Optimum therapeutic approaches for lupus nephritis: what therapy and for whom?

The optimum therapy for patients with lupus nephritis is a hotly debated topic. Prospective randomized studies in patients with proliferative lupus nephritis have established the superiority of cyclophosphamide to azathioprine, both of which are used in combination with corticosteroids. Although high-dose, intermittent administration of cyclophosphamide (pulse therapy) has significantly reduced the toxicity associated with this drug, premature ovarian failure and infections remain considerable problems. Short-term to intermediate-term, randomized controlled trials have shown that mycophenolate mofetil is a good option for the induction and maintenance of remission in lupus nephritis patients. Additional longer-term trials involving more patients and stricter outcomes based on renal function are needed, however, before claims that mycophenolate mofetil is superior to cyclophosphamide can be substantiated. Until such data are available, physicians caring for patients with lupus nephritis can use mycophenolate mofetil as induction or maintenance therapy for selected patients under close observation. Small noncontrolled trials with short-term follow-up suggest that up to 50% of patients who are refractory to cyclophosphamide might have a clinically significant response to rituximab, a monoclonal antibody directed against B cells.     

CAR T in adult ALL: When and for whom?

Chimeric antigen receptor T cell therapy targeting CD19 (CART19) has shown remarkable results in patients with relapsed/refractory (r/r) B cell acute lymphoblastic leukemia (ALL). In patients 25 years of age or younger CART19 therapy is an accepted standard of care, while the treatment of older adults is less straight forward and possible only in the context of a clinical trial. Treatment of older patients with CAR T cells requires careful consideration of overall treatment goals, suitability of a consolidative hematopoietic stem cell transplant (HSCT), alternative treatment options, patient risk profile, and anticipated responses and toxicities of the specific CAR T cell products available. Here we use patient guided examples to inform approaches to care.     

Off-pump coronary artery bypass grafting through sternotomy: for whom?

PURPOSE OF REVIEW: Off-pump coronary artery bypass grafting hopes to avoid morbidity associated with cardiopulmonary bypass, improving clinical outcomes. Yet its technical difficulty and unfamiliarity raise concern that adoption of off-pump coronary artery bypass might be associated with poorer outcomes. Both surgeon-specific and patient-related factors are believed to play roles in the success of off-pump coronary artery bypass. This review sought to elucidate these factors. RECENT FINDINGS: Current prospective data suggest that both techniques have similar rates of mortality but off-pump coronary artery bypass does provide patients with a lower morbidity. Multiple prospective studies suggest a decrease in stroke rates for off-pump coronary artery bypass grafting. There is a consensus that certain patients will have better outcomes if done off-pump. Surgeon experience with the procedure does impact patient outcome. SUMMARY: Though every patient must be dealt with on an individual basis, it would appear that almost any patient is a candidate for off-pump coronary artery bypass and that, given time and an appropriate desire, most any surgeon can perform the procedure.     

Biologic therapies in juvenile idiopathic arthritis: why and for whom?

With greater understanding of pathophysiological, genetic and environmental influences on juvenile arthritis, there is an opportunity to develop new targets for therapy and greater control of disease. Early, aggressive control of arthritis is essential in order to prevent long-term disability. For those children that are resistant to standard therapy, new and exciting alternative medications are emerging. However, continued research is needed to gain a greater understanding of immunological and genetic profiles of the disease. Pharmaco-vigilance is essential to establish efficacy and side effect profiles. Physiotherapy, occupational therapy, nursing issues, and psychology remain integral to the management of JIA, along with liaison with ophthalmology, orthopaedic and dental colleagues. This article reviews the current biologic treatment options available for children with arthritis and the evidence base that supports their use.     

Cell therapy for cardiovascular disease: what cells, what diseases and for whom?

Experimental and human data suggesting progenitor cells possess the capacity to regenerate tissue and augment repair in injured organs has generated widespread interest in the basic research and clinical communities. Nowhere have these findings been more tantalizing than in human cardiovascular disease, in which vasculogenesis and myocardial regeneration logically and understandably remain as attractive therapeutic targets. Burgeoning experimental evidence attests to the proangiogenic, vasculogenic and tissue reparative capabilities of a broad range of progenitor cells derived from the bone marrow, circulation and a number of other tissues in vivo. Studies demonstrating the most apparent therapeutic success are those implicated in revascularization and repair of acute or chronically ischemic tissues in the heart and the peripheral vascular system. Numerous small clinical trials have yielded promising preliminary results without clear evidence of a superiority for a specific cell type or clinical disease entity as the most suitable target for cell therapy. This review will evaluate the scientific rationale for use of a specific cell or cells, the cardiovascular disease states most appropriate for targeted cell therapy, and the patient-specific barriers to therapeutic success, including emerging hurdles such as cardiovascular risk factors and comorbidities in eligible subjects.     

Fusion of imaging technologies: how,when, and for whom?

Over the past decade, electroanatomic mapping has emerged as a useful tool for complex ablation procedures. A more recent advancement is the development of image integration. Image integration refers to the process of registering a previously acquired MRI or CT scan of the heart with the mapping space during the ablation procedure. The technique of image integration is now relied on by many electrophysiology laboratories to guide complex ablation procedures, particularly atrial fibrillation ablation and ablation of patients with ventricular tachycardia in the setting of structural heart disease. An even more recent development is image fusion. This refers to taking information about the myocardial substrate, especially intramyocardial scar, and registering it with the active mapping space. This technique remains in its infancy but shows great promise in facilitating complex ablation procedures. The purpose of the article is to review the development, state of the art, and future of these image integration and fusion techniques.     

Allogeneic hematopoietic cell transplantation for MDS: For whom,when and how?

Hematopoietic cell transplantation (HCT) is currently the only treatment with curative potential for patients with myelodysplastic syndrome (MDS). However, treatment-related mortality and relapse have remained major barriers to uniform success. Therefore, important questions remain to be answered, such as whom to transplant, when and how. With reduced intensity conditioning (RIC) regimens, patients in their 70s and patients with comorbid conditions have been transplanted successfully, although the relapse incidence with this approach tends to be increased in comparison to high intensity regimens. Success rates are higher in patients transplanted at an early stage of their disease. Encouraging is the fact, that results with unrelated donors who are HLA-matched by high resolution typing are comparable to those achieved with HLA genotypically identical siblings. The establishment of cord blood as a source of stem cells, and the recent success with HLA-haploidentical related donors will allow the offering of HCT to virtually all patients. Dependent upon disease stage and characteristics, some 25% to 75% of transplanted patients will be cured. While 20%–30% of patients experience chronic medical problems after HCT, 70% report a “good to excellent” quality of life. New studies must focus on further reducing GVHD for all patients and on overcoming high relapse rates in patients with high risk disease.     

Dose intensity for induction in acute myeloid leukemia: what,when, and for whom?

Intensive chemotherapy has been the backbone of the treatment of acute myeloid leukemia (AML) for decades. However, an increase in novel targeted agents, which has been brought about in part by a deeper understanding of the genetic makeup of AML, has led to remission- inducing regimens that do not require traditional cytotoxic agents. Combinations of a hypomethylating agent (HMA) and venetoclax have doubled the chance of remission for patients considered unfit for induction chemotherapy who would have traditionally been offered singleagent HMA. In fact, this regimen may rival the complete remission rate achieved with induction chemotherapy for certain populations such as the very elderly and those with secondary AML, but equivalency has yet to be established. Further advances include the addition of gemtuzumab ozogamicin and FLT3 inhibitors to induction chemotherapy, which improves survival for patients with core-binding factor and FLT3-mutated AML, respectively. Still, much work is needed to improve the outcomes of the highest-risk subgroups: frail patients and those with high-risk cytogenetics and/or TP53 mutations. Promisingly, the landscape of AML therapy is shifting dramatically and no longer is intensity, when feasible, always the best answer for AML.