The Impact of Graft CD3 Cell/Regulatory T Cell Ratio on Acute Graft-versus-Host Disease and Post-Transplantation Outcome: A Prospective Multicenter Study of Patients with Acute Leukemia Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation

Although it is well known that tumor site- or bone marrow-infiltrating regulatory T cells (Tregs) might be correlated with worse outcomes in solid tumors and acute leukemias by promoting immune surveillance escape, their contribution to the immediate post-allogeneic transplantation phase by peripheral blood (PB) allografts remains unclear. Moreover, the Treg content in stem cells harvested from PB has been suggested to be correlated with acute graft versus-host-disease (aGVHD) and immunologic recovery after allogeneic PB stem cell transplantation (allo-PBSCT). This study aimed to investigate the impact of the graft content of Tregs, as graft CD3+/Tregs ratio (gCD3/TregsR), on acute GVHD and post-allo-PBSCT outcomes. We prospectively enrolled 94 consecutive patients at 9 Italian centers of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) with acute myelogenous (n = 71; 75%) or lymphoblastic (n = 23; 25%) leukemia in complete remission who underwent matched related donor (n = 35; 37%) or unrelated donor (n = 59; 63%) allo-PBSCT. The median graft CD3+ cell, Treg, and gCD3/TregsR values were 196 × 106/kg body weight (range, 17 to 666 × 106/kg), 3 × 106/kg (range, 0.1 to 35 × 106/kg), and 71 (range, 1 to 1883), respectively. The discriminatory power of the gCD3/TregsR value to predict grade ≥II aGVHD was assessed by estimating the area under the receiver operating characteristic (ROC) curve (AUC). Any grade and grade ≥II aGVHD occurred in 24 (26%) and 17 (18%) allo-PBSCT recipients, respectively. By ROC analysis, AUC (0.74; 95% confidence interval [CI], 0.608 to 0.866; P =.002) identified 70 as the optimal gCD3/TregsR cutoff value predicting the appearance of grade ≥II aGVHD with 76% sensitivity and 71% specificity. Patients were subdivided into a high (ROC curve value ≥70) gCD3/TregsR group (HR; n = 48) and a low (ROC curve value <70) gCD3/TregsR group (LR; n = 46). The incidence of grade II-IV aGVHD was lower in the LR group compared with the HR group (9% [4 of 46] versus 27% [13 of 48]) in both univariate analysis (odds ratio [OR], 4.8; 95% CI, 1.44 to 16.17; P =.015) and multivariate analysis (OR, 5.0; 95% CI, 1.34 to 18.93; P =.017), whereas no differences were documented taking into account aGVHD of any grade. The overall survival, disease-free survival, nonrelapse mortality, and relapse rates at 2 and 3 years were 61% and 54%, 62% and 55%, 15% and 23%, and 27% and 30%, respectively. Of note, gCD3/TregsR did not significantly correlate with relapse (P =.135). Taken together, our data from this prospective multicenter study confirm the value of Tregs in preventing aGVHD while maintaining the graft-versus-leukemia effect. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc

Effect of HLA mismatch on post-transplant infections in allogeneic hematopoietic stem cell transplantation with PTCy-based GvHD prophylaxis

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Busulfan or Treosulfan Conditioning Platform for Allogeneic Stem Cell Transplantation in Patients Aged >60 y with Acute Myeloid Leukemia/Myelodysplastic Syndrome: A Subanalysis of the GITMO AlloEld Study

Background. The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing. Methods. With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%). Results. No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P < 0.001); more active diseases at the time of SCT (P < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 (P < 0.001) or a good Karnofsky performance status (P = 0.025); increased use of peripheral blood stem cells as graft sources (P < 0.001); and greater use of reduced intensity conditioning regimens (P = 0.013) and of haploidentical donors (P < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P = 0.0003). This was not observed in the TREO-based group. Conclusions. Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome

High-dose chemotherapy with autologous stem cell transplants in adult primary non-seminoma mediastinal germ-cell tumors. A report from the Cellular Therapy and Immunobiology working party of the EBMT

BACKGROUND: Primary mediastinal germ-cell tumors (PMGCTs) account for 1%-3% of all germ-cell tumors (GCTs). Non-seminoma have a poorer prognosis compared to their gonadal counterpart and, according to the International Germ Cell Cancer Collaborative Group, they are considered 'poor risk' disease. Medical treatment is the same, with overall survival (OS) being ∼40%, declining to 10%-15% at 3 years in case of lung and non-visceral metastases. Patients failing first-line chemotherapy have a dismal prognosis, with only 5%-10% of cases being cured in the salvage setting. High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been successfully used to treat patients with relapsed or refractory gonadal GCTs. PATIENTS AND METHODS: This retrospective study aimed to investigate the value of HDC with ASCT in the whole population and define primary mediastinal non seminoma germ cell tumor (PMNSGCT) patient subgroups, who were registered in the European Society for Blood and Marrow Transplantation database from January 2000 to January 2018. Sixty-nine adult male patients with PMNSGCT were included. HDC consisted mainly of carboplatin/etoposide doublet, and most patients received HDC as part of a multiple sequential HDC program. RESULTS: OS was 43.3% at 2 years, and 34.7% at 5 and 10 years for the entire cohort. Analysis of outcomes showed that patients undergoing HDC as upfront therapy had a better progression-free survival (PFS) and OS compared to those treated in subsequent relapses (5-year PFS 51.8% versus 26.8% and 5-year OS 51.3% versus 25.9%). Better remission status before transplantation was predictive of the benefit of HDC. Three treatment-related deaths were recorded. CONCLUSIONS: To our knowledge, this is the most extensive retrospective study of HDC in PMNSGCTs patients and the first to thoroughly investigate potential predictors of benefit from this treatment. HDC with ASCT may well represent a therapeutic option in patients with PMNSGCTs after the first relapse or even as a front-line program

Impact of SARS-CoV-2 vaccination and monoclonal antibodies on outcome post–CD19-directed CAR T-cell therapy: an EPICOVIDEHA survey

Patients with previous CD19-directed chimeric antigen receptor (CAR) T-cell therapy have a prolonged vulnerability to viral infections. Coronavirus disease 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real-world data on the impact of vaccination and treatment on patients with COVID-19 after CD19-directed CAR T-cell therapy are lacking. Therefore, this multicenter, retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared with patients infected with previous variants (7% vs 58% [P = .012]). Twenty-six patients were vaccinated at the time of the COVID-19 diagnosis. Two vaccinations showed a marked but unsignificant reduction in the risk of COVID-19–caused mortality (33.3% vs 14.2% [P = .379]). In addition, the course of the disease appears milder with less frequent intensive care unit admissions (39% vs 14% [P = .054]) and a shorter duration of hospitalization (7 vs 27.5 days [P = .022]). Of the available treatment options, only monoclonal antibodies seemed to be effective at reducing mortality from 32% to 0% (P = .036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death. This trial was registered at www.clinicaltrials.gov as #NCT04733729

The Impact of Graft CD3 Cell/Regulatory T Cell Ratio on Acute Graft-versus-Host Disease and Post-Transplantation Outcome: A Prospective Multicenter Study of Patients with Acute Leukemia Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation

Although it is well known that tumor site- or bone marrow-infiltrating regulatory T cells (Tregs) might be correlated with worse outcomes in solid tumors and acute leukemias by promoting immune surveillance escape, their contribution to the immediate post-allogeneic transplantation phase by peripheral blood (PB) allografts remains unclear. Moreover, the Treg content in stem cells harvested from PB has been suggested to be correlated with acute graft versus-host-disease (aGVHD) and immunologic recovery after allogeneic PB stem cell transplantation (allo-PBSCT). This study aimed to investigate the impact of the graft content of Tregs, as graft CD3+/Tregs ratio (gCD3/TregsR), on acute GVHD and post-allo-PBSCT outcomes. We prospectively enrolled 94 consecutive patients at 9 Italian centers of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) with acute myelogenous (n = 71; 75%) or lymphoblastic (n = 23; 25%) leukemia in complete remission who underwent matched related donor (n = 35; 37%) or unrelated donor (n = 59; 63%) allo-PBSCT. The median graft CD3+ cell, Treg, and gCD3/TregsR values were 196 × 106/kg body weight (range, 17 to 666 × 106/kg), 3 × 106/kg (range, 0.1 to 35 × 106/kg), and 71 (range, 1 to 1883), respectively. The discriminatory power of the gCD3/TregsR value to predict grade ≥II aGVHD was assessed by estimating the area under the receiver operating characteristic (ROC) curve (AUC). Any grade and grade ≥II aGVHD occurred in 24 (26%) and 17 (18%) allo-PBSCT recipients, respectively. By ROC analysis, AUC (0.74; 95% confidence interval [CI], 0.608 to 0.866; P =.002) identified 70 as the optimal gCD3/TregsR cutoff value predicting the appearance of grade ≥II aGVHD with 76% sensitivity and 71% specificity. Patients were subdivided into a high (ROC curve value ≥70) gCD3/TregsR group (HR; n = 48) and a low (ROC curve value &lt;70) gCD3/TregsR group (LR; n = 46). The incidence of grade II-IV aGVHD was lower in the LR group compared with the HR group (9% [4 of 46] versus 27% [13 of 48]) in both univariate analysis (odds ratio [OR], 4.8; 95% CI, 1.44 to 16.17; P =.015) and multivariate analysis (OR, 5.0; 95% CI, 1.34 to 18.93; P =.017), whereas no differences were documented taking into account aGVHD of any grade. The overall survival, disease-free survival, nonrelapse mortality, and relapse rates at 2 and 3 years were 61% and 54%, 62% and 55%, 15% and 23%, and 27% and 30%, respectively. Of note, gCD3/TregsR did not significantly correlate with relapse (P =.135). Taken together, our data from this prospective multicenter study confirm the value of Tregs in preventing aGVHD while maintaining the graft-versus-leukemia effect. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc

Four cases of transfusion-transmitted Hepatitis E virus infection: Is it time to introduce donor screening in Italy?

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Cord blood resilience in a patient with relapsing Ph + B lymphoblastic acute leukemia after hematopoietic stem cell transplantation

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Late HBV reactivation after hematopoietic stem cell transplantation, despite long-term prophylaxis

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