In myelofibrosis, the introduction of reduced-intensity conditioning (RIC) preceding allogeneic stem cell transplantation (SCT) resulted in lower transplant-related mortality rates compared with myeloablative conditioning. However, lowering the intensity of conditioning may increase the risk of graft failure in myelofibrosis, although hitherto this has not been indisputably proven. We here report the outcome of 53 patients who underwent allogeneic SCT with different conditioning regimens (RIC and nonmyeloablative (NMA)) in three transplantation centers in the Netherlands. The cumulative incidence of graft failure within 60 days after SCT was high (28%), and this was primarily associated with the intensity of the conditioning regimen. Cumulative neutrophil engraftment at 60 days was lower in patients who received NMA conditioning compared with those who received RIC (56% vs 84%, P = 0.03). Furthermore, of six patients who received a second transplantation after graft failure, the three patients with RIC regimens subsequently engrafted, whereas the three patients who received a second NMA regimen did not. This study indicates that in myelofibrosis, NMA regimens result in high engraftment failure rates. We propose the use of more intensive conditioning regimens, incorporating busulfan or melphalan.

A 24-month treatment course with risedronate 35 mg once weekly, concomitant with calcium and vitamin D supplementation, in osteopenic Crohn's disease patients improved bone density at lumbar spine. NTR 163 Dutch Trial Register.

Background: Refractory coeliac disease type II (RCDII) frequently transforms into an enteropathy-associated T-cell lymphoma (EATL) and therefore requires intensive treatment. Current evaluated treatment strategies for RCDII include cladribine (2-CdA) and autologous stem cell transplantation (auSCT). Objective: The purpose of this study was to evaluate long-term survival and define clear prognostic criteria for EATL development comparing two treatment strategies. Methods: A total of 45 patients were retrospectively analysed. All patients received 2-CdA, after which they were either closely monitored (monotherapy, n ¼ 30) or a step-up approach was used including auSCT (step-up therapy, n ¼ 15). Results: Ten patients (22%) ultimately developed EATL; nine of these had received monotherapy. Absence of histological remission after monotherapy was associated with EATL development (p ¼ 0.010). Overall, 20 patients (44%) died with a median survival of 84 months. Overall survival (OS) within the monotherapy group was significantly worse in those without histological remission compared to those with complete histological remission(p ¼ 0.030). The monotherapy group who achieved complete histological remission showed comparable EATL occurrence and OS as compared to the step-up therapy group (p ¼ 0.80 and p ¼ 0.14 respectively). Conclusion: Histological response is an accurate parameter to evaluate the effect of 2-CdA therapy and this parameter should be leading in the decisions whether or not to perform a step-up treatment approach in RCDII.

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Background Patients presenting with arthralgia and a positive test for anti-cyclic citrullinated peptide antibodies (aCCP) and/or IgM rheumatoid factor (IgM-RF) (seropositive) are at risk for developing RA. Objectives To predict the development of arthritis in seropositive arthralgia patients using antibody characteristics and clinical variables. Methods A prediction rule was developed using a prospective cohort of 374 seropositive arthralgia patients. Patients were followed biannually in the first year and then annually for the development of arthritis, which was defined as presence of one or more swollen joints at clinical examination. 18 prediction variables were selected based on clinical applicability, biologic plausibility, previous research and expert opinion. Backward stepwise Cox regression was used to create a prediction model (p removal 0.1). Regression coefficients were rounded to half points to make a prediction rule. Scores were multiplied by 2 for easier clinical applicability. The diagnostic performance of the prediction rule was evaluated using the area under the curve (AUC) of ROC curves. Results Patients were followed for a median of 32 months (IQR: 13-48). 131 arthralgia patients (35%) developed arthritis after a median of 12 months (IQR: 6-23), of whom 121 (92%) were diagnosed with RA according to the 2010 ACR/EULAR criteria. The prediction model consisted of 9 variables: antibody status (double positive, or high titer aCCP confers higher risk), RA in a first degree family member, VAS pain over 50, presence of morning stiffness, duration of symptoms shorter than 12 months, presence of intermittent complaints, arthralgia in both upper and lower extremities, history of swollen joints as reported by the patient and alcohol non-use. The variables age, sex, smoking, NSAID use, symmetric symptoms, symptoms in small joints, tender joint count, CRP and Shared Epitope were excluded. Patients scored 0 to 12 points on the prediction rule. The AUC value of the prediction rule was 0.83 (95% CI: 0.78-0.87). According to Cox regression analysis with the prediction rule as categorical variable, patients could be categorized in three risk groups: low risk (0-4 points), intermediate risk (5-6 points) and high risk (7-12 points). 155 (41%) patients had low, 102 (27%) intermediate and 117 (31%) had high risk. The percentages of arthritis development per risk group are tabulated below. With the low risk group as a reference, the intermediate risk group had a hazard ratio (HR; 95% CI) of 4.3 (2.3-8.1) and the high risk group had a HR of 14 (7.7-25). Arthritis development over time Time (months)01224364860 Number at risk3742541821217439 Arthritis in low risk group n=1550%3%7%7%12%12% Arthritis in intermediate risk group n=1020%17%29%36%38%44% Arthritis in high risk group n=1170%43%63%74%81%81% Conclusions In patients who present with seropositive arthralgia, the risk of developing arthritis and subsequent RA can be predicted. The prediction rule that was made in this patient group can help 1) to inform patien...