Low‐dose fludarabine and cyclophosphamide combined with standard dose rituximab (LD‐FCR) is an effective and safe regimen for elderly untreated patients with chronic lymphocytic leukemia: The Israeli CLL study group experience

Chronic lymphocytic leukemia (CLL) is a disease of elderly patients. The fludarabine, cyclophosphamide, and rituximab (FCR) regimen is considered the treatment of choice for young fit patients with CLL; however, this combination is toxic for older patients. At the time this study was first planned and initiated, there was no standard chemo‐immunotherapy regimen regarded as standard therapy for the less fit elderly patient with CLL. Here, we conducted a single‐arm, phase II trial to examine the efficacy and safety of lower‐dose fludarabine and cyclophosphamide combined with a standard dose of rituximab (LD‐FCR) in elderly patients with previously untreated CLL. Forty patients received LD‐FCR and were included in the efficacy analysis. Two patients treated with FC alone were only included in the safety analysis. The median age was 72.7 years (range, 65.0 to 85.0). The overall response and complete response rates were 67.5% and 42.5%, respectively. Median progression‐free survival (PFS) was 35.5 months (95% CI, 29.27‐41.67). Two patients (4.8%) died during the study period. Hematological toxicities and infections were the most common complications encountered; grade 3 to 4 treatment‐related neutropenia occurred in 20 (47.6%) patients. During the entire study follow‐up, 26 patients (61.9%) had all grades of infection including six (14.3%) with neutropenic fever and eight (19%) with grade 3 to 4 non‐neutropenic infections. In conclusion, LD‐FCR is an effective and relatively safe regimen for previously untreated patients with CLL. It has the advantage of being both “time and cost limited” and, even in the era of novel agents, can still be considered when planning treatment for elderly patients without high‐risk biomarkers. However, recent results in fit elderly patients using the combination of bendamustine and rituximab which have achieved longer PFS with good safety profile must be taken into consideration in this regard.     

miR‐155 is involved in tumor progression of mycosis fungoides

Biopsy specimens from 23 early stage and 19 tumor‐stage mycosis fungoides (MF) patients were evaluated for miR‐155 expression by real‐time qualitative PCR and compared with 15 biopsy specimens from patients with T‐cell‐rich inflammatory skin diseases. Significant upregulation of miR‐155 was found in MF tumors compared with both early‐stage MF lesions and controls. There was no difference in miR‐155 expression between early‐stage and inflammatory dermatoses. Using laser capture microdissection, it was found that miR‐155 was significantly higher in the lymphoma cells in tumor stage compared with the intraepidermal lymphocytes in early stage. In contrast, there was no difference in miR‐155 expression between the intraepidermal lymphocytes and the dermal lymphocytes in early‐stage MF. These findings suggest that although miR‐155 expression cannot serve to discriminate early‐stage MF from inflammatory dermatoses; however, it is involved in the switch from the indolent early stage into the aggressive tumor stage of the disease.     

Human factors in computing systems: Focus on patient-centered health communication at the ACM SIGCHI conference

Health Information Technologies, such as electronic health records (EHR) and secure messaging, have already transformed interactions among patients and clinicians. In addition, technologies supporting asynchronous communication outside of clinical encounters, such as email, SMS, and patient portals, are being increasingly used for follow-up, education, and data reporting. Meanwhile, patients are increasingly adopting personal tools to track various aspects of health status and therapeutic progress, wishing to review these data with clinicians during consultations. These issues have drawn increasing interest from the human–computer interaction (HCI) community, with special focus on critical challenges in patient-centered interactions and design opportunities that can address these challenges. We saw this community presenting and interacting at the ACM SIGCHI 2013, Conference on Human Factors in Computing Systems, (also known as CHI), held April 27–May 2nd, 2013 at the Palais de Congrès de Paris in France. CHI 2013 featured many formal avenues to pursue patient-centered health communication: a well-attended workshop, tracks of original research, and a lively panel discussion. In this report, we highlight these events and the main themes we identified. We hope that it will help bring the health care communication and the HCI communities closer together.     

Plasma homocysteine, methylenetetrahydrofolate reductase genotypes, and age at onset of symptoms of myocardial ischemia

Elevated fasting plasma homocysteine is a graded risk factor of coronary artery disease (CAD) and may accelerate onset of CAD. Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is commonly but inconsistently associated with hyperhomocysteinemia. In the present study we examined the possible relation between levels of fasting plasma homocysteine and age at CAD onset in different MTHFR genotypes. We studied 182 patients with CAD, 74 patients with early onset CAD (aged < or = 45 years), and 108 patients with later onset CAD (aged 46 to 65 years). Plasma homocysteine levels in 90 subjects without CAD were used for control. Fasting plasma homocysteine levels in T/T homozygotes with early onset CAD (20.2 +/-12.5 micromol/L) was markedly higher than in T/T homozygotes with later onset CAD (13.4 +/- 6.8 micromol/L) and in patients with early onset CAD who were not T/T homozygotes (11.9 +/- 3.7 micromol/L; p = 0.034 and p = 0.0001, respectively). CAD developed earlier in T/T homozygotes who were hyperhomocysteinemic (>15 micromol/L) than in the T/T homozygotes who were not (p = 0.036). Plasma homocysteine levels had no effect on age at onset of CAD in patients who were non-T/T genotypes. Homocysteine levels in control subjects and in patients who were non-T/T genotypes were comparable and were not influenced by age. The results reveal an inverse relation between the level of fasting plasma homocysteine and age at onset of CAD in T/T homozygotes as opposed to no association in patients who were non-T/T genotypes. Additionally, these results show that hyperhomocysteinemia and the T/T genotype have a stronger effect on the pathogenesis of CAD when they are combined, and that a marked increase (>15 micromol/L) in fasting plasma homocysteine in T/T homozygotes is a risk factor for early onset of CAD.     

Acute myelogenous leukemia associated with extreme symptomatic thrombocytosis and chromosome 3q translocation: case report and review of literature

Acute leukemias with thrombocytosis have been recently linked with structural abnormalities of the short arm of chromosome 3. A 46-year-old man with a 2-month history of recurrent transient ischemic attacks and abdominal pain developed an ischemic left foot and a gangrenous toe as his initial symptoms. Platelet count was 3.5 x 10(6)/microL, and despite plateletpheresis, the patient required left-leg amputation. Pathologic examination was remarkable for arterial thrombosis in the absence of atherosclerotic lesions. A diagnosis of acute myeloid leukemia with a novel translocation between chromosomes 3q21, 16, and 7 was made. Induction therapy was unsuccessful, and the patient died of overwhelming sepsis within 5 weeks of diagnosis. The striking features of this case were extreme symptomatic thrombocytosis, peripheral gangrene without atherosclerosis, and a novel three-way chromosomal translocation involving chromosome 3q21.