Childhood post-transplant lymphoproliferative disorder

Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of neoplasms that occur as a serious complication of haematopoetic stem cell or solid organ transplantation. They are Epstein Barr virus (EBV) driven in over 90% of the cases. Incidence of PTLD varies from 1 to 20 % depending on the organ transplanted, the intensity of immunosuppression and the recipient's pre transplant EBV status. The pathology of PTLD varies from polymorphic to monomorphic/monoclonal disease which is indistinguishable from a high-grade lymphoma. The clinical course varies from indolent to rapidly progressive, fulminant disease. Over two thirds to 90% of PTLDs are of B cell origin. The current standard of treatment involves reduction of immunosuppressive drugs and if that is not sufficient, use of anti CD20 monoclonal antibody (Rituximab) alone or in combination with conventional chemotherapy. This review offers an overview for healthcare professionals looking after children and young people who may be at risk of or have PTLD. It discusses the pathophysiology, the risk factors, classification and diagnosis of PTLD. It also summarises the current approach to management and monitoring strategies.     

Melanoma en pacientes receptores de un trasplante de órgano sólido

In this review, we analyze the 3 clinical scenarios related to the development of melanoma in solid organ transplant recipients: melanoma in patients with a history of the tumor prior to a transplant, de novo melanoma following a transplant, and melanoma of donor origin. The main factors to consider in organ-transplant candidates with a history of melanoma are tumor stage, presence or absence of residual disease, and time from diagnosis to transplantation. Solid organ transplant recipients have a greater risk of melanoma than immunocompetent individuals. Mortality is also higher in this population, especially in patients with advanced melanoma, as treatment is especially challenging. Clinical history and physical examination provide the most useful information for preventing donor-to-recipient transmission of melanoma. Donor-derived melanoma has a very poor prognosis.     

Leg weakness in a lung transplant patient

Progressive multifocal leukoencephalopathy (PML) is associated with JC polyomavirus (JCV) infection of central nervous system oligodendrocytes resulting in demyelinization and progressive focal neurologic deficits. Reactivation of dormant JCV occurs in the setting of immunosuppression, most commonly in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) or hematological malignancies. PML has also been reported in solid organ transplant recipients. We report the case of a 61‐year‐old man after bilateral lung transplantation for chronic hypersensitivity pneumonitis who presented with leg weakness, cognitive decline, and expressive aphasia at 5 months post transplantation. Magnetic resonance imaging and brain biopsy were consistent with PML. Treatment attempt with cytarabine was unsuccessful, and immunomodulation resulted in recurrent grade A3 rejection. The difficulty of managing PML in lung transplant patients is highlighted by the lack of directed therapy and risk of graft rejection or failure with attempts at decreasing immunosuppression.     

Bladder transitional cell carcinoma and BK virus in a young kidney transplant recipient

Kidney transplant recipients have a heightened risk of developing neoplasms. Immunosuppressive treatments decrease the incidence of transplant rejection but increase the risk of infections, including BK virus (BKV). This infection is acquired in childhood and remains latent in the renal and urinary epithelium. In cases of immunodeficiency, BKV has been implicated as a tumor virus, but the role of BKV in cancer is a controversial topic and is difficult to determine. In the tumor cells, it is possible to detect fragments of the viral genome that could alter the control mechanisms of the cell cycle and DNA repair. We report the case of a kidney transplant recipient who developed BKV nephropathy and carcinoma of the bladder, supporting a possible role for BKV in the oncogenic pathway in this clinical setting, but the role of BKV in cancer remains a controversial topic and difficult to determine.     

I-131 tositumomab

Importance of the field: Follicular lymphoma (FL) is a subgroup of B-cell Non-Hodgkin's lymphomas (NHL) that account for 15 – 30% of all lymphomas. I-131 tositumomab is a radiommunoconjugate of ¹³¹I and the anti-CD20 monoclonal antibody tositumomab. It is one of two available radioimmunoconjugates for the treatment of recurrent, refractory, or transformed FL.

Areas covered in this review: This review describes the clinical pharmacology of I-131 tositumomab, dosing and administration guidelines, and the key clinical trials providing evidence of its efficacy and safety in patients with FL, transformed, or other aggressive B-NHL, in combination with chemotherapy, or its incorporation in transplant conditioning regimens. This review also covers safety and regulatory concerns regarding the use of I-131 tositumomab.

What the reader will gain: This review critically appraises the clinical trials behind approval of I-131 tositumomab as a second-line agent for FL and also outlines the data supporting its use in the upfront setting.

Take home message: I-131 tositumomab is a safe and effective option for patients with recurrent, refractory, or transformed FL and carries promise in the upfront treatment of FL, aggressive B-NHL, and as a transplant conditioning regimen.     

Therapeutic strategies for cytomegalovirus infection in haematopoietic transplant recipients: a focused update

Introduction: Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality in immunocompromised patients, particularly following allogeneic haematopoietic transplantation. One of the principal factors leading to this increased risk is the loss of T-cell immunity.

Areas covered: In a recent review, we assessed the treatment strategies for prophylaxis and pre-emptive treatment of CMV, particularly where relevant to the high-risk patient populations following allogeneic haematopoietic transplantation. This review is a focused update to our previous article and presents a more detailed analysis of the developments in drugs, vaccines and adoptive T-cell therapies since that time. Relevant studies were selected from PubMed and clinicaltrials.gov. The search terms include allogeneic transplant, cytomegalovirus, multidrug-resistant virus and adoptive T-cell therapy.

Expert opinion: The current randomised controlled studies evaluating pharmacological agents for CMV should inform as to whether these provide significant clinical benefits. Adoptive cell therapy provides a more physiological approach to the problem of lack of CMV-specific immunity. Recent reports add to the evidence that culture-based techniques can create cellular products that are safe and efficacious, although without Phase III data to definitively support their routine application and the difficulty of satisfying GMP standards.     

Obesity in heart failure: impact on survival and treatment modalities

Heart failure (HF) and obesity are commonly seen in the USA. Although obesity is associated with traditional cardiovascular disease, its relationship with HF is complex. Obesity is an accepted risk factor for incident HF. However, in patients with established HF, there exists a paradoxical correlation, with escalating BMI incrementally protective against adverse outcomes. Despite this relationship, patients with HF may desire to lose weight to reduce comorbidities or to improve quality of life. Thus far, studies have shown that intentional weight loss in obese patients with HF does not increase risk, with strategies including dietary modification, physical activity, pharmacotherapy, and/or surgical intervention.