Frequency of Infectious Agents after Bone Marrow Transplantation in Various Regions of Iran (2001 - 2017): A Systematic Review

Context: Infections are a major cause of disease and mortality in transplant recipients. Despite the studies conducted in Iran, no comprehensive and general research is available in this area. The present study aimed to determine the frequency of infectious agents in patients after bone marrow transplantation in Iran. Method: In this systematic review, relevant studies were selected based on type and objective, and data were collected from the articles published in Iran regarding the frequency of infectious agents after bone marrow transplantation in different regions of Iran. The studies were collected using systematic search methods. Results: In total, 11 studies were identified regarding infectious agents after bone marrow transplantation. Six studies were conducted in Tehran, three studies were performed in Shiraz, and Mashhad and Semnan provinces were the locations of two separate studies. Most of the case studies identified viral agents (54.5%; n = 6), followed by fungal infectious agents (27.3%; n = 3) and bacterial agents (18.2%; n = 2). Gram-positive bacteria (bacterial agents), cytomegalovirus (viral agents), and Candida and Aspergillus (fungi) had the highest frequency after bone marrow transplantation. Conclusions: According to the results, viral, fungal, and bacterial infectious agents were respectively most frequent in patients receiving bone marrow transplants. Gram-positive bacteria (bacterial agents), cytomegalovirus (viral agents), and Candida and Aspergillus (fungi) had the highest frequency after bone marrow transplantation.

To the 30th anniversary of the first children’s department of bone marrow transplantation in Russia

The article is devoted to the history of the creation of the bone marrow transplantation department and the development of pediatric oncology in the Russian Federation.

Donor T-Cell Repertoire Profiling in Recipient Lymphoid and Parenchyma Organs Reveals GVHD Pathogenesis at Clonal Levels After Bone Marrow Transplantation in Mice

The diversity and composition of T-cell receptor (TCR) repertoire, which is the result of V, (D), and J gene recombination in TCR gene locus, has been found to be implicated in T-cell responses in autoimmunity, cancer, and organ transplantation. The correlation of T-cell repertoire with the pathogenesis of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation remains largely undefined. Here, by utilizing high-throughput sequencing of the genes encoding TCRβ-chain, we comprehensively analyzed the profile of T-cell repertoire in recipient lymphoid and GVHD target organs after bone marrow transplantation (BMT) in mice. In lymphoid organs, TCR diversity was narrowed, accompanied with reduced numbers of unique clones while increased accumulation of dominant clones in allogeneic T cells compared to syngeneic T cells. In an individual allogeneic recipient, donor-derived TCR clones were highly overlapped among tissue sites, and the degree of overlapping was increasing from day 7 to 14 after allogeneic BMT. The top clones in peripheral blood, gut, liver, and lungs were highly mutually shared in an allogenic recipient, indicating that blood has the potential to predict dominant clones in these GVHD target organs. T cells in GVHD target organs from allogeneic recipients had fewer overlapped clones with pre-transplant donor T cells compared to those from syngeneic recipients. Importantly, the top 10 clones in allogeneic recipients were not detectable in pre-transplant donor T cells, indicating clonal expansion of rare rearrangements. Interestingly, even starting from the same pool of donor repertoires, T cells had very few overlapped clones between each allogeneic recipient who developed completely different dominant clones. We were only able to trace a single clone shared by three replicate allogeneic recipients within the top 500 clones. Although dominant clones were different among allogeneic recipients, V26 genes were consistently used more frequently by TCR clones in allogeneic than syngeneic recipients. This is the first study to extensively examine the feature of T-cell repertoire in multiple lymphoid and parenchyma organs, which establishes the association between T-cell activation and GVHD pathogenesis at the level of TCR clones. Immune repertoire sequencing-based methods may represent a novel personalized strategy to guide diagnosis and therapy in GVHD.

FK506 and Lactobacillus Acidophilus Ameliorate Acute Graft-Versus-Host Disease by Modulating the T Helper 17/Regulatory T-Cell Balance

Background Graft-versus-host disease (GvHD) is critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbiome and the host immune system, potentially leading to dysbiosis and inflammation, and may affect immune function and bone marrow transplantation. The intestinal microbiome is a target for the development of novel therapies for GvHD. Lactobacillus species are in widely used supplements to induce production of antimicrobial and anti-inflammatory factors. Methods We determined the effect of the combination of Lactobacillus acidophilus and FK506 on GvHD following major histocompatibility complex-mismatched bone marrow transplantation. Results The combination treatment suppressed IFN-γ and IL-17-producing T cell differentiation, but increased Foxp3+Treg differentiation and IL-10 production. Also, the combination treatment and combination treated-induced Treg cells modulated the proliferation of murine alloreactive T cells in vitro. Additionally, the combination treatment upregulated Treg-related genes—Nt5e, Foxp3, Ikzf2, Nrp1 and Itgb8—in murine CD4+-T cells. The combination treatment also alleviated GvHD clinically and histopathologically by controlling the effector T cell and Treg balance in vivo. Moreover, the combination treatment decreased Th17 differentiation significantly and significantly upregulated Foxp3 and IL-10 expression in peripheral blood mononuclear cells from healthy controls and liver transplantation (LT) patients. Conclusions Therefore, the combination of L. acidophilus and FK506 is effective and safe for patients undergoing allogeneic hematopoietic stem cell transplantation.

Brazilian Consensus Guidelines for Hematopoietic Stem Cell Transplantation - Inborn errors of metabolismo

Hematopoietic stem cell transplantation (HSCT) has the potential to cure a significant proportion of patients with malignant and nonmalignant diseases. The main rationale for HSCT in inborn errors of metabolism (IEM) is based on correcting the decreases enzymes by the donor cells within and outside the intravascular compartment. In this article, Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation and Cellular Therapy (SBTMO) provides a review of HSCT indications in IEM.