RESUMO
Prophylaxis with fluoroquinolone (FQ) for patients undergoing autologous stem cell transplantation (ASCT) remains controversial. We performed a retrospective review of patients undergoing ASCT with and without bacterial prophylaxis to compare endpoints of interest. In accordance with institutional policy, patients undergoing ASCT for multiple myeloma routinely receive levofloxacin prophylaxis during their period of neutropenia, whereas patients undergoing the ASCT for lymphoma do not. We retrospectively examined patients with multiple myeloma (MM) or lymphoma undergoing ASCT between July 2015 and July 2018 for evidence of positive blood cultures. A total of 172 patients underwent ASCT for lymphoma and 343 underwent ASCT for MM. The 2 cohorts were similar in terms of baseline characteristics. Almost 20% (35 of 172) of the patients with lymphoma and 5.2% (18 of 342) of those with MM had a bloodstream infection (BSI). BSI occurred an average of 2 days earlier in patients with lymphoma compared with patients with MM (day +5 versus day +7; P = .0003). The 2 cohorts recovered absolute neutrophil count at the same time. Hospital length of stay was 2 days shorter for patients with MM (median, 20 days versus 18 days; P = .01). The majority of the organisms were gram-negative in both cohorts. Of the organisms commonly tested for FQ sensitivity, only 1 of 25 was resistant in the lymphoma cohort, compared with 7 of 9 in the MM cohort (P < .0001), with 4 being multidrug resistant. The odds of developing a BSI were 4.6 times greater in the lymphoma cohort compared with the MM cohort (95% confidence interval [CI], 2.52 to 8.40; P < .0001). In total, 23 of 172 patients with lymphoma (13.4%) and 28 of 342 patients with MM (8.2%) developed Clostridium difficile infection (odds ratio, 1.73; 95% CI, .96 to 3.11; P = .066). Two infection-related deaths occurred in the MM cohort. Our data indicate that FQ prophylaxis reduces the risk of BSI in patients undergoing ASCT but increases the incidence of resistant organisms. We recommend routine antimicrobial prophylaxis in patients undergoing ASCT to reduce the risk of BSI, along with a systematic and regular review of outcomes.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Antibioticoprofilaxia , Fluoroquinolonas/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Transplante de Células-Tronco , Transplante AutólogoAssuntos
Antineoplásicos/uso terapêutico , Metilação de DNA/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Indução de Remissão , Resultado do TratamentoRESUMO
Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab tesirine (loncaT) are approved in R/R LBCL. The efficacy of these CD19 directed therapies in patients who relapse after CD19 directed CAR-T (CD19-CART) therapy is not well understood. We conducted a multi-center study of patients with R/R LBCL that received either tafa-len or loncaT at any timepoint for R/R disease after CD19-CART therapy. Fifty-three patients were included in this study with the median follow up of 56 (9.1-199) weeks from CAR-T infusion. Median number of systemic therapies pre-CAR-T therapy was 3 (range: 1-6); axicabtagene ciloleucel was the most utilized CAR-T product (n = 32,60%). Median time from CAR-T therapy to tafa-len or loncaT was 7.3 (1.2-38.2) months with median number of lines of therapy between CAR-T therapy and these regimens of 1 (0-5). Combined overall response rate and complete response rates were 27% and 10%, respectively. Median duration of response was 13.3 (2.1-56.7) weeks. In this real-world study, the use of currently approved CD19-directed therapies to treat R/R LBCL after CD19-CAR-T therapy showed limited clinical activity and duration of responses.
Assuntos
Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Antígenos CD19 , Terapia Baseada em Transplante de Células e Tecidos , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Receptores de Antígenos Quiméricos/uso terapêuticoRESUMO
We report an 85-year-old male, with history of interstitial pulmonary fibrosis (IPF), who was presented with progressive dyspnea, hypoxia, and anemia of 2 months duration. Six months before presentation, the patient was placed on Dabigatran etexilate (Dabigatran) (110 mg BID) for atrial fibrillation. His prior anemia workup included a negative upper endoscopy and colonoscopy. Bronchoscopy revealed copious amounts of bloody secretions. The bronchial tree was washed and Dabigatran was discontinued. The patient's medical condition improved and was subsequently discharged home. Our case illustrates the failure of current literature to predict the isolated bronchoalveolar bleed secondary to Dabigatran therapy.
Assuntos
Antitrombinas/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Benzimidazóis/efeitos adversos , Hemorragia/induzido quimicamente , Alvéolos Pulmonares , Fibrose Pulmonar/tratamento farmacológico , beta-Alanina/análogos & derivados , Idoso de 80 Anos ou mais , Anemia/tratamento farmacológico , Anemia/etiologia , Antitrombinas/administração & dosagem , Fibrilação Atrial/etiologia , Benzimidazóis/administração & dosagem , Dabigatrana , Dispneia/tratamento farmacológico , Dispneia/etiologia , Hemorragia/terapia , Humanos , Masculino , Fibrose Pulmonar/complicações , beta-Alanina/administração & dosagem , beta-Alanina/efeitos adversosRESUMO
Patients with thalassemia are often exposed to several risk factors for developing hepatocellular carcinoma (HCC) due to their repeated transfusions. However, even transfusion-independent patients with thalassemia intermedia (TI) can develop HCC, which is mainly attributed to a state of iron overload. We report here two cases and review the literature for the association between TI and HCC. Along with our cases, a total of 36 cases of HCC in thalassemic patients were reported in the literature. Of these, 22 (61%) were TI patients with 6 (27%) of them being hepatitis B and C negative. There was no consistency in their characteristics; therefore, we recommended screening thresholds for HCC in TI patients based on their total liver iron concentration (LIC).
Assuntos
Carcinoma Hepatocelular/etiologia , Sobrecarga de Ferro/complicações , Neoplasias Hepáticas/etiologia , Talassemia beta/complicações , Hematopoese Extramedular , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Reação TransfusionalRESUMO
Thalassemia intermedia is a genetically diverse group of diseases that is the result of an imbalance in the production of the alpha and beta chains with ensuing chronic hemolysis, ineffective erythropoiesis, and iron overload. Resulting complications include bone changes, hypercoagulability, and end-organ damage due to iron overload. This decade has witnessed major breakthroughs in the management of thalassemia. In this article, we examine these novelties in therapy including iron chelation therapy, stem cell transplant, and gene therapy. Iron chelation therapy has been revolutionized with the advent of deferasirox, a once-daily oral iron chelator, that has been shown to be safe and efficacious. Gene therapy was also at the core of this revolution with the discovery of novel gene elements and viral vectors allowing for better control and improved outcomes.
Assuntos
Países em Desenvolvimento , Terapia Genética , Transplante de Células-Tronco Hematopoéticas , Quelantes de Ferro/uso terapêutico , Talassemia beta/terapia , Animais , Humanos , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/genética , Camundongos , Talassemia beta/diagnóstico , Talassemia beta/genéticaRESUMO
Essential thrombocythemia is one of the myeloproliferative neoplasms with a plethora of thrombohemorrhagic complications.Hydroxyurea has been proven to be an effective treatment for this condition. However, it is not without side effects. We herein report 3 patients with essential thrombocythemia treated with hydroxyurea who developed refractory leg ulcers, and we outline their successful management. We also review the literature to shed light on the mechanism of this toxicity. Awareness of this important treatment complication is important to avoid the pitfall of futile invasive interventions.
RESUMO
In the last decade, chimeric antigen receptor-T (CAR-T) cells have revolutionized the treatment of hematological malignancies. With six different products for five diseases in various settings, CAR-T use has increased, and the comfort level of prescribers continues to expand. These therapies carry substantial toxicities that may limit their applicability to all patient populations. In the registrational trials, older adults are represented as part of a whole and risks specific to older age may not be clearly outlined. The aim of this review is to summarize the data from clinical trials, as well as real-life evidence, that outline the safety of CAR-T in older adults. With most of the data coming from CD19 CAR-T for diffuse large B-cell lymphoma, it appears that CAR-T can be safely administered to older individuals.
Assuntos
Neoplasias Hematológicas , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Idoso , Receptores de Antígenos Quiméricos/uso terapêutico , Receptores de Antígenos de Linfócitos T , Imunoterapia Adotiva/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Hematológicas/terapiaRESUMO
Autologous hematopoietic stem cell transplantation (ASCT) improves survival for patients with chemotherapy-sensitive lymphoma. Validated scoring systems are used in the clinical setting to predict treatment toxicity and survival; however, complications related to disease and treatment still occur, highlighting challenges in optimal patient selection and the need for novel predictors. Analysis of body composition and muscle mass can provide an objective assessment to identify vulnerable populations, as sarcopenia and frailty have been reported to predict outcomes in other tumor types. In this retrospective cohort study of patients undergoing ASCT for lymphoma, we investigated associations of sarcopenia with clinically significant outcomes, including overall survival (OS) and progression-free survival (PFS). Computed tomography (CT) images of 78 patients obtained routinely pretransplantation were used to assess skeletal muscle mass and are reported as skeletal muscle index (SMI). OS, PFS, and clinical outcomes of interest were compared between groups. Twenty-seven patients (34.6%) in the cohort met the criteria for sarcopenia. Patients with sarcopenia had a significantly shorter 3-year PFS (59% [95% confidence interval (CI), 38% to 75%] versus 84% [95% CI, 71% to 92%]; P = .02) after 3 years of follow up, whereas there was no difference in OS between patients with and those without sarcopenia (78% [95% CI, 57% to 89%] versus 88% [95% CI, 76% to 95%]; P = .25). Interestingly, no difference in survival was found with stratification based on the Karnofsky Performance Scale or Hematopoietic Cell Transplantation-Specific Comorbidity Index. There also were no significant between-group differences in length of hospital stay and the incidences of other clinical outcomes of interest, including febrile neutropenia, mucositis, total parenteral nutrition requirement, acute kidney injury, rate of readmission, or intensive care unit admission. This is the first study to our knowledge to correlate sarcopenia with disease control and PFS after ASCT in lymphoma. Possible explanations include a higher rate of chemotherapy-related toxicity, leading to disruptions of treatment as well as dysfunction of antitumor immunity secondary to impaired regulations from myokines from the loss of muscle mass or an unknown cause that is yet to be elucidated. Physical therapy programs and personalized regimens for treatment based on the analysis of body composition indices can be further studied and implemented to mitigate treatment-related toxicity and to optimize survival in patients with sarcopenia.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma , Sarcopenia , Humanos , Linfoma/terapia , Intervalo Livre de Progressão , Estudos Retrospectivos , Sarcopenia/complicações , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of many patients with aggressive relapsed or refractory large B-cell lymphoma (LBCL). Treatment can be complicated by clinically evident cytokine release syndrome (CRS), which is characterized by the development of fever, hypoxia, and hypotension, and can be life-threatening. Most patients treated with CAR-T cells develop CRS, which is thought to represent an immune phenomenon. It was previously unknown whether patients who did not develop CRS had reduced CAR-T cell activity and were therefore likely to have worse outcomes. We conducted a multicenter retrospective analysis of 352 adult patients treated at 8 academic medical centers in the United States who received axicabtagene ciloleucel or tisagenlecleucel for the treatment of LBCL. The outcomes of interest included progression-free survival, overall survival, complete response rate, and overall response rate. Of the included patients, 262 (74.4%) developed CRS. There was no significant difference in progression-free survival (P = .99) or overall survival (P = .16) between patients who developed CRS and those who did not develop CRS. Peak ferritin levels >5000 ng/mL during treatment and lactate dehydrogenase levels greater than the institutional upper limit of normal before lymphodepleting chemotherapy were associated with significantly worse progression-free and overall survival in the multivariate analysis. There was no significant difference in the complete response or overall response rates between patients who did and did not develop CRS. In this retrospective analysis, we report that patients who develop CRS have clinical outcomes similar to those of patients without CRS treated with commercial anti-CD19 CAR-T cells.
Assuntos
Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Adulto , Humanos , Estados Unidos , Receptores de Antígenos Quiméricos/uso terapêutico , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/terapia , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Antígenos CD19 , Terapia Baseada em Transplante de Células e TecidosRESUMO
Graft-versus-host disease (GVHD) is the major toxicity of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that a GVHD prophylaxis regimen of post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) would be associated with incidences of acute and chronic GVHD in patients receiving a matched or single antigen mismatched HCT. This Phase II study was conducted at the University of Minnesota using a myeloablative regimen of either total body irradiation (TBI) at a total dose of 1320 cGy, administered in 165-cGy fractions, twice daily from day -4 to day -1, or busulfan (Bu) 3.2 mg/kg daily (cumulative area under the curve, 19,000 to 21,000 µmol/min/L) plus fludarabine (Flu) 40 mg/m2 once daily on days -5 to -2, followed by a GVHD prophylaxis regimen of PTCy 50 mg/kg on days +3 and +4, Tac, and MMF beginning on day +5. The primary endpoint was the cumulative incidence of chronic GVHD necessitating systemic immunosuppression (IST) at 1 year post-transplantation. Between March 2018 and May 2022, we enrolled 125 pediatric and adult patients, with a median follow-up of 813 days. The incidence of chronic GVHD necessitating systemic IST at 1 year was 5.5%. The rate of grade II-IV acute GVHD was 17.1%, and that of grade III-IV acute GVHD was 5.5%. Two-year overall survival was 73.7%, and 2-year graft-versus-host disease-free, relapse-free survival was 52.2%. The 2-year cumulative incidence of nonrelapse mortality was 10.2%, and the rate of relapse was 39.1%. There was no statistically significant difference in survival outcomes between recipients of matched donor transplants versus recipients of 7/8 matched donor transplants. Our data show that myeloablative HCT with PTCy/Tac/MMF results in an extremely low incidence of severe acute and chronic GVHD in well-matched allogeneic HCT.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Criança , Tacrolimo/uso terapêutico , Ácido Micofenólico/uso terapêutico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Bussulfano/uso terapêuticoRESUMO
Celiac disease, an autoimmune disease once thought to be uncommon, is now being increasingly identified. Our improved diagnostic modalities have allowed us to diagnose more and more patients with atypical symptoms who improve on gluten-free diet (GFD). We discuss here the latest findings regarding the various hematological manifestations of celiac disease and their management. Anemia remains the most common hematological manifestation of celiac disease due to many mechanisms, and can be the sole presenting symptom. Other manifestations include thrombocytosis and thrombocythemia, leukopenia, thromboembolism, increased bleeding tendency, IgA deficiency, splenic dysfunction, and lymphoma. The diagnosis of celiac disease should always be kept in mind when a patient presents with unexplained and isolated hematological finding. Once diagnosed, patients should adhere to GFD and be educated about the potential complications of this disease. We herein present an algorithm for adequate management and follow-up.
Assuntos
Doença Celíaca/complicações , Doenças Hematológicas/etiologia , Anemia/etiologia , Doença Celíaca/sangue , Humanos , Deficiência de IgA/complicações , Leucopenia/complicações , Linfoma/complicações , Baço/fisiopatologia , Trombocitopenia/complicações , Trombocitose/complicações , Tromboembolia/complicaçõesRESUMO
Endothelial dysfunction is characterized by altered vascular permeability and prothrombotic, pro-inflammatory phenotypes. Endothelial dysfunction results in end-organ damage and has been associated with diverse disease pathologies. Complications observed after hematopoietic stem cell transplantation (HCT) and chimeric antigen receptor-T cell (CAR-T) therapy for hematologic and neoplastic disorders share overlapping clinical manifestations and there is increasing evidence linking these complications to endothelial dysfunction. Despite advances in supportive care and treatments, end-organ toxicity remains the leading cause of mortality. A new strategy to mitigate endothelial dysfunction could lead to improvement of clinical outcomes for patients. Statins have demonstrated pleiotropic effects of immunomodulatory and endothelial protection by various molecular mechanisms. Recent applications in immune-mediated diseases such as autoimmune disorders, chronic inflammatory conditions, and graft-versus-host disease (GVHD) have shown promising results. In this review, we cover the mechanisms underlying endothelial dysfunction in GVHD and CAR-T cell-related toxicities. We summarize the current knowledge about statins and other agents used as endothelial protectants. We propose further studies using statins for prophylaxis and prevention of end-organ damage related to extensive endothelial dysfunction in HCT and CAR-T.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Inibidores de Hidroximetilglutaril-CoA Redutases , Receptores de Antígenos Quiméricos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/genéticaRESUMO
Higher CD34 cell dose is associated with improved engraftment after peripheral blood allogeneic hematopoietic stem cell transplantation (alloHCT) but also may increase the risk of long-term complications, such as graft-versus-host disease (GVHD). Prior studies examining the relationship between CD34 cell dose and long-term survival outcomes have yielded conflicting results. In this study, we sought to clarify the prognostic impact of CD34 cell dose by examining a large contemporary cohort of patients undergoing alloHCT with a matched sibling peripheral blood stem cell (PBSC) donor. We retrospectively examined the impact of CD34 cell dose on overall survival (OS), neutrophil engraftment, platelet engraftment, treatment-related mortality, relapse, acute GVHD grade II-IV and III-IV, and chronic GVHD in 377 consecutive patients undergoing alloHCT with a PBSC graft source from a matched sibling donor at the University of Minnesota between 2002 and 2015. The patients were classified into 3 groups based on the tertile (T) of CD34 cell dose received: T1, <5 × 106 cells/kg; T2, 5 to 7.5 × 106 cells/kg; and T3, ≥7.5 × 106 cells/kg. Multivariable analysis demonstrated that high CD34 cell dose was associated with superior 5-year OS (hazard ratio [HR], 0.57; P = .01) and more rapid platelet engraftment (HR, 1.70; P < .01). Higher CD34 cell dose also was associated with improved absolute neutrophil count engraftment (T2: HR, 1.54; T3: HR, 1.52; P < .01). There was no association between CD34 cell dose and TRM or relapse at 5 years. Although higher CD34 cell dose was not associated with acute GVHD grade II-IV, it was associated with chronic GVHD (T2: HR, 1.68; T3: HR, 1.50; P = .04). Our data indicate that higher CD34 cell dose (>7.5 × 106/kg) is associated with superior OS at 5 years and improved engraftment but carries an increased risk of chronic GVHD. These data support a target CD34 cell dose goal of 7.5 × 106/kg for sibling PBSC graft donors.
Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Adulto , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recidiva Local de Neoplasia/complicações , Estudos RetrospectivosRESUMO
Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60-64; 65-69; 70+). With median follow-up of nearly 3 years, patients aged 60-64 had modestly, though significantly better OS, DFS and lower TRM than those either 65-69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Idoso , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Neoplasia Residual , Receptores de Complemento 3b/uso terapêutico , Recidiva , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversosRESUMO
CD33 is a transmembrane protein that is found on cells of myeloid lineage. It is also intensely expressed on acute myeloid leukemia (AML) progenitor cells but not on normal stem cells. It internalizes on binding and dimerization, making it a specific and ideal target for AML therapeutics and drug delivery. Several targeted therapies have been tested and many are still currently in development. Gemtuzumab ozogamicin was the first and only CD33-directed antibody-drug conjugate to be US Food and Drug Administration approved for AML. Other targeted agents have not achieved such success. Promising new strategies include cellular therapy mechanisms and linker molecules. This is an exciting target that requires a considerable amount of precision to yield clinical benefit.
Assuntos
Gemtuzumab/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/uso terapêutico , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Gemtuzumab/administração & dosagem , Gemtuzumab/efeitos adversos , Gemtuzumab/imunologia , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/uso terapêutico , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/administração & dosagem , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/efeitos adversos , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Células-TroncoRESUMO
INTRODUCTION: Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have poor outcomes. Treatment with CD19 chimeric antigen receptor (CAR-T) cells, tisagenlecleucel and axicabtagene ciloleucel, has been associated with improved outcomes. Cytopenias were observed in clinical trials with both products; however, little is known regarding the patterns and outcomes of these cytopenias. SUBJECTS AND METHODS: We reviewed DLBCL patients (n=32) receiving either product between January and September 2018 at our institution. RESULTS: Median duration of leukopenia, neutropenia, lymphopenia, anemia, and thrombocytopenia was 49, 9, 117.5, 125, and 95.5 days after CAR-T infusion, respectively. Filgrastim was used in 63% of patients, and 50% of patients received red cell or platelet transfusions. With the exception of neutropenia, increase in the duration of cytopenia of any lineage was associated with improvement in progression-free survival, and in overall survival in case of anemia. There was no association between the duration of cytopenias with either cytokine release syndrome or neurotoxicity. DISCUSSION: Our data suggest a correlation between cytopenias and survival outcomes after CD19 CAR-T therapy. If validated, cytopenia may be proven useful as a biomarker of response and survival after CAR-T therapy.
RESUMO
BACKGROUND: Newly diagnosed patients with acute myeloid leukemia (AML) who receive induction with a hypomethylating agent (HMA) are often neutropenic with an increased risk for invasive fungal infections (IFIs). This study analyzed the incidence and risk factors for IFIs in these patients, evaluated clinical patterns in antifungal prophylaxis, and assessed the diagnostic utility of tests in this setting. PATIENTS AND METHODS: We studied 117 newly diagnosed patients with AML treated with HMAs at our center, divided into groups based on concern for IFI (cIFI: all possible, probable, and proven IFIs) versus no concern for IFI. The Fisher exact test compared patients with cIFI versus without, and a multivariable logistic regression model estimated odds for cIFI. RESULTS: Sixty-seven (57%) patients had cIFI, with 48 possible IFIs, 17 probable, and 2 proven cases. There was no difference in incidence based on home zip code, but the presence of chronic obstructive pulmonary disease was highly associated with cIFI (P = .001), as was male gender (P = .01). Neutropenia at treatment initiation was borderline in significance (P = .08). In diagnostics, 9% of patients had positive serum fungal markers, and 30 patients underwent bronchoscopy, with only 27% of cases yielding positive results. There was a difference in treatment regimens between patients receiving antifungal prophylaxis with mold coverage versus without mold coverage with respect to cIFI (P = .04). CONCLUSIONS: cIFI in patients with AML treated with HMAs remains significant, especially in males and those with chronic obstructive pulmonary disease, who were found to be at higher risk. This may prompt clinicians to consider anti-mold prophylaxis in this setting.
Assuntos
Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Leucemia Mieloide Aguda/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/farmacologia , Feminino , Humanos , Incidência , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Initial therapy for acute myeloid leukemia (AML) remained stagnant for approximately four decades despite advances in improved understanding of pathogenesis and prognostication of the disease. Treatment has typically consisted of an anthracycline combined with continuous infusion of cytarabine for 7 days, the "7 + 3" regimen. Attempts have been made to improve on this regimen with modest improvements in response rates but no change in overalll survival, until the recent introduction of mutation-specific agents. However, the re-vamping of the delivery of both daunorubicin and cytarabine in a liposomal encapsulation, known as CPX-351, did show improvements of overall survival compared to traditional 7 + 3 in newly diagnosed secondary and therapy-related AML in patients aged 60-75. This led to the Food and Drug Administration (FDA) approval of the agent for both of these subtypes of AML in August of 2017. Herein we will review the rationale and preclinical development of CPX-351 and discuss the pivotal studies that led to its FDA approval.