Martin Mohren

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-1&agr; (SDF-1&agr;), 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±2.3×103/mL versus SR, 5.0±1.6×103/mL; P <0.01) were increased during persistAF only. Highest SDF-1&agr; levels were also observed during persistAF. Successful and unsuccessful cardioversion decreased CD34+HPCs temporarily (7.0±2.3×103/mL versus 24 hours: 5.0±1.5×103/mL; P <0.05). Forty-eight hours after successful cardioversion, SDF-1&agr; 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-1&agr; (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-1&agr; and possibly ANP, occurs within several weeks after successful cardioversion.

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.

Lenalidomide, bendamustine and prednisolone exhibits a favourable safety and efficacy profile in relapsed or refractory multiple myeloma: final results of a phase 1 clinical trial OSHO – #077

This phase 1 dose finding study tested a combination of lenalidomide, bendamustine and prednisolone (RBP) in 21 patients in five cohorts with advanced multiple relasped/refractory myeloma (MM) to determine the maximum tolerable dose (MTD) of the combination. The first cohort received a starting dose of lenalidomide 10 mg/d, days 1–21, bendamustine 60 mg/m2/d, days 1–2, and prednisolone 100 mg/d, days 1–4. Dose escalation was done in cohorts of three to six patients with lenalidomide dose increasing to 15, 20 and 25 mg, and after reaching 25 mg/d, bendamustine was increased to 75 mg/m2. A total of 21 patients were enrolled and all completed at least two cycles. Two patients developed dose‐limiting haemotoxicity: one patient on lenalidomide 25 mg/d and bendamustine 60 mg/m2 and another patient at the highest dose level (lenalidomide 25 mg/d and bendamustine 75 mg/m2). The MTD was not reached. Sixteen patients (76%) responded after at least two cycles of RBP with one stringent complete response (CR), one near CR, five very good partial response and nine partial response. After a median observation time of 16 months, progression‐free survival at 18 months was 48% and overall survival was 64%. In conclusion, RBP with lenalidomide 25 mg/d, days 1–21 and bendamustine 75 mg/m2 days 1–2 is well tolerated in patients with relapsed/refractory MM.

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.

Lymphomatoid Granulomatosis in a Patient with Rheumatoid Arthritis Receiving Methotrexate: Successful Treatment with the Anti-CD20 Antibody Mabthera

oxicam 15 mg/day for 21 months, showing little inflammatory activity of the RA when she complained about impaired nasal breathing and a tumour-like lesion of the nasal wing. Computed tomography showed a mass in the nasal septum (fig. 1). Histologic examination revealed LYG II°. EBV-nuclear-IgG and EBV-capsid-IgG were positive whereas EBV-capsid-IgM was negative, consistent with prior but not acute EBV infection. MTX was discontinued immediately. Since IFN-α has been implicated in the activation of arthritis [7], we felt reluctant to its use. However, CHOP seemed too aggressive in this elderly patient with low-grade LYG. Because of its effectiveness in the treatment of B cell lymphoma as well as RA, we decided to give 4 doses of mabthera 375 mg/m weekly. Complete remission (CR) of LYG was confirmed 4 weeks after the last dose. 19 months later, the patient was in ongoing CR of LYG and shows no clinical signs of active RA under sulfasalazine 2000 mg/day.

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.

Staphylococcal Scalded Skin Syndrome in an Adult Patient with T-Lymphoblastic Non-Hodgkin’s Lymphoma

Background: Staphylococcal scalded skin syndrome (SSSS) is an exfoliative dermatitis caused by Staphylococcus aureus infection. In contrast to infants, it is rarely observed in adults. SSSS in adults usually occurs in predisposed individuals such as those with renal failure or immunodeficiency, but has also been reported in otherwise healthy subjects. The reported mortality rate in adults is usually high because of serious underlying disease. Patient and Methods: We report a case of SSSS in a young female patient with T-lymphoblastic lymphoma, who survived this potentially lethal complication. Conclusions: To the best of our knowledge, this is the first case of SSSS in an adult patient with T-lymphoblastic non-Hodgkin’s lymphoma. Clinicians should be aware of SSSS as a rare but potentially fatal disorder, particularly in adult patients with malignancies undergoing aggressive chemotherapy.

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

Abstract Relapse after anthracycline based combination chemotherapy is frequently seen in patients with aggressive non Hodgki ns 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 distinct neoplasms 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.

Kapilläre Blutbildanalysen in der klinischen Praxis: eine sichere, zuverlässige und valide Methode / Capillary blood count analyses in clinical practice: a safe, reliable and valid method

Zusammenfassung In der Hämatologie erfolgen Blutbildbestimmungen teilweise durch kapilläre Punktion. Akzeptiert sind jedoch nur venöse Werte. Ziel dieser Arbeit war es daher, die Problematik der kapillären Blutbildbestimmung aus labormedizinischer und klinischer Sicht zu beleuchten. Dazu führten wir eine selektive Literaturrecherche durch. Ergänzend wurden eigene Daten dargestellt. Bei Erwachsenen lagen die kapillär-venösen Differenzen im Mittel für Hämoglobin bei +0,3 g/dL bzw. +0,2 mmol/L (+2,1%), für Hämatokrit bei +1,5% bzw. +0,02 L/L (+3,6%), für Leukozyten bei +0,2×103/μL (+2,7%), für neutrophile Granulozyten (absolut) bei +0,22×103/μL (+4,7%), für Thrombozyten bei –19×103/μL (–8,3%) und für Erythrozyten bei +0,1×106/μL (+1,8%). Bei Kindern waren die Differenzen größer als bei Erwachsenen: Hämoglobin +1,1 g/dL bzw. +0,7 mmol/L (+6,3%), Hämatokrit +3,1% bzw. +0,03 L/L (+6,0%), Leukozyten +2,0×103/μL (+14,6%), neutrophile Granulozyten (absolut) +0,91×103/μL (+11,0%), Thrombozyten –33×103/μL (–14,1%) und Erythrozyten +0,3×106/μL (+6,0%). Die kapillären Werte korrelierten sehr gut mit den entsprechenden venösen Werten. Die kapilläre Blutbildbestimmung ist risikoarm, zuverlässig, gegenüber einer venösen Bestimmung durchaus vorteilhaft und erbringt mit hoher Wahrscheinlichkeit richtig-positive bzw. richtig-negative Werte für Patienten mit Anämie, Polyglobulie, Thrombo- oder Neutrozytopenie im Vergleich zur venösen Blutbildbestimmung. Die kapilläre Blutbildbestimmung kann damit zumindest bei Erwachsenen in der klinischen Praxis eingesetzt werden. Abstract In haematology, blood count analyses are often performed on samples obtained by capillary puncture. However, only venous values are well accepted. This paper reviews the data available and highlights this topic from the viewpoint of laboratory medicine and clinical practice. We also present our own data. Mean capillary-venous differences were +0.3 g/dL or +0.2 mmol/L (+2.1%) for haemoglobin, +1.5% or +0.02 L/L (+3.6%) for haematocrit, +0.2×103/μL (+2.7%) for white blood cells, +0.22×103/μL (+4.7%) for absolute neutrophil counts, –19×103/μL (–8.3%) for platelets and +0.1×106/μL (+1.8%) for red blood cells. Differences were greater in children than in adults: +1.1 g/dL or +0.7 mmol/L (+6.3%) for haemoglobin, +3.1% or +0.03 L/L (+6.0%) for haematocrit, +2.0×103/μL (+14.6%) for white blood cells, +0.91×103/μL (+11.0%) for absolute neutrophil counts, –33×103/μL (–14.1%) for platelets and +0.3×106/μL (+6.0%) for red blood cells. The capillary values correlated very well with the venous values. Capillary blood count analysis is safe, reliable and advantageous compared to venous analysis and has high probability for true-positive and true-negative values for patients with anaemia, polyglobulia, thrombocytopenia and neutrocytopenia in comparison to venous blood count analysis. Therefore, at least in adults, capillary blood count analysis can be used as a substitute for venous blood count analysis in clinical practice.

Capillary blood count analyses in clinical practice: a safe, reliable and valid method 1

Abstract In haematology, blood count analyses are often performed on samples obtained by capillary puncture. However, only venous values are well accepted. This paper reviews the data available and highlights this topic from the viewpoint of laboratory medicine and clinical practice. We also present our own data. Mean capillary-venous differences were +0.3 g/dL or +0.2 mmol/L (+2.1%) for haemoglobin, +1.5% or +0.02 L/L (+3.6%) for haematocrit, +0.2×103/μL (+2.7%) for white blood cells, +0.22×103/μL (+4.7%) for absolute neutrophil counts, –19×103/μL (–8.3%) for platelets and +0.1×106/μL (+1.8%) for red blood cells. Differences were greater in children than in adults: +1.1 g/dL or +0.7 mmol/L (+6.3%) for haemoglobin, +3.1% or +0.03 L/L (+6.0%) for haematocrit, +2.0×103/μL (+14.6%) for white blood cells, +0.91×103/μL (+11.0%) for absolute neutrophil counts, –33×103/μL (–14.1%) for platelets and +0.3× 106/μL (+6.0%) for red blood cells. The capillary values correlated very well with the venous values. Capillary blood count analysis is safe, reliable and advantageous compared to venous analysis and has high probability for true-positive and true-negative values for patients with anaemia, polyglobulia, thrombocytopenia and neutrocytopenia in comparison to venous blood count analysis. Therefore, at least in adults, capillary blood count analysis can be used as a substitute for venous blood count analysis in clinical practice.