Facing mortality: a qualitative in-depth interview study on illness perception, lay theories and coping strategies of adult patients with acute leukemia 1 week after diagnosis.

In patients with acute leukemia we investigated the illness perceptions, lay theories and coping strategies 1 week after diagnosis. Semi-structured in-depth interviews were conducted with 12 patients. The transcribed interviews were analyzed by methods of qualitative research. Dramatic narrations of overwhelming threat in younger patients contrast to rationalization in elderly patients. Feelings of helplessness and efforts of normalization become apparent. Intense descriptions of physical injury due to invasive procedures allow verbalizing the fear of the disease. While coping strategies are complex, the overall importance of trust is recognized. Mortal fears are indirectly indicated. The results have consequences for psycho-oncological training and patient education.

Effect of atrial fibrillation on hematopoietic progenitor cells: a novel pathophysiological role of the atrial natriuretic peptide?

BACKGROUND: Injury to the heart causes hematopoietic progenitor cells (HPCs) to migrate to the site of damage and to undergo cell differentiation. Studies suggest that myocardial progenitor cells invade atrial tissue. So far it is unclear, however, whether an atrial disease per se affects circulating HPCs. METHODS AND RESULTS: Seventeen patients with persistent atrial fibrillation (persistAF), 12 with paroxysmal AF (paroxAF), and 17 matched patients with sinus rhythm (SR) were studied. HPCs (CD34+ and CD34+/CD117+) were quantified with the use of a fluorescence-activated cell sorter; stromal cell-derived factor-1alpha (SDF-1alpha), vascular endothelium growth factor (VEGF), and atrial natriuretic peptide (ANP) were determined by immunoassays. In patients with persistAF, blood samples were obtained before as well as 10 minutes, 24 hours, and 48 hours after electrical cardioversion. CD34+HPCs (AF, 7.0+/-2.3x10(3)/mL versus SR, 5.0+/-1.6x10(3)/mL; P<0.01) were increased during persistAF only. Highest SDF-1alpha levels were also observed during persistAF. Successful and unsuccessful cardioversion decreased CD34+HPCs temporarily (7.0+/-2.3x10(3)/mL versus 24 hours: 5.0+/-1.5x10(3)/mL; P<0.05). Forty-eight hours after successful cardioversion, SDF-1alpha and CD34+HPC levels started to decline, reaching control levels after 59+/-19 days. CD34+/CD117+ and VEGF levels, however, were increased by DC energy but not by AF. ANP levels correlated with CD34+HPC (r=0.76; P<0.01) and SDF-1alpha (r=0.56; P<0.01). HPCs from patients with AF had a greater tendency to differentiate into cells expressing (cardio)myocyte markers ANP and myocyte enhancer factor-2. CONCLUSIONS: PersistAF appears to increase the potential of HPCs for (cardio)myogenesis. Restitution of CD34+HPC levels, mediated by SDF-1alpha and possibly ANP, occurs within several weeks after successful cardioversion.

Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma.

PURPOSE: This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study. PATIENTS AND METHODS: Three hundred twelve patients with "aggressive" non-Hodgkin's lymphoma aged

[Illness perceptions of patients suffering from acute leukaemia one week after diagnosis]. / Subjektive Krankheitsvorstellungen bei Patienten mit akuter Leukämie eine Woche nach Diagnostellung.

OBJECTIVES: To investigate illness perceptions, treatment expectations, and treatment experiences of patients suffering from acute leukaemia in the initial stage of their disease. METHODS: In the first week of treatment we interviewed twelve patients with acute leukaemia using a detailed semi-structured interview guide. To investigate the transcribed interviews we applied methods of qualitative research. Case analyses were assigned to interindividual comparison tables representing the following subject areas: complaints, diagnostics, causes, controllability, treatment experiences, and prognosis. This allowed us to describe similarities and contrasts. RESULTS: Dramatic narrations of overwhelming threat in younger patients are in contrast to downplaying, rationalizing, and factual descriptions especially in elderly patients. Feelings of helplessness and efforts of normalization become apparent. Experiences of visible and sensible physical injury are perceived as threatening. Prognosis is estimated as too positive. Mortal fears are only indirectly indicated. CONCLUSIONS: Our results have practical consequences for both patient education and psycho-oncological training.

Complete molecular remission in a patient with Philadelphia-chromosome positive acute myeloid leukemia after conventional therapy and imatinib.

Philadelphia-chromosome (Ph)-positive acute myeloid leukemia (AML) is rare and prognosis is poor with a median survival of six to seven months only. We report on a patient with Ph-positive AML (FAB M2, major BCR/ABL1 mRNA transcript, b2a2), who is in sustained complete cytogenetic and molecular remission for 15 months. Cytarabine-based chemotherapy was discontinued after two courses due to infectious complications. Since the b2a2 transcript was still detectable, imatinib was started with quantitative RT-PCR monitoring. This result is promising and worth further evaluation to establish the role of imatinib in patients with Ph-positive AML.

Pulmonary low-grade MALT-lymphoma associated with localized pulmonary amyloidosis. A case report.

We report on a female patient, who, at the age of 63 years, was found to suffer from low-grade MALT-lymphoma localized at her right upper eyelid. At the time of initial diagnosis, clinical staging showed no further organ involvement. Within the following two months, nodular infiltrates occurred in both lungs. Histopathological investigation of the pulmonary lesions showed pulmonary involvement by the low-grade MALT-lymphoma associated with large globular amyloid deposits of lambda-light chain origin. Since the tumor cells of the MALT-lymphoma showed restriction to lambda-light chain the amyloid deposits in this case were interpreted as being related to the MALT-lymphoma.

Fludarabine combination therapy for the treatment of chronic lymphocytic leukemia.

Fludarabine combination therapies have attained an increased popularity in the treatment of chronic lymphocytic leukemia (CLL). Among them, the combination of fludarabine/cyclophosphamide (FC) is by far the best regimen studied. Patients receiving FC at relapse show response rates (RRs) of 70%-94% with 11%-34% complete remission (CR) rates. In previously untreated patients with CLL, RRs of 64%-88% with 21%-46% CR rates were observed. The main side effects of FC are myelotoxicity and infections; most complications are reported as fever of unknown origin, infections of the upper respiratory tract, or herpes virus infection. There is probably a correlation between the higher dose of cyclophosphamide (> 750 mg/m2 per treatment course) and an increase in the number of severe infectious complications. Similar results were reported regarding the RRs and side effects of the combination of fludarabine/epirubicin. The triple combination of fludarabine/cyclophosphamide/mitoxantrone and fludarabine combinations with anti-CD20 (rituximab) or anti-CD52 (Campath-1H) antibody, might be even be more promising, since a relevant number of complete molecular remissions are achieved with these drugs. The precise role of fludarabine combinations within the overall treatment strategy remains to be determined. Our current recommendation is to use these combinations at relapse, while their use in first-line therapy should be investigated in clinical protocols. It remains to be shown whether patients with CLL achieve improved overall survival with these combination chemotherapies.

Thymic hyperplasia following successful treatment for nodular-sclerosing Hodgkin's disease.

A young female patient showed up with mediastinal bulky disease and lymph node swelling in her left supraclavicular region. Clinical and histological investigations proved nodular-sclerosing Hodgkin's lymphoma. The patient received combined modality treatment according to the protocols of the German Hodgkin's Disease Study Group and achieved complete remission. Six months later the chest X-ray and thoracic CT-scan showed mediastinal tumor masses suggesting relapsed Hodgkin's disease. Surprisingly, the histological investigation showed thymic hyperplasia as well as the absence of any signs of Hodgkin lymphoma. Thymic hyperplasia is well known as a potential differential diagnosis of mediastinal space-occupying lesions and also as a long-term complication in patients cured of Hodgkin's disease. A detailed case report and a complete review of literature are provided.

Acute myelofibrosis in a patient with diffuse large cell non Hodgkin's lymphoma and renal cancer.

Relapse after anthracycline based combination chemotherapy is frequently seen in patients with aggressive non Hodgkin's Lymphomas (NHL), whereas complications such as secondary leukemia or solid tumor rarely occur. We report a patient with diffuse large cell (DLC) NHL and concurrent renal cancer, who developed acute myelofibrosis (AMF) later in the course of her disease. This 60-year-old female patient presented with pancytopenia and a right sided renal mass. Diagnostic work up revealed severe bone marrow infiltration by DLC NHL and renal cancer T1N0M0G2. Cytogenetic and molecular evaluation of bone marow cells showed three distinct clones, (a normal 46XX karyotype, a ringed chromosome 7 and a third clone with an enlarged chromosome 2 as well as several fragments). The patient underwent nephrectomy and eventually received 6 cycles of CHOP 14 chemotherapy. Anemia persisted followed by severe granulocytopenia and thrombocytopenia 6 weeks later. Repeated bone marrow biopsy showed absence of lymphoma and/or cancer metastasis, but massive myelofibrosis with an increased number of atypical megakaryocytes. Considering the short clinical course and the absence of hepatosplenomegaly AMF was diagnosed. The concurrence of three distinctneoplasms within a short period of time as well as the complex cytogenetic aberrations found in her bone marrow cells reflect a strong individual susceptibility to malignant disease in this patient.

Fludarabine and bendamustine in refractory and relapsed indolent lymphoma--a multicenter phase I/II Trial of the east german society of hematology and oncology (OSHO).

The therapy of patients with relapsed or refractory indolent lymphoma relies on the development of new drug combinations. The drugs bendamustine and fludarabine have cytotoxic activity as monotherapy in indolent lymphoma and show synergism in vitro. In this study, we combined both drugs in a multicenter clinical phase I/II trial to evaluate their toxicity and efficacy. Bendamustine was given at 30 or 40 mg/m2/d (dose levels 1 and 2), fludarabine at 30 mg/m2/d, each drug on days 1 to 3. Six cycles were to be given every 4 weeks. A total of 29 patients with relapsed or refractory indolent lymphoma were included in the study. During phase I, 9 patients were treated at dose level 1 and 7 patients at dose level 2. Thirteen patients were added to the study during phase II. Fourteen patients had follicular lymphoma, 11 patients mantle cell lymphoma, 2 patients lymphoplasmocytic and 2 patients nodal marginal zone lymphoma. Median age was 62 years (range 39-74). All patients were in stages III or IV of their disease and had received prior chemotherapy with or without additional radio- or immunotherapy. The dose limiting toxicity was hematotoxicity in all cases and occurred in 3 of 7 evaluable patients at dose level I and in 3 of 7 patients at dose level 2. One patient at dose level 2 died of sepsis in neutropenia with persistent thrombocytopenia. The study was continued at dose level 1 (phase II). Analysis of 19 evaluable patients treated at dose level 1 reveiled hematotoxicity CTC grade III in 47% and grade IV in 26%. Neutropenic fever occurred in 4 patients (21%). On an intent-to-treat basis, 45% or 32% of all patients at dose level 1 reached CR or PR, respectively. Nine of 9 patients with mantle cell lymphoma responded to therapy. The overall response rate was 77%. Eight of 15 responders relapsed after a median follow-up time of 14 months (range 2-43). The major complication of fludarabine in combination with bendamustine is hematotoxicity. Dose level 1 with 30 mg/m2/d of both drugs on days 1 to 3 was defined as the recommended dose. Despite unfavorable prognostic features (histologic subtype, stage of disease, pretreatment) response rates were good with this regimen.

G-CSF-induced mobilization of CD34(+) progenitor cells and proarrhythmic effects in patients with severe coronary artery disease.

AIM: Granulocyte colony stimulating factor (G-CSF) therapy has been reported to be proarrhythmic. The in vivo mobilization of endothelial progenitor cells (EPCs) and the possible proarrhythmic effects in patients with severe coronary artery disease (CAD) and inducible ischemia have not been described. METHODS: We treated 8 patients (mean age = 69 +/- 10) suffering from severe CAD and angina pectoris (CCS 3 +/- 0.5) despite optimal medical therapy with subcutaneous G-CSF over 7 days to mobilize EPCs (CD34(+), CD117(+)). ECG monitoring was performed throughout the treatment period. A 24-hour ECG was recorded before and after G-CSF application. Mobilization of EPCs was monitored by fluorescent activated cell sorter (FACS-Calibur, Becton-Dickinson, Franklin Lakes, NJ, USA) analysis. Other medications remained unchanged. RESULTS: G-CSF therapy significantly increased peripheral leukocyte count from 7.45 +/- 2.4 to a peak of 42.2 +/- 10.9 x 10(3)/muL with a parallel rise in CD34(+) EPCs from 4.35 +/- 1.94 to 33.0 +/- 22.8/muL. The percentage of CD34(+)/CD117(+) cells changed from 0.32 +/- 0.25 to 0.24 +/- 0.28% (day of discharge, P = ns). During continuous ECG monitoring, no significant bradycardia, tachycardia, or changes in conduction were observed. Holter data collected after 7 days of G-CSF therapy showed no significant differences from baseline. A linear correlation (r = 0.76) was observed for the absolute values of deltaP wave duration and deltaCD34(+) concentration on day 2 compared to follow-up at 142 +/- 33 days, though it did not reach statistical significance (P = 0.29). CONCLUSION: This is the first study showing that mobilization of CD34(+) EPCs is safe in patients with severe CAD. The accompanying leukocytosis did not appear proarrhythmic. Changes in P wave duration might be attributable to G-CSF therapy.

Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study.

PURPOSE: Rituximab has been shown to be active in follicular lymphoma (FL), both as monotherapy and in combination with chemotherapy. We conducted a randomized trial comparing mitoxantrone, chlorambucil, and prednisolone (MCP) chemotherapy plus rituximab with MCP alone. PATIENTS AND METHODS: Previously untreated patients with stage III or IV CD20+ indolent or mantle cell lymphoma were randomly assigned to either eight 28-day cycles of MCP plus rituximab (R-MCP; n = 181) or eight cycles of MCP alone (n = 177). All patients who achieved a complete or partial remission were treated with interferon maintenance until relapse. Herein, we report the results from the primary analysis population of patients with FL, who constituted the majority of patients (56%) recruited to the trial (n = 201; R-MCP, n = 105; MCP, n = 96). RESULTS: Rates of overall and complete response were significantly higher in the R-MCP arm than the MCP arm (overall response, 92% v 75%, respectively; P = .0009; complete response, 50% v 25%, respectively; P = .004). With a median follow-up time of 47 months, median event-free survival (EFS) and progression-free survival (PFS) times were significantly prolonged with R-MCP compared with MCP (EFS, not reached v 26 months, respectively; P < .0001; PFS, not reached v 28.8 months, respectively; P < .0001), and overall survival (OS) was significantly improved with R-MCP compared with MCP (4-year OS rate, 87% v 74%, respectively; P = .0096). CONCLUSION: The R-MCP regimen significantly improves complete and overall response rates, EFS, PFS, and OS in patients with previously untreated advanced FL, without a clinically significant increase in toxicity.

Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial.

PURPOSE: To investigate whether combined-modality treatment (CMT) with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by extended-field radiotherapy (EF-RT) is superior to EF-RT alone in patients with early favorable Hodgkin's lymphoma (HL). PATIENTS AND METHODS: Between 1993 and 1998, 650 patients with newly diagnosed, histology-proven HL in clinical stages IA to IIB without risk factors were enrolled onto this multicenter study and randomly assigned to receive 30 Gy EF-RT plus 10 Gy to the involved field (arm A) or two cycles of ABVD followed by the same radiotherapy (arm B). Results At a median observation time of 87 months, there was no difference between treatment arms in terms of complete response rate (arm A, 95%; arm B, 94%) and overall survival (at 7 years: arm A, 92%; arm B, 94%; P = .43). However, freedom from treatment failure was significantly different, with 7-year rates of 67% in arm A (95% CI, 61% to 73%) and 88% in arm B (95% CI, 84% to 92%; P

Cardiac uptake of progenitor cells in patients with moderate-to-severe left ventricular failure scheduled for cardiac resynchronization therapy.

AIMS: Injury to the heart causes haematopoietic and endothelial progenitor cells (PCs) to migrate to the site of damage and to undergo PC differentiation, which may contribute to angiogenesis and myocardial tissue repair. We sought to determine the cardiac uptake of PC in patients with moderate-to-severe congestive heart failure (CHF) scheduled for cardiac resynchronization therapy. METHODS AND RESULTS: A total of 28 patients was included in the study. Fourteen patients had moderate-to-severe CHF with a mean left ventricular ejection fraction (LVEF) of 20 +/- 9%. The remaining patients had a normal LVEF and served as controls. PCs (CD34(+) and CD34(+)/CD117(+)) were quantified using a fluorescence-activated cell sorter. In CHF patients, PCs were determined from whole blood samples taken from the aorta, the coronary sinus (CS), and the superior vena cava (SVC) during right and left heart catheterization. Cardiac PC uptake was determined as the difference in PC levels between the aorta and the CS. Differences in CD34(+)PC counts (Delta0.11 +/- 0.98 x 10(3) mL(-1)) and relative amount of CD34(+)/CD117(+)PC (Delta0.08 +/- 0.31%) between the aorta and the CS were not significant. PC levels were comparable between the SVC, CS, and aorta. CD34(+) and PC levels did not correlate with New York Heart Association class (r(2) = 0.22), LVEF (r(2) = 0.01), LV diameter (r(2) = 0.05), QRS complex duration (r(2) = 0.1), or maximal O(2) uptake during exercise (r(2) = 0.08). There was no difference between patients with ischaemic cardiomyopathy (ICM) and non-ICM. Systemic PC levels were not different compared with age-matched controls without LV failure (CD34(+): 4.61 +/- 1.83 x 10(3) mL(-1) vs. control: 5.25 +/- 1.67 x 10(3) mL(-1); P = n.s.). CONCLUSION: Moderate-to-severe chronic CHF is not associated with elevated PC levels in the systemic circulation. A measurable cardiac uptake of CD34(+) and CD34(+)/CD117(+)PC cannot be demonstrated by FACS analysis in this cohort of patients.

Zygomycoses in patients with acute leukaemia.

Zygomycoses are rare invasive mould infections which mainly occur in immunocompromised patients, especially during prolonged neutropenia. The high mortality rate is due to a high failure rate of both intravital diagnosis and treatment. Exact diagnosis requires microscopic examination and proof by culture. The treatment consists of amphotericin B and surgical debridement. We report four recent cases of zygomycosis among 89 patients with intensively treated acute leukaemia at our institution. Three cases were breakthrough infections since the patients were under voriconazole treatment prior to diagnosis of zygomycosis. Only one patient had premortal diagnosis (paranasal sinus infection) and showed clinical response with amphotericin B and surgical debridement. A review of the literature of these emerging fungal infections is given and is focused on patients with acute leukaemia. In addition, the importance of autopsy as a tool for quality control and epidemiological studies is pointed out.

Lymphocyte subsets' reference ranges in an age- and gender-balanced population of 100 healthy adults--a monocentric German study.

Region-specific reference ranges for adult peripheral blood lymphocyte subsets have been established in few countries around the world, but most studies were restricted to younger adults for monitoring of HIV patients. The aim of this investigation was to establish age- and gender-specific reference ranges for healthy adults. Lymphocyte subsets were examined in 100 healthy volunteers (50 males, 50 females) aged 19-85 years by two-color flow cytometric analysis with a FACSCalibur. A statistically significant decline in the mean numbers of CD3+/CD8+ T cells and CD19+ B cells was observed beyond an age of 50 years, whereas the mean counts of NK cells and CD4+/CD8+ ratio significantly increased beyond the age of 50. Females < or = 50 years had significantly higher mean CD4+ T cell counts and lower NK cell counts than males < or = 50 years. Based on these results, we established reference values for three subgroups: males < or = 50 years, females < or = 50 years, and males/females > 50 years.

Metastatic adrenal neuroblastoma in an adult.

BACKGROUND: Neuroblastoma (NB) is a common malignancy in children, but rarely occurs in adults. Accepted unfavourable prognostic factors include age > 1 year, low histologic grade and advanced stage, MYCN amplification, chromosomal aberrations, elevations of neuron specific enolase and lactate dehydrogenase, and increased catecholamine metabolites in urine or serum. In adults, abdomen/retroperitoneum are the primary sites and in children the adrenal gland. CASE REPORT: A 51- year-old man was admitted to our hospital with hypertension and a large right retroperitoneal mass. Clinically, phaeochromocytoma was suspected. Tumour resection revealed adrenal NB grade III. Chemotherapy according to the paediatric German Neuroblastoma Trial (NB97) was started. Follow-up computed tomography showed regression of the enlarged mediastinal and retroperitoneal lymph nodes. Because of local and systemic progression palliative radiochemotherapy was started. The patient died 9 months after diagnosis. CONCLUSION: To the best of our knowledge this is the oldest NB patient registered so far in Germany. Currently there are no standard treatment guidelines for patients with NB in adulthood. Collection and evaluation of data in adult patients with this tumour are warranted in order to optimise treatment strategies.

The role of diagnosis in patients failing peripheral blood progenitor cell mobilization.

BACKGROUND: Failure to mobilize PBPCs for auto-logous transplantation has mostly been attributed to previous therapy and poses therapeutic problems. STUDY DESIGN AND METHODS: The role of underlying disease was analyzed in 17 of 73 (23%) patients with PBPC mobilization failure, and secondary mobilization with high-dose filgrastim was attempted. RESULTS: Of 16 patients with acute leukemia, 13 (81%) mobilized poorly. In contrast, of 57 patients with non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, and solid tumor, 53 (93%, p < 0.001) showed good PBPC mobilization. Relapsed disease did not predispose to poor mobilization. As secondary mobilization attempt, 7 patients received 25 micro g per kg per day filgrastim without chemotherapy leading to a 3.7 +/- 2.8-fold (SD) increase in the maximum number of circulating CD34+ cells (p = 0.104). PBPC apheresis yielded 3.3 (+/-0.5) x 10(6) CD34+ cells per kg of body weight in 5 patients. Four poor mobilizers received 50 micro g per kg per day filgrastim as second or third mobilization attempt. Circulating CD34+ cells in these patients increased by 1.5 (+/-0.7) compared with the primary G-CSF application. CONCLUSION: Selective PBPC mobilization failure was seen in patients with acute leukemia whereas remarkably good mobilization was seen in other malignancies. Increasing the filgrastim dose to 25 micro g per kg per day may allow PBPC collection in patients failing PBPC mobilization.

Thromboembolic complications after splenectomy for hematologic diseases.

Thromboembolic complications following splenectomy for hematologic diseases occur in up to 10% of patients and may range from portal vein thrombosis (PVT) to pulmonary embolism (PE) and deep vein thrombosis (DVT). Up to now there exist no recommendations for the duration and intensity of prophylactic anticoagulation, which usually follows local institutional protocols. We report on three consecutive patients with severe portal vein thrombosis and/or pulmonary embolism--one with fatal outcome--7 to 35 days after splenectomy for autoimmune hemolytic anemia, immunothrombocytopenia, and indolent lymphoma, respectively. Incidence and pathophysiology of thromboembolic events (TE) in this patient group as well as prophylactic anticoagulation will be discussed, including a review of the current literature on this topic.