Case Reports in Hematology

VEXAS syndrome stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. The syndrome is a combined hematological and rheumatological condition caused by a somatic mutation in the UBA1. There is an association between VEXAS and hematological conditions such as myelodysplastic syndrome (MDS), monoclonal gammopathies of uncertain conditions (MGUS), multiple myeloma (MM), and monoclonal B-cell lymphoproliferative conditions. There are not many descriptions of patients having VEXAS in combination with myeloproliferative neoplasm (MPN). With this article, we want to present a case history of a man in his sixties with a JAK2V617F mutated essential thrombocythemia (ET) developing VEXAS syndrome. The inflammatory symptoms occurred three and a half years after the ET diagnosis. He started to experience symptoms of autoinflammation and an overall worsening of his health, and blood work showed high inflammatory markers, leading to repeated hospitalizations. His major complaint was stiffness and pain, and high dosages of prednisolone were necessary to obtain pain relief. He subsequently developed anemia and significantly variable levels of thrombocytes, which previously were at a steady level. To evaluate his ET, we made a bone marrow smear demonstrating vacuolated myeloid and erythroid cells. Having VEXAS syndrome in mind, genetic testing identifying the UBA1 gene mutation was performed, thus confirming our suspicion. The work-up with myeloid panel on his bone marrow identified genetic mutation in the DNMT3 too. After developing VEXAS syndrome, he experienced thromboembolic events with both cerebral infarction and pulmonary embolism. Thromboembolic events are also common in JAK2 mutated patients, but in his case, they presented first after VEXAS had developed. Throughout the course of his condition, several attempts with prednisolone tapering and steroid sparing drugs were tried. He could not get pain relief unless the combination of medications included a relatively high dose of prednisolone. Currently, the patient uses prednisolone, anagrelide, and ruxolitinib, with partial remission and fewer hospitalizations and more stabilized hemoglobin and thrombocytes.

Mixed phenotype acute leukemia (MPAL) is characterized by leukemic blasts that express markers of multiple lineages. Compared with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), MPAL is considered to have a poor treatment outcome. We report a case of MPAL T/myeloid not otherwise specified that was initially presented as multilineage lymphoblastic lymphoma and subsequently developed into leukemic MPAL. An acute lymphoblastic leukemia-based treatment regimen was ineffective, but azacitidine and venetoclax therapy resulted in hematological complete remission. Our case suggests that multilineage lymphoblastic lymphoma should be considered to be the same disease as MPAL, albeit with different clinical presentations. Optimal treatment for MPAL has not been established yet, but azacitidine and venetoclax therapy may be a potential approach.

Plasma cell dyscrasias are a subset of hematological malignancies involving the production of monoclonal immunoglobulins. This spectrum of disorders includes asymptomatic conditions such as monoclonal gammopathy of unknown significance as well as extremely aggressive malignancies such as plasma cell leukemia. Monoclonal gammopathies are occasionally associated with renal failure, which can occur via many pathophysiological processes. The most common of these is light chain cast nephropathy, but many rare renal complications exist, including thrombotic microangiopathy (TMA) and focal segmental glomerulosclerosis (FSGS). Here, we report a patient with new renal failure with features of TMA and FSGS on biopsy and found to be secondary to plasma cell leukemia.

Background. Human monocytic ehrlichiosis (HME) is a potentially life-threatening tick-borne illness. HME-associated hemophagocytic lymphohistiocytosis (HLH) is a rare entity with a paucity of published literature regarding treatment and outcome. We present the clinical features, treatment, and outcomes of 4 patients at our institutions with HME-associated HLH. This review also summarizes the current literature regarding the presentation, treatment, and outcome of this infection-related HLH. Methods. We searched the PubMed database for case reports and case series. All cases were diagnosed according to the HLH-04 criteria. Results. Four cases of HME-associated HLH were included from our institutions. The literature review yielded 30 additional cases. About 41% of the cases were in the pediatric population; 59% were female; and all patients had fever, cytopenia, and elevated ferritin. Most patients were immunocompetent; all but one patient with available data were treated with doxycycline, and eight of the patients with available data received the HLH-94 treatment protocol. The mortality rate was 17.6%. Conclusions. HME-associated HLH is a rare but serious syndrome with significant mortality. Early treatment with doxycycline is critical, but the role of immunosuppressive therapy is individualized.

Background. Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare, primary immunodeficiency syndrome characterized by warts, hypogammaglobulinemia, immunodeficiency, and characteristic bone marrow features of myelokathexis. The pathophysiology of WHIM syndrome is due to an autosomal dominant gain of function mutation in the CXCR4 chemokine receptor resulting in increased activity that impairs neutrophil migration from the bone marrow into the peripheral blood. This results in bone marrow distinctively crowded with mature neutrophils whose balance is shifted towards cellular senescence developing these characteristic, apoptotic nuclei termed myelokathexis. Despite the resultant severe neutropenia, the clinical syndrome is often mild and accompanied by a variety of associated abnormalities that we are just beginning to understand. Case Report. Diagnosis of WHIM syndrome is incredibly difficult due to phenotypic heterogeneity. To date, there are only about 105 documented cases in the scientific literature. Here, we describe the first case of WHIM syndrome documented in a patient of African ancestry. The patient in question was diagnosed at the age of 29 after a comprehensive work-up for incidental neutropenia discovered at a primary care appointment at our center in the United States. In hindsight, the patient had a history of recurrent infections, bronchiectasis, hearing loss, and VSD repair that could not be previously explained. Conclusions. Despite the challenge of timely diagnosis and the wide spectrum of clinical features that we are still discovering, WHIM syndrome tends to be a milder immunodeficiency that is highly manageable. As presented in this case, most patients respond well to G-CSF injections and newer treatments such as small-molecule CXCR4 antagonists.

Primary cardiac lymphoma (PCL) is a rare, potentially fatal subtype of non-Hodgkin’s lymphoma. Thrombocytopenia has also infrequently been reported in association with other primary cardiac tumours and can add substantial morbidity to an already life-threatening diagnosis if present. We report a rare case of a 70-year-old man who presented with thrombocytopenia (91 × 10⁹/L) and progressive right heart failure. Transthoracic echocardiogram revealed a large 8 × 4 cm right atrial mass with severe tricuspid obstruction, confirmed as PCL on subsequent endomyocardial biopsy and immunohistochemistry. He deteriorated into cardiogenic shock precipitated by atrial fibrillation, with worsening thrombocytopenia (18 × 10⁹/L) in the setting of ischaemic hepatitis. The patient stabilised with initiation of high dose steroids prior to tissue diagnosis and platelet counts normalised following chemotherapy. This case demonstrates the importance of considering PCL as a diagnosis and preemptive initiation of high dose steroids to improve outcomes in PCL associated with cardiogenic shock. This case also elucidates a potential pathophysiological association between PCL and thrombocytopenia.