Feasibility and outcomes after dose reduction of immunochemotherapy in young adults with Burkitt lymphoma and leukemia: results of the BURKIMAB14 trial.

High dose-intensive or infusional intermediate-dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non-bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose-intensity of chemotherapy was reduced in patients ≤55 years old after achieving complete metabolic response (CMR). Their outcomes were compared with those of similar patients included in the former BURKIMAB08 trial, in which there was no dose reduction. CMR was attained in 86 of 107 (80%) patients (17/19 in localized stages and 69/88 in advanced stages). Patients from the BURKIMAB14 trial ≤55 years old showed similar overall survival (OS), fewer infections and cytopenias than patients from the BURKIMAB08 trial. Patients >55 years old had a significantly higher treatment- related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4-year OS probability was 73% (range, 63-81%). Age (≤55 vs. >55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV-positive versus HIV-negative patients. The results of BURKIMAB14 are similar to those of other dose-intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473).

The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations.

Chromosome banding analysis and genomic microarrays are both useful but not equivalent methods for genomic complexity risk stratification in chronic lymphocytic leukemia patients.

Genome complexity has been associated with poor outcome in patients with chronic lymphocytic leukemia (CLL). Previous cooperative studies established five abnormalities as the cut-off that best predicts an adverse evolution by chromosome banding analysis (CBA) and genomic microarrays (GM). However, data comparing risk stratification by both methods are scarce. Herein, we assessed a cohort of 340 untreated CLL patients highly enriched in cases with complex karyotype (CK) (46.5%) with parallel CBA and GM studies. Abnormalities found by both techniques were compared. Prognostic stratification in three risk groups based on genomic complexity (0-2, 3- 4 and ≥5 abnormalities) was also analyzed. No significant differences in the percentage of patients in each group were detected, but only a moderate agreement was observed between methods when focusing on individual cases (κ=0.507; P<0.001). Discordant classification was obtained in 100 patients (29.4%), including 3% classified in opposite risk groups. Most discrepancies were technique-dependent and no greater correlation in the number of abnormalities was achieved when different filtering strategies were applied for GM. Nonetheless, both methods showed a similar concordance index for prediction of time to first treatment (TTFT) (CBA: 0.67 vs. GM: 0.65) and overall survival (CBA: 0.55 vs. GM: 0.57). High complexity maintained its significance in the multivariate analysis for TTFT including TP53 and IGHV status when defined by CBA (hazard ratio [HR] 3.23; P<0.001) and GM (HR 2.74; P<0.001). Our findings suggest that both methods are useful but not equivalent for risk stratification of CLL patients. Validation studies are needed to establish the prognostic value of genome complexity based on GM data in future prospective studies.

Adherence to the Western, Prudent, and Mediterranean dietary patterns and chronic lymphocytic leukemia in the MCC-Spain study.

Diet is a modifiable risk factor for several neoplasms but evidence for chronic lymphocytic leukemia (CLL) is sparse. Previous studies examining the association between single-food items and CLL risk have yielded mixed results, while few studies have been conducted on overall diet, reporting inconclusive findings. This study aimed to evaluate the association between adherence to three dietary patterns and CLL in the multicase-control study (MCC-Spain) study. Anthropometric, sociodemographic, medical and dietary information was collected for 369 CLL cases and 1605 controls. Three validated dietary patterns, Western, Prudent and Mediterranean, were reconstructed in the MCC-Spain data. The association between adherence to each dietary pattern and CLL was assessed, overall and by Rai stage, using mixed logistic regression models adjusted for potential confounders. High adherence to a Western dietary pattern (i.e. high intake of high-fat dairy products, processed meat, refined grains, sweets, caloric drinks, and convenience food) was associated with CLL [ORQ4 vs. Q1=1.63 (95%CI 1.11; 2.39); P-trend=0.02; OR 1-SD increase=1.19 (95%CI: 1.03; 1.37)], independently of Rai stages. No differences in the association were observed according to sex, Body Mass Index, energy intake, tobacco, physical activity, working on a farm, or family history of hematologic malignancies. No associations were observed for Mediterranean and Prudent dietary patterns and CLL. This study provides the first evidence for an association between a Western dietary pattern and CLL, suggesting that a proportion of CLL cases could be prevented by modifying dietary habits. Further research, especially with a prospective design, is warranted to confirm these findings.

Prevalence and characteristics of breakthrough cancer pain in an outpatient clinic in a Catalan teaching hospital: incorporation of the Edmonton Classification System for Cancer pain into the diagnostic algorithm.

BACKGROUND: Breakthrough cancer pain (BTcP) is defined according to its principal characteristics: high intensity, short time interval between onset and peak intensity, short duration, potential recurrence over 24 h and non-responsiveness to standard analgesic regimes. The Edmonton Classification System for Cancer Pain (ECS-CP) is a classification tool that evaluates different dimensions of pain. The aim of this study was to measure prevalence and the main characteristics of BTcP in a sample of advanced cancer patients and to explore the complexity observed when ECS-CP is incorporated into BTcP diagnostics algorithm. METHODS: Descriptive prevalence study (Retrospective chart review). Davies' algorithm was used to identify BTcP and ECS-CP was used to recognize appropriate dimensions of pain. The study was conducted in a sample of advanced cancer patients attending hospital outpatient clinic in Lleida, Spain. 277 patients were included from 01/01/2014 to 31/12/2015. No direct contact was made with participants. The following information was extracted from the palliative care outpatient clinic database: age, gender, civil status, cognitive impairment status, functional performance status and variables related to tumour. Only BTcP cases were included. RESULTS: Prevalence of BTcP was 39.34% (63.9% men). Mean of age was 68.2 years. Main diagnosis was lung cancer (n = 154; 31.6%). Metastases were diagnosed in 83% of the sample. 138 patients (49.8%) were diagnosed with 1 type of BTcP and 139 (50.2%) were diagnosed with more than one type of BTcP. In total, 488 different types of BTcP were recorded (mean 1.75 ± 0, 9), 244 of these types (50%) presented a component of neuropathic pain. Addictive behaviour, measured through CAGE test, was present in 29.2% (N = 81) of the patients and psychological distress was present in 40.8% (n = 113). CONCLUSIONS: Prevalence of BTcP (39.34%) is similar to the one reflected in the existing literature. Study results indicate that the routine use of ECS-CP in a clinical setting allows us to detect more than one type of BTcP as well as additional complexity associated with pain (neuropathic, addictive behavior and psychological distress).

Are the classic signs of infection in concordance with results from percutaneous aspiration to diagnose infection in pressure injuries?

AIM: To explore the concordance between the presence of classic signs of infection and the positive diagnosis identified by the microbiological culture of fluid collected by percutaneous aspiration. BACKGROUND: The classic signs of infection are commonly applied in some contexts to confirm infection in pressure injuries, but its accuracy has been questioned in chronic wounds. Little is known about the concordance of this method with others, such as the deep fluid culture from pressure injuries collected by percutaneous aspiration. DESIGN: Multicentre, cross-sectional observational study. METHODS: Pressure injuries of patients from four health centres were analysed. Three types of data were recorded between February 2011 and March 2012: i) socio-demographic and clinical data, ii) number and type of infection signs and iii) microbiological results of deep fluid culture from injuries. The concordance was calculated with the kappa index to find a possible concordance between both methods. RESULTS: On 40·2% (n = 47) of injuries, two or more classic signs of infection or purulent exudate as unique sign were present, while the total positive results in the microbiological cultures were 50·4% (n = 59). The disparity of positive results, depending on the location and the stage of the pressure injury and the method applied, suggested a poor concordance between methods. The -0·092 kappa index confirmed the non-concordance of the analysed methods. CONCLUSIONS: The tandem strategy is not useful to indicate an infection in pressure injuries. We advocate exploring other signs of infection and the adoption of other more reliable signs together with the classic signs of infection.

Interstitial 13q14 deletions detected in the karyotype and translocations with concomitant deletion at 13q14 in chronic lymphocytic leukemia: different genetic mechanisms but equivalent poorer clinical outcome.

Deletion of 13q14 as the sole abnormality is a good prognostic marker in chronic lymphocytic leukemia (CLL). Nonetheless, the prognostic value of reciprocal 13q14 translocations [t(13q)] with related 13q losses has not been fully elucidated. We described clinical and biological characteristics of 25 CLL patients with t(13q), and compared with 62 patients carrying interstitial del(13q) by conventional G-banding cytogenetics (CGC) [i-del(13q)] and 295 patients with del(13q) only detected by fluorescence in situ hybridization (FISH) [F-del(13q)]. Besides from the CLL FISH panel (D13S319, CEP12, ATM, TP53), we studied RB1 deletions in all t(13q) cases and a representative group of i-del(13q) and F-del(13q). We analyzed NOTCH1, SF3B1, and MYD88 mutations in t(13q) cases by Sanger sequencing. In all, 25 distinct t(13q) were described. All these cases showed D13S319 deletion while 32% also lost RB1. The median percentage of 13q-deleted nuclei did not differ from i-del(13q) patients (73% vs. 64%), but both were significantly higher than F-del(13q) (52%, P < 0.001). Moreover, t(13q) patients showed an increased incidence of biallelic del(13q) (52% vs. 11.3% and 14.9%, P < 0.001) and higher rates of concomitant 17p deletion (37.5% vs. 8.6% and 7.2%, P < 0.001). RB1 involvement was significantly higher in the i-del(13q) group (79%, P < 0.001). Two t(13q) patients (11.8%) carried NOTCH1 mutations. Time to first treatment in t(13q) and i-del(13q) was shorter than F-del(13q) (67, 44, and 137 months, P = 0.029), and preserved significance in the multivariate analysis. In conclusion, t(13q) and del(13q) patients detected by CGC constitute a subgroup within the 13q-deleted CLL patients associated with a worse clinical outcome.

Complex Karyotype Detection in Chronic Lymphocytic Leukemia: A Comparison of Parallel Cytogenetic Cultures Using TPA and IL2+DSP30 from a Single Center.

Current CLL guidelines recommend a two parallel cultures assessment using TPA and IL2+DSP30 mitogens for complex karyotype (CK) detection. Studies comparing both mitogens for CK identification in the same cohort are lacking. We analyzed the global performance, CK detection, and concordance in the complexity assessment of two cytogenetic cultures from 255 CLL patients. IL2+DSP30 identified more altered karyotypes than TPA (50 vs. 39%, p = 0.031). Moreover, in 71% of those abnormal by both, IL2+DSP30 identified more abnormalities and/or abnormal metaphases. CK detection was similar for TPA and IL2+DSP30 (10% vs. 11%). However, 11/33 CKs (33%) were discordant, mainly due to the detection of a normal karyotype or no metaphases in the other culture. Patients requiring treatment within 12 months after sampling (active CLL) displayed significantly more CKs than those showing a stable disease (55% vs. 12%, p < 0.001). Disease status did not impact cultures' concordance (κ index: 0.735 and 0.754 for stable and active). Although CK was associated with shorter time to first treatment (TTFT) using both methods, IL2+DSP30 displayed better accuracy than TPA for predicting TTFT (C-index: 0.605 vs. 0.580, respectively). In summary, the analysis of two parallel cultures is the best option to detect CKs in CLL. Nonetheless, IL2+DSP30 could be prioritized above TPA to optimize cytogenetic assessment in clinical practice.

Evaluation of 4 prognostic indices in follicular lymphoma treated in first line with immunochemotherapy.

Several clinical risk models have been proposed to predict the outcome of follicular lymphoma (FL). The development of next-generation sequencing technologies has allowed the integration of somatic gene mutations into clinical scores to build genotyped-based risk models, such as the m7-Follicular Lymphoma International Prognostic Index (FLIPI). We explored 4 clinical or clinicogenetic-risk models in patients with symptomatic FL who received frontline immunochemotherapy. Of 191 patients with FL grades 1 to 3a, 109 were successfully genotyped. The treatment consisted of rituximab (R) plus cyclophosphamide, vincristine, and prednisone (R-CVP)/cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (72.5%) or R-bendamustine (R-B) (27.5%). The proportion of cases classified as high risk for FLIPI, FLIPI-2, PRIMA-prognostic index, or m7-FLIPI were 39.3%, 14%, 30.3%, and 22%, respectively. No case with low-intermediate FLIPI was upgraded in the m7-FLIPI, but 18 of the 42 high-risk patients with FLIPI were downgraded to low-risk m7-FLIPI. The sensitivity and specificity for the prediction of POD24 were highest for FLIPI. The discrimination between progression-free survival (PFS) and overall survival (OS) was the best for FLIPI (c-index: 0.644 and 0.727, respectively). When analyzed only in patients treated with R-B, m7-FLIPI showed a higher discrimination between PFS and OS. Thus, the FLIPI remains the clinical risk score with higher discrimination in patients with advanced FL treated with immunochemotherapy; however, the performance of the m7-FLIPI should be further investigated in patients treated with R-B.

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.

Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001). Interpretation: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS. Funding: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.

Gastroprotection in NSAID and low-dose aspirin users: a cross-sectional study in primary care.

Gastrointestinal (GI) complications are common side effects related to non-steroidal anti-inflammatory drugs (NSAID) and low-dose aspirin (LDA) use. The guidelines to prevent GI complications establish that patients at high risk should receive gastroprotection. However, different reports have suggested that these strategies are not greatly executed. To determine the prevalence of use of preventive strategies to reduce GI complications in NSAID and/or LDA users in primary care in Spain, we performed an observational, cross-sectional, multicentre study in which primary care physicians from Spain participated. From January 2009 to May 2009, physicians collected demographic, clinical and treatment data from the last visit in 2008 of the first 5 consecutive patients who met the selection criteria. A multivariate logistic regression was carried out to identify independent predictors of the preventive strategies used. A total of 713 primary care physicians included 3357 patients: 68% NSAID users, 19.1% LDA users and 12.9% NSAID/LDA users. 31.5% of patients did not have a risk factor for GI complications, 25.6% had one risk factor and 42.9% had 2 or more risk factors. The overall prevalence of preventive strategy use was 75.8%. The prevalence of gastroprotection use increased with the number of risk factors. The underutilization of gastroprotection in at-risk patients treated with NSAIDs is low and not as marked as those previously reported at the primary care level in other countries. We also found high rates of gastroprotection use in LDA users.

Sézary syndrome patient-derived models allow drug selection for personalized therapy.

Current therapeutic approaches for Sézary syndrome (SS) do not achieve a significant improvement in long-term survival of patients, and they are mainly focused on reducing blood tumor burden to improve quality of life. Eradication of SS is hindered by its genetic and molecular heterogeneity. Determining effective and personalized treatments for SS is urgently needed. The present work compiles the current methods for SS patient-derived xenograft (PDX) generation and management to provide new perspectives on treatment for patients with SS. Mononuclear cells were recovered by Ficoll gradient separation from fresh peripheral blood of patients with SS (N = 11). A selected panel of 26 compounds that are inhibitors of the main signaling pathways driving SS pathogenesis, including NF-kB, MAPK, histone deacetylase, mammalian target of rapamycin, or JAK/STAT, was used for in vitro drug sensitivity testing. SS cell viability was evaluated by using the CellTiter-Glo_3D Cell Viability Assay and flow cytometry analysis. We validated one positive hit using SS patient-derived Sézary cells xenotransplanted (PDX) into NOD-SCID-γ mice. In vitro data indicated that primary malignant SS cells all display different sensitivities against specific pathway inhibitors. In vivo validation using SS PDX mostly reproduced the responses to the histone deacetylase inhibitor panobinostat that were observed in vitro. Our investigations revealed the possibility of using high-throughput in vitro testing followed by PDX in vivo validation for selective targeting of SS tumor cells in a patient-specific manner.

Worse outcome and distinct mutational pattern in follicular lymphoma with anti-HBc positivity.

Epidemiological studies have demonstrated the association between hepatitis B virus (HBV) infection and B-cell non-Hodgkin lymphoma (NHL), mainly for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). We studied a cohort of 121 patients with FL for HBV infection status, clinical features, and gene mutational profile. Anti-HBc was detectable in 16 patients (13.2%), although all had undetectable HBV DNA. Anti-HBcore+ (anti-HBc+) cases presented with older age at diagnosis than anti-HBc- cases (68.1 vs 57.2 years; P = .007) and higher ß2-microglobulin (56.3% vs 28.9%; P = .04). All patients included in the study fulfilled criteria for treatment and received therapy with rituximab or rituximab-containing chemotherapy. There were no episodes of HBV reactivation or HBV hepatitis during treatment and/or maintenance. Remarkably, anti-HBc+ patients had significantly lower 10-year progression-free survival (PFS; 12.9% vs 58.3%; P < .0001) and overall survival (OS; 22.0% vs 86.2%; P < .0001), that remained at multivariate analysis. Gene mutational profiling of all cases showed that anti-HBc+ cases had higher incidence of ARID1A mutations and absence of EP300 mutations, 2 key epigenetic regulators in FL. Overall, our study shows that FL patients with resolved HBV infection have a worse outcome independently of other well-known clinical risk factors and a distinct gene mutational profile.

Optical Genome Mapping: A Promising New Tool to Assess Genomic Complexity in Chronic Lymphocytic Leukemia (CLL).

Novel treatments in chronic lymphocytic leukemia (CLL) have generated interest regarding the clinical impact of genomic complexity, currently assessed by chromosome banding analysis (CBA) and chromosomal microarray analysis (CMA). Optical genome mapping (OGM), a novel technique based on imaging of long DNA molecules labeled at specific sites, allows the identification of multiple cytogenetic abnormalities in a single test. We aimed to determine whether OGM is a suitable alternative to cytogenomic assessment in CLL, especially focused on genomic complexity. Cytogenomic OGM aberrations from 42 patients were compared with CBA, FISH, and CMA information. Clinical−biological characteristics and time to first treatment (TTFT) were analyzed according to the complexity detected by OGM. Globally, OGM identified 90.3% of the known alterations (279/309). Discordances were mainly found in (peri-)centromeric or telomeric regions or subclonal aberrations (<15−20%). OGM underscored additional abnormalities, providing novel structural information on known aberrations in 55% of patients. Regarding genomic complexity, the number of OGM abnormalities had better accuracy in predicting TTFT than current methods (C-index: 0.696, 0.602, 0.661 by OGM, CBA, and CMA, respectively). A cut-off of ≥10 alterations defined a complex OGM group (C-OGM, n = 12), which included 11/14 patients with ≥5 abnormalities by CBA/CMA and one patient with chromothripsis (Kappa index = 0.778; p < 0.001). Moreover, C-OGM displayed enrichment of TP53 abnormalities (58.3% vs. 3.3%, p < 0.001) and a significantly shorter TTFT (median: 2 vs. 43 months, p = 0.014). OGM is a robust technology for implementation in the routine management of CLL patients, although further studies are required to define standard genomic complexity criteria.

TP53 Abnormalities Are Underlying the Poor Outcome Associated with Chromothripsis in Chronic Lymphocytic Leukemia Patients with Complex Karyotype.

Chromothripsis (cth) has been associated with a dismal outcome and poor prognosis factors in patients with chronic lymphocytic leukemia (CLL). Despite being correlated with high genome instability, previous studies have not assessed the role of cth in the context of genomic complexity. Herein, we analyzed a cohort of 33 CLL patients with cth and compared them against a cohort of 129 non-cth cases with complex karyotypes. Nine cth cases were analyzed using optical genome mapping (OGM). Patterns detected by genomic microarrays were compared and the prognostic value of cth was analyzed. Cth was distributed throughout the genome, with chromosomes 3, 6 and 13 being those most frequently affected. OGM detected 88.1% of the previously known copy number alterations and several additional cth-related rearrangements (median: 9, range: 3-26). Two patterns were identified: one with rearrangements clustered in the region with cth (3/9) and the other involving both chromothriptic and non-chromothriptic chromosomes (6/9). Cases with cth showed a shorter time to first treatment (TTFT) than non-cth patients (median TTFT: 2 m vs. 15 m; p = 0.013). However, when stratifying patients based on TP53 status, cth did not affect TTFT. Only TP53 maintained its significance in the multivariate analysis for TTFT, including cth and genome complexity defined by genomic microarrays (HR: 1.60; p = 0.029). Our findings suggest that TP53 abnormalities, rather than cth itself, underlie the poor prognosis observed in this subset.

Cognitive behavioral therapy for insomnia (CBT-i) in patients with fibromyalgia: a systematic review and meta-analysis.

PURPOSE: We aimed to evaluate the effectiveness of CBT-i in patients with fibromyalgia in comparison with other non-pharmacological treatments. METHODS: Randomized controlled trials assessing the effects of CBT-i in adults with fibromyalgia, published in English or Spanish, were eligible. Electronic searches were performed using PubMed, Scopus, The Cochrane Library, WebOfKnowledge and Psicodoc databases in March 2021. The main outcome measures were sleep efficiency and sleep quality. Secondary outcomes included pain, depression, and anxiety. RESULTS: Of 226 studies reviewed, five were included in the meta-analysis. CBT-i compared with non-pharmacological treatments showed no significant improvements in sleep efficiency (p = 0.05; standardized mean difference (SMD) [95% CI] 0.31 [-0.00 to 0.61]). CBT-i showed significant improvements in sleep quality (p = 0.009; SMD [95% CI] - 0.53 [-0.93 to -0.13]), pain (p = 0.002; SMD [95% CI] - 0.41 [-0.67 to -0.16]), anxiety (p = 0.001; SMD [95% CI] - 0.46 [-0.74 to 0.18]) and depression (p = 0.02; SMD [95% CI] - 0.33 [-0.61 to -0.05]), compared to non-pharmacological treatments. Effect sizes ranged from small to moderate. CONCLUSIONS: CBT-i was associated with a significant improvement in sleep quality, pain, anxiety, and depression, although these results are retrieved from very few studies with only very low to low quality evidence. Trial registration: The review protocol was registered with PROSPERO (Record ID = CRD42016030161).IMPLICATIONS FOR REHABILITATIONCBT-i has been proven to improve sleep quality, pain, anxiety and depression, although with small effect sizes.Implementing hybrid CBT for pain and sleep or combining CBT and mindfulness may improve symptoms in people diagnosed with FM.This meta-analysis results highlight the need to enhance sleep management skills among people suffering from this health condition.

Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Chronic lymphocytic leukemia-like monoclonal B-cell lymphocytosis exhibits an increased inflammatory signature that is reduced in early-stage chronic lymphocytic leukemia.

Several studies in chronic lymphocytic leukemia (CLL) patients have reported impaired immune cell functions, which contribute to tumor evasion and disease progression. However, studies on CLL-like monoclonal B-cell lymphocytosis (MBL) are scarce. In the study described here, we characterized the immune environment in 62 individuals with clinical MBL, 56 patients with early-stage CLL, and 31 healthy controls. Gene expression arrays and quantitative reverse transcription polymerase chain reaction were performed on RNA from CD4+ peripheral blood cells; serum cytokines were measured with immunoassays; and HLA-DR expression on circulating monocytes, as well as the percentages of Th1, cytotoxic, exhausted, and effector CD4+ T cells, were evaluated by flow cytometry. In addition, cell cultures of clonal B cells and CD14-enriched or -depleted cell fractions were performed. Strikingly, MBL and early-stage CLL differed in pro-inflammatory signatures. An increased inflammatory drive orchestrated mainly by monocytes was identified in MBL, which exhibited enhanced phagocytosis, pattern recognition receptors, interleukin-8 (IL8), HMGB1, and acute response signaling pathways and increased pro-inflammatory cytokines (in particular IL8, interferon γ [IFNγ], and tumor necrosis factor α). This inflammatory signature was diminished in early-stage CLL (reduced IL8 and IFNγ levels, IL8 signaling pathway, and monocytic HLA-DR expression compared with MBL), especially in those patients with mutations in IGHV genes. Additionally, CD4+ T cells of MBL and early-stage CLL exhibited a similar upregulation of Th1 and cytotoxic genes and expanded CXCR3+ and perforin+ CD4+ T cells, as well as PD1+ CD4+ T cells, compared with controls. Cell culture assays disclosed tumor-supporting effects of monocytes similarly observed in MBL and early-stage CLL. These novel findings reveal differences in the inflammatory environment between MBL and CLL, highlighting an active role for antigen stimulation in the very early stages of the disease, potentially related to malignant B-cell transformation.

Evaluation of routine CT scans in the follow-up of diffuse large B-cell lymphomas.

OBJECTIVE: Our aim was to retrospectively assess the role of routine CT scans within the first year of follow-up with a limited surveillance policy prior to Lugano recommendations in diffuse large B-cell lymphomas (DLBCL) achieving complete metabolic remission (CMR). We also evaluated the type of relapse detection and exposure to CT scans within the first five years. METHODS: Patients diagnosed with DLBCL who achieved CMR after first-line immunochemotherapy were included. Imaging studies and medical records were thoroughly reviewed. RESULTS: Among 101 DLBCL patients in the first CMR, a total of 19 relapses were identified in the study period (18.8% of DLBCL patients included). Nine patients relapsed within the first year (47.4% of all relapses) but only 3 of them were detected by the 202 surveillance CT scans performed during this first year of follow-up. CONCLUSIONS: Our real-world data provide clinically applicable results which are in agreement with the Lugano recommendations based on trial data, highlighting the lack of utility of routine CTs in DLBCL patients achieving CMR.