ABSTRACT
The long-term clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has been little explored. A prospective multicenter registry-based cohort study conducted from December 2020 to July 2022 by the Spanish Transplant and Cell Therapy group, was used to analyze the relationship of antibody response over time after full vaccination (at 3-6 weeks, 3, 6 and 12 months) (2 doses) and of booster doses with breakthrough SARS-CoV-2 infection in 1551 patients with hematological disorders. At a median follow-up of 388 days after complete immunization, 266 out of 1551 (17%) developed breakthrough SARS-CoV-2 infection at median of 86 days (range 7-391) after full vaccination. The cumulative incidence was 18% [95% confidence interval (C.I.), 16-20%]. Multivariate analysis identified higher incidence in chronic lymphocytic leukemia patients (29%) and with the use of corticosteroids (24.5%), whereas female sex (15.5%) and more than 1 year after last therapy (14%) were associated with a lower incidence (p < 0.05 for all comparisons). Median antibody titers at different time points were significantly lower in breakthrough cases than in non-cases. A serological titer cut-off of 250 BAU/mL was predictive of breakthrough infection and its severity. SARS-CoV-2 infection-related mortality was encouragingly low (1.9%) in our series. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant.
Subject(s)
COVID-19 , Humans , Female , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , SARS-CoV-2 , Cohort Studies , Prospective StudiesABSTRACT
We report our experience with venetoclax/hypomethylating agents (Ven/HMA) in 8 AML patients not candidates for intensive CT or refractory/relapsed with limited treatment options. The response rate was 50%. Venetoclax was well-tolerated in 62.5% of the patients. Ven/HMA provides a benefit particularly when used in patients without prior HMA exposure.
ABSTRACT
Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.
Subject(s)
Antineoplastic Agents , COVID-19 , Antibodies, Monoclonal , Antibodies, Viral , BNT162 Vaccine , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19 Vaccines , Early Detection of Cancer , Humans , SARS-CoV-2 , VaccinationABSTRACT
The hypomethylating agents, decitabine (DEC) and azacitidine (AZA), allowed more elderly acute myeloid leukemia (AML) patients to be treated. However, there are little direct comparative data on AZA and DEC. This multicenter retrospective study compared the outcomes of AZA and DEC in terms of response and overall survival (OS). Potential predictors associated with response and OS were also evaluated. A total of 626 AML patients were included (487 treated with AZA and 139 with DEC). Response rates were similar in both groups: CR was 18% with AZA vs. 23% with DEC (p = 0.20), CR/CRi was 20.5% vs. 25% (p = 0.27) and ORR was 32% vs. 39.5% (p = 0.12), respectively. Patients with leukocytes < 10 × 109/L, bone marrow blasts < 50% and ECOG ≥ 2 had higher ORR with DEC than with AZA. OS was similar in both groups: 10.4 months (95% CI: 9.2−11.7) vs. 8.8 months (95% CI: 6.7−11.0, p = 0.455), for AZA and DEC, respectively. Age (≥80 years), leukocytes (≥ 10 × 109/L), platelet count (<20 × 109/L) and eGFR (≥45 mL/min/1.73 m2) were associated with higher OS with AZA compared to DEC. In conclusion, we found no differences in response and OS rates in AML patients treated with AZA or DEC.
ABSTRACT
The effectiveness of venetoclax (VEN) in relapsed or refractory acute myeloid leukemia (RR-AML) has not been well established. This retrospective, multicenter, observational database studied the effectiveness of VEN in a cohort of 51 RR-AML patients and evaluated for predictors of response and overall survival (OS). The median age was 68 years, most were at high risk, 61% received ≥2 therapies for AML, 49% had received hypomethylating agents, and ECOG was ≥2 in 52%. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi), was 12.4%. Additionally, 10.4% experienced partial response (PR). The CR/CRi was higher in combination with azacitidine (AZA; 17.9%) than with decitabine (DEC; 6.7%) and low-dose cytarabine (LDAC; 0%). Mutated NPM1 was associated with increased CR/CRi. Median OS was 104 days (95% CI: 56-151). For the combination with AZA, DEC, and LDAC, median OS was 120 days, 104 days, and 69 days, respectively; p = 0.875. Treatment response and ECOG 0 influenced OS in a multivariate model. A total of 28% of patients required interruption of VEN because of toxicity. Our real-life series describes a marginal probability of CR/CRi and poor OS after VEN-based salvage. Patients included had very poor-risk features and were heavily pretreated. The small percentage of responders did not reach the median OS.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces higher morbidity and mortality in hematological malignancies, but evidence in acute myeloid leukemia (AML) is scarce. A multicenter observational study was conducted to determine the clinical outcomes and assess the impact of therapeutic approaches in adult AML patients with SARS-CoV-2 infection in the first wave (March-May 2020). Overall, 108 patients were included: 51.9% with active leukemia and 70.4% under therapeutic schedules for AML. Signs and symptoms of SARS-CoV-2 were present in 96.3% of patients and 82.4% received specific treatment for SARS-CoV-2. The mortality rate was 43.5% and was correlated with age, gender, active leukemia, dyspnea, severe SARS-CoV-2, intensive care measures, neutrophil count, and D-dimer levels. A protective effect was found with azithromycin, lopinavir/ritonavir, and normal liver enzyme levels. During the SARS-CoV-2 first wave, our findings suggested an increased mortality in AML in a short period. SARS-CoV-2 management could be guided by risk factors in AML patients.
Subject(s)
COVID-19 , Leukemia, Myeloid, Acute , Adult , Humans , Leukemia, Myeloid, Acute/epidemiology , Leukemia, Myeloid, Acute/therapy , Lopinavir , Risk Factors , SARS-CoV-2ABSTRACT
El tratamiento con metotrexato (MTX) a dosis elevadas implica una monitorización estrecha de los niveles del fármaco para confirmar su correcta eliminación. Uno de los posibles efectos secundarios es el fracaso renal, lo que ocasiona una acumulación de fármaco y un mayor efecto tóxico. La glucarpidasa (carboxipeptidasa-G2 o CPDG2) es una enzima recombinante que se utiliza para disminuir los niveles de MTX en pacientes que desarrollan fallo renal durante el tratamiento con altas dosis de MTX. La enzima reduce la concentración de MTX en un 95-99% de 15 a 30min después de la dosis. La glucarpidasa escinde el MTX en glutamato y ácido 2,4-diamino-N10-metilpteroico un metabolito menor e inactivo. Es conocida la reactividad cruzada del ácido 2,4-diamino-N10-metilpteroico en la medición de MTX mediante ensayos inmunológicos, que da lugar a una enorme sobreestimación de MTX. Sin embargo, los ensayos inmunológicos son la técnica mayoritariamente empleada en los laboratorios clínicos para la medición de MTX. Se presenta un caso de interferencia explicando la detección de MTX en las muestras de suero mediante cromatografía líquida acoplada a espectrometría de masas (LC-UHR-QTOF)
High-dose methotrexate (MTX) treatment involves close monitoring of drug level in order to confirm its proper elimination. One of the possible side effects of this therapy is renal failure, causing accumulation of the drug, and therefore is a mayor toxic effect. Glucarpidase (carboxypeptidase-G2 or CPDG2) is a recombinant enzyme used to reduce MTX serum levels in patients who develop acute renal failure during high-dose MTX treatment. The enzyme reduces MTX concentration by 95-99% within 15-30minutes after the dose. Glucarpidase cleaves MTX into glutamate and 2,4-diamino-N10-methylpteroic acid, a minor and non-active metabolite. Cross-reactivity of 2,4-diamino-N10-methylpteroic acid in immunological assays of MTX has been previously reported, and is said to cause an enormous overestimation in serum MTX analysis. However immunoassay is a widely used technique for MTX analysis, being the main method for its determination in most clinical laboratories. An interference case report is presented and MTX analysis in serum samples by liquid chromatography coupled with Ultra-High Resolution Q-Time of Flight Mass Spectrometry (LC-UHR-QTOF) is described
