Programmed death-ligand 1 expression in patients with primary or secondary myelofibrosis.

BACKGROUND: It has been described in mice models that myeloproliferative neoplasm (MPN) with JAK2-V617F mutation has an increased expression of programmed death-ligand 1 (PD-L1) in megakaryocytes leading to cancer immune evasion by inhibiting the T-lymphocytes. AIMS: To quantify and compare the PD-L1 expression on bone marrow (BM) of patients with MPN JAK2 positive, negative, and normal controls. METHODS: We collected BM of patients with MPN JAK2 positive, negative and normal controls from 1990 to 2019. We also created a scoring system to quantify PD-L1 expression in megakaryocytes. RESULTS: We obtained 14 BM with JAK2 positive PMF, 5 JAK2 negative PMF, and 10 patients with normal BM biopsies. PD-L1 expression was higher in the JAK2 positive group compared with the control group with a score of 212.6 versus 121.1 (t-value 2.05, p-value 0.025). In addition, the score was higher in the PMF group regardless of JAK2 mutational status when compared with the control group with score of 205.9 versus 121.1 (t-value 2.12, p-value 0.021). There was no difference in the PD-L1 score between the JAK2 negative versus the control group 187.2 versus 121.1 (t-value 1.02, p-value 0.162). CONCLUSION: These findings suggest that PMF patients with a JAK2 mutation have a higher PD-L1 expression in megakaryocytes compared with the control group. We postulate that the combination of checkpoint and JAK2 inhibitors may be an active treatment option in JAK2 mutated PMF given the higher PD-L1 expression.

The utility of hyperbaric oxygen therapy in post-transplant cyclophosphamide-induced hemorrhagic cystitis: a case report and review of the literature.

BACKGROUND: To date, there are only a few case reports of cyclophosphamide (Cy)-induced hemorrhagic cystitis (HC) in adult or pediatric allogeneic stem cell transplant (SCT) patients treated successfully with hyperbaric oxygen (HBO). In all the reported cases, Cy was used as a part of the conditioning regimen, rather than post-transplant for graft-versus-host-disease (GVHD) prophylaxis. More recently, the risk of HC in allogeneic SCT is further increased by the widespread use of post-transplantation cyclophosphamide (PTCy) as a highly effective strategy for GVHD prophylaxis. This is the first case reported of PTCy-induced HC successfully treated with HBO to the best of our knowledge. CASE PRESENTATION: In this article, we present a 58-year-old Caucasian male case of allogeneic SCT complicated by severe HC following PTCy, which was successfully treated with HBO, eliminating the need for cystectomy. CONCLUSION: HBO can be a safe, noninvasive, alternative treatment modality for PTCy-induced HC developing in allogeneic SCT patients.

Think Melkersson-Rosenthal Syndrome: A Fissured Tongue With Facial Paralysis.

Melkersson-Rosenthal syndrome (MRS) was first described and named after E. Melkersson in 1928 and C. Rosenthal in 1931. MRS is a rare cause of recurrent facial nerve palsy and can manifest as facial paralysis, orofacial edema, and/or tongue fissuring. Presenting with the complete triad, it was scarcely reported in literature. However, the patient reported here had the complete triad. MRS should be considered when facial paralysis is recurrent or when it presents with orofacial edema, and/or tongue fissuring.

Glioblastoma Multiforme in a Patient with Multiple Myeloma: A Case Report and Literature Review.

INTRODUCTION: Lenalidomide is an immunomodulatory drug approved by the US Food and Drug Administration in 2006 for the treatment of multiple myeloma. In 2012, the Food and Drug Administration issued a statement warning physicians of the increased risk with lenalidomide treatment of the following secondary primary malignancies: Acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma. The statement did not mention glioblastoma multiforme, a Grade 4 astrocytoma, or other high-grade astrocytomas that have been reported on rare occasions in the setting of multiple myeloma. CASE PRESENTATION: A 72-year-old man, who had been in complete remission from multiple myeloma for 1 year after treatment that included lenalidomide, presented with confusion, headache, nausea and vomiting, and recurrent falls. A magnetic resonance image of his brain revealed a mass that on stereotactic biopsy was found to be glioblastoma multiforme. DISCUSSION: We present the seventh reported case of high-grade astrocytoma as a second primary malignancy in multiple myeloma and the first reported occurrence of glioblastoma multiforme after the use of lenalidomide in multiple myeloma. This report adds to the pool of cases that reveal associations between use of lenalidomide and increased risk of developing secondary primary high-grade astrocytomas in multiple myeloma.

Two Catastrophes in One Patient: Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Shock Syndrome.

A 70-year-old, immunocompromised patient presented to the emergency room (ER) five weeks after she was started on clopidogrel. She complained of skin eruption, mouth ulcers, fatigue, and myalgia over the past two weeks. Labs showed severe hyponatremia, acute kidney injury, rhabdomyolysis, hyperkalemia, and elevated liver enzymes. She was treated with steroids and discharged after her condition improved. However, a month later, she returned to the ER, complaining of nausea, vomiting, diarrhea, dizziness, chills, and shortness of breath over the past two days. She was lethargic and had orthostatic hypotension. She deteriorated clinically within a few days, with worsening lethargy and the development of respiratory distress along with profound hypotension. She needed mechanical ventilation and vasopressors. In addition, she had melena, severe thrombocytopenia, and hemolytic anemia. With supportive care, she improved and was discharged after a long stay in the intensive care unit. Retrospectively, the first hospitalization was believed to be caused by drug reaction with eosinophilia and systemic symptoms (DRESS). Treating that with steroids compromised her immune system beyond her pre-existing primary immunodeficiency status. At the time of her second hospitalization, she met the Centers for Disease Control and Prevention (CDC) criteria for a toxic shock syndrome (TSS) diagnosis. Her TSS started four days after a skin biopsy, which was done as part of her skin rash workup. It was thought that the source of the exotoxin that mediated her TSS was her skin, given the temporal relationship of the skin biopsy to her TSS. Another potential source of the exotoxin was the gastrointestinal tract, given the predominant gastrointestinal symptoms she had at the time of her second admission.