Genome Engineering as a Therapeutic Approach in Cancer Therapy: A Comprehensive Review.

Cancer is one of the foremost causes of mortality. The human genome remains stable over time. However, human activities and environmental factors have the power to influence the prevalence of certain types of mutations. This goes to the excessive progress of xenobiotics and industrial development that is expanding the territory for cancers to develop. The mechanisms involved in immune responses against cancer are widely studied. Genome editing has changed the genome-based immunotherapy process in the human body and has opened a new era for cancer treatment. In this review, recent cancer immunotherapies and the use of genome engineering technology are largely focused on.

Explosive Disease Progression After Single-Agent B-cell Maturation Antigen-Targeted Treatment in Multiple Myeloma: A Report of Three Cases in Sheikh Shakhbout Medical City.

Patients with "penta-refractory" multiple myeloma (MM) are challenging to treat given the limited treatment options available to them. Belantamab mafodotin is the first B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate approved for the treatment of relapsed/refractory MM (RRMM). In this case report, we reviewed in detail three female patients who were diagnosed with MM international scoring system (ISS)-3 and were heavily pretreated, and refractory to CD38 monoclonal antibodies, two proteasome inhibitors, and two immunomodulatory agents. These patients were started on belantamab mafodotin and experienced rapid and explosive clinical, biochemical, and extramedullary disease progression within a short period of time. All three patients experienced worsening cytopenia, increased transfusion requirement, severe uncontrolled bony pain, recurrent infections, and frequent hospital admissions. Two of them passed away due to disease progression complications within a few months of starting belantamab mafodotin. Although belantamab mafodotin as a single agent was withdrawn from the market after the DREAMM-3 trial failed to achieve its primary endpoint in late RRMM, BCMA-targeted therapy may still be a promising treatment approach, and the role of belantamab mafodotin is yet to be revealed in combination therapy in early RRMM.

Establishment of the First Comprehensive Adult and Pediatric Hematopoietic Stem Cell Transplant Unit in the United Arab Emirates: Rising to the Challenge.

Hematopoietic stem cell transplantation (HSCT) is increasingly indicated for various malignant and non-malignant diseases. In the United Arab Emirates (UAE), patients that could benefit from the procedure commonly need to seek medical care abroad in view of the lack of a comprehensive HSCT facility that could offer the full spectrum of interventions and monitoring protocols. This comes with considerable challenges related to coverage and logistics of travel. It also limits the continuity of clinical care, and presents inconvenience to patients who come from a different cultural background. In this article, we share our experiences and lessons learned during the establishment of the first comprehensive adult and pediatric HSCT unit in the UAE that is designed to cater for local citizens and residents, as well as neighboring countries facing similar availability challenges.

Impact of the relative dose intensity on survival of patients with high-risk myelodysplastic syndromes treated with Azacitidine.

We performed a retrospective analysis of 93 myelodysplastic syndromes (MDS) patients with intermediate 2 or high-risk IPSS score to study the impact of Azacitidine (AZA) relative dose intensity (RDI) <80% on the overall survival (OS). There were 51.6% of patients who had full dose and 48.4% had dose reduction or delayed with a RDI <80%. Nineteen patients (20.4%) had RDI <80% before getting objective response. Overall and progression-free survivals (OS, PFS) probabilities for the whole population were 58% (95% CI: 48-69) and 47% (95% CI: 38-58) at 1 year; 35% (95% CI: 26-47) and 31% (95% CI: 23-43) at two years, respectively. When analyzing the outcomes according to the response to AZA, median OS was 32 months (range: 26-55) for responders and 8 months (range: 7-12) for nonresponders, with a respective 1-year and 2-year OS probabilities of 91% vs 28% and 66% vs 6%, respectively (P < 0.001). Interestingly, there was no impact of dose reduction on OS nor on PFS, however, when analyzing the timing of dose reduction as time-dependent variable, we found that patients who had dose reduction before achieving the objective response, had significantly lower OS (P = 0.02) and PFS (P = 0.01) compared to patients who had dose reduction after achieving the objective response. In multivariate analysis, acute myeloid leukemia with 21%-30% blasts in BM and poor and very poor karyotype significantly impacted OS, (HR = 2.09, 95% CI: 1.27-3.44, P = 0.004, and HR = 2.73, 95% CI: 1.6-4.6, P < 0.001 respectively), as well as PFS (HR = 1.84, 95% CI: 1.07-3.17, P = 0.028, and HR = 3.03, 95% CI: 1.7-5.39, P < 0.001, respectively).