Posttransplant Autoimmune Hemolytic Anemia with Anti-D Specificity Successfully Treated with Daratumumab: A Case Report.

Introduction: Autoimmune hemolytic anemia (AIHA) occurs in 0.7-5.6% of patients undergoing hematopoietic stem cell transplantation, especially from unrelated or haploidentical donor or after lympho-depleted transplant; the majority of cases are represented by warm AIHA, occurring in a full donor chimerism setting. Standard treatments (corticosteroids, intravenous immunoglobulin, splenectomy, rituximab, cyclophosphamide, plasma exchange) lead to lower response rates than those reported in primary AIHA. Daratumumab use has been proposed in many autoimmune conditions (immune thrombocytopenic purpura, aplastic anemia, thrombotic thrombocytopenic purpura, systemic lupus erythematosus, multiple sclerosis), but only few reports have been published on its use for post-HSCT AIHA, mainly in pediatric patients. Case Presentation: We report the successful use of daratumumab in a 68-year-old patient, suffering from post-HSCT AIHA. Five months after Rh-mismatched HSCT, the patient was diagnosed with anti-D AIHA. After first-line treatment (oral prednisone, rituximab, and plasma exchange) failure, being still transfusion-dependent with symptomatic anemia, he underwent treatment with daratumumab, achieving both clinical and laboratory responses. Discussion: Daratumumab may represent a safe and effective alternative to conventional immunosuppressive therapy, and it deserves further investigations.

Safety Results for Geographic Atrophy Associated with Age-Related Macular Degeneration Using Subretinal Cord Blood Platelet-Rich Plasma.

Purpose: To evaluate the safety of subretinal injection of cord blood platelet-rich plasma (CB-PRP) and its possible effect in eyes affected by geographic atrophy (GA) associated with dry age-related macular degeneration (d-AMD). Design: Interventional, open-label study started in January 2021 with follow-up at 12 months (the Si.Cord Study). This study was a single-center, nonrandomized, sequential-assigned clinical trial conducted in Rome, Italy, at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (ClinicalTrials.gov NCT04636853). Participants: Thirteen patients (26 eyes) with bilateral d-AMD-related GA were enrolled. One eye from each patient (with more advanced GA) underwent CB-PRP treatment, and the fellow eye was considered the control. All patients participated in follow-up at 12 months. Intervention: All 13 eyes received 23-gauge (G) vitrectomy and subretinal injection of CB-PRP using a 41-gauge needle. Main Outcomes and Measures: Best-corrected visual acuity (BCVA) with ETDRS letters, central macular thickness using OCT, and atrophic area measured on en face OCT images were assessed at baseline, 1, 3, 6, and 12 months. Results: The BCVA in the treated group was 34.46 ± 20.8 ETDRS at baseline, 40.84 ± 20.52 at 1 month, 40.07 ± 20.34 at 3 months, 39.38 ± 19.84 at 6 months, and 35.84 ± 18.38 at 12 months. In the untreated group, the BCVA was 53 ± 21.1 ETDRS letters at baseline, 51.54 ± 20.99 at 1 month, 46.62 ± 19.47 at 3 months, 46.85 ± 18.58 at 6 months, and 43.92 ± 17.97 at 12 months (2-way analysis of variance: interaction of treatment by eye or time, P = 0.084). Central macular thickness did not show a significant intereye difference at 12 months (P = 0.97). The atrophic geographic areas tended to increase in both treated and fellow eyes at 12 months (P < 0.0001). No inflammatory reaction, endophthalmitis, retinal detachment, uveitis, or other complications due to the subretinal injection of CB-PRP were observed during the follow-up. Conclusions: Subretinal injection of CB-PRP could be safely used for d-AMD in its GA form. Despite its safety, a larger cohort of patients, and probably a new way of administration, will be needed to understand whether the CB-PRP could have a role in the GA treatment. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Iron metabolism in sickle cell disease patients undergoing chronic red blood cell exchange: A delicate homeostasis in balance.

Sickle cell disease (SCD) is an inherited haemoglobinopathy associated with significant morbidity and mortality. Automated red blood cell exchange (aRCE) plays a key role in managing SCD, eliciting both therapeutic and prophylactic effects. The ideal post-apheresis Ht target for chronic aRCE treatment is not yet unanimously recognized, as well as iron homeostasis can be different among patients. Ross et al. reported their experience on the chronic management of SCD patients undergoing aRCE with a final post-exchange Ht higher than the value commonly adopted, analysing red blood cell transfusion requirements and iron-related outcomes in the study population. Commentary on: Ross et al. Automated red blood cell exchange with a post-procedure haematocrit targeted at 34% in the chronic management of sickle cell disease. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19674.

Pure red cell aplasia among ABO mismatched hematopoietic stem cell transplant recipients: a 13-years retrospective study and literature review.

Background: Pure red cell aplasia (PRCA) is a possible complication after allogeneic hematopoietic stem cell transplantation (HSCT) with major ABO incompatibility. Patients experience delayed engraftment of the erythroid series, with prolonged transfusion-dependent anemia and iron overload. Methods: We performed a revision of the most recent literature about post-HSCT PRCA treatment procedures. Moreover, we conducted a retrospective study, over the last 13-years, which included all consecutive major ABO mismatched HSCT performed in our unit, with the aim to assess PRCA incidence, risk factors, and response to different treatments. Overall, 194 patients received a major ABO mismatched transplant from 2010 to 2022. For each patient, data about demographic and transplant characteristics, engraftment, blood transfusion, and possible treatment received were collected. Results: The literature review returned 23 eligible papers on PRCA treatment, with high success rate using plasma-exchange (PEX) and immunoadsorption procedures, daratumumab, and eltrombopag. Our study identified a total of 24 cases of PRCA. Among risk factors for PRCA development, we have found older recipient age (p=0.01), high pre-HSCT IgG and IgM IHA titer (p<0.0001), major rather than bidirectional ABO incompatibility (p=0.02), low T CD8 lymphocyte count in the graft (p=0.006), relative donor (p=0.02) and bone marrow as stem cell source (p=0.002). However, multivariate analysis confirmed only pre-HSCT IgG IHA titer as the unique risk factor for PRCA occurrence. The optimal cut-off value of pre-HSCT IgG IHA for PRCA development, resulted to be 1/64, with a 100% sensitivity and 68.8% specificity (p<0.0001). All patients with PRCA had received rhEPO and transfusion support and 20 patients received additional treatments like PEX, rituximab, and more recently daratumumab. Comprehensively, PEX and rituximab obtained a response in half of the cases, at a variable time, while the few cases of patients we treated with daratumumab suggest promising results. The overall response rate in our cohort was 75%, with significantly better survival (94.4% vs. 16.7%) and lower transplant-related mortality (6.3% vs. 80%) for PRCA responders. Conclusions: Standardized guidelines on when and how to treat PRCA are necessary because the current treatment is controversial among centers.

Sodium-glucose cotransporter 2 inhibitors and the cancer patient: from diabetes to cardioprotection and beyond.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class initially designed and approved for treatment of diabetes mellitus, have been shown to exert pleiotropic metabolic and direct cardioprotective and nephroprotective effects that extend beyond their glucose-lowering action. These properties prompted their use in two frequently intertwined conditions, heart failure and chronic kidney disease. Their unique mechanism of action makes SGLT2i an attractive option also to lower the rate of cardiac events and improve overall survival of oncological patients with preexisting cardiovascular risk and/or candidate to receive cardiotoxic therapies. This review will cover biological foundations and clinical evidence for SGLT2i modulating myocardial function and metabolism, with a focus on their possible use as cardioprotective agents in the cardio-oncology settings. Furthermore, we will explore recently emerged SGLT2i effects on hematopoiesis and immune system, carrying the potential of attenuating tumor growth and chemotherapy-induced cytopenias.

Hematopoietic stem cell transplantation: an Italian monocentric experience on the health assessment and eligibility of adult-related donors.

Introduction: Indications for HSCT are increasing worldwide, paralleled by a growing demand for donors of therapeutic cells. Methods: Herein, we report our real-world experience of adult HPC donor assessment during a 5-year study period (2018-2023): we have retrospectively revised data of 455 potential related stem cell donors, consecutively evaluated at our center. Donor medical history was assessed by a questionnaire and an interview with a trained physician experienced in donation procedures to evaluate donor fitness and medical history. Pre-existing health disorders were fully investigated. Behavioral risk factors for communicable infectious diseases were also routinely explored. Results and discussion: Overall, 351 donors were finally assessed as eligible for HPC donation, and 233 underwent stem cell collection, 158 through apheresis from mobilized peripheral blood, and 75 through bone marrow harvest. Among them, 27 donors were selected despite the presence of pre-existing health conditions, which would be potential exclusion criteria for unrelated donors: 16 suffered from well-controlled cardiovascular diseases (CVD) and 11 from allergic diathesis. Most of the selected donors with pre-existing disorders were candidates for apheresis HPC collection (21, 77.8%), while only six (22.2%) underwent BM harvest. We then analyzed the data relative to the corresponding 233 allogeneic HSCT to explore if the presence of pre-existing diseases in the donors could show any association with transplant characteristics. Transplants from CVD and allergy donors showed no significant disparities in comparison with those from healthy donors. A significant difference emerged regarding the disease severity, with a higher proportion of patients with high/very high disease risk index (DRI) among those receiving grafts from CVD donors (68.7% in transplants from CVD donors versus 36.0% in transplants from healthy donors, p=0.005). Multivariate analysis confirmed that high/very high DRI patients had an increased probability of receiving donations from CVD donors (OR, 4.89; 95%CI, 1.15-20.86; p=0.031). Among donors with well-controlled pre-existing conditions, no adverse events were recorded during stem cell collection or at follow-up. Our results suggest that in patients at high risk for relapse requiring a prompt allogeneic transplant, a familiar donor might be accepted for HPC apheresis donation on less strict criteria than unrelated donors, without risk for both donor and patient.

Pros and Cons of Cryopreserving Allogeneic Stem Cell Products.

The COVID-19 pandemic has precipitously changed the practice of transplanting fresh allografts. The safety measures adopted during the pandemic prompted the near-universal graft cryopreservation. However, the influence of cryopreserving allogeneic grafts on long-term transplant outcomes has emerged only in the most recent literature. In this review, the basic principles of cell cryopreservation are revised and the effects of cryopreservation on the different graft components are carefully reexamined. Finally, a literature revision on studies comparing transplant outcomes in patients receiving cryopreserved and fresh grafts is illustrated.

Allogenic Cord Blood Transfusion in Preterm Infants.

Repeated red blood cell (RBC) transfusions in preterm neonates cause the progressive displacement of fetal hemoglobin (HbF) by adult hemoglobin. The ensuing increase of oxygen delivery may result at the cellular level in a dangerous condition of hyperoxia, explaining the association between low-HbF levels and retinopathy of prematurity or bronchopulmonary dysplasia. Transfusing preterm neonates with RBC concentrates obtained from allogeneic umbilical blood is a strategy to increase hemoglobin concentration without depleting the physiologic HbF reservoir. This review summarizes the mechanisms underlying a plausible beneficial impact of this strategy and reports clinical experience gathered so far in this field.

Discrepancy between recipient and donor rs4364254 heparanase single nucleotide polymorphism impacts graft-versus-host disease after allogeneic stem cell transplant.

INTRODUCTION: The heparanase (HPSE) gene is highly polymorphic, but only a minority of its single nucleotide polymorphisms (SNPs) have been studied. Among these, rs4693608 and rs4364254 SNPs are closely associated with mRNA expression and HPSE protein levels in healthy subjects. Given the association between HPSE and inflammatory response, we aimed to evaluate whether HPSE rs4693608 and rs4364254 SNPs could have an impact on graft-versus-host disease after allogeneic stem cell transplants (HSCT). METHODS: A total of 228 consecutive patients who underwent HSCT at our center between 2005 and 2018 were included. The rs4693608 SNP was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, while the rs4364254 was detected by allele-specific amplification. RESULTS: The recipient-donor discrepancy for rs4364254 HPSE SNP was significantly associated with grade II-IV aGvHD (HR 1.75, p = 0.03). Patients were stratified into risk groups as follows: low-risk group (LDR) including TT-TT, TT-CT, CT-TT, CC-CC; high-risk group (HDR) including CC-CT, CC-TT, CT-CC, CT-CT, TT-CC. Day 100 cumulative incidence of grade II-IV aGvHD was 23.4% in the LDR group and 41.4% in the HDR group (p = 0.01). One-year cumulative incidence of moderate/severe cGvHD was 42.6% in the LDR group and 58.6% in the HDR group (p = 0.04). Independent variables for moderate/severe cGvHD in patients who received myeloablative conditioning included donor rs4693608 SNP (GA/AA vs. GG: HR 6.86, p = 0.008), rs4693608-rs4364254 SNP combination in recipient (HR/MR vs. LR: HR 3.67, p = 0.01), and previous grade II-IV aGvHD (HR 3.28, p = 0.0005). Finally, donors with rs4364254 SNP CC conferred increased transplant-related mortality (TRM) (39.1% vs. 25%, p = 0.03) and decreased graft-relapse free survival (GRFS) (23.5% vs. 34.4%, p = 0.04) compared with CT or TT genotypes. CONCLUSION: The differences in incidence of GvHD according to recipient-donor genotype combinations suggests a possible role for rs4364254 HPSE SNP in predicting GvHD. A high level of HPSE, particularly linked to CC genotype of rs4364254 SNP may promote alloreactive T lymphocytes activation and migration toward target organs.

Peripheral Blood Allogeneic Stem Cell Mobilization: Can We Predict a Suboptimal Mobilization?

Allogeneic peripheral blood stem cells mobilization is now the basis of most stem cell transplants. In a very limited number of cases, mobilization is suboptimal leading to further collection procedures, to suboptimal cell doses infusion with delayed engraftment time, increased risks of transplant procedure and of related costs. To date we have no recognized and shared criteria for early estimating the probability of poor mobilization in healthy donors. We then analyzed allogeneic peripheral blood stem cell donations performed at the Fondazione Policlinico Universitario A.Gemelli IRCCS Hospital from January 2013 to December 2021 in order to identify premobilization factors associated with successful mobilization. The following data were collected: age, gender, weight, complete blood cell count at baseline, G-CSF dose, number of collection procedures, CD34+ cell count in peripheral blood on the first day of collection, CD34+ cell dose per kg body weight of recipient. Mobilization efficacy was defined according to the number of CD34+ cells in peripheral blood on day +5 of G-CSF administration. We classified donors as sub-optimal mobilizers or good mobilizers according to the achievement of the 50 CD34+ cell/µL threshold. We observed 30 suboptimal mobilizations in 158 allogeneic peripheral blood stem cell donations. Age and baseline white blood cell count were factors significantly associated with negative or positive impact on mobilization, respectively. We did not find significant differences in mobilization based on gender or G-CSF dose. Using cut-off values of 43 years and 5.5×109/L WBC count, we built a suboptimal mobilization score: donors who reach 2, 1 or 0 points have a 46%, 16% or 4% probability of suboptimal mobilization, respectively. Our model explains 26% of the variability of mobilization confirming that most of the mobilization magnitude depends on genetically determined factors; however, suboptimal mobilization score is a simple tool providing an early assessment of mobilization efficacy before G-CSF administration begins in order to support allogeneic stem cells selection, mobilization and collection. Through a systematic review, we looked for confirmation of our findings. According to the published articles, all the variables we included in our model are confirmed to be strongly related to the success of mobilization. We believe that score system approach could be applied in clinical practice to assess the risk of mobilization failure at baseline allowing for a priori intervention.

Impact of Covid 19 pandemic on hematopoietic stem cell transplantation activities: Report from a single center.

The current COVID-19 pandemic has placed unprecedented stress on the healthcare system, including HSCT. Several international organizations have created guidelines for managing different aspects of HSCT in the context of the pandemic. Comparing 2019 and 2020, our transplant center performed the same number of transplants. In both periods, transplants were mainly for patients with acute leukemia; thus, the urgency criteria was respected in light of pandemic restraints. Transplants by sibling donors and cord blood units remained the same, while transplants by unrelated donors were increased, in particular from European registries, and transplants by haploidentical donors were decreased. This change was made in light of the necessity of cryopreserving all apheresis products. We decided against cryopreserving bone marrow products due to the greater risk of drastic reduction in CD34 + cell count during the process. For urgent cases with only a haploidentical donor available, we opted for the use of PBSC following stimulation with G-CSF. GvHD prophylaxis was performed with PTCY on days + 3 + 5, cyclosporine with tapering from day + 100, and mycophenolic acid until day + 90 post-HSCT. Post-transplant outcomes such as graft failure, sepsis, and GVHD were not affected by the changes implemented. As a result of logistic difficulties, we halted our Car-T program from the start of the lockdown in March 2020 until September 2020. In accord with international guidelines, we were able to continue our HSCT program in the order to ensure a lifesaving treatment for patients with hematologic diseases for whom this procedure cannot be postponed.

Day -1 CD34+ Cells and Platelet Count Predict the Number of Apheresis in Poor-Mobilizer Patients Rescued by Plerixafor.

Plerixafor is widely used as up-front treatment with G-CSF to enhance peripheral blood hematopoietic stem cell output in patients failing previous mobilizations. Less frequently, plerixafor is used to rescue an unsatisfactory mobilization following chemotherapy (CT) and G-CSF. This study investigates if pre-collection factors affect the CD34+ cell harvest in chemotherapy and G-CSF mobilizations rescued by plerixafor. Clinical and hematological data relative to patients, mobilization, and apheresis products were retrospectively examined. The outcome was completing a target cell dose ≥ 2 × 106 CD34+ cells/kg at first apheresis. The effect exerted on the outcome by patient- and disease-related factors was investigated by univariate and multivariate logistic regression analysis. The analysis included data from 42 patients affected by hematological (39 patients) and non-hematological malignancies (three patients). Twenty-nine patients (69%) attained the target cell dose at first apheresis. Twelve out of the remaining 13 patients received an additional plerixafor administration, and all accomplished the transplant dose at a second apheresis procedure. Day -1 CD34+ PB count (OR1.46, 95% CI 1.1-1.9, p = 0.008) and platelet count (OR1.0, 95% CI 1.0-1.0, p = 0.033) predicted the achievement of the target dose at first apheresis, independently of pre-mobilization CT, radiation therapy, and disease status at mobilization. At ROC curve analysis, the best cut-off value predicting the successful collection at first apheresis was 7.5/µL for Day -1 CD34+ cell count (AUC 0.830, 0.69 sensitivity, and 0.92 specificity) and 75 × 109/L for Day -1 platelet count (AUC = 0.736, 0.65 sensitivity and 0.85 specificity). In conclusion, on-demand plerixafor rescue allows a successful stem cell collection, irrespectively of disease type and status, prior CT lines, and radiation exposure. Pre-apheresis CD34+ cells and platelet count predict the need for one or two aphereses.

Single shot of intravenous iron in cardiac surgery: The ICARUS study.

BACKGROUND: Iron deficiency (ID), with or without anemia, is commonly observed among patients scheduled for cardiac surgery. We investigated if screening ID in the immediate preoperative period and treating ID patients regardless of anemia could reduce perioperative transfusion requirements. METHODS: This is an observational single-center propensity score-matched study including candidates to elective cardiac surgery prospectively and retrospectively enrolled. Prospectively enrolled patients were screened for ID at hospital admission: if ferritin was ≤100 µg/L or ≤ 300 µg/L with transferrin saturation index ≤20% they received intravenous ferric carboxymaltose, B12-vitamin, and folic acid. A retrospective series of patients not screened for ID and matched for gender, type of surgery, BMI, Goudie transfusion risk score, hemoglobin level, and red blood cell (RBC) indices, served as controls. The primary outcome was the proportion of patients requiring ≤1 packed RBC (pRBC) unit within day 7 or discharge The main secondary outcomes were intraoperative and postoperative pRBC transfusions, duration of hospitalization, and cost-effectiveness of ID screening and treatment. RESULTS: We included 479 prospective and 833 retrospective cases: 442 patients screened for ID and 442 matched controls with unknown iron status were analyzed. ID was observed in 196 patients (44.3%) and iron was administered 1 day (IQR 1-2) before surgery. Overall, 76.9% of patients in the prospective group and 69.7% of controls received ≤1 pRBC transfusion (p = 0.014). The risk for multiple transfusions was lower in patients screened for ID (OR 0.689, 95% CI 0.510-0.930). Despite similar Hb levels at day 7, patients in the prospective group received fewer postoperative pRBC transfusions (p < 0.001) and had a shorter hospital length of stay (p < 0.001). Globally, hospitalization costs were lower in patients screened and treated for ID. CONCLUSIONS: Short-term pre-operative iron therapy is associated with a reduction in postoperative transfusions in anemic and non-anemic ID cardiac surgery patients and has a favorable impact on hospitalization costs. CLINICAL TRIAL REGISTRATION: NCT04744181.

Acute Promyelocytic Leukemia in a Woman with Thalassemia Intermedia: Case Report and Review of Literature on Hematological Malignancies in ß-Thalassemia Patients.

Patients affected by transfusion-dependent ß-thalassemia are prone to developing several clinical complications, mostly related to the iron overload. We report the case of a patient affected by transfusion-dependent ß-thalassemia (TDT) developing acute promyelocytic leukemia (APL). In our case, the therapeutic management was significantly complicated not only by myocardial dysfunction, but also by the occurrence of the differentiation syndrome following all-trans retinoic acid (ATRA) administration. We carried out a careful revision of the current literature on the occurrence of hematological malignancies in ß-thalassemia patients to investigate the major complications so far described. APL occurrence in ß-thalassemia patients has been very rarely reported, and our experience suggests that TDT patients suffering pre-existing comorbidities may develop a potentially fatal complication during ATRA therapy.

Day +60 WT1 assessment on CD34 selected bone marrow better predicts relapse and mortality after allogeneic stem cell transplantation in acute myeloid leukemia patients.

The aim of this study was to evaluate the role of WT1 expression after allogeneic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML). We studied WT1 expression in bone marrow cells from 50 patients in complete remission on day +60 after transplant. WT1 was assessed on unfractionated bone marrow mononuclear cells (MNC) and on CD34+ selected cells (CD34+). A ROC curve analysis identified 800 WT1 copies on CD34+ selected cells, as the best cut-off predicting relapse (AUC 0.842, p=0.0006, 85.7% sensitivity and 81.6% specificity) and 100 copies in MNC (AUC 0.819, p=0.007, 83.3% sensitivity and 88.2% specificity). Using the 800 WT1 copy cut off in CD34+ cells, the 2 year cumulative incidence of relapse was 12% vs 38% (p=0.005), and 2 year survival 88% vs 55% (p=0.02). Using the 100 WT1 copy cut off in unfractionated MNC, the 2 year cumulative incidence of relapse 13% vs 44% (p=0.01) and the 2 year survival 88% vs 55% (p=0.08). In a multivariate Cox analysis WT1 expression in CD34 cells proved to highly predictive of relapse (p=0.004); also WT1 expression on unfractionated cells predicted relapse (p=0.03). In conclusion, day-60 WT1 expression after allogeneic HSCT is a significant predictor of relapse, particularly when tested on CD34+ selected bone marrow cells.

High Arterial Lactate Levels after Hepatic Resection Are Associated with Low Oxygen Delivery and Predict Severe Postoperative Complications.

High End-Surgery Arterial Lactate Concentration (ES-ALC) predicts poor outcome after hepatectomy. The aim of this study was to identify intraoperative hemodynamic parameters predicting high ES-ALC during elective liver resection. Patients who underwent liver resection between 2017 and 2018, under FloTrac/EV1000TM hemodynamic monitoring, were included. The ES-ALC cutoff best predicting severe postoperative complications was identified. Association between high ES-ALC and preoperative and intraoperative variables was assessed. 108 patients were included; 90-day mortality was 0.9% and severe morbidity 14.8%. ES-ALC cutoff best discriminating severe complications was 5.05 mmol/L. Patients with ES-ALC > 5.0 mmol/L had a relative risk of severe complications of 2.8% (p = 0.004). High ES-ALC patients had longer surgery and ischemia duration, larger blood losses and higher requirements of fluids and blood transfusions. During surgery, hemoglobin concentration and oxygen delivery (DO2) decreased more significantly in patients with high ES-ALC, although they had similar values of stroke volume and cardiac output to those of other patients. At multivariate analysis, surgery duration and lowest recorded DO2 value were the strongest predictors of high ES-ALC. ES-ALC > 5.0 mmol/L in elective liver resection predicts postoperative morbidity and is essentially driven by the impaired DO2. Timely correction of blood losses might prevent the ES-ALC increase.

Triple post transplant cyclophosphamide (PTCY) based GVHD prophylaxis: HLA matched versus HLA haploidentical transplants.

We report a retrospective analysis of 198 allogeneic hematopoietic stem cell transplant (HSCT) recipients with post-transplant cyclophosphamide (PTCY), cyclosporine and mycophenolate mophetil as graft-versus-host-disease (GVHD) prophylaxis: the donors were HLA-matched (n = 78), or haploidentical relatives (HAPLO) (n = 120). The two groups were comparable except for older age in the HAPLO group. The main diagnosis were acute leukemia (57%) and myelofibrosis (21%). In the HLA-matched and HAPLO group the outcomes were as follows: aGVHD grade II-IV, 10% vs 27% (p = 0.005); moderate-severe cGVHD, 4% vs 19% (p = 0.004); transplant related mortality (TRM) at 1 year 10% vs 21% (p = 0.04); relapse at 1 year 24% vs 10% (p = 0.051) respectively. Disease free survival (DFS) at 1 year was 65% for matched and 68% for HAPLOs (p = 0.85). DFS and OS were independently predicted by age over 60 and higher DRI, whether the only independent predictive variable for GVHD and relapse free survival (GRFS) was age over 60. In conclusion: given the same PTCY based, GVHD prophylaxis, HLA-mismatched grafts are exposed to a higher risk of acute and chronic GVHD. This translates in increased TRM. DFS is comparable for HLA matched and HAPLO grafts.