Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL.

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Myelodysplastic syndromes (MDSs) are a group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis and peripheral blood cytopenias. Lenalidomide has dramatic therapeutic effects in patients with low-risk MDS and a chromosome 5q31 deletion, resulting in complete cytogenetic remission in >60% of patients. The molecular basis of this remarkable drug response is unknown. To gain insight into the molecular targets of lenalidomide we investigated its in vitro effects on growth, maturation, and global gene expression in isolated erythroblast cultures from MDS patients with del(5)(q31). Lenalidomide inhibited growth of differentiating del(5q) erythroblasts but did not affect cytogenetically normal cells. Moreover, lenalidomide significantly influenced the pattern of gene expression in del(5q) intermediate erythroblasts, with the VSIG4, PPIC, TPBG, activin A, and SPARC genes up-regulated by >2-fold in all samples and many genes involved in erythropoiesis, including HBA2, GYPA, and KLF1, down-regulated in most samples. Activin A, one of the most significant differentially expressed genes between lenalidomide-treated cells from MDS patients and healthy controls, has pleiotropic functions, including apoptosis of hematopoietic cells. Up-regulation and increased protein expression of the tumor suppressor gene SPARC is of particular interest because it is antiproliferative, antiadhesive, and antiangiogenic and is located at 5q31-q32, within the commonly deleted region in MDS 5q؊ syndrome. We conclude that lenalidomide inhibits growth of del(5q) erythroid progenitors and that the up-regulation of SPARC and activin A may underlie the potent effects of lenalidomide in MDS with del(5)(q31). SPARC may play a role in the pathogenesis of the 5q؊ syndrome.gene expression profiling ͉ myelodysplastic syndromes ͉ microarray ͉ erythropoiesis ͉ osteonectin

We recently reported that Swedish V H 3-21-using chronic lymphocytic leukemia (CLL) patients showed restricted immunoglobulin gene features and poor prognosis despite V H mutation status. To investigate this further, we analyzed the V H and V L gene rearrangements in 90 V H 3-21 ؉ patients from Sweden, Germany, Italy, United States, Finland, and Australia and correlated these data with survival and other prognostic markers. Sixty-three percent exhibited mutated V H genes and 37% unmutated V H genes. Fifty (56%) patients displayed a short and homologous heavy-

BACKGROUNDConventional interferon‐α (IFN) is an effective treatment for patients with myeloproliferative disorders. However, many patients discontinue therapy because of side effects.METHODSIn this 24‐month, Phase II feasibility study of pegylated interferon α‐2b (PEG‐IFN) treatment, a starting dose of 0.5 μg/kg per week was received by 21 patients with polycythemia vera (PV) and 21 patients with essential thrombocythemia (ET). The treatment objective, a complete platelet response (CR), was a platelet count <400 × 109/L in symptomatic patients and <600 in asymptomatic patients. Neutrophil polycythemia rubra vera‐1 (PRV‐1) messenger RNA expression was analyzed prior to and during therapy. Quality of life (QoL) was investigated by using the European Organization for Research and Treatment of Cancer QLQ‐C30 questionnaire.RESULTSAt 6 months, 29 of 42 patients (69%) had achieved a CR after a median of 83 days. The CR rate was not related to diagnosis, gender, or previous therapy. Nineteen patients completed the planned 2‐year treatment in CR. No thromboembolic or bleeding complications were observed. Phlebotomy requirements were reduced in the majority of patients with PV. Five of 14 patients (36%) who initially were positive for PRV‐1 achieved normalized PRV‐1 expression under PEG‐IFN treatment. Side effects were the cause of therapy failure in 16 of 23 patients. However, only 8 of 19 patients reported any side effects at 2 years. The QLQ‐C30 revealed clinically significant impairments in several aspects of QoL at 6 months; however, at 2 years, QoL measurements were not different from baseline.CONCLUSIONSPEG‐IFN effectively reduced platelet counts in 29 of 42 patients, but only 19 patients maintained a CR at 2 years. The reversal of PRV‐1 positivity noted in a subset of patients suggested that PEG‐IFN may have an effect on the malignant clone. PEG‐IFN is a valuable therapeutic alternative for patients who tolerate its initial side effects. Cancer 2006. © 2006 American Cancer Society.

SummaryAllogeneic haematopoietic stem cell transplantation remains the only curative treatment of myelofibrosis with myeloid metaplasia (MMM). Previous reports have indicated significant treatment-related mortality (TRM) for patients transplanted after myeloablative conditioning but superior survival has been reported after reduced-intensity conditioning (RIC). We report the results of a survey of all allogeneic transplantations for MMM performed in Sweden at six transplant units between 1982 and 2004. Twenty-seven patients were transplanted; 17 with a myeloablative conditioning regimen and 10 with RIC. The median age was 50 years (5-63 years) at transplantation. After a median follow up of 55 months, 20 patients are alive. TRM was 10% in the RIC group and 30% in the myeloablative group. There was no difference in survival for high or low-risk patients according to Cervantes score or between sibling and unrelated donor transplantations.