Help-seeking behaviour of patients with haematological malignancies treated with autologous stem cell transplantation.

Patients with haematological malignancies undergoing autologous stem cell transplantation face a life-threatening illness and stressful treatment. Although many patients report problems, relatively few patients report a need for additional professional care after treatment. We aimed to gain insight into the factors underlying this discrepancy by exploring patients' needs and help-seeking behaviour in relation to their experienced symptoms and problems. A qualitative research design following the grounded theory approach was used. Twenty patients, treated with autologous stem cell transplantation in the past 2 years, participated in an individual semi-structured interview. Factors contributing to patients' help-seeking behaviour were derived from our data and ordered in the following categories: (1) transition from symptoms to problems; (2) preference for dealing with problems themselves and with help from relatives; (3) problem categories and coping strategies; and (4) motives for (not) bringing in professional help. We concluded that the mere presence of a symptom does not lead to help-seeking behaviour: this relationship is modified by patients' personal goals, future perspective and phase of recovery. Patients seem to prefer to deal with problems without professional care. Patients' actual appeal for professional care depends on their coping strategies, social network and knowledge of available 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.

Allogeneic transplantation after reduced-intensity conditioning with fludarabine-CY for both indolent and aggressive lymphoid malignancies.

We studied the outcome of allo-SCT after reduced-intensity conditioning in relapsed or refractory indolent and aggressive lymphoid malignancies. All 54 patients (diagnosis: B-CLL n=13, indolent lymphoma n=12, aggressive lymphoma n=13, transformed lymphoma n=16) received conditioning with fludarabine and CY between July 2001 and November 2010. They underwent allo-SCT because of relapse after auto-SCT or because no other therapy could lead to a meaningful remission. Patients received an unmanipulated peripheral blood stem-cell graft. Median follow-up was 67 months. Thirty-two patients had received rituximab. Immediately after transplantation, remission status had improved in 21 patients, all without DLI. During the follow-up six additional patients achieved CR without further therapy. Four-year OS (EFS) was 46% (46%) for B-CLL, 83% (75%) for indolent lymphoma, 69% (55%) for aggressive lymphoma and 74% (67%) for transformed lymphoma (P=0.28 (P=0.54)). Forty two percent developed acute GVHD, 68% chronic GVHD (16% limited, 52% extensive). Previous auto-SCT did not influence OS, while acute GVHD did. Two-year non-relapse mortality was 16%. In conclusion, reduced-intensity conditioning with fludarabine-CY is feasible and effective for both indolent and aggressive lymphoid malignancies, even after previous auto-SCT. Because of the excellent anti-B-cell/lymphoma activity fludarabine-CY decreases tumor load, gaining time for the development of a graft versus lymphoma effect.

Nutritional support in patients with GVHD of the digestive tract: state of the art.

An important complication of allo-SCT is GVHD, which commonly affects the skin, liver and digestive tract. Clinical symptoms of GVHD of the digestive tract (GVHD-DT) include excessive diarrhoea, abdominal pain and cramps, nausea and vomiting, gastrointestinal bleeding, dysphagia, and weight loss. Treatment is complicated and regarding nutritional support, only a few guidelines are available. Our aim was to critically appraise the literature on nutritional assessment, nutritional status and nutritional support for patients with GVHD-DT. Evidence shows that GVHD-DT is often associated with malnutrition, protein losing enteropathy, magnesium derangements, and deficiencies of zinc, vitamin B12 and vitamin D. Limited evidence exists on derangements of magnesium, resting energy expenditure, bone mineral density and pancreatic function, and some beneficial effects of n-3 polyunsaturated fatty acids and pancreatic enzyme replacement therapy. Expert opinions recommend adequate amounts of energy, at least 1.5 g protein/kg body weight, supplied by total parenteral nutrition in cases of severe diarrhoea. When diarrhoea is <500 mL a day, a stepwise oral upgrade diet can be followed. No studies exist on probiotics, prebiotics, dietary fibre and immunonutrition in GVHD-DT patients. Future research should focus on absorption capacity, vitamin and mineral status, and nutritional support strategies.

Auto-SCT in refractory celiac disease type II patients unresponsive to cladribine therapy.

Autologous hematopoietic SCT (auto-SCT) has been effective therapy for refractory disease, in both malignancies and severe autoimmune diseases. It seems feasible and safe for refractory celiac disease (RCD) type II, although long-term results have not been evaluated yet. With current therapies, progression into enteropathy-associated T-cell lymphoma (EATL) occurs in 60-80% patients, with a high mortality rate. Therefore, it is important to evaluate new treatment strategies. Between March 2004 and February 2010, 18 RCD II patients were evaluated for auto-SCT preceded by conditioning with fludarabine and melphalan, as a consequence of unresponsiveness to cladribine therapy. Adverse events, survival rate, EATL development and change in clinical, histological and immunological course were monitored. Thirteen patients were transplanted successfully and followed up for >2 years, 4-year survival rate was 66%. Only one patient died because of transplant-related complications. The majority of patients showed an impressive clinical improvement and five a complete histological remission. In five patients, auto-SCT could not be performed; they all died with a median survival of 5.5 months. EATL was observed in one transplanted patient, only after 4 years of follow-up. Auto-SCT after conditioning with high-dose chemotherapy in RCD II patients unresponsive to cladribine therapy is feasible and seems promising.

Disappointing outcome of autologous stem cell transplantation for enteropathy-associated T-cell lymphoma.

BACKGROUND: Despite treatment, enteropathy-associated T-cell lymphoma has a very poor outcome. Chemotherapy can be complicated by small bowel perforation, gastrointestinal bleeding and development of enterocolic fistulae. Here we report on the feasibility, safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation in patients with enteropathy-associated T-cell lymphoma (three upfront and one at relapse), with or without prior partial small bowel resection. METHODS: Four patients [two males, two females, mean age 65 years (range 60-69 years)] received high-dose chemotherapy followed by autologous stem cell transplantation. Partial small bowel resection has been performed in three patients. RESULTS: All four patients completed the mobilization and leucopheresis procedures successfully and subsequently received conditioning chemotherapy and transplantation. Engraftment occurred in all patients. No major non-haematological toxicity or transplantation-related mortality was observed. One patient has ongoing complete remission 32 months after transplantation. Three patients died from relapse within few months after autologous stem cell transplantation. CONCLUSIONS: Autologous stem cell transplantation seems unsatisfactory for patients with enteropathy-associated T-cell lymphoma. More intensive conditioning and aggressive chemotherapy with/or without targeted immunotherapy as well as allogenous stem cell transplantation needs to be explored.

[Radio-immunotherapy for B-cell non-Hodgkin lymphoma]. / Radio-immunotherapie bij het B-cel-non-hodgkinlymfoom.

Radio-immunotherapy is a new treatment modality for patients with B-cell non-Hodgkin lymphoma. In radio-immunotherapy, a therapeutic radionuclide is coupled to a monoclonal antibody directed against a tumour-specific or tumour-associated antigen. Biodistribution studies and dosimetry are used in the planning of radio-immunotherapy. Clinical studies, notably in patients with indolent non-Hodgkin lymphoma, have demonstrated the clinical feasibility and efficacy of this treatment. The use of a high dose ofradio-immunotherapy in combination with (high-dose) chemotherapy and peripheral stem-cell transplantation constitutes a supplemental treatment for patients who respond insufficiently or not at all to standard therapy. The exact place of radio-immunotherapy in the treatment of patients with non-Hodgkin lymphomas is not yet clear.

[Acute dyspnoea following transfusion of plasma-containing blood products]. / Acute kortademigheid na transfusie van plasmabevattende bloedproducten.

A 35-year-old male patient who was given chemotherapy because of chronic myeloid leukaemia became dyspnoeic after transfusion of thrombocytes; initially, no explanation could be found for this dyspnoea. He went home before all diagnostic procedures were evaluated. Chest X-ray revealed bilateral pulmonary oedema, which could be due to transfusion-related acute lung injury (TRALI), especially since there were no indications for a cardiac aetiology. The patient was sent to the nearest hospital where he was treated with diuretics and observed for 24 hours. There were no complications. The pathogenesis of TRALI has been attributed to an interaction between anti-granulocyte antibodies and granulocytes. In addition, bioactive compounds produced during the storage of blood products have been implicated. It is important to recognize TRALI as the cause of dyspnoea when cardiac or pulmonary causes are excluded. The overall prognosis is good when treatment is started in time. The management of TRALI is supportive, with mechanical ventilation when necessary. After excluding donors with proven anti-granulocyte antibodies from further donation, there is no increased risk for recurrent episodes after future transfusion of plasma-containing blood products.

[Sternal pain: not always harmless]. / Pijn in het sternum: niet altijd onschuldig.

In two patients, men aged 39 and 66 years, a sternal mass in combination with pain developed. One patient was diagnosed with a non-Hodgkin lymphoma located in the sternum and the other one with a primary chondrosarcoma of the sternum. They both recovered after treatment. The differential diagnosis of disorders of the chest wall is troublesome and includes haematologic, rheumatologic and infectious processes. Tietze's syndrome is a rare cause of pain and non-suppurative swelling of the costosternal joints. However, tumours of the anterior chest wall can also cause these symptoms and these must therefore be excluded if the complaints persist or the swelling progresses. The most common malignant tumours of the chest wall are non-Hodgkin lymphoma, primary chondrosarcoma and metastases. Diagnostics should consist of blood tests and X-rays. CT and MRI scans are more helpful in establishing the diagnosis. A definitive diagnosis can only be determined by biopsy.

Inactivation and repair of double-stranded DNA damaged by the aziridinyl nitroimidazole RSU 1069.

Incubation of RSU 1069 in the presence of biologically active double-stranded phi X174 DNA resulted in, depending on pH, ionic strength and concentration of drug, inactivation of the DNA. A variety of lesions are induced including a high number of single-strand breaks and alkali-labile lesions, which are at most partly lethal. The main inactivating damage consists probably of base damage, induced by alkylation. A considerable part of the damage induced by RSU 1069 can be repaired by the various repair enzymes of the bacterial host of the phi X174 DNA. Finally the damage (pattern) depends considerably on the ionic composition of the reaction solution, which can be explained by an equilibrium model presented in this paper.

Interaction of RSU 1069 and 1137 with DNA in vitro. Biological implications and mechanistic aspects.

We have examined the capacity of the nitroimidazole aziridine antitumour drug RSU 1069 to react with DNA in vitro in order to get a better understanding of its mechanism of action. Moreover, we have utilized biologically active phi X174 DNA to investigate the biological relevance of the chemical DNA modification induced by the drug. Incubation of RSU 1069 in the presence of single-stranded phi X174 DNA resulted in extensive inactivation of the DNA, which is dependent on the concentration of drug and temperature. Only about 2% of the inactivating damage can be attributed to strand breakage. The main damage most probably consists of base damage, of which a part is non-lethal and alkali-labile which in turn can be converted into lethal lesion and subsequently into a break applying a post-incubation alkali treatment. Furthermore, from the dependence of the inactivation and also the formation of breaks on pH and ionic strength, it is concluded that the reaction most probably takes place between a protonated RSU 1069 and a negative DNA coil and that the damage pattern reflects the difference in reactivity of RSU 1069 with the phosphate groups and the bases in DNA. Comparison between RSU 1069 and its ring-open hydrolysis product RSU 1137 revealed that (lethal) damage induced in the DNA must be ascribed to the alkylating properties of the aziridine moiety.