Pediatric Cancer Immunotherapy and Potential for Impact on Fertility: A Need for Evidence-Based Guidance.

The use of immunotherapies for the treatment of cancer in children, adolescents, and young adults has become common. As the use of immunotherapy has expanded, including in earlier lines of therapy, it has become evident that several aspects of how these immunotherapies impact longer term outcomes among survivors are understudied. Traditional cancer therapies like alkylating and platin agents carry the greatest risk of infertility, but little is known about the impact of novel immunotherapies on fertility. This topic is of great interest to patients, patient advocates and clinicians. In this paper, we review immunotherapeutic agents used to treat childhood and young adult cancers and discuss potential mechanisms by which they may impact fertility based on the known interplay between the immune system and reproductive organs. We highlight the relative paucity of high-quality literature examining these late effects. We discuss interventions to optimize fertility preservation for our patients. Conducting longitudinal, collaborative, and prospective research on the fertility outcomes of pediatric and young adult patients with cancer who receive immunotherapy is critical to learn how to effectively counsel our patients on long-term fertility outcomes and indications for fertility preservation procedures. Collection of patient-level data will be necessary to draft evidence-based guidelines on which providers can make therapy recommendations.

Relationship between Aging and Hematopoietic Cell Transplantation.

Hematopoietic cell transplantation (HCT) is increasingly utilized as a treatment for malignancies in the elderly population. At the same time, research has elucidated the impacts of HCT on bone marrow progenitor cells, one of which is accelerated aging. Clonal hematopoiesis has also been observed to occur in the aging population, both with and without HCT. The interplay between natural aging, clonal hemoatpoiesis, and the effects of HCT on the bone marrow, has not yet been addressed. Herein we explore this relationship, and its important clinical implications.

EBV-PTLD, Adenovirus, and CMV in Pediatric Allogeneic Transplants With Alemtuzumab as Part of Pretransplant Conditioning: A Retrospective Single Center Study.

The risk of viral infections and reactivation occurring in the setting of pediatric allogeneic hematopoietic stem cell transplantation is a concern in the pediatric patient, especially with the use of Alemtuzumab (Campath) as a conditioning agent. The purpose of this study was to determine the incidence of Epstein-Barr virus posttransplant lymphoproliferative disorder (EBV-PTLD), cytomegalovirus (CMV), and adenovirus among pediatric recipients of alemtuzumab at our institution. We found that EBV-PTLD occurred in 2.1% of transplants (1 matched unrelated donor [MUD] recipient), CMV reactivation occurred in 12.5% of transplants (4 MUD and 2 matched related donor [MRD] recipients) with disseminated CMV in 2.1% of cases (1 MRD recipient), and adenovirus infection occurred in 8.3% of the total transplants (2 MUD and 2 MRD recipients). Alemtuzumab continues to be used as a method of graft-versus-host disease and graft failure prevention among pediatric recipients of hematopoietic stem cell transplantation and seems to be safer than previously reported. At our institution, alemtuzumab has not increased the risk for EBV-PTLD, CMV infection, or adenovirus.

Biology of premature ageing in survivors of cancer.

Over 30 million cancer survivors exist worldwide. Survivors have an earlier onset and higher incidence of chronic comorbidities, including endocrinopathies, cardiac dysfunction, osteoporosis, pulmonary fibrosis, secondary cancers and frailty than the general population; however, the fundamental basis of these changes at the cellular level is unknown. An electronic search was performed on Embase, Medline In-Process & Other Non-Indexed Citations, and the Cochrane Central Register of Controlled Trials. Original articles addressing the cellular biology of ageing and/or the mechanisms of cancer therapies similar to ageing mechanisms were included, and references of these articles were reviewed for further search. We found multiple biological process of ageing at the cellular level and their association with cancer therapies, as well as with clinical effects. The direct effects of various chemotherapies and radiation on telomere length, senescent cells, epigenetic modifications and microRNA were found. We review the effects of cancer therapies on recognised hallmarks of ageing. Long-term comorbidities seen in cancer survivors mimic the phenotypes of ageing and likely result from the interaction between therapeutic exposures and the underlying biology of ageing. Long-term follow-up of cancer survivors and research on prevention strategies should be pursued to increase the length and quality of life among the growing population of cancer survivors.

Lemierre Syndrome: A Retrospective Study of the Role of Anticoagulation and Thrombosis Outcomes.

Lemierre syndrome (LS) is a multisystemic infection beginning in the oropharynx and leading to thrombosis of the internal jugular vein (IJV) with septic emboli and potential thrombotic extension to the central nervous system. Although patient outcomes have improved with early initiation of antimicrobial therapies, there is no consensus regarding the role of anticoagulation in LS. To better define the role of anticoagulation therapy in LS and determine whether anticoagulation improves thrombosis outcomes, we conducted a retrospective chart review of pediatric and adult patients diagnosed with LS and managed at our institution from January 1998 to December 2014. Eighteen patients (9 females and 9 males) were included in this analysis, 6 of whom received ≥4 weeks of anticoagulation therapy (median 23.1 weeks, range 6.9-32.9 weeks). Six patients were in the pediatric age group (<18 years). All patients received broad-spectrum antibiotics. All patients had improvement in their thrombi by 3 months (nonanticoagulated patient group: complete response [CR], n = 9; partial response [PR], n = 3; anticoagulated patient group: CR, n = 2; PR, n = 4). No patient developed recurrent thrombosis or progression during the follow-up period, regardless of anticoagulation status. Our study suggests that anticoagulation in LS may not affect thrombosis outcomes.