Hematopoietic progenitor cell content of vertebral body marrow used for combined solid organ and bone marrow transplantation

While cadaveric vertebral bodies (VB) have long been proposed as a suitable source of bone marrow (BM) for transplantation (BMT), they have rarely been used for this purpose. We have infused VB BM immediately following whole organ (WO) transplantation to augment donor cell chimerism. We quantified the hematopoietic progenitor cell (HPC) content of VB BM as well as BM obtained from the iliac crests (IC) of normal allogeneic donors (ALLO) and from patients with malignancy undergoing autologous marrow harvest (AUTO). Patients undergoing WO/BM transplantation also had AUTO BM harvested in the event that subsequent lymphohematopoietic reconstitution was required. Twenty-four VB BM, 24 IC BM-ALLO, 31 IC AUTO, and 24 IC WO-AUTO were harvested. VB BM was tested 12 to 72 hr after procurement and infused after completion of WO grafting. IC BM was tested and then used or cryopreserved immediately. HPC were quantified by clonal assay measuring CFU-GM, BFU-E, and CFU-GEMM, and by flow cytometry for CD34+ progenitor cells. On an average, 9 VB were processed during each harvest, and despite an extended processing time the number of viable nucleated cells obtained was significantly higher than that from IC. Furthermore, by HPC content, VB BM was equivalent to IC BM, which is routinely used for BMT. We conclude that VB BM is a clinically valuable source of BM for allogeneic transplantation. © 1995 by Williams & Wilkins

Evidence for engraftment of human bone marrow cells in non-lethally irradiated baboons

Background. Prior to organ harvesting, an attempt was made to modulate the donor's immune responses against prospective xenogeneic recipients by infusion of 'recipient-type' bone marrow. Methods. For this purpose, baboons conditioned with total lymphoid irradiation were given 6x108 unmodified human bone marrow cells/kg body weight with no subsequent treatment. Results. Animals survived until they were euthanized at 18 months. Using primers specific for human chorionic gonadotrophin gene, the presence of human DNA was confirmed by polymerase chain reaction in the blood of one animal for up to 18 months after cell transplantation; in the other animal, xenogeneic chimerism became undetectable in the blood at 6 months after bone marrow infusion. However, tissue samples obtained from both animals at the time they were euthanized bad evidence of donor (human) DNA. Additionally, the presence of donor DNA in individually harvested colonies of erythroid and myeloid lineages suggested that infused human bone marrow cells had engrafted across the xenogeneic barrier in both baboons. Conclusions. Bone marrow transplantation from human to baboon leads to establishment of chimerism and modulation of donor-specific immune reactivity, which suggests that this strategy could be reproducibly employed to crease 'surrogate' tolerogenesis in prospective donors for subsequent organ transplantation across xenogeneic barriers

SAPHO: has the time come for tailored therapy?

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a heterogeneous condition combining osteoarticular and cutaneous manifestations. Conventional treatments are mostly ineffective. We hereby report two patients, the first with an aggressive form of disease and the second with an incomplete response to two different anti-TNF-α agents. Both were successfully treated with tocilizumab and ustekinumab, respectively, over a long period of time. A narrative review of a biological therapy in SAPHO syndrome yielded very little information on the specific use of these agents. We highlight the advantages of personalising therapy and describe emerging promising treatments for this disease.info:eu-repo/semantics/publishedVersio

Immune status of recipients following bone marrow - Augmented solid organ transplantation

It has been postulated that the resident “passenger” leukocytes of hematolymphoid origin that migrate from whole organ grafts and subsequently establish systemic chimerism are essential for graft acceptance and the induction of donor-specific nonreactivity. This phenomenon was augmented by infusing 3 × 108 unmodified donor bone-marrow cells into 40 patients at the time of organ transplantation. Fifteen of the first 18 analyzable patients had sequential immunological evaluation over postoperative intervals of 5 to 17 months, (which included 7 kidney (two with islets), 7 liver (one with islets), and one heart recipient). The evolution of changes was compared with that in 16 kidney and liver nonmarrow controls followed for 4 to5 months. The generic immune reactivity of peripheral blood mononuclear cells (PBMC) was determined by their proliferative responses to mitogens (PHA, ConA). Alloreactivity was measured by the recipient mixed lymphocyte reaction (MLR) to donor and HLA-mis-matched third-party panel cells. Based on all 3 tests,the recipients were classified as donor-specific hyporeactive, intermediate, and responsive; patients who were globally suppressed made up a fourth category. Eight (53%) of the 15 marrow-treated recipients exhibited progressive modulation of donor-specific reactivity (3 hyporeactive and 5 intermediate) while 7 remained antidonor-responsive. In the nonmarrow controls, 2 (12.5%) of the 16 patients showed donor-specific hyporeactivity, 10 (62.5%) were reactive, and 4 (25%) studied during a CMV infection had global suppression of responsiveness to all stimuli. © 1995 by Williams and Wilkins