Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA).

We administered one course of 2-chlorodeoxyadenosine (2CdA) at 4 mg/m2 daily for 7 days by continuous intravenous infusion to 46 patients with hairy cell leukemia. Complete remissions occurred in 36 patients (78%; 95% confidence limits, 63% to 89%), partial remissions in five (11%), and a minor response in one. One patient died of candida sepsis 3 weeks after beginning treatment and three patients were clearly resistant to therapy. These three either had morphologically atypical hairy cells, less than 20% of which expressed Ig light chain on the cell surface, or had failed prior treatment with deoxycoformycin and interferon-alpha. At a median of 37 weeks since discontinuation of therapy, recurrent thrombocytopenia has developed in one patient, whose marrow remains normal, while a bone marrow relapse has occurred in another patient, whose blood counts remain normal. Treatment produced a greater than 50% decrease in neutrophil count in 26 patients, which lasted 3 to 4 weeks and was associated with an increased incidence of febrile episodes. These episodes occurred in 21 patients but were associated with documented infection in only four patients. Decreases in the number of CD4+ lymphocytes appeared to occur regularly after treatment and have persisted for a median of 18 weeks without obvious clinical significance. Although years of follow-up will be needed, our results confirm Piro et al's observation (N Engl J Med 322: 1117, 1990) that 2CdA appears to be highly effective in the treatment of hairy cell leukemia.     

Trauma Care and Case Fatality during a Period of Frequent, Violent Terror Attacks and Thereafter

Background

From September 1999 through January 2004 during the second Intifada (al-Aqsa), there were frequent terror attacks in Jerusalem. We assessed the effects on case fatality of introducing a specialized, intensified approach to trauma care at the Hebrew University-Hadassah Hospital Shock Trauma Unit (HHSTU) and other level I Israeli trauma units. This approach included close senior supervision of prehospital triage, transport, and all surgical procedures and longer hospital stays despite high patient-staff ratios and low hospital budgets. Care for lower income patients also was subsidized.

Methods

We tracked case fatality rates (CFRs) initially during a period of terror attacks (1999–2003) in 8,127 patients (190 deaths) at HHSTU in subgroups categorized by age, injury circumstances, and injury severity scores (ISSs). Our comparisons were four other Israeli level I trauma centers (n?=?2,000 patients), and 51 level I U.S. trauma centers (n?=?265,902 patients; 15,237 deaths). Detailed HHSTU follow-up continued to 2010.

Results

Five-year HHSTU CFR (2.62?%) was less than half that in 51 U.S. centers (5.73?%). CFR progressively decreased; in contrast to a rising trend in the US for all age groups, injury types, and ISS groupings, including gunshot wounds (GSW). Patients with ISS?>?25 accounted for 170 (89?%) of the 190 deaths in HHSTU. Forty-one lives were saved notionally based on U.S. CFRs within this group. However, far more lives were saved from reductions in low CFRs in large numbers of patients with ISS?Conclusions Sustained reductions in trauma unit CFRs followed introduction of a specialized, intensified approach to trauma care.     

Radical cystectomy for clinically muscle invasive bladder cancer: does prior non-invasive disease affect clinical outcomes?

Purpose

To compare clinical and pathologic outcomes of radical cystectomy for muscle invasive bladder cancer in relation to prior history of non-invasive urothelial carcinoma.

Materials and methods

Retrospective data collected from 1,150 patients managed by radical cystectomy for urothelial carcinoma of the bladder from the Canadian Bladder Cancer Network were analysed. Patients with clinical stage T2 or more were included and divided into two groups: (Group 1) patients with prior history of non-invasive urothelial carcinoma (N?=?365) and (Group 2) patients with clinical muscle invasive cancer de novo (N?=?785). Variables analysed included patient age, gender, pathologic stage, adjuvant chemotherapy, recurrence and mortality.

Results

Both groups were nearly equal in mean age and gender distribution, with mean ages of 67.2 and 66.7?years, and 79.7 and 79.5%, respectively (P?=?0.4 and 0.9, respectively). The presence of preoperative hydronephrosis was 20.8 and 32.6% (P?=?0.0007) for groups 1 and 2, respectively. The rate of higher pathological stage (T3 or T4) was 36.3 and 58% (P?<?0.0001), positive lymph nodes were 20.1 and 28.8% (P?=?0.002), and lymphovascular invasion was 31.7 and 46.2% (P?=?0.0001) for groups 1 and 2, respectively. The rate of adjuvant chemotherapy was 15.5 and 23.3% (P?=?0.002) for groups 1 and 2, respectively. None of the sampled patients received neoadjuvant chemotherapy. The overall survival (OS) and disease-specific survival (DSS) rates at 5?years were 62 and 70% for group 1 and 51 and 60% for group 2, respectively, while at 10?years, OS and DSS were 46 and 66% for group 1 and 35 and 49% for group 2, respectively (P?=?0.0001 and 0.0002, respectively). Using multivariate analysis examining factors affecting recurrence and survival, we found that previous non-invasive bladder tumour history was associated with a significantly reduced risk of mortality and recurrence (Hazard ratio of 0.7 for all risks, P?=?0.0002).

Conclusion

Our retrospective study suggests that patients with non-invasive urothelial carcinoma of the bladder that progress to muscle invasion and require radical cystectomy appear to have better pathologic and clinical outcome than patients presenting with clinical muscle invasive disease de novo.     

Who benefits from maintenance therapy in acute promyelocytic leukemia?

Acute promyelocytic leukemia (APL) is remarkable for its upfront mortality rate from disseminated intravascular coagulation and its high cure rate with therapy. Although induction and consolidation regimens continue to evolve, newer approaches combine an anthracycline with or without cytarabine and the highly effective differentiating drugs all-trans retinoic acid and arsenic trioxide. Early trials showed a benefit of maintenance therapy on overall survival, although this benefit has been less clear in subsequent trials. This review assesses the differences in these trials and outlines a rational approach to maintenance therapy in APL, generally advising against maintenance in patients who underwent adequate consolidation therapy, particularly if they presented with low-risk disease (WBC < 10,000) and experienced molecular complete remission after completion of consolidation.