We have assessed autologous stem cell transplantation after treatment with fludarabine in previously untreated patients with chronic lymphocytic leukemia (CLL). This study is the first to enroll previously untreated patients and follow them prospectively. The initial response rate to fludarabine was 82% (94 of 115 patients). Stem cell mobilization was attempted in 88 patients and was successful in 59 (67%). Overall 65 of 115 patients (56%) entered into the study proceeded to autologous transplantation. The early transplant-related mortality rate was 1.5% (1 of 65 patients). The number of patients in complete remission after transplantation increased from 37% (24 of 65) to 74% (48 of 65), and 26 of 41 patients (63%) who were not in complete remission at the time of their transplantation achieved a complete remission after transplantation. The 5-year overall and disease-free survival rates from transplantation were 77.5% (CI, 57.2%-97.8%) and 51.5% (CI, 33.2%-69.8%), respectively. None of the variables examined at study entry were found to be predictors of either overall or disease-free survival. Sixteen of 20 evaluable patients achieved a molecular remission on a polymerase chain reaction (PCR) for immunoglobulin heavy-chain gene rearrangements in the first 6 months following transplantation. Detectable molecular disease by PCR was highly predictive of disease recurrence. IntroductionChronic lymphocytic leukemia (CLL) is characterized by the gradual accumulation of small mature B lymphocytes in the blood, bone marrow, and lymphoid organs. Alkylating agents such as chlorambucil, either alone or with steroids, have traditionally been the mainstay of treatment for patients with advanced stage disease, 1 but do not appear to improve overall survival. Combination chemotherapy, 1-5 particularly with the addition of an anthracycline, 3,6,7 has also been effective at palliating disease. More recently the nucleoside analogues, in particular fludarabine, have induced good responses both in previously untreated patients 7-9 and in patients who are refractory to standard therapy. [10][11][12] When fludarabine is used to treat previously untreated patients, it is demonstrably better than chlorambucil, 9 and at least as effective as CHOP 7 (cyclophosphamide, hydroxydaunorubicin, Oncovin [vincristine], prednisone) in terms of responses obtained. Evidence indicates that the duration of remissions induced by fludarabine in previously untreated patients is longer, 9,12 although this has not yet been shown to translate into a benefit in overall survival. Fludarabine is also an effective agent when used as second-line therapy 11,12 and is more effective in this setting than combination chemotherapy such as CAP (cyclophosphamide, Adriamycin [doxorubicin], prednisolone). 7 Recently there has been considerable interest in antibody-based approaches [13][14][15][16][17][18][19] both alone and in combination. These can result in excellent responses in some patients, with a proportion becoming negative for molecular markers for CLL. 20 A ...

SummaryInhibition of histone deacetylases may be an important target in patients with myeloproliferative neoplasms. This investigator-initiated, nonrandomized, open-label phase II multi-centre study included 63 patients (19 essential thrombocythaemia, 44 polycythaemia vera) from 15 centres. The primary objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by European Leukaemia Net. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention-to-treat response rate of 35% was identified. Pruritus was resolved [19% to 0% (P = 0Á06)] and the prevalence of splenomegaly was lowered from 50% to 27% (P = 0Á03). Sixty-five per cent of the patients experienced a decrease in JAK2 V617F allele burden (P = 0Á006). Thirty-three patients (52% of patients) discontinued study drug before end of intervention due to adverse events (28 patients) or lack of response (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies.