Allografting for chronic myeloid leukaemia

Marrow transplantation from human leukocyte antigen (HLA) matched related donors offers a high probability of prolonged treatment-free survival for patients with chronic myeloid leukaemia in chronic phase. Delay, patient and donor gender, patient age and previous palliation with busulphan predict outcome in this setting. Because of the median age at diagnosis and the genetics of the HLA system, transplants from HLA-matched related donors are available to less than 15% of newly diagnosed patients. Alternative donors include relatives with minor degrees of incompatibility and HLA-compatible unrelated volunteers. The probability of finding suitable unrelated donors has increased with the development of a network of registries now containing more than 3.6 million donors worldwide. Survival prospects will be improved by transplantation earlier in the course of the disease, better-matched donors and the discovery of new approaches for the prevention of graft-versus-host disease and opportunistic infections.     

An evaluation of the effectiveness and safety of razoxane when used as an adjunct to surgery in colo-rectal cancer. Report of a controlled randomised study of 603 patients

A prospective controlled randomised trial to evaluate the effectiveness and safety of razoxane is reported. Some 603 patients with colo-rectal cancer having curative surgery entered the study, and all have been followed up for a minimum of five years. Statistical analysis showed that razoxane treatment had no effect either beneficial or adverse on the rates of recurrence or on five year survival of patients with colo-rectal cancer. It is possible that a more prolonged course of razoxane might have significantly influenced survival. The incidence of severe adverse reaction was low but it is of concern that one patient developed leukaemia. Should razoxane be considered for future use it is recommended that continuous low dose therapy be given for no longer than 12 months. No renal, hepatic, pulmonary or cardiac toxicity was noted.     

Experiences with high-frequency oscillatory ventilation in premature infants with respiratory distress syndrome

BACKGROUND: High-frequency oscillatory ventilation (HFOV) has been used in treating premature infants with respiratory distress syndrome who have a low incidence of ventilation-associated lung injury. Herein, we report our initial clinical experience in using HFOV to treat such infants. METHODS: From October 1996 to February 1997, 10 premature infants with severe respiratory distress syndrome treated with HFOV were retrospectively evaluated. Clinical course and laboratory data collected during treatment were analyzed. Parameters evaluated included patient survival rate, incidence of chronic lung disease and morbidity associated with HFOV usage. RESULTS: The mean gestational age was 29 +/- 2 weeks; mean birth weight, 1,182 +/- 342 g; and mean period of HFOV treatment, 3.4 +/- 1.9 days. One patient died of sepsis due to infective pancarditis. Two patients developed moderate chronic lung disease at 30 days post delivery and in one of these patients, the disease persisted at 36 weeks' of age. The overall survival rate was 90%. No patient developed air-leak syndrome during the course of treatment. CONCLUSIONS: Our initial experience demonstrated that using HFOV in treating premature infants with severe respiratory distress syndrome was safe and effective. The incidence of moderate to severe chronic lung disease or air-leak syndrome following HFOV was low.     

Decerebrate rigidity in acute head injury

A comprehensive study of the motor patterns, usually grouped under the heading "decerebrate rigidity," was carried out in a series of 800 patients with severe head injuries. The incidence of these manifestations was 39.6%, and when they were present chances of survival were reduced from 79.4% to 28.1%. Clinical and electromyographic investigations revealed heterogeneous and unstable motor manifestations that did not fit into the classical groups of experimental models of decerebrate rigidity. Combinations of extensor and flexor attitudes and/or responses were frequently found in same patient, but could be separated into homogeneous groups. Each recognized postural pattern had its own distinct neurological signs and prognosis. Age did not significantly affect the outcome, however, intracranial exapnding lesions (73.5%), impairment of the brain-stem oculomotor system (49.8%), and deep coma (88.9%) all contributed to an unfavorable course. Surgical treatment was effective when performed for intracranial hematomas and in patients with incomplete extensor rigidity. Good recovery was achieved in 16% of decerebrate patients, while 12.1% survived in prolonged coma or with severe disabilities. All clinical and neuropathological data suggest that extensor motor abnormalities in the acute phase of cerebral traumatic disease do not always conclusively indicate structural brain-stem damage. A critical analysis of so-called "decerebrate rigidity" (rejecting in some instances its Sherringtonian implications) may allow for a more accurate clinical assessment of the severity of head injury.     

Guideline 'Radiotherapy in non-small-cell lung carcinoma. Working Group, National Organization for Quality Assurance in Hospitals, Netherlands

8000-9000 new patients with lung cancer are diagnosed yearly in the Netherlands. Of these 10-30% can be treated by surgery, which because of co-morbidity or the extent of the disease is impossible in the others. There is agreement on the terms 'curative', 'radical' and 'palliative' radiotherapy: curative radiotherapy aims at cure through destruction of all tumour cells, on the assumption that the neoplasia has not metastasized (this applies to patients with tumours in stage I and II and sometimes in stage III); radical radiotherapy aims at postponement of locoregional tumour growth; this has a positive effect on the patient's duration of survival and quality of life, but it is to be expected that the patient will die from distant metastases (this treatment is indicated for patients with stage IIIA disease); palliative radiotherapy aims at improvement of the quality of life rather than on prolonging the duration of survival. Patients with a stage III tumour (locoregional invasion making surgical treatment impossible but without distant metastases) without complaints should receive radiotherapy, because these patients are candidates for prolonged survival. In the future the best therapy for these patients could be a combined modality (chemotherapy in combination with radiotherapy). Lung cancer patients with an irresectable tumour should be included as often as possible in clinical trials. During treatment checking quality of life, taking into account the objective and the side effects of the treatment, is important. All medical experts who look after the patient, should inform each other on the actual state of health of the patient and any appointments made. A personal file with this information, kept by the patient himself, has been advocated for this purpose.     

A recombinant adenovirus expressing wild type p53 induces apoptosis in drug-resistant human breast cancer cells: a gene therapy approach for drug-resistant cancers

The different therapeutic options available for the treatment of chronic leukemias and myelofibrosis are discussed. In reference to chronic myeloid leukemia (CML), the choice of the most appropriate treatment must take into account not only the clinical condition but also the age of the patient. While subjects under 50 might benefit from the options offered by alpha-interferon, bone marrow and peripheral stem cell transplant, in older age groups treatment of the chronic phase must still rely on standard treatment. Chronic lymphocytic leukemia (CLL) and its variants is a disease of mostly middle and late life, with a variable clinical course. Patients show wide differences in morbidity and mortality. Many features have been shown to influence the prognosis, and the most important ones are incorporated into the staging systems currently in use. The results obtained from the study of large trials support the concept that treatment of patients with stable stage A CLL should be postponed until progression of disease. Treatment relies principally on alkylating agents, corticosteroids and radiation therapy; the new nucleoside analogues, such as fludarabine and 2-chlorodeoxyadenosine, have recently acquired established value in improving overall survival. With regard to myelofibrosis, the histological and biological features that influence the natural course of the disease are described, as well as the choice of the most appropriate treatment, which ranges from the use of alkylating agents and androgens, to splenectomy and splenic irradiation.     

Phase II study of carboplatin in blast crisis of chronic myeloid leukemia: Eastern Cooperative Oncology Group Study E1992

This study was a phase II evaluation of the activity of carboplatin in patients with Philadelphia chromosome positive accelerated or blastic phase of CML. Carboplatin, 250 mg/m2/day as an intravenous continuous infusion was given for 5 days, for a total dose of 1250 mg/m2 per course. If necessary, a second induction course could be given, and patients achieving complete remission were to receive an additional consolidation cycle at the same dose. Thirty-six patients were eligible and evaluable. There were five complete and three partial remissions for an overall response rate of 22% (95% CI 10.1-39.1%). The complete remission rate was 13.9% (95% CI 4.7-29.9%). The median remission duration was 3 months (range 1.4-8.94 months) and the median survival on study for all patients was 3.5 months (95% CI, 2.4-11.4 months). The median survival of responders was 12.8 months (95% CI, 3.6-17.2 months). Three eligible patients survived 2.0, 2.5 and 3.5 years following carboplatin therapy. Carboplatin has activity in blast crisis of CML, but responses are brief. Response did allow one patient to proceed to bone marrow transplantation and two other patients to continue therapy for chronic phase disease before returning to blast crisis. Activity in combination regimens should be explored.     

Fever, headache and weakness. Primary cytomegalovirus infection

We report on an acute primary infection with cytomegalo virus in a 26 year old immunocompetent and hitherto healthy man. The course of the disease was characterized by prolonged febrile state, headaches, myalgias and markedly reduced general condition. Indicators leading to diagnosis were in view of otherwise unremarkable clinical findings, reactive lymphocytosis, mild splenomegaly as well as elevated transaminases interpreted as concomitant hepatitis. The evolution was benign under symptomatic treatment. The patient recovered rapidly and completely. The clinical picture of primary CMV infection in nonimmunosuppressed adults is discussed.     

Radioiodine treatment of Graves' disease in young people

In Europe young patients with Graves' disease are usually treated with antithyroid drugs initially, then if hyperthyroidism recurs after a prolonged course of such medication, they are offered definitive treatment by subtotal or total thyroidectomy. Neither of these forms of treatment is free from problems. Impressed with the simplicity and safety record of radioiodine therapy, we have treated 8 young patients with radioiodine. The patients all presented with typical Graves' disease and relapsed after 18-24 months of treatment with antithyroid drugs. They were then given the option of a further course of antithyroid medication or definitive treatment with radioiodine or surgery. Those who opted for radioiodine were treated with 131iodine in a dose of 300 MBq with the intention of ablating the thyroid. Antithyroid medication was resumed for 4-6 months and then withdrawn. Four patients became hypothyroid after a single dose of radioiodine but 4 needed a second dose. All became hypothyroid within 2 years. No adverse effects were observed, in particular no patient showed any deterioration in their eye disease. Radioiodine offers a simple, effective and inexpensive method of treatment for Graves' disease in young patients. There are no immediate adverse effects and, although some theoretical concerns remain, to date the long-term safety record of thyroid ablation is excellent and the potential risks seem to us to be outweighed by the advantages. Even when a moderately high initial dose of radioiodine is used, a second dose may be needed.     

Patient management strategies for interferon alfa-2b as adjuvant therapy of high-risk melanoma

PURPOSE/OBJECTIVES: To review results of Eastern Cooperative Oncology Group (ECOG) trial E1684 in the context of nursing issues concerning interferon alfa-2b (IFN alpha-2b) as adjuvant therapy for high-risk melanoma. DATA SOURCES: Published results of ECOG trial E1684 and additional safety data provided by the trial sponsor. Selection of material was based on information that would expand on published safety results and present patient-management strategies relevant to oncology nurses. DATA SYNTHESIS: High-dose IFN alpha-2b significantly prolonged median relapse-free survival (< 0.01) and overall survival (p = 0.047), but side effects required extensive nursing interventions. With appropriate patient management, including dose modifications, 74% of patients who did not relapse received a full course of therapy. CONCLUSIONS: Adjuvant, high-dose IFN alpha-2b can significantly prolong relapse-free and overall survival in patients with high-risk melanoma, but nursing interventions are required to ensure patient compliance. IMPLICATIONS FOR NURSING PRACTICE: Accurate nursing assessment and appropriate interventions can help patients safely complete this effective adjuvant therapy.     

Hyperuricaemia as an index of the response to chemotherapy in solid tumors

A transient increase in uric acid level following administration of high doses of Cyclophosphamide in the 1st course of cytostatic therapy applied for various solid tumors (mostly lung cancer) was observed in 10 patients with measurable disease simultaneously with complete or partial (above 50%) regression of the tumor. The same effect was noted in further 5 patients, who, however, had non-measurable disease. On the other hand, the clinical course of the disease and survival were similar in these 5 patients and in the former 10 patients. No corresponding increase in the uric acid level was observed in 87 patients with similar disease and treatment, but not responding to chemotherapy and with short survival. It is concluded, that hyperuricaemia may indicate responsiveness to chemotherapy in cancer patients with non-measurable disease.     

Recurrences from malignant parotid salivary gland tumors

The clinical course of 130 patients treated for malignant parotid tumors at the three institutions have been reviewed. Fifty-six of these 130 patients developed recurrences following their primary treatment by a surgical procedure. There were a total of 109 recurrences among these 56 patients. The average number of recurrences was two per patient. The average survival from first recurrence was 3.7 years, with the median survival 2 years. The range of survival was 0.5 to 17 years. Once recurrence developed, treatment was by surgery, radiation therapy, chemotherapy, or a combination. Of 56 patients with recurrence, 33 are dead and 9 patients are alive with disease. Fourteen patients are alive and well with no evidence of disease. These NED patients had an average number of 1.6 recurrences and a median survival to date of only 3 years. Our study indicates that for the majority of patients who develop recurrence, survival is relatively short and treatment is usually ineffective in three of four patients. The authors conclude that after a surgical procedure for malignant salivary gland tumors, a trial of wide field postoperative radiation therapy to high dose should be considered as part of the initial treatment.     

One-hour paclitaxel plus carboplatin in the treatment of advanced non-small cell lung cancer: results of a multicentre, phase II trial

The aim of this phase II study was to determine the activity and toxicity of paclitaxel (administered by 1-h infusion) and carboplatin in advanced non-small cell lung cancer when used in a multicentre, community-based treatment setting. 100 chemotherapy-naive patients with stage IIIB or IV non-small cell lung cancer were treated between March 1995 and February 1996. All patients had Karnofsky performance status 70-100, measurable disease and adequate bone marrow, kidney and liver function. All patients received intravenous (i.v.) paclitaxel 225 mg/m2 by 1-h infusion followed immediately by carboplatin at a targeted area under the concentration time curve (AUC) of 6.0 using the Calvert formula. Courses were repeated every 21 days. Colony stimulating factors were not used routinely. 38 of 94 evaluable patients (40%) had objective responses to treatment (3 complete responses, 35 partial responses). An additional 32 patients had stable disease at initial re-evaluation. Weight gain during treatment was experienced by 47% of patients with objective response or stable disease. The median survival in this group of 100 patients was 8 months, with an actuarial 1-year survival of 42%. Leucopenia was common, but hospitalisation for treatment of neutropenia and fever occurred in only 3% of courses. Cumulative peripheral neuropathy was common, but usually appeared after the third or fourth course and was severe (grade 3) in only 15% of patients. Other grade 3 and 4 toxicity was uncommon. There was one treatment-related death due to sepsis. This large multicentre community-based phase II trial demonstrated the efficacy of paclitaxel and carboplatin combination chemotherapy in advanced non-small cell lung cancer. When paclitaxel is given by 1-h infusion, this regimen is easily administered in the outpatient setting.     

Hodgkin's disease presenting as pericarditis

Two patients presented with initial symptoms of pericarditis. Palpable lymph nodes developed a few weeks later and a diagnosis of Hodgkin's disease was made. Although rare, this mode of presentation of Hodgkin's disease has been reported previously, and it should be considered in the differential diagnosis of any patient with pericarditis with severe general symptoms or a prolonged course.     

Ureaplasma urealyticum, erythromycin and respiratory morbidity in high-risk preterm neonates

BACKGROUND: Response rate (RR) has been used as a defining endpoint of new-agent phase II trials for non-small-cell lung cancer (NSCLC). However, tumor responses to chemotherapy do not always result in prolonged survival of patients with this disease. DESIGN: Single-agent phase II trials were identified by a MEDLINE search of the period from 1976 to 1995. Associations between RR, median survival time (MST) and characteristics of patients who entered the trial, including tumor extent, performance status and prior chemotherapy, were studied by using the logistic regression model. RESULTS: A total of 183 treatment arms in 176 trials (including 10 randomized phase II trials) were identified. The overall RR in the 6768 evaluable patients was 11%. Eleven drugs, cisplatin, epirubicin, ifosfamide, edatrexate, irinotecan, vinorelbine, docetaxel, paclitaxel, etoposide, vindesine, and 254-S, produced a RR of more than 20%. An MST of eight months or longer was obtained with 12 drugs, but there were cases in which no objective responses were produced by these drugs. MST was correlated with RR (r = 0.504, P < 0.0001), but ranged broadly at a given level of RR. Multiple linear regression analysis showed a significant correlation between RR and MST (regression coefficient = 0.60, P = 0.00003) after adjustment for other variables. CONCLUSIONS: RR was significantly correlated with MST in single-agent phase II trials for NSCLC, but there is room for further consideration of the endpoint of these trials.     

A comparison of the costs of paclitaxel and best supportive care in stage IV non-small-cell lung cancer

PURPOSE: To compare the expenditures associated with single-agent paclitaxel (Taxol) with those of best supportive care as treatment for stage IV non-small-cell lung cancer (NSCLC). METHODS: The primary data sets of 2 phase II trials of paclitaxel in advanced NSCLC were obtained. Paclitaxel delivery costs were estimated at the Ottawa Regional Cancer Centre using the mean paclitaxel dose from the 2 phase II trials, 214 mg/m2, a 3-week schedule and a median of 3 treatment cycles. Data regarding dosage, costs and survival were incorporated into the Statistics Canada POpulation HEalth Model (POHEM), which generated hypothetical cohorts of patients treated either with best supportive care or paclitaxel. The POHEM model assigned diagnostic workup, treatment, disease progression and survival characteristics to each of these cohorts and tabulated the costs associated with each. RESULTS: The total cost of administering 3 cycles of chemotherapy was Can$8143 per patient. The strategy of treating NSCLC patients with paclitaxel cost $3375 more per patient than best supportive care. On the basis of the difference in survival duration between stage IV patients treated in the best supportive care arm of a previous National Cancer Institute of Canada trial and those represented in the pooled phase II survival results, the cost per life-year saved was $4778. For sensitivity analyses, the days of hospitalization for terminal care, number of cycles given and survival benefit produced were varied. The sensitivity analysis produced a cost per life-year saved of up to $21,377 under the least favourable assumptions. CONCLUSION: If large phase III trials confirm the survival benefits observed in the phase II trials, paclitaxel can be considered to be a cost-effective agent in the management of advanced NSCLC.     

Uptake and intracellular trafficking of asialoglycoprotein-polylysine-DNA complexes in isolated rat hepatocytes

Receptor-mediated gene delivery has been reported for a number of different receptor systems although the intracellular fate of such systems has not been systematically investigated. In this study, we have determined the fate of a commonly used asialoglycoprotein (ASGP)-dependent DNA delivery system in isolated rat hepatocytes. ASPG-polylysine (PLL296) was ionically complexed with pSV-CAT DNA at a molar ratio of 10:1. The resulting complex inhibited 125I-ASGP binding to rat hepatocytes but ASGP only partially inhibited the binding of complex. The ASGP-independent binding was due to the interaction of the PLL component of the complex with plasma membranes and could be minimised by replacing PLL296 with PLL19. Following internalisation, ASGP was cleaved from the complex and translocated to the lysosomes where it was degraded. The DNA, however, remained in an intracellular compartment that cosedimented with plasma membranes in Percoll density gradients. This study shows first that hepatocytes do not process DNA internalised as ASGP complexes in a manner similar to ASGP itself, and second that the differential sorting of the two cleaved molecules leads to a rapid intracellular compartmentalisation of the DNA. Controlled release from this compartment may be a means for prolonged gene expression in gene therapy protocols.     

Lung transplantation in chronic obstructive lung diseases

Lung transplantation (uni- or bilateral) is an accepted treatment option for patients with end-stage chronic obstructive pulmonary disease. Pulmonary function improves significantly and 5-year-actuarial survival is more than 70% at acceptable early mortality rates. Careful evaluation of risks and benefits in necessary because of the known donor-organ shortage and the risks of life-long immunosuppressive treatment. The bronchiolitis obliterans syndrome is still a nonsolved problem in the long-term course after LTx and it can influence late graft function and patient survival.     

p21 (WAF1/CIP1) expression is induced in newly nondividing cells in diverse epithelia and during differentiation of the Caco-2 intestinal cell line

The incidence of brain metastases secondary to small cell lung cancer (SCLC) is about 35% and the treatment strategy of brain irradiation with respect to dose and fractionation is controversial. In order to evaluate treatment outcome of brain irradiation in SCLC patients with brain relapse, we retrospectively evaluated all patients treated with brain irradiation in the eastern part of Denmark from 1988 to 1992 (PCI patients excluded). During this 5-year period, 101 evaluable patients were included (44 females, 57 males) (median age 61 years; range, 39-75 years). Forty-four patients, of whom 43 were in extracerebral complete remission (CR), received extended course (EC) brain irradiation (> 45 Gy, treatment schedule > 4 weeks). Fifty-seven patients received short course (SC) brain irradiation (< 30 Gy, treatment schedule < 1 week). Among the SC treated patients, 14 were in CR, 20 had partial remission or stable disease and 23 had progressive extracerebral disease. The median survival (from diagnosis of brain metastases) in the group receiving irradiation with EC (44 patients) was 160 days (range, 74-2021 days), while the 57 patients treated with SC had a median survival of 88 days (range, 20-948 days) (P = 0.00001, Log-Rank analysis). In a subgroup of 14 patients in extracerebral CR, receiving SC irradiation, the median survival was 83 days (range, 15-948 days). When the latter patients were compared to the 43 patients in CR in the group treated with EC, a statistically significant difference was shown (P = 0.034, Log-Rank analysis). Using Cox-hazard regression analysis with backward elimination, liver metastases and poor performance status were adverse prognostic signs, although the only significant parameters of survival were gender (female vs. male, relative risk of dying 1 and 1.52, P = 0.05) and schedule of brain irradiation (extended course vs. short course, relative risk of dying, 0.36 and 1, P < 0.001). Extended course irradiation of brain relapse secondary to SCLC seems in general to be of limited value, although a significant prolonged survival at approximately 7 weeks, was obtained. The prolongation of survival does not seem worthwhile considering the length of treatment time (5-6 weeks) compared to SC treatment (1 week). However, the data do not permit evaluation of the quality of life of the patients. This retrospective evaluation suggests the need for randomized trials with carefully planned quality-of-life assessments.     

Is there a role for low doses of mitotane (o,p'-DDD) as adjuvant therapy in adrenocortical carcinoma?

Four patients suffering from adrenocortical carcinoma were treated with low doses (1.5-2.0 g) of mitotane (o,p'-DDD) for the complete follow-up time following surgery (21-68 months). Treatment with mitotane was started shortly after surgical removal of the tumor (three patients) or the tumor and multiple lung metastasis (one patient). No significant side effects or complications from the medication were noted. Two patients remain disease free after 57 and 21 months on treatment. A third patient died of an unrelated reason (varicose vein bleeding) after 68 months on mitotane without evidence of tumor recurrence or metastasis. In the fourth patient, two lung metastasis were successfully removed after 48 months of follow-up. The patient is doing well and is disease free 6 months later. Though our series is too small to draw final conclusions, we suggest that low doses of mitotane, which are well tolerated, might offer prolonged disease-free survival in adrenocortical carcinoma. To be beneficial treatment has to be started early after surgical removal of the tumor and metastasis, and be continued for long periods of time.