Bortezomib in a phase 1 trial for patients with relapsed AL amyloidosis: cardiac responses and overall effects.

BACKGROUND: Bortezomib is approved for the treatment of multiple myeloma and a role has been suggested in the treatment of systemic AL amyloidosis (AL). METHODS: In this phase 1 dose-escalation portion of the first prospective study of single-agent bortezomib in AL, 31 patients with relapsed disease, including 14 (45%) with cardiac involvement, received bortezomib in seven dose cohorts on once-weekly (0.7, 1.0, 1.3, 1.6 mg/m(2)) and twice-weekly (0.7, 1.0, 1.3 mg/m(2)) schedules. Electrocardiographic, Holter and echocardiographic studies were evaluated in all patients to determine safety and response. RESULTS: During therapy (median treatment period 210 days), no patient developed significant ventricular or supraventricular rhythm disturbance on 24-h Holter monitoring; however, no patient satisfied study criteria for cardiac response using echocardiographic assessment or New York Heart Association classification. Seven patients (23%) had a ≥ 10% fall in left ventricular ejection fraction, but only one met criteria for cardiac deterioration. The predominant cardiac adverse events were peripheral edema (23%), orthostatic hypotension (13%) and hypotension (10%). Two patients developed grade 3 congestive heart failure, which resolved following treatment interruption. In this Phase 1 portion, the maximum tolerated dose of bortezomib on either schedule was not reached. Hematologic responses occurred in 14 patients (45%), including seven (23%) complete responses. In non-responders mean left ventricular wall thickness increased during the course of treatment. CONCLUSION: AL is frequently rapidly progressive; in these patients who had relapsed or progressed following previous conventional therapies, these results suggest that bortezomib may slow the progression of cardiac amyloid with limited toxicity.

Is antenatal antibody screening worthwhile in the Zimbabwean population?

OBJECTIVES: To determine the incidence of clinically significant allo-antibodies in antenatal care (ANC) patients, and make recommendations on laboratory management of such cases in similar settings in Zimbabwe. DESIGN: A retrospective study. SETTING: Harare Central Hospital, a tertiary medical centre in Harare. SUBJECTS: Patients attending the ANC clinic at Harare Central Hospital. MAIN OUTCOME MEASURES: Blood group tests, allo-antibody screen, development of haemolytic disease of the newborn. RESULTS: 3,000 patients were grouped and screened and 96.7% were found to be Rhesus positive, 0.5% were Rhesus Du positive and 2.8% were Rhesus negative. An overall antibody incidence of 1.7% (n = 50) was obtained, 1.0% (n = 30) of which were strongly positive and 0.7% (n = 20) were so weakly positive so that no antibodies could be identified. Antibodies identified from those patients with strongly positive antibody screen were anti-D 13.3% (n = 4), anti-E 6.7% (n = 2), anti-Jsb 3.2% (n = 1), anti-Lea 23.3% (n = 7) and anti-Leb 20% (n = 6). Antibodies of unknown specificity were detected from 20% (n = 6) of the patients. Four (13.3%) of the specimens were insufficient for antibody identification. Clinical records of those patients with a strongly positive antibody screen were examined and anti-D and anti-Jsb were observed to have caused severe to fatal Haemolytic Disease of the Newborn (HDN). The four anti-D positive cases resulted in two still births and two jaundiced babies. The single anti-Jsb positive antibody case resulted in an intra-uterine death. Antibodies that are generally considered of no clinical significance did not cause HDN in this study. CONCLUSION: Anti-D remains the most important allo-antibody causing HDN, regardless of the availability of anti-D immunoglobulin for prophylaxis. Only Rhesus D negative women and those who have clinically significant antibodies need have repeat antibody screens during the rest of the pregnancy. In line with the current policy of screening all patients at booking, the policy on repeats is not clear and was not evident in this study.

Use of packed red cells in a major hospital in Harare, Zimbabwe.

OBJECTIVES: To document the current pattern of packed red cell (PC) usage and the crossmatch to transfusion ratio (C/T ratio) in a major city teaching hospital in Harare, Zimbabwe. DESIGN: Restropective, (audit). SETTING: Harare Central Hospital, a 1,200 bed multidisciplinary hospital located in Harare, Zimbabwe. MAIN OUTCOME MEASURES: Amount of PC ordered and proportion collected for the year 1995. Quantity of PC used by different medical specialties. RESULTS: In 1995 a total of 8,292 PC were collected from Harare Hospital blood bank. This translates to an average PC usage for a 1,200 bed hospital of seven units per hospital bed per year. Only 48.5% of PC crossmatched was collected with a C/T ratio of 2.1:1. Revenue loss of Z$478,434 is estimated to have occurred due to expired units and resource wastage from uncollected crossmatched units. The largest consumer of PC was the Department of Gynaecology, followed by Surgery and Paediatrics. CONCLUSION: Regular auditing of blood usage is recommended to promote the efficient use of PC in accordance with accepted international standards and local guidelines and practice.