Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. Each patient received sequential transplants of αβ T-cell-depleted and CD19 B-cell-depleted haploidentical hematopoietic stem cells and a kidney from the same donor. Full donor hematopoietic chimerism and functional ex vivo T-cell tolerance was achieved, and the patients continued to have normal renal function without immunosuppression at 22 to 34 months after kidney transplantation. (Funded by the Kruzn for a Kure Foundation.).

Sequential Stem Cell-Kidney Transplantation in Schimke Immuno-osseous Dysplasia.

Pediatric organ failure and transplant populations face significant risks of morbidity and mortality. The risk of organ failure itself may be disproportionately higher among pediatric oncology patients, as cancer may originate within and/or metastasize to organs and adversely affect their function. Additionally, cancer directed therapies are frequently toxic to organs and may contribute to failure. Recent reports suggest that nearly half of providers find it difficult to provide prognostic information regarding organ failure due to unknown disease trajectories. Unfortunately, there is a lack of uniform methodology in detecting the early symptoms of organ failure, which may delay diagnosis, initiation of treatment and hinder prognostic planning. There remains a wide array of outstanding scientific questions regarding organ failure in pediatrics but emerging data may change the landscape of prognostication. Liquid biopsy, in which disease biomarkers are detected in bodily fluids, offers a noninvasive alternative to tissue biopsy and may improve prompt detection of organ failure and prognostication. Here, we review potential liquid biopsy biomarkers for organ failure, which may be particularly useful among pediatric oncology patients. We synthesized information from publications obtained on PubMed, Google Scholar, clinicaltrials.gov, and Web of Science and categorized our findings based on the type of biomarker used to detect organ failure. We highlight the advantages and disadvantages specific to each type of organ failure biomarker. While much work needs to be done to advance this field and validate its applicability to pediatric cancer patients facing critical care complications, herein, we highlight promising areas for future discovery.

/pdf/the-organ-trail-a-review-of-biomarkers-of-organ-failure-5e6956zp14.pdf

The Organ Trail: A Review of Biomarkers of Organ Failure.

HLA matching, transplantation technique, or underlying disease greatly influences the probability of long-term transplantation success. It has been hypothesised that genetic variation affecting antigen presentation also contributes to the outcomes of both solid organ transplantation and allogeneic haematopoietic stem cell transplantation (AHSCT). Those genes, along with those responsible for innate and adaptive immunity, have become targets of investigation. In this review, we focus on the role of CTLA4 in the process of acute graft rejection and summarise the progress in our understanding of its role in predicting the outcome. We present the results of the latest studies investigating the link between CTLA4 gene variability and AHSCT, as well as organ transplantation outcomes. While some studies found a link between +49 A/G and −318 C/T and transplantation outcomes, comprehensive meta-analyses have failed to present any association. The most recent field reviews suggest that the −1772 T/C (rs733618) CC genotype is weakly associated with a lower risk of acute graft rejection, while +49 A/G might be clinically meaningful when investigated in the context of combinations with other polymorphisms. Studies verifying associations between 12 CTLA4 gene SNPs and AHSCT outcomes present inexplicit results. Some of the most commonly studied polymorphisms in this context include +49 A/G (rs231775) and CT60 A/G (rs3087243). The results signify that, in order to understand the role of CTLA4 and its gene polymorphisms in transplantology, further studies must be conducted.

The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation.

We report a child with Fanconi anemia who, after hematopoietic stem cell transplantation (HSCT) complicated by acute graft-versus-host disease (GVHD), underwent orthotopic liver transplantation (OLT). Approximately 1 month after OLT, the presence of third-party genetic material from the liver donor was noted and in the next few weeks, the chimerism assessment revealed 100% liver donor leukocytes in the peripheral blood. The rapidly progressing GVHD with gut involvement resulted in patient’s death 6 months after OLT. The liver can act as a clinically significant source of hematopoietic stem cells, and the liver donor’s young age must be emphasized as potentially predisposing to this phenomenon. Transfer of OLT hematopoietic stem cells may not have clinical significance unless the patient is not immunocompetent or develops liver-transplantation associated GVHD, that can result in lymphocyte mediated elimination of original hematopoiesis. Patients with preexisting immunity disorder (such as primary or secondary immunodeficiency) might require intensified immunosuppressive therapy in peritransplant period as a prevention of liver-transplantation associated GVHD. Close monitoring of hematopoietic chimerism after OLT is warranted in patients at risk, because cytopenia or OLT hematopoiesis can reflect subclinical GVHD and further studies are necessary to elucidate this phenomenon.

Case Report: Liver as a Source of Hematopoietic Stem Cells After Liver Transplantation Following Hematopoietic Stem Cell Transplantation

Kidney Disease Following Hematopoietic Stem Cell Transplantation.

Solid organ transplantation after hematopoietic stem cell transplantation in childhood : A multicentric retrospective survey

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Solid organ transplantation after hematopoietic stem cell transplantation in childhood : A multicentric retrospective survey