Usefulness and Limitations of Polymerase Chain Reaction (PCR) for the Diagnosis and Management of Toxoplasmosis Following Allogeneic Hematopoietic Cell Transplant: Single-center Experience With 31 Patients Over 16 Years.

Background: Toxoplasmosis is an early post-transplant complication in recipients of allogeneic hematopoietic cell transplant (HCT), typically arising from reactivation of latent infection. polymerase chain reaction (PCR) has improved detection.

Methods: Single-center, retrospective review of allogeneic HCT recipients who developed toxoplasmosis from August 2008 to November 2024.

BK virus kinetics and associated cystitis/urethritis symptoms after PTCy-based allogeneic hematopoietic cell transplant.

BK virus-associated cystitis/urethritis (BK-C) is a major cause of morbidity in allogeneic hematopoietic cell transplantation (HCT) recipients. We prospectively followed weekly plasma and urine BK viral loads and associated symptoms in 169 recipients of post-transplantation cyclophosphamide (PTCy)-based HCT. Patients with ≥2 positive BK specimens before day +100 were considered at-risk for developing BK-C.

REMOVED: Post-Transplantation Cyclophosphamide Protects the Thymus from Alloreactive T-Cell Damage after T-Cell-Replete MHC-Haploidentical Hematopoietic Cell Transplantation but Does Not Rescue Normal Medullary Thymic Epithelial Cell Differentiation or Intrathymic Clonal Deletion.

This abstract has been removed: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal).

Infection after CD19 chimeric antigen receptor T cell therapy for large B cell lymphoma: Real-world analysis from CIBMTR.

Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 R/R LBCL patients receiving commercial CD19 CAR T-cell (n=2804 axicabtagene ciloleucel, n=546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 (24.

Choosing Between HLA-Mismatched Unrelated and Haploidentical Donors: Donor Age Considerations.

Haploidentical donors and HLA-mismatched unrelated donors (MMUDs) are increasingly utilized for hematopoietic cell transplantation (HCT), with post-transplantation cyclophosphamide (PTCy) emerging as an effective graft-versus-host disease (GVHD) prophylaxis strategy. Despite the growing use of these donor types, comparative data to guide donor selection remain limited. Donor age is a known predictor of HCT outcomes, yet its specific impact when choosing between haploidentical and MMUD donors with PTCy-based prophylaxis has not been thoroughly explored.

Role of Donor Cytomegalovirus Serostatus in Cytomegalovirus-Seronegative Recipients of Unrelated Donor Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide Prophylaxis.

While donor age significantly impacts allogeneic hematopoietic cell transplantation (HCT) outcomes, the effect of donor cytomegalovirus (CMV) serostatus, particularly in CMV-seronegative recipients, remains a critical consideration. Donor CMV seropositivity is linked to increased CMV viremia and non-relapse mortality (NRM) in these recipients. Given the limited scope of novel antiviral prophylaxis drugs, eg, letermovir solely for CMV-seropositive recipients and the association of post-transplant cyclophosphamide (PTCy) with increased CMV reactivation, this study investigates the impact of donor CMV serostatus on outcomes in CMV-seronegative acute myeloid leukemia (AML) patients undergoing HLA-matched or mismatched unrelated donor HCT with PTCy.

Interleukin 35-producing B cells prolong the survival of GVHD mice by secreting exosomes with membrane-bound IL-35 and upregulating PD-1/LAG-3 checkpoint proteins.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for aggressive hematologic malignancies. However, the risk of developing graft-versus-host disease (GVHD) is a significant barrier to allo-HSCT. GVHD is a debilitating condition with high mortality rates and current therapeutic options for GVHD are limited, with corticosteroids being the standard treatment.

Impact of Donor Age and Donor Cytomegalovirus Serostatus on Outcomes After Related Donor Allogeneic Hematopoietic Stem Cell Transplantation.

Cytomegalovirus (CMV) infection post-hematopoietic cell transplantation (HCT) remains a significant cause of morbidity and mortality. While letermovir prophylaxis is available for CMV-seropositive recipients, optimal donor selection for CMV-seronegative recipients remains unclear, with donor age often prioritized over CMV serostatus. We investigated the relative impact of donor age and CMV serostatus in CMV-seronegative recipients (n = 1013) with either CMV-seropositive (n = 318) or CMV-seronegative donors (n = 695), who underwent HCT with HLA-matched sibling donors with calcineurin inhibitor-based or post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease prophylaxis, or haploidentical donors with PTCy.

Intermediate-dose posttransplantation cyclophosphamide for myeloablative HLA-haploidentical bone marrow transplantation.

High-dose posttransplantation cyclophosphamide (HD-PTCy), given at 50 mg/kg/day on days +3/+4, is a standard-of-care graft-versus-host disease (GVHD) prophylaxis for allogeneic hematopoietic cell transplantation (HCT). Our murine MHC-haploidentical HCT studies suggested intermediate-dose PTCy produces superior GVHD control compared with HD-PTCy and PTCy is maximally effective on day +4. We conducted a single-institutional prospective phase 1/2 trial to reduce PTCy dosing to 25 mg/kg/day on days +3/+4 or on day +4 only for myeloablative HLA-haploidentical bone marrow HCT using PTCy, sirolimus, and mycophenolate mofetil.

Donor Type Does Not Impact Late Graft Failure Following Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis.

Background: Post-transplant cyclophosphamide (PTCy) is a commonly used graft-vs-host disease (GVHD) prophylaxis, particularly in the setting of haploidentical (haplo) hematopoietic cell transplantation (HCT). The rate of graft failure has been reported to be as high as 12% to 20% in haplo-HCT recipients using PTCy. The objective of this study was to determine whether donor type influenced the risk of late graft failure following reduced-intensity conditioning (RIC) HCT using PTCy-based GVHD prophylaxis.

Acanthamoeba Infection in a Hematopoietic Cell Transplant Recipient: Challenges in Diagnosis, Management, and Source Identification.

We report a case of Acanthamoeba infection in an HCT recipient with steroid-refractory GVHD. We highlight the multiple challenges that free-living ameba infections present to the clinician, the clinical laboratory, transplant infectious disease for review, hospital epidemiology if nosocomial transmission is considered, and public health officials, as exposure source identification can be a significant challenge. Transplant physicians should include Acanthamoeba infections in their differential diagnosis of a patient with skin, sinus, lung, and/or brain involvement.

F-FLT PET and Blood-based Biomarkers for Identifying Gastrointestinal Graft versus Host Disease after Allogeneic Cell Transplantation.

Purpose To determine whether fluorine 18 (F) fluorothymidine (FLT) PET imaging alone or combined with Mount Sinai Acute GVHD International Consortium (MAGIC) biomarkers could help identify subclinical gastrointestinal graft versus host disease (GI-GVHD) by day 100 following hematopoietic stem cell transplantation (HSCT). Materials and Methods F-FLT PET imaging was analyzed in a prospective pilot study (ClinicalTrials.gov identifier no.

Challenges with sirolimus experimental data to inform QSP model of post-transplantation cyclophosphamide regimens.

Dose optimization of sirolimus may further improve outcomes in allogeneic hematopoietic cell transplant (HCT) patients receiving post-transplantation cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD). Sirolimus exposure-response association studies in HCT patients (i.e.

Safety but limited efficacy of donor lymphocyte infusion for post-transplantation cyclophosphamide-treated patients.

The therapeutic efficacy of donor lymphocyte infusions (DLIs) given after allogeneic hematopoietic cell transplantation (HCT) is limited by risk of graft-versus-host disease (GVHD). Post-transplantation cyclophosphamide (PTCy) effectively prevents severe GVHD, but there are limited data on outcomes of DLIs given to PTCy-treated patients. We reviewed 162 consecutive PTCy-treated patients transplanted between 2015-2022 within the Center for Immuno-Oncology at the National Cancer Institute.

Effect of donor age in patients with acute myeloid leukemia undergoing haploidentical hematopoietic cell transplantation vary by conditioning intensity and recipient age.

We investigated the impact of donor age (younger [≤35 years] vs. older [>35 years]) after accounting for other non-HLA and HLA factors on outcomes of patients with acute myeloid leukemia undergoing HLA-haploidentical hematopoietic cell transplantation (n = 790). The effect differed by conditioning-partly related to the differences in the recipient age in myeloablative (MAC; median 46 years) versus reduced-intensity/non-myeloablative conditioning (RIC/NMA; median 61 years) groups.

Allogeneic hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a CIBMTR analysis.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

Co-expression of Foxp3 and Helios facilitates the identification of human T regulatory cells in health and disease.

Foxp3 is regarded as the major transcription factor for T regulatory (T) cells and expression of Foxp3 is used to identify and quantitate Treg cells in mouse models. However, several studies have demonstrated that human CD4 T conventional (T) cells activated by T cell receptor (TCR) stimulation can express Foxp3. This observation has raised doubt as to the suitability of Foxp3 as a T marker in man.

Immunosuppressant adherence in adult outpatient hematopoietic cell transplant recipients.

Introduction: Medication nonadherence continues to be challenging for allogeneic hematopoietic cell transplant (HCT) recipients. The risk and severity of chronic graft-versus-host disease (GVHD) are associated with low immunosuppressant concentrations (which can be improved with model-informed precision dosing (MIPD)) and with immunosuppressant nonadherence (which can be improved with acceptable interventions).

Methods: With the goals of improving adherence and achieving therapeutic concentrations of immunosuppressants to eliminate GVHD, we characterized the feasibility of using the Medication Event Monitoring (MEMS) Cap in adult HCT recipients.

HLA Class I Genotype Is Associated with Relapse Risk after Allogeneic Stem Cell Transplantation for NPM1-Mutated Acute Myeloid Leukemia.

Mutation-bearing peptide ligands from mutated nucleophosmin-1 (NPM1) protein have been empirically found to be presented by HLA class I in acute myeloid leukemia (AML). We hypothesized that HLA genotype may impact allogeneic hematopoietic stem cell transplantation (allo-HCT) outcomes in NPM1-mutated AML owing to differences in antigen presentation. We evaluated the effect of the variable of predicted strong binding to mutated NPM1 peptides using HLA class I genotypes from matched donor-recipient pairs on transplant recipients' overall survival (OS) and disease-free survival (DFS) as part of the primary objectives and cumulative incidence of relapse and nonrelapse mortality (NRM) as part of secondary objectives.

Impact of Donor Age in Haploidentical-Post-Transplantation Cyclophosphamide versus Matched Unrelated Donor Post-Transplantation Cyclophosphamide Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia.

Haploidentical hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis is associated with inferior overall survival (OS) compared to HLA-matched unrelated donor (MUD) HCT with PTCy prophylaxis in patients receiving reduced-intensity conditioning (RIC). Given prognostic implications of donor age, we investigated the differences in outcomes of patients with acute myeloid leukemia (AML; n = 775) undergoing RIC-HCT with a younger MUD (age <35 years; n = 84) versus a younger haploidentical donor (age <35 years; n = 302) versus an older haploidentical donor (age ≥35 years; n = 389). The older MUD group was excluded from the analysis because of small numbers.

Haploidentical vs matched unrelated donors for patients with ALL: donor age matters more than donor type.

Haploidentical hematopoietic cell transplantation (HCT) with posttransplant cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis yields a similar overall survival (OS) to HLA-matched unrelated donor (MUD) HCT with conventional prophylaxis. Given the prognostic implications of donor age, we investigated the impact of donor age (younger [<35 years, n = 868] vs older [≥35 years, n = 418]) and donor type (haploidentical [n = 373] vs MUD [n = 913]) on OS in adult patients with acute lymphoblastic leukemia (ALL). Older donor age was independently associated with significantly poor OS, whereas donor type was not.

Posttransplantation cyclophosphamide expands functional myeloid-derived suppressor cells and indirectly influences Tregs.

Posttransplantation cyclophosphamide (PTCy), given on days +3 and +4, reduces graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), but its immunologic underpinnings are not fully understood. In a T-cell-replete, major histocompatibility complex-haploidentical murine HCT model (B6C3F1→B6D2F1), we previously showed that PTCy rapidly induces suppressive mechanisms sufficient to prevent GVHD induction by non-PTCy-exposed donor splenocytes infused on day +5. Here, in PTCy-treated mice, we found that depleting Foxp3+ regulatory T cells (Tregs) in the initial graft but not the day +5 splenocytes did not worsen GVHD, yet depleting Tregs in both cellular compartments led to fatal GVHD induced by the day +5 splenocytes.

The incidence and impact of clostridioides difficile infection on transplant outcomes in acute leukemia and MDS after allogeneic hematopoietic cell transplant-a CIBMTR study.

Clostridioides difficile infection (CDI) is common after allogeneic hematopoietic cell transplantation (alloHCT). The determination of incidence, risk factors, and impact of CDI on alloHCT outcomes is an unmet need. The study examines all patients aged 2 years and older who received first alloHCT for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic syndrome (MDS) between 2013 and 2018 at US centers and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) data registry.