Prolonged haematological toxicity from the hyper-CVAD regimen: manifestations,frequency, and natural history in a cohort of 125 consecutive patients

The hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (hyper-CVAD) regimen has impressive efficacy in several haematological malignancies but is associated with considerable short-term haematological toxicity. Secondary myelodysplasia (MDS) or acute myeloid leukaemia (AML) also occurs. In this retrospective study, we also describe other prolonged haematological sequelae of this regimen. One hundred and twenty-five patients were treated with a median of six hyper-CVAD cycles and followed for a median of 28 months. Follow-up for cytopenias was censored at the next cytotoxic therapy. At 3 months post-therapy, 77 patients were evaluable. Cytopenias persisted in 59% of patients. Requirement for dose attenuation was the only factor significantly associated with persisting cytopenias (p<0.05). The median time to normalisation of counts for those with post-treatment cytopenias in the respective lineages was 9 months (range, 6-12) for anaemia, 6 months (range, 6-30) for neutropenia and 9 months (range, 6-30) for thrombocytopenia. MDS/AML was diagnosed in four patients at 4, 21, 24 and 37 months after therapy with a cumulative incidence rate of 4.43% at 4 years. These results indicate a considerable rate of prolonged haematological toxicity after hyper-CVAD and a modest rate of MDS at this limited follow-up. These findings likely reflect cumulative damage to haematopoietic stem cells.     

Effect of renin-angiotensin-aldosterone system inhibition, dietary sodium restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease: a post hoc analysis of a randomized controlled trial

BACKGROUND: Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels. STUDY DESIGN: Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. SETTING & PARTICIPANTS: 34 proteinuric patients without diabetes from our outpatient renal clinic. INTERVENTION: Stepwise 6-week interventions of losartan, sodium restriction (low-sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet. OUTCOMES & MEASUREMENTS: Urinary excretion of KIM-1, total protein, and N-acetyl-beta-d-glucosaminidase (NAG) as a positive control for tubular injury. RESULTS: Mean baseline urine protein level was 3.8 +/- 0.4 (SE) g/d, and KIM-1 level was 1,706 +/- 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 +/- 388 ng/d; P = 0.04), losartan/high sodium (1,184 +/- 296 ng/d; P = 0.09), losartan/LS (921 +/- 176 ng/d; P = 0.008), losartan/high sodium plus HCT (862 +/- 151 ng/d; P = 0.008) and losartan/LS plus HCT (743 +/- 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria (R = 0.523; P < 0.001), but not blood pressure or creatinine clearance. 16 patients reached target proteinuria with protein less than 1 g/d, whereas KIM-1 levels normalized in only 2 patients. Urinary NAG level was increased at baseline and significantly decreased during the treatment periods of combined losartan plus HCT only. The decrease in urinary NAG levels was not closely related to proteinuria. LIMITATIONS: Post hoc analysis. CONCLUSIONS: Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, sodium restriction, their combination, losartan plus HCT, and the latter plus sodium restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long-term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria.     

Surgical revascularization in patients with end-stage renal disease: results using a new paradigm in outcomes assessment

Studies evaluating the outcome of surgical revascularization (SR) for critical limb ischemia in patients who have end-stage renal disease (ESRD) have differed widely in their findings and conclusions. Differences in definitions of success are largely responsible for the varying outcomes. We developed a method of outcomes assessment that incorporates four all-inclusive endpoints to define success. These include primary graft patency to the point of wound healing, postoperative survival of at least 6 months, limb salvage of at least 1 year, and maintenance of ambulatory status of at least 6 months. The purpose of this study was to use this novel method of defining success to determine the outcome of SR in patients with ESRD. From 1998 to 2004, 40 patients (52 limbs) with ESRD and tissue loss underwent SR for limb salvage. Secondary graft patency and limb salvage rates at 36 months were 54.7 per cent and 53 per cent, respectively. When considering each of the four components used to define success separately, success encouragingly ranged between 60 per cent (patent graft until wound healing) and 87.5 per cent (survival for 6 months). However, if all parameters were combined, clinical success was achieved in only 40 per cent (16/40) of patients. Coronary artery disease was the only factor found to significantly reduce success (P = 0.04). In conclusion, using this multiparameter definition of success, which combines four rather modest outcome milestones, favorable outcome occurred in the minority of cases. This study challenges our current method of analyzing success and questions our therapeutic approach to patients with critical limb ischemia and ESRD.     

When the safety net of treatment has been removed: Patients’ unmet needs at the completion of treatment for haematological malignancies

Objective

To determine patients’ information, emotional and support needs at the completion of treatment for a haematological malignancy.

Methods

A self-report questionnaire was mailed to 113 adult patients.

Results

Sixty-six questionnaires were returned. The most frequently endorsed patient needs related to care co-ordination and help to manage the fear of recurrence. The most frequently endorsed unmet needs included managing the fear of recurrence, the need for a case-manager and the need for communication between treating doctors. Predictors of unmet needs included younger patients (p = 0.01), marital status (p = 0.03) and employment (p = 0.03). Almost two-thirds of patients (59%) reported they would have found it helpful to talk with a health care professional about their experience of diagnosis and treatment at the completion of treatment and endorsed significantly more need in the arenas of Quality of Life (p = 0.03) and Emotional and Relationships (p = 0.04).

Conclusion

This study provides valuable data on haematological cancer patients’ needs in the first 12 months of finishing treatment. It appears that many needs emerge or remain unresolved at this time.

Practice implications

An opportunity for patients to talk with a health professional about making the transition from active treatment to extended survivorship may be helpful.     

Contemporary outcomes of iliofemoral bypass grafting for unilateral aortoiliac occlusive disease: a 10-year experience

Current treatment of complex aortoiliac occlusive disease (AIOD) includes the aortobifemoral bypass or the femoral-femoral bypass. However, because of bilateral groin exposure and associated risks, there is a significant morbidity associated with these procedures. In appropriate patients with unilateral AIOD, the iliofemoral bypass graft (IFBPG) via a lower abdominal retroperitoneal incision can be an acceptable alternative. The purpose of this study is to review the safety and efficacy as well as long-term outcomes of IFBPG in patients with unilateral AIOD. From July 1997 through June 2006, 40 patients (64.3 +/- 11.2-years-old, range 41-89-years-old, 57.5% critical limb ischemia, 70% male, 95% smokers) with unilateral AIOD were treated with IFBPG. Perioperative complications and symptom resolution were measured and Kaplan-Meier life table analysis was used to analyze outcomes of primary and secondary patency, survival, limb salvage, contralateral intervention, and maintenance of ambulation and independent living status. The perioperative complication rate was 12.5 per cent (n = 5) including one patient who developed atrial-fibrillation and one who developed acute renal failure. Both patients experienced resolution of these symptoms before discharge. Other complications included one limb thrombosis and two wound infections. There were no perioperative deaths. Secondary patency was 97.5 per cent and 93.3 per cent at 1 and 5 years. Limb salvage in patients with critical limb ischemia (CLI) was 85.1 per cent and 79.1 per cent at 1 and 5 years. Limb amputation occurred due to infection (n = 2), or failed IFBPG (n = 2). Thirty-one patients (77.5%) experienced symptom resolution including 15 (88.2%) of the patients treated for claudication. Two patients (5%) required contralateral iliac intervention. Patient survival was 97.5 per cent and 64.5 per cent at 1 and 5 years. Greater than 90 per cent of patients maintained their functional independence at 5 years. IFBPG achieved excellent technical and functional outcomes, particularly in patients treated for vasculogenic claudication. This procedure is relatively safe and efficacious in a population of patients with complex unilateral AIOD and can be an acceptable alternative to the aortobifemoral bypass or fem-fem procedure.     

Surgical implications of early failed endovascular intervention of the superficial femoral artery

BACKGROUND: It is generally accepted that failed infrainguinal bypass with prosthetic material significantly compromises arterial run off, which may limit future revascularization. It is well known that the negative consequences of early vein graft thrombosis are limited, but the effect of failed peripheral angioplasty on the distal vasculature is poorly studied. The purpose of this study was to determine whether early failure after superficial femoral artery intervention influences subsequent revascularization options. METHODS: Between July 1, 1998, and June 30, 2006, 276 patients underwent endovascular intervention of the superficial femoral artery. A prospective analysis of angiograms done before the intervention and after early failure (相似文献   

Surgical considerations for ‘intrinsic＇ brainstem gliomas： proposal of a modification in classification

BACKGROUND： Brainstem gliomas are highly heterogeneous tumors both in their clinical manifestation and in their pathology. Despite significant advances in the surgery for brainstem gliomas many aspects of this pathology are still unelear. OBJECTIVE： To evaluate the clinical, radiological and surgical outcome of 40 focal ＂intrinsic＂ brainstem gliomas and propose a surgical strategyoriented classification. MATERIALS AND METHODS： A total of 40 focal ‘intrinsie’ （＂expanding variety＂） tumors have been operated over a period of 8.5-years （January 1998-June 2007）. Our criteria included patients with （1） well-defined gadolinium enhancing tumor, （2） relatively long duration of symptoms （〉 six months） and （3） good neurological functional status and independent for all activities of davy living. The cutoff size of 2 cm was not rigidly adhered to. RESULTS： The ＂intrinsic＂ brainstem tumors were classified into three types： Expanding, diffuse infiltrative and pure ventral varieties.     

High and Low Perceived Self-Control of Epileptic Seizures

PURPOSE: To define behaviours and to identify psychological, demographic, and epilepsy-related variables associated with high as opposed to low perceived self-control of seizures. METHOD: In a semistructured interview, 100 adults with intractable seizures were asked about their seizure precipitants and attempts at self-control of seizures. They also completed four psychological questionnaires. Latent Class Analysis was used to analyse the interview data to create two groups, High Controllers and Low Controllers, who were then compared on demographic, epilepsy, and psychological characteristics. RESULTS: Being able to identify and seeking out low-risk-for-seizure situations, avoiding high-risk-for-seizure situations, and making attempts at seizure inhibition were seizure behaviours that discriminated High from Low Controllers. The general probability of being a High Controller was greater than that of being a Low Controller. Perceived high self-control of seizures was associated with low chance-health locus of control. For Low Controllers, current age, age at onset of seizures, and duration of epilepsy history were related to psychological variables. A significantly higher proportion of the Low Controllers than High Controllers were women. CONCLUSIONS: Many people with intractable seizures do not accept their epilepsy as a condition over which they have no control. Perceived self-control of seizures, however, involves a complex interaction between epilepsy and psychological factors, with health locus of control an apparently important discriminator between High and Low Controllers.