Stavroula Masouridi-Levrat

• attending physician at Hôpitaux Universitaires de Genève

Following the introduction of tyrosine kinase inhibitors (TKI), the number of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic phase chronic myeloid leukemia (CP-CML) has dramatically decreased. Imatinib was the 1st TKI introduced into the clinical arena, predominantly utilized in the 1st line setting....

There are very limited data regarding the outcomes of elderly patients with acute lymphoblastic leukemia (ALL) who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). A total of 316 ALL patients aged ≥ 60 years who underwent alloHSCT between 2010 to 2022 were identified in the SFGM‐TC registry. The primary objective was to evalua...

Background Haploidentical allogeneic hematopoietic cell transplantation recipients (allo-HCTr) receiving post-transplant cyclophosphamide (haplo-PTCy) are at higher risk for infectious complications, including viral infections. Methods We performed a retrospective, single-center, propensity-score matched-pair study including adult haplo-PTCy and a...

Background Hospital-acquired bloodstream infections (HA-BSI), including catheter-associated bloodstream infections (CABSI), cause preventable harm in haemato-oncology patients but surveillance data are limited. Methods We performed a retrospective cohort study using prospectively collected data in a large hospital network in Switzerland from 2017–...

There is still an unmet need for the treatment of high-risk hematological malignancies. To date, allogeneic stem cell transplantation remains the only chance of cure. Most patients suffering from high-risk hematological malignancies are of an older age and often present with comorbidities. Moreover, patients achieving remission often suffer from ea...

Introduction: Donor lymphocyte infusions (DLI) are a widely employed strategy to increase the graft-versus-tumor (GvT) effect of allogeneic hematopoietic stem cell transplantation (HSCT) and/or to sustain donor engraftment in case of mixed chimerism but can increase non-relapse mortality (NRM) risk mainly secondary to the induction of graft-versus-...

Optimization of conditioning regimens is a cornerstone of hematopoietic stem cell transplant medicine. Over time, various combinations of chemotherapy, immunosuppressants, and radiation-based regimens have been proposed for both malignant and non-malignant hematological disorders. The advent of reduced intensity conditioning (RIC) regimens has popu...

Introduction: Sorafenib maintenance reduces the risk of relapse and improves survival in FLT3-ITD acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mechanisms underlying the beneficial effect of sorafenib in the context of allo-HSCT are largely unknown. In addition to FLT3 inhibition, on...

Background Bacteremia is a common complication in allogeneic hematopoietic cell transplant recipients (alloHCTr), especially during the pre‐engraftment period. International guidelines recommend antibacterial prophylaxis (ABP), despite potential selection for multidrug‐resistant organisms (MDRO). Limited contemporary data exist on the epidemiology...

Given the selection of elderly patients with AML in first complete remission (CR1) the advantage of consolidation with allogeneic hematopoietic cell transplantation (HCT) over chemotherapy is still unclear. Newly diagnosed AML patients in CR1 aged 60-75 years were registered and a donor search initiated. After one consolidation cycle, patients with...

Besides genetic influences, non-genetic factors such as graft-versus-host disease (GvHD) and viral infections have been shown as important shapers of the immune reconstitution and diversification processes after hematopoietic stem cell transplantation (HSCT). However, the differential susceptibility to immune modulation by non-genetic factors is no...

AIM: Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was the main indication for allogeneic HCT. The introduction of tyrosine kinase inhibitors changed the treatment of CML patients dramatically. Allogeneic HCT was rapidly replaced b...

Anaphylactic reactions at the time of chimeric antigen receptor T (CAR‐T) cell infusion are adverse events that have not been reported in pivotal clinical trials or in real‐world series. We report the case of patient with severe anaphylaxis with cardiac arrest after tisagenlecleucel injection for Diffuse Large B cell Lymphoma, who recovered after r...

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with highly chemorefractory Hodgkin lymphoma (HL). The CD30-targeting antibody-drug conjugate Brentuximab-Vedotin (BV) and programmed cell death protein-1 (PD-1) blocking agents have demonstrated clinical activity with durable resp...

The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25 years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared...

Background: despite rapid development of new highly efficient targeted and cellular-therapies, allogeneic stem cell transplantation (allo-HSCT) represents so far the only potentially curable treatment according to a longest follow-up in a setting of relapse/refractory Non-Hodgkin lymphoma (rrNHL). However, late effect (LE) issues of allo-HSCT in rr...

Background There are very scarce data regarding the outcome of elderly patients with acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic stem cell transplantation (alloHSCT) as consolidation therapy in 1rst or higher complete remission (CR). Most studies evaluating the benefit of alloHSCT in ALL include both young and elderly p...

Among 292 allogeneic hematopoietic cell transplant recipients (allo-HCTr, 2018-2022), 64 (21.9%) tested positive for anti-HEV-IgG and among 208 allo-HCTr tested by plasma/serum-HEV-PCR (2012-2022) 3 (1.4%) primary HEV infections were diagnosed; in one patient plasma HEV-PCR relapsed positive for 100 days. HEV infection remains rare albeit associate...

Background A transplant infectious disease (TID) assessment is essential to select recipients for an allogeneic hematopoietic cell transplant (HCT) and tailor prophylactic and empirical treatment recommendations. Methods We performed a retrospective single-center study to describe our model of care based on a routine TID consultation prior to an a...

Background Allogeneic hematopoietic cell transplant recipients (allo-HCTRs) with positive cytomegalovirus (CMV) serology may have false-positive results due to blood product transfusion–associated passive immunity. Methods This single-center cohort study included allo-HCTRs with negative baseline (at malignancy diagnosis) CMV serology and indeterm...

Metagenomics revealed novel and routinely overlooked viruses, representing sources of unrecognized infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to describe DNA and RNA virus prevalence and kinetics in allo-HSCT recipients’ plasma for one year post HSCT. We included 109 adult patients with first allo-HSCT f...

Relapse after allogeneic hematopoietic cell transplantation (allo-HCT) remains a major concern because it is associated with poor survival. A second allo-HCT is a valid option in this situation. During the 13th annual harmonization workshops of the francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC), a designated worki...

We present two allogeneic hematopoietic cell transplantation recipients (HCTr) treated with pritelivir for acyclovir-resistant/refractory (r/r) HSV infection based on the expanded access program of the pritelivir manufacturer. Outpatient treatment with pritelivir was administered, with partial response by week 1 of treatment and complete response b...

In this single-center study of 61 allogeneic hematopoietic cell transplant (HCT) recipients receiving letermovir primary CMV-prophylaxis for the first 100 days, we report 23% incidence of clinically significant CMV infection during the first 100 days after letermovir discontinuation, predominately in haploidentical HCT recipients, without any assoc...

Sorafenib significantly improves survival of FLT3-ITD mutated AML patients when used as a post-allogeneic HSCT maintenance. Importantly, clinical trials reported a low rate of toxicities requiring sorafenib discontinuation. The aim of our analysis was to evaluate the real-world experience in patients treated with post-allogeneic HSCT sorafenib main...

Introduction Human pegivirus-1 (HPgV-1) is a so-called commensal virus for which no known associated organ disease has been found to date. Yet, it affects immune-reconstitution as previously studied in the HIV population, in whom active co-infection with HPgV-1 can modulate T and NK cell activation and differentiation leading to a protective effect...

We report on a case of probable invasive Auerobasidium spp. pulmonary infection in a patient with myelodysplastic syndrome. The patient was successfully treated with liposomal amphotericin B monotherapy, with transition to orally administered isavuconazole. This case shows an atypical initial radiological presentation with diffuse ground-glass opac...

Despite the high cure rate with initial therapy, approximately 10% of Hodgkin lymphoma (HL) patients are refractory to initial treatment, and up to 30% of patients will relapse after achieving initial complete remission. Despite promising initial results of treatment by immune checkpoint inhibitors, most patients will eventually progress. We analyz...

Due to relatively high nonrelapse mortality (NRM), allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in non‐Hodgkin's lymphoma (NHL) remains the ultimate line of treatment but the only curable approach in a setting of relapse/refractory disease. Here, we conducted a retrospective, multicenter, registry‐based analysis on patients who un...

HLA antigen presentation and T-cell immunity are critical to control viral infection such as SARS-CoV-2. This study performed on samples collected in the pre-COVID-19 era demonstrates that individuals are fully equiped at the genetic level in terms of TCR repertoire and HLA variants to recognize and kill SARS-CoV-2 infected cells. HLA diversity, he...

Background Some conventional vaccines have been recognized as a cause of secondary immune thrombocytopenia (ITP). According to recent publications, mRNA vaccines are probably associated with an increased risk of ITP. Case presentation Our patient developed severe ITP one week after the second dose of COVID-19 mRNA vaccine. Medical management was n...

Background: Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a well-known complication of allogeneic hematopoietic stem cell transplantation (HSCT) associated with a mortality rate of up to 85%. Defibrotide has shown efficacy in treatment of SOS/VOD. Moreover, evidence exists supporting the efficacy of d...

Background Limited data exist to describe end‐of‐treatment (EOT) parameters of antifungal therapy for invasive mould infections (IMI). Methods In a 10‐year cohort of consecutive adult allogeneic haematopoietic cell transplant recipients with proven/probable IMI, we describe treatment duration and patient profile at EOT. Results There were 61 pati...

With balanced safety-efficacy profile, letermovir anti-cytomegalovirus (CMV) prophylaxis is used in hematopoietic stem cell transplant recipients (HSCTR). We assessed feasibility and usefulness of letermovir therapeutic drug monitoring (TDM) in HSCTR.

Respiratory viral infections (RVIs) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients can be of concern due to the patients’ depressed immune status, but few data are available about the significance of a pre-transplant positive testing. In this retrospective observational study, we analyzed a cohort of patients that were tran...

Allogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We p...

Background Antifungal treatment duration and changes for invasive mould infections (IMI) have been poorly described. Methods We performed a 10‐year cohort study of adult (≥18‐year‐old) allogeneic haematopoietic cell transplant recipients with proven/probable IMI to describe the duration and changes of antifungal treatment. All‐cause‐12‐week mortal...

Background There are limited real-life data on isavuconazole prophylaxis and treatment of invasive mold infections (IMI) in hematological patients and allogeneic hematopoietic cell transplant (HCT) recipients. Objectives Primary objective was to describe the indications of real-life isavuconazole administration at a university hospital. Secondary...

Background Despite progress in diagnostic, prevention and treatment strategies, invasive mold infections (IMI) remain leading cause of mortality in allogeneic hematopoietic cell transplant recipients (allo-HCT-recipients). Methods We describe the incidence, risk factors, and mortality of allo-HCT-recipients with proven/probable IMI in a retrospect...

Background: T cell senescence is a physiological process typically associated with aging. In addition, lymphopenia and chronic immune activation can result in T cell senescence. CD57, a member of the N-CAM family initially described as a natural killer cell marker, has been reported as a marker of human senescent CD8 T cells. Percentages of CD57+ C...

Background: Antifungal combination treatment is frequently administered for invasive mold infections (IMIs) after allogeneic hematopoietic cell transplantation (HCT). Here, we describe the indications, timing, and outcomes of combination antifungal therapy in post-HCT IMI. Methods: A single-center, 10-year, retrospective cohort study including all...

HLA compatibility is a key factor for survival after unrelated hematopoietic cell transplantation (HCT). HLA-A, B, C, DRB1 and DQB1 are usually matched between donor and recipient. By contrast, HLA-DPB1 mismatches are frequent although it is feasible to optimize donor selection and DPB1 matching with prospective typing. Yet, because classical DPB1...

We sought in this case-control retrospective study to compare posaconazole/isavuconazole (PCZ/IVC)-C trough in high-risk allogeneic hematopoietic cell transplant (HCT) recipients who received letermovir (LET) or not. PCZ/IVC-C trough were not found to be significantly different between cases and controls: 1.31 mg/l (median) (0.90; IQR) vs 1.36 mg/l...

Letermovir prophylaxis in allogeneic hematopoietic cell transplant recipients significantly reduces the incidence of clinically significant cytomegalovirus infection. However, breakthrough infections still occur despite adequate prophylaxis. In the present retrospective cohort study, we identified clinically relevant predictive factors for clinical...

Background: Real-life data on the administration of letermovir as cytomegalovirus (CMV) primary prophylaxis after allogeneic hematopoietic cell transplantation (HCT) remain limited. Methods: We conducted a retrospective single-center matched cohort study, comparing consecutive high-risk allogeneic HCT recipients (cases) receiving primary prophyl...

Background Viral infections are common complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients with steroid-refractory/dependent graft-versus-host disease (GvHD) are highly immunosuppressed and are more vulnerable to infections with weakly pathogenic or commensal viruses. Here, twenty-five adult...

There is a paucity of data on posaconazole (PCZ) dosing and therapeutic-drug-monitoring (TDM) in allogeneic hematopoietic cell transplant recipients (allogeneic-HCTr). This was a 3-year retrospective multicenter study (January 1, 2016 to December 31, 2018) in adult allogeneic-HCTr who received PCZ (intravenously, IV and/or as delayed-release tablet...

Busulfan and cyclophosphamide (BuCy) is a frequently used myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT). Theoretical considerations and pharmacological data indicate that application of busulfan prior to subsequent cyclophosphamide (BuCy) may trigger liver toxicity. Reversing the order of applicatio...

Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic modality for a variety of hematological malignancies and congenital disorders. One of the major complications of the procedure is graft-versus-host-disease (GVHD) initiated by T cells co-administered with the graft. Removal of donor T cells from...

Introduction: FLT3-Internal Tandem Duplication (FLT3-ITD) mutations of the gene encoding the FLT3 tyrosine kinase receptor are found in 25-30% of AML patients and are associated with a poor prognosis despite intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). FLT3 tyrosine kinase inhibitors (TKI) significantly impr...

Background: The AML EBMT Cytogenetic Risk score is a new prognostic model recently published (Canaani et al. Leukemia. 2019 Aug;33(8):1944-1952; Nagler el al. Am J Hematol. 2020 Jun 12) combining cytogenetics and FLT3ITD status for AML patients in complete remission (CR) at transplant time. The AML EBMT Cytogenetic Risk score is prognostic for leuk...

Outcomes of haematopoietic stem cell transplantation (HSCT) are influenced by comorbidities, disease type and status at transplantation. Several prognostic scores can be used, such as the Disease Risk Index (DRI) or the Haematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). Recently a new prognostic tool, the Disease Risk Comorbid...

Résumé La drépanocytose est une pathologie associée à des complications sévères et une mortalité précoce chez l’adulte. Chez l’enfant, l’allogreffe familiale HLA-identique de cellules souches hématopoïétiques permet de stopper la progression de la maladie et ainsi de « guérir » plus de 95 % patients, mais cette thérapeutique reste peu proposée chez...

In a large multi-center contemporary 8-year cohort study, one third of allogeneic hematopoietic cell transplant recipients (allogeneic-HCT recipients) with Pseudomonas aeruginosa (PSA) infection developed a recurrent infection within 3 months. Antibiotic treatment duration of ≥14-days was the only significantly associated variable with reduced recu...

Impaired immune reconstitution after allogeneic hematopoietic stem cell transplantation (HSCT) contributes to increased risk of cancer relapse and infection resulting in significant morbidity and mortality. Unfortunately, effective strategies to functionally assess the quality of immune reconstitution are still missing. Quantification of in vivo re...

After allogeneic hematopoietic stem cell transplantation (HSCT), immune reconstitution leads to the development of a new T-cell repertoire. Immune reconstitution could be influenced by events such as conditioning, infections, and graft versus host disease (GVHD). Factors influencing the TCR diversity are of great interest to fine-tune the strategy...

Background Infections are an important complication after allogeneic hematopoietic cell transplantation (allo‐HCT). The present study aimed at determining the landscape of infections occurring in a large cohort of allo‐HCT patients, as well as associated risk factors for infections and for one‐year non‐relapse mortality. Methods This is a retrospe...

Background: Nowadays, most blood products are leukocyte-reduced. After this procedure, the residual risk for transfusion transmitted cytomegalovirus (TT-CMV) is mostly attributed to cell-free viruses in the plasma of blood donors following primary infection or viral reactivation. Here, objectives are: 1) to study the behaviour of cell-free CMV thr...

We report a case of cytomegalovirus encephalitis in a hematopoietic stem cell transplant recipient. A previously uncharacterized V787E mutation in UL54 gene was identified in cerebrospinal fluid but not in plasma. The EC50 values for ganciclovir, foscarnet and cidofovir against V787E recombinant virus were 8.6-, 3.4- and 2.9-fold higher compared to...

Résumé L’encéphalopathie liée à l’utilisation des lymphocytes dotés de récepteur à l’antigène chimérique (CAR-T) (CAR-T cell-related encephalopathy syndrome, CRES) traduit la neurotoxicité potentielle de cette approche thérapeutique et doit être envisagée devant la survenue de tout symptôme neurologique après l’infusion des cellules CAR-T. Il s’agi...

Immune exhaustion contributes to treatment failure after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. Immune checkpoint blockade, including programmed cell death protein-1 (PD-1) blockade, is a promising strategy to improve the antitumor effect of allogeneic HSCT with high rates of response reported in p...

The cytokine release syndrome (CRS) is the most common complication after adoptive immunotherapies such as chimeric antigen receptor T cells (CAR-T). The incidence varies from 30 to 100% depending on the CAR-T construct, cell doses and the underlying disease. Severe cases may involve 10 to 30% of patients. The triggering event is the activation of...

Résumé Après allogreffe de cellules souches hématopoïétiques (allo-CSH), la rechute de la maladie initiale et le dysfonctionnement du greffon restent aujourd’hui parmi les causes majeures d’échec de cette thérapeutique tant pour les hémopathies malignes que non malignes. Une seconde allo-CSH est une option pour pallier ces situations. Dans le cadre...

Tolerance induction through simultaneous hematopoietic stem cell‐ and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft‐versus‐host disease. Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor‐specific tolerance resul...

Objectives: As commensal viruses are defined by the immunological tolerance afforded to them, any immunomodulation, such as is received during haematopoietic stem cell transplantation, may shift the demarcation between innocuous viral resident and disease-causing pathogen. Methods: We analysed by deep-sequencing the plasma virome of 40 allogenei...

Background: Respiratory syncytial virus (RSV) is associated with significant mortality rates amongst hematopoietic stem cell transplant (HSCT) recipients, with less known about other immunocompromised patients. Methods: Ten-year retrospective cohort study of immunocompromised patients presenting with RSV disease documented at University Hospital...

In 1997, the Swiss Blood Stem Cell Transplantation Group (SBST) initiated a mandatory national registry for all haematopoietic stem cell transplants (HCTs) in Switzerland. As of 2016, after 20 years, information was available for 7899 patients who had received an HCT (2781 allogeneic [35%] and 5118 autologous [65%]). As some patients had more than...

Résumé La rechute reste la première cause de mortalité des hémopathies malignes après allogreffe de cellules souches hématopoïétiques (allo-CSH) (van den Brink et al., 2010). Le risque de récurrence de la maladie est élevé chez les patients présentant des marqueurs cytogénétiques ou moléculaires de mauvais pronostic, et/ou allogreffés en situation...

Graft-versus-host disease (GvHD)-free, relapse-free survival (GRFS) is a recently reported composite endpoint that allows to simultaneously estimate risk of death, relapse and GvHD after allogeneic hematopoietic stem cell transplantation (HSCT). In this retrospective study comprising 333 patients transplanted for hematologic malignancies, we compar...

Key Clinical Message We report here the clinical course of a Ph+ ALL patient who was treated with ponatinib 15 mg/day, as maintenance therapy, and developed a BCR‐ABL T315I mutation leading to ALL relapse. This clonal evolution was reversed, without adverse effects, by increasing ponatinib to 45 mg/day. To our knowledge, we have been confronted wit...

Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in acute myeloid leukemia (AML) patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory h...

Backgound : Sinusoidal obstruction syndrome [SOS, also known as hepatic veno-occlusive disease (VOD)] is frequent after HSCT and may have a mortality rate of up to 85%. Defibrotide has shown efficacy not only in the treatment of established SOS (Richardson et al. Blood 1998:92;737 and 2016:127;1656) but also in SOS prevention in children (prospecti...

Reactive hemophagocytic syndrome (HS) is a rare but serious complication that may occur after both autologous and allogeneic hematopoietic stem cells transplantation (HSCT). Our knowledge of this post-HSCT complication mainly derives from single reports or small series and only about sixty cases have been reported in the literature so far. We prese...

Résumé Une allogreffe de cellules souches hématopoïétiques dépend de l’éradication de la pathologie traitée et d’une reconstitution satisfaisante de l’hématopoïèse (et de la lymphopoïèse) issues des cellules du donneur. Cependant, des retards de reconstitution, l’apparition secondaire ou la persistance de cytopénies sont régulièrement observées et...

Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments...