Therapy of lymphoid and undifferentiated chronic myelogenous leukemia in blast crisis with continuous vincristine and adriamycin infusions plus high-dose decadron

Thirty patients with Philadelphia chromosome-positive lymphoid (20 patients) or undifferentiated (ten patients) chronic myelogenous leukemia in blast crisis were treated with 0.4 mg of vincristine by continuous intravenous infusion (CIV) daily for 4 days; (doxorubicin) 12 mg/m2 of Adriamycin (Adria Laboratories, Columbus, OH) by continuous intravenous infusion daily for 4 days; and 40 mg of decadron daily on days 1 through 4, 9 through 12, and 17 through 20 (VAD). Course 2 was given starting on day 24 with the addition of cyclophosphamide 1 g/22. Overall nine patients achieved complete remission (30%) and three attained a partial remission (10%), for an overall response rate of 40%. Four patients expired during induction whereas 14 had resistant disease. Response rate was significantly higher for patients with lymphoid compared to undifferentiated morphology (55% versus 10%; P = 0.05). In lymphoid blast crisis, Calla-positive disease was associated with a higher response rate compared to Calla-negative disease (75% versus 25%; P = 0.08). Eleven patients developed infections, and seven had fever without documented infections. The median overall survival was 29 weeks. Median survival was 43 weeks for patients achieving complete remission and 20 weeks for those with resistant disease. Remission duration was 39 weeks. After primary and salvage therapy, nine patients are alive, six of them in continuous remission for 19+ to 112+ weeks. The authors conclude that VAD chemotherapy is an effective regimen with acceptable toxicity in patients with lymphoid blast crisis especially those with Calla-positive disease. Alternate induction regimens for undifferentiated disease and for maintenance therapy are currently being investigated.     

Cancer incidence in migrants to New South Wales (Australia) from the Middle East, 1972–91

The incidence of cancer in migrants to New South Wales (NSW) from Cyprus, Egypt, Iran, Iraq, Israel, Lebanon, Syria, and Turkey has been compared with that in the Australian-born population using data from the NSW Central Cancer Registry for 1972–91. Age-standardized incidence rates showed overall cancer incidence to be less common in migrants from each Middle Eastern country than in the Australian-born. There was a clear pattern of generally low rates for cancers of the mouth and pharynx, esophagus, colon and rectum, lung (men only), ovary, prostate and testis, and melanoma. Cancers which tended to be more common in migrants were nasopharynx, stomach (women only), liver (men only), gallbladder (chiefly in women), bladder (men only), and thyroid. Breast cancer did not show a uniform pattern among migrant groups, rates being high in the Egyptian-born but low in Lebanese-born women. The overall low incidence of cancers related to tobacco and alcohol, and to a high fat, low fiber diet, emphasizes the potential role of preventable lifestyle factors in the burden of cancer in Australia.     

Melorheostosis and the sclerotomes: A radiological correlation

Melorheostosis is characterised radiologically by hyperostotic linear densities in bone. These densities have a peculiarly segmental distribution which does not correspond with the anatomical course of blood vessels or mixed nerve roots of the limbs. So far this distribution has lacked any valid explanation, although it has been suggested to be a developmental error as a result of an embryonic metameric disturbance. Inman and Saunders in 1944 described a sensory nerve supply to skeletal structures with sclerotomes representing the zones of the skeleton supplied by individual spinal sensory nerves. Radiographs of 30 cases from the Radiological Museum of the Institute of Orthopaedics, London, have been reviewed and an attempt has been made to correlate the sclerosing lesions with the sclerotomes. The investigation was handicapped by paucity of films and clinical information, but in 19 cases the skeletal abnormalities were considered to correspond with a single sclerotome or part thereof. These studies were convincing when films of an affected hand or foot were available. In the remaining 11 cases multiple sclerotomes appeared to be involved and the clinical manifestations were correspondingly more severe. It is proposed that melorheostosis may be the late result of a segmental sensory nerve lesion, to account for its sclerodermal distribution. The association with linear scleroderma is discussed, since it has been suggested that these cutaneous lesions are related to the same nerve segment. Eight cases showed para-articular ossification of soft tissues which may be related to involvement of a corresponding myotome.     

Breast cancer in Australian women under the age of 40

Objectives: A case-control-family study of breast cancer in women under the age of 40 was carried out in Melbourne and Sydney, Australia, from 1992 to 1995 to determine the risk factors for these women. Subjects included 467 incident cases identified by state cancer registries and 408 population-based controls. Methods: All participants completed a structured risk-factor questionnaire and family pedigree during an in-person interview. Where possible, cancers in first- and second-degree relatives were verified. Results: Multiple logistic regression analysis showed that the strongest risk factor for breast cancer was a family history of the disease - having at least one affected first-degree relative trebled the risk (relative risk [RR] = 3.3, 95 percent confidence interval [CI] = 1.9-5.8). Risk increased with height by three percent (standard error [SE] of one percent) per cm, and after adjusting for height, there was evidence for a decreased risk in women weighing 73 kg or more. There was an increased risk of breast cancer after the first full-term birth (RR = 1.8, CI = 1.0-3.5) but this risk fell by 30 percent (SE = 11 percent) with each subsequent livebirth. Conclusions: The effects of other reproductive factors and oral contraceptive use, although not nominally significant, were in accord with published findings from similar studies in young women. This study of Australian women has indicated that some risk factors for breast cancer in women under age 40 differ from those reported for older women either in direction (e.g., weight) or relative importance (e.g., family history).     

Prospective randomized trial of antibiotic prophylaxis in acute leukemia

Patients undergoing initial remission induction chemotherapy for acute leukemia in a protected environment unit were randomly assigned to parenteral antibiotic prophylaxis or oral and parenteral antibiotic prophylaxis. Complete remissions were obtained in 82 percent of the 45 patients receiving oral and parenteral antibiotic prophylaxis and 76 percent of the 41 patients receiving parenteral antibiotic prophylaxis. Approximately 20 percent of the patients in both groups have had a continuous complete remission for more than five years. The episodes of fever of unknown origin and major infection were significantly more common in patients receiving parenteral antibiotic prophylaxis, although the episodes of local infection were similar in both groups. The duration of remission and survival was similar in both groups. Hence, the oral and parenteral antibiotic regimen was more effective for infection prophylaxis, but had no effect on response to antileukemic chemotherapy.     

The effectiveness of rubidazone in hairy cell leukemia (leukemic reticuloendotheliosis).

Two patients with hairy cell leukemia treated with the anthracycline antibiotic rubidazone are presented. One achieved a complete remission and the other a good partial hematologic and bone marrow remission. Neither has relapsed (at 20 and 13 mo, respectively), and neither has been retreated. Intensive supportive measures were required during the prolonged myelosuppression that followed treatment. The relative youth of the patients (ages 24 and 39 yr) may have contributed to their ability to survive until normal marrow recovered. Chemotherapy should not be employed in the initial management of hairy cell leukemia. However, if life-threatening granulocytopenia and thrombocytopenia occur secondary to bone marrow replacement by leukemic cells, and improvement does not occur using alternative methods of therapy, consideration could be given to chemotherapy with rubidazone. Facilities for intensive supportive care should be available.     

Necrotizing colitis in patients with cancer.

Necrotizing lesions of the colon occur in patients with malignancy. We identified 26 patients with cancer (23 with acute leukemia and three with solid tumors) who died from necrotizing colitis. Autopsies revealed three pathologic categories: pseudomembranous colitis in 69 per cent, agranulocytic colitis in 19 per cent and ischemic colitis in 12 per cent. Most died from sepsis. A comparison of characteristics was made with a control population matched for diagnosis, age, cause of death and duration of neoplasia. Nearly all patients in both groups had fever and were granulocytopenic secondary to chemotherapy. Most received antineoplastic and antimicrobial regimens during the month prior to their terminal illness. Abdominal pain and distention, stomatitis and necrotizing pharyngitis were frequently associated with colitis. Hyperbilirubinemia was a frequent late complication in those with colitis and the control group. Single and multiorganism septicemia were found more frequently in patients with colitis. As antemortem diagnosis was unusual, aggressive attempts at diagnosis are necessary to assess the true incidence of this disorder and the best therapy.     

Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women

OBJECTIVE Oestrogen replacement therapy is associated with a marked reduction in coronary event rates in post-menopausal women. As older age is associated with progressive arterial endothelial damage, a key event in atherosclerosis, we assessed whether hormone replacement therapy (HRT) with oestrogen alone, or oestrogen and progesterone combined, is associated with improved endothelial function in healthy women after the menopause. DESIGN Using high resolution external vascular ultrasound, brachial artery diameter was measured at rest and in response to reactive hyperaemia, with increased flow causing endothelium-dependent dilatation (flow-mediated dilatation). PATIENTS We investigated 135 healthy women; 40 were pre-menopausal (mean±SD age/26±6 years, group 1), 40 were post-menopausal and had never taken HRT (aged 58±3 years; group 2) and 55 were age-matched post-menopausal women who had taken HRT for >2 years, from within 2 years of the menopause (aged 57±4 years; group 3). In group 3, 40 women were on combined oestrogen and progesterone and 15 on oestrogen-only HRT. RESULTS In group 2, flow-mediated dilatation was significantly reduced compared with group 1 (4.4±3.4 vs 9.6±3.6%, P<0.001), consistent with a decline in arterial endothelial function after the menopause. In group 3, however, flow-mediated dilatation was significantly better than group 2 (6.2±3.3 vs 4.4±3.4%, P=0.01), suggesting a protective effect of HRT. Flow-mediated dilatation was similar in women taking oestrogen alone and in those on combined HRT (5.5±2.8 vs 6.5±3.4%, P=0.40). CONCLUSIONS Long-term HRT is associated with improved arterial endothelial function in healthy post-menopausal women. This benefit was observed in both the combined hormone replacement and unopposed oestrogen therapy groups. This may explain some of the apparent cardioprotective effect of HRT after the menopause.