Introduction In most cases, haploidentical stem cell transplantation (haplo-HSCT) with negative depletion of α/β(+) T cells and CD19+ B lymphocytes from the graft is used to treat pediatric patients. The results are promising. However, the results of this method in adult patients is controversial. The accumulation of experience in haplo-HSCT with TCRαβ / CD19 + depletion in the group of adult patients is relevant. Aim Evaluation of the effectiveness and characterization of the most frequent complications in adult patients with hematological malignancies who underwent allo-HSCT from a haploidentical donor with depletion of TCRαβ/CD19 + cells. Patients and methods The analysis included 32 patients (14 males/18 females) with acute myeloid leukemia (AML, n=12), acute lymphoblastic leukemia (ALL, n=11), myelodysplastic syndrome (MDS, n = 6), chronic myeloid leukemia (CML, n = 1), primary myelofibrosis (PMF, n = 1), lymphoproliferative disease (LPD, n = 1). Median age was 28 years (range, 17-58). Disease status of acute leukemia at the beginning of pre-transplant conditioning was first complete remission (CR1) in 14 patients, CR2 in 7 and active disease in 2 patients. Pre-transplant conditioning regimen: RIC (Treosulfan 42 g/m2, Melphalan 140 mg/m2, Fludarabine 150mg/m2), MAC (Treosulfan 42 g / m2, Thiophosphamide 10 mg / kg, Fludarabine 150 mg / m2). Immunosuppressive therapy: Rituximab, Bortezomib, Tocilizumab, Abatacept. Immunomagnetic separation was performed using a CliniMACS Plus device. Descriptive statistics methods were used for analysis. The probabilities of survival and graft versus host disease (GVHD) rate were estimated using the Kaplan-Meier method. Results Log of TCRαβ + depletion was 1.61-5.33 (Me = 3.66). The median dose of CD34+ cells in transplant was 6.8 * 106/kg (range, 2.0-10.8). The median time to white blood cells recovery was +13 days after haplo-HSCT (range, 9-26). Median follow-up was 6.4 months. Transplant related mortality was 3.1%. Primary engraftment - 96.8%. Graft hypofunction - 16.2%. The probabilities of overall and disease-free survival for 12 months were 94.1% and 70,5%, respectively. The probability of relapse was 24.4% (Fig. 1). The probability of developing acute GVHD was 25%, GVHD rate was 18,75% including grade I (n=1), grade II (n=2), grade III (n=3) (data not shown). In 4 cases complete response was achieved with administration of first line immunosuppression therapy. 1 case (grade III GVHD) required administration of second line immunosuppression therapy - methylprednisolone, and the response was complete. 1 patient developed chronic GVHD. Nonclassical infectious complications prevail: viral infections (CMV, HHV6 and EBV) was 58.8%, fever with an unverified infectious agent was 15.6%, and tuberculosis in two cases (6.2%). Immunological events not associated with GVHD - 21.8% (TMA, TTP, myasthenia gravis, AIHA, PRCA). Conclusion In some cases, haplo-HSCT is the only HSCT option for an adult patient. The frequency of viral infectious complications and relapses in adult patients after haplo-HSCT TCRαβ / CD19 + depletion is comparable to the results in the pediatric population. Haplo-HSCT with TCRαβ / CD19 + depletion is characterized by minimal toxicity and a short period of myelotoxic agranulocytosis. Among the undesirable phenomena in the first place are infectious complications and frequent immunological events that do not fit into the criteria for GVHD, but affect the patient's quality of life and length of hospital stay. Figure 1 Disclosures Maschan: Miltenyi Biotec: Other: lecture fee.
Transplantation allows us to confidently save the lives of previously doomed patients. Unfortunately, this colossal achievement of human progress has a problematic side – the shortage of donor organs. The use of animal organs could solve it. Currently, the issues of xenotransplantation have become relevant again after the experimental xenotransplantation of the kidney of a genetically modified pig in 2021, and the xenotransplantation of the heart in 2022. This practice raises a number of ethical questions. Is it ethical to put humanity at risk by saving one person? Is it ethical to limit the civil rights of a xeno-recipient? Will xenotransplantation create another reason for discrimination? Can the creation of xenochimeras be considered an unacceptable interference in the Divine plan from a religious point of view? Is it ethical to use higher animals for xenotransplantation? Will an increase in the number of xenotransplants create a risk of the identity of the human race? Will xenotransplantation create new questions about equitable organ allocation? The sources of scholars of theologians related to the main Abrahamic religions on this topic are analyzed. Consideration of theological approaches to the new ethical problems presented by xenotransplantation does not allow us to find a unanimity of opinion. However, as this new branch of medical science makes concrete clinical progress, the attitude of society, religious leaders and ordinary believers towards it will improve. From an individual point of view, Judaism does not object to xenotransplantation to prolong and save human life, even in the case of non-kosher animals with genetic modifications. The preservation of life outweighs other values almost without exception. Xenotransplantation, even from a pig, is hailed as a life-sustaining medical intervention from a Jewish ethical perspective by most authors. In Christianity, the motivation is to try to follow the example of Jesus Christ in bringing healing to all those in need. While physiological healing is important, the ultimate goal is the overall well-being of the individual, which requires spiritual, mental, and social well-being in addition to physical health. The most correct generalization about Islamic bioethical views on xenotransplantation would be that, given the state of science, the final ethical and legal definition remains ambiguous, but in general, xenotransplantation as a means of saving human life may be acceptable.
Background: Nutritional problem is a key aspect of all severe diseases that always "keep in the shadows". There are different factors, such as intensive chemotherapy, constant nausea, severe infections, time for donor search that affect nutritional status in leukemia patients who underwent allogeneic stem cell transplantation (allo-HSCT). This study aimed to evaluate the impact of different "nutritional status assessment tools" on outcomes of allogeneic hematopoietic cell transplantation. Materials and methods: 307 leukemia patients who underwent allo-HSCT in National Research Center for Hematology from 2011-2019 were included on this study. Detailed patients' characteristics are given in Table 1. All data were collected directly before allo-HSCT conditioning regimen. Nutritional Risk Index (NRI) was calculated by NRI = (1.519 × serum albumin, g/dL) + (41.7 × present weight (kg)/ideal body weight(kg)). Ideal body weight (IBW) was calculated by Lorentz IBW formula: for men IBW = (height, cm− 100) − ((height − 150)/4); for women: IBW = (height, cm − 100) − ((height, cm − 150)/2). All patients were stratified according to NRI: NRI < 83.5 - Major; 83.5 ≤NRI < 97.5 - Moderate; 97.5 ≤NRI < 100 - Mild; NRI≥100 - No risk group. Moreover all patients were stratified according to serum albumin level (more and less than 4.3 mg/dl ). Groups stratified by NRI and serum albumin was balanced for factors that can affect long-term results: disease type and status, graft source, conditioning regimen, donor's type, graft failure, acute and chronic GVHD. Data analysis was performed with R version 3.5.2 (Core Team, 2018). Chi-square and Fisher's exact test were used for contingency tables. Kaplan-Meier analysis was provided to assess the probability of overall survival. Log-rank test was used to compare two groups. Cox regression model was used to identify independent prognostic factors and its hazard ratio (HR) with a 95% confidence interval (95% CI). Age, sex, disease status before allo-HSCT (CR vs not in CR), serum albumin level (83.5 <4.3 vs ≥4.3 mg/dl), NRI, donor type (MUD, MMUD, Haplo vs MRD), conditioning regimen (MAC vs RIC) was included as independent covariates.P-value of 0.05 was considered as significant. Results: As we can see on Figure 1A NRI-based stratification can't help us to predict long-term results in contrast with serum albumin level (Figure 1B). At the same time level of albumin >4.3 was associated with better results compared to serum albumin level <4.3 mg/dl (p=0.02). According to Cox model there are several independent prognostic factors : disease status before allo-HSCT (CR vs not in CR) - HR=3.79 (95% CI 2.45-5.8; p=0.0001); donor type (MMUD vs MRD and Haplo vs MRD) - HR=1.67 (95% CI 1.09-2.57; p=0.017) and HR=2.7 (95% CI 1.2-5.8; p=0.011) respectively. Serum albumin level was also identified as an independent prognostic with HR=1.76 (95% CI 1.14-2.72; p=0.011). Other factors including NRI were not significant. Conclusion: These data showed that serum albumin level, but not NRI index, in leukemia patients before allo-HSCT can predict long term outcomes. Identification of these high risk patients could be a start point for future interventions and could change care protocols. Disclosures No relevant conflicts of interest to declare.
donor grafts were associated with faster neutrophil recovery (15d vs. 33d; p < 0,05). The 100-day mortality risk was 10,3% ( ± 5,7%). In FA pts there were 4 graft failures (3 primary, 1 secondary) and, interestingly, primary graft failures occurred only in pts with unrelated donors. The overall survival (OS) at 1 year was 75,4% ( ± 8,1%) and at 3, 5 and 10 years was 67,9% ( ± 8,9%). One patient died due to a secondary solid neoplasia, 16 years after AlloHCT. Summary/Conclusion: It is currently accepted that AlloHCT is curative of the BM failure in IBMFS. However, there is no clear evidence on the best approach to the transplant. There are still many unanswered questions, especially those concerning the conditioning regimen, the choice of donor, the graft source and the prophylaxis of GVHD. We present the results of a cohort of patients with IBMFS, 6 of them surviving more than 10 years and with a relatively low incidence of transplant related complications.
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