Isolated Cutaneous Chronic Lymphocytic Leukemia: A Case Report.

Skin lesions in chronic lymphocytic leukemia (CLL) have been reported in between 4% and 20% of patients with CLL and are a rare entity compared with T-cell leukemia. They can present mainly as leukemic cutis or, frequently, as secondary lesions such like urticaria, itching, pyoderma gangrenosum, cutaneous vasculitis, Sweet's syndrome, and erythroderma. We report on an adult patient who developed a skin lesion of forearms and hands, leading to the discovery of isolated cutaneous CLL after two biopsies. Isolated CLL cutaneous location is very rare and may be diagnosed late, as in the case of our patient. A better knowledge of the course of the illness and rapid diagnosis of this CLL cutis leukemia will enhance the therapeutic efficacy of the disease.

Progressive multifocal leukoencephalopathy in a patient with B-cell chronic lymphocytic leukemia after COVID-19 vaccination, complicated with COVID-19 and mucormycosis: a case report.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare and fatal opportunistic viral demyelinating infectious disease of the central nervous system (CNS). There are various clinical presenting symptoms for the disease. CASE PRESENTATION: This paper presents a clinical case of PML in a patient with B-Chronic lymphocytic leukemia (B-CLL), previously treated with Chlorambucil, later complicated later with COVID-19 and mucormycosis. CONCLUSION: PML can develop in the setting of cellular immune dysfunction. Late diagnosis of this disease based on nonspecific symptoms is common, therefore when we face a neurological complication in a CLL or immunocompromised patient, we should consider PML infection. A remarkable feature of this case is the possible triggering effect of COVID-19 vaccination for emergence of PML as the disease can be asymptomatic or sub-clinical before diagnosis.

Comparing the impact of acupressure and reflexology on fatigue in chronic lymphocytic leukemia patients: A randomized controlled trial with three arms.

PURPOSE: This study aimed to evaluate the effects of acupressure and reflexology on fatigue in chronic lymphocytic leukemia patients. METHOD: In this randomized controlled trial with three arms and a pretest-posttest design, 102 CLL patients were randomly allocated to acupressure (n = 34), reflexology (n = 34), or control (n = 34) groups. Pre-intervention assessments were conducted using a demographic questionnaire and a fatigue scale for cancer patients. The acupressure group received routine care with acupressure targeting the SP6 point for 10 min twice daily over four weeks. The reflexology group received daily 10-minute reflexology sessions over four consecutive weeks following the preparation and lubrication of the soles of their feet with sweet almond oil. Post-intervention assessments were administered to all groups using the same instruments. RESULTS: Results showed both acupressure and reflexology significantly reduced fatigue compared to the control group (P < 0.001). While differences were noted between acupressure, reflexology, and control groups initially, the post-intervention analysis revealed no significant variance between acupressure and reflexology in reducing fatigue (P < 0.05), suggesting similar improvement between acupressure and reflexology. CONCLUSIONS: Acupressure and reflexology are recommended as cost-effective and low risk complementary approaches for managing fatigue in chronic lymphocytic leukemia patients. These therapies offer promise in alleviating fatigue and enhancing the quality of life for cancer patients.

Electro-anatomically-guided endomyocardial biopsy in a patient with focal myocardial infiltration and chronic lymphocytic leukemia.

A 53-year-old female was admitted to the cardiology department on account of signs and symptoms of congestive heart failure (HF) with severe peripheral edema and dyspnea on exertion (New York Heart Association class III) for the past 3 months.

Hybrid immunity to SARS-CoV-2 in patients with chronic lymphocytic leukemia.

OBJECTIVE: Preventing severe COVID-19 remains a priority globally, particularly in the immunocompromised population. As shown in healthy individuals, immunity against SARS-CoV-2 can be yielded by previous infection, vaccination, or both (hybrid immunity). The objective of this observation study was to investigate hybrid immunity in patients with chronic lymphocytic leukemia (CLL). METHODS/RESULTS: Blood samples of six patients with CLL were collected 55 days after fourth COVID-19 vaccination. All patients had a SARS-CoV-2 infection within 12 months before the second booster (fourth vaccination). SARS-CoV-2 spike receptor binding domain (RBD)-specific IgG antibodies were detectable in 6/6 (100.0%) CLL patients after four compared to 4/6 (66.7%) after three vaccinations. The median number of SARS-CoV-2 spike-specific T cells after repeated booster vaccination plus infection was 166 spot-forming cells (SFC) per million peripheral blood mononuclear cells. Overall, 5/5 (100%) studied patients showed a detectable increase in T cell activity. CONCLUSION: Our data reveal an increase of cellular and humoral immune response in CLL patients after fourth COVID-19 vaccination combined with SARS-CoV-2 infection, even in those undergoing B cell-depleting treatment. Patients with prior vaccination failure now show a specific IgG response. Future research should explore the duration and effectiveness of hybrid immunity considering various factors like past infection and vaccination rates, types and numbers of doses, and emerging variants.

Prevention and management of infectious complications in patients with chronic lymphocytic leukemia (CLL) treated with BTK and BCL-2 inhibitors, focus on current guidelines.

CLL is associated with an increased risk of infectious complications. Treatment with BTK or BCL-2 inhibitors does not seem to increase significantly the risk of opportunistic infections, but the role of combination therapies including BTK and/or BCL-2 inhibitors remains to be established. Various infectious complications can be successfully prevented with appropriate risk management strategies. In this paper we reviewed the international guidelines on prevention and management of infectious complications in patients with CLL treated with BTK or BCL-2 inhibitors. Universal pharmacological anti-herpes, antibacterial or antifungal prophylaxis is not warranted. Reactivation of HBV should be prevented in HBsAg-positive subjects. For HBsAg-negative/HBcAb-positive patients recommendations differ, but in case of combination treatment should follow those for other, particularly anti-CD20, agent. Immunization should be provided preferably before the onset of treatment. Immunoglobulin therapy has favourable impact on morbidity but not mortality in patients with hypogammaglobulinemia and severe or recurrent infections. Lack of high-quality data and heterogeneity of patients or protocols included in the studies might explain differences among the main guidelines. Better data collection is warranted.

Prediction of severe infections in chronic lymphocytic leukemia: a simple risk score to stratify patients at diagnosis.

Chronic Lymphocytic Leukemia (CLL) is well-known for increasing susceptibility to infections. Factors such as immune dysregulation, IGHV status, hypogammaglobulinemia, and patient comorbidity and treatment, contribute to higher infection rates and mortality. However, the impact of hypogammaglobulinemia on infection rates is controversial. We aimed to identify clinical and biological parameters linked to the risk of severe infectious events. Additionally, we set up a straightforward risk infection score to stratify CLL patients at diagnosis, thereby enabling the development of suitable infection prevention strategies. We retrospectively evaluated 210 unselected CLL patients diagnosed between 1988 and 2018. This evaluation encompassed demographics, Binet stage, immunoglobulin (Ig) levels, treatment history, comorbidities, and IGHV mutational status at diagnosis. The frequency and severity of infectious events were recorded. Analysis revealed that age, IGHV mutational status, Binet stage, and hypogammaglobulinemia were statistically associated with the Time to First Infection (TTFI) in univariate and multivariate analyses. Using hazard ratios from the multivariate analysis, we finally devised a risk scoring system that integrated age, IGHV mutational status, immunoglobulin levels, and Binet stage to stratify patients at diagnosis based on their specific infection risk. In our cohort, disease progression and infections were the leading cause of death. These findings pointed out the clinical need for a screening process strategic for defining infectious risk at the time of CLL diagnosis, with a significant enhancement in the clinical management of these patients.

Leukemic pulmonary infiltrates in chronic lymphocytic leukemia: Clinical and imaging features.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries. Although various patterns of lung involvement with CLL have been reported, data on clinicoradiologic presentation are sparse. METHODS: A computer-assisted search was conducted to identify patients encountered at Mayo Clinic from 1998 to 2022 and had leukemic pulmonary infiltrates (LPI) with CLL demonstrated on lung biopsy. Medical records and chest imaging studies were reviewed to identify clinical and radiologic features. RESULTS: Among 13 patients, median age was 77 years (range: 60-88) and included 10 men (77 %). All patients were known to have CLL with a median duration of 96 months (range: 50-408), and none were on treatment. Most common symptoms were dyspnea (62 %), cough (54 %), and fatigue (46 %); 2 patients (15 %) were asymptomatic. Dominant abnormality on CT consisted of single or multiple nodular/mass-like opacities in 10 patients (77 %), while diffuse centrilobular nodules, pleural mass, and diffuse bronchial wall thickening were each seen in one patient, respectively; intrathoracic lymphadenopathy was present in all. After diagnosis of LPI, treatment for CLL was administered to 7 patients (54 %); 6 patients (86 %) exhibited improvement. During follow-up (median 41 months), 8 (62 %) patients died. Causes of death included progressive CLL or treatment-related complications (2 patients), pneumonia (1 patient), unrelated causes (3 patients), and unknown in 2 patients. CONCLUSIONS: LPI in CLL is generally encountered in patients with known untreated CLL. The main imaging feature is single mass-like opacity or multiple nodular/mass-like opacities, associated with intrathoracic lymphadenopathy.

Cutaneous malignancies in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy that is associated with an increased risk of developing cutaneous malignancies. Clinical outcomes for these malignancies, including melanoma and keratinocyte cancers (KC), are worse for patients with CLL. Individuals with CLL develop an immunodeficiency of both the adaptive and innate immune system, which plays a role in the increased prevalence of skin cancers. This review focuses on the complex interplay between genetics, immunity, and pathogens that influence the cellular composition and biology of skin tumors and their microenvironment in CLL patients, and in comparison with other chronic hematological malignancies. It is paramount for dermatologists to be aware of the association between CLL (and chronic hematological malignancies more broadly) and cutaneous malignancies. This is a high-risk population who require regular and vigorous dermatologic follow-up.

Acquired von Willebrand's Syndrome in a Patient with Concomitant Chronic Lymphocytic Lymphoma and Smoldering Multiple Myeloma.

An African-American female in her sixties presented to the hospital with intermittent gum bleeding for the past two years along with severe anemia. This case details the differential and workup that lead to the diagnosis of acquired von Willebrand's syndrome (AvWS). A thorough investigation in the possible etiologies of AvWS revealed that the patient had concomitant chronic lymphocytic lymphoma (CLL) and smoldering multiple myeloma (SMM). Due to the concomitant diagnosis of CLL and SMM, there was a dilemma regarding whether CLL, SMM, or both was driving this patient's AvWS. Decision was made to treat the underlying CLL initially with rituximab and later on at recurrence with obinutuzumab/venetoclax with complete resolution of patient's bleeding and normalization of her factor VIII activity, von Willebrand factor antigen levels, and vWF:ristocetin cofactor levels. We believe this is first case in the literature of a patient with AvWS with concurrent CLL and SMM.

[Severe systemic vasculitis induced by ibrutinib]. / Vascularite systémique sévère induite par l'ibrutinib.

INTRODUCTION: The specific cutaneous toxicity of Bruton's tyrosine kinase inhibitors is poorly described. We report a case of severe systemic vasculitis induced by ibrutinib. OBSERVATION: A 73-year-old woman with chronic lymphocytic leukemia was treated with ibrutinib. Eighteen months after treatment onset, ulceronecrotic lesions on toes and tongue occurred. Skin biopsy found vasculitis of small and medium vessels. Biologic tests were negative. This vasculitis was refractory to systemic corticosteroid therapy and azathioprine. Ibrutinib was stopped on the hypothesis of drug-induced vasculitis. Skin lesions improved after discontinuation of ibrutinib. CONCLUSION: The mechanism of action of ibrutinib does not explain the occurrence of vasculitis and an immunoallergic mechanism is suspected.

A diagnostic challenge-First case of chronic lymphatic leukemia-associated necrotizing sweet syndrome.

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare disorder typically characterized by the clinical triad including a sudden onset of fever, painful skin lesions, and neutrophilia. The histopathological findings are a dense neutrophilic infiltrate and oedema of the dermis and epidermis without evidence of a vasculitis. Besides treatment of the underlying cause, sweet syndrome is typically treated with high-dose corticosteroids leading to a relapse-free response in 70% of patients. However, if left unrecognized or untreated, the condition may lead to serious complications. Here, we report on the case of a 38-year-old patient in whom, under the assumption of the presence of necrotizing fasciitis, exarticulation of the right arm was performed. In the absence of pathogen detection and insufficient response to anti-infective therapies, the diagnosis of a sweet syndrome was assumed and, later, confirmed by an excellent response to high-dose administration of systematic glucocorticoids. The case emphasizes the need to be aware of this rare syndrome, which can be easily misdiagnosed due to its close resemblance to infection and stresses the need of further research to define distinct diagnostic tools.