BackgroundBloodstream infections (BSI) remain a frequent complication during the pre-engraftment period after hematopoietic stem cell transplantation (HSCT), resulting in high mortality rates. This study evaluated risk factors for mortality in hematopoietic stem cell transplant recipients with BSI in the pre-engraftment period.MethodsThis prospective case control study was performed at the Center of Hematology and Bone Marrow Transplantation in Minsk, Republic of Belarus. Data relating to patient age and gender, date and type of transplantation, conditioning chemotherapy regimen, microorganisms isolated from blood, and antibacterial therapy were prospectively collected from all hematopoietic stem cell recipients with microbiologically proven cases of BSI in the pre-engraftment period. The primary outcome was all-cause 30-day mortality after onset of febrile neutropenia.ResultsA total of 135 adult patients with microbiologically proven BSI after HSCT were studied, with 65.2% of cases caused by gram-negative microorganisms and 21.5% by non-fermenting bacteria. Inadequate empiric antibacterial therapy and isolation of carbapenem-resistant non-fermenting gram-negative bacteria (Acinetobacter baumannii and Pseudomonas aeruginosa) were independently associated with increased all-cause 30-day mortality in these patients.ConclusionThe risk factors for mortality in adult patients with BSI in the pre-engraftment period after HSCT were inadequacy of empirical antibacterial therapy and isolation of carbapenem-resistant A. baumannii or P. aeruginosa.

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Presepsin may be recommended in adult patients with suspected gram-negative BSI after HSCT as a possible additional supplementary test with a cut-off value of 218pg/mL. PCT is inferior to presepsin in terms of sensitivity and specificity, but still shows a good quality of diagnostic value with an optimal cut-off value of 1.5ng/mL. CRP showed an average diagnostic value with low sensitivity (40%) and should not be routinely recommended as a biomarker in adult patients with suspected BSI after HSCT in a condition of high prevalence of gram-negative pathogens.

The role of MSCs in infection prevention and treatment is still discussed in transplant and hematological patients. The spectrum and risk factors for infections after MSCs transplantation in patients with acute GVHD have not been studied before. To determine the risk factors and spectrum of infectious complications in patients received mesenchymal stem cell transplantation as a treatment for acute GVHD. A prospective observational study was performed to evaluate the risk factors and characteristics of infectious complications after MSCs transplantation in adult patients having acute GVHD. Thirty-four episodes of MSCs transplantation in patients with acute GVHD after allogeneic HSCT were enrolled in the study. MSCs were given at a median dose of 1.32 (interquartile range 0.87-2.16) mln cells/kg per infusion at 91 days (interquartile range 31-131 days) after HSCT. Data relating to age, gender, date, and type of transplantation, characteristics of MSCs, infectious agents, and antimicrobial therapy and prevention regimens were prospectively collected in all of the enrolled patients. The episode of proven infectious complication was set as a primary outcome. There were totally 68 patients with acute GVHD in the study; among them there were 34 cases of MSCs transplantation performed. Among the registered infectious episodes were viral infections (CMV-associated disease, EBV-associated disease), invasive pulmonary aspergillosis, bacterial bloodstream infections, and pneumonia. MSCs transplantation has shown no statistically significant association with risk of infectious complications in patients with acute GVHD in a performed multivariate analysis. Among the most frequent infections in acute GVHD, we have described CMV, invasive aspergillosis, and bacterial infections (bloodstream infections or pneumonia). Among risk factors for infectious complications in patients with acute GVHD with/without MSCs transplantation are progression of main disease and neutropenia below 500 cells/mm (for aspergillosis) and unrelated HSCT in the past history and progression of main disease (for bacterial bloodstream infections and pneumonia).

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The Bone Marrow Transplantation Program in Belarus was founded in 1992, and in 1993, a Bone Marrow Transplantation Centre was created in Minsk. From February 1994 to April 1996,19 allogeneic bone marrow, 16 autologous bone marrow and 10 autologous peripheral blood stem cell transplantations were performed. Reasons for transplantation included chronic myeloid leukemia, multiple myeloma, severe aplastic anemia, acute myeloid leukemia, acute lymphoblastic leukemia, progressive myelofibrosis, Hodgkin's disease, non‐Hodgkin's lymphoma, and neuroblastoma. Among the patients were two liquidators involved in the Chernobyl cleanup activity, both of whom underwent allogeneic bone marrow transplantation. A variety of ablative preparative regimens were used, and blood progenitor cells were mobilized by treatment with Cytoxan and granulocyte colony‐stimulating factor. Therapy‐related deaths resulted from graft‐versus‐host disease, septic shock, veno‐occlusive disease bleeding and intestinal pulmonary fibrosis. Because the transplantation procedures were carried out on people who continued to be exposed to low‐level irradiation, the post‐transplantation period included a conservative strategy for prevention of graft‐versus‐host disease. There was nothing unusual about the post‐transplantation period, although uncertainty about the continuing radiation dose should be taken into account when interpreting these data. Stem Cells 1997; 15(suppl 2): 299‐303

Background:In the context of significant advances in the treatment of hematological diseases using the method of autologous hematopoietic stem cell transplantation (auto‐HSCT), the number of patients requiring early vaccination against pneumococcal infection increases worldwide. Current guidelines indicate the early initiation of pneumococcal vaccination starting from 3 months after HSCT. Still, the topical issue is the determination of the earliest optimal dates for the start of vaccination after transplantation, taking into account the dynamics of immunological recovery.Aims:The aim of this study was to determine the optimal timeline for the onset of vaccination with conjugated pneumococcal vaccine in patients with multiple myeloma after auto‐HSCT.Methods:The immune response to the conjugated pneumococcal vaccine is based on the T‐dependent (CD4+) activation of B‐cells, what was taken into account when estimating the timing of immune reconstitution after auto‐HSCT in candidates for vaccination.An immunological study using flow cytometry was performed in 37 adult patients with multiple myeloma prior to the auto‐HSCT procedure, as well as on days +30, +60, +90, +180 after transplantation.Results:After auto‐HSCT, the level of naive B‐cells returns to its original value by the 60th day from transplantation (Kruskal‐Wallis test 41.97; P < 0.001), shown on Fig. 1. At the same time, the level of CD4 + cells did not fall below 200 cells/μl starting from day +30, what indicates the effectiveness of early vaccination with T‐dependent vaccines in this category of patients with immunosuppression. Dendritic cells (DC1 and DC2) are restored in parallel by the 30th day from auto‐HSCT (Kruskal‐Wallis test 25.78; P <0.001 for DC‐1 cells and Kruskal‐Wallis test 11,17; P <0.025, respectively), what confirms the basis for the early vaccination with conjugated pneumococcal vaccines in this category of patients.Summary/Conclusion:The obtained data allows planning the introduction of the first dose of the conjugated pneumococcal vaccine 60 days after autologous HSCT, with the perspective of introducing an individualized vaccination calendar based on immunological parameters. It is also necessary to further implement immunization programs for immunocompromised patients, especially in hematology and cancer setting with the participation of a multidisciplinary team of specialists.image

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