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Hypercalcemia as the Initial Presentation of Acute T-cell Leukemia/Lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a T-cell malignancy that generally presents with widespread involvement of lymph nodes, peripheral blood, and/or skin. It is an uncommon malignancy linked to the human T-lymphotropic virus 1 (HTLV-1). Herein, we present a case of ATLL that was diagnosed after a patient presented to our hospital with nonspecific symptoms of fatigue and weakness and was subsequently found to have hypercalcemia secondary to his blood malignancy. We engage in a discussion of the etiology, epidemiology, and management of patients with this rare malignancy as well as the mech…

Present and Future Role of Immune Targets in Acute Myeloid Leukemia.

It is now well known that the bone marrow (BM) cell niche contributes to leukemogenesis, but emerging data support the role of the complex crosstalk between AML cells and the BM microenvironment to induce a permissive immune setting that protects leukemic stem cells (LSCs) from therapy-induced death, thus favoring disease persistence and eventual relapse. The identification of potential immune targets on AML cells and the modulation of the BM environment could lead to enhanced anti-leukemic effects of drugs, immune system reactivation, and the restoration of AML surveillance. Potential targets

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… These facts suggest that selective FLT3 inhibition in leukemia cells can block excessive FLT3 leukemia activation with acceptable hematopoietic side effects [ 90 ]. … Targeting cell membrane HDM2: A novel therapeutic approach for acute myeloid leukemia. Leukemia. 2020;34:75–86. doi: 10.1038/s41375-019-0522-9. 25. …

The Emerging Role of Venetoclax-Based Treatments in Acute Lymphoblastic Leukemia.

Venetoclax, a B-cell lymphoma (BCL-2) inhibitor, in combination with hypomethylating agents has become the new standard of care in elderly and unfit patients with acute myeloid leukemia, with significantly improved overall survival and quality of life. Studies of venetoclax combined with high-dose chemotherapy are emerging with evidence of higher rates of molecular remission. Recently, a growing number of publications bring forth the use of venetoclax in patients with acute lymphoblastic leukemia (ALL). In the current review, we present the biological rationale of BCL-2 inhibition in ALL, how …

Utility of therapeutic drug monitoring of venetoclax in acute myeloid leukemia.

The favorable outcomes of venetoclax-based regimens in older adults with acute myeloid leukemia (AML) may result in its regimen becoming the standard treatment. However, the dosage of venetoclax is fixed, irrespective of body surface area (BSA) or weight. Therefore, individualized dosing using therapeutic drug monitoring (TDM) may help optimize treatment in a safe and effective manner. Twelve patients with AML who received venetoclax-based treatment were enrolled in this study. Blood samples were collected before venetoclax administration, and the minimum plasma concentration (Cmin) was evalua…

Modulation of RNA splicing enhances response to BCL2 inhibition in leukemia.

Therapy resistance is a major challenge in the treatment of cancer. Here, we performed CRISPR-Cas9 screens across a broad range of therapies used in acute myeloid leukemia to identify genomic determinants of drug response. Our screens uncover a selective dependency on RNA splicing factors whose loss preferentially enhances response to the BCL2 inhibitor venetoclax. Loss of the splicing factor RBM10 augments response to venetoclax in leukemia yet is completely dispensable for normal hematopoiesis. Combined RBM10 and BCL2 inhibition leads to mis-splicing and inactivation of the inhibitor of apop…

Avascular necrosis in patients with chronic myeloid leukemia: A systematic review.

UNLABELLED: Objective: Avascular necrosis (AVN)has been encountered in hematological malignancies; nonetheless, AVN is extremely uncommon in patients with chronic myeloid leukemia (CML). This review aims to describe the pathophysiology, clinical characteristics, and outcomes of AVN in CML. To our knowledge, this is the first systematic review of this topic. METHODS: We searched PubMed and Google Scholar for the case reports and series of patients with CML who developed AVN from inception to July 2021. RESULTS: We found 21 cases of AVN in CML patients,17 cases with avascular necrosis of the f…

Regulation of hematopoietic and leukemia stem cells by regulatory T cells.

Adult bone marrow (BM) hematopoietic stem cells (HSCs) are maintained in a quiescent state and sustain the continuous production of all type … ical (e.g. mesenchymal stromal cells) and non-classical niche cells (e.g. immune cells). In myeloid leukemia, some of these regulatory mechanisms that evolved to maintain HSCs, to protect them from exhaustion and immune destruction and to minimize the risk of malignant transformation are hijacked/disrupted by leukemia stem cells (LSCs), the malignant count …

The Progression of Chronic Myeloid Leukemia to Myeloid Sarcoma: A Systematic Review.

Chronic myeloid leukemia (CML) is a slow-growing type of cancer that originates in the blood-forming cells of the bone marrow and is caused by a chromosomal mutation that is thought to occur spontaneously. CML could potentially lead to the development of myeloid sarcoma (MS), which is a rare neoplasm composed of immature myeloid cells that could evolve into a tumor mass at any anatomical site other than the bone marrow. MS can develop spontaneously or as a result of another form of myeloid neoplasm. Most instances of CML precede blast phase (BP) within two to three years after the first diagno…

Erythema nodosum after azacitidine in a patient with acute myeloid leukemia.

INTRODUCTION: Nodular skin lesions in patients with acute myeloid leukemia (AML) raise clinical suspicion for leukemia cutis versus fungal infections. Here, we report a rare case of treatment-related erythema nodosum (EN) in a patient with AML. CASE REPORT: Approximately 5 weeks after the initiation of sorafenib and one week after azacitidine initiation, a 32-year-old man with primary refractory AML presented with several painful red nodules on the lower extremities. Histological examination established a diagnosis of EN. MANAGEMENT AND OUTCOME: Treatment with topical and oral steroids led t…

Bilateral anterior and posterior scleritis in a patient with acute myelogenous leukemia.

PURPOSE: To report a novel case of bilateral anterior and posterior scleritis in a patient with acute myelogenous leukemia (AML). OBSERVATIONS: A 69-year-old African American man was admitted to the hospital for relapse of AML. After admission, but prior to induction of chemotherapy, the patient developed ocular redness and proptosis. The diagnosis of bilateral anterior and posterior scleritis was made following an ophthalmic examination, infectious and autoimmune lab work-up, and neuroimaging. The patient was administered immunosuppressive therapy, clinically monitored, and initiated on chem…

Prevalence and Clinical Characteristics of Paraproteinemia Associated with Chronic Myeloid Leukemia.

INTRODUCTION: Data regarding the prevalence of paraproteinemia in patients with chronic myeloid leukemia (CML) are lacking. METHODS: To evaluate for the prevalence of paraproteinemia, we undertook this cross-sectional study among consecutive chronic-phase CML patients. Complete blood count, chemistry, immunoglobulins, serum-free light chains, serum-protein electrophoresis and immunofixation were collected. Further analyses evaluated whether various patient-, disease-, and treatment-related variables are associated with paraproteinemia. RESULTS: One hundred patients, median age 63.5 (IQR 48.1…

Chronic lymphocytic leukemia, a rare cause of spontaneous rupture of the spleen.

INTRODUCTION: Spleen Spontaneous Rupture SRS is a rare phenomenon in which the spleen ruptures without associated trauma. This pathology is rarely caused by Chronic Lymphocytic Leukemia. PRESENTATION OF THE CASE: We present a case of a 59-year-old male patient with chronic Lymphocytic Leukemia, who was admitted with an acute abdomen whose clinical and paraclinical examinations revealed a spleen spontaneous rupture. The treatment consisted of a splenectomy. DISCUSSION: Spontaneous spleen rupture was first described by Rokitansky in 1861 and mentioned in many cases since, the common causes of …

Understanding the hematopoietic microenvironment in chronic myeloid leukemia: A concise review.

Chronic myeloid leukemia (CML) is a myeloproliferative disease that results from the BCR-ABL gene-induced transformation of a primitive hematopoietic cell. This disease has been extensively studied, and, as a result, a very effective therapy has been developed: the tyrosine kinase inhibitors. Although, there is a significant knowledge about the intrinsic biology of CML cells, alterations in their bone marrow microenvironment are not yet completely understood. In this concise review, we summarized recent findings on the composition and function of the bone marrow microenvironment in CML, and th…

Discovery of pyrrole derivatives for the treatment of glioblastoma and chronic myeloid leukemia.

Long-term survivors of glioblastoma multiforme (GBM) are at high risk of developing second primary neoplasms, including leukemia. For these patients, the use of classic tyrosine kinase inhibitors (TKIs), such as imatinib mesylate, is strongly discouraged, since this treatment causes a tremendous increase of tumor and stem cell migration and invasion. We aimed to develop agents useful for the treatment of patients with GBM and chronic myeloid leukemia (CML) using an alternative mechanism of action from the TKIs, specifically based on the inhibition of tubulin polymerization. Compounds 7 and 25,…

Invasive Fungal Infections in Children with Leukemia: Clinical Features and Prognosis.

OBJECTIVE: The incidence of invasive fungal infections (IFIs) has increased due to intensive chemotherapy in childhood leukemia. The aim of this study was to evaluate the incidence, risk factors, causative pathogens, and impact on survival of IFIs among pediatric leukemia patients. MATERIALS AND METHODS: The hospital records of 307 children with acute lymphoblastic leukemia (ALL, n=238), acute myeloid leukemia (AML, n=51), and relapsed leukemia (n=18) between January 2010 and December 2015 were retrospectively evaluated. RESULTS: A total of 1213 febrile neutropenia episodes were recorded and…