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  • 1
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5648-5648
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4562-4562
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 3
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1987-1987
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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