoras Induzidas por Citocinas/imunologia , Testes Imunológicos de Citotoxicidade , Feminino , Sangue Fetal/citologia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Células K562 , Leucemia/imunologia , Leucemia/mortalidade , Masculino , Transplante de Células-Tronco Mesenquimais , Pessoa de Meia-Idade , Recidiva , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: Bortezomib has proven to be effective as single agent in myeloma patients. Aim of this study was to evaluate the efficacy and toxicity of bortezomib in combination with dexamethasone in a cohort of multiple myeloma (MM) relapsed/refractory patients treated in a single center. PATIENTS AND METHODS: In this single center study, 70 patients were treated with bortezomib alone (9) or in combination with dexamethasone (61). RESULTS: Forty-one patients (59%) achieved at least a partial response (PR), including 7% complete response (CR), 36% very good partial response (VGPR) reaching the best response within four cycles. The duration of response was significantly longer for patients achieving CR/VGPR than for those achieving PR (7.3 vs. 3.8 months, P = 0.03). Likewise, time to progression, time to alternative treatment, and treatment free interval were significantly better for patients obtaining CR/VGPR (6.8, 9.4, 6.5 months respectively) as compared with PR (4.9, 6.3, 2 months respectively). The only dose-limiting toxicity was peripheral neuropathy (PN), which occurred in 38/70 patients (55%) and was of grade 3-4 in 12 (17%). PN led to a dose reduction or treatment discontinuation in 17 (24%) patients. Complete resolution or improvement of PN occurred in 29/38 (76%) after a median time of 100 d (range: 17-202). CONCLUSIONS: Bortezomib in combination with dexamethasone is highly effective in relapsed/refractory MM producing an impressive rate of CR/VGPR, but responses are short-lived.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/prevenção & controle , Adulto , Idoso , Ácidos Borônicos/administração & dosagem , Bortezomib , Dexametasona/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Pirazinas/administração & dosagem , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de TempoRESUMO
We analyzed the impact of alloHSCT in a single center cohort of 89 newly diagnosed NPM1mut AML patients, consecutively treated according to the Northern Italy Leukemia Group protocol 02/06 [NCT00495287]. After two consolidation cycles, the detection of measurable residual disease (MRD) by RQ-PCR was strongly associated with an inferior three-year overall survival (OS, 45% versus 84%, p = 0.001) and disease-free survival (DFS, 44% versus 76%, p = 0.006). In MRD-negative patients, post-remissional consolidation with alloHSCT did not provide a significant additional benefit over a conventional chemotherapy in terms of overall survival [OS, 89% (95% CI 71-100%) versus 81% (95% CI 64-100%), p = 0.59] and disease-free survival [DFS, 80% (95% CI 59-100%) versus 75% (95% CI 56-99%), p = 0.87]. On the contrary, in patients with persistent MRD positivity, the three-year OS and DFS were improved in patients receiving an alloHSCT compared to those allocated to conventional chemotherapy (OS, 52% versus 31%, p = 0.45 and DFS, 50% versus 17%, p = 0.31, respectively). However, in this group of patients, the benefit of alloHSCT was still hampered by a high incidence of leukemia relapse during the first year after transplantation (43%, 95% CI 25-60%). Consolidative alloHSCT improves outcomes compared to standard chemotherapy in patients with persistent NPM1mut MRD positivity, but in these high-risk patients, the significant incidence of leukemia relapse must be tackled by post-transplant preemptive treatments.
RESUMO
Herein, we report on a patient with splenic marginal zone lymphoma who initially presented without splenomegaly and bone marrow (BM) or peripheral blood involvement. At first, the patient showed moderate leukothrombocytopenia; she was completely asymptomatic, and BM examination excluded a hematologic disease. After 7 months, spleen enlargement was detected without determining any symptoms or worsening of the bilinear cytopenia. Bone marrow histologic, immunohistochemic, cytologic, and immunophenotypic examinations were normal. Splenectomy was performed, and a diagnosis of splenic marginal zone B-cell lymphoma was established. A monoclonal IgVH gene rearrangement was identified in the spleen tissue (VH3 gene family) and subsequently detected in the BM mononuclear cells. Because of the large surgical debulking and the absence of histologic, cytologic, and immunophenotypic BM involvement, no further treatment was proposed. After the splenectomy, the blood cell count normalized, and neither BM nor peripheral blood involvement appeared after 12 months of follow-up.
Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Esplenectomia , Neoplasias Esplênicas/patologia , Fosfatases de Especificidade Dupla/genética , Feminino , Rearranjo Gênico/genética , Humanos , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/cirurgia , Pessoa de Meia-Idade , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/cirurgiaRESUMO
Bcl-2/IgH rearrangement is the molecular hallmark of follicular lymphoma which is present in 70 - 90% of cases at diagnosis. The significance of the bcl-2 rearrangement at onset of disease and of its clearing after treatment (molecular response) is still controversial. The aims of the present analysis are: to evaluate the incidence of bcl-2 rearrangement in blood and marrow in a cohort of patients systematically investigated at diagnosis, to describe the correlation between bcl-2 and presenting features, to clarify the correlation of molecular response with outcome. Of 98 patients studied at initial staging for the presence of bcl-2 rearrangement, 64 (65%) showed bcl-2/IgH rearrangement in peripheral blood (PB) and/or bone marrow (BM) (58 at Major Breakpoint Region, MBR, and 6 at minor cluster region, mcr) while no bcl-2/IgH rearrangement was detected in the remaining 34 (35%) (germline status). No statistically significant differences were found between bcl-2 positive and bcl-2 negative cases as concerns presenting clinical features and response to first-line therapy. The median event-free survival, EFS, was not reached for the bcl-2 negative patients in PB and was 11 months for bcl-2 positive patients (statistically significant, P = 0.01) and, similarly, the median EFS was not reached for the bcl-2 negative patients in BM and was 11 months for bcl-2 positive patients (statistically significant, P = 0.04). Of the 64 bcl-2 positive cases, patients were analysed for molecular response (48 in BM and 40 in PB): 16 were molecular responders in BM and 20 were molecular responders in PB. The median EFS was 19 months for molecular responders in PB and 9 months for non-responders; 1-year-EFS was 68% (95% CI; 49 - 88), for responders in PB and 42% (95% CI; 22 - 61) for non-responders (P = 0.05). The median EFS was 11 months both for molecular responders and non-responders in BM; 1-year-EFS was 52% for responders in BM (CI; 30 - 73), and 43% (CI 33 - 71) for non-responders (P = 0.7). No clinical feature showed significant correlation with PB and BM molecular responses. This analysis shows that bcl-2 rearrangement in blood and bone marrow is frequently detected at staging, even in stage I disease. Absence of the bcl-2 rearrangement is related to a better EFS and the achievement of a molecular response in peripheral blood after therapy is associated with a better EFS.
Assuntos
Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/terapia , Estadiamento de Neoplasias/métodos , Idoso , Células da Medula Óssea/metabolismo , Intervalo Livre de Doença , Feminino , Rearranjo Gênico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Indução de Remissão , Resultado do TratamentoRESUMO
Outcome of systemic peripheral T-cell lymphomas (PTCL) is unsatisfactory and no controlled clinical study guides the therapy. Phase II studies suggest to consolidate response achieved after front-line treatment with stem cell transplant (SCT). We retrospectively evaluate the impact of front-line SCT consolidation in a single Center cohort of 209 patients treated during the last two decades. Median age was 49 years (range 15-85) with a prevalence of male sex (61%), advanced stage (68%) while IPI was >2 in 44%. Primary treatment was MACOP-B (39%) CHO(E)P (39%), intensive regimens (18%) or others (4%). Complete response to primary treatment (i.e. before SCT) was 60% (5% partial remission). Forty-four patients further proceeded to SCT while 92 did not receive consolidation. Outcome of primary responders was good, with a 3-year overall survival of 74% (82% in ALCL ALK+ and 69% for the other histologies). By multivariate analysis a better overall survival was significantly associated with IPI<2 (P=0.001), primary response (P=0.000), and ALCL ALK+ (P=0.012). The multivariate analysis performed on responders, showed that only IPI was predictive of a better survival while ALCL ALK+ and undergoing SCT were not. Response to primary treatment rather than post-remission programs is the crucial determinant of PTCL outcome.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Mesenchymal stromal cells (MSC) are tested in clinical trials to treat graft versus host disease (GvHD) after stem cell transplantation (SCT). In vitro studies demonstrated MSC's broad immunosuppressive activity. As infections represent a major risk after SCT, it is important to understand the role of MSC in this context. We analyzed 24 patients (pts) receiving MSC for GvHD in our Unit between 2009 and 2011. We recorded viral reactivations as measured in whole blood with polymerase chain reaction for 100 days following MSC administration. In patients with a documented viral reactivation in the first 3 days following MSCs infusion the frequency of virus-specific IFNgamma-producing cells was determined through enzyme-linked immunospot assay. In our cohort of patients viral reactivation after MSC infusion occurred in 45% of the cases, which did not significantly differ from the incidence in a historical cohort of patients affected by steroid resistant GvHD and treated with conventional immunosuppression. No patient presented severe form of infection. Two cases could be checked for immunological response to viral stimulus and demonstrated virus specific T-cytotoxic lymphocyte activity. In our experience MSC infusion did not prove to trigger more frequent or severer viral reactivations in the post transplantation setting.