Kuhn, Alexis K

ABSTRACT As interest in the use of cannabinoids for supportive care in pediatric cancers grows, there are emerging concerns about potential interactions with antineoplastic agents. This review provides an overview of potential drug–drug interactions between cannabinoids and 25 antineoplastic agents commonly used in pediatric hematology/oncology. Antineoplastic agents were stratified into low, medium, or high interaction risk based on the potential impact of cannabinoids on metabolic and/or pharmacodynamic pathways. The antineoplastic agents identified as high risk for interactions with cannabinoids included cyclophosphamide, doxorubicin, etoposide, ifosfamide, irinotecan, vinblastine, and vincristine. Key mechanisms of interaction include inhibition of cytochrome P450 enzymes and UDP‐glucuronosyltransferases and modulation of drug transporters such as P‐glycoprotein and breast cancer resistance protein. There is emerging evidence of a synergistic effect between cannabinoids and antineoplastic agents such as temozolomide, vinblastine, vinorelbine, and irinotecan. Pediatric patients exhibit developmental differences in drug metabolism and transporter expression, yet most pharmacokinetic data on cannabinoids are extrapolated from adult studies. There is a lack of pediatric‐specific safety, efficacy, and dosing data that underscores the need for age‐appropriate studies to ensure safe and effective integration of cannabinoids in pediatric cancer care.

Summary Recipients of haploidentical and unrelated haematopoietic cell transplants (HCTs) historically had a higher risk for graft‐versus‐host disease (GvHD). However, with improved GvHD prophylaxis, recent data suggest adult patients undergoing transplantation from unrelated or mismatched donors now experience the rates of GvHD similar to those receiving matched related donor grafts. This finding is not yet explored in paediatric patients. The objectives of this study were to: (1) compare acute and chronic GvHD incidence, mortality and GvHD‐free relapse‐free survival (GRFS) among matched related donor (MRD), matched unrelated donor (MUD) and haploidentical paediatric HCT recipients in the era of enhanced GvHD prophylaxis for high‐risk patients, (2) identify independent risk factors for GvHD and (3) evaluate the efficacy of various GvHD prophylactic regimens in our cohort. We conducted a retrospective, single‐centre medical record abstraction among patients aged 0–25 years who underwent allogeneic HCT for any indication. The results demonstrated that 5‐year cumulative incidence rates of any GvHD, all‐cause mortality and GRFS are similar across the haploidentical, MRD and MUD groups. Tacrolimus‐containing doublet/triplet regimens were associated with decreased GvHD, as compared to ciclosporin. Adding alemtuzumab also decreased risk for GvHD, without increasing relapse rates. Prospective studies with larger cohorts are warranted to further optimize outcomes for paediatric allogeneic HCT patients.

ABSTRACT Background Patients at high risk for cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplant (HCT) should receive CMV prophylaxis. Historically, ganciclovir has been the preferred agent. However, its side effect profile, particularly myelosuppression, is undesirable. Letermovir is a newer agent that is not myelosuppressive and has replaced ganciclovir as the preferred agent for CMV prophylaxis in high‐risk adult patients. Methods The primary objective was to compare the incidence of dose modifications or discontinuation of CMV prophylaxis between pediatric patients who received ganciclovir versus letermovir. Secondary objectives included comparing the use of granulocyte colony‐stimulating factor (G‐CSF) support and the incidence of CMV DNAemia. We reviewed records of all pediatric patients who received an HCT at our institution between 2000 and 2024 and received either ganciclovir/valganciclovir or letermovir for CMV prophylaxis. Results Between 2000 and 2024, 65 pediatric patients receiving prophylactic ganciclovir, valganciclovir, or letermovir were evaluated. The median age at transplant was 12.2 years. No patients receiving letermovir required dose modification or discontinuation as opposed to 14 (29.2%) patients receiving ganciclovir ( p = 0.014). After engraftment, 12 (25%) patients receiving ganciclovir required G‐CSF support compared to seven (41.2%) patients receiving letermovir ( p = 0.23). In the ganciclovir group, 10 (20.8%) patients experienced CMV infection versus one (5.9%) patient receiving letermovir ( p = 0.26). Conclusion Compared with those receiving letermovir, a significantly higher proportion of patients in the ganciclovir/valganciclovir group experienced dose modifications or discontinuation of CMV prophylaxis due to adverse effects. Letermovir shows great promise as a CMV prophylactic agent in pediatric HCT patients due to its favorable side effect profile.

A 13-year-old male undergoing maintenance chemotherapy with methotrexate and 6-mercaptopurine (6MP), for very high-risk B-cell acute lymphoblastic leukemia (ALL), presented with vomiting due to severe hypoglycemia with metabolic acidosis. While his laboratory values were concerning for a critically ill child, the patient was relatively well appearing. Hypoglycemia is a rare but serious side effect of 6MP with an unexpectedly variable presentation; therefore, a high index of suspicion is needed for its prompt detection and treatment. This patient also had severe metabolic acidosis, likely secondary to hypoglycemia, creating a serious clinical picture despite a well-appearing child. This example of incongruity between laboratory tests and clinical appearance adds nuance to the existing literature. Moreover, although 6MP-associated hypoglycemia is rare, it may be more prevalent than the literature suggests, as symptoms of hypoglycemia—nausea, vomiting, and somnolence—mirror common chemotherapy side effects. 6MP-induced hypoglycemia can be ameliorated with the addition of allopurinol to shunt metabolism in favor of the production of therapeutic metabolites over hepatotoxic metabolites. Additionally, a morning administration of 6MP and frequent snacks may also help to prevent hypoglycemia. Overall, this case adds to the literature of unusual reactions to 6MP including hypoglycemia in an older child without traditional risk factors.

Introduction: Acrocyanosis and erythema pernio are 2 dermatologic manifestations of vasospastic changes. Primary care providers should consider that these conditions can occur as primary or idiopathic conditions and as secondary conditions related to another disease or medication. Herein we describe a case of acrocyanosis and erythema pernio attributed to vincristine therapy. Case Description: A 22-year-old man was evaluated for discomfort and red lesions involving the toes of both feet for several weeks. He had completed chemotherapy 1 month earlier for Ewing sarcoma in the right femur. Local control for the primary tumor included wide local excision and reconstruction with a vascularized fibular allograft from the right fibula. On examination, his right foot was dark blue and cool. Toes on both feet had nonpainful erythematous papules. After the case was discussed with the patient’s oncology team, the diagnosis was medication-induced acrocyanosis of the right foot and bilateral erythema pernio. Treatment consisted of supportive care to keep the feet warm and promote circulation to the feet. At 2-week follow-up, the patient’s symptoms and the appearance of his feet had markedly improved. Discussion: Primary care clinicians should be able to recognize dermatologic manifestations of vasospastic changes, including acrocyanosis and erythema pernio, and rule out possible secondary causes, such as pharmacologic agents. This patient’s history of therapy for Ewing sarcoma prompted consideration of medication-induced vasospastic changes most likely related to the adverse vasospastic effects of vincristine. Symptoms should improve with cessation of the offending medication.