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Patients with FLT3-mutated acute myeloid leukaemia (AML) that relapse or are refractory (R/R) to intensive induction have poor outcomes. Gilteritinib has recently become standard-of-care for patients with R/R FLT3-mutated AML. We investigated whether adding venetoclax to gilteritinib (gilt-ven) improves outcomes as compared with gilteritinib monotherapy. We included patients treated with gilteritinib (n = 19) and gilt-ven (n = 17) for R/R AML after intensive chemotherapy. Gilteritinib and gilt-ven groups did not differ in terms of mCRc rates (53% and 65%, p = 0.51) and realization of allogeneic haematopoietic stem-cell transplantation (HSCT, 47% and 35%, p = 0.5). Overall survival (OS) was comparable between groups, although a trend towards better OS was seen with gilt-ven (12-month OS 58.8% [95% CI 39.5%-87.6%]) versus gilteritinib (42.1% [95% CI 24.9%-71.3%] for gilteritinib). Early salvage with gilt-ven versus any other gilteritinib-based approach was associated with the best outcome (p = 0.031). Combination therapy was associated with increased haematological toxicity. In summary, gilt-ven did not improve remissions or HSCT-realization rates in patients with R/R FLT3-mutated AML as compared with gilteritinib and was associated with increased haematological toxicity. Although OS did not differ, a trend towards better survival was suggested with gilt-ven and a survival benefit was shown for gilt-ven approach when sequenced early for salvage.
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INTRODUCTION: Hemato-oncology patients are vulnerable to bloodstream infections due to immunocompromised state and use of intravascular catheters. Data regarding risk of infective endocarditis (IE) among those with gram positive bacteremia is limited. We aimed to evaluate the incidence of IE among neutropenic hemato-oncology patients, and to explore the yield of echocardiogram in this population. METHODS: we conducted a single retrospective study of all hospitalized hemato-oncology neutropenic patients with gram positive blood cultures between 2007 and 2021. Data regarding Patients' characteristics, blood cultures and echocardiogram was collected. RESULTS: Study included 241 patients, with 283 isolates. Coagulase negative staphylococcus (CONS) were the most commonly isolates found, followed by streptococcus viridans. Trans thoracic echocardiography (TTE) was performed in 45% of patients overall, of which 5.8% had additional Trans esophageal echocardiogram (TEE). Only a single case of IE was identified; 47 y/o multiple myeloma patient with neutropenic fever, streptococcus viridans bacteremia, and stroke caused by septic emboli. TTE and TEE failed to demonstrate valvular pathology consistent with IE. Conclusion In our experience, the yield of echocardiogram in hemato-oncological neutropenic patients with bacteremia is extremely low, owing to reduced probability of IE in this population, and thus could be avoided in most cases.
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INTRODUCTION: Using immunotherapy to fight cancer, and specifically, the use of engineered T-cells expressing a chimeric receptor against an antigen found on malignant cells (chimeric antigen receptor, CAR-T cells) constitutes a significant breakthrough in the treatment of the disease. In recent years, several CAR-T therapies have been approved in Europe and the USA, and some are already approved and funded through the national health basket in Israel, for the indications of diffuse large B-cell lymphoma, mantle cell lymphoma and B-cell acute lymphoblastic leukemia, after the failure of at least two lines of treatment. The treatment with CAR-T cells achieves prolonged remissions and even long-term cure of patients who had a very poor prognosis. However, the treatment involves significant side effects, and requires specific expertise in the management of patients both during the period of preparation for cell transplantation, and following the treatment. During the immediate post-infusion period, the most common adverse reactions are cytokine release syndrome (CRS) which stems from the activation of the immune system, and neurological toxicity that can accompany CRS. These effects require close monitoring, grading their severity, and providing anti-cytokine therapy or steroid therapy until control of symptoms is achieved. Later effects can be persistent cytopenias, immune over-activation, and prolonged immune deficiency. Treatments for additional indications and new CAR-T constructs are being developed and will allow more effective and safer treatment. This article summarizes the principles for CAR-T administration that, as currently provided in Israel, include the short- and long-term follow-up of the patients.
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Neoplasias Hematológicas , Receptores de Antígenos Quiméricos , Medicina Transfusional , Humanos , Adulto , Israel , Linfócitos B , Neoplasias Hematológicas/terapiaRESUMO
OBJECTIVES: To evaluate the role of additional chemotherapy before autologous hematopoietic cell transplantation (HCT) in patients with relapse/refractory diffuse large B-cell lymphoma (DLBCL) who achieve partial remission following first salvage therapy. METHODS: We conducted a multicenter retrospective study of all adult patients with DLBCL who underwent HCT between 2008 and 2020 and achieved partial response (PR) after the first salvage and were either referred directly to HCT (n = 47) or received additional salvage therapy before HCT (n = 22). RESULTS: Post-HCT CR rate and progression-free survival were comparable between the two groups (66% vs. 68%, p = .86 and median not reached vs. 10.2 months [95% confidence interval, CI 7.1-12.3], p = .27, respectively). Median overall survival (OS) and estimated 3-year OS favored patients who were directly referred to HCT (105.8 [95% CI 63-148] months vs. 14.5 [95% CI 0-44] months, p = .035, and 65% [95% CI 51%-75%] vs. 40% [95% CI 21%-53%], p = .035, respectively). In Cox regression model, while International Prognostic Index and primary refractory versus relapse disease did not impact OS, allocation to a second salvage regimen and older age were both associated with inferior survival (hazard ratio [HR] = 2.57 95% CI 1.1-5.8, p = .023 and HR = 1.04 95% CI 0.99-1.2, p = .064, respectively). CONCLUSIONS: Referring patients with chemotherapy-sensitive disease in PR directly to HCT is associated with better OS compared to those receiving additional lines of treatment.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Recidiva Local de Neoplasia , Adulto , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Transplante AutólogoRESUMO
Viridans group streptococci (VGS) bloodstream infection (BSI) in neutropenic patients can be a severe complication. A higher prevalence of vancomycin use has been reported due to reduced susceptibility to penicillin. We aimed to assess the impact on mortality of both penicillin minimal inhibitory concentration (MIC) and the use of vancomycin. We conducted a retrospective multicenter study including consecutive neutropenic patients with VGS BSI between 2007 and 2019. Univariable and multivariable analyses were conducted to evaluate risk factors for mortality, including penicillin susceptibility as an independent variable. Non-susceptibility to penicillin was defined as MIC ≥ 0.25. We included 125 neutropenic patients with VGS BSI. Mean age was 53 years and ~ 50% were women. Overall, 30-day mortality rate was 25/125 (20%), and 41 patients (33%) had a VGS isolate non-susceptible to penicillin. In univariable analysis, no significant association was demonstrated between penicillin non-susceptibility and mortality (9/25, 26% vs. 32/100, 32%, p = 0.81). Among patients with a non-susceptible strain, the use of vancomycin was not significantly associated with mortality (empirical, p = 0.103, or definitive therapy, p = 0.491). Factors significantly associated with increased mortality in multivariable analysis included functional status (ECOG > 1, adjusted odds ratio [aOR] 12.53, 95% CI 3.64-43.14; p < 0.0001); allogeneic transplantation (aOR 6.33, 95% CI 1.96-20.46; p = 0.002); and co-pathogen in blood cultures (aOR 3.99, 95% CI 1.34-11.89; p = 0.013). Among neutropenic hemato-oncological patients with VGS BSI, penicillin non-susceptibility and the use of vancomycin were not associated with mortality. Thus, vancomycin should not be used routinely as empirical therapy in neutropenic patients with suspected VGS BSI.
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Sepse , Infecções Estreptocócicas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Penicilinas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Estreptococos Viridans , Sepse/tratamento farmacológico , Testes de Sensibilidade MicrobianaRESUMO
INTRODUCTION: Extracorporeal photopheresis (ECP) is considered an effective treatment for patients with chronic graft vs host disease (cGVHD) and demonstrates efficacy in ameliorating GVHD. The mechanism by which ECP acts against cGVHD is not fully understood. Preliminary observations have hinted at the potential involvement of neutrophil extracellular traps (NETs) formation in the pathogenesis of cGVHD. We aimed to assess the influence of ECP on the formation of NETs in patients with cGVHD as a potential mechanism in this setting. METHODS: Patients treated with ECP for cGVHD at the Rabin Medical Center were included in this study. Blood samples were obtained at three different time points: before starting an ECP cycle, at the end of the first day of treatment, and 24 h following the initiation of the ECP treatment cycle. Neutrophils were harvested from all blood samples. NET formation was assessed by measurement of NET-bound specific neutrophil elastase activity and by immunofluorescence staining. RESULTS: Six patients (two females and four males) with cGVHD were included in the study. We observed a significant increase in NET formation among all six patients following ECP. Net-bound specific neutrophil elastase activity was elevated from a median value of 2.23 mU/mL (interquartile range [IQR] 2.06-2.47 mU/mL) at baseline to a median value of 13.06 mU/mL (IQR 10.27-15.97 mU/mL) immediately after the treatment and to a peak median value of 14.73 mU/mL (IQR 9.6-22.38 mU/mL) 24 h following the initiation of the ECP cycle. A qualitative assessment of NET formation using immunofluorescence staining has demonstrated markedly increased expression of citrullinated histone H3, a marker of NET formation, following ECP treatment. CONCLUSIONS: Our preliminary data indicate that ECP induces NET formation among patients with cGVHD. The contribution of increased NET formation to the therapeutic effect of cGVHD should be further investigated.
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Treatment with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered standard of care (SOC) second-line treatment for relapsed or refractory large B-cell lymphoma (LBCL). However, outcomes remain suboptimal. A systematic review and meta-analysis of randomised controlled trials comparing efficacy and safety of SOC versus chimeric antigen receptor T-cell (CAR-T) therapy as second-line for patients with LBCL refractory or relapsing within 12 months. Outcomes included overall survival (OS), event-free survival (EFS), overall response rate (ORR) and safety. Three trials published in 2021 (involving 865 participants) fulfilled the eligibility criteria. EFS as well as OS were significantly improved with CAR-T therapy as compared to SOC, hazard ratio (HR) 0.57 (95% confidence interval [CI] 0.49-0.68) and HR 0.77 (95% CI 0.60-0.98) respectively. CAR-T therapy was associated with significantly better ORR, relative risk (RR) 1.55 (95% CI 1.12-2.13, p = 0.001). The risk of Grade III/IV adverse event was comparable between the two arms, RR 1.03 (95% CI 0.93-1.14). In summary, CAR-T therapy has superior outcomes as compared to SOC in patients with LBCL refractory or relapsing within 12 months, without excess of toxicity. Longer follow-up is needed to confirm these results and determine the optimal sequencing of CAR-T therapy in the management of LBCL.
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Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Antígenos CD19 , Humanos , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/terapia , Recidiva Local de Neoplasia/terapia , Receptores de Antígenos de Linfócitos T , Padrão de Cuidado , Transplante AutólogoRESUMO
The combination of hypomethylating agents and venetoclax has revolutionized the therapeutic landscape of acute myeloid leukemia (AML), especially for patients previously deemed unfit for curative-intent treatment. Some of these patients undergo allogeneic hematopoietic cell transplant (alloHCT); yet, there are scarce data regarding transplantation outcomes. We conducted a multicenter nationwide retrospective cohort study, including patients with AML who underwent alloHCT in CR1 after frontline treatment with azacitidine plus venetoclax only (aza-ven group). We collected a historical control group of patients who achieved CR1 after first-line intensive chemotherapy only, followed by alloHCT (intensive group). Patients in the aza-ven group (n = 24) were transplanted between 2019 and 2021. Compared to the intensive group, patients in the aza-ven group were older (median age 71.7 vs. 58.4 years), had higher incidence of therapy-related AML and AML with antecedent hematologic disorder and had more often adverse cytogenetics. They had a higher percentage of allografts from matched-unrelated donors, and reduced intensity conditioning was more commonly used. The estimated 12 months non relapse mortality was 19.1% in the aza-ven group and 11.8% in the intensive group. The estimated 12 months relapse-free survival and overall survival were 58% and 63% in the aza-ven group and 54% and 70% in the intensive group, respectively. The cumulative incidence of acute GVHD at 6 months and of chronic GVHD at 12 months were 58% and 40% in the aza-ven group and 62% and 42% in the intensive group, respectively. Analysis of the aza-ven group revealed that HCT-CI score and ELN risk category were predictive of RFS in both univariate analysis as well as multivariate analysis. Our data suggests that alloHCT for AML patients achieving first CR with aza-ven appears feasible, with short-term post-transplant outcomes similar to those expected after traditional intensive chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Sulfonamidas/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
Venetoclax in combination with intensive therapies is explored in both the upfront and relapse/refractory (R/R) setting, and available data suggest that such regimens are effective albeit with added hematological and infectious toxicity. We conducted a multicenter retrospective cohort study of patients with acute myeloid leukemia (AML) treated with venetoclax in combination with FLAG-IDA protocol. Twenty-five patients were included in this analysis (median age 53.4 years). Most patients were treated for R/R AML (n = 24, 96%) with a median of one (range 0-3) previous lines of therapy and 44% of patients (n = 11) having prior allogeneic hematopoietic cell transplantation (HCT). Median follow-up was 10 (range, 4-26) months. Platelet and neutrophil recovery were observed at a median of 31 (95% CI 17.6-38.3) and 23 (95% CI 20-28) days, respectively. The most common adverse events were infectious (blood stream infections, 48% and invasive fungal infections, 32%). Thirty-day mortality was 12%. Composite complete remission (CRc) was 72% for the entire cohort and 91% in patients treated for post-HCT relapse. Incidences of relapse-free and overall survival at 12 months were 67% (95% CI 58-76%) and 50% (95% CI 31-69%), respectively. Real-world data show that the addition of venetoclax to FLAG-IDA protocol is effective in patients with high-risk AML, most notably in the post-HCT relapse setting. Prophylaxis and surveillance for infections are crucial.
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Citarabina , Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Retrospectivos , SulfonamidasRESUMO
BACKGROUND: For patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) for acute myeloid leukemia (AML), disease relapse remains the most common reason for transplant failure and patient death. Recent randomized controlled trials (RCTs) have aimed to reduce the risk of relapse by means of post-transplant maintenance therapy. METHODS: We performed a systematic review and meta-analysis of RCTs comparing the efficacy and safety of maintenance with observation or placebo in patients with AML after allogeneic HSCT. We searched Cochrane Library, PubMed and conference proceedings up to Febuary 2021. RESULTS: Our search yielded five trials including 736 patients. Maintenance therapy consisted of tyrosine kinase inhibitors (TKIs) in 3 studies (sorafenib 2 studies; midostaurin 1 study) and hypomethylating agents (HMAs) in 2 studies (decitabine and azacytidine 1 study each). Maintenance therapy was associated with an improved overall survival (OS), HR = 0.61 (95% CI 0.47-0.80). Subgroup analysis revealed advantage in OS with either TKI or HMA maintenance. Relapse free survival (RFS) was also improved in the maintenance arm compared with the control arm HR = 0.51(95% CI 0.40 - 0.66). There was no difference between the two arms in overall grade 3/4 adverse events or overall infections, in grade 3/4 infections, or in acute and chronic graft versus host disease. CONCLUSIONS: Our meta-analysis shows that post-transplant maintenance therapy in AML patients is effective in improving RFS and OS, with a satisfactory safety profile.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva , SorafenibeRESUMO
The question of which chemotherapy induction provides the best results for indolent lymphoma patients is yet unanswered. Different regimens have been compared, none of which has been shown to improve overall survival. The use of bendamustine is growing. A number of trials evaluated its efficacy for patients with indolent B-cell lymphoid neoplasms, including chronic lymphocytic leukaemia (CLL). To evaluate the efficacy of bendamustine in that population we performed a systematic review and meta-analysis of 9 randomised controlled trials (2726 patients). Bendamustine was compared to fludarabine-containing regimens, CVP (cyclophosphamide, vincristine, prednisolone), CHOP (CVP+ doxorubicin) and chlorambucil. Due to insufficient reported data, six of the nine trials were included in analysis of overall survival. Bendamustine was associated with a prolonged overall survival, (hazard ratio 0·79, 95% confidence interval 0·65-0·95). Data regarding quality of life was reported for two trials, therefore too scarce to pool. The risk of neutropenia was reduced with bendamustine treatment compared to other chemotherapy. Bendamustine induction is an efficacious option for patients with indolent lymphoma, and CLL. Maintenance therapy was not evaluated after bendamustine induction, and potentially there is an interaction between the two. Chemotherapy-free approach was shown to be efficacious for patients with CLL, while toxicity with that approach is not negligible.
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Cloridrato de Bendamustina/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/mortalidade , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/metabolismo , Linfócitos B/patologia , Cloridrato de Bendamustina/efeitos adversos , Clorambucila/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma de Células B/metabolismo , Quimioterapia de Manutenção , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Vincristina/efeitos adversos , Vincristina/uso terapêuticoAssuntos
Antifúngicos , Aspergillus fumigatus , Sistema Enzimático do Citocromo P-450 , Farmacorresistência Fúngica , Proteínas Fúngicas , Mutação , Triazóis , Humanos , Masculino , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergillus fumigatus/genética , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/isolamento & purificação , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica/genética , Evolução Fatal , Proteínas Fúngicas/genética , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/microbiologia , Testes de Sensibilidade Microbiana , Neuroaspergilose/genética , Neuroaspergilose/microbiologia , Neuroaspergilose/tratamento farmacológico , Triazóis/farmacologia , Triazóis/uso terapêutico , AdultoRESUMO
We aimed to test the efficacy and toxicity of autologous hematopoietic cell transplant (HCT) in Multiple Myeloma (MM) patients aged ≥65 years compared to patients aged 60-64. Two hundred twenty consecutive patients (age ≥65, n = 87) with MM aged 60 and above, who underwent HCT as part of an upfront MM treatment, at four Israeli centers between 2000 and 2014 were included. A melphalan dose of 200 mg/m2 was more frequent in the 60-64 age group vs. the ≥65 age group (77 vs. 57%, p = 0.002). There were no differences between groups in median day of neutrophil engraftment, incidence of infections, grades 3-4 mucositis, cardiovascular events, or non-relapse mortality at 100 days post HCT (4.7, vs. 5%, p = 0.9). A similar rate of improvement in response level was observed (36, vs. 35%, p = 0.87). At 3 years post HCT progression-free survival (PFS) was higher in the 60-64 age group (42 vs. 29%, p = 0.04); however, it was no longer so after adjustment for disease status prior to HCT (p = 0.49). In a Multivariate analysis, melphalan doses and age did not predict PFS. There was no difference in overall survival (OS) between age groups (p = 0.2). We conclude that toxicity profile, response, PFS, and OS of HCT in aged ≥65 patients with myeloma is similar to patients aged 60-64.
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Transplante de Células-Tronco Hematopoéticas/tendências , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante/tendências , Idoso , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/mortalidade , Transplante Autólogo/efeitos adversos , Transplante Autólogo/mortalidade , Transplante Autólogo/tendências , Resultado do TratamentoRESUMO
Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a nonpsychotropic ingredient of Cannabis sativa, possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT. We conducted a phase II study. GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Patients transplanted from an unrelated donor were given low-dose anti-T cell globulin. CBD 300 mg/day was given orally starting 7 days before transplantation until day 30. Forty-eight consecutive adult patients undergoing alloHCT were enrolled. Thirty-eight patients (79%) had acute leukemia or myelodysplastic syndrome and 35 patients (73%) were given myeloablative conditioning. The donor was either an HLA-identical sibling (n = 28), a 10/10 matched unrelated donor (n = 16), or a 1-antigen-mismatched unrelated donor (n = 4). The median follow-up was 16 months (range, 7 to 23). No grades 3 to 4 toxicities were attributed to CBD. None of the patients developed acute GVHD while consuming CBD. In an intention-to-treat analysis, we found that the cumulative incidence rates of grades II to IV and grades III to IV acute GVHD by day 100 were 12.1% and 5%, respectively. Compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II to IV acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was .3 (P = .0002). Rates of nonrelapse mortality at 100 days and at 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients surviving more than 100 days, the cumulative incidences of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively. The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double-blind controlled study is warranted. (clinicaltrials.gov: NCT01385124).
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Anti-Inflamatórios/uso terapêutico , Canabidiol/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Adulto , Idoso , Aloenxertos , Ciclosporina/uso terapêutico , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Incidência , Infecções/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Purpose: We hereby describe a case of persistent cytomegalovirus (CMV) viremia and retinitis following allogeneic hematopoietic cell transplantation (HCT) that was successfully treated with infusion of CMV-specific cytotoxic T lymphocytes (CTL) despite previous treatment with Epstein Bar Virus (EBV) -specific CTL, which occurred 5 months earlier. Observations: Following several anti- viral medication treatment trials that failed to eradicate the infectious process, the patient was treated with infusions of CMV-CTL from a biobank of cryopreserved virus-specific cells. Shortly after the first infusion, a remarkable response was noted. A few days after the second infusion, the retinitis resolved completely. No recurrence was noted at the one-year follow-up, and there was no evidence of GVHD. Conclusions and importance: The case is unique for two reasons: use of virus-specific CTL for an indication of CMV retinitis; and successive administration, in the same patient, of third-party virus-specific CTL to treat two different infections (Epstein-Barr virus and cytomegalovirus) on two separate occasions following hematopoietic cell transplantation.
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We aimed to describe the current status of infection prevention practices among EBMT centers. Questionnaires were distributed to all 553 EBMT transplant centers to capture clinical practices regarding antimicrobial prophylaxis, protective measures, isolation procedures and growth-factor support of patients undergoing hematopoietic cell transplantation. Responses from 127 centers in 32 countries were obtained. Most centers housed patients in single rooms (autologous-82%; allogeneic-98%), with high-efficiency particulate air (HEPA)-filters (autologous-73%; allogeneic-100%) and positive pressure (autologous-61%; allogeneic-88%). Pre-engraftment G-CSF was utilized by 77 and 31% of centers after autologous and allogeneic transplantation, respectively (P < 0.00001). Antibacterial prophylaxis was provided by 57 and 69% (P = 0.086) of centers and antifungal prophylaxis by 65 and 84% (P = 0.0008) of centers, to patients undergoing autologous and allogeneic transplantation, respectively. Yet, 16 and 3% of centers provided neither antibacterial nor antifungal prophylaxis to patients undergoing autologous and allogeneic transplantation, respectively. Considerable variation existed between centers and across countries in antimicrobial prophylaxis practices, medications employed and duration of preventive therapy. There were considerable discordances between guidelines and daily practices. JACIE accredited and non-accredited centers did not differ significantly in their antimicrobial prophylaxis practices. Whether these differences between transplant centers translated into differences in infectious morbidity, mortality and financial costs, warrants further research.
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Anti-Infecciosos , Doenças Transmissíveis , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Antifúngicos/uso terapêutico , Inquéritos e Questionários , Anti-Infecciosos/uso terapêutico , Antibacterianos/uso terapêuticoRESUMO
Therapeutic options in relapsed refractory (R/R) light-chain (AL) amyloidosis patients are limited. Given the encouraging results in t(11;14) multiple myeloma and the high prevalence of t(11;14) in AL amyloidosis, venetoclax is an attractive treatment option in this setting. We report here the results of a multi-center retrospective study on 26 R/R AL amyloidosis patients treated off-label with venetoclax. The median lines of therapy prior to venetoclax was 3.5 (range 1-7), and 88% of our cohort had t (11;14). Twenty-two patients (85%) were previously treated with daratumumab. The overall hematologic response rate was 88%, 35% achieved a CR, and 35% achieved VGPR. The median event-free survival was 25 months (m) (95% CI 9.7 m-not reached), and the median overall survival was 33 m (95% CI 25.9-39.2 m). Most of the patients in this cohort are in ongoing deep responses and continuing venetoclax therapy. The treatment was relatively safe. One patient died due to infection, and there were two grade 3 infections in our cohort. Tumor lysis syndrome (TLS) was not seen in any patient. Dose reductions were frequent but did not affect the efficacy. These promising results require confirmation in a randomized controlled trial.
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Anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy has transformed the care of patients with relapsed/refractory large B cell lymphoma (LBCL). However, approximately 60% of CAR-T recipients ultimately will experience disease recurrence or progression. Salvage therapies after CAR-T treatment failures are of limited efficacy and have a short duration of response. The objective of the present study was to evaluate the role of allogeneic hematopoietic cell transplantation (allo-HCT) after CAR-T therapy in LBCL patients. This was a multicenter observational study reporting the outcome of 39 adult LBCL patients who underwent allo-HCT following anti-CD19 CAR-T therapy. The median patient age was 47 years (range, 20 to 68 years). HLA-matched sibling, HLA-matched unrelated, and alternative donors were used in 36%, 36%, and 28% of transplantations, respectively. Conditioning regimens were primarily of low or intermediate intensity. Disease status at allo-HCT was complete response in 41%, partial response in 38%, and progressive disease in 21%. Allo-HCT was performed at a median of 127 days (range, 82 to 206 days) after CAR-T therapy. A high incidence of hepatic toxicity (28%), including sinusoidal obstruction syndrome (15.4%; 95% confidence interval; [CI], 6.2% to 28.5%), was observed. The 1-year cumulative incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) was 38.5% (95% CI, 23.2% to 53.6%) and 15.4% (95% CI, 6.1% to 28.5%), respectively. The 2-year cumulative incidence of moderate-severe chronic GVHD was 11.1% (95% CI, 3.3% to 24.3%). Overall, 2-year nonrelapse mortality and relapse/progression incidence were 26% (95% CI, 13% to 41%) and 43% (95% CI, 27% to 59%), respectively. With a median follow-up of 32 months, the 2-year overall survival (OS) and progression-free survival (PFS) were 45% (95% CI, 31% to 66%) and 31% (95% CI, 19% to 50%), respectively. In multivariable analyses, pre-HCT elevated lactate dehydrogenase level and transformed lymphoma were predictive of OS and PFS, respectively. Our data suggest that allo-HCT after anti-CD19 CAR-T treatment failure is feasible with a relatively promising efficacy but possibly high toxicity rate.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Recidiva Local de Neoplasia/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Linfoma Difuso de Grandes Células B/terapiaRESUMO
To the best of our knowledge, this is the first published report of anti-immunoglobulin-like transcript 3 (ILT3)-induced myocarditis. A 48-year old female patient with refractory acute myeloid leukemia who was given a single dose of anti-ILT3 monotherapy presented with fever, hypotension, chest pain, and elevated cardiac biomarkers. Systolic bi-ventricular function was in normal limits. The patient was promptly treated with pulse dose steroids with a rapid hemodynamic and clinical improvement and declining levels of cardiac biomarkers. The diagnosis of acute myocarditis was confirmed using cardiac magnetic resonance imaging applying the revised Lake Lewis criteria. While larger-scale data are needed in order to assess the incidence, management and prognosis of anti-ILT-3 induced myocarditis, we believe a high level of suspicion for adverse non-target cardiac effects is required in patients receiving this novel class of drugs.