Hemophagocytic Syndrome Associated with Hematologic Malignancies

Hemophagocytic syndromes may occur in patients of all age groups. Secondary HS is more frequent than primary (familial) and is usually described in patients with an underlying immune disorder. This clinicopathological entity is the result hemophagocytosis of hemopoetic cells due to activation of morphologically benign macrophages in the bone marrow. Clinical symptoms include fever, hepatosplenomegaly, severe cytopenias, dyslipidemia, and frequent coangulopathy. The prognosis is dismal. Hematologic malignancies are often involved in HS, which may present at any disease phase. Non-Hodgkin lymphomas and less frequently Hodgkin disease have been associated with HS. Lymphoma associated hamophagocytic syndrome (LAHS) accounts for 40-50% of HS where an underlying condition can be defined. NK/T and T peripheral lymphomas are responsible for 80% of LAHS. As far as B-cell lymphomas are concerned, intravascular usually present with LAHS. The pathogenesis of HS is not fully understood, but it seems to differ between T- and B-cell lymphomas. EBV is thought to have an important part in the pathogenetic procedure, since it has been detected both in Hodgkin and Non-Hodgkin lymphomas presenting with HS. Treatment decisions depend upon the underlying condition and its phase. However the most acceptable treatment option is currently immunochemotherapy followed by myeloablative stem cell transplantation

Mechanisms of blood homeostasis: lineage tracking and a neutral model of cell populations in rhesus macaques

BACKGROUND: How a potentially diverse population of hematopoietic stem cells (HSCs) differentiates and proliferates to supply more than 10(11) mature blood cells every day in humans remains a key biological question. We investigated this process by quantitatively analyzing the clonal structure of peripheral blood that is generated by a population of transplanted lentivirus-marked HSCs in myeloablated rhesus macaques. Each transplanted HSC generates a clonal lineage of cells in the peripheral blood that is then detected and quantified through deep sequencing of the viral vector integration sites (VIS) common within each lineage. This approach allowed us to observe, over a period of 4-12 years, hundreds of distinct clonal lineages. RESULTS: While the distinct clone sizes varied by three orders of magnitude, we found that collectively, they form a steady-state clone size-distribution with a distinctive shape. Steady-state solutions of our model show that the predicted clone size-distribution is sensitive to only two combinations of parameters. By fitting the measured clone size-distributions to our mechanistic model, we estimate both the effective HSC differentiation rate and the number of active HSCs. CONCLUSIONS: Our concise mathematical model shows how slow HSC differentiation followed by fast progenitor growth can be responsible for the observed broad clone size-distribution. Although all cells are assumed to be statistically identical, analogous to a neutral theory for the different clone lineages, our mathematical approach captures the intrinsic variability in the times to HSC differentiation after transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-015-0191-8) contains supplementary material, which is available to authorized users

Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond

Adoptive immunotherapy with virus-specific cytotoxic T cells (VSTs) has evolved over the last three decades as a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after solid organ or allogeneic hematopoietic cell-transplantation (allo-HCT). Since the early proof-of-principle studies demonstrating that seropositive donor-derived T cells, specific for the commonest pathogens post transplantation, namely cytomegalovirus or Epstein-Barr virus (EBV) and generated by time- and labor-intensive protocols, could effectively control viral infections, major breakthroughs have then streamlined the manufacturing process of pathogen-specific T cells (pSTs), broadened the breadth of target recognition to even include novel emerging pathogens and enabled off-the-shelf administration or pathogen-naive donor pST production. We herein review the journey of evolution of adoptive immunotherapy with nonengineered, natural pSTs against infections and virus-associated malignancies in the transplant setting and briefly touch upon recent achievements using pSTs outside this context