Introduction. Natural killers are the "first line" of antitumor and antiviral protection in the early stages after аllogeneic hematopoietic stem cell transplantation. Quantitative characteristics reach normal values already in the first month after the infusion of blood stem cells to the recipient. Self-tolerance of natural killers is achieved due to many receptors on their surface, but killer immunoglobulin-like receptors play a key role. Their role is to recognize "self" cells and block signals aimed at destroying their own cells. Knowledge of the functional activity of natural killers urged to studying the impact of mismatches between the inhibitory receptor gene and the ligand on the development of allogeneic hematopoietic stem cell transplant failure.The aim of research was to study the probability of the graft failure development in allogeneic hematopoietic stem cell transplantation depending on the recipient's killer immunoglobulin-like receptor genotype.Material and methods. Genotyping of killer-cell immunoglobulin-like receptors in 66 recipients of blood stem cells by the polymerase chain reaction method was performed in the study. Using an online calculator, receptors were classified as "best", "better" and "neutral" depending on the genotype. The end point of the assessment was the development of graft failure in the presence of different genotypes of immunoglobulin-like receptors in the recipient.Results. According to the data obtained, the presence of the “best” and "better" killer-cell immunoglobulin-like receptor genotype in the recipient significantly increased the risks of developing various forms of graft failure.Conclusion. The presence of the KIR2DL3 genotype in a recipient of hematopoietic stem cells significantly (by 3 times) reduces the likelihood of primary graft failure. This result is of great prognostic significance, although at present no ways of influencing it have been developed. The presence of the “best” killer immunoglobulin-like receptors genotype in the recipient increases the likelihood of developing graft failure by more than 3 times compared to the best and neutral genotype (44.4% vs. 13.4%).
Background: Natural killer cells (NK) are a component of innate immunity and are capable of cytotoxic lysis and cytokine secretion without prior antigen presentation. They are among the first to recover after transplantation, so they can play a decisive role in preventing early relapses and infectious complications. The killer immunoglobulin-like receptor (KIR), which is expressed on NK cells, mediates the immune response, both anti-tumor and directed against infectious agents. In the case of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), if the donor has inhibitory KIR, to which the recipient has no ligand, donor NK
Background: Natural killer cells (NK) can play a decisive role in preventing early relapses and infectious complications after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) due to their comparatively fast reconstitution after HSCT. And when performing haplo-HSCT with depletion of TCRαβ-positive T-lymphocytes, the graft versus leukemia (GVL) effect is carried out only at the expense of donor NK cells. NK differentiate from immature (CD56bright) to mature (CD56dim) and terminally differentiated. NK differentiation to the subpopulation CD56dimCD16+ is necessary to implement an alloreactive NK cell immune response. Aims: To study the rate and features of NK cell reconstitution after haplo-HSCT. Methods: The study included 16 patients with acute myeloid leukemia (AML) and 13 patients with acute lymphoblastic leukemia (ALL) who underwent haplo-HSCT at the National Medical Research Center for Hematology from April 2020 to June 2021. 15 patients - with the use of post-transplant cyclophosphamide (PT-Cy), 14 - with previous TCRαβ-depletion. To assess the reconstitution of NK, all patients underwent immunophenotypic studies of peripheral blood samples at +14, +30, +60, +90 and +180 days after haplo-HSCT using a 12-color flow cytometer (CytoFlex Beckman Coulter, USA). Monoclonal antibodies to human differentiation antigens CD3, CD8, CD158a, CD158b, CD158e, CD159a, CD57, CD16, CD56, CD14, CD45, CD62L were used in the analysis of subpopulations of NK cells. The SAS 9.4 software (Sas institute inc., Cary, NC, USA) was used for statistical data processing. Differences were considered statistically significant at p<0.05. Results: NK reached a mature immunophenotype faster in the case of haplo-HSCT with TCRαβ-depletion: by day +30 after HSCT, the median proportion of CD56dimCD16+ NK cells with TCRαβ-depletion was 57% versus 9% when using PT-Cy, p= 0.0045. Significant differences persisted up to +60 (74% vs. 41% (p=0.0079)) and +90 days after haplo-HSCT (81% vs. 46% (p=0.0076)) (Fig. 1). Image:Summary/Conclusion: The rate of reconstitution and the acquisition of an alloreactive phenotype by NK depends on the variant of T-cell depletion; faster recovery occurs when performing haplo-HSCT with TCRαβ-depletion. When using PT-Cy, the recovery of the mature NK cell population occurs at a later time after haplo-HSCT (from +3 to + 6 months) and such patients may benefit from transfusions of donor NK cells at the post-transplant stage. This approach can be considered as a worthy alternative to donor.
The graft-versus-host disease (GVHD) is among the most common complications after hematopoietic stem cell transplantation (allo-HSCT). The main tools for GVHD prevention remain calcineurin inhibitors (cyclosporin A, tacrolimus), methotrexate, mycophenolate mofetil. Upon implementation of reduced-intensity conditioning regimens, antithymocyte globulin was widely introduced. However, negative effects upon reconstitution of T-cell immunity have been noted, thus increasing risk of severe infectious complications and disease relapse. With extended practice of HSCT from alternative (partially matched or haploidentical) donors, cyclophosphamide was increasingly used. Our aim was to study reconstitution of immune cell subpopulations in the patients undergoing bone marrow transplantation (BMT), when using different GVHD prophylaxis regimens, including the schedules with post-transplant CP usage. The study concerned 44 cases classified into 2 groups. The first one included patients with standard immunosuppressive therapy, antithymocyte therapy, cyclosporine A, methotrexate, mycophenolate mofetil. The second group included the patients who received CP as immunosuppressive drug combined with other treatments (cyclosporine A, methotrexate, mycophenolate mofetil). At specified control terms, (D+14, +30, +60, +90) the blood leukocyte subpopulations were assayed by means of multicolor flow cytometry. Absolute counts of CD4+ cells in HSCT recipients treated with CP post-BMT proved to be sufficiently lower at D+14 and +30, than in those treated with classical immunosuppressive therapy. However, at later terms, (D+60, +90), these differences were not observed. Moreover, in CP-treated bone marrow recipients, absolute numbers of CD8+ cells was significantly higher, compared to the patients who received conventional GVHD prophylaxis. Reconstitution of the studied lymphocyte populations in hematopoietic cell recipients did not depend on the GVHD prophylaxis regimen. Usage of CP combined with bone marrow as a source of stem cells, brings about sufficient decrease of some cell populations (CD4+; CD8+; NK cells) at early terms post-transplant. Administration of CP combined with hematopoietic stem cells as the source of hematopoietic graft seems to be more reasonable.
Introduction: T-regulatory cells (Treg) prevent the development of graft-versus-host disease (GVHD) after allo-HSCT (Beres & Drobyski, 2013). At the same time, this cell population can limit the anti-tumor response (graft-versus-leukemia, GVL), which can cause relapses. We report data of chimerism in a Treg population and the frequency of relapses in acute leukemia patients (ALL and AML) after allo-HSCT. Objective: To evaluate a possible relationship between mixed chimerism in Treg cells and the rate of relapses in acute leukemia patients after allo-HSCT. Methods: The study included 31 patients after allo-HSCT (ALL n = 6, AML n = 25). The median age was 38 years (19–66). Peripheral blood samples for analysis were taken on day +30 after transplantation. Immunomagnetic separation (Miltenyi Biotec, Germany) was used to isolate cell population with CD4+CD25+ phenotype, which is predominantly associated with Treg cells. Extraction of DNA was performed from the obtained cells. Chimerism in DNA samples was determined using the STR-PCR method. The percentage of donor chimerism was calculated using standard procedures (Nollet et al., 2001). Statistical analysis of the data was carried out using SPSS ver 23 (IBM, Chicago, IL, USA). Fisher’s exact test was used to analyze the 2 × 2 contingency tables. Results: In the group of patients with less than 11% of cells with host genotype (more than 89% of cells of donor origin), the relapse rate was significantly higher: 52.6% (10 of 19) than in the other group of patients with 11% and more cells with host genotype: 8.3% (1 of 12; p = 0.02). At the same time, donor chimerism in the unselected bone marrow did not differ significantly from the groups (p = 0.36) and reached 100% (75–100%) and 97.5% (90–100%). The study groups were balanced for all other factors that could affect the relapse rate: disease status, graft source, and GVHD. Conclusions: According to our data, we proposed that host Treg cells are not capable to suppress GVL, which explains significant differences in relapse frequencies in patients with acute leukemia after allo-HSCT. Predominance of host Treg cells may be a favorable prognostic sign, but this hypothesis needs to be confirmed on the larger cohort of patients.
Context One of the main causes of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia (AL) patients is the disease relapse. Minimal residual disease (MRD) detected by multiparameter flow cytometry (MFC) is a strong prognostic marker of increased risk of relapse. Objective To determine the impact of MRD detected by MFC before allo-HSCT on clinical outcomes of acute leukemia patients. Patients and methods To assess the impact of MRD status before transplantation we included 84 AML patients and 46 ALL patients in their first or second morphologic remission who underwent allo-HSCT between July 2016 and April 2020. 6-color MFC was performed on bone marrow samples obtained before allo-HSCT. Positive MRD was identified as a cell population deviating from the normal patterns of antigen expression on specific cell lineages at specific stages of maturation for all patients. For patients with LAIP at diagnosis, positive MRD was also defined as a cell population carrying LAIP markers at diagnosis. The probabilities of overall survival (OS), relapse-free survival (RFS), and cumulative incidence of relapse (CIR) were estimated using the Kaplan–Meier method. Results Among 84 AML patients before allo-HSCT 23 patients (27.4%) were identified as MRD+. 11 out of 46 ALL patients (23.9%) before allo-HSCT were MRD+. Subsequently, 9 out of in 23 MRD+AML patients and 4 out of 61 MRD−AML patients relapsed (CIR 50.6% vs. 10%, p < 0.0001); 6 out of 11 MRD+ALL and 3 out of 35 MRD−AML relapsed (CIR 76.6% vs. 11.6%, p=0.0023). Statistical analysis revealed significant differences between MRD− and MRD+ patients: MRD+ had significantly worsened RFS both in AML (44.3% vs. 74.4%, p < 0.0001) and ALL (20% vs. 72%, p=0.0325) patients and OS in AML patients (58.6% vs. 79.7%, p=0.0185). Conclusions Despite the presence of morphological complete remission before allo-HSCT, MRD persistence before allo-HSCT influences OS and RFS in patients with AL. Because of the association between MRD and relapse risk, MRD-testing before allo-HSCT may help to identify a subgroup of acute leukemia patients who need preemptive treatment. One of the main causes of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia (AL) patients is the disease relapse. Minimal residual disease (MRD) detected by multiparameter flow cytometry (MFC) is a strong prognostic marker of increased risk of relapse. To determine the impact of MRD detected by MFC before allo-HSCT on clinical outcomes of acute leukemia patients. To assess the impact of MRD status before transplantation we included 84 AML patients and 46 ALL patients in their first or second morphologic remission who underwent allo-HSCT between July 2016 and April 2020. 6-color MFC was performed on bone marrow samples obtained before allo-HSCT. Positive MRD was identified as a cell population deviating from the normal patterns of antigen expression on specific cell lineages at specific stages of maturation for all patients. For patients with LAIP at diagnosis, positive MRD was also defined as a cell population carrying LAIP markers at diagnosis. The probabilities of overall survival (OS), relapse-free survival (RFS), and cumulative incidence of relapse (CIR) were estimated using the Kaplan–Meier method. Among 84 AML patients before allo-HSCT 23 patients (27.4%) were identified as MRD+. 11 out of 46 ALL patients (23.9%) before allo-HSCT were MRD+. Subsequently, 9 out of in 23 MRD+AML patients and 4 out of 61 MRD−AML patients relapsed (CIR 50.6% vs. 10%, p < 0.0001); 6 out of 11 MRD+ALL and 3 out of 35 MRD−AML relapsed (CIR 76.6% vs. 11.6%, p=0.0023). Statistical analysis revealed significant differences between MRD− and MRD+ patients: MRD+ had significantly worsened RFS both in AML (44.3% vs. 74.4%, p < 0.0001) and ALL (20% vs. 72%, p=0.0325) patients and OS in AML patients (58.6% vs. 79.7%, p=0.0185). Despite the presence of morphological complete remission before allo-HSCT, MRD persistence before allo-HSCT influences OS and RFS in patients with AL. Because of the association between MRD and relapse risk, MRD-testing before allo-HSCT may help to identify a subgroup of acute leukemia patients who need preemptive treatment.
Granzyme B is known to be a serine protease contained in granules of cytotoxic T cells. We have previously reported an influence of granzyme B expression in T regulatory cells (Tregs) on the risk of acute graft versus host disease (GVHD) onset. However, it is still unknown if conventional T cells (Tcon) use the granzyme B pathway as a mechanism of alloimmunity. We hypothesized that granzyme B in Tcon may affect recurrence within the first 6 months after allogeneic transplantation (allo-HSCT). A total of 65 patients with different hematological malignancies were included in this study. Blood samples were collected on day +30 after allo-HSCT. The percentage of granzyme B positive conventional T cells in patients who developed relapse in the first 6 months after allo-HSCT was 11.3 (4.5-35.3) compared to the others in continuous complete remission-1.3 (3.65-9.7), p = 0.011. The risk of relapse after allo-HSCT was in 3.9 times higher in patients with an increased percentage of granzyme B positive conventional T cells. The findings demonstrated that the percentage of granzyme B positive conventional T cells on day +30 after allo-HSCT could be a predictable marker of relapse within the first 6 months after alloHSCT.
Background:Programmed cell death protein 1 (PD‐1) is a surface receptor expressed normally on distinct immune cells. It's well known PD‐1 pathway blockade is a negative immune regulatory mechanism that has detrimental effects on anti‐tumor immunity. Currently some studies have revealed different immune cells overexpressed PD‐1 as a predictable marker of leukemia relapse. On the other hand its assay after allo‐HSCT could be controversial due to alternative GVHD prophylaxis regimens that might affect PD‐1 expression, such as post‐transplant high dose Cyclophosphamide (PT‐Cy) or graft‐manipulated TCR αβ‐depletion are taken place if mismatched or haploidentical donors are used.Aims:To evaluate PD‐1 expression on bone marrow (BM) resident CD8+ memory T‐cell subsets in leukemia patients after allo‐HSCT and its input on immunosuppressive mechanisms of different GVHD prophylaxis regimens after allo‐HSCT.Methods:BM samples were collected from 56 leukemia patients with a median age of 33 years on day +30, +60 and +90 after allo‐HSCT. Detailed patients characteristics are presented in Table 1. Flow cytometry analysis was performed on BD FACS Canto II (Becton Dickinson, USA) to define CD8+ T‐memory subsets with PD‐1 expression: T‐naive and T‐stem cell memory (Tnv+Tscm) –CD45R0‐CCR7+CD28+; T‐central memory (Tcm) ‐ CD45R0+CCR7+CD28+; T‐transitional memory (Ttm) ‐ CD45R0+CCR7‐CD28+; T‐effector memory (Tem) ‐ CD45R0+CCR7‐CD28‐; T‐terminal effector (Tte) ‐ CD45R0‐CCR7‐CD28‐. Sysmex XE‐2100 was used to calculate absolute count of different CD8+ T‐ memory cell subsets with PD‐1. Mann–Whitney U test was used for nonparametric data analysis. A p‐value less than 0.05 was considered as significant.Table 1. Patients characteristics.Results:During all follow‐up period PD‐1 expression remains increased on all CD8+ T‐memory cell subsets after TCR αβ‐depletion compared to PT‐Cy–based and classical immunosuppressive regimen based on Cyclosporine+MMF. On day +30 we observe significantly higher expression of PD‐1 on Tnv+scm, Tcm, Ttm after TCR αβ‐depletion compared to PT‐Cy or classical regimen (p < 0.05). On day +60 PD‐1 is still overexpressed on Tnv+scm after TCR αβ‐depletion compared to PT‐Cy or classical regimen (p = 0.008). Moreover on day +60 and +90 PD‐1 expression is elevated on terminally differentiated CD8+ T cells (Ttm, Tem) after TCR αβ‐depletion comparing PT‐Cy or classical regimen (р<0.05). (Figure 1).imageSummary/Conclusion:According to our data PD‐1 is overexpressed on distinct subsets of BM resident CD8+ T‐memory cells after TCR αβ‐depletion during follow‐up period in first 3 months after allo‐HSCT. Since other immune signaling pathways are inhibited due to the other immunosupressive agents had been used, PD‐1 pathway seems to be a key mechanism of immunological tolerance after haploidentacal allo‐HSCT with TCR αβ‐depletion.image
Introduction. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be curative for acute myeloid leukemia (AML) patients. However, the disease relapse after allo-HSCT lead to poor outcomes almost in all cases. Minimal residual disease (MRD) is a strong prognostic marker of increased risk of relapse and reflects overall (OS) and relapse-free survival (RFS) in patients with AML. Immunophenotypic evaluation using multiparameter flow cytometry (MFC) is an important strategy for detecting MRD, because of its simplicity and wide availability. Aim. Determine the impact of MRD detected by MFC before allo-HSCT on clinical outcomes. Patients and methods. To assess the impact of MRD status before transplantation we include 56 AML patients who underwent allo-HSCT in National Research Center for Hematology between July 2016 and June 2019. Patient's characteristics are shown in table 1. All these patients were in first compete morphologic remission at the time of allo-HSCT. MRD was evaluated by MFC. Bone marrow samples were obtained before allo-HSCT and were analyzed by 6-color MFC (BD FACS Canto II, USA). Positive MRD was identified as a cell population deviating from the normal patterns of antigen expression on specific cell lineages at specific stages of maturation for all patients. In addition, for patients with LAIP at diagnosis, positive MRD was also defined as a cell population carrying LAIP markers at diagnosis. The probabilities of OS and RFS were estimated using the Kaplan-Meier method. Results. Among 56 AML patients before allo-HSCT (all were in CR at the time of MRD analysis). Median of follow-up was 9.3 months.11 patients (19,6%) were identified as MRD+ (0,011%-5,08%, mean 1%). And 5 of them relapsed (45,5%). Out of 45 MRD negative patients before HSCT relapse was registered in one (relapse rate 2,2%). Statistical analysis revealed significant differences between MRD- and MRD+ patients: MRD+ had much worse OS (22,9% vs. 85.5%, p=0.0047, Fig.1A) and RFS (26% vs. 97.4%, p<0,0001, Fig.1B). Conclusions. Despite the presence of morphological CR before allo-HSCT, MRD persistence can lead to worse probabilities of OS and RFS, which is comparable to patients who were transplanted in relapse. Because of the association between MRD and relapse risk, it can be assumed, that testing for MRD before allo-HSCT may help to identify a subgroup of patients at high risk of relapse who might benefit from preemptive posttransplantation treatment. Disclosures No relevant conflicts of interest to declare.
Aim. To assess the rehospitalization data of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), to determine possible risk factors for rehospitalization, and to work out a strategy of post-transplantation follow-up for this category of patients. Materials & Methods. From 2009 to 2019 at the National Research Center for Hematology 418 patients received allo-HSCT. The final analysis included 374 patients who were discharged from hospital after allo-HSCT. The reasons for rehospitalizations of patients with allo-HSCT within 30 days after their hospital discharge were subjected to analysis. Independent risk factors for rehospitalizations were identified by the Cox model. Risk density was visually estimated within 365 days after hospital discharge with the purpose of working out the optimal strategy of post-transplantation follow-up for this category of patients. Results. The probability of rehospitalization within 30 days after hospital discharge was 30.7 % for all patients with allo-HSCT. The data assessment showed that the majority of rehospitalizations (55.7 %) were associated with infectious complications. Acute graft-versus-host disease (GVHD) during the first hospitalization, i.e. immediately after allo-HSCT during the hospital stay, proved to enhance the probability of rehospitalizations within 30 days after hospital discharge by 1.7 times compared with the patients without acute GVHD. Conclusion. The leading cause of rehospitalizations of patients with allo-HSCT within 30 days after hospital discharge was acute GVHD which occurred before, i.e. during the first hospital stay. The data obtained demonstrate the necessity of close monitoring of a patient’s status within the first 120 days after discharge from the hospital where allo-HSCT was performed.
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.
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.