RESUMO
ABSTRACT: Histologic transformation of Waldenström macroglobulinemia (HT-WM) carries a poor prognosis with standard treatments. Here, we report the first series of HT-WM treated with chimeric antigen receptor T cells showing a high efficacy and no unexpected toxicity.
Assuntos
Antígenos CD19 , Imunoterapia Adotiva , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/terapia , Macroglobulinemia de Waldenstrom/imunologia , Macroglobulinemia de Waldenstrom/patologia , Masculino , Idoso , Imunoterapia Adotiva/métodos , Feminino , Antígenos CD19/imunologia , Pessoa de Meia-Idade , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Linfócitos T/patologia , Resultado do TratamentoRESUMO
Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a major advance in the treatment of relapsed/refractory aggressive B-cell lymphomas. However, a significant number of patients experience failure. Among 550 patients registered in the French registry DESCAR-T, 238 (43.3%) experienced progression/relapse, with a median follow-up of 7.9 months. At registration, 57.0% of patients presented an age-adjusted International Prognostic Index of 2 to 3, 18.9% had Eastern Cooperative Oncology Group performance status ≥2, 57.1% received >3 lines of treatment prior to receiving CAR T-cells, and 87.8% received bridging therapy. At infusion, 66% of patients presented progressive disease, and 38.9% had high lactate dehydrogenase (LDH). Failure after CAR T-cell treatment occurred after a median of 2.7 months (range: 0.2-21.5). Fifty-four patients (22.7%) presented very early failure (day [D] 0-D30); 102 (42.9%) had early failure (D31-D90), and 82 (34.5%) had late (>D90) failure. After failure, 154 patients (64%) received salvage treatment: 38.3% received lenalidomide, 7.1% bispecific antibodies, 21.4% targeted treatment, 11% radiotherapy, and 20% immunochemotherapy with various regimens. Median progression-free survival was 2.8 months, and median overall survival (OS) was 5.2 months. Median OS for patients failing during D0-D30 vs after D30 was 1.7 vs 3.0 months, respectively (P = .0001). Overall, 47.9% of patients were alive at 6 months, but only 18.9% were alive after very early failure. In multivariate analysis, predictors of OS were high LDH at infusion, time to CAR-T failure Assuntos
Imunoterapia Adotiva
, Linfoma de Células B
, Humanos
, Imunoterapia Adotiva/efeitos adversos
, Recidiva Local de Neoplasia/patologia
, Antígenos CD19
, Linfócitos T
RESUMO
Distinguishing between follicular lymphoma (FL) and nodal marginal zone lymphoma (NMZL) can be difficult when morphologic and phenotypic features are unusual and characteristic cytogenetic rearrangements are absent. We evaluated the diagnostic contribution of ancillary techniques-including fluorescence in situ hybridization (FISH)-detected 1p36 deletion; reverse-transcriptase, multiplex, ligation-dependent probe amplification (RT-MLPA); and next-generation sequencing (NGS)-for tumors that remain unclassified according to standard criteria. After review, 50 CD5-negative small B-cell lymphoid neoplasms without BCL2 and BCL6 FISH rearrangements were diagnosed as FLs (n = 27), NMZLs (n = 5), or unclassified (n = 18) based on the 2016 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. FISH helped identify the 1p36 deletion in 3 FLs and 1 unclassified tumor. Most classified FLs had an RT-MLPA germinal center B-cell (GCB) signature (93%) or were noncontributive (7%). Classified NMZLs had an RT-MLPA activated B-cell signature (20%), had an unassigned signature (40%), or were noncontributive (40%). Among unclassified tumors, the RT-MLPA GCB signature was associated with mutations most commonly found in FLs (CREBBP, EZH2, STAT6, and/or TNFRSF14) (90%). An RT-MLPA-detected GCB signature and/or NGS-detected gene mutations were considered as FL identifiers for 13 tumors. An activated B-cell signature or NOTCH2 mutation supported NMZL diagnosis in 3 tumors. Combining the RT-MLPA and NGS findings successfully discriminated 89% of unclassified tumors in favor of one or the other diagnosis. NGS-detected mutations may be of therapeutic interest. Herein, we detected 3 EZH2 and 8 CREBBP mutations that might be eligible for targeted therapies.
Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma Folicular , Humanos , Hibridização in Situ Fluorescente , Reação em Cadeia da Polimerase Multiplex , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma Folicular/diagnóstico , Linfoma Folicular/genética , Sequenciamento de Nucleotídeos em Larga Escala , Deleção Cromossômica , RNA Polimerases Dirigidas por DNA , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-bcl-6RESUMO
The aim of this study was to evaluate the prognostic impact of the F-fluorodeoxyglucose positron emission tomography response at 1 month (M1) and 3 months (M3) after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a multicenter cohort of 160 patients with relapsed/refractory large B-cell lymphomas (R/R LBCL). In total, 119 (75%) patients reached M1 evaluation; 64 (53%, 64/119) had a complete response (CR); 91% were Deauville Score (DS) 1-3. Progressionfree survival (PFS) and overall survival (OS) were significantly worse in patients with DS-5 at M1, than in patients with DS 1-3 (PFS hazard ratio [HR]=6.37, 95% confidence interval [CI]: 3.5-11.5 vs. OS HR=3.79, 95% CI: 1.7-8.5) and DS-4 (PFS HR=11.99, 95% CI: 5.0-28.9 vs. OS HR=12.49, 95% CI: 2.8-55.8). The 1-year PFS rates were 78.9% (95% CI: 58.9-89.9) for DS-4 at M1, similar to 67.3% (95% CI: 51.8-78.8) for patients with DS 1-3 at M1, very different to 8.6% (95% CI: 1.8-22.4) for DS-5, respectively. Only eight of 30 (26%) patients with DS-4 progressed. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3.28, 95% CI: 1.5-7.0; P=0.003) but did not predict OS (HR=0.61, 95% CI: 0.2-2.3; P=0.45). Patients with a high baseline total metabolic tumor volume (TMTV) >80 mL had worse PFS (HR=2.05, 95% CI: 1.2-3.5; P=0.009) and OS (HR=4.52, 95% CI: 2.5-8.1; P<0.001) than patients with low TMTV. Multivariable analyses identified baseline elevated lactate dehydrogenase, DS-5, CAR T cells at M1 for PFS and baseline elevated lactate dehydrogenase, TMTV >80 mL, and DS-5 at M1 for OS. In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cell therapy.
Assuntos
Imunoterapia , Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons , Humanos , Lactato Desidrogenases , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Estudos Retrospectivos , Linfócitos T/metabolismoRESUMO
Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia (R/R BCP-ALL) have very poor outcome. Blinatumomab as single agent has shown activity in R/R BCP-ALL. We aimed to assess the activity of blinatumomab in concomitant association with intensive chemotherapy. Seventeen patients with R/R BCP-ALL were treated with combination of blinatumomab and VANDA (etoposide, cytarabine, mitoxantrone, dexamethasone and asparaginase) regimen. Complete remission (CR) was achieved in 14/17 patient (82%) and 11/17 (65%) were transplanted. One-year leukaemia-free survival was 58.8% for the whole cohort and 90.9% for transplanted patients. These preliminary data suggest that the VANDA-blinatumomab salvage regimen leads to a very high rate of CR and HSCT in suitable patients.
Assuntos
Anticorpos Biespecíficos , Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Adulto , Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , RecidivaRESUMO
Inactivated and fowlpox virus (FP)-vectored vaccines have been used to control H5 avian influenza (AI) in poultry. In H5 AI endemic countries, breeder flocks are vaccinated and therefore, maternally-derived antibodies (MDA) are transferred to their progeny. Results of three immunogenicity and one efficacy studies performed in birds with or without MDA indicated that the immunogenicity of an inactivated vaccine based on a H5N9 AI isolate (inH5N9) was severely impaired in chicks hatched from inH5N9-vaccinated breeders. This MDA interference was lower when breeders received only one administration of the same vaccine and could be overcome by priming the chicks at day-of-age with a live recombinant FP-vectored vaccine with H5 avian influenza gene insert (FP-AI). The interference of anti-FP MDA was of lower intensity than the interference of anti-AI MDA. The highest interference observed on the prime-boost immunogenicity was in chicks hatched from breeders vaccinated with the same prime-boost scheme. The level of protection against an antigenic variant H5N1 highly pathogenic AI isolate from Indonesia against which the FP-AI or inH5N9 alone was poorly protective could be circumvented by the prime-boost regimen in birds with either FP or AI MDA. Thus, the immunogenicity of vaccines in young chicks with MDA depends on the vaccination scheme and the type of vaccine used in their parent flocks. The heterologous prime-boost in birds with MDA may at least partially overcome MDA interference on inactivated vaccine.
Assuntos
Anticorpos Antivirais/biossíntese , Galinhas , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Aviária/prevenção & controle , Animais , Varíola Aviária/imunologia , Vírus da Varíola das Aves Domésticas/imunologia , Influenza Aviária/imunologia , Vacinas de Produtos Inativados/imunologiaRESUMO
Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.
Assuntos
Antígenos CD19 , Síndrome da Liberação de Citocina , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Antígenos CD19/imunologia , Prognóstico , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/imunologia , Síndrome da Liberação de Citocina/etiologia , Idoso , Adulto , Síndromes Neurotóxicas/etiologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , França , Idoso de 80 Anos ou mais , Receptores de Antígenos de Linfócitos TRESUMO
INTRODUCTION: Measurable residual disease (MRD) is becoming increasingly important in the chronic lymphocytic leukemia (CLL) context. It is of independent prognostic significance in terms of favorable progression-free and overall survival. The standardized methods used to assess CLL MRD are based on flow cytometry and real-time quantitative PCR. We here present a nine-color assay for CLL MRD with the ROR-1 marker antigen as recommended by the European Research Initiative (ERIC) on CLL; the sensitivity is at least 10-5. MATERIALS AND METHODS: We used 54 samples to develop a new principal component analysis (PCA) method based on the Kaluza© "radar" presentation mode. We used a Navios flow cytometer (Beckman Coulter©). RESULTS: We confirmed the linearity of our method over more than five dilutions. The specificity limit was 1.3×10-6 and the lower limit of detection was 3.6×10-6. Compared to the Boolean method, the sensitivity, specificity, and positive and negative predictive values of our PCA method were 100%. When MRD was detectable, PCA and Boolean assays were in agreement (linear regression, R2 = 0.99). CONCLUSION: We developed a new PCA-based method for detection of CLL MRD. Our method is comparable to that of the consensus method in terms of sensitivity, and it is also much easier and faster.
Assuntos
Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Análise de Componente Principal , Citometria de Fluxo/métodos , Reação em Cadeia da Polimerase em Tempo Real , Neoplasia Residual/diagnósticoRESUMO
Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to standard of care as second-line therapy in patients with high-risk relapsed/refractory (R/R) large B cell lymphoma (LBCL) considered eligible for autologous stem cell transplantation (ASCT); however, in clinical practice, roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT. The efficacy of axi-cel remains to be ascertained in transplant-ineligible patients. ALYCANTE, an open-label, phase 2 study, evaluated axi-cel as a second-line therapy in 62 patients with R/R LBCL who were considered ineligible for ASCT. The primary end point was investigator-assessed complete metabolic response at 3 months from the axi-cel infusion. Key secondary end points included progression-free survival, overall survival and safety. The study met its primary end point with a complete metabolic response of 71.0% (95% confidence interval, 58.1-81.8%) at 3 months. With a median follow-up of 12.0 months (range, 2.1-17.9), median progression-free survival was 11.8 months (95% confidence interval, 8.4-not reached) and overall survival was not reached. There was no unexpected toxicity. Grade 3-4 cytokine release syndrome and neurologic events occurred in 8.1% and 14.5% of patients, respectively. These results support axi-cel as second-line therapy in patients with R/R LBCL ineligible for ASCT. ClinicalTrials.gov Identifier: NCT04531046 .
Assuntos
Produtos Biológicos , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Humanos , Transplante Autólogo , Linfoma Difuso de Grandes Células B/terapia , Produtos Biológicos/uso terapêutico , Síndrome da Liberação de Citocina , Imunoterapia Adotiva/efeitos adversos , Antígenos CD19RESUMO
Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study ( NCT04328298 ). After 1:1 propensity score matching (n = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively (P < 0.001 for both ORR and CRR comparisons). After a median follow-up of 11.7 months, the 1-year progression-free survival was 46.6% for axi-cel and 33.2% for tisa-cel (hazard ratio (HR) = 0.61; 95% confidence interval (CI), 0.46-0.79; P = 0.0003). Overall survival (OS) was also significantly improved after axi-cel infusion compared to after tisa-cel infusion (1-year OS 63.5% versus 48.8%; HR = 0.63; 95% CI, 0.45-0.88; P = 0.0072). Similar findings were observed using the inverse probability of treatment weighting statistical approach. Grade 1-2 cytokine release syndrome was significantly more frequent with axi-cel than with tisa-cel, but no significant difference was observed for grade ≥3. Regarding immune effector cell-associated neurotoxicity syndrome (ICANS), both grade 1-2 and grade ≥3 ICANS were significantly more frequent with axi-cel than with tisa-cel. In conclusion, our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL.
Assuntos
Produtos Biológicos , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Antígenos CD19 , Produtos Biológicos/efeitos adversos , Estudos Clínicos como Assunto , Síndrome da Liberação de Citocina , Humanos , Imunoterapia Adotiva/efeitos adversos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Estudos Retrospectivos , Linfócitos TRESUMO
Mixtures of turkey herpesvirus (HVT) and Rispens poultry vaccines have been used worldwide for over 20 yr, mainly for vaccination of future layers and breeders. With increasing virulence of Marek's disease (MD) virus strains, vaccination strategies are evolving toward the use of vaccines combining HVT and Rispens. A single vaccination either in ovo or at 1 day of age with the HVT + infectious bursal disease (IBD) vector vaccine is efficient against IBD. However, with vaccination programs that include a hatchery administration of the HVT + IBD vaccine, additional protection against very virulent and very virulent-plus MD viruses is needed, especially for layers and breeders. This study looked at the combination of four commercially available Rispens vaccines with the HVT + IBD vector vaccine injected at 1 day of age. MD challenge tests that were superior to 90% in relative score in all the groups vaccinated with both vaccines showed that the mixture of HVT + IBD and Rispens vaccines had no effect on clinical protection against MD, and IBD challenge tests showed that the mixture of HVT + IBD and Rispens vaccines had no effect on clinical protection against IBD, which was equal to 100% protection in all the groups vaccinated with both vaccines.
Assuntos
Galinhas , Herpesvirus Meleagrídeo 1/imunologia , Vírus da Doença Infecciosa da Bursa/imunologia , Vacinas contra Doença de Marek/imunologia , Doenças das Aves Domésticas/prevenção & controle , Animais , Infecções por Birnaviridae/prevenção & controle , Infecções por Birnaviridae/veterinária , Feminino , Doença de Marek/prevenção & controle , Organismos Livres de Patógenos EspecíficosRESUMO
In this retrospective study, we report 70 cases of Epstein-Barr virus (EBV)+ diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) among 1696 DLBCL-NOS cases diagnosed between 2006 and 2019 (prevalence of 4.1%). At diagnosis, median age was 68.5 years; 79% of the cases presented with an advanced-stage disease (III-IV), 48% with extranodal lesions, and 14% with an hemophagocytic lymphohistiocytosis (HLH) (8 at diagnosis and 1 on therapy). A total of 46 cases presented a polymorphic pattern, and 21 were monomorphic. All had a non-germinal center B phenotype, with the majority of tumor cells expressing CD30 and programmed death ligand 1 (98% and 95%, respectively). Type II and III EBV latency was seen in 88% and 12% of the cases, respectively. Patients were treated with immunochemotherapy (59%) or chemotherapy (22%), and 19% received palliative care due to advanced age and altered performance status. After a median follow-up of 48 months, progression-free survival (PFS) and overall survival (OS) at 5 years were 52.7% and 54.8%, respectively. Older age (>50 years) and HLH were associated with shorter PFS and OS in multivariate analysis (PFS: hazard ratio [HR], 14.01; 95% confidence interval [CI], 2.34-83.97; and HR, 5.78; 95% CI, 2.35-14.23; OS: HR, 12.41; 95% CI, 1.65-93.53; and HR, 6.09; 95% CI, 2.42-15.30, respectively). Finally, using a control cohort of 425 EBV- DLBCL-NOS, EBV positivity was associated with a shorter OS outcome within patients >50 years (5-year OS, 53% [95% CI, 38.2-74] vs 60.8% [95% CI, 55.4-69.3], P = .038), but not in younger patients.
Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Difuso de Grandes Células B , Idoso , Herpesvirus Humano 4 , Humanos , Antígeno Ki-1 , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Estudos RetrospectivosRESUMO
Fowlpox (FP)-vectored avian influenza (FP-AI) vaccines are used in 1-day-old chickens, but they have also recently been shown to be immunogenic in ducks. The objectives of this work were 1) to evaluate safety and to compare the immunogenicity in ducks of three poxvirus vectors (fowlpox, canarypox, and vaccinia) expressing the same hemagglutinin gene from an H5N1 isolate, 2) to study the effect of the dose of the FP-AI and the presence of an adjuvant in 1-day-old Pekin ducks on antibody response after a boost with inactivated vaccine given 3 wk later, and 3) to confirm the immunogenicity of such a heterologous prime-boost vaccination scheme in 1-day-old Muscovy ducks. Immunogenicity induced by the three poxvirus vectors was comparable, and the FP vector was selected for the other studies. As published previously, there was a strong dose effect of the FP-AI priming on the hemagglutination inhibition (HI) titers induced after the boost with an inactivated vaccine. In contrast, the two tested adjuvants did not significantly increase the activity of FP-AI priming. The heterologous prime-boost regimen given to both Muscovy and Pekin ducklings at 1 and 14 or 21 days of age, respectively, was shown to be at least as immunogenic as two administrations of inactivated vaccines given at 2 and 5 wk of age. However, HI antibody titers were of short duration for both vaccine schemes, and their persistence was heterogeneous among individual birds.
Assuntos
Avipoxvirus , Patos/genética , Vacinas contra Influenza/imunologia , Influenza Aviária/prevenção & controle , Animais , Esquema de Medicação , Feminino , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/administração & dosagem , Fatores de Tempo , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologiaRESUMO
BACKGROUND: Patients presenting with acute myeloid leukemia (AML) at diagnosis are at high risk of severe complications and death, particularly with high white blood cell (WBC) count. In this retrospective study, we evaluate interest of early and systematic support in the intensive care unit (ICU) for AML with hyperleukocytosis (AML-HL) at diagnosis. METHODS: Patients with AML-HL, defined by WBC > 50 × 109/L, primary referred in ICU ("Early ICU") without organ failure and before initiating chemotherapy induction were compared to patients first admitted in the Hematology Department who required a secondary transfer in ICU ("Late ICU") or not ("No ICU"). Primary end point was mortality during the first month, and secondary end points were the use of life-sustaining therapies in ICU and risk factors for ICU transfer and mortality. RESULTS: One hundred fifty-four patients were included: 77 (50%) to the group "No ICU", 18 (12%) to "Late ICU" and 59 (38%) to "Early ICU". Mortality at day 30 was higher in "Late ICU" than in "Early ICU" and "No ICU", with 27.8%; 16.9% and 2.6% respectively (P < 0.001). "Late ICU" patients had an increased use of life-sustaining therapy comparing to "Early ICU" patients (56% vs. 29%, P = 0.04). CONCLUSIONS: Early referral to ICU reduces morbidity and seems an effective strategy to reduce short-term mortality in AML-HL at diagnosis.
RESUMO
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)-like, acute lymphoid leukemia (ALL)-like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])-like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.
Assuntos
Células Dendríticas/patologia , Leucemia/diagnóstico , Leucemia/terapia , Doença Aguda , Biomarcadores , Contagem de Células Sanguíneas , Medula Óssea/patologia , Aberrações Cromossômicas , Evolução Clonal/genética , Células Dendríticas/metabolismo , Gerenciamento Clínico , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunofenotipagem , Leucemia/etiologia , Leucemia/metabolismo , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Resultado do TratamentoRESUMO
The objective of this study was to compare the efficacy of two avian influenza (AI) H5-inactivated vaccines containing either an American (A/turkey/Wisconsin/68 H5N9; H5N9-WI) or a Eurasian isolate (A/chicken/Italy/22A/98 H5N9; H5N9-It). Three-week-old specific pathogen-free chickens were vaccinated once and challenged 3 wk later with a H5N1 highly pathogenic AI (HPAI) virus isolated from a chicken in Thailand in 2004. All unvaccinated challenged birds died within 2 days, whereas 90% and 100% of chickens vaccinated with H5N9-WI and H5N9-It, respectively, were protected against morbidity and mortality. Both vaccines prevented cloacal shedding and significantly reduced oral shedding of the challenge HPAI virus. Additional chickens (vaccinated or unvaccinated) were placed in contact with the directly challenged birds 18 hr after challenge. All unvaccinated chickens in contact with unvaccinated challenged birds died within 3 days after contact, whereas unvaccinated chickens in contact with vaccinated challenged birds either showed a significantly delayed mortality or did not become infected. All vaccinated contacts were protected against clinical signs, and most chickens did not shed detectable amount of HPAI virus. Altogether, these data indicate that both vaccines protected very well against morbidity and mortality and reduced or prevented shedding induced by direct or contact exposure to Asian H5N1 HPAI virus.