Multiple Myeloma in the Era of Novel Agents and Stem Cell Therapies

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

Outpatient Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

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

An Update on Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

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

Correlation between Genetic Variations and Serum Level of Interleukin 28B with Virus Genotypes and Disease Progression in Chronic Hepatitis C Virus Infection

Recent studies have demonstrated that polymorphisms near the interleukin-28B (IL-28B) gene could predict the response to Peg-IFN-a/RBV combination therapy in HCV-infected patients. The aim of the study was to correlate the serum level of IL28B in HCV-infected patients with virus genotype/subgenotype and disease progression. IL28B serum level was detected and variations at five single nucleotide polymorphisms (SNPs) in IL28B gene region were genotyped and analyzed. The variation of IL28B genetic polymorphisms was found to be strongly associated with HCV infection when healthy control group was compared to HCV-infected patients with all P values <0.0001. Functional analysis revealed that subjects carrying rs8099917-GG genotype had higher serum level of IL28B than those with GT or TT genotypes (P=0.04). Also, patients who were presented with cirrhosis (Cirr) only or with cirrhosis plus hepatocellular carcinoma (Cirr+HCC) had higher levels of serum IL28B when compared to chronic HCV-infected patients (P=0.005 and 0.003, resp.). No significant association was found when serum levels of IL28B were compared to virus genotypes/subgenotypes. This study indicates that variation at SNP rs8099917 could predict the serum levels of IL28B in HCV-infected patients. Furthermore, IL28B serum level may serve as a useful marker for the development of HCV-associated sequelae

Brucella bacteremia in patients with acute leukemia: a case series

<p>Abstract</p> <p>Background</p> <p>Brucellosis may cause serious infections in healthy individuals living in countries that are endemic for the infection. However, reports of brucella infections in immunocompromised hosts are relatively rare.</p> <p>Case Presentations</p> <p>Reported here are two patients with acute leukemia who developed <it>Brucella melitensis </it>bacteremia during their follow up at the Armed Forces Hospital in Riyadh. The first patient developed <it>B. melitensis </it>bacteremia during the transformation of his myelodysplasia into acute myeloid leukemia. The second patient developed <it>B. melitensis </it>bacteremia while his acute lymphoblastic leukemia was under control. Interestingly, he presented with acute cholecystitis during the brucella sepsis. Both brucella infections were associated with a marked reduction in the hematological parameters in addition to other complications. The bacteremic episodes were successfully treated with netilmicin, doxycycline and ciprofloxacin.</p> <p>Conclusion</p> <p>Brucellosis can cause systemic infections, complicated bacteremia and serious morbidity in patients with acute leukemia living in endemic areas. These infections may occur at the presentation of the leukemia or even when the leukemia is in remission. Nevertheless, the early diagnosis of brucellosis and the administration of appropriate antimicrobial therapy for sufficient duration usually improves the outcome in these immunocompromised patients.</p

The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease

Viral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (preC/C) region of HBV, and investigate their impact on disease progression toward hepatocellular carcinoma (HCC). Patients were categorized according to the severity of their disease, and were divided into the following groups: inactive HBV carriers, active HBV carriers, liver cirrhosis patients, and HCC patients. Two precore mutations, W28* and G29D, and six core mutations, F24Y, E64D, E77Q, A80I/T/V, L116I, and E180A were significantly associated with the development of cirrhosis and HCC. Six of the seven significant core mutations that were identified in this study were located within immuno-active epitopes; E77Q, A80I/T/V, and L116I were located within B-cell epitopes, and F24Y, E64D, and V91S/T were located within T-cell epitopes. Multivariate risk analysis confirmed that the core mutations A80V and L116I were both independent predictors of HBV-associated liver disease progression. In conclusion, our data show that mutations within the preC/C region, particularly within the immuno-active epitopes, may contribute to the severity of liver disease in patients with chronic hepatitis. Furthermore, we have identified several distinct preC/C mutations within the study population that affect the clinical manifestation and progression of HBV-related disease. The specific identity of HBV mutations that are associated with severe disease varies between different ethnic populations, and so the specific preC/C mutations identified here will be useful for predicting clinical outcomes and identifying the HBV-infected patients within the Saudi population that are at high risk of developing HCC

Hepatotoxicity induced by horse ATG and reversed by rabbit ATG: a case report

<p>Abstract</p> <p>Background</p> <p>The use of antilymphocyte agents has improved patient and graft survival in hematopoietic stem cell and solid organ transplantation but has been associated with the development of short-term toxicities as well as long-term complications.</p> <p>Case presentation</p> <p>We report a young female with Fanconi anemia who received antithymocyte globulin as part of the conditioning regimen prior to her planned allogeneic hematopoietic stem cell transplant at King Faisal Specialist Hospital and Research Centre in Riyadh. She developed sudden and severe hepatotoxicity after receiving the first dose of horse antithymocyte globulin, manifested by marked elevation of serum transaminases and mild elevation of serum bilirubin level. Immediately after withdrawal of the offending agent and shifting to the rabbit form of antithymocyte globulin, the gross liver dysfunction started to subside and the hepatic profile results returned to the pre-transplant levels few weeks later. The patient had her allogeneic hematopoietic stem cell transplant as planned without any further hepatic complications. After having a successful allograft, she was discharged from the stem cell transplant unit. During her follow up at the outpatient clinic, the patient remained very well and no major complication was encountered.</p> <p>Conclusion</p> <p>Hepatotoxicity related to the utilization of antithymocyte globulin varies considerably in severity and may be transient or long standing. There may be individual or population based susceptibilities to the development of side effects and these adverse reactions may also vary with the choice of the agent used. Encountering adverse effects with one type of antithymocyte agents should not discourage clinicians from shifting to another type in situations where continuation of the drug is vital.</p