Malcolm Holterhus
Postdoctoral Scholar, Hematology-Oncology
Contact
https://orcid.org/0000-0002-0317-1097All Publications
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Parvovirus B19 infection in pediatric allogeneic hematopoietic cell transplantation - Single-center experience and review
TRANSPLANT INFECTIOUS DISEASE
2023: e14028
Abstract
Parvovirus B19 (B19V) infection following pediatric hematopoietic cell transplantation (HCT) is a rare complication and available data is scarce. Therefore, we present the experience with B19V Infection in allogeneic pediatric HCT recipients at our transplant center together with a systematic review of the literature.Pediatric HCT patients with Parvovirus B19 infection treated at the University Children's Hospital Münster between 1999 and 2021 were retrospectively identified and clinical data were analyzed. Additionally, a systematic MEDLINE search to identify relevant articles was performed.We identified three out of 445 patients (0.6%) with B19V infection post-transplantation. B19V infection occurred in combination with other complications like Graft-versus-Host disease, additional infections, or autoimmune-mediated hemolysis potentially triggered by B19V. In one patient these complications lead to a fatal outcome. The review of the literature showed considerable morbidity of B19V infection with the potential for life-threatening complications. Most patients were treated by red blood cell transfusion and intravenous immunoglobulins (IVIG) with a high succession rate.Symptomatic B19V infection following HCT remains a rare but potentially challenging complication. A causal antiviral therapy does not exist as well as general recommendations on dosage and duration of IVIG therapy. Despite this, most patients are treated successfully with these measures. Additionally, transmission via blood or stem cell products is also rare and no general recommendations on B19V screenings exist.
View details for DOI 10.1111/tid.14028
View details for Web of Science ID 000932452900001
View details for PubMedID 36748962
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Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients
PEDIATRIC DRUGS
2023; 25 (2): 225-232
Abstract
Cytomegalovirus (CMV) infection is a frequent event in patients undergoing allogeneic haematopoietic cell transplantation (HCT) and is associated with increased morbidity and mortality due to eventual progress to end-organ disease. Letermovir prophylaxis for CMV infections has become a standard of care in adult HCT recipients due to its efficacy and high tolerability. However, it is not yet approved for paediatric patients.In a retrospective single-centre observational study we evaluated the use of letermovir for prophylaxis or pre-emptive treatment of cytomegalovirus (CMV) infection in seropositive paediatric HCT recipients receiving the compound outside of clinical trials. The primary endpoint was CMV reactivation requiring a change of medication.A total of 17 patients (seven female/ten male; median age 12.2 [range 3.5-19] years, median body weight 39.5 [range 15-63] kg; median follow-up time 463.7 [range 41-1022] days) were identified who were started on oral (14) or intravenous (3) followed by oral (2) letermovir shortly after neutrophil engraftment at doses determined on the basis of age, weight, and concomitant cyclosporine use.Five patients had no evidence of viral replication (prophylactic use), while 12 patients had varying extents of viral replication (pre-emptive therapy). A change of therapy was required in one patient due to a sustained increase in CMV viral load, and in two patients, letermovir was stopped without later reactivation after initiation of palliative care for recurrent leukaemia. Of the 14 patients who completed treatment, 3 had evidence of transient viral replication after end of treatment that required no further antiviral treatment. No patients (of 17) discontinued letermovir due to an adverse event.Letermovir was effective in controlling CMV infection in seropositive paediatric allogeneic HCT recipients and was overall well tolerated. Pending completion of the still ongoing paediatric investigation plans, letermovir will be an important adjunct to our options for control of infectious complications in this special population.
View details for DOI 10.1007/s40272-022-00547-6
View details for Web of Science ID 000904045900001
View details for PubMedID 36572834
View details for PubMedCentralID PMC9931806
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The Cellular Tumor Immune Microenvironment of Childhood Solid Cancers: Informing More Effective Immunotherapies
CANCERS
2022; 14 (9)
Abstract
Common pediatric solid cancers fail to respond to standard immuno-oncology agents relying on preexisting adaptive antitumor immune responses. The adoptive transfer of tumor-antigen specific T cells, such as CAR-gene modified T cells, is an attractive strategy, but its efficacy has been limited. Evidence is accumulating that local barriers in the tumor microenvironment prevent the infiltration of T cells and impede therapeutic immune responses. A thorough understanding of the components of the functional compartment of the tumor microenvironment and their interaction could inform effective combination therapies and novel engineered therapeutics, driving immunotherapy towards its full potential in pediatric patients. This review summarizes current knowledge on the cellular composition and significance of the tumor microenvironment in common extracranial solid cancers of childhood and adolescence, such as embryonal tumors and bone and soft tissue sarcomas, with a focus on myeloid cell populations that are often present in abundance in these tumors. Strategies to (co)target immunosuppressive myeloid cell populations with pharmacological anticancer agents and with selective antagonists are presented, as well as novel concepts aiming to employ myeloid cells to cooperate with antitumor T cell responses.
View details for DOI 10.3390/cancers14092177
View details for Web of Science ID 000794604300001
View details for PubMedID 35565307
View details for PubMedCentralID PMC9105669