Background: In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM. Methods: We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM. Results: We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event-free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly. Conclusion: Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants.

ABSTRACTmedian age who had been transplanted over the same period, was examined for correlation of the post-transplantation disease course with JAK2 p.V617F allele burden at day 28. The clinical profiles of the patients are shown in Table 1, individual risk profile, MPN subtype and JAK2 p.V617F allele burden prior to SCT are presented in Table 2A/B. Applying the Dynamic International Prognostic Scoring System (DIPSS) for risk stratification, the patients with primary myelofibrosis (n=16) were classified into either the intermediate-2 risk group or the high risk group. The patients were followed for a median of 43.5 months (range, 20.3 -104.4 months). All patients gave written informed consent to participation in the study in accordance with the Declaration of Helsinki, and the study was approved by the local ethics committee and the national health authorities. Within the first cohort the JAK2 p.V617F allele burden of one patient (UPN6) never exceeded 4%. This patient had an abnormal karyotype and atypical spindle-shaped mast cell aggregates were seen following allogeneic SCT. Together with the molecular pathological finding of a KIT p.D816V mutation the disease was identified as systemic mastocytosis associated with a JAK2 p.V617F-positive MPN. The other 13 patients were determined to have classical MPN which in four of them had transformed to secondary acute myeloid leukemia prior to the allogeneic SCT. All patients in the second cohort (n=16) had classical MPN which in seven cases had transformed to secondary AML prior to transplantation. Patients were transplanted due to progression under conventional treatment with at least one of the following features: secondary AML; increased transfusion frequency; pancytopenia or uncontrolled white blood cell counts under therapy.The success of allogeneic SCT was assessed on the basis of clinical data, cytological, histomorphological and laboratory findings. Relapse was indicated by the reappearance of MPN-typical changes in peripheral blood (i.e. progressive cytopenia, leukerythroblastic blood counts) and/or by clinical symptoms (i.e. increase in splenomegaly, constitutional symptoms) together with characteristic changes in the bone marrow such as progressive fiber density in a trephine biopsy or an increase of atypical blasts in the absence of uncontrolled graft-versushost disease, graft rejection or poor bone marrow function and infections. Response or remission of MPN was indicated by constant or decreasing spleen size and blood count parameters as well as a return to normal histomorphology. SamplesFor the initial study of 14 patients a total of 70 peripheral blood samples were immediately frozen at -80°C. At the same time as the blood sampling, 76 bone marrow biopsies were obtained from the posterior iliac crest. The biopsies were fixed in phosphate-buffered formaldehyde solution (4%) for 12 h. Further processing included decalcification in 10% buffered ethylene-diamine tetra-acetic acid (EDTA), pH 7.2 for 6 h and embedding in paraffin. Early sampling was carried ...

BackgroundAnemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35–54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of action, anemia was a frequently reported adverse event. In clinical practice, anemia is sometimes managed with erythropoiesis-stimulating agents (ESAs). This post hoc analysis evaluated the safety and efficacy of concomitant ruxolitinib and ESA administration in patients enrolled in COMFORT-II, an open-label, phase 3 study comparing the efficacy and safety of ruxolitinib with best available therapy for treatment of myelofibrosis. Patients were randomized (2:1) to receive ruxolitinib 15 or 20 mg twice daily or best available therapy. Spleen volume was assessed by magnetic resonance imaging or computed tomography scan.ResultsThirteen of 146 ruxolitinib-treated patients had concomitant ESA administration (+ESA). The median exposure to ruxolitinib was 114 weeks in the +ESA group and 111 weeks in the overall ruxolitinib arm; the median ruxolitinib dose intensity was 33 mg/day for each group. Six weeks before the first ESA administration, 10 of the 13 patients had grade 3/4 hemoglobin abnormalities. These had improved to grade 2 in 7 of the 13 patients by 6 weeks after the first ESA administration. The rate of packed red blood cell transfusions per month within 12 weeks before and after first ESA administration remained the same in 1 patient, decreased in 2 patients, and increased in 3 patients; 7 patients remained transfusion independent. Reductions in splenomegaly were observed in 69 % of evaluable patients (9/13) following first ESA administration.ConclusionsConcomitant use of an ESA with ruxolitinib was well tolerated and did not affect the efficacy of ruxolitinib. Further investigations evaluating the effects of ESAs to alleviate anemia in ruxolitinib-treated patients are warranted (ClinicalTrials.gov identifier, NCT00934544; July 6, 2009).

SummaryThis phase 1 dose finding study tested a combination of lenalidomide, bendamustine and prednisolone (RBP)

A median number of two (range 1-7) BPV treatment cycles were given to the patients. The majority of the patients (n = 54; 69 %) responded after at least one cycle of chemotherapy with 3 CR, 10 nCR, 10 VGPR and 31 PR. Median PFS and OS for patients without severe hematological toxicities due to previous treatments (n = 45) were 11 and 50 months, respectively. Outcome for these patients was significantly better than that for patients with severe hematological toxicities (grade 3 or 4, n = 33) with a PFS, and OS of 3 months (p < 0.05) and 5 months (p < 0.001), respectively. The regimen was well tolerated with few significant side effects in patients without severe hematological toxicities due to previous treatments. These results indicate that the combination of bortezomib, bendamustine and prednisone is well tolerated in patients with relapsed or refractory MM.