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Simple Summary: This HEMATO-MADRID COVID-19 study assessed COVID-19 outcomes in 1818 hematologic cancer patients from February 2020 to October 2022 across different phases, including the Omicron period. Severe cases were more common in patients over 70 years with comorbidities or chronic lymphocytic leukemia. However, during the Omicron period, rates of severe illness reduced notably, especially among vaccinated individuals. Hospitalization, intensive care admissions, and overall mortality decreased in the Omicron phase compared to pre-Omicron, yet mortality rates in hospitalized patients remained high. Older age consistently correlated with higher mortality risk in both phases. Factors like prior stem cell transplantation, vaccination, and specific treatments were linked to improved survival rates among hematologic cancer patients facing COVID-19. A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64–2.87), with >1 comorbidity (2.44, 1.85–3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19–2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2–0.37) or BA.4/BA.5 (0.13, 0.08–0.19) periods and among patients vaccinated with one or two (0.51, 0.34–0.75) or three or four (0.22, 0.16–0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03–3.25) and Omicron (3.19, 95% CI 1.59–6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent advances in treating elderly patients with chronic lymphocytic leukemia (CLL) have emphasized the importance of geriatric assessment (GA) to evaluate patient fitness and predict treatment outcomes. Targeted therapies (BTK inhibitors and venetoclax) have demonstrated significant clinical benefits and are now a reality in CLL treatment. They have a different toxicity profile that may affect frailty. Therefore, incorporating GA before treatment initiation, considering physical and cognitive function, emotional health, comorbidity, polypharmacy, nutrition, and social support, is essential. Chronic lymphocytic leukemia (CLL) is a disease of the elderly, but chronological age does not accurately discriminate frailty status at the inter-individual level. Frailty describes a person's overall resilience. Since CLL is a stressful situation, it is relevant to assess the patient´s degree of frailty, especially before starting antineoplastic treatment. We are in the era of targeted therapies, which have helped to control the disease more effectively and avoid the toxicity of chemo (immuno) therapy. However, these drugs are not free of side effects and other aspects arise that should not be neglected, such as interactions, previous comorbidities, or adherence to treatment, since most of these medications are taken continuously. The challenge we face is to balance the risk of toxicity and efficacy in a personalized way and without forgetting that the most frequent cause of death in CLL is related to the disease. For this purpose, comprehensive geriatric assessment (GA) provides us with the opportunity to evaluate multiple domains that may affect tolerance to treatment and that could be improved with appropriate interventions. In this review, we will analyze the state of the art of GA in CLL through the five Ws. [ABSTRACT FROM AUTHOR]

Simple Summary: There are contradictory data about coronavirus disease (COVID-19) in patients with hematological malignancies. In this population-based study we evaluated severity and survival of unvaccinated patients with hematological malignancies (HM) and COVID-19 in the Madrid region, Spain, between early February 2020 and February 2021. Also, a comparison was made with non-cancer patients from the SEMI-COVID registry and post COVID-19 conditions were evaluated. Overall, 30-day mortality was 32.7%, with higher mortality among certain groups of patients (aged ≥ 60 years, presence of ≥ 3 comorbidities, diagnosis of AML/ALL, treatment with conventional chemotherapy within 30 days of COVID-19 diagnosis, recipients of systemic corticosteroids as COVID-19 therapy). Mortality rates were similar between earlier and later phases of the pandemic, not paralleling the reduction of mortality in non-cancer patients. Up to 27.3% patients had a post COVID-19 condition. These findings will be useful to understand COVID-19 morbidity and mortality in unvaccinated patients diagnosed with HM. Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis. [ABSTRACT FROM AUTHOR]

Chronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by uncontrolled proliferation of B-cells and severe immune dysfunction. Chemo(immuno)therapies (CIT) have traditionally aimed to reduce tumor burden without fully understanding their effects on the immune system. As a consequence, CIT are usually associated with higher risk of infections, secondary neoplasms and autoimmune disorders. A better understanding of the biology of the disease has led to the development of therapeutic strategies which not only act against malignant B-cells but also reactivate and enhance the patient's own anti-tumor immune response. Here, we review the current understanding of the underlying interplay between the malignant cells and non-malignant immune cells that may promote tumor survival and proliferation. In addition, we review the available evidence on how different treatment options for CLL including CIT regimens, small molecular inhibitors (i.e, BTK inhibitors, PI3K inhibitors, BCL-2 inhibitors) and T-cell therapies, affect the immune system and their clinical consequences. Finally, we propose that a dual therapeutic approach, acting directly against malignant B-cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL. [ABSTRACT FROM AUTHOR]

The article offers information on COVID-19 in patients with hematological malignancies. Topics icnlude the patients with cancer have a higher susceptibility to infections due to their immunosuppression state caused by the malignancy itself or by antineoplastic treatments, and the infections has caused by community respiratory viruses had been associated with poor outcome in patients with hematological malignancies.

Background: Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. Methods: In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. Results: Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60–79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17–10.1 vs < 50 years), > 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). Conclusions: In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification. [ABSTRACT FROM AUTHOR]