Mesenchymal Stem Cells — Their Antimicrobial Effects and Their Promising Future Role as Novel Therapies of Infectious Complications in High Risk Patients
Mesenchymal stem cells (MSCs) are heterogeneous progenitor cells that have the capacity of self-renewal and multi-lineage differentiation. These adult stem cells can be derived from several sources including bone marrow (BM), peripheral blood, cord blood, placenta, amniotic fluid, skin and adipose tissue. They have certain distinguishing features and their immunomodulatory and immunosuppressive properties enable them to have several therapeutic and clinical applications. Recently, MSCs have gained enormous potential as they can potentially cure various intractable and chronic diseases and as they have shown effectiveness in the treatment of various infections in animal models and in early clinical trials. MSCs are essential constituents of the framework that supports organ integrity and tissue barriers. Suppression of both T and B cells allows them to be major players in the innate response to bacterial infection and in controlling inflammatory response. Human BM-MSCs possess direct antibacterial activity against Gram-negative bacilli and they have been shown to improve survival and reduce mortality in animal models having septic complications. BM-MSCs are effective in treating sepsis and acute respiratory distress syndrome in high-risk patients such as those with malignant hematological disorders, recipients of solid organ and hematopoietic stem cell transplantation (HSCT) and patients receiving advanced level of care in intensive care units. Additionally, human BM-MSCs can act as drug delivery vehicles by enhancing the effectiveness of conventional antimicrobials and thus they may prevent the evolution of drug-resistant microbes. MSCs contain a subset of interleukin-17+ that is capable of inhibiting the growth of Candida albicans (C. albicans). Also, CD 271+ BM-MSCs may provide a long-term protective intracellular niche in the host where Mycobacterium tuberculosis (M.TB) organisms remain viable but in a dormant state. Two recent clinical trials in humans that included 57 patients have shown that autologous transplantation of MSCs can successfully treat multidrug resistant (MDR) strains of M.TB. Animal studies have demonstrated that MSCs enhance host defenses against malaria. MSC therapy improves liver function and promotes hepatocellular regeneration in patients with hepatic fibrosis caused by schistosomiasis. Transplantation of MSCs has been shown to reverse right ventricular dilatation, cardiomyopathy and advanced cardiac involvement caused by Trypanosoma cruzi infection.
Part of the book: Progress in Stem Cell Transplantation
Update on Leukemia in Pregnancy
Leukemia is a rare event in pregnancy. Acute leukemia represents 90% of leukemias occurring during pregnancy with AML accounting for two thirds of these cases. During the first trimester of pregnancy, standard chemotherapy has a teratogenicity rate of up to 20% depending on the specific agent employed. Exposure to cytotoxic agents during the second and third trimesters is not teratogenic but may predispose the fetus to growth retardation, premature delivery and bone marrow suppression. Additionally, the mother and the fetus are at risk of thromboembolism and sepsis. Only absolutely necessary radiologic work-up is justified during the first trimester of pregnancy as exposure to radiation during the first 2 weeks of pregnancy is usually lethal. Thereafter, radiation predisposes to congenital malformations, growth retardation and malignancy in the newborn. Although most infants exposed to multi-agent chemotherapy seem to suffer no long-term detrimental consequences, studies have shown that: (1) cytotoxic chemotherapy can cross the placenta and cause teratogenicity, (2) there is a potential risk of adult cancer after intrauterine exposure to radiation, and (3) cytotoxic chemotherapy and radiotherapy increase genetic defects in germ cells. In the first trimester, the termination of pregnancy should seriously be considered if the disease is aggressive and if intensive chemotherapy is needed. In the second and third trimesters, standard chemotherapy can safely be administered without resorting to pregnancy termination. The choice of specific regimens depends upon several factors that include: the gestational age, the clinical status of the patient, the specific type of leukemia and the anticipated toxicity of the cytotoxic agents employed. The decision is often difficult and confounded by several concerns, but the management of each pregnant patient with leukemia has to be individualized and should have a multidisciplinary approach. Vaginal delivery is preferable while caesarean section is reserved for certain obstetric complications. It is preferable to time delivery between 32 and 36 weeks of gestation to ensure optimal fetal maturation and it is recommended to avoid maternal bone marrow suppression prior to delivery.
Part of the book: Leukemias
Myelodysplastic Disorders, Monosomy 7
Myelodysplastic syndromes (MDSs) are heterogeneous hematopoietic disorders associated with various degrees of myelosuppression and transformation into acute leukemia. Chromosome 7 abnormalities occur at any age, have several disease associations, and are generally associated with poor outcome. Treatment of the associated disease conditions may have a positive impact on the outcome of certain types of MDSs. For patients eligible for hematopoietic stem cell transplantation (HSCT), allografts are the standard of care, while supportive measures and the use of hypomethylating agents, such as 5-azacytidine and decitabine, constitute the mainstay of management in individuals who are not fit for allogeneic HSCT. However, the use of hypomethylating agents in conjunction with allogeneic HSCT using nonmyeloablative conditioning therapies may be an appealing therapeutic option for older patients with comorbid medical conditions.
Part of the book: Myelodysplastic Syndromes
Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in the Era of Novel Therapies
Recently, the outcomes of patients with acute lymphoblastic leukemia have improved significantly due to the progresses achieved in diagnostics and various therapeutic interventions. In particular, the availability of several novel agents and targeted therapies as well as the provision of safer modalities of stem cell transplants have yielded higher responses and improved survival rates. The role of hematopoietic stem cell transplantation is reviewed in children and adults with acute lymphoblastic leukemia in the era of novel agents and targeted therapies. Various modalities of stem cell therapies in different types of acute lymphoblastic leukemia as well as closely related issues such as graft versus tumor effect, minimal residual disease, and conditioning therapies are discussed thoroughly. In addition, various modalities of novel therapies have been discussed to be efficacious in clinical practice.
Part of the book: Stem Cells in Clinical Practice and Tissue Engineering
Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Therapies
Multiple myeloma is the second commonest hematologic malignancy. It is characterized by neoplastic proliferation of a single clone of plasma cells in the bone marrow producing a monoclonal immunoglobulin and ultimately causing various complications and organ dysfunction. Over the last 10 years, management of multiple myeloma has dramatically changed due to the introduction of several novel therapies that have improved the disease outcome and prognosis, as well as the quality of life of patients with myeloma due to their safety, tolerability and efficacy. Additionally, the widespread utilization of autologous hematopoietic stem cell transplantation, which is still the standard of care for transplant-eligible patients, and the implementation of new therapeutic strategies such as drug combinations in addition to consolidation and maintenance therapies have resulted in further improvements in response rates and survival in patients with multiple myeloma. This book chapter will be an update on the novel therapies and the recent treatment strategies in myeloma. The role of stem cell treatments in the era of novel therapies will be discussed thoroughly.
Part of the book: Update on Multiple Myeloma
Infections in Patients with Multiple Myeloma in the Era of Novel Agents and Stem Cell TherapiesView all chapters
Multiple myeloma is a common hematologic malignancy that is associated with reduced cellular as well as humoral immunity ultimately causing various infectious complications. The recent advances in the management of myeloma have led not only to prolonged survival but also to shifts in the incidence as well as the spectrum of infections encountered. This book chapter will be an updated review on the infectious complications in patients with multiple myeloma in the era of novel agents, stem cell therapies, and monoclonal antibodies. It will cover causes of immunosuppression, timing, and types as well as management of the various infections reported with various therapeutic modalities that are currently utilized in the management of myeloma patients.
Part of the book: Update on Multiple Myeloma