Denosumab versus zoledronic acid for patients with beta-thalassemia major-induced osteoporosis.

ABSTRACT: The main aim of this study is to compare the 2 medications denosumab and zoledronic acid for patients with beta-thalassemia major induced osteoporosis. Patients with B-thalassemia major induced osteoporosis will undergo baseline assessment of the bone densitometry by bone density(DEXA) scan as a standard of care by the radiology department, then a blood test for bone-specific alkaline phosphatase and type-1 collagen telopeptide will be measured by the chemistry laboratory.Patients with B-thalassemia major induced osteoporosis, who are 18 years of age or more and willing to participate in the study will be enrolled after consenting by the primary investigator in hematology outpatient clinics. Patients with osteoporosis will receive 1 of the 2 medications; at the end of the year, DEXA scan will be done to compare the response of the 2 medications. The potential risks include drug-related side effects.The outcome will be measured biochemically by measuring bone-specific alkaline phosphatase and type 1 collagen carboxy telopeptide and radiologically by DEXA scan at baseline and 1 year using Z score.

A Case of Acquired von Willebrand Disease Secondary to Myeloproliferative Neoplasm.

Acquired von Willebrand Disease (AVWD) is a rare disorder in which qualitative or quantitative defects in von Willebrand factor (VWF) occur secondary to other conditions. AVWD occurs in patients with myeloproliferative disorders due to formation of autoantibodies against VWF and development of excessive shear stress causing disruption of VWF multimers. AVWD is different from congenital VWD in its acute onset and absence of family history. We report a 42-year-old gentleman with essential thrombocythemia, who was on cytoreductive therapy with hydroxyurea, and presented with an acute history of gum bleeding with hemoptysis, without any antecedent trauma or infections. His platelet count was very high, and prothrombin time and activated partial thromboplastin time were prolonged. The VWF ristocetin cofactor assay (VWF: RCo) was low, but VWF antigen level (VWF: Ag) was normal. Their ratio (VWF: RCo/VWF: Ag) was much lower than the acceptable lower limit. Treatment in AVWD is focused on addressing the underlying disorder. Early recognition of AVWD and its primary cause is mandatory in providing adequate therapy and achieving a cure.

Cerebral Venous Thrombosis in a Patient with Immune Thrombocytopenia, an Apparent Paradox.

We present a paradoxical case of immune thrombocytopenia (ITP) that presented with cerebral venous thrombosis. A 39-year-old female patient diagnosed with chronic ITP, who failed treatment on multiple-line agents, was started on eltrombopag (thrombopoietin receptor agonist), which she was not compliant to. The patient later developed extensive cerebral venous thrombosis, along with venous infarcts, and intracranial and subarachnoid hemorrhage. She was treated with intravenous immunoglobulins as well as steroid therapy and was simultaneously started on anticoagulation. The patient improved clinically and radiologically. This case is among few reported cases which signify that patients with ITP are inherently prone to thrombosis despite low platelet count and treating these patients can be a dilemma. Judicious use of anticoagulation and immunosuppressive therapy is recommended based on available evidence pending further recommendations and guidelines about treatment of thrombosis in ITP.

The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice.

Research on CAR T cells has achieved enormous progress in recent years. After the impressive results obtained in relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell lymphomas, two constructs, tisagenlecleucel and axicabtagene ciloleucel, were approved by FDA. The role of CAR T cells in the treatment of B-cell disorders, however, is rapidly evolving. Ongoing clinical trials aim at comparing CAR T cells with standard treatment options and at evaluating their efficacy earlier in the disease course. The use of CAR T cells is still limited by the risk of relevant toxicities, most commonly cytokine release syndrome and neurotoxicity, whose management has nonetheless significantly improved. Some patients do not respond or relapse after treatment, either because of poor CAR T-cell expansion, lack of anti-tumor effects or after the loss of the target antigen on tumor cells. Investigators are trying to overcome these hurdles in many ways: by testing constructs which target different and/or multiple antigens or by improving CAR T-cell structure with additional functions and synergistic molecules. Alternative cell sources including allogeneic products (off-the-shelf CAR T cells), NK cells, and T cells obtained from induced pluripotent stem cells are also considered. Several trials are exploring the curative potential of CAR T cells in other malignancies, and recent data on multiple myeloma and chronic lymphocytic leukemia are encouraging. Given the likely expansion of CAR T-cell indications and their wider availability over time, more and more highly specialized clinical centers, with dedicated clinical units, will be required. Overall, the costs of these cell therapies will also play a role in the sustainability of many health care systems. This review will focus on the major clinical trials of CAR T cells in B-cell malignancies, including those leading to the first FDA approvals, and on the new settings in which these constructs are being tested. Besides, the most promising approaches to improve CAR T-cell efficacy and early data on alternative cell sources will be reviewed. Finally, we will discuss the challenges and the opportunities that are emerging with the advent of CAR T cells into clinical routine.

Graves' Disease-Related Pancytopenia Improved after Radioactive Iodine Ablation.

Graves' disease is an autoimmune disease that affects the thyroid glands which often results in enlarged thyroid glands, and it is the most common cause of clinical hyperthyroidism especially in young patients. Radioiodine ablation is a radiation therapy in which radioactive iodine is administered to destroy or ablate thyroid cells. It is commonly used for the treatment of Graves' disease. We report on a 39-year-old male, who presented with Graves' disease, found to have pancytopenia and hypocellular bone marrow. Pancytopenia is a rare complication of thyrotoxicosis that is usually not severe and does not require supportive blood product transfusions. Our patient was treated with antithyroid medications followed by radioactive iodine ablation followed by a spontaneous recovery of pancytopenia.