Nilotinib as frontline and second-line therapy in chronic myeloid leukemia: open questions

Nilotinib is a second generation ABL tyrosine kinase inhibitor (TKI) that exerts major anti-leukemic effects in newly diagnosed patients with chronic myeloid leukemia (CML) as well as in most patients with imatinib-resistant CML. In freshly diagnosed patients, the anti-leukemic activity of nilotinib exceeds the efficacy of imatinib, and although long-term data for nilotinib are not available yet, the drug has recently been approved for firstline treatment of chronic phase CML in various countries. Still however, several questions concerning the optimal dose, follow-up parameters, long-term safety, and patient selection remain open. Likewise, it remains uncertain whether both Sokal low-risk and high-risk patients should receive nilotinib as frontline therapy in the future. Another question is whether nilotinib can completely eradicate CML in a subset of patients. Furthermore, it remains unclear whether and what comorbidity must be regarded as relative or absolute contra-indication for this TKI. To discuss these issues, the Austrian CML Working Group organized a series of meetings in 2010. In the current article, the outcomes from these discussions are summarized and presented together with recommendations for frontline use of TKIs in various groups of patients with CML. These recommendations should assist in daily practice as well as in the preparation and conduct of clinical trials.     

Ultrasound-guided versus computed tomography-controlled periradicular injections in the middle and lower cervical spine: a prospective randomized clinical trial

Purpose

We conducted this study to evaluate accuracy, time saving, radiation doses, safety, and pain relief of ultrasound (US)-guided periradicular injections versus computed tomography (CT)-controlled interventions in the cervical spine in a prospective randomized clinical trial.

Methods

Forty adult patients were consecutively enrolled and randomly assigned to either a US or a CT group. US-guided periradicular injections were performed on a standard ultrasound device using a broadband linear array transducer. By basically following the osseous landmarks for level definition in “in-plane techniques”, a spinal needle was advanced as near as possible to the intended, US-depicted nerve root. The respective needle tip positioning was then verified by CT. The control group underwent CT-guided injections, which were performed under standardized procedures using the CT-positioning laser function.

Results

The accuracy of US-guided interventions was 100 %. The mean time to final needle placement in the US group was 02:21 ± 01:43 min:s versus 10:33 ± 02:30 min:s in the CT group. The mean dose-length product radiation dose, including CT confirmation for study purposes only, was 25.1 ± 16.8 mGy cm for the US group and 132.5 ± 78.4 mGy cm for the CT group. Both groups showed the same significant visual analog scale decay (p < 0.05) without “inter-methodic” differences of pain relief (p > 0.05).

Conclusions

US-guided periradicular injections are accurate, result in a significant reduction of procedure expenditure under the avoidance of radiation and show the same therapeutic effect as CT-guided periradicular injections.     

Treatment of stress urinary incontinence using polyacrylamide hydrogel in women after radiotherapy: 1-year follow-up

Introduction and hypothesis

Information on urethral bulking therapy in women after previous pelvic radiotherapy is lacking. This study compared the safety and efficacy of polyacrylamide intraurethral injections in patients with and without previous radiotherapy.

Methods

A total of 46 patients with severe stress urinary incontinence (SUI) were enrolled in this multicenter prospective trial. Group A consisted of 24 patients with previous radiotherapy to the pelvis for the treatment of a gynaecological malignancy. Group B consisted of 22 patients without previous radiotherapy. All patients were treated with a transurethral injection of a bulking solution (Bulkamid). The average follow-up was 12.4 months. The paired Wilcoxon test was used to compare the results before and after the procedure within the groups, and the two-sample Wilcoxon test was used for comparisons between groups.

Results

Complete continence was achieved in 25 % of patients in group A and in 36.4 % of patients in group B. Significantly reduced urine leakage was observed in both groups (p?=?0.0164 in group A and p?=?0.0002 in group B). The total scores in the International Consultation on Incontinence Questionnaire decreased by 5.2 in group A (p?=?0.0000) and 6.36 in group B (p?=?0.0001). The scores for the Total Patient Perception of Bladder Condition decreased by 1.54 in group A (p?=?0.0001) and 2.59 in group B (p?=?0.0000), with a significant difference between groups (p?=?0.0224). No clinically significant changes in urodynamic parameters were observed. No severe adverse events were noted.

Conclusions

Based on our results, we conclude that urethral bulking therapy is a valuable treatment option in patients with severe SUI who have undergone pelvic radiotherapy for the treatment of gynaecological malignancy.

     

Effect of a miniaturized extracorporeal circulation (MECC System) on liver function

OBJECTIVE: To evaluate the effect of a miniaturized extracorporeal circulation system (MECC System) compared to conventional extracorporeal circulation (ECC) regarding liver function in cardiac surgical patients. METHODS: Double indicator dilution measurements were achieved by bolus injection of indocyanine green (ICG) for assessment of cardiac index (CI) and plasma disappearance rate of ICG (PDRig). Measurements were simultaneously performed preoperatively after induction of anaesthesia (T1), following admission on the ICU (T2) and 6 h postoperatively (T3). RESULTS: CI and PDRig were markedly increased after cardiac surgery without significant differences between groups. The percentage increase in CI was significantly correlated to the percentage increase in PDRig in both groups. CONCLUSION: Liver function improved after cardiac surgery in both groups of patients, which may partly be explained by an increase in CI under mild inotrope support. Differences between the extracorporeal circuits with respect to PDRig appear to be minimal in a group of patients without pre-existing liver injury.     

Is there an association between periprosthetic joint infection and low vitamin D levels?

Purpose

Vitamin D is increasingly being recognized as an important mediator of immune function and may have a preventive role in the pathogenesis of periprosthetic joint infection. To the best of our knowledge, no other study has examined possible associations between periprosthetic joint infection and vitamin D deficiency. We investigated the rate of vitamin D deficiency in patients treated for periprosthetic joint infection and whether vitamin D deficiency is independent of other risk factors for vitamin D deficiency in patients with periprosthetic joint infection.

Methods

Serum 25-hydroxyvitamin D (25OHD) levels of every patient scheduled to receive a total prosthesis either of the hip, knee, or shoulder in the orthopaedic department of the Johannes-Guttenberg-University Hospital in Mainz, Germany (109 patients), were measured after admission. Furthermore, serum 25OHD levels were measured for every patient presenting with periprosthetic joint infection (n = 50) or aseptic loosening of the prosthesis (n = 31) scheduled to undergo revision surgery. The prevalence of normal (>30 ng/ml), insufficient (20–30 ng/ml), and deficient (<20 ng/ml) 25OHD levels was determined.

Results

All tested patient subgroups showed low vitamin D levels. Statistical analysis found no significant difference in vitamin D levels comparing patients with prosthesis and patients with aseptic prosthesis loosening (p = 0.58). Significant differences in 25OHD levels were found comparing patients with periprosthetic joint infection and patients scheduled for primary arthroplasty (p < 0.001). In addition, we found a significant difference (p < 0,001) in 25OHD levels of patients with periprosthetic joint infection compared with patients with aseptic prosthesis loosening.

Conclusion

We found a high frequency of vitamin D deficiency in patients being treated by primary arthroplasty and those with aseptic joint prosthetic loosening and periprosthetic joint infection. Vitamin D deficiency was severe in patients with periprosthetic joint infection.     

Explaining survival differences between two consecutive studies with allogeneic stem cell transplantation in patients with chronic myeloid leukemia

Purpose

In the two consecutive German studies III and IIIA on chronic myeloid leukemia, between 1995 and 2004, 781 patients were randomized to receive either allogeneic hematopoietic stem cell transplantation with a related donor or continued drug treatment. Despite comparable transplantation protocols and most centers participating in both studies, the post-transplant survival probabilities for patients transplanted in first chronic phase were significantly higher in study IIIA (144 patients) than in study III (113 patients). Prior to the decision on a combined analysis of both studies, reasons for this discrepancy had to be investigated.

Methods

The Cox proportional hazard cure model was used to identify prognostic factors for post-transplant survival.

Results

Donor–recipient matching for human leukocyte antigen, patient age, time between diagnosis and transplantation, and calendar time showed a significant influence on survival and/or the incidence of cure. Added as a further factor, affiliation to study IIIA had no significant impact any longer.

Conclusions

Discrepancies in influential prognostic factors explained the different post-transplant survival probabilities between the studies. The significance of calendar time suggests a lack of consistency of transplantation practice over time. Accordingly, the prerequisite for a common assessment of overall survival in the two randomized transplantation arms was not met. Moreover, our analyses provide an independent validation of established prognostic factors and their cutoffs. The statistical approach in investigating and modeling potential prognostic factors for survival sets an example for the examination of studies with unexpected outcome differences in concurrent treatment arms.