Hematol. Rep., Volume 10, Issue 2 (May 2018) – 6 articles

We present an unusual case of myeloid sarcoma with ascites and abdominal pain in which initial clinical, laboratory, and imaging studies suggested a gastrointestinal malignancy or lymphoma. Subsequent detection of leukemic ascites and blasts in a gastric, small bowel, and skin biopsy supported a diagnosis of myeloid sarcoma. Bone marrow biopsy revealed 15% blasts, and cytogenetics with an inversion 16 rearrangement was diagnostic of acute myeloid leukemia (AML). Positron emission tomography-computed tomography performed at presentation to stage a presumptive lymphoma found later utility in following the burden of extramedullary disease. Standard AML induction chemotherapy resulted in complete remission and was followed by three rounds of high dose cytarabine consolidation. The patient unfortunately relapsed leading to re-induction followed by allogeneic stem cell transplantation. This report describes the presentation, assessment, and management of myeloid sarcoma. Full article

We propose antenatal blood tests using high-resolution DNA melting (HRM) analysis for beta thalassemia mutation detection after hemoglobin A₂ estimation as a modified strategy for the identification of beta thalassemia at-risk couples. Antenatal blood samples of 1115 couples were transferred from the antenatal care clinic. Hemoglobin A₂ was quantified, and proportions ≥3.5% were further assessed for beta thalassemia mutation using HRM analysis. Twelve types of beta thalassemia mutations, including hemoglobin E, were identified. There were 23 couples who were detected as at-risk. All at-risk couples were identified within 7 working days after sample receipt. Prenatal diagnosis revealed 6 affected fetuses. One fetus was homozygous CD17 (AT), and five fetuses exhibited beta⁰ —thalassemia/ hemoglobin E disease. These results were consistent with the outcomes calculated using the Hardy-Weinberg equation. Antenatal blood tests for mutation detection using high-resolution DNA melting analysis after hemoglobin A₂ estimation is a feasible laboratory method for the recruitment of couples with a fetus that is at risk for beta thalassemia. This modified strategy is cost-effective and may be beneficial for use in a beta thalassemia prevention program. Full article

For many patients with sickle cell disease (SCD), jaundice is a significant clinical disease manifestation that impacts on patient well-being. We report a case of a patient with SCD and chronic jaundice treated with voxelotor (GBT440), a novel small molecule hemoglobin oxygen affinity modulator and potential disease-modifying therapy for SCD. The case patient is a 27-year-old Black male with a long history of SCD with clinical jaundice and scleral icterus. After starting voxelotor, the patient reported that his jaundice cleared within one week, and that he felt much better with more energy, and was relieved after his eyes cleared. Voxelotor reduced bilirubin and unconjugated bilirubin (by up to 76%), and hemoglobin improved from 9.9 g/dL at baseline to 11.1 g/dL at 90 days. Jaundice impacts many adults with SCD, significantly impacting self-image. Voxelotor treatment reduced bilirubin levels and improved jaundice, resulting in an improved sense of well-being in our case patient. Full article

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication of organ transplantation. Progress has recently been made in the pathological classification of PTLD. However, the clinical course has not been clarified because of the rarity of this disease. We experienced a case of PTLD with a fulminant clinical course. The patient had been under longterm immunosuppressive treatment for aplastic anemia. He received related allogeneic hematopoietic stem cell transplantation. Soon after transplantation, he developed PTLD. According to the guidelines, we reduced immunosuppression. However, the disease course was so fulminant that there was no time for the patient to respond, and he died of multi-organ failure. There may be various clinical types of PTLD, which may include some fulminant cases. In such a case, it is not sufficient to reduce immunosuppression. The patient should be carefully observed and an appropriate individual treatment should be chosen. Full article

Extramedullary hematopoiesis (EMH) is a presence of hematopoietic activity in the extramedullary sites. EMH can occur in both benign and malignant hematologic diseases. The liver and spleen are the most common sites, but may also occur infrequently at other sites. EMH often occurs in more than one site and quite rare in an isolated organ. In this study we describe an unusual case of generalized lymphadenopathy secondary to isolated extramedullary hematopoiesis as an initial manifestation of primary myelofibrosis. Computed tomography revealed generalized lymphadenopathy including mediastinal, abdominal and pelvic lymph nodes with extensive illdefined sclerotic lesions throughout the skeletal system suggestive of lymphoma/leukemia. Lymph node biopsy showed no evidence of malignancy or granuloma, however, large abnormal cells with multilobated nuclei were seen scattered in the lymph nodes. These abnormal cells were proved to be megakaryocytes. Granulocytic precursors were less obvious on the H&E section. The diagnosis was determined as EMH in the lymph node. Bone marrow (BM) examination showed hypercellular marrow for patient’s age with granulocytic and megakaryocytic proliferation with increase in BM fibrosis and reported as a myeloproliferative neoplasm, consistent with primary myelofibrosis. In summary, although EMH is not always a malignant process; it is important to stress that the patient should be investigated for underlying hematological disorders, when it is noted elsewhere. Full article

Sickle cell disease is characterized by hemolytic anemia, vasoocclusion and early mortality. Polymerization of hemoglobin S followed by red blood cell sickling and subsequent vascular injury are key events in the pathogenesis of sickle cell disease. Sickled red blood cells are major contributors to the abnormal blood rheology, poor microvascular blood flow and endothelial injury in sickle cell disease. Therefore, an agent that can prevent and or reverse sickling of red blood cells, may provide therapeutic benefit for the treatment of sickle cell disease. We report here that GBT440, an anti-polymerization agent being developed for the chronic treatment of sickle cell disease, increases hemoglobin oxygen affinity and reverses in vitro sickling of previously sickled red blood cells under hypoxic conditions. Our results suggest that besides preventing sickling of red blood cells, GBT440 may mitigate vasoocclusion and microvascular dysfunction by reversing sickling of circulating sickled red blood cells in vivo. Full article