In contrast, immunohistochemical stains

on the core biopsy may yield more reproducibility R428 in quantitative determination of MRD. Administration of combined chemo-immunotherapy in an effort to totally eradicate MRD must be based upon an acceptable toxicity profile and the time frame for this analysis. While many advise waiting several months before examining the remission bone marrow for evidence of MRD, a recent study by Ravandi evaluated the bone marrow one month following therapy with cladribine [59]. The subsequent administration of eight weeks of rituximab was reported to produce a complete remission in 100% of the patients. It is not clear whether or not some of these patients would have achieved an MRD-negative bone marrow if adequate time had elapsed before analysis. Despite caution from the authors that this combined approach to

chemo-immunotherapy should not be considered standard of care, the published results may be used to justify the administration of eight weeks of immunotherapy in many non-protocol circumstances. In addition to the additional cost of the immunotherapy, there may be added immunosuppression as a result of this combined chemo-immunotherapy. While this combination Vorinostat concentration of chemoimmunotherapy has been utilized in patients who relapsed following an initial purine analog therapy, it is unclear if this combination is justified as an actual front-line therapy. Therefore, there is ample opportunity for continued clinical research to refine our best therapeutic approach. Kreitman and colleagues at NCI are investigating whether a purine analog and immunotherapy with an anti-CD20 antibody are better administered as combined or sequential therapy. It is unclear how many doses of the monoclonal antibody are needed for an optimal response or even whether or not rituximab is the monoclonal antibody of choice. Considering the successes

of newer anti-CD20 monoclonal antibodies (for example, the glycoengineered anti-CD20 obinutuzumab [60]) in similar diseases like chronic lymphocytic leukemia and non-Hodgkin lymphoma, additional investigation with these agents in HCL is certainly needed. Novel biologic therapies show great promise and are areas for further evaluation in the optimization of therapy [61]. Liothyronine Sodium The rarity of this form of leukemia and the tendency for these patients to be treated in a non-protocol setting confound the investigations. Consequently, efforts are underway to develop global protocols to address these questions. Inter-institutional collaboration will be required to answer such questions in this rare disease (e.g., perhaps through the Hairy Cell Leukemia Research Foundation). For patients who relapse following the standard therapy with classic hairy cell leukemia or for those rare patients with the variant of this disease, there is an urgent need to enter patients onto organized clinical trials.