Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study

The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400 mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a minimum follow-up of 42 months or discontinued early. Major molecular response (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day, respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were no differences in event-free survival (EFS), progression-free survival (PFS), or overall survival (OS) between arms. The estimated rates of PFS on treatment and OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18 months compared with those without MMR. Adverse events were more frequent with high-dose imatinib. Patients with ≤1 treatment interruption (vs >1) and those able to maintain imatinib ≥600 mg/day (vs <600 mg/day) in the first year of treatment had faster and higher response rates, but no improvement in EFS or PFS. Adherence to prescribed dose without interruption may be more important than initiation of therapy with higher doses of imatinib. Achievement of MMR correlated with long-term clinical outcomes.     

Second cancers in MPN: Survival analysis from an international study

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A “poor prognosis” SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a “non-poor prognosis” SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.     

Spontaneous clostridial myonecrosis after pregnancy – emergency treatment to the limb salvage and functional recovery: a case report

Clostridial myonecrosis (CM) is a rare, life threatening necrotizing infection of a skeletal muscle caused by Clostridium perfringens in the majority of cases. The diagnosis may be difficult because of few diagnostic and cutaneous signs early in its course. Standard therapy involves surgical debridements of a devitalized tissue and high‐dose organism‐specific antibiotic therapy. The hyperbaric oxygen has also showed its usefulness in the treatment of these infections. Autograft systems as tissue replacement, based on bioengineered materials, have been demonstrated to be safe and effective treatments for chronic wounds and a suitable physiotherapy is recommended for the recovery of functional impairments of upper extremities. We present a rare case of CM of right upper limb treated with a combination of standard treatments and new techniques.     

Intravenous use of tranexamic acid reduces postoperative blood loss in total knee arthroplasty

Introduction

Blood transfusion is often required in total knee replacement (TKR); several methods of blood preservation are commonly used but the ideal solution is to reduce the blood loss during and after surgery. Aim of the study was to evaluate the hemostatic efficacy and safety of intravenous use of tranexamic acid in patients receiving TKR (cemented).

Materials and methods

Forty-five patients after TKR receive treatment with tranexamic acid (TXA, treatment group), and 45 were managed with fibrin tissue adhesive (control group). Hemoglobin values decrease and transfusions in both groups were recorded. Statistical analysis was performed with Student t test and χ ² test. A statistical model was elaborated to evaluate together all variables and to underline what data can increase transfusions need.

Results

A significant reduction was detected in hemoglobin values in the first 3 days after surgery in the treatment group. The difference in all cases was significant. When tranexamic acid was administered, the need for transfusions was lower (difference statistically significant). No major adverse events were recorded in our series. The use of autologous blood preparation before surgery led to a higher transfusion rate.

Conclusion

Tranexamic acid reduced blood loss in TKR and significantly reduced the blood transfusion need also when compared to fibrin tissue adhesive. The use of tranexamic acid is safe and in future may avoid preparation of autologous blood unit before surgery with a decrease of cost and medical figures involved.