Hematopoietic stem cell transplantation in children with Griscelli syndrome: A single-center experience.

GS2 is a rare autosomal recessive disease characterized by hypopigmentation, variable immunodeficiency with HLH. HSCT is the only curative treatment for GS2. We analyzed the outcome of 10 children with GS2 who underwent HSCT at our center between October 1997 and September 2013. The median age of the patients at transplant was 13.5 months (range, 6-58 months). All of the patients developed HLH before HSCT and received HLH 94 or HLH 2004 protocols. Donors were HLA-identical relatives in 8 patients, HLA-mismatched relatives in 2 patients. Engraftment was achieved in all except one patient. None of the patients developed acute GVHD. Chronic GVHD occurred in one and veno-occlusive disease occurred in four patients. Eight of the patients are under remission without any neurologic sequelae-median time of disease-free survival is 92.4 months. The present study shows successful transplant outcome without long-term neurologic sequelae in patients with GS2 who underwent HSCT from HLA-related donors.

Selective depletion of a minor subpopulation of B-chronic lymphocytic leukemia cells is followed by a delayed but progressive loss of bulk tumor cells and disease regression.

Cancer precursor/progenitor cells may initiate and sustain the growth of tumors, but evidence for their existence in human disease is indirect, relying on their in vitro properties and animal models. More directly, specific elimination of these rare cells from cancer patients should produce a delayed but progressive disappearance of differentiated malignant progeny. Here, we describe selective eradication of a putative precursor population in a patient with B-cell chronic lymphocytic leukemia, followed 6 months later by a progressive loss of mature tumor cells without further treatment. This outcome supports the presence of a rare population of precursor/progenitor cells in human malignancies, and suggests benefit from their removal.

Stem cell transplantation in childhood non-Hodgkin's lymphomas.

Despite the high cure rates achieved with intensified primary therapies for childhood non-Hodgkin's lymphomas (NHL), the prognosis for children with relapsed or refractory disease is poor. Optimal treatment for this group remains a challenge. Dose intensification followed by stem cell transplantation has been used in these circumstances and may provide a curative treatment option for these patients, but the number of children treated using this approach is relatively small and its effectiveness has been difficult to judge. Moreover, the limited experience is insufficient to define the patient most likely to benefit from transplantation. Likewise, the selection of autologous or allogeneic transplantation and the optimal conditioning regimen are debated. We summarize the current experience for stem cell transplantation in childhood NHL and offer our recommendations.

Cellular immunotherapy of cancer.

Standard therapies for many common cancers remain toxic and are often ineffective. Cellular immunotherapy has the potential to be a highly targeted alternative, with low toxicity to normal tissues but a high capacity to eradicate tumor. In this chapter we describe approaches that generate cellular therapies using active immunization with cells, proteins, peptides, or nucleic acids, as well as efforts that use adoptive transfer of effector cells that directly target antigens on malignant cells. Many of these approaches are proving successful in hematologic malignancy and in melanoma. In this chapter we discuss the advantages and limitations of each and how over the next decade investigators will attempt to broaden their reach, increase their efficacy, and simplify their application.

Overview of gene therapy clinical progress including cancer treatment with gene-modified T cells.

It is now twenty years since the first legal gene transfer studies were approved, and there has been considerable disappointment in the slow rate of progress that followed the initial studies. Gradually, however, as the limitations of available vectors are acknowledged and overcome, and with advances in our understanding of the molecular and cell biology of genetic diseases and of cancer, unequivocal successes are now being reported. In this paper we describe the remaining major roadblocks to successful gene therapy and outline approaches to overcome them. We also illustrate how genetically modified immune system cells are already being used for the effective treatment of hematological and other malignancies, and how these approaches are being modified so that they can be effective in treating a broader range of malignancies.