ABSTRACT
Hemophagocytic lymphohistiocytosis (HLH) is an immune dysregulatory syndrome characterized by severe inflammation and end-organ damage. Due to significant organ dysfunction, patients often require extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). In this report, we describe consideration for adjusting treatment in the context of extracorporeal organ support. We describe agents commonly used and dosing adjustments made in light of extracorporeal organ support. We report six cases that illustrate the feasibility of initiating standard HLH therapies in patients requiring these modalities.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Dexamethasone/therapeutic use , Etoposide/therapeutic use , Extracorporeal Membrane Oxygenation , Lymphohistiocytosis, Hemophagocytic/drug therapy , Child, Preschool , Continuous Renal Replacement Therapy , Humans , Infant , Infant, Newborn , Intensive Care Units, Pediatric , Retrospective StudiesABSTRACT
As survival rates in allogeneic hematopoietic stem cell transplantation (HSCT) continue to improve, attention to long-term complications, including cardiovascular disease, becomes a major concern. Cardiovascular disease and dyslipidemia are a common, yet often overlooked occurrence post-HSCT that results in significant morbidity and mortality. Also, increasing evidence shows that several anti-hyperlipidemia medications, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in particular, may have a role in modulating graft-versus-host disease (GVHD). However, factors such as drug-drug interactions, adverse effect profiles, and the relative efficacy in lowering cholesterol and triglyceride levels must be taken into account when choosing safe and effective lipid-lowering therapy in this setting. This review seeks to provide guidance to the clinician in the management of dyslipidemia in the allogeneic HSCT population, taking into account the recently published American College of Cardiology/American Heart Association guidelines on hyperlipidemia management, special considerations in this challenging population, and the evidence for each agent's potential role in modulating GVHD.
Subject(s)
Dyslipidemias/drug therapy , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Allografts , Drug Interactions , Dyslipidemias/blood , Graft vs Host Disease/blood , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Practice Guidelines as TopicSubject(s)
Cord Blood Stem Cell Transplantation , Immunologic Deficiency Syndromes/diagnosis , Receptors, Interferon/genetics , Sequence Deletion/genetics , DNA Mutational Analysis , Humans , Immunologic Deficiency Syndromes/therapy , Infant , Male , Phosphorylation , STAT1 Transcription Factor/metabolism , Interferon gamma ReceptorABSTRACT
Introduction: Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency. Methods: We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity. Results: From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026). Discussion: As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.
Subject(s)
Antigens, CD19 , Cyclophosphamide , Immunotherapy, Adoptive , Lymphoma, Non-Hodgkin , Vidarabine , Humans , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Male , Middle Aged , Female , Antigens, CD19/immunology , Vidarabine/analogs & derivatives , Vidarabine/administration & dosage , Vidarabine/therapeutic use , Retrospective Studies , Lymphoma, Non-Hodgkin/therapy , Lymphoma, Non-Hodgkin/immunology , Aged , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Adult , Lymphocyte Depletion/methods , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biological Products/therapeutic use , Biological Products/adverse effects , Biological Products/administration & dosage , Receptors, Antigen, T-CellSubject(s)
Adenosine Deaminase/deficiency , Anemia, Aplastic/drug therapy , Anemia, Aplastic/etiology , Bone Marrow Diseases/drug therapy , Bone Marrow Diseases/etiology , Hemoglobinuria, Paroxysmal/drug therapy , Hemoglobinuria, Paroxysmal/etiology , Intercellular Signaling Peptides and Proteins/deficiency , Tumor Necrosis Factor-alpha/therapeutic use , Anemia, Aplastic/diagnosis , Biomarkers , Biopsy , Bone Marrow/pathology , Bone Marrow Diseases/diagnosis , Bone Marrow Failure Disorders , Hematologic Tests , Hemoglobinuria, Paroxysmal/diagnosis , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Severe Combined Immunodeficiency/diagnosis , Severe Combined Immunodeficiency/etiology , Symptom Assessment , Treatment OutcomeABSTRACT
Chemotherapy-induced nausea and vomiting (CINV) involves multiple neurotransmitter and receptor systems; thus, its optimal treatment is likely to require a combination of therapies targeting multiple systems. Antiemetic regimens have evolved from use of dopamine antagonists alone to combination regimens such as a corticosteroid plus an antagonist of the serotonin (5-hydroxytryptamine) type 3 receptor or this combination with a neurokinin-1 receptor antagonist. The net result is that antiemetic efficacy has markedly increased with the addition of each new class of agent to treatment regimens. Further research is needed to determine optimal uses of available classes and agents for managing CINV, to elucidate the roles of additional neurotransmitters and receptors in both nausea and vomiting, and to develop new antiemetic agents.