COVID-19 in Patients with Chronic Lymphocytic Leukemia: What Have We Learned?

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a prevalent hematological malignancy (HM) characterized by inherent immunodeficiency, which is further pronounced by disease-directed therapy. The COVID-19 pandemic has had devastating outcomes, and although its impact has diminished over time, it continues to be a cause of significant morbidity and mortality, particularly among immunodeficient patients. SUMMARY: In this review, we describe mechanisms of immune dysfunction in CLL in relation to COVID-19, provide an overview of the clinical outcomes of the disease in this patient population, and identify risk factors associated with severe morbidity and mortality. Additionally, we acknowledge the influence of the rapidly evolving landscape of new disease variants. The review further delineates the humoral and cellular responses to vaccination and their clinical efficacy in preventing COVID-19 in CLL patients. Moreover, we explore potential approaches to enhance these immune responses. Pre- and post-exposure prophylaxis strategies are discussed, along with description of common agents in the treatment of the disease in both outpatient and inpatient setting. Throughout the review, we emphasize the interplay between novel therapies for CLL and COVID-19 outcomes, prevention, and treatment and describe the impact of COVID-19 on the utilization of these novel agents. This information has the potential to guide clinical decision making in the management CLL patients. KEY MESSAGES: CLL patients are at risk for severe COVID-19 infection. Vaccinations and COVID-19 directed therapy have improved outcomes in patients with CLL, yet clinical challenges persist.

Rituximab versus obinutuzumab-based first-line chemoimmunotherapy for follicular lymphoma-a real-world multicenter retrospective cohort study.

The GALLIUM study showed a progression-free survival advantage of 7% in favor of obinutuzumab vs. rituximab-based immunochemotherapies as first-line therapy in follicular lymphoma (FL) patients. Yet, the toxicity appears to be increased with obinutuzumab-based therapy. This is a multicenter retrospective-cohort study including adult FL patients comparing the toxicity of first-line rituximab vs. obinutuzumab-based chemo-immunotherapies (R and O groups, respectively). We compared the best standard-of-care therapy used per time period, before and after obinutuzumab approval. The primary outcome was any infection during induction and 6 months post-induction. Secondary outcomes included rates of febrile neutropenia, severe and fatal infections, other adverse events, and all-cause mortality. Outcomes were compared between groups. A total of 156 patients were included in the analysis, 78 patients per group. Most patients received bendamustine (59%) or CHOP (31.4%) as adjacent chemotherapy. Half of the patients received growth-factor prophylaxis. Overall, 69 patients (44.2%) experienced infections, and a total of 106 infectious episodes were recorded. Patients in the R and O groups had similar rates of any infection (44.8% and 43.5%, p = 1), severe infections (43.3% vs. 47.8%, p = 0.844), febrile neutropenia (15% vs. 19.6%, p = 0.606), and treatment discontinuation, as well as similar types of infections. No covariate was associated with infection in multivariable analysis. No statistically significant difference was evident in adverse events of grades 3-5 (76.9% vs. 82%, p = 0.427). To conclude, in this largest real-life study of first-line treated FL patients comparing R- to O-based therapy, we did not observe any difference in toxicity during the induction and 6 months post-induction period.

Enzyme replacement therapy leading to improvement in myeloma indices in a patient with concomitant Gaucher disease.

Patients with Gaucher disease (GD) have been shown previously to carry an increased risk for cancer, most commonly multiple myeloma (MM). It is currently unknown whether treatment for GD has an effect on the prevention or amelioration of MM. We present the case of a 41-year-old patient simultaneously diagnosed with GD and smouldering MM. Enzyme replacement therapy with Velaglucerase-alfa significantly improved myeloma indices.

[PANCREATIC NEUROENDOCRINE TUMORS (PNET): THE DILEMMA OF SURGERY VS. WATCHFUL WAITING APPROACH].

INTRODUCTION: Neuroendocrine tumors (NEN) originate from hormone producing cells located in various organs and tissues. NEN are unique tumors in terms of their diverse and particular clinical presentations, growth pattern, location and relatively good prognosis. NEN can be either secreting or non-secreting tumors. The clinical presentation and symptoms are according to the specific hormone produced by the tumor. A non-secreting tumor will eventually cause symptoms that relate to a mass-effect or a metastatic disease. There are various familial and genetic syndromes that are related to NEN. The most common neuroendocrine genetic syndrome is Multiple Endocrine Neoplasia syndrome type 1 (MEN 1). The clinical approach and treatment of NEN are unlike any other cancer. The gold standard management is surgery but unlike other cancerous diseases, surgical intervention is also indicated in cases of metastatic disease. There are several surgical approaches, and they all depend on tumor size, location, grade, stage, lymph node involvement, remote metastases and patients' age and comorbidities. Besides surgery, some cases are also treated with systemic therapies such as Somatostatin analogues, chemotherapy, immunotherapies, targeted therapies and occasionally radiation therapy is used. In the last decade there is a significant increase in the number of patients diagnosed with small non-secreting pancreatic tumors (PNET) due to advanced imaging techniques and diagnostic tools. This incidental increase is the reason for the emerging dilemma of whether to operate or merely conduct a watchful waiting policy. Small non-secreting tumors are commonly not considered malignant and thus the question is if surgery is always the right approach. The benefits of surgery must be carefully considered against the potential damage that may occur during these complex and radical procedures. Moreover, new and progressive systemic pharmacological therapies are now available to efficiently suppress tumor hormonal secretion. Recent studies have challenged surgery as the only treatment of choice, and in some cases suggest conservative treatment and follow up. The aim of this present literature review is to describe PNET diagnostic tools and evaluation, and to examine the different approaches of PNET treatment.

[NOTES FROM A SIX MONTHS VOLUNTEER MISSION AS MEDICAL STAFF IN A DISTRICT HOSPITAL IN UGANDA].

INTRODUCTION: In December 2014 my husband and I flew for a stay of six months in Uganda. We went there in order to volunteer in the district hospital of Kiboga, one of the most impoverished districts of this poverty stricken country. A district in which over 60% of the population lives off less than a dollar and twenty five cents a day, in which the average life expectancy is 46.7 years (9.1 years lower than the national average expectancy). Kiboga's district hospital serves the 300,000 residents of the district, of whom 20,000 live in the district capital, while the rest are mainly farmers and cattle keepers, scattered in small villages that have limited and weather-dependent access. The hospital houses 120 beds, which are divided into four wards (maternity, pediatric, male and female), and is manned routinely by one on-call local physician, who (when present) is almost exclusively occupied by emergency cesarean sections. Therefore, the majority of hospitalized patients are not inspected by a doctor at any point of their stay. The hospital functions with no running water and in the absence of a reliable power supply. The nursing staff, composed largely of people with limited or no training, is always desperately understaffed, and many of the means needed for a patient's stay (starting with a bed pan and linens and ending with many of the medications prescribed) are not supplied by the hospital. Perhaps it would have been appropriate to continue by describing unsettling data about the health infrastructure in Kiboga (such as the fact that infant mortality rate is a staggering 15%, or that nearly 10% of the districts population have HIV), however, it appears to me that it would be more educating to learn from the story of the patients we encountered.

COVID-19 among patients with hematological malignancies: a national Israeli retrospective analysis with special emphasis on treatment and outcome.

This national Israeli multicenter retrospective study aimed to characterize the clinical course of COVID-19 infection among patients with hematological malignancies, with special emphasis on treatment efficacy and outcome. Clinical and laboratory data from haemato-oncological patients diagnosed with COVID-19 from 16 medical centers were centrally reported. Multivariate regression analyses were used to determine variables associated with severe disease, hospitalization, and mortality. In total, 313 patients were included: 103 (35.7%) developed severe/critical respiratory infection, 178 (61.4%) were hospitalized, and 60 (20.0%) died. Age > 70 years was associated with severe/critical disease (p = 0.036) and mortality (p = 0.023), hypertension with severe/critical disease (p = 0.046) and hospitalization (p = 0.001), active haemato-oncological treatment with hospitalization (p = 0.009), and remdesivir treatment was associated with decreased mortality (p = 0.021). Convalescent plasma, enoxaparin, and corticosteroids resulted in no clinical benefit. In conclusion, COVID-19 infection seems particularly severe in patients with hematological malignancies, and of all examined therapies, remdesivir appears to be the most effective.

Malaria Disease and Chemoprophylaxis Usage among Israeli Travelers to Endemic Countries.

Prevention of malaria in travelers to endemic countries is one of the complex challenges of travel medicine. Israel has a widespread culture of travel to developing countries, but information regarding malaria prevention is limited so far. Our study, conducted in Sheba Medical Center, Israel, during the years 2008-2018 examined malaria chemoprophylaxis usage and malaria cases in a large group of Israeli travelers returning from endemic countries with any medical complaint. Data were collected regarding travel destinations, conditions, duration of stay, and pretravel consultation. Altogether, 4,708 travelers were included in our study. Travel destinations included Asia (51%), Latin America (31%), and sub-Saharan Africa (SSA) (17%). Median travel duration was 26 days. Only 11.9% reported taking malaria chemoprophylaxis. Of the travelers to SSA, 41.3% took prophylaxis as opposed to only 6% outside of Africa. During the study years, 136 cases of malaria were diagnosed; among them, 82 (60%) were infected with Plasmodium falciparum, of whom all but two were from SSA and none adhered to prophylaxis. Malaria chemoprophylaxis usage was found to be negligible in travel to many countries still considered endemic. Higher prophylaxis usage was found among travelers to SSA, but numbers are still lower than recommended. The low number of malaria cases seen in destinations outside SSA, as documented in our cohort, is likely to represent travel to low risk areas and not high prophylaxis usage. We urge re-evaluation of current CDC and Israeli guidelines which still recommend using chemoprophylaxis in many low-risk countries, as focus on high-risk countries may increase adherence.

Pocket-size point-of-care ultrasound in rural Uganda - A unique opportunity "to see", where no imaging facilities are available.

BACKGROUND: In the developing world, only a small minority of patients have access to radiological services. Over the past decade, technological developments of ultrasound equipment have led to the emergence of point-of-care ultrasonography (POCUS), which is widely used by healthcare professionals of nearly all specialties. We hypothesized that physicians with only basic POCUS training, but with telemedicine support, can use POCUS successfully in rural hospitals in sub-Saharan Africa. METHOD: During a 14-day voluntary clinical work session in a rural hospital in central Uganda, bedside ultrasound scans were performed by use of a pocket-size portable machine by a physician who underwent a five-day training period. All the POCUS studies were reviewed by radiologists and cardiologists abroad with the use of telemedicine. RESULTS: During the study period, 30% of patients received a POCUS-augmented physical examination. 16 out of 23 patients (70%) had positive findings; in 20 of them (87%), the management was changed. The technique was successfully used on trauma casualties, patients suffering from shock, patients with cardiorespiratory symptoms, and patients undergoing invasive procedures. CONCLUSIONS: In a very resource-limited environment, POCUS conducted by basically trained primary care physicians with telemedicine support is a powerful diagnostic tool in a variety of medical conditions.