A Case Study in Process Improvement to Minimize Delays from Obtaining Blood for Red Cell Exchange for a Patient with Sickle Cell Disease and Multiple Red Blood Cell Alloantibodies

The process of procuring several units of red blood cells for red cell exchange can sometimes take several hours to days, especially for patients with multiple clinically significant red cell alloantibodies. This can introduce delays, inconveniences, and even health challenges for the patient. For most planned exchanges, these delays are preventable with some foresight and process modifications that are relatively minor yet high leverage. We report a case study of process improvement whereby the apheresis nurse sends an e-mail to the blood bank when the nurse makes the patient’s next red cell exchange appointment as the signal to order blood about 6–8 weeks before the exchange.

Salvage Therapy in Early Relapse of T-Lymphoblastic Leukemia/Lymphoma Using Daratumumab/Nelarabine Combination: Two Consecutive Cases

Treatment of early relapses of T lymphoblastic leukemia/lymphoma is often unsuccessful. We tested an experimental regimen containing daratumumab and nelarabine in two young patients with early relapses of T lymphoblastic lymphoma and T-ALL, respectively. Both patients achieved a deep complete remission. Combining daratumumab with chemotherapy may have a role in relapsing T lymphoblastic leukemia/lymphoma.

Familial Hemophagocytic Lymphohistiocytosis Secondary to PRF1 Mutation

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that causes systemic inflammation which can progress to multiorgan failure and death. Symptoms and signs commonly seen in HLH include high fever, hepatosplenomegaly, pancytopenia, and hypertriglyceridemia. This report describes the 8-month clinical course of a 17-year-old male with G6PD deficiency who presented with intermittent high fever of unknown origin for 8 months accompanied by pancytopenia and bilateral lower limb weakness. A pathogenic homozygous missense mutation (c.1081A > T p.(Arg361Trp)) in the PRF1 gene was detected by whole exome sequencing (WES). The brain and the whole spine MRI showed leptomeningeal enhancement at different levels involving both the brain and the spine. Therefore, a diagnosis of familial HLH type 2 with CNS involvement was confirmed. Accordingly, treatment with dexamethasone, cyclosporin, and etoposide in addition to intrathecal methotrexate and hydrocortisone was given. The patient showed a dramatic response with significant neurological improvement of the bilateral lower limb weakness. Genetic analysis has helped the patient’s family with appropriate genetic counselling. This case highlights the importance of immediate treatment with immunosuppressants and the high clinical suspicion of physicians regarding HLH in areas where consanguinity is common.

NGS Analysis of Clonality and Minimal Residual Disease in a Patient with Concurrent Richter’s Transformation and CLL/SLL

B-cell lymphomas are neoplastic proliferations of clonal B lymphocytes. Clonality is generally determined by PCR amplification of VDJ rearrangements in the IgH heavy chain or VJ rearrangements in Igκ/Igλ light chain genes followed by capillary electrophoresis. More recently, next-generation sequencing (NGS) has been used to detect clonality in B-cell lymphomas because of the exponential amount of information that is obtained beyond just detecting a clonal population. The additional information obtained is useful for diagnostic confirmation, prognosis assessment, and response to therapy. In this study, we utilized NGS analysis to characterize two histologically distinct lymphomas (DLBCL and CLL/SLL) that were detected contemporaneously in an asymptomatic patient. NGS analysis showed that the same VDJ rearrangement was present in nodal (DLBCL) and marrow (CLL/SLL) biopsies confirming that the DLBCL resulted from Richter’s transformation of a subclinical CLL/SLL. The V region of the rearrangement remained unmutated without somatic hypermutation. In silico analysis showed that the HCDR3 sequence was heterogeneous and not stereotypic. Minimal residual disease analysis by NGS showed that the tumor clone decreased by 2.84 logs in the bone marrow after R-CHOP therapy. However, a small number of tumor cells were still detected in the peripheral blood after R-CHOP therapy. Subsequent allogeneic transplantation was successful in eradicating the tumor clone and achieving deep molecular remission. We show that NGS analysis facilitated clinical management in our patient by helping to characterize the VDJ rearrangement in detail and by tracking minimal residual disease with high sensitivity and specificity.

An Unusual Cause of Secondary ITP in a 34-Year-Old Hispanic Male

Secondary immune thrombocytopenic purpura (ITP) associated with Helicobacter pylori (H. pylori) infection has been described in the literature. It appears to have a geographic distribution; mostly encountered in countries with a higher prevalence for H. pylori such as Italy or Japan. H. pylori eradication has been recommended in the management of ITP with studies showing improvement in the platelet count in some patients. Substantial platelet count increases in patients with severe thrombocytopenia (platelet counts <30 × 103 microliter), however, are uncommon with H. pylori treatment alone. Here, we present a 34-year-old Hispanic male with worsening chronic thrombocytopenia that resolved following eradication of his H. pylori infection. Herein, we highlight a rare and reversible cause of secondary ITP. With this case report, we hope to encourage physicians to include H. pylori testing in the evaluation of thrombocytopenia.

Necrotizing Bacterial Myositis as the Initial Presentation of Severe Aplastic Anaemia

Introduction. Necrotizing soft tissue infections are rapidly progressing infections associated with severe inflammation and cytokine release. Early recognition and surgical intervention are key factors to secure survival. The current case presents a patient with multifocal necrotizing soft tissue infection as the initial presentation of severe aplastic anaemia. Case Presentation. A man in his fifties was admitted with septic shock with multiorgan failure and severe pancytopenia, after two days of malaise with high fever and right flank pain. The diagnosis streptococcal necrotizing myositis was significantly delayed due to atypical clinical findings. After initial surgical exploration, the decision was made to defer from surgical debridement due to extensive involvement of several muscle groups, grave pancytopenia, and suspected dismal prognosis. Surprisingly, the patient stabilized after antibiotics and intensive care treatment. Based on severe pancytopenia and hypocellular bone marrow, with no evidence of other bone marrow disorders, the patient was diagnosed with aplastic anaemia. Treatment for aplastic anaemia with antithymocyte globulin, cyclosporine, and eltrombopaq was started, and 2 months later, a partial haematological recovery was observed. The patient could be discharged from hospital without antibiotic treatment. Conclusions. This case illustrates the crucial role of a multidisciplinary approach on admission and further during the clinical course. Clinical improvement despite severe neutropenia and stabilization during immunosuppressive therapy suggest that immunological factors modulate clinical course in necrotizing soft tissue infections.

Reactivation of Coccidioides immitis in a Prosthetic Knee after Initiation of Chemotherapy

Coccidioides is an endemic fungus in the Southwestern United States and Central and South America. Coccidioidomycosis primary infections are typically of the lung with an asymptomatic or self-limiting course. Some infections disseminate to other parts of the body and a few can remain latent for many years. Reactivation of latent fungal disease can occur following an insult to the host immune system. Here, we describe a case of a 76-year-old Caucasian male patient who moved from California to Wisconsin with a history of coccidioidomycosis infection of the left knee that reactivated decades later in his prosthetic knee shortly after being initiated on ibrutinib (Imbruvica), a Bruton tyrosine kinase (BTK) inhibitor, for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). There have been some case reports regarding coccidioidomycosis infections after initiating ibrutinib therapy but none with a 50 year latency period before reactivation. Readers will learn the immunological effects of ibrutinib on the hosts’ innate and adaptive immunity and its role in putting the host at risk for invasive fungal infections. We also review the literature and data on treatment regimens and recommendations based on current guidelines.

Mimicking Myelodysplastic Syndrome: Importance of Differential Diagnosis

Copper deficiency is a rare nutritional deficiency with hematological manifestations that mimic those found in myelodysplastic syndrome, a hematological malignancy incurable without allogeneic hematopoietic stem cell transplantation. Bone marrow biopsy findings and peripheral blood counts are oftentimes insufficient to differentiate the two conditions. Moreover, the symptoms of copper deficiency can arise years after the surgery, making diagnosis a challenge. In patients with new-onset pancytopenia, copper deficiency must be considered on the differential, especially in the setting of known risk factors such as bariatric surgery, zinc supplementation, and celiac disease. Herein, we present a case of a 61-year-old female with a remote history of gastric bypass being evaluated for MDS in the context of progressive pancytopenia and new-onset paresthesias. The patient was found to have low serum copper and ceruloplasmin. Copper supplementation largely resolved the hematological abnormalities, but the limb paresthesias remain. This case highlights the need to identify copper deficiency early and distinguish it from MDS in order to prevent permanent neurological deficits and catastrophic response should the patient undergo hematopoietic stem cell transplantation.

A Rare Cause of Acquired Factor X Deficiency in an 87-Year-Old Female

Factor X deficiency is a rare coagulopathy that can be inherited or acquired. Acquired factor X deficiency has been associated with plasma cell dyscrasias, amyloids, and use of vitamin K antagonists. Of plasma cell dyscrasias, most cases in the literature have been associated with multiple myeloma with or without concomitant AL amyloidosis. Here, we present a rare case of acquired isolated factor X deficiency in an elderly patient with immunoglobulin A (Ig A) monoclonal gammopathy of undetermined significance (MGUS). Herein, we highlight a rare cause of acquired factor X deficiency, and we hope to contribute to the growing literature of plasma cell dyscrasias associated with factor X deficiency.

Life-Threatening Retroperitoneal Hematoma in a Patient with COVID-19

COVID-19 is a respiratory illness that affects the human body in many different ways. The disease carries both thrombotic and hemorrhagic complications, especially in those patients who are anticoagulated to prevent the thromboembolic manifestations. In this report, we discuss a case of retroperitoneal hemorrhage in a patient treated with therapeutic anticoagulation which ultimately led to the patient’s death. The literature highlights the importance of anticoagulation because it reduces mortality in patients hospitalized with COVID-19. Although, more recent studies suggest that patients treated with therapeutic anticoagulation are at a higher risk of hemorrhage and increased mortality. Therefore, our case stresses the importance of active monitoring of these patients to detect any suspected case of hemorrhage early to reduce mortality. Overall, more research should be conducted to determine the optimal dosing of anticoagulation that balances safety and efficacy.