In-Vivo Expansion of T Regulatory Cells by Rapamycin in a Calcineurin-Inhibitor Free GVHD Prophylaxis in Unmanipulated Haploidentical Stem Cell Transplantation (SCT)

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Case Report: Invasive Fungal Infection and Daratumumab: A Case Series and Review of Literature

Life expectancy of multiple myeloma (MM) patients has improved in last years due to the advent of anti-CD38 monoclonal antibodies in combination with immunomodulators and proteasome inhibitors. However, morbidity and mortality related to infections remain high and represent a major concern. This paper describes the “real life” risk of invasive fungal infections (IFI) in patients treated with daratumumab-based therapy and reviews the relevant literature. In a series of 75 patients we only observed three cases of fungal pneumonia. Unfortunately, the early signs and symptoms were not specific for fungal infection. Diagnostic imaging, microbiology and patient history, especially previous therapies, are critical in the decision to start antifungal treatment. Recognising the subgroup of MM patients with high risk of IFI can increase the rate of diagnosis, adequate treatment and MM-treatment recovery

MOLECULAR INTERNATIONAL PROGNOSTIC SCORING SYSTEM FOR MYELODYSPLASTIC SYNDROMES: A MONOCENTRIC EXPERIENCE

Introduction: Allogeneic HSCT (aHSCT) is the only curative treatment, reserved for IPSS-R higher risk (HR, > 3.5) MDS. Molecular data have been integrated within the recently validated IPSS-Mol score system, in order to better predict clinical outcome. However, IPSS-Mol is not still used to guide clinical decisions. We aim to investigate IPSS-Mol significance in a cohort of MDS patients transplanted at our center. Methods: We retrospectively analyzed a cohort of 74 MDS patients undergoing aHSCT between 2010-2022 at our center according to IPSS-R risk score. All patients received treosulfan-based conditioning regimens and PBSC as stem cell source from matched related/unrelated or haploidentical donors. NGS testing for somatic myeloid mutations was performed retrospectively on cryopreserved marrow cells at diagnosis and MDS risk score was then re-calculated according to IPSS-Mol. Results: 27 patients (36%) were lower risk (LR) at diagnosis and underwent aHSCT for disease progression. All the other patients were HR (IPSS-R > 3.5) and received aHSCT as upfront or consolidation treatment. At least one oncogenic mutation was found in 86.5% of cases by NGS testing. With IPSS-Mol 10 LR patients (37%) were re-stratified as HR (of note, 6/12 patients with intermediate IPSS-R ≤ 3.5), while 7 HR patients (15%) were re-stratified as LR. Conclusions: aHSCT remains the only curative strategy in HR MDS. NGS testing and application of IPSS-Mol allow to better prognosticate MDS, mostly in patients with LR MDS and specifically in intermediate risk (≤3.5) group. This could help in guiding treatment and specifically optimizing the use of aHSCT in MDS

IL-7 receptor expression identifies suicide gene-modified allospecific CD8+ T cells capable of self-renewal and differentiation into antileukemia effectors

In allogeneic hematopoietic cell transplantation (HSCT), donor T lymphocytes mediate the graft-versus-leukemia (GVL) effect, but induce graft-versus-host disease (GVHD). Suicide gene therapy-that is, the genetic induction of a conditional suicide phenotype into donor T cells-allows dissociating the GVL effect from GVHD. Genetic modification with retroviral vectors after CD3 activation reduces T-cell alloreactivity. We recently found that alloreactivity is maintained when CD28 costimulation, IL-7, and IL-15 are added. Herein, we used the minor histocompatibility (mH) antigens HA-1 and H-Y as model alloantigens to directly explore the antileukemia efficacy of human T cells modified with the prototypic suicide gene herpes simplex virus thymidine kinase (tk) after activation with different stimuli. Only in the case of CD28 costimulation, IL-7, and IL-15, the repertoire of tk(+) T cells contained HA-1- and H-Y-specific CD8(+) cytotoxic T cells (CTL) precursors. Thymidine kinase-positive HA-1- and H-Y-specific CTLs were capable of self-renewal and differentiation into potent antileukemia effectors in vitro, and in vivo in a humanized mouse model. Self-renewal and differentiation coincided with IL-7 receptor expression. These results pave the way to the clinical investigation of T cells modified with a suicide gene after CD28 costimulation, IL-7, and IL-15 for a safe and effective GVL effect.Tumorimmunolog