Peter Meusers

Improvement of Overall Survival in Advanced Stage Mantle Cell Lymphoma

PURPOSE Mantle cell lymphomas (MCLs) represent a clinically aggressive lymphoma subtype with a poor prognosis. To explore a potential progress in outcome a historical comparison was performed using data from the Kiel Lymphoma Study Group (KLSG; 1975 to 1986) and the German Low Grade Lymphoma Study Group (GLSG; 1996 to 2004). PATIENTS AND METHODS All patients with the histologically confirmed diagnosis of advanced-stage nonblastoid MCL were eligible. To minimize the potential heterogeneity of different risk profiles frequency matching was pursued. In addition, we adjusted for potential confounding variables by multiple Cox regression. RESULTS A total of 520 patients were assessable, 150 from KLSG and 370 from GLSG studies. The median overall survival was 2.7 years for KLSG patients as compared with 4.8 years for GLSG patients (P < .0001). The 5-year survival rates were 22% in the KLSG group (95% CI, 13% to 31%) as compared with 47% for GLSG treated patients (95% CI, 38% to 55%). The hazard ratio adjusted for performance status, lactate dehydrogenase, and age was 0.44 for GLSG patients (95% CI, 0.32 to 0.59). CONCLUSION Median overall survival of patients with advanced nonblastoid MCL almost doubled during the past 30 years. Potential reasons for this apparent improvement in overall survival include the application of anthracycline-containing regimens and new approaches, such as antilymphoma antibodies or stem cell transplantation. Advances in general supportive care, new diagnostic tools, and general improvement of life span might have also reinforced this effect. However, our results are questioning the validity of historical comparisons which had been frequently applied in previous trials.

Infection by Alcaligenes xylosoxidans subsp. xylosoxidans in Neutropenic Patients

Alcaligenes xylosoxidans subsp. xylosoxidans (A. x. xylosoxidans) is a nonfermenting gram-negative peritrichous rod and opportunistic pathogen. The organism is frequently found in an aqueous environment. In the past few years, nosocomial infections caused by A. x. xylosoxidans have become more evident. The literature suggests that systemic infections are severe and often lethal and an optimal antibiotic therapy is not well established. This report describes nosocomial infections in 11 patients of a hematology ward over a 2-month period. Primary infection occurred during the neutropenic phase after cytotoxic chemotherapy. Reinfection spread from central venous catheters that had been implanted before the first infection. The bacteremia was successfully treated by imipenem. None of the 11 patients died from the bacteremia, but 3 died of their underlying diseases. Despite an intensive search for the source, the route of infection remained uncertain. Nosocomial infections by A. x. xylosoxidans are of growing importance in high-risk patients. Although the source of infection often remains unknown, infection seems to originate from contaminated solutions. Treatment with imipenem and the removal of central venous catheter systems successfully eliminated A. x. xylosoxidans, which adheres to plastic material.

Repp86: a new prognostic marker in mantle cell lymphoma.

Abstract:  Objectives: Proliferation indices are important prognostic factors for the clinical outcome of patients with mantle cell lymphoma (MCL). We investigated whether the expression of repp86 (restrictedly expressed proliferation‐associated protein 86 kDa), a new proliferation specific marker expressed in the cell cycle phases G2, S and M, but not in G1, correlates with the clinical course in patients with MCL. Patients and Methods: Biopsy specimens from 94 untreated patients enrolled in two multicenter trials were investigated immunohistochemically with monoclonal antibodies against CD20, CD5, CD3, CD23, cyclin D1, and repp86 (Ki‐S2). Results: Patients with 0–1% repp86 expression had a median overall survival time of 71.0 months, compared with 38.2 months for patients with 1–5% positive cells and 25.4 months for patients with 5–10% positive tumor cells. Patients with repp86 expression of more than 10% showed the shortest survival (median: 15.0 months). Kaplan–Meier analysis revealed a significant difference in the overall survival time between patients with very high (>10%) and very low (0–1%) repp86 expression (P < 0.0001) in the tumor cells. The multivariate analysis revealed repp86 expression to be superior to other clinical characteristics as a prognostic factor (P = 0.0016). Conclusion: Based on these findings, repp86 expression is a new important prognostic factor in MCL.

Growth pattern and distribution of follicular dendritic cells in mantle cell lymphoma: a clinicopathological study of 96 patients

Mantle cell lymphoma (MCL) is an aggressive lymphoma with accepted risk factors such as proliferation markers. To date, the different follicular dendritic cell (FDC) patterns have never been analyzed in comparison with the overall survival time. Lymph node biopsy specimens from 96 patients were analyzed by conventional morphology and immunohistochemistry with antibodies against cluster differentiation (CD)20, CD5, CD23, cyclin D1, and FDC (Ki-M4P). Two groups can be distinguished with different FDC patterns: a nodular pattern in 79 cases and a diffuse pattern in 17 cases. A Kaplan–Meier analysis revealed significantly better survival for the nodular group (p=0.0312). This group was subdivided into a group with a nodular FDC pattern similar to the FDC distribution in primary follicles (PF-nodular in 72 cases) and one with a nodular FDC pattern resembling the colonization of germinal centers (GCs) by tumor cells (GC-nodular in seven cases). A Kaplan–Meier analysis showed that patients with MCL with a PF-nodular FDC pattern had a significantly better clinical outcome than patients with the other two patterns (p=0.0033). If only cases with classical cytology (n=79) were analyzed (blastoid types excluded), patients with a PF-nodular FDC pattern had a better clinical outcome (p=0.0008). The distribution of FDC in MCL is a diagnostic tool for identifying patients with a better clinical prognosis.

Lysosomal acid phosphatase: Differences between normal and chronic lymphocytic leukaemia T and B lymphocytes

SummaryLysosomal acid phosphatase was assayed in homogenates of isolated normal and B cell type chronic lymphocytic leukaemia (B-CLL) T and B lymphocytes by biochemical means. Unlike the results of cytochemical studies reported in the literature enzyme activity was considerably higher in normal B lymphocytes than in corresponding T cells. This finding offers the possibility to use acid phosphatase as a marker for normal B lymphocytes. The diminution of acid phosphatase in unseparated B-CLL lymphocytes depends predominantly upon a loss of enzyme activity in the B cell fraction indicating an intrinsic abnormality of these neoplastic lymphocytes.ZusammenfassungDie lysosomal lokalisierte saure Phosphatase wurde in Homogenaten isolierter T- und B-Lymphozyten von Gesunden und Patienten mit chronischer lymphatischer Leukämie des B-Zellen-Typs (B-CLL) biochemisch bestimmt. Im Gegensatz zu in der Literatur beschriebenen zytochemischen Studien war die Enzymaktivität in normalen B-Lymphozyten beträchtlich höher als in entsprechenden T-Lymphozyten. Dieser Befund bietet die Möglichkeit, die saure Phosphatase als einen Marker für normale B-Lymphozyten zu benutzen. Die Verminderung der Saure-Phosphatase-Aktivität in unfraktionierten B-CLL-Lymphozyten beruht vorwiegend auf einem Verlust der Enzymaktivität in den B-Zellen und weist damit auf die Abnormität dieser neoplastischen Lymphozyten hin.

POEMS-Syndrom@@@POEMS-syndrome: Rare variant of Osteosclerotic myeloma with polyneuropathy, organomegaly, endocrinopathy, M-gradient, and skin lesions: Seltene Variante des osteosklerotischen multiplen Myeloms mit Polyneuropathie, Organomegalie, Endokrinopathie, M-Gradient und Hautläsionen

Zusammenfassung□ HintergrundEine seltene Multiorganbeteiligung bei einer Plasmazellerkrankung wurde nach den klinischen Manifestationen mit dem Akronym POEMS-Syndrom bezeichnet: Es handelt sich um die Kombination einer monoklonalen Gammopathie (M-Gradient) mit osteosklerotischen Knochenläsionen, einer sensomotorischen Polyneuropthie, Organomegalie, Endokrinopathie sowie Hautläsionen (“skin”).□ FalldarstellungDer in dieser Arbeit vorgestellte Patient zeigt in exemplarischer Weise Symptome dieser vor allem in Japan auftretenden multisystemischen Erkrankung. Als Ursache einer schubweise progredienten Polyneuropathie wurde eine monoklonale IgA-Lambda-Gammopathie festgestellt. Es fielen ein hypergonadotroper Hypogonadismus, eine Hyperprolactinämie sowie ossäre Sklerosezonen auf. Zusätzlich lagen eine wechselnde Organomegalie und eine Hyperpigmentation vor.□ SchlußfolgerungDie Ätiologie und Pathophysiologie des Syndroms sind bisher unbekannt. Die Bestrahlung oder chirurgische Resektion eines oder mehrerer sklerotischer Knochenherde können die Progression der Polyneuropathie verhindern, gelegentlich auch zur Rückbildung der Symptome führen. Insofern sollte bei allen unklaren Polyneuropathien nach einer monoklonalen Gammopathie und gegebenenfalls nach weiteren Symptomen des POEMS-Syndroms gesucht werden.Abstract□ BackgroundA rare multi-organ involvement in plasma-cell dyscrasias has been named POEMS-syndrome: it is a synopsis of monoclonal gammopathy (M-gradient), osteosclerotic bone lesions, peripheral polyneuropathy, organomegaly, endocrinopathy and skin lesions.□ Case ReportA patient is presented who had a classical manifestation of this disease known mainly in Japan. A monoconal IgA-lambda-gammopathy was determined as cause of a gradually progressive polyneuropathy. The patient had a hypergonadotropic hypogonadism, hyperprolactinaemia, and sclerotic bone lesions. In addition, he showed a changing organomegaly, and hyperpigmentation of the skin.□ ConclusionAs yet, aetiology and pathophysiology are not fully understood. Irradiation or surgical resection of one or several osteosclerotic bone lesions may improve the polyneuropathy or may even lead to a complete remission of all symptoms. Thus, monoclonal immunoglobulins should be searched for in any unclear polyneuropathy, as should be for other symptoms of the POEMS-syndrome.

Mechanisms of Chromosomal Translocations in Malignant Lymphomas

Recurring and highly consistent chromosomal abnormalities are a feature of many hematopoietic neoplasms. They are carried throughout the malignant cells indicating that they occurred prior to clonal expansion. Over the last decade it has become clear that distinct translocations play a major role in the pathogenesis of malignant lymphomas. The main cytogenetic changes are exhibited by deletions, translocations and inversions of genetic material, resulting in loss of tumor suppressor genes, activation of proto-oncogene products or creation of tumor-specific fusion proteins.