Hematopoietic cell transplant nurse coordinators' perceptions of related donor care: a European survey from the EBMT Nurses Group.

Allogeneic haematopoietic cell transplantation (HCT) is a curative procedure for patients with haematological malignancies and immune deficiencies. A human leukocyte antigen (HLA) identical sibling is only available for 25-35% of patients in need. The improvement in haplo-identical transplantation has led to a marked increase in cell donation from relatives. Despite international recommendations, discrepancies in related-donors (RD) care exist between centres, particularly regarding medical suitability criteria, consenting procedures and donor follow-up. This European survey aimed to explore hematopoietic cell transplantation coordinators nurses' (HCT-CNs) perceptions of RD care, in particular the association with the presence or not of an independent unit (IU). Ninety-three HCT-CNs from seventy-six EBMT centres responded, representing 19 countries (response rate: 27%). Our results did not show a significant association between IU and HCT-CNs perceptions of related-donors care. The practices for RD care vary among centres regarding presence or not of an IU (48%), person caring for RD (haematologist in 54%, HCT physician in 17%, HCT-CNs in 20%), person to whom the results of HLA typing are communicated, use of a booklet for RD, follow-up or not and periodicity of follow-up. Qualitative data highlight the related-donation ethical issues and the need for improvement in RD care. HCT-CNs' main concerns were: the necessary confidentiality to insure the voluntary status of RD, the perceived conflict of interest felt by professionals when managing both patients and RD, plus the psychosocial aspects of related-donation. Even if there is a variety of a practice among centres, the presence of an IU is not significantly associated with an improvement in RD care.

A randomized clinical trial on the effectiveness of an intervention to treat psychological distress and improve quality of life after autologous stem cell transplantation.

Psychological distress contributes to impaired quality of life in hematological cancer patients. Stepped care treatment, in which patients start with the least intensive treatment most likely to work and only receive more intensive interventions if needed, could improve distress. We aimed to evaluate the outcome of stepped care treatment on psychological distress and physical functioning in patients treated with autologous stem cell transplantation for hematological malignancies. In the present study, we performed a randomized clinical trial with two treatment arms: stepped care and care as usual. Baseline assessment and randomization occurred during pre-transplant hospitalization. Stepped care was initiated after 6 weeks, consisting of (1) watchful waiting, (2) Internet-based self-help intervention, and (3) face-to-face counseling/ psychopharmacological treatment/ referral. Follow-up measurements were conducted at 13, 30, and 42 weeks after transplantation. Stepped care (n = 47) and care as usual (n = 48) were comparable on baseline characteristics. The uptake of the intervention was low: 24 patients started with step 1, 23 with step 2, and none with step 3. Percentages of distressed patients ranged from 4.1 to 9.7 %. Ten percent of patients received external psychological or psychiatric care. No statistically significant differences were found between stepped care and care as usual on psychological distress or physical functioning in intention to treat analyses, nor in per protocol analyses. The stepped care program was not effective in decreasing psychological distress. The low intervention uptake, probably related to the low levels of psychological distress, offers an explanation for this outcome. Future research should take into account patients' specific care needs. Netherlands Trial Registry identifier: NTR1770.

Chemotherapy-induced neuropathy in multiple myeloma: influence on quality of life and development of a questionnaire to compose common toxicity criteria grading for use in daily clinical practice.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) may negatively influence multiple myeloma (MM) patients' health-related quality of life (HRQOL). Dose modification is the only way to minimize CIPN. To measure CIPN in daily practice, the Indication for Common Toxicity Criteria (CTC) Grading of Peripheral Neuropathy Questionnaire (ICPNQ) was developed which can be completed within five minutes by the patient. The aims of this study were to (1) perform a psychometric evaluation of the ICPNQ and (2) examine the prevalence of CIPN and its influence on HRQOL in population-based MM patients. METHODS: One hundred fifty-six MM patients, diagnosed between 2000 and 2014, completed the ICPNQ, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20), and EORTC QLQ-C30 (65 % response). RESULTS: The psychometric analyses showed a Cronbach's alpha of 0.84, 0.74, and 0.61 for, respectively, the sensory, motoric, and autonomic subscales of the ICPNQ. Test-retest reliability and construct validity were good for all subscales. Overall, 65 % of patients reported grade 2-3 neuropathy according to the ICPNQ. Patients with the highest CTC grades (grade 2 with neuropathic pain and grade 3 (38 %)) according to the ICPNQ reported significantly worse scores on all EORTC QLQ-CIPN20 subscales compared to patients with lower CTC grades (p ≤ 0.002). In addition, they reported statistically significant and clinically relevant worse HRQOL scores on almost all EORTC QLQ-C30 subscales. CONCLUSIONS: CIPN is a common side effect in MM patients, which has a negative impact on HRQOL. The ICPNQ is a valid instrument to distinguish the highest CIPN CTC grades from the lower CTC grades necessary to decide on dose modifications of chemotherapy in daily clinical practice.

Nurses' practice patterns in relation to adherence-enhancing interventions in stem cell transplant care: a survey from the Nurses Group of the European Group for Blood and Marrow Transplantation.

Recipients of stem cell transplants (SCT) must accurately manage multiple medications as non-adherence jeopardises treatment benefits. There is an evidence base for the efficacy of adherence-enhancing interventions; however, level of clinical implementation is unknown. This study aimed to identify patterns of practice in assessing medication adherence, screening for risk factors of non-adherence, interventions used in SCT to improve adherence and how nurses perceive the effectiveness of such interventions. A convenience sample of 143 European nurses completed a 29-item questionnaire measuring the frequency and perceived effectiveness of assessment/screening methods for adherence and three types of intervention (educational/cognitive, counselling/behavioural and psychological/affective). Questioning patients about adherence was the most regularly used assessment method (51.5%). Nurses used a median of seven interventions (interquartile range: six) 'frequently', the most popular being provision of reading materials (79%). The interventions perceived as most effective were; providing individual patient/family with teaching and reading materials. This is the first study exploring patterns of practice relating to adherence in SCT. Educational interventions were the most frequently employed style of intervention, which is at odds with recent data suggesting limited efficacy with this style of intervention. Combining educational, behavioural and psychological interventions would more accurately embrace current understanding.

[Less use of alternative treatments by cancer patients in 2002 than in 1999]. / Minder gebruik van alternatieve behandelingen door kankerpatiënten in 2002 dan in 1999.

OBJECTIVE: To determine the use of alternative diets and other alternative treatments in 2002 compared to 1999. DESIGN: Descriptive, questionnaire. METHOD: During the period 13-26 May 2002 a survey was held among all patients visiting the outpatient clinic of the Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital, Amsterdam, the Netherlands. Patients were asked about their current and past use of alternative therapies, their reasons for using these therapies, the way they were informed about these therapies and the expenses involved. The data were compared with the results of a similar study during the period 15-19 March 1999. RESULTS: Of the 729 patients who fulfilled the inclusion criteria, 66 (9%) declined to participate in the study. Of the remaining 663 patients (average age 58.5 years; 28% male), 131 (20%) used an alternative therapy. Of these, 43 patients (7%) used an alternative diet, mainly the Houtsmuller diet, and 88 patients (13%) used a mixture of alternative therapies such as homeopathy, vitamins and herbs. In 1999, 131 patients (30%) used an alternative form of treatment, 51 (13%) of whom used a diet. Of the 43 users of diets in 2002, 11 (26%) believed that the diet would slow down the disease process; in 1999 this was 53% (27/51). Of the 131 users of alternative therapies in 2002, 55% had been made aware of the possibilities of alternative treatments via family and friends. Internet and TV played a minor role as a source of information. 33 (79%) of the diet users informed their physician or nurse about the use. The diet users spent an average of 170 euro per month on their diets. CONCLUSION: Both the percentage of cancer patients who used an alternative diet and the percentage of diet users who believed that a diet could affect the course of the disease were reduced by half compared to three years earlier.

Pharmacokinetics of amifostine and its metabolites in patients.

The pharmacokinetics of the cytoprotective agent amifostine (EthyolR; WR 2721) and its main metabolites (WR 1065 and the disulphides) were studied in patients participating in two phase I trials concerning carboplatin or cisplatin in combination with amifostine. Patients were treated with a single dose or three doses of amifostine (740 or 910 mg/m2). The single or first dose was given as a 15 min i.v. infusion just before administration of the chemotherapeutic agent. The additional two infusions were administered 2 and 4 h thereafter. Amifostine was rapidly cleared from the plasma, due to, at least in part, the fast conversion into WR 1065. A biphasic decrease with a final half-life of 0.8 h was observed. The active metabolite WR 1065 was cleared from the plasma with a final half-life of 7.3 +/- 3.6 h. The short initial half-life of WR 1065 can be explained by its fast uptake in tissues and the formation of disulphides. The disulphides were cleared with a final half-life of 8.4-13.4 h and were detectable for at least 24 h after treatment. They may serve as an exchangeable pool of WR 1065. The amifostine peak values at the end of each 15 min infusion did not accumulate in the multiple dosing schedule. For WR 1065 a trend towards an increase in the peak levels was observed [C1,max: 47.5 +/- 11.9 microM, C2,max: 79.0 +/- 13.2 microM, C3,max: 84.8 +/- 15.1 microM, (n = 6)], whereas a trend towards a small decrease was observed for the peak levels of the disulphides [C1,max: 184.2 +/- 12.6 microM, C2,max: 175.0 +/- 23.7 microM, C3,max: 166.0 +/- 17.2 microM, (n = 6)]. This latter finding might suggest a saturation of the disulphide formation or a change in the uptake or elimination of WR 1065, which would result in higher WR 1065 levels in plasma and tissues, after multiple doses of amifostine.

Pharmacokinetics of carboplatin with and without amifostine in patients with solid tumors.

We showed previously that amifostine (WR 2721; Ethyol), a protector against carboplatin-induced toxicities, changed the pharmacokinetics of carboplatin in tumor-bearing nude mice. In the present study, the influence of amifostine on the pharmacokinetics of carboplatin was studied in patients when carboplatin was given in combination with three doses of amifostine, administered just before the carboplatin infusion and 2-4 h thereafter. Compared with a control group of patients who received carboplatin alone, the patients receiving the combination had a longer final half-life of ultrafilterable platinum species [5.0 h versus 3.5 h in patients with a normal creatinine clearance (Clcr > 80 ml/min); 5.6 h versus 4.2 h in those with an impaired renal function (50 < Clcr < 80 ml/min)]. This might be caused by an influence of amifostine on the renal clearance of carboplatin as suggested by a transient increase in serum creatinine levels 24 h after treatment in the patients receiving the combination (mean +/- SD: 34.1% +/- 17.2% versus -1.8% +/- 16.5% in patients treated with carboplatin alone). The impact of these changes on the area under the concentration-time curves of the ultrafilterable platinum species was hardly noticeable in patients with a normal renal function but led to a significant increase in patients with an impaired renal function (395 +/- 59 micromol/l.h versus 280 +/- 62 micromol/l.h in patients receiving carboplatin alone). The clinical relevance of this influence is unclear, although theoretically it may result in an increase in the efficacy of carboplatin, as has been observed in tumor-bearing nude mice.

A dose-finding and pharmacokinetic study of reversal of multidrug resistance with SDZ PSC 833 in combination with doxorubicin in patients with solid tumors.

Forty-two patients with advanced solid tumors were entered into a dose-finding study of the combination of doxorubicin with the cyclosporin analogue SDZ PSC 833 (PSC), given by oral route. Patients received PSC at escalating doses, ranging from 2.5 to 25 mg/kg/day, for 5 days, in doses given every 12 h. Doxorubicin was given by i.v. push on day 3 of PSC administration, 4 h after the morning dose of PSC. Pharmacokinetic analyses of PSC and doxorubicin were performed. A total of 38 patients received a combination of PSC and doxorubicin, and 27 received doxorubicin alone in the first course. The major toxicity of the combination was hematological and was significantly more severe than that with doxorubicin alone; severe myelosuppression was already observed at the first PSC dose level, which required doxorubicin dose reduction from 50 to 35 mg/m2. At all dose levels of PSC, up to 17.5 mg/kg/day, there were at least two patients with grade 3 or 4 hematological toxicity, which was manageable in less heavily pretreated patients. A further PSC dose escalation was performed to 25 mg/kg/day, together with doxorubicin, at a further reduced dose of 20 mg/m2. At this dose, central nervous system toxicity became the most relevant side effect. The increase of toxicity in the combined treatment was supported by a significant increase of the area under the plasma concentration-time curve to infinity of doxorubicin (54%) and a 10-fold increase of the area under the plasma concentration-time curve to infinity of doxorubicinol. The pharmacological interaction was not dependent on the plasma concentration of PSC. The total body clearance of doxorubicin decreased by 30%. PSC plasma concentrations of >1 microM at the time of doxorubicin administration were, in general, found at a dose of 7.5 mg/kg/day or higher. One patient had a partial response. In conclusion, PSC plasma concentrations that can revert multidrug resistance in experimental models could be achieved in patients who have solid tumors and who are treated with doxorubicin. However, a marked pharmacological interaction was found between doxorubicin and PSC, which led to substantial increase in hematological toxicity and required marked reduction of the doxorubicin dose. Further study of PSC may be warranted, in association with the investigation of P-glycoprotein expression and concentration of drugs in the tumor tissues.

Paclitaxel (Taxol) concentrations in brain tumor tissue.

BACKGROUND: Paclitaxel (Taxol) is a novel chemotherapeutic agent, active against a variety of tumors. It is not known whether the drug penetrates brain tumor tissue. PATIENTS AND METHODS: Three patients with a recurrent glioma received paclitaxel (175 mg/m2) in a 3-hour i.v. infusion prior to surgery. Paclitaxel concentrations were measured in the tumor tissue, cerebrospinal fluid, cyst fluid, plasma and, in one patient, normal brain tissue. RESULTS: Tumor tissue concentrations were in the therapeutic range in all three patients. Brain tissue concentration, however, was below the detection limit of the trial. CONCLUSIONS: These findings suggest that paclitaxel may have a place in brain tumor therapy. The low concentration in normal brain tissue, as observed in one patient, may suggest, however, that the drug does not cross the intact bloodbrain barrier.

Maternal haemolysis, elevated liver enzymes and low platelets syndrome: specific problems in the newborn.

To evaluate the effects of maternal haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome on the fetus and neonate we retrospectively investigated the outcome of 87 pregnancies. All women showed thrombocytopenia, elevated liver enzymes and haemolysis. None of them died. Nine infants were stillborn (9.9%). Of the 82 liveborn infants, 66 were delivered by caesarean section. Median gestational age of the liveborn infants was 32.6 weeks, mean birth weight was 1576 g +/- 699 g (mean +/- SD). Of these infants, 44% were small for gestational age. Perinatal asphyxia rate was 21.6%. Nine infants died in the 1st week after birth. Complications during admission included neonatal respiratory disease (43.2%), hyperbilirubinaemia (44.7%), persistent ductus arteriosus (16.2%), thrombocytopenia (34%) and hypoglycaemia (16.2%). Artificial ventilation was necessary in 37 infants. Mean duration of admission was 51 days. HELLP syndrome is associated with poor perinatal outcome; the incidence of caesarean section is high and there is an increased risk for preterm birth and growth retardation. No specific neonatal pathology due to maternal HELLP syndrome was found.