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1.
Int J Lab Hematol ; 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33949096

RESUMEN

INTRODUCTION: Multiple flow cytometry scores/diagnostic systems for the classification of leukemic lymphoproliferative disorders (LPD) have been published but few have been compared between them. PATIENTS AND METHODS: We classified a cohort of leukemic LPD based on eleven published flow cytometry scores/diagnostic systems and compared their classification as chronic lymphocytic leukemia (CLL) or non-CLL LPD. RESULTS: 329 patients were included. Patients classified as CLL ranged from 46% to 73%, depending on the score/diagnostic system used. All eleven scores/diagnostic systems agreed in 184/324 (57%) of patients while in 58/324 (18%) at least two scores/diagnostic systems classified the patient differently (from the majority). Fleiss kappa was 0.74, but pairwise agreement was variable (Cohen's kappa: 0.48 to 0.87). CONCLUSION: This study found a suboptimal agreement between published flow cytometry scores/diagnostic systems for the classification of LPD.

2.
Leuk Lymphoma ; : 1-9, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33546574

RESUMEN

Findings regarding the role of sex in follicular lymphoma (FL) are contradictory and the prognostic value of sex among patients with early progression of disease (POD) remains unclear. We collected real-life data from nine hospitals in Finland and Spain including 1020 FL patients to study the influence of sex on disease outcome. The median follow-up duration was 67 months (range 0-226 months). Female patients showed better progression-free survival (PFS) (hazard ratio [HR], 0.720; 95% confidence interval [CI], 0.588-0.881), disease-specific survival (DSS) (HR, 0.653; 95% CI, 0.448-0.951), and overall survival (OS) (HR, 0.653; 95% CI, 0.501-0.853) than male patients. However, there were no significant sex differences in prognosis in patients with early POD. This study strengthens the understanding that male sex is an adverse prognostic factor for FL. However, this difference does not apply to patients with early POD.

3.
Cancer Med ; 10(4): 1314-1326, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33492774

RESUMEN

The use of non-pegylated liposomal doxorubicin (Myocet® ) in diffuse large B-cell lymphoma (DLBCL) has been investigated in retrospective and single-arm prospective studies. This was a prospective phase 2 trial of DLBCL patients ≥60 years old with left ventricular ejection fraction (LVEF) ≥55% randomized to standard R-CHOP or investigational R-COMP (with Myocet® instead of conventional doxorubicin). The primary end point was to evaluate the differences in subclinical cardiotoxicity, defined as decrease in LVEF to <55% at the end of treatment. Secondary objectives were efficacy, safety, and variations of troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and LVEF along follow-up. Ninety patients were included, 45 in each group. No differences were observed in the percentage of patients with LVEF <55% at end of treatment (11% in R-CHOP arm vs. 7% in R-COMP arm, p = 0.697) or at 4 months (10% vs. 6%, respectively, p = 0.667) and 12 months (8% vs. 7%, respectively, p = 1). However, a higher percentage of R-CHOP compared with R-COMP patients showed increased troponin levels in cycle 6 (100% vs. 63%, p = 0.001) and at 1 month after treatment (88% vs. 56%, respectively, p = 0.015). Cardiovascular adverse events were seen in five R-CHOP patients (nine episodes, four grade ≥3) and in four R-COMP patients (five episodes, all grade 1-2). No significant differences in efficacy were observed. In conclusion, R-COMP is a feasible immunochemotherapy schedule for DLBCL patients ≥60 years, with similar efficacy to R-CHOP. However, the use of non-pegylated doxorubicin instead of conventional doxorubicin was not associated with less early cardiotoxicity, although some reduced cardiac safety signals were observed. Trial registration: ClinicalTrials.gov Identifier: NCT02012088.

4.
Expert Rev Hematol ; 2020 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-33249940

RESUMEN

OBJECTIVES: CD43 can be useful in routine flow cytometry. We conducted a systematic review aiming to describe when CD43 is used by flow cytometry in malignant hematology and to determine its value in these settings. METHODS: Systematic review of MEDLINE (search "CD43" AND "flow cytometry," starting in 2010). RESULTS: Twenty-one of 103 entries retrieved were included in this systematic review. CD43 is used in 3 settings: 1) in the classification of mature B cell lymphoproliferative disorders, 2) as part of a strategy to quantify residual disease in chronic lymphocytic leukemia (CLL) and 3) to help classify CD10-positive B cell populations. In this section, the published data is summarized, the clinical usefulness in each of these settings is evaluated and illustrative cases are shown. CONCLUSION: CD43 has a growing role in the diagnosis and management of B cell malignancies; it has become essential for the classification of B cell lymphoproliferative disorders and may be of help in the differential diagnosis of CD10-positive lymphomas by FC. It is also required for optimal quantification of CLL residual disease, which will soon have therapeutic value.

6.
Blood Rev ; : 100778, 2020 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-33187810

RESUMEN

The clinical relevance of flow cytometry (FC)-based bone marrow involvement (BMI) in B cell non-Hodgkin lymphoma (B-NHL) is not well established. We conducted a systematic review of MEDLINE regarding the use of FC to establish BMI in B-NHL to determine the prevalence of BMI by FC, to understand the interrelation between FC and bone marrow biopsy (BMB), and to explore the prognostic impact of BMI by FC. Relevant exclusion criteria included publication before 2010. Eleven publications (of 18 screened) were included, with 2803 patients involved. Relevant methodological details were often unreported. The prevalence of BMI by FC varied based on histological subtypes included. The median kappa agreement between BMB and FC was 0.68 and the type of discordance (FC+/BMB- vs. FC-/BMB+) was highly variable across studies. Only 4 studies (all in diffuse large B cell lymphoma) assessed the prognostic impact of BMI by FC. Two found a worse prognosis for patients with FC+/BMB- than those without BMI. To conclude, studies assessing BMI by FC are retrospective, of low methodological quality and with heterogeneous findings.

8.
Artículo en Inglés | MEDLINE | ID: mdl-32961011

RESUMEN

INTRODUCTION: Pre-analytical and analytical errors can threaten the reliability of flow cytometry (FC) results. A potential solution to some of these is the use of dry, pre-mixed antibodies, such as the ClearLLab 10C system. The purpose of the present study was to compare the diagnostic performance of the ClearLLab 10C B cell tube with that of our standard laboratory practice. METHODS: We compared the diagnoses made with the ClearLLab 10C B cell tube (experimental strategy) with those made with standard laboratory practice (standard strategy). Samples were selected aiming for representation of the full spectrum of B cell disorders, with an emphasis on mature B cell malignancies, as well as healthy controls. RESULTS: We included 116 samples (34 normal controls, 4 acute lymphoblastic leukemias, 54 mature lymphoproliferative disorders in peripheral blood and bone marrow, 3 myelomas, 6 bone marrow samples with involvement by lymphoma and 1 with elevated hematogone count, 14 lymph node samples, 1 cerebrospinal fluid, and 1 pleural effusion). There were two diagnostic errors (1.7%). The agreement between the two strategies in the percentage of CD19 cells and fluorescence intensity of CD5, CD19, CD20, CD200, and CD10 was very good. CONCLUSIONS: In this study, the ClearLLab 10C B cell tube performed similarly to our standard laboratory practice to diagnose and classify mature B cell malignancies.

10.
Hematol Oncol ; 2020 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-32700331

RESUMEN

Current care for patients with follicular lymphoma (FL) offers most of them long-term survival. Improving it further will require careful patient selection. This review focuses on predictive biomarkers (ie, those whose outcome correlations depend on the treatment strategy) in FL, because awareness of what patient subsets benefit most or least from each therapy will help in this task. The first part of this review aims to summarize what biomarkers are predictive in FL, the magnitude of the effect and the quality of the evidence. We find predictive biomarkers in the setting of (a) indication of active treatment, (b) front-line induction (use of anthracyline-based regimens, CHOP vs bendamustine, addition of rituximab), (c) post-(front-line)induction (rituximab maintenance, radioimmunotherapy), and (d) relapse (hematopoietic stem cell transplant) and targeted agents. The second part of this review discusses the challenges of precision medicine in FL, including (a) cost, (b) clinical relevance considerations, and (c) difficulties over the broad implementation of biomarkers. We then provide our view on what biomarkers may become used in the next few years. We conclude by underscoring the importance of assessing the potential predictiveness of available biomarkers to improve patient care but also that there is a long road ahead before reaching their broad implementation due to remaining scientific, technological, and economic hurdles.

11.
Cytometry B Clin Cytom ; 98(5): 421-428, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32530577

RESUMEN

BACKGROUND: Within the hematopoietic compartment, fibromodulin (FMOD) is almost exclusively expressed in chronic lymphocytic leukemia (CLL) lymphocytes. We set out to determine whether FMOD could be of help in diagnosing borderline lymphoproliferative disorders (LPD). METHODS: We established 3 flow cytometry-defined groups (CLL [n = 65], borderline LPD [n = 28], broadly defined as those with CLLflow score between 35 and -20 or discordant CD43 and CLLflow, and non-CLL LPD [n = 40]). FMOD expression levels were determined by standard RT-PCR in whole-blood samples. Patients were included regardless of lymphocyte count but with tumor burden ≥40%. RESULTS: FMOD expression levels distinguished between CLL (median 98.5, interquartile range [IQR] 37.8-195.1) and non-CLL LPD (median 0.012, IQR 0.003-0.033) with a sensitivity and specificity of 1. Most borderline LPDs were CD5/CD23/CD200-positive with no loss of B-cell antigens and negative or partial expression of CD43. 16/22 patients with available cytogenetic analysis showed trisomy 12. In 25/28 (89%) of these patients, FMOD expression levels fell between CLL and non-CLL (median 3.58, IQR 1.06-6.21). DISCUSSION: This study could suggest that borderline LPDs may constitute a distinct group laying in the biological spectrum of chronic leukemic LPDs. Future studies will have to confirm these results with other biological data. Quantification of FMOD can potentially be of help in the diagnosis of phenotypically complex LPDs.

12.
J Immunother Cancer ; 8(1)2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32527933

RESUMEN

BACKGROUND: Acute myeloid leukemia (AML) is a hematopoietic malignancy which is biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies for patients with refractory or relapse (R/R) AML are challenging because of the absence of a universal pan-AML target antigen and the shared expression of target antigens with normal hematopoietic stem/progenitor cells (HSPCs), which may lead to life-threating on-target/off-tumor cytotoxicity. CD33-redirected and CD123-redirected CARTs for AML are in advanced preclinical and clinical development, and they exhibit robust antileukemic activity. However, preclinical and clinical controversy exists on whether such CARTs are myeloablative. METHODS: We set out to comparatively characterize in vitro and in vivo the efficacy and safety of 41BB-based and CD28-based CARCD123. We analyzed 97 diagnostic and relapse AML primary samples to investigate whether CD123 is a suitable immunotherapeutic target, and we used several xenograft models and in vitro assays to assess the myeloablative potential of our second-generation CD123 CARTs. RESULTS: Here, we show that CD123 represents a bona fide target for AML and show that both 41BB-based and CD28-based CD123 CARTs are very efficient in eliminating both AML cell lines and primary cells in vitro and in vivo. However, both 41BB-based and CD28-based CD123 CARTs ablate normal human hematopoiesis and prevent the establishment of de novo hematopoietic reconstitution by targeting both immature and myeloid HSPCs. CONCLUSIONS: This study calls for caution when clinically implementing CD123 CARTs, encouraging its preferential use as a bridge to allo-HSCT in patients with R/R AML.

14.
Pol Arch Intern Med ; 130(10): 878-886, 2020 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-32329983

RESUMEN

Atrial fibrillation and cancer are common comorbidities. Given an increased risk of arterial thrombosis caused by the former and an increased risk of bleeding in patients with the latter, the management of anticoagulation in patients in whom they coexist is complex. On the basis of generally low­quality evidence, numerous documents have been published in the past 3 years providing practice points for physicians to offer the best treatment plan to their patients. The present review begins with a summary of these recommendations and then proceeds to outline 9 practical challenges that fit into the larger questions of when and in whom anticoagulation is indicated, and what is the best agent in patients with atrial fibrillation and active cancer. For each of these 9 challenges, the evidence available is presented, the author's personal practical advice is given and the most pressing need to move the field forward is stated. I conclude by emphasizing the need for high­quality evidence and, more practically, by stressing 1) the importance of patient preference and values in the decision on whether and how to anticoagulate, and 2) the need for periodic reassessment of the benefits of anticoagulation with changes in cancer status and treatment plan.

16.
Leuk Lymphoma ; 61(6): 1277-1291, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31960713

RESUMEN

Venous thromboembolism (VTE) is a common complication of cancer. Its treatment is challenging because of the high risk for both VTE recurrence and bleeding. Evidence is particularly scarce for patients with hematological malignancies. This review aims to summarize new developments in anticoagulation for the prevention and treatment of VTE in patients with active cancer, largely derived from the formal introduction of direct anticoagulants (DOACs) in this population. We then offer our recommendations for the thromboprophylaxis and treatment of VTE in patients with hematological disorders (mature lymphoid disorders, plasma cell disorders, myeloproliferative neoplasms, myelodysplastic syndrome and acute leukemia/stem cell transplant). We conclude by emphasizing the lack of high-quality evidence in a majority of these settings, caution about the use of DOACs in clinical situations where evidence is lacking and, finally, note the importance of involving patients in the decision-making process.

18.
Lab Med ; 51(4): 385-393, 2020 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-31834933

RESUMEN

BACKGROUND: Differences between follicular lymphoma (FL) and diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBL) by flow cytometry are underexplored. METHODS: We retrospectively assessed flow cytometry results from 191 consecutive lymph node biopsies diagnosed with FL or DLBCL/HGBL. RESULTS: The only parameters that differed between the 2 groups in the derivation cohort were forward scatter and side scatter (P < 10-6; area under the curve [AUC], 0.75-0.8) and %CD23 (P = .004; area under the receiver characteristic operating curve, 0.64). However, since light scatter characteristics did not distinguish between grade 3 FL and DLBCL/HGBL, we set out to develop a model with high sensitivity for the exclusion of the latter. Several models, including FS and %CD23, were tested, and 2 models showed a sensitivity of >0.90, with negative predictive values of ≥0.95, albeit with low specificity (0.45 to 0.57). CONCLUSION: Two simple models enable the exclusion of DLBCL/HGBL with a high degree of confidence.

20.
Eur J Haematol ; 104(3): 198-206, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31769545

RESUMEN

OBJECTIVES: To clarify the impact of histological grades in follicular lymphoma. METHODS: We retrospectively analysed 250 patients diagnosed with FL treated with chemoimmunotherapy: 188 patients were grades 1-2 and 62 grade 3A. RESULTS: In our series, grade 3A FL patients were older, higher proportion of localised disease and lower bone marrow infiltration at diagnosis comparing grades 1-2 FL patients. Estimated six-year progression-free survival and time to progression showed no differences between both groups [grade 3A: 56% (95%CI: 39%-73%) and 51% (95%CI: 41%-61%) vs grades 1-2:55% (95%CI: 46%-63%) and 57% (95%CI: 49%-65%), P = .782 and P = .521, respectively]. Estimated six-year overall survival was lower, 76% (95%CI: 64%-88%) for the grade 3A group than grades 1-2 83% (95%CI: 77%-89%); P = .044. In addition to that, cumulative incidence curves of death not related to lymphoma at 10 years between groups were as follows: [0.26 (95%CI: 0.25-0.27) and 0.05 (95%CI: 0.04-0.06) for G3AFL and G1-2FL, respectively], P = .010. Grade 3A FL showed in PFS curve no relapses after 6 years. These results were absolutely reproduced in 199 patients receiving R-CHOP regimen as induction. CONCLUSIONS: Our results indicate similar long-term outcomes in terms of progression-free survival and time to progression in grades 1-2 and 3A. No relapses were observed in G3AFL group after 6 years.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Adulto , Anciano , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Causas de Muerte , Femenino , Humanos , Quimioterapia de Inducción , Linfoma Folicular/mortalidad , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
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