Naveed Ali

New-onset acute thrombocytopenia in hospitalized patients: pathophysiology and diagnostic approach

ABSTRACT Thrombocytopenia is a hematological finding commonly encountered in daily clinical practice from asymptomatic clinic patients to critically ill intensive care unit patients. A broad spectrum of etiologies and variation in clinical presentation often present a diagnostic challenge. Furthermore, concomitant presence of thrombosis and thrombocytopenia, as in cases of thrombotic thrombocytopenia, complicates the management. In hospitalized patients, new-onset thrombocytopenia is an important reason for hematology consultation. Therefore, it is of utmost importance that the etiology is diagnosed accurately. In addition, a basic understanding of the pathophysiology and the differential diagnosis avoids delay in the diagnosis and leads to rapid initiation of treatment. This review will address causes of thrombocytopenia that arises in hospitalized patients with an emphasis on the pathophysiological basis of each disorder.

Left atrial abnormality (LAA) as a predictor of ibrutinib-associated atrial fibrillation in patients with chronic lymphocytic leukemia

ABSTRACT Results from several recent studies in chronic lymphocytic leukemia (CLL) have demonstrated an association between ibrutinib exposure and the development of atrial fibrillation, estimated incidence of 11% with long-term follow up. This is a common cause of ibrutinib discontinuation. Risk factors for atrial fibrillation include advanced age, hypertension (HTN), mitral valve disease (MVD), left atrial remodeling, coronary artery disease (CAD) and risk factors for cardiovascular dysfunction We conducted a retrospective case control study using the presence of left atrial abnormality identified on pre-ibrutinib EKGs, defined as either (1) Lead II-bifed p wave, with 40 mcsec between peaks for ≥ 2.5 mm wide ≥ 100 msec in duration, (2) Lead V1-biphasic P wave with terminal portion ≥ 40 msec in duration or terminal portion ≥ 1 mm deep or (3) PR interval ≥ 200 msec (intra-atrial conduction delay) as a predictor for development of atrial fibrillation. 183 consecutively CLL patients treated with ibrutinib were identified. 44 patients met inclusion criteria (20 cases, 24 controls). 20 (11.3%) of patients developed atrial fibrillation. Left atrial enlargement was identified as a significant predictor of development of atrial fibrillation (OR 9.1, 95% CI 2.2–37.3, p=0.02). Age, baseline HTN, CAD, diabetes, age and sex were not significant predictors. Area under the ROC curve for the model was estimated to be 75%. LAA identified by EKG is a moderately specific and sensitive finding that can identify patients at increased risk for this toxicity.

Guillain-Barré syndrome occurring synchronously with systemic lupus erythematosus as initial manifestation treated successfully with low-dose cyclophosphamide.

Systemic lupus erythematous (SLE) is frequently encountered in clinical practice; a widespread immunological response can involve any organ system, sometimes leading to rare and diagnostically challenging presentations. We describe a 38-year-old female who presented with symmetric numbness and tingling of the hands and feet, and cervical pain. Imaging studies were not diagnostic of any serious underlying pathology. The patient developed ascending paresis involving lower extremities and cranial muscles (dysphagia and facial weakness). Guillain–Barré syndrome (GBS) was diagnosed on the basis of electromyography and lumbar puncture showing albuminocytologic dissociation. Intravenous immunoglobulins (IVIG) were administered for 5 days. Supported by anti-dsDNA antibody, oral ulcers, proteinuria of 0.7 g in 24 h, and neurological manifestation, she was diagnosed with lupus. After completion of IVIG, she received pulse-dose corticosteroids and one dose of low-dose cyclophosphamide. Her neurological symptoms improved and she had complete neurological recovery several months after her initial presentation. Literature search provides evidence of co-occurrence of lupus and GBS occurring mostly later in the course of the disease. However, GBS as initial manifestation of SLE is exceedingly rare and less understood. The association of GBS with lupus is important to recognize for rapid initiation of appropriate therapy and for consideration of immunosuppressive therapy which may affect the outcome.

A diagnostic challenge in a young woman with intractable hiccups and vomiting: a case of neuromyelitis optica.

Intractable nausea and vomiting along with hiccups is a commonly encountered problem on any general medicine or gastroenterology service. These symptoms are usually not appreciated as the possible initial manifestation of neuromyelitis optica (NMO). Missing diagnosis at this early stage will lead to a delay in the treatment, and hence, irreversible complications including blindness and paraplegia could occur. We report a case of a 22-year-old young female who presented with intractable hiccups and vomiting. After extensive evaluation, she was found to have NMO which involved the area postrema, the vomiting center of the brain. Early diagnosis from the clinical picture aided by aquaporin-4 serologic testing is extremely important to allow early initiation of immunosuppressive therapy. Immunosuppression gives an opportunity to modify the disease at an earlier stage rather than waiting for evolution of disease to fulfill the diagnostic criteria of NMO.

The tell-tale heart: A case of recurrent vulvar carcinoma with cardiac metastasis and review of literature

A 50-year-old female was diagnosed with vulvar cancer treated with left partial vulvectomy and bilateral lymphadenectomy. Ten months after her surgery, she presented with increased labial swelling, pain and discharge. Biopsy confirmed recurrence of squamous cell vulvar carcinoma. Incidentally, on restaging radiographic scans, she was found to have a large right ventricular mass which, after surgical debulking, was shown to be a squamous cell cancer of vulvar origin. She was commenced on chemotherapy with carboplatin and paclitaxel along with concurrent radiation therapy. Restaging PET scan showed persistent metastatic disease. She was switched to Cisplatin/Taxol after having hypersensitivity reaction to Carboplatin. She received 5 cycles with progression of disease in the follow up scans. She then received Nivolumab for 2 cycles. The patient then opted for comfort directed care given worsening functional status and progression of disease on repeat imaging. Secondary cardiac tumors are very rare and not extensively studied in oncology. Therefore, optimal management is not entirely clear. It is extremely rare for vulvar cancer to metastasize to the heart and only two cases have been reported in the literature. However, vulvar cancer metastasizing to the right ventricular cavity and endocardium has not been described before. We believe that this is the first ever such reported case.

Casual or Causal? Two Unique Cases of Hodgkin’s Lymphoma: A Case Report and Literature Review

Case series Patient: Male, 38 • Male, 30 Final Diagnosis: Hodgkin’s lymphoma Symptoms: Lymphadenopathy • shortness of breath Medication: — Clinical Procedure: — Specialty: Oncology Objective: Rare disease Background: Immunosuppressive diseases and therapies have long been connected to risk of malignancies, especially lymphoma. With some diseases and drugs, the association is well established but the data is mostly anecdotal because of the rarity of the situation. Case Reports: We present 2 rare cases. The first patient had psoriasis, was on etanercept, and developed Hodgkin’s lymphoma. This case is rare because psoriasis and etanercept do not usually cause lymphoma, and if they do, it is predominantly Epstein-Barr virus-positive non-Hodgkin’s lymphoma. The second patient had acquired immune deficiency syndrome (AIDS) and developed Hodgkin’s lymphoma while on highly active antiretroviral therapy (HAART). This case is rare because AIDS mostly causes Kaposi’s sarcoma or non-Hodgkin’s lymphoma due to immunosuppression, but whether it is AIDS or HAART therapy that leads to development of Hodgkin’s lymphoma in these patients is not clear. Conclusions: Immunosuppression seems to be the primary culprit leading to lymphomas in these cases. The exact mechanism is still not completely understood.

Immunoglobulin D Multiple Myeloma, Plasma Cell Leukemia and Chronic Myelogenous Leukemia in a Single Patient Treated Simultaneously with Lenalidomide, Bortezomib, Dexamethasone and Imatinib.

Multiple myeloma (MM) is a neoplastic lymphoproliferative disorder characterized by uncontrolled monoclonal plasma cell proliferation. Among different isotypes of MM, immunoglobulin D (IgD) MM is very rare, representing only 1 to 2% of all isotypes. Chronic myelogenous leukemia (CML) is a neoplastic myeloproliferative disorder of pluripotent hematopoietic stem cell, which is characterized by the uncontrolled proliferation of myeloid cells. An 88-year-old male was diagnosed simultaneously with IgD kappa MM and CML. A distinctive feature in this patient was the progression to plasma cell leukemia without any symptomatic myeloma stage. He was treated simultaneously with lenalidomide, bortezomib and imatinib. Synchronous occurrence of these rare hematological malignancies in a single patient is an exceedingly rare event. Multiple hypotheses to explain co-occurrence of CML and MM have been proposed; however, the exact etiological molecular pathophysiology remains elusive.

Analysis of Efficacy and Tolerability of Bruton Tyrosine Kinase Inhibitor Ibrutinib in Various B-cell Malignancies in the General Community: A Single-center Experience

Background Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B‐cell malignancies. The primary objective of the present study was to investigate the efficacy of ibrutinib therapy in various B‐cell malignancies in the general community. The secondary objectives included studying the adverse effects, ibrutinib‐induced peripheral lymphocytosis, and effect on immunoglobulin levels. Patients and Methods The present study was a retrospective observational cohort analysis conducted at Abington Jefferson Health. The clinical response was determined from the hematologists assessment and evaluated independently using the response criteria for each B‐cell malignancy. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The Wilcoxon signed‐rank test was used to compare immunoglobulin levels before and after ibrutinib. Forty five patients with B‐cell malignancies and receiving ibrutinib therapy were eligible. Results The median age was 73 years (range, 49‐96 years), and 84.4% of the patients had received ≥ 1 previous therapy. The best overall response rate of all cohorts combined was 63.8%. The greatest overall response rate was observed in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (76.1%), followed by those with Waldenström macroglobulinemia (75%). Of the 45 patients, 88.9% experienced adverse effects. Antiplatelet activity of ibrutinib was most commonly observed (30.5%). Of note, 5 patients (11%) developed new‐onset atrial fibrillation after drug initiation. Peripheral lymphocytosis after drug initiation was observed in most patients, with a peak level at 1 month (median lymphocyte count, 2.7 × 103 cells/&mgr;L). Although the IgG levels at 3, 6, and 12 months had decreased (P = .01 for all) compared with the levels before ibrutinib, the IgA levels had not increased at 3, 6, 12, and 24 months (P = .6, P = .5, P = .3, and P = .9, respectively). Conclusion Ibrutinib is a highly effective and tolerable drug for B‐cell malignancies in the general community. In contrast to the previously reported rate of 5% to 7%, we observed a higher rate (11%) of atrial fibrillation, which might have resulted from the smaller sample size in the present study and the multiple comorbidities. Nonetheless, this treatment‐limiting side effect requires further elucidation. Paradoxical lymphocytosis at the outset of therapy was a common and benign finding. In conjunction with the reported trials, the IgG levels decreased in the first year of continued therapy. However, the IgA levels did not increase, even after 2 years of therapy. Micro‐Abstract Ibrutinib, a novel Bruton tyrosine kinase inhibitor, has revolutionized the treatment of various B‐cell malignancies. In this retrospective study, we analyzed the data of 45 patients with various B‐cell malignancies to determine ibrutinibs clinical efficacy and adverse effects in a real‐world setting. Results showed an excellent efficacy and a favorable toxicity but a higher incidence of atrial fibrillation.

Bulky scalp melanoma with metastasis responding completely to ipilimumab

A 69-year-old man noticed a ‘pimple’ on the scalp vertex for the first time about 4 months prior to presentation. The lesion was associated with itching, bleeding and an accelerated growth noticed by his wife. Examination demonstrated a 6×7 cm fungating mass with numerous satellite lesions measuring 3–5 mm and associated alopecia (figure 1A). Right occipital and supraclavicular lymphadenopathy was also noted. Biopsy of the lesion revealed BRAF (V600K) mutated malignant melanoma with ulceration, high mitotic index and vascular invasion. Systemic staging with positron emission tomography (PET) and CT scans detected an avid 6 mm right lung nodule and a 1.5 cm mass in the right lobe of the …

Real world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States

Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with chronic lymphocytic leukemia treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients, the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study.