Advancing the understanding of venetoclax in t(11;14)-positive multiple myeloma: a comprehensive review of clinical evidence and future prospects.

Venetoclax is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (BCL2), as a targeted therapy for multiple myeloma (MM) patients. It was initially approved by the United States Food and Drug Administration for the treatment of chronic lymphocytic leukemia in April 2016 and later for acute myeloid leukemia in October 2020. However, venetoclax is used as an off-label in a subset group of relapsed and refractory multiple myeloma (RRMM) patients with the presence of translocation t(11;14). Preclinical and clinical studies have highlighted the potential of venetoclax in the management of MM patients, with a specific focus on t(11;14) as a predictive biomarker for initiating venetoclax-based treatment. Later, several studies in RRMM patients that used venetoclax in combination with dexamethasone or/and proteasome inhibitors have shown promising results, in which management guidelines have included venetoclax as one of the options to treat MM patients. Hence, this review focuses on the use of venetoclax in RRMM, clinical efficacy, safety, dosing strategies, and predictive biomarkers for initiating venetoclax. Additionally, we discuss ongoing studies that are investigating different combination of venetoclax regimens in MM patients.

Use of Thrombopoietin Receptor Agonists in Pregnancy: A Review of the Literature.

The management of immune thrombocytopenic purpura (ITP) involves several lines of therapy such as corticosteroids and intravenous immunoglobulin. With the emergence of novel therapies such as thrombopoietin receptor agonists (TPO-RAs), there has been a shift in treatment modalities. Eltrombopag and romiplostim have proven to be effective in the management of ITP through clinical studies, but their safety in pregnancy remains uncertain. The purpose of the study is to review the literature to evaluate the safety of TPO-RAs in pregnant women. Ten case reports and a cohort study pertaining to the use of TPO-RAs in pregnancy were obtained. According to the reported cases and prospective study, the use of eltrombopag and romiplostim appears to be relatively safe in the first, second, and third trimesters, as there were no reported congenital malformations. Low fetal birth weight has been observed following the administration of eltrombopag during the second trimester, whereas preterm birth has occurred following the administration of eltrombopag in the third trimester. Eltrombopag and romiplostim seem relatively safe. Further studies are necessary to clarify their safety during pregnancy.

Clinical course and outcomes of COVID-19 in hematopoietic cell transplant patients, a regional report from the Middle East.

The coronavirus disease-2019 (COVID-19) caused by SARS Coronavirus 2 (SARS-CoV-2) is a potentially lethal infection. Cancer patients, and specifically hematopoietic cell transplant (HCT) recipients are severely immunocompromised and may be at a higher risk of a complicated course with this infection. We aimed to study the COVID-19 outcomes and severity in post HCT patients. We retrospectively reviewed post-HCT patients diagnosed with COVID-19 between March 15, 2020, and December 1, 2020 at 10 transplant centers across the Middle East. We identified 91 patients with confirmed SARS-CoV-2 infection across 10 transplant centers. The median age upon presentation with COVID-19 was 35. Fifty two patients were post allo-HCT while the remaining 39 patients were post auto-HCT. The median time from transplant was 14.9 months. Mortality rate was 4.4%. Hospital admission rate was 53%. ICU admission rate was 14%. Mechanical ventilation rate was 10%. Oxygen supplementation rate was 18%. Time from HCT to COVID-19 >6 months was associated with lower admission rates and lower rates of the "severity" composite endpoint. Antibody responses was seen 67% of evaluable patients. In this series of HCT recipients, we report overall favorable clinical outcomes for patients with COVID-19 and provide preliminary insights into the clinical course of this disease in this specific population.

Prolonged Survival of a Patient with Chronic Myeloid Leukemia in Accelerated Phase with Recurrent Isolated Central Nervous System Blast Crisis.

BACKGROUND Chronic myeloid leukemia (CML) is usually a tri-phasic myeloproliferative neoplasm, characterized by the presence of the BCR-ABL1 fusion gene, derived from a balanced translocation, t(9;22)(q34;q11). BCR-ABL tyrosine kinase inhibitors (TKI) are used to treat patients with CML. The addition of pegylated interferon-alpha2b to imatinib or dasatinib results in promising deep molecular responses. Because imatinib shows poor penetration into the central nervous system (CNS), the CNS may become a sanctuary site in patients on prolonged imatinib therapy for CML. It is extremely rare for the blast phase in patients with chronic phase CML to affect the CNS without concomitant bone marrow involvement. CASE REPORT This report describes a 57-year-old woman who was diagnosed with accelerated phase (AP) CML and failed high dose imatinib therapy. Despite achieving an excellent molecular response to dasatinib in 6 months, she developed recurrent isolated CNS blast crisis. Survival was prolonged after treatment with intrathecal chemotherapy and whole-brain radiation therapy combined with dasatinib. After achieving long and deep molecular remission with dasatinib and a few months of pegylated interferon-alpha2a, she lived for 18 months in treatment-free-remission (TFR). At age 65 years, she died of progressive rectal carcinoma with septic shock, cancer-related venous thromboembolism, and a possible autoimmune disorder. CONCLUSIONS This patient with accelerated phase CML and 2 isolated CNS blast crises died in TFR 8.5 years after her initial diagnosis and 7.5 years after her first isolated CNS blast crisis. Survival resulted from tailoring of therapies around her comorbidities.

The use of 5-azacytidine in pregnant patient with Acute Myeloid Leukemia (AML): a case report.

BACKGROUND: The management of Acute Myeloid Leukemia (AML) during pregnancy remains challenging as both the maternal and fetal outcomes should be considered. Several reports suggested that chemotherapy can be administered safely during the second and third trimester of pregnancy. However, the use of 5-azacytidine presents limitation due to lack of data. CASE PRESENTATION: A 28-years-old woman in the 26th week of gestation diagnosed with FLT3/ITD-mutated AML, complete remission was induced by Daunorubicin and Cytarabine, and subsequently with 5-azacytidine (75 mg/m2 daily for 7 days) with no fetal hematological or toxicity issues. Fetal ultrasound showed no aberrant morphology. Fetal size below the 5th percentile with normal umbilical artery dopplers, normal middle cerebral artery dopplers and ductus venosus doppler. Three weeks post 5-azacytidine, the team determined the most appropriate time for delivery after balancing the risks of prematurity and prevention of disease relapse since patient in hematological remission. The patient underwent elective lower segment caesarian section and had a baby girl delivered at 35 weeks of gestation weighing 1670 g without apparent anomalies. CONCLUSION: Treatment using 5-azacytadine during last trimester of pregnancy resulted in no major fetal and maternal complications. These findings concluded that 5-azacytadine during the third trimester of pregnancy seems to be safe however, potential risks of this agent should be considered.

Systemic Lupus Erythematosus Presenting as Hematoma of the Hand Due to Acquired Inhibitors to Factor VIII: Early and Prolonged Remission Achieved with Upfront Rituximab.

Acquired hemophilia is a rare autoimmune disorder that is a result of antibodies against clotting factor VIII and it presents with excessive or prolonged bleeding, often into the muscles. Thrombotic phenomena with lupus anticoagulant are common in patients with systemic lupus erythematosus (SLE). We report a rare case of a young female with no significant past medical history presenting with hematoma of the hand who was later on found to have acquired hemophilia, SLE with antiphospholipid antibodies (APLA). She was successfully treated with upfront rituximab and prednisolone leading to early and prolonged remission. No increased incidence of infections was noted. Upfront rituximab appears to be a safe and effective option in the management of such patients when compared to use of cytotoxic agents such as cyclophosphamide; however, further data from randomized studies is needed. Neutropenia and acquired hemophilia should also be considered to be listed under hematological manifestations of SLE diagnostic criteria, as they are not uncommon in such patients.

Surgeon and haematologist: a review of comprehensive care for patients with inherited bleeding disorders in Northern Ireland.

BACKGROUND: Management of patients with inherited bleeding disorders has improved since the introduction of Comprehensive Care Centres (CCC) in the United Kingdom (UK). In the event such patients need surgery, the aim of the multidisciplinary team is to facilitate outcomes as good as what would be expected in a non-bleeding disorder patient. A review of such comprehensive care was carried out in patients with inherited bleeding disorders when they needed surgery at Northern Ireland CCC. Aims of the study were to evaluate surgical morbidity and mortality in these patients. METHODS: All patients with inherited bleeding disorders who underwent non-orthopaedic surgery between 2008 and 2012 were identified from the CCC records within the Belfast Health and Social Care Trust (BHSCT) in Northern Ireland (NI) and their case records reviewed. RESULTS: 28 patients received elective and emergency surgery during this period. There was minimum morbidity and no mortality in this cohort. CONCLUSIONS: Surgery in patients with inherited bleeding disorders has become safe with the advent of multidisciplinary CCCs. Close communication between surgeon and haematologist is key in the successful management of these complex patients.