Prolonged Disease Control Despite ALK Inhibitor Discontinuation in Advanced ALK-Positive NSCLC.

Introduction: EML4-ALK is an oncogenic driver, seen in around five per cent of advanced non-small-cell lung cancer (NSCLC) patients, which can be targeted with anaplastic lymphoma kinase tyrosine kinase inhibitors with great response rates. Disease flare refers to sudden rapid disease worsening on tyrosine kinase inhibitors (TKI) discontinuation, which is associated with shorter survival and worse outcomes. Here, we review cases previously published in the literature where patients developed disease flares, and contrast this with our patients who had prolonged survival despite TKI discontinuation. Case description: We report three different patients with advanced ALK-positive NSCLC seen at our institute, who had EML4-ALK translocation variant 1 oncogenic driver on next-generation sequencing. They received treatment with several different ALK inhibitors before opting to discontinue TKI. They were able to come off TKI safely without developing disease flare and had prolonged survival. Discussion: Shorter time to progression on TKI, presence of symptoms with disease progression or central nervous system/pleural metastasis have been previously linked with development of flare, although this was not seen in our case series. Tumour response at the time of treatment discontinuation, line of therapy, overall disease burden, fusion variant and co-alteration status can affect the prognosis of these patients after ALK TKI cessation. In particular, variant 1 and wild-type TP53 status may be a suitable patient population for dose optimisation strategies. Intermittent TKI dosing strategies may help to avoid acquiring resistance mutations and prevent long-term treatment toxicities. Conclusion: It is important for clinicians to identify patients at risk for developing disease flare on TKI discontinuation to improve outcomes. Intermittent TKI dosing strategies require further investigation. LEARNING POINTS: Patients who develop disease flare after cessation have poor survival and worse outcomes.Certain phenotypic and molecular characteristics of the tumour may help clinicians identify which patients are likely and which are unlikely to develop disease flare on TKI discontinuation.Advanced ALK-positive NSCLC with variant 1 and wild-type TP53 may be a suitable patient population for intermittent TKI dosing investigations.

Acquired Amegakaryocytic Thrombocytopenic Purpura: A Review of Therapeutic Options.

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare bone marrow disorder characterized by either a marked decrease or a complete absence of megakaryocytes with the preservation of all other cell lines. To date, more than 60 cases of AATP have been reported in the literature. Due to the rarity of this disease, no standard treatment guidelines have been established, and therapy is based on a handful of case studies and expert opinions. Herein, we provide a comprehensive review of currently utilized therapeutic options for AATP.

Infectious Complications After Tocilizumab in Patients with COVID: A Real-World Experience.

Introduction: Controversies remain regarding the safety of tocilizumab in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we seek to describe the infectious complications after tocilizumab in COVID patients and determine the related risk factors. Methods: A single-center retrospective observational study was conducted among adult patients with SARS-CoV-2 infection admitted between 06/01/2020 and 12/31/2021 who received tocilizumab at our institution. Baseline demographics and laboratory values are obtained through reviewing electronic medical records. Risk factors of infectious complications after tocilizumab are identified through regression analysis. Statistics are performed using SPSS. P-value <0.05 is considered statistically significant. Results: Out of the 52 patients identified, infectious complications after tocilizumab were documented in 30 patients (57.7%). The most common infections include pneumonia, urinary tract infections, and bacteremia of unknown sources. Overall mortality was 42.3%. Through multivariate regression analysis, age more than 65, hyperglycemia on admission, and tocilizumab administration more than 2 days after hospital admission are independent risk factors associated with developing infections. Conclusions: In real-world experience, infectious complications are not uncommon in COVID patients who receive tocilizumab. Early use of tocilizumab may be of benefit. More rigorous patient selection and monitoring should be explored in future studies.

Extramedullary chronic lymphocytic leukemia disguised as urinary tract infection.

Extramedullary and nonlymphoid organ involvement in chronic lymphocytic leukemia (CLL) is exceedingly rare, with only a few cases of bladder infiltration reported to date. Here, we present a case of a 71-year-old man with advanced-stage CLL who presented with gross hematuria initially thought to be secondary to a urinary tract infection. However, a cystoscopy with biopsy confirmed the diagnosis of extramedullary CLL with bladder involvement. The patient was started on venetoclax with improvement in symptoms and no recurrence of hematuria.

Acquired Amegakaryocytic Thrombocytopenia Progressing to Aplastic Anaemia.

Acquired amegakaryocytic thrombocytopenia (AAMT) is a rare disorder of the bone marrow characterized by a lack of megakaryocytes and preservation of other cell lines. It can occur due to an intrinsic stem cell defect or secondary to viral infections, autoimmune disorders, lymphoproliferative disorders or environmental toxins. With time, it can progress to aplastic anaemia (AA) and can have a poor prognosis. No standard guidelines exist for the treatment of AAMT progressing to AA. Herein, we report a rare case of AAMT leading to AA and review the handful of cases previously published in the literature. LEARNING POINTS: Acquired amegakaryocytic thrombocytopenia can present as isolated severe thrombocytopenia which can initially be misdiagnosed as immune thrombocytopenia.Lack of response to steroids and intravenous immunoglobulin should raise suspicion for acquired amegakaryocytic thrombocytopenia.Over time, acquired amegakaryocytic thrombocytopenia can progress to aplastic anaemia, which confers a worse prognosis.

Angioimmunoblastic T-cell lymphoma with exuberant plasmacytosis and spontaneous tumor lysis syndrome.

We present a 67-year-old man with complaints of confusion, chills, night sweats, and several days of poor oral intake. He had severe plasmacytosis on lab work, which initially raised concern for plasma cell leukemia. However, further workup led to the diagnosis of angioimmunoblastic T-cell lymphoma. His initial hospital course was complicated by spontaneous tumor lysis syndrome. Early recognition and prompt interventions are pivotal to improve survival outcomes in such patients.

Adenovirus-Associated Disseminated Intravascular Coagulation.

A 21-year-old previously healthy Caucasian female presented to the emergency department (ED) in the pre-COVID-19 era for evaluation of thrombocytopenia after a flu-like illness. The patient reported fever, cough, headache and myalgias for one week. She was on oral contraceptive pills (OCPs) for five years but discontinued one week ago. She was found to be in disseminated intravascular coagulation (DIC) and her hospital course was complicated by intraparenchymal hemorrhage, deep vein thrombus (DVT) in the right arm veins, bilateral pulmonary embolus (PE) and multiple splenic infarcts. An extensive workup was negative but nasopharyngeal swab came back positive for adenovirus by polymerase chain reaction (PCR).