Long-Term Efficacy and Safety of Ibrutinib in the Treatment of CLL Patients: A Real Life Experience

Ibrutinib has demonstrated a significant clinical impact in patients with de novo and relapsed/refractory chronic lymphocytic leukemia (CLL), even in cases with unfavorable cytogenetics and molecular markers. All CLL patients’ data treated at our Institute with ibrutinib have been retrospectively reviewed. Forty-six patients received ibrutinib either as frontline (10) or second or more advanced treatment (36). Five patients presented with TP53 mutations; 11 had the deletion of chromosome 17p; 17 displayed an unmutated immunoglobulin variable heavy chain status. The median number of cycles administered was 26. Among patients treated frontline, the best overall response rate (ORR) was 90.0%. In patients receiving ibrutinib as a second or later line ORR was 97.2%. Median progression-free survival was 28.8 and 21.1 months for patients treated frontline and as second/later line, respectively. Median overall survival was not reached for those treated frontline and resulted in 4.9 years for patients treated as second/later line. Grade 3–4 hematological toxicities were neutropenia, thrombocytopenia, and anemia. Grade 3–4 extrahematological toxicities included diarrhea, cutaneous rash, utero-vesical prolapse, vasculitis, and sepsis. Ibrutinib is effective and well tolerated in CLL. Responses obtained in a real-life setting are durable and the safety profile of the drug is favorable.

Life-threatening reaction of a pediatric cancer patient to sodium hypochlorite

The use of sodium hypochlorite (NaOCl) as irrigation solution in endodontics is widespread and accidents of apical extravasation may occur, being in most cases mild to moderate situations of simple management. However, in immunosuppressed patients, the reaction may be exacerbated, with significant systemic changes and potentially life-threatening. Even so, there is a lack of information about the management of these special cases, especially in oncopediatric cases. Therefore, the aim is to report a case of severe reaction post-accident with NaOCl in a 13-year-old adolescent undergoing chemotherapy, with significant edema, gingival necrosis, cutaneous rash, edema of the extremities, pleural effusion, and bronchopneumonia, with a 30-day evolution. It is understood that several factors, including anatomical, may predispose this situation, which can occur even with expert and experienced professionals, not necessarily associated with poor practice. The authors raise the importance of further studies to discuss the real need and indication of the use of NaOCl as an irrigating solution for these patients and suggest the adoption of extra safety measures to avoid the occurrence of similar situations.

Case Report: Contrasting BCL2 Upregulation With Venetoclax in a Case of Refractory Lymphomatoid Papulosis and Progressive Chronic Lymphocytic Leukemia

A 57-year-old man affected by high-risk progressive chronic lymphocytic leukemia (CLL), primary resistant to first-line chemoimmunotherapy, developed a type A lymphomatoid papulosis (LyP) during a second progression of CLL. The two blood tumor entities were clonally unrelated. LyP presented with a diffuse (>90% body surface area) cutaneous rash and was characterized by intensely pruriginous dusky nodules (n = 10) and red flat-topped papules (n = 60). No response to topical corticosteroids and psoralen plus ultraviolet A (PUVA) phototherapy was observed. In order to effectively treat progressive TP53-mutated CLL, the potent BCL2 inhibitor, venetoclax, was initiated with no treatment-related complications. While CLL only achieved a partial response, a complete remission of LyP-associated cutaneous rash and of the intractable pruritus was obtained within 2 months from venetoclax initiation. BCL2 immunostaining of the original cutaneous specimen showed a strong over-expression of the anti-apoptotic protein, restricted to CD30+ lymphoid cells and reactive microenvironment. At 12 months follow-up, the patient is still in complete remission of LyP. Our findings underline the probable pathogenic role of BCL2 in LyP and the potential therapeutic efficacy of venetoclax for the treatment of this primary cutaneous CD30+ lymphoproliferative disorder, especially in the setting of severe and refractory disease.

Immune-mediated adverse events in immune checkpoint inhibitors therapy: literature review

Immune-mediated adverse events (imAEs) are complications of therapy with immune checkpoint inhibitors, which arise as a result of autoimmune inflammation. The article summarizes systemic (fatigue, fever), cutaneous (rash, itching), gastrointestinal (diarrhea, colitis, hepatitis, pancreatic dysfunction), endocrinological (hypothyroidism, hypophysitis, adrenal insufficiency, diabetes mellitus), pulmonary (pneumonitis, pleuritis), rheumatological (arthralgia), neurological (headache, sensory and motor disorders), renal (acute interstitial nephritis, lupus-like nephritis, granulomatous nephritis, diffuse interstitial nephritis and minimal change disease), hematological (anemia, cytopenia), cardiovascular (myocarditis) and ocular (conjunctivitis, episcleritis, ceratitis, blepharitis and uveitis) imAE. Pathogenetic mechanisms and treatment approaches (in accordance with toxicity grade and clinical recommendations) are discussed. Early symptom recognition, patient education and timely intervention are crucial for imAE correction.

Case Report: Mitral Valve Involvement and First-Degree Atrial-Ventricular Block in Two Patients With Multisystem Inflammatory Syndrome in Children

COVID-19 seems to be less frequent and severe in children compared to adults. Despite the very few symptoms usually found in children, great attention was recorded when in April 2020 a hyperinflammatory process in children with fever and multiorgan involvement after a paucisymptomatic COVID infection was reported. The United States Centers for Disease Control and the World Health Organization recognized and defined this syndrome as “Multisystem Inflammatory Syndrome in Children (MIS-C).” We describe two cases of MIS-C presenting with fever, cutaneous rash, and a mild cardiac involvement expressed with a transient mitral valve involvement and a first-degree atrioventricular block. Acute treatment was managed with intravenous immunoglobulin, oral aspirin, and intravenous corticosteroids reaching consequent good outcome. Clinical characteristics, treatment management, follow-up, and long-term evolution of children with MIS-C are still poorly defined. Further research is needed to better understand the pathogenesis of this newly described condition, to validate a high-level recommended therapy and a specific therapy tapering timings.

The Neurasthenic Nipper-Juvenile Idiopathic Arthritis

Juvenile Idiopathic Arthritis (JIA) is a heterogeneous group of paediatric, idiopathic, inflammatory arthritis exceeding >six weeks duration and commonly arising in children beneath <16 years. International League of Associations for Rheumatology (ILAR) has categorized juvenile idiopathic arthritis into distinctive subclasses as pauciarticular variant or oligoarthritis, Rheumatoid Factor (RF) positive polyarthritis, Rheumatoid Factor (RF) negative polyarthritis, systemic arthritis, psoriatic arthritis, enthesitis-related arthritis and undifferentiated arthritis. The condition is posited to arise from environmental factors, viral or bacterial infection or demonstrates a genetic predisposition. Juvenile idiopathic arthritis depicts decimated joint function with reduced Range of Motion (ROM), joint pain, morning stiffness, limping due to pain in the lower extremities, joint deformity and joint swelling commonly discerned within the knee, hand or foot, anomalous limb growth with leg length discrepancies,, uveitis, reoccurring pyrexia, cutaneous rash, myalgia, weight loss and disorders of skeletal growth. An intense, synovial infiltration of T lymphocytes, B lymphocytes, plasma cells, macrophages and dendritic cells is observed along with villous hyperplasia and hypertrophy, endothelial activation and hyperplasia and hyperplasia of synoviocytes.

A Case of Disseminated Cutaneous Herpes Simplex Virus-1 as the First Manifestation of Human Immunodeficiency Virus Infection

Reported clinical manifestations of active herpes simplex virus type 1 (HSV-1) infection include typically painful vesicular cutaneous rash in a dermatomal distribution, temporal lobe encephalitis, and rarely, fulminant septic shock with multiorgan failure. In immunocompromised patients, the cutaneous rash can become disseminated. We report a case of a 33-year-old male patient with undiagnosed human immunodeficiency virus (HIV) infection who presented to our emergency department (ED) with a disseminated cutaneous rash. The rash was extensive, involved 90% of his total body surface area. It began 5 days prior as small ulcerations localized to the left arm, sought care at an outside ED, diagnosed as severe dermatitis with bacterial superinfection and discharged with a cephalexin prescription. Laboratory results were positive for HIV test with a CD4 count of 254, white blood cell count (WBC) of 7.4 k/microL with 54% neutrophils, 9% lymphocytes, 0% eosinophils, 0% basophils, and serum creatinine and sodium of 3.05 mg/dL and 119 mEq/L, respectively. The burn team and dermatology ruled out Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis due to the absence of mucosal involvement, negative nikolsky sign, and absence of skin sloughing. Polymerase chain reaction of samples obtained from the skin lesions was positive for HSV-1. The rash resolved with intravenous acyclovir and was started on highly active antiretroviral therapy (HAART) on outpatient follow-up. To the best of our knowledge, comparable cases of significantly disseminated cutaneous HSV-1 infection as the initial presentation of HIV infection have been rarely reported.

Multisystem Inflammatory Syndrome in Children associated with COVID-19: Report of four cases in Mexico across the Mexico-US Border

Multisystem Inflammatory Syndrome in Children (MIS-C) is a newly described autoimmune disease mostly occurring in older children, adolescents, and young adults associated with Severe Acute Respiratory Syndrome-Coronavirus type 2 (SARS-CoV-2) infection. Several MIS-C publications from Europe and North America are available, with only a few from Latin America. This is the first Mexican publication of four case reports of MIS-C. Median age at admission was of 8.2 years. All cases manifested with fever, cutaneous rash, conjunctivitis, abdominal pain, and nausea/vomiting. All were admitted with shock, developed coronary abnormalities in the echocardiogram, and had lung abnormalities in the computerized tomography scan. Three needed medical care at the Pediatric Intensive Care Unit, all were resistant to intravenous immunoglobulin, and one patient died of severe myocarditis, shock and acute myocardial infarction. All four cases had a positive SARS-CoV-2 RT-PCR from nasopharynx.