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Weekly blood Toxoplasma gondii DNA screening using real-time quantitative polymerase chain reaction (qPCR) has been implemented in all allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients at our hospital. We retrospectively analyzed the consequences of a positive blood qPCR in the management of Toxoplasma infection (TI) and disease (TD).From 2011 to 2020, 52 (4.13%) of 1 257 alloHSCT recipients had at least one positive qPCR, 45 (3.5%) with TI and seven (0.56%) with TD (central nervous system involvement). Forty-four patients were qPCR-positive before day 100, 30 without and 14 with anti-Toxoplasma prophylaxis. Twenty-five of them (56.8%) started or continued prophylactic dosage treatment: all became qPCR-negative, including 20 (80%) receiving only prophylactic dosage treatment. Twenty-four of them (54.5%) received non-prophylactic dosage treatment: qPCR became negative in 22/24 (91.7%), while TI contributed to death in two cases. Six of the eight patients diagnosed after D100 had breakthrough TI or TD. No death was attributable to TI or TD. qPCR kinetics available for 24 patients increased until anti-Toxoplasma treatment began, then decreased with all treatment regimens.Clinical follow-up and qPCR monitoring with quantification of the parasitic load appears a reasonable strategy to avoid TD and to use minimal effective dosage of anti-Toxoplasma treatments.

Background Letermovir (LET) prophylaxis in CMV seropositive (R+) allogeneic (allo) HCT recipients was approved in 2017 based on a Phase 3 randomized clinical trial (RCT) demonstrating lower rates of CMV infection, disease, and all-cause mortality among LET treated participants. While RCTs demonstrate causal effects between treatments and outcomes, RW data answer practical aspects of utilization such as time to initiation of LET and duration of use. The objective of this study was to assess LET RW utilization pattern in adult CMV R+ recipients of allo-HCT in a large cohort of multiple centers in Europe participating in the EBMT registry. Methods A retrospective observational cohort design was used to examine the RW utilization patterns of LET among CMV R+ of an allo-HCT in France, Germany & Italy. Inclusion criteria were CMV R+ recipients >18 years who received LET for any reason between Jan 1 2018- Dec 31, 2020 and had data available for at least until 100 days post-HCT. Results In this interim analysis, 138 allo-HCT recipients (52% male) with median age 55 years (range 19-72) received LET as primary prophylaxis. Donor/recipient CMV serostatus was D+/R+ 64% D-/R+ 36%. Donor type was 65% unrelated, 20% mismatched relative, 15% sibling. Standard conditioning was used in 56% and reduced-intensity in 44%. Peripheral blood stem cells were the source in 89%. T-cell depletion was performed in 48%. All centers followed WHO standardization guidelines for CMV viral load assay by PCR. Viral load was determined at time of LET initiation in 86% patients. Oral (PO) only LET formulation was used in 98% of patients (median 2 days post HCT; LET was initiated prior to HCT in 3% of the recipients). Centers indicated that intravenous (IV) formulation was administered only if patients could not tolerate PO. The median duration of PO use was 98 days. LET dose was 240 mg (86%) mostly in patients receiving cyclosporine, 480 mg (9%) or sequentially 240/480 mg (5%). Conclusion Some differences were observed in this interim RW LET analysis compared to the phase 3 RCT. Notably, patients began LET at a median of D+2 post HCT (compared to D+9 in the trial), and 98% received only PO LET (as compared to 26.5% receiving IV LET in the trial). Further studies are needed to determine drivers of LET utilization in RW settings. Disclosures Jan Styczynski, MD, PhD, MSD: Honoraria Amit D. Raval, PhD, Merck and Co., Inc.: Employee of Merck|Merck and Co., Inc.: Stocks/Bonds Sanjay Merchant, PhD, Merck & Co., Inc.: Stocks/Bonds Rafael de la Camara, MD, MSD: Honoraria.

Weekly bloodToxoplasma gondiiDNA screening using real-time quantitative polymerase chain reaction (qPCR) has been implemented in all allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients at our hospital. We retrospectively analyzed the consequences of a positive blood qPCR in the management ofToxoplasmainfection (TI) and disease (TD).From 2011 to 2020, 52 (4.13%) of 1 257 alloHSCT recipients had at least one positive qPCR, 45 (3.5%) with TI and seven (0.56%) with TD (central nervous system involvement). Forty-four patients were qPCR-positive before day 100, 30 without and 14 with anti-Toxoplasmaprophylaxis. Twenty-five of them (56.8%) started or continued prophylactic dosage treatment: all became qPCR-negative, including 20 (80%) receiving only prophylactic dosage treatment. Twenty-four of them (54.5%) received non-prophylactic dosage treatment: qPCR became negative in 22/24 (91.7%), while TI contributed to death in two cases. Six of the eight patients diagnosed after D100 were breakthrough TI or TD. No death was attributable to TI or TD.qPCRkinetics available for 24 patients increased until anti-Toxoplasmatreatment began, then decreased with all treatment regimens.Clinical follow-up and qPCR monitoring with quantification of the parasitic load appears a reasonable strategy to avoid TD and to use minimal effective dosage of anti-Toxoplasmatreatments.

International audience; We report the results of the French Temporary Authorization of Use (ATU) compassionate program of letermovir for primary prophylaxis conducted in 21 transplant centers. Patients were CMV seropositive allogeneic hematopoietic cell transplantation recipients and at high risk for CMV infection. Primary prophylaxis was defined as initiation of letermovir between day 0 and day +28 post-transplant. Between November 2017 and January 2019, 96 patients with a median age of 56 years received letermovir and follow-up data were available for 78 patients. The median time from transplant to letermovir initiation was 4 days, and the median duration of exposure to letermovir was 78 days, with 57 patients still on treatment at the cutoff date. Letermovir was temporarily discontinued in 4 patients (5.1%) and stopped in 39 patients (50.0%), in most cases due to planned end of treatment (n = 16, 20.5%). Fifteen patients (19.2%) each presented one positive CMV PCR, in median 13 days after letermovir initiation. Clinically significant CMV infection was reported in 5 patients (6.4%). No CMV disease was reported. At least one adverse drug reaction was reported for 12 patients (15.4%). In this early access program, letermovir was effective with comparable results of the phase 3 study with a low rate of clinically significant CMV infection, including in patients who were at high-risk for CMV infection.

Acute graft-versus-host disease (aGVHD) remains one of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. No consensus exists on the best second-line treatment of steroid-refractory acute GVHD (SR-aGVHD). Previously published smaller studies on the use of sirolimus in SR-aGVHD treatment report a response rate of 57 to 86%, with 40% overall survival. The association of tacrolimus and mTOR inhibitor is supported by pre-clinical data and has been used as GVHD prophylaxis. We report 42 patients who received tacrolimus and mTOR inhibitor as a second- or third-line treatment of SR-aGVHD. Thirty-one patients were treated in second-line, with an overall response rate of 48.5% (complete response: 42%). Eleven patients were treated in third-line, with an overall response rate of 27%. Thirty-eight patients had at least one episode of infection, due to bacteria, viruses, fungi and parasites in 61, 42, 12 and two episodes, respectively. For patients treated in second-line, six-month and one-year survival were 61% and 42%, respectively. None of the patients treated in third-line survived. These results were not promising enough to initiate a phase three randomized clinical trial, but tacrolimus and mTOR inhibitor can be discussed among other options for patients with SR-aGVHD.

In absence of available matched-related or unrelated donor (MUD), mismatched unrelated donors (MMUD) and unrelated cord blood (UCB) are both considered to be suitable donors, with similar post-transplant overall survival. In most of these retrospective comparisons, HLA typing of adult donors was performed at eight loci. The aim of this study was to compare the outcome of patients transplanted from UCB (N = 64) with those transplanted from 9/10-HLA MMUD (N = 84) or 10/10-HLA MUD (N = 196). In multivariate analysis, UCB was associated with less Grade II-IV acute GVHD in comparison with MUD (aHR 1.97, 95% CI 1.19-3.27, P = 0.009) and MMUD transplants (aHR 1.79, 95% CI 1.02-3.15, P = 0.042), while the cumulative incidence of chronic GVHD was not significantly different between the three groups. Overall survival (OS), non-relapse mortality, and relapse were not different between MMUD and UCB transplantation, whereas OS was impaired after UCB in comparison with MUD (aHR 0.65, 95% CI 0.43-0.99, P = 0.043). Factors also impacting OS were the donor/recipient CMV serostatus (Donor-/Recipient+ aHR 1.76, 95% CI 1.23-2.52, P = 0.002 compared with D-/R-), the donor/recipient gender combination (Female/Male versus other combinations aHR 1.57, 95% CI 1.11-2.22, P = 0.012) and disease risk (aHR 1.58, 95% CI 1.05-2.38, P = 0.027 for high vs. low risk disease). Our data confirm that UCB and 9/10-HLA MMUD are both relevant alternative options when no 10/10-HLA donor is available. Donor/recipient gender combination and CMV serostatus had a significant impact on survival and may be taken into account, along with donor type, in the setting of MMUD and UCB transplants.

Introduction Acute graft versus host disease is a frequent and life threatening complication following HSCT. Some predictive factors have been identified in the last decades. Experimental studies in mice suggest that the naïve cytotoxic T cells (CD3+/CD8+/CD45RA+/CD62L+) are the major mediators of acute GVHD and that removing this subset of the donor T cells, called ‘naïve T cells’, before transplant may reduce the frequency and intensity of GVHD. Detailed immunophenotyping of the graft including naïve and memory (CD3+/CD8+/CD45RA-/CD62L- ; CD3+/CD8+/CD45RA+/CD62L- ; CD3+/CD8+/CD45RA-/CD62L+ ) T-cell contents have never been explored in human GVHD. We studied the correlation between memory and naive T cell in bone marrow and peripheral blood grafts and development of acute GVHD after hematopoietic stem cell transplant. Methods We analyzed by detailed immunophenotyping, the grafts of a cohort of 210 patients among 402 patients who received an allogeneic stem cell transplantation from bone marrow and peripheral blood between January 2009 and June 2012 at a single center. There were no differences between the 210 studied patients and the other 192 in whom grafts were not studied. Characteristics of patients investigated for naïve and memory T cells were compared using Wilcoxon rank-sum tests and Fisher’s exact tests. The main outcome was occurrence of acute GVHD grade II – IV. Cumulating incidence of acute GVHD was estimated using usual methods and compared according to tertiles of T cytotoxic lymphocytes subpopulations using Gray’s test. Adjusted analyses were performed using Fine- Gray proportional hazards models. All tests were two - sided and p-values ≤ 0.05 were considered as indicating significant association. T cytotoxic lymphocytes were typed in all 210 grafts using CD3, CD8, CD45 RA and CD62L four colors immuphenotyping. Clinical and histological characteristics of patients were recorded. Including age, gender, ABO group and rhesus, viral serology of both the donor and the patient, characteristic of the grafts including HLA compatibility, bone marrow or peripheral blood, lymphocytes and nucleated cell and CD34 numeration, conditioning regimens, GVHD prophylaxis, characteristics of GVHD (date of onset, organs involved, stage and grade). Results Median follow up from transplant was 18 months. Cumulative incidence of acute GVHD was 59% (95% CI range 45 to 59) overall, and 49% (95% CI 42 to 56) at 100 days. In univariate analysis increased absolute counts of memory T cell subtypes were significantly correlated with the onset of an acute GVHD grade II – IV. Risk factors for acute GVHD (multivariate analysis) were use of an unrelated donor, positive CMV donor for a negative recipient, and use of TBI 12Gy. In a multivariate analysis the subtype CD3+/CD8+/CD45 RA-/CD62L- was associated with the onset of acute GVHD grade II-IV (adjusted Hazard Ratio = 1.26 and 1.98, p=0.02). Adjusting analysis on the total number of total nucleated cells infused did not affect the results. Restricting analyses to patients receiving peripheral blood stem cells also provided same conclusions. Conclusion This first study on the relation between rate of memory T cell and GVHD revealed that CD3+/CD8+/CD45 RA-/CD62 L- T-cells numbers and percentage were associated with acute GVHD grade II – IV. In contrast to murine models we did not find evidence for a link between naïve T-cells and GVHD risk Disclosures: Robin: novartis: Research Funding.