Khalid Ahmed Al-Anazi

Background: Adult patients with Acute Myeloid Leukemia (AML) have traditionally been hospitalized for the duration of intensive consolidation chemotherapy until blood count recovery to avoid complications. Recently, there has been a trend to shift the care of AML patients treated with intensive chemotherapy from inpatient to outpatient settings to reduce treatment costs and save beds. Methods and materials: A retrospective study of AML patients who received cytarabine consolidation chemotherapy between the 1st of August 2016 and the 31st of December 2023 at King Fahad Specialist Hospital in Dammam, Saudi Arabia was performed. Results: Over a period of 7 years and 4 months, 62 patients received a total of 127 cycles of intensive consolidation chemotherapy at outpatient setting. At diagnosis: 12 patients had extramedullary disease, and 17 patients had adverse cytogenetic abnormalities. Following the 127 cycles of chemotherapy, 38 episodes of febrile neutropenia were encountered, and 46 hospital admissions were required. No complications were encountered following 62.2% of the cycles of consolidation therapy and no early mortality due to intensive consolidation therapy was reported. Out of 62 patients studied, 36 patients underwent various forms of hematopoietic stem cell transplantation. Disease relapses were encountered in 24 patients and the 5-year incidence of relapse for the entire group of patients was 42%. The 5-year leukemia-free survival for the: entire study patients, transplanted patients, and non-transplanted patients were: 43%, 38%, and 50% respectively. The 5-year overall survival for the: entire study patients, transplanted patients, and non-transplanted patients were: 44%, 34%, and 65% respectively. At the end of follow-up: 37 patients (59.68%) were alive, 24 patients (38.71%) were dead, and the fate of 1 patient (1.61%) was unknown as the patient moved to another hospital. Conclusion: Administration of intensive consolidation chemotherapy for patients with AML at outpatient setting is safe, feasible, and cost-effective. The incidence of infectious complications was relatively low. No early treatment-related mortality due to intensive consolidation therapy was encountered. Outpatient administration of intensive consolidation therapy can save beds, reduce hospital costs, and is associated with short-term and long-term outcomes that are comparable to inpatient administration of consolidation therapy.

Background: Patients with acute and chronic leukemia presenting with hyperleukocytosis are at risk of developing leukostasis which has serious and life-threatening complications. Leukapheresis is usually performed to reduce the complications of leukostasis in patients presenting with hyperleukocytosis and clinical manifestations compatible with leukostasis. Methods and materials: A retrospective study of patients with acute and chronic leukemia who received leukapheresis for hyperleukocytosis between the 1st of January 2013 and the 31st of December 2023 at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia was performed. Results: Over a period of 11 years, a total of 50 patients with acute and chronic leukemia presenting with hyperleukocytosis and clinical manifestations of leukostasis; 32 patients with acute leukemia (AL) and 18 patients with chronic myeloid leukemia (CML); received leukapheresis at our institution. Among the 32 patients with AL who received leukapheresis, 24 patients (75%) had acute myeloid leukemia (AML), 7 patients (21.88%) had acute lymphoblastic leukemia (ALL) and 1 patient (3.13%) had bilineage acute leukemia (BAL). At presentation of their AL: 3 patients (9.38%) had fever, 9 patients (28.13%) had infections, 4 patients (12.5%) had palpable spleen or liver, 6 patients (18.75%) had palpable external lymph nodes, and 9 patients (28.13%) had extramedullary disease (EMD). After receiving induction and consolidation cycles of chemotherapy, 11 patients (34.38%) of AL patients received allogeneic hematopoietic stem cell transplantation (HSCT). At the end of the follow-up, 17 patients (53.1%) with AL were alive while 15 patients (46.9%) were dead. The 8-year overall survival (OS) for all patients with AL subjected to leukapheresis was 47%. The 5 years OS for patients with AL who subsequently received HSCT and those who did not receive allogeneic HSCT were 70% and 40% respectively. The mean white blood cell (WBC) count of CML patients subjected to leukapheresis was 465.5 × 10⁹/L, 11 patients (61.11%) had clear signs of leukostasis, and 8 patients (44.44%) had splenomegaly at presentation. Regarding the disease stage at presentation, 14 CML patients (77.78%) had chronic phase (CP), 2 patients (11.11%) had accelerated phase (AP) and 2 patients (11.11%) had blast phase (BP). Regarding the fate of CML patients at the end of the study were: 15 (83.33%) were alive, 1 (5.56%) dead, and 2 (11.11%) were unknown as they lost follow-up. However, the 10-year OS of patients with CML subjected to leukapheresis was 90%. Methods and materials: Patients with acute or chronic leukemia presenting with hyperleukocytosis and either ongoing or impending leukostasis should have urgent cytoreductive chemotherapy and leukapheresis to prevent life-threatening complications. Although the outcome of AL patients presenting with leukostasis is generally poor, prompt cytoreductive therapy and leukapheresis, followed by induction chemotherapy and allogeneic HSCT may improve the outcome. Also, urgent cytoreduction including leukapheresis improves the outcome of patients with CML presenting with hyperleukocytosis and leukostasis.

Mesenchymal Stromal/Stem Cells (MSCs); which can be isolated from Bone Marrow (BM) in addition to several tissues and body fluids; have the following characteristic features: self-renewal, differentiation into various cell types, plastic adherence, and specific surface markers on flow cytometry [1-3].

Mesenchymal stem cells are heterogenous adult multipotent stromal cells that can be isolated from various sources including bone marrow, peripheral blood, umbilical cord blood, dental pulp, and adipose tissue. They have certain regenerative, anti-inflammatory, immunomodulatory, immunosuppressive, antimicrobial, and other properties that enable them to have several therapeutic and clinical applications including treatment of various autoimmune disorders; role in hematopoietic stem cell transplantation and regenerative medicine; treatment of skin, pulmonary and cardiovascular disorders; treatment of neurological and eye diseases; as well as treatment of various infections and their complications. Different factors including donor age, biological source, route of administration, and signaling pathways have an impact on the functions and consequently the clinical applications of mesenchymal stromal cells. The products of mesenchymal stem cells such as extracellular vesicles and exosomes reproduce the biological effects and most of the therapeutic actions of the parent stem cells. Genetic engineering and the use of specific mesenchymal stromal cell products have improved their clinical efficacy and decreased their adverse effects. However, despite the recent progress in the use of mesenchymal stem cells, the clinical application of these cells in the treatment of several diseases still faces real challenges that need to be resolved. The current status of mesenchymal stem cells and the controversies related to their clinical utilization in various disease conditions will be thoroughly discussed in this review.

Mesenchymal Stem Cells (MSCs) have antimicrobial, anti-inflammatory, immunomodulatory, and regenerative potentials. Additionally, utilization of MSCs in the clinical arena has been shown to be safe and well tolerated. Hence, this form of cellular therapy has gained particular attention in the treatment of several infectious disorders and their complications. MSCs have been successfully used in the treatment of the following infections and their complications: bacterial infections including complicated sepsis; viral infections including Human Immunodeficiency Virus (HIV), hepatitis B and C viruses, and Coronavirus disease (COVID-19) complicated by acute respiratory distress syndrome; parasitic infections including schistosomiasis, malaria, and Chagas disease; and mycobacterial infections including tuberculosis. The use of MSCs derived from certain sources and Extracellular Vesicles (ECVs) derived from MSCs has improved their efficacy and reduced their side effects. However, the clinical application of MSCs in the treatment of several infectious diseases still faces real challenges that need to be resolved. The current status of MSCs and the controversies related to their utilization in various infections will be thoroughly discussed in this review.

Graft Versus Host Disease (GVHD) is a major limitation to the success of allogeneic Hematopoietic Stem Cell Transplantation (HSCT) as Steroid-Refractory (SR) acute GVHD carries poor prognosis due to the absence of an efficacious second-line therapy. Mesenchymal Stem Cells (MSCs) which have immunosuppressive, immunomodulatory, and regenerative properties may become a highly effective therapeutic modality for SR-GVHD in the near future. MSCs have already been approved to treat childhood SR-GVHD in Japan, and they have been conditionally licensed in New Zealand and Canada. It is expected that MSCs will be approved for the treatment of SR-GVHD in adults in Europe, North America, and other parts of the world within a few years. Utilization of the recently introduced techniques including the use of MSC products such as exosomes and Extracellular Vesicles (ECVs) instead of the parent MSCs, robotic manufacturing technology, and genetic engineering of MSCs will ultimately overcome the remaining obstacles facing the widespread utilization of MSCs and their products as therapeutics not only in HSCT but also in other medical fields. The aim of this review is to provide an update on the remarkable progress achieved in the use of MSCs and their products in the field of HSCT.

Open access peer-reviewed chapter

Over the past two decades, treatment of multiple myeloma (MM) has advanced dramatically. However, despite the introduction of several lines of novel therapeutics, autologous hematopoietic stem cell transplantation (HSCT) followed by maintenance therapy is the current standard of care in transplant eligible patients. Autologous HSCT can be performed with or without cryopreservation with equivalent short-term and long-term outcomes. In patients with MM, performance of autologous HSCT at outpatient setting is safe, feasible and has a number of advantages such as saving hospital beds and reducing treatment costs. Autologous HSCT can be safely performed in patients with MM having renal dysfunction or failure although particular attention should be made to the timing of administering medications and stem cells with respect to hemodialysis and dose reduction of specific medications according to creatinine clearance. Tandem autologous HSCT is of value in younger patients with adverse cytogenetics and extramedullary disease. Allogeneic HSCT is the only potentially curative therapeutic modality in MM, but it can only be performed in a small fraction of highly selected patients due to the relatively high treatment-related morbidity and mortality. Despite its valuable role in the treatment of MM, autologous HSCT has its own short-term as well as long-term complications.

Autologous hematopoietic stem cell transplantation is still the standard of care in patients with multiple myeloma who are eligible for transplantation, despite the recent availability of several lines of novel therapies. Several studies have shown that autologous transplantation using non-cryopreserved stem cells is safe, cost-effective, and leads to outcomes that are equivalent to transplantation of cryopreserved autologous stem cells. With daily clinical evaluation and intensive supportive care, performance of autologous stem cell transplantation at outpatient setting is safe, feasible, and cost-effective. However, there are specific inclusion and exclusion criteria that should be taken into consideration to select the right candidates for this modality of transplantation. Recipients of outpatient transplantation may require hospitalization in case of certain complications, such as febrile neutropenia, sepsis, decrease in performance status, and severe mucositis. Following outpatient autologous transplantation, maintenance therapy is usually given till disease progression.

The recent availability of several lines of novel therapeutic agents such as immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies; the widespread utilization of hematopoietic stem cell transplantation; the use of advanced diagnostic techniques that allow risk stratification and monitoring of treatment responses; and the general improvement in health care have revolutionized treatment of patients with multiple myeloma and this has translated into significant improvements in survival outcomes. Monitoring of minimal residual disease can guide the intensity of treatment, and the efficient application of modern diagnostic tools in monitoring treatment responses in real-world clinical practice can hopefully be achieved in the near future. The recent use of quadruplet regimens in the treatment of patients with multiple myeloma has translated into unprecedented treatment responses and survival outcomes. Also, chimeric antigen receptor T-cell therapy and bispecific antibodies represent a new dimension in the precision medicine in MM. Additionally, our ability to induce deep responses has improved, and the treatment goal in myeloma patients tolerating the recommended therapy has moved from delay of disease progression to induction of the deepest possible response.