Revisiting intrathecal thiotepa: Efficacy and safety in secondary CNS malignancies.

Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal (IT) drug administration into the cerebrospinal fluid (CSF) is a strategy to overcome this problem. Thiotepa has effective CNS penetration but its popularity has waned over the last two decades due to concerns about its efficacy and potential systemic toxicity. This review evaluates the available evidence for the use of IT thiotepa in hematologic malignancies and non-CNS solid tumors with leptomeningeal disease metastases (LMD). Our search shows that IT thiotepa is a reasonable alternative in hematologic malignancies and LMD due to solid organ malignancies. This suggests a potential role of IT thiotepa in second-or third-line treatment or a substitute role in cases of drug-shortages and adverse effects with other agents. Future research should focus on rigorous comparative trials to establish its definitive role in the evolving landscape of CNS-directed chemotherapy.

Role of Anti-CD38 Monoclonal Antibodies in the Treatment of Adult Immune Hematological Diseases.

Daratumumab is a first-in-class human anti-CD38 IgG1 monoclonal antibody approved for treating newly diagnosed and relapsed refractory multiple myeloma. Pre-clinical data supported daratumumab's ability to deplete autoantibodies producing plasma cells, B-cells, and NK cells. Those reports showed promising results on using daratumumab in autoimmune disorders that are refractory to multiple lines of therapies, which encouraged using daratumumab in various autoimmune conditions that are refractory to standard therapies. This review aims to summarize the literature reporting experience using anti-CD38 antibodies in hematological autoimmune diseases, focusing on the most common autoimmune hematological diseases, including autoimmune hemolytic anemia, immune thrombocytopenia, post-transplant cytopenia, and pure red blood cell aplasia.

Full Dose Cyclophosphamide with the Addition of Fludarabine for Matched Sibling Transplants in Severe Aplastic Anemia.

The recommended therapy for severe aplastic anemia (SAA) in younger patients with a matched sibling donor (MSD) is allogeneic hematopoietic cell transplantation (allo-HCT). A number of conditioning regimens and protocols have been used for these patients. Here we report a homogeneous cohort of SAA patients receiving a uniform transplantation protocol. This study is a retrospective analysis of 82 consecutive patients with SAA who underwent MSD allo-HCT at a single center. The median duration of follow-up for survivors was 100 months, the 10-year overall survival (OS) was 87.5%, and the 10-year event-free survival was 75.3%. The OS was 97.4% for "mobilized" bone marrow (BM) graft recipients and 78.9% for "nonmobilized" BM graft recipients (P = .01. The cumulative incidence of acute graft-versus-host disease (GVHD) was 25.6%, that of chronic GVHD was 27.16%, and that of graft failure was 16.2%. Recipient age ≥30 years and transplantation at >6 months after SAA diagnosis were associated with a increased risk of events. In the presence of a fully matched sibling donor, allo-HCT with a mobilized BM graft and fludarabine-cyclophosphamide conditioning is an efficacious and safe approach. Early transplantation is associated with a better outcome, emphasizing the importance of not delaying transplantation in these patients. Prospective trials are needed to determine the optimal regimen.

Cancer Management in Saudi Arabia: Recommendations by the Saudi Oncology HeAlth Economics ExpeRt GrouP (SHARP).

Cancer is widely recognized as a major global health problem and is estimated to rank as one of the leading causes of death worldwide. Saudi Arabia has undergone remarkable socioeconomic development in the past 40 years which has contributed to the increase in cancer incidence. The high costs of new oncology medications in combination with uncertainty of long-term effectiveness and safety outcomes highlight the importance of considering value, in terms of clinical outcomes, relative to cost. We convened a group of experts to discuss key factors impacting the current state of cancer management in Saudi Arabia and to agree on a list of recommendations, with a focus on value-based care, considering evidence, patients, and costs.

Cardiovascular Toxicity Associated With Tyrosine Kinase Inhibitor Therapy In Chronic Myeloid Leukemia.

Treatment of Chronic myeloid leukemia (CML) typically entails a long-term course of tyrosine kinase inhibitors (TKI) therapy. This review provides a summary on the cardiotoxic effects of TKIs. Five small molecular TKIs were evaluated in our review. The cardiotoxic effects of TKIs can range from superficial edema to potentially fatal conditions such as congestive heart failure (HF) and acute coronary syndrome (ACS). With the constant introduction of newer generations of TKIs, it has been demonstrated that different TKIs have distinct cardiovascular safety profiles. Amongst which, the first-generation TKI - imatinib appears to have the safest profile, mainly causing edema along with nausea, rash and muscle cramps. Other TKIs, like the second-generation dasatinib, bosutinib,and nilotinib, have shown an increased incidence of pleural effusion and QT prolongation. Ponatinib, a third generation TKI, has shown a relatively high incidence of serious adverse effects including thrombotic vascular occlusion and heart failure, particularly in patients with a prior history of cardiovascular impairment. Therefore, it is advisable that at-risk patients taking TKIs be screened with an Electrocardiogram (ECG) and have a careful cardiovascular risk assessment before starting TKI therapy to avoid potential cardiotoxic effects such as arrhythmias, acute coronary syndrome (ACS), congestive heart failure, and pleural effusion. Keywords: tyrosine kinase inhibitor, TKI, chronic myelogenous leukemia, CML, cardiotoxicity, side effects, imatinib, dasatinib, bosutinib, nilotinib, ponatinib.

Practical strategies to manage cancer patients during the COVID-19 pandemic: Saudi Oncology Pharmacy Assembly Experts recommendations.

PURPOSE: During COVID-19 pandemic, cancer patients are considered one of the most vulnerable to infection since they tend to have advanced age, multiple comorbidities, and are often immunosuppressed by their cancer or therapy. Hence, the Saudi Oncology Pharmacy Assembly has issued recommendations to reduce the frequency of cancer patients' visits to oncology centers during the pandemic while maintaining the access to cancer therapy and minimize the risk of exposure to coronavirus disease. MATERIALS AND METHODS: A qualitative methodological approach was conducted in April 2020 using a virtual panel discussion for collection of recommendations. RESULTS: A total of 12 expert oncology pharmacy practitioners shared their knowledge and experiences in managing oncology patients during the COVID-19 pandemic. The participants recognized many fundamental recommendations that were already applied in many cancer centers since the start of the COVID-19 outbreak. On that basis, the panelists developed eight practice-related recommendations for action, with a main focus on cancer treatment modification. CONCLUSIONS: In conclusion, delivering cancer care during the COVID-19 pandemic carries significant challenges. This paper addressed suggestions to properly manage cancer patients during difficult times. Implementing changes in practice mandates a national collaborative effort from different sectors to guarantee the quality and continuity of care. The SOPA expert panel developed these recommendations, to ultimately contribute in maintaining access to cancer therapy while minimizing the risk of COVID-19 exposure.