The alloreactive potency of the hematopoietic stem cell graft provides powerful anticancer activity. Unfortunately, the potential for harm (by graft-versus-host disease [GVHD]) is often as strong as the potential for good. The measures used to control GVHD, such as steroids and antithymocyte globulin, often seem like elephant guns causing similar harmful effects (toxicity and vulnerability for infection) as the GVHD itself, and they rob much of the anticancer effects of the donor graft. GVHD is indeed the thorniest problem of allogeneic hematopoietic cell transplantation (HCT).
The myelodysplastic syndromes (MDS) have often been called the poster child for apoptosis gone awry: in some cases death (to hematopoietic progenitors) comes too infrequently, in other cases it comes too readily. The quest to better understand its basis and to translate this understanding into therapeutics is only beginning, but already several therapies have emerged and others are in development. For now, there is only one curative therapy for MDS: hematopoietic cell transplantation (HCT).
Invasive fungal infections have become the chief infectious threat to allogeneic hematopoietic cell transplant (HCT) recipients. New drugs such as the echinocandins (caspofungin, micafungin, and anidulafungin) and the extended-spectrum azoles (itraconazole, voriconazole, and posaconazole) offer more effective and safer options today. Although these potent antifungal agents make treatment prospects better, there still is considerable risk for death from Candida, Aspergillus, and other mold infections.
This Grand Rounds in Hematology monograph, Improving the Treatment of Hematologic Malignancies:
Chronic Lymphocytic Leukemia, is based on our selection of key abstracts from the ASH meeting in December 2006 and related publications in the following areas of chronic lymphocytic leukemia (CLL): new advances in prognosis, approaches to frontline therapy including the use of chemoimmunotherapies, management of the relapsed refractory patient, and, finally, novel drugs for the treatment of CLL.
For years, considerable attention was devoted to just getting it right: figuring out how to do a transplantation as safely as possible and preventing acute complications during the first 100 days from unraveling the effort. Tremendous advances in transplantation practice have made this therapy safer and outcomes have improved. In recent years, attention has shifted increasingly to other important considerations.
Management of myelodysplastic syndrome has been disappointing for years. The mainstay approach was only supportive care. A malaise settled all around. Today there are new Food and Drug Administration cleared therapies, and novel agents are on the horizon. True progress has been small to date, but with the number of new therapies and new classes of agents undergoing study, the future is hopeful.