Editorial [Hot Topic: Advances in Hematopoietic Stem Cell Transplantation (Executive Editor: David A. Jacobsohn) ]

Hematopoietic stem cell transplantation (HSCT) has been established as a curative procedure for malignant diseases such as leukemia and non-malignant diseases such as severe combined immunodeficiency. Because HSCT carries significant risk of morbidity and mortality, it has up to now been reserved for patients with very high-risk diseases, where the chance of mortality is unacceptable without doing a transplant. The major barriers to successful HSCT are organ toxicity from the high-dose chemotherapy (and/or radiotherapy) preparative regimen, graft-versus-host disease, and infection. Organ toxicity occurs early, generally a few weeks into transplant. Patients at higher risk are the older ones, and the more heavily pre-treated ones. An example of organ toxicity that occurs within the first three weeks of HSCT is veno-occlusive disease (VOD) of the liver. Patients have hyperbilirubinemia, ascites, weight gain, and tender hepatomegaly. When accompanied with additional organ toxicity, the survival after this complication is close to 10%. This complication is clearly associated with intensity of the preparative regimen and/or intensity of prior therapy. The last 10 years have witnessed a number of novel regimens that in general are very immunosuppressive but less myeloablative. The idea is to rely, for the eradication of malignancy, more on the graft-versus-tumor effect from the hematopoietic stem cells and less on the preparative chemotherapy. By doing this, one may have less upfront morbidity and mortality, and thus may be able to transplant older, sicker patients that were not candidates for transplant in the past. There have been successes already with certain diseases using novel regimens, and these are described in more detail by Lekakis et al. [1]. Given that busulfan is one of the key drugs used in transplant, Russell et al. [2] discuss its implications in therapeutic monitoring of this drug. Busulfan levels that are too high are associated with more organ toxicity whereas lower levels are associated with more relapse. Therefore, careful monitoring of this drug is essential now in the transplant setting. In the last decade, a lot of the HSCT collections from related or unrelated donors have shifted from bone marrow harvest to peripheral blood stem cells (PBSC). PBSC collections can be done in the clinic and without sedation to the healthy donor. PBSC is also associated with faster engraftment for the recipient but also a higher risk of chronic graft-versus-host disease (GVHD). Because PBSC is such an important method of collection now, Pusic et al. [3] discuss the different agents, either available or under investigation, for mobilization of these cells prior to collection. These agents also may have a role posttransplant in shortening time to engraftment. Once engraftment occurs, GVHD is a big concern. GVHD is essentially donor cells recognizing foreign tissues, generally skin, liver, and GI tract in the acute form. The risk of acute and chronic GVHD is higher in older patients and is higher with increasing degree of HLA mismatch. Chronic GVHD can last for many years and lead to significant disability and poor quality of life. Because GVHD can be associated with major morbidity as well as mortality, research is desperately needed in finding both therapies for prophylaxis and treatment of both acute and chronic GVHD. Cutler et al. [4] and Bolanos-Meade et al. [5] bring us up to date on the standard and investigational approaches in acute and chronic GVHD, respectively. Many of these therapies for GVHD are associated with signification complications. Both organ toxicity (e.g. renal insufficiency) and major immunosuppression leading to infections are commonplace. Therefore, novel, less toxic, approaches are being looked at to treat and prevent GVHD. One of these is extracorporeal photopheresis (ECP), which relies on ex vivo treatment of lymphocytes with UV rays, leading to apoptosis and shifting the balance more towards immune tolerance rather than severe immunosuppression. Schneiderman et al. [6] brings us up to date on novel, non-pharmacologic, methods to treat and/or prevent GVHD which include ECP and mesenchymal stem cells (MSC). Finally, infectious complications deserve major attention. The more intensive the therapy to prevent or treat GVHD, the higher the likelihood of infections we encounter. Because our therapies cause profound lymphopenia, fungal and viral are the most worrisome infections. The last few years have witnessed an incredible growth to the armamentarium of both monitoring and treating these infections. For example, it is now standard-of-care to follow CMV viral copies in the blood and treat preemptively, which has led almost to disappearance of CMV disease. Anderson et al. [7] discuss novel approaches with viruses and Almyroudis et al. [8] discuss novel approaches with fungi.