GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell therapy techniques. In this review, current cell therapies are taken into consideration, which are based on the use of TCR alpha/beta depletion, CD45RA depletion, T regulatory cell enrichment, NK-cell-based immunotherapies, and suicide gene therapies in order to prevent GvHD and maximally amplify the GvL effect in the setting of haploidentical transplantation.

GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell therapy techniques. In this review, current cell therapies are taken into consideration which are based on the use of TCR alpha/beta depletion, CD45 RA depletion, T regulatory cells enrichment, NK cell-based immunotherapies and suicide gene therapies in order to prevent GvHD and maximally amplify the GvL effect in the setting of haploidentical transplantation.

DOI: 10.20452/pamw.17009, Published online: May 12, 2025, Authors: Paola Ranalli^1,2, Gianfranco Lessiani³, Francesco Guardalupi¹, Mauro Di Ianni^1,2

Background. Essential Thrombocythemia (ET) is characterized by enhanced platelet generation and high risk of both arterial and venous thrombosis, as the leading cause of morbidity and mortality. Thus, chronic low-dose aspirin is recommended for primary and secondary thrombosis prevention. In ET, the accelerated platelet turnover has been shown to reduce the stability and degree of platelet inhibition by standard low dose aspirin given once-daily, due to the increased daily regeneration of the drug’s target. Clopidogrel, a thienopyridine prodrug, given once-daily is used in case of aspirin allergy or intolerance, for primary and secondary thrombosis prophylaxis in ET patients. Similar to aspirin, clopidogrel active metabolite acts irreversibly, and its target is the P2Y12, ADP receptor. Whether clopidogrel given once-daily can produce a steady and optimal 24-hour inhibition of platelets is currently unknown Our study has different aims: 1. Measure the degree of platelet inhibition in patients affected by ET receiving clopidogrel and in a non-ET population with an indication for clopidogrel therapy due to cardiovascular disorders; 2) to compare the capacity of two different platelet function methods to detect the pharmacodynamics of clopidogrel ex vivo.Methods. A total of 25 adult patients with Essential Thrombocythemia (ET) and 25 age- and sex-matched non-ET patients on standard clopidogrel (75 mg) once-daily will be enrolled. All patients will be instructed to take the clopidogrel tablet always at breakfast time, for 7-10 days. ADP-induced platelet aggregation in whole blood (Verify Now-P2Y12) and in platelet-rich plasma will be measured. At the morning routine visit a blood sample will be collected 24 hours after the last intake of clopidogrel for platelet aggregation testing.Results. This study has received the approval of the Local Ethical Committee. The first patient was studied on 31th March 2026. At present, 16 patients gave their informed consent.Conclusions. This study will verify the hypothesis that the same mechanisms reducing aspirin responsiveness in ET patients may also contribute to a reduced ADP induced platelet inhibition under standard clopidogrel 75 mg OD.

We report the case of a patient with a conclusive diagnosis of “MDS/MPN” Overlap Syndrome preceded by platelet disorder and hemorrhagic phenotype. We want to induce a reflection about diagnosis of oncohematological disorders in patient with a documented personal history of bleeding and/or platelet disorder, considering all the possible differential diagnosis: 1) Bleeding as the epiphenomenon of a still undiagnosed Myeloid Neoplasm or 2) Myeloid Neoplasm with germline predisposition and pre-existing platelet disorder; 3) Inherited platelet disorder successively developing MPN/MDS Overlap Syndrome. This case report underlines the importance of genetic testing in case of patient with documented platelet function disorder, including both mutations associated with inherited platelet disorders and germline mutations more strictly predisposing to Myeloid Neoplasms.

Aims: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) increase haematocrit and may cause erythrocytosis, creating uncertainty in type 2 diabetes management. Most available data derive from administrative registries or mixed, non-diabetic and/or non-European population. This study aimed to assess the onset, clinical characteristics and management outcomes of people with type 2 diabetes developing SGLT2i-associated erythrocytosis in a routine clinical setting. Methods: This retrospective, single-centre cohort study included adults with type 2 diabetes who developed at least one episode of erythrocytosis (haematocrit ≥ 48% in women, ≥ 49% in men) during the first year after initiation of SGLT2i therapy. Haemoglobin and haematocrit were collected at baseline, at erythrocytosis onset, and at 6 and 12 months with the first erythrocytosis episode defined as the “index date”. No time effect or effect modification across predictive variables was observed. Management included no intervention in 84.1%, SGLT2i discontinuation in 5.3%, and phlebotomy in 4.5%. JAK2 V617F testing was performed in 19 cases, yielding negative results. Results: Erythrocytosis was detected in 3.4% of subjects ( n = 132 out of 3,848). The cohort was predominantly male (87.9%), with a median age of 68.4 years and diabetes duration of 10.5 years. Cardiovascular comorbidities were common. The median time from SGLT2i initiation to erythrocytosis was 11.9 months. Over 12 months, haematocrit and haemoglobin levels remained stable, with no thrombotic events. Conclusions: SGLT2i-associated erythrocytosis is an uncommon, stable, and seemingly low-risk phenomenon. However, it may trigger unnecessary interventions, including treatment discontinuation. These findings highlight a gap between the benign nature of this effect and real-world practice, supporting the need for evidence-based, multidisciplinary guidelines to preserve SGLT2i cardiorenal benefits and optimise patient management.