Introduction:With an increasing number of allogeneic hematopoietic cell transplantations (allo-HCT) bloodstream infections (BSI) are still among the most common and serious complications. This study aimed to analyze the incidence, etiology, risk factors, and outcomes of pre-engraftment BSI after the first and the second allo-HCT.
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.
Objective. To analyze treatment results of 172 patients with acute myeloid leukemia (AML) aged 18-60 years in National Medical Research Center for Hematology of MHRF. Materials and methods. Inductive and consolidation program for 139 (80%) patients was based on a standardized protocol: 4 courses “7+3” with different anthracycline use (2 courses of daunorubicin, idarubicin, mitoxantrone) and continuous use of cytarabine on the second inductive course. In 20% of patients cytarabine courses at the dose of 1 g/m2 2 times a day for 1-3 days combined with idarubicin and mitoxantrone were used as two consolidation courses. Allogenic bone marrow transplantation was performed in the first complete remission (CR) period in 40% of patients. Results. The frequency of CR achievement in all patients was 78.6%, refractory forms were observed in 13.9% of patients, early mortality - in 7.5% of patients. Seven-year overall survival (OS) rate was 40.7%, relapse free survival (RFS) - 43.2%. When estimating effectiveness depending on cytogenetic risk group it was demonstrated that 5-year OS and RFS in patients with translocation (8; 21) cannot be considered as satisfying, it accounted for 50 and 34%, respectively. At the same time in patients with 16th chromosome inversion (inv16) these characteristics accounted for 68.6 and 63.5%. Acquired results forced reconsidering of the consolidation program in AML patients of this subgroup. The median time to allogenic blood stem cells transplantation (allo-BSCT) in patients with first CR was 6.5 months that was taken as a reference point in landmark analysis of patients in whom allo-BSCT was not performed. Landmark analysis showed that in AML patients of favorable prognosis group allo-BSCT does not significantly reduce the probability of relapse (0 and 36%) and does not influence RFS (33 and 64%). In patients of border-line and poor prognosis allo-BSCT significantly reduces relapse probability (26 and 66%; 20 and 100%) and significantly increases a 7-year RFS (68.7 and 30%; 45.6 and 0%). Allo-BSCT also results in significant RFS increase and reduces the probability of relapse (25 and 78%) in patients in whom CR was achieved only after the second induction course. At the same time allo-BSCT does not influence patients who achieved CR after the first treatment course: 55 and 50%. Conclusion. Multivariate analysis showed that cytogenetic risk group (HR=2.3), time of CR achievement (HR=2.9), and allo-BSCT transplantation (HR=0.16) are independent factors for disease relapse prognosis after achieving CR.
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