Randomised comparison of CHOEP versus alternating hCHOP/IVEP for high-grade non-Hodgkin's lymphomas: Treatment results and prognostic factor analysis in a multi-centre trial

Background: With CHOP, the standard protocol of recent decades,about 30% of long-term survival has been reported. A numberof studies using more aggressive multidrug regimens or alternatingchemotherapies have recently suggested higher CR rates and increasedsurvival. In 1989 we reported similar results with a combined-modalitytreatment administering 6 cycles of CHOP supplemented with etoposideand an involved field irradiation for patients in PR or CR. Patients and methods: To confirm the efficacy of this approach,we initiated a prospective randomised trial comparing 4 cyclesof CHOP-VP 16 (CHOEP) with 4 cycles of two alternating regimens,‘hCHOP and IVEP’. One hundred seventy-five patientswith high-grade non-Hodgkin's lymphomas stages II-IV were stratifiedfor age, stage and LDH and randomised to receive either fourcycles of cyclophosphamide, doxorubicin, vincristine, etoposide,prednisolone (CHOEP) in arm A or four cycles of chemotherapywith a dose-intensified CHOP (hCHOP) alternating with ifosfamide,etoposide, vindesine, prednisolone (IVEP) in arm B. After fourcycles of chemotherapy an involved field irradiation with atotal dose of 35 Gy was given to all patients demonstrated tobe in complete or partial remission. Results: Of the 185 randomised patients, 175 were eligible and171 evaluable for response and survival. One hundred forty-sixof the 171 patients (85%) achieved complete remission (CR) with87% and 84% CRs in arms A and B, respectively. With a medianfollow-up of 36 months the estimated overall survival at 2 yearsis 66% and 73% for arms A and B. The percentage of all patientsin first CR is estimated to be 59% and 55% at 2 years for armsA and B, respectively. None of the differences in CR rate, survival,or relapse-free survival are statistically significant. Multivariateanalysis of subgroups incorporating the factors of sex, age,performance status, stage, B symptoms, bulky disease, LDH andhistology revealed that only stage and LDH were factors whichindependently affected outcome. The estimated 2-year survivalrate of patients with stages II, III and IV is predicted tobe 84%, 62% and 52%, respectively. Patients with LDH >250U/I have an estimated survival of 52% at 2 years versus 84%for patients with LDH     

Über die Erkennung von Keimzentrumszellen im Lymphknotenausstrich

Zusammenfassung Im Lymphknotenausstrich kommen basophile Zellen vor, die weitgehend spezifisch für die Keimzentren der Sekundärknötchen sind und als Germinoblasten bezeichnet werden. Sie sind bei follikulärer lymphatischer Hyperplasie und bei M. Brill-Symmerserheblich vermehrt. Ihre Morphologie wird im einzelnen beschrieben und durch Abbildungen belegt. Eine Unterscheidung von den basophilen Stammzellen, den großen lymphatischen Reticulumzellen der Literatur, ist möglich und nötig, da diese Zellen in Sekundärknötchen und Pulpa gleichermaßen vorkommen.     

Histiocytic necrotizing lymphadenitis without granulocytic infiltration

Summary Twenty-seven cases of an unusual necrotizing lymphadenitis previously described only in Japan are reported as occurring in West Germany (23 cases), Iran (1 case), Italy (1 case), Korea (1 case) and Spain (1 case). The lesion frequently develops in the cervical lymph nodes of young women. It is characterized by infiltration of the cortex and/or paracortex by large collections of proliferating histiocytes and is devoid of granulocytes. Complete or, more often, incomplete necrosis of lymphoid tissue is seen in all cases. In cases with incomplete necrosis, the histiocytes are interspersed with pyknotic cells and nuclear debris. Based on the histological findings, the term histiocytic necrotizing lymphadenitis without granulocytic infiltration is proposed. Lesions to be considered in a differential diagnosis are malignant histiocytic neoplasms and necrotizing lymphadenitis with granulocytic infiltration, which is seen in lupus erythematosus and bacterial infections. The aetiology of histiocytic necrotizing lymphadenitis without granulocytic infiltration is still unclear. Some clinical and histological features indicate the possibility of an underlying viral infection.This study was supported by the Kind-Philipp-Stiftung     

Distribution pattern of follicular dendritic cells in low grade B-cell lymphomas of the gastrointestinal tract immunostained by Ki-FDC1p: a new paraffin-resistant monoclonal antibody

This study surveyed 97 cases of low grade B-cell lymphoma (LGBL) of the gastrointestinal tract (GIT) by conventional morphology and immunohistochemistry, focusing on the most frequent subtype: the so-called LGBL of the mucosa-associated lymphoid tissue (MALT). Special reference was made to the follicular dendritic cells (FDCs) selectively visualized by a new paraffin-resistant monoclonal antibody Ki-FDC1p. LGBL of the MALT accounted for 83 cases. The diagnosis was based on (a) a characteristic cytology, which included centrocytoid cells, a varying degree of plasma cell differentiation, and some blasts; (b) the presence of lymphoepithelial lesions; and (c) the occurrence of two types of follicles easily detectable with Ki-FDC1p. Some were restricted to the mucosa, contained normal germinal center cells, and were indistinguishable from reactive follicles. Others consisted of small clusters of FDCs, were randomly distributed throughout the tumor, and escaped detection in conventional stainings. Such small clusters of FDCs were found to be restricted to LGBL of the MALT, not occurring in other types of LGBL, and were interpreted as tumor-associated abortive follicles discernable from residues of reactive follicles due to their cellular constituents, localization, and distribution pattern. Eight cases showed closed sheets of blasts and were classified as high grade malignant lymphoma secondary to LGBL of the MALT. In two cases the LGBL of the MALT were restricted to the mucosa, in 31 cases the submucosa was also infiltrated, and in the remaining 50 cases the infiltration also involved deeper wall layers of the GIT.(ABSTRACT TRUNCATED AT 250 WORDS)     

Follicular dendritic cells in Hodgkin's disease

The distribution of follicular dendritic cells (FDCs) was studied in 66 lymph nodes affected by Hodgkin's disease (HD) from as many patients with the use of the monoclonal antibody Ki-FDC1P, which stains FDCs in paraffin sections. Two distinct FDC patterns were distinguishable in the neoplastic areas: pattern A, showing FDC networks occupied by nongerminal center cells, often expanded and disrupted; and pattern B, with FDCs rare or lacking. Pattern A, with follicle-occupying cells represented by epithelioid and lymphocytic and histiocytic (L and H) cells, was found in about 90% of the cases of nodular lymphocyte predominance type and in about half of the cases of nodular sclerosis type, with the follicle-occupying cells being lacunar cells. In the group of mixed cellularity type, approximately one-fifth of the cases exhibited pattern A and in these cases the follicle-occupying cells were Sternberg-Reed, Hodgkin's, and epithelioid cells. The presence of follicular structures, although abnormal, is a more common occurrence in HD than is appreciable with the use of conventional histologic methods.     

Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases.

The trisomy 8 found in malignancies may derive from a constitutional trisomy 8 mosaicism (CT8M), and in these cases the trisomy itself may be regarded as the first mutation in a multistep carcinogenetic process. To assess the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8, an informative sample of 14 patients was collected. The data ascertained included chromosome analyses of fibroblast cultures and of PHA-stimulated blood cultures in patients with normal blood differential count, as well as possible CT8M clinical signs. One patient showed trisomy 8 in all cell types analyzed and undoubtedly has a CT8M; a second patient consistently showed trisomy 8 in PHA-stimulated blood cultures when no immature myeloid cells were present in blood and should be considered as having CT8M; a third patient, with Philadelphia-positive chronic myelocytic leukemia, was more difficult to interpret, but the possibility that she had CT8M is likely. A few clinical signs of CT8M were also present in these three patients. Our data indicate that the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8 is approximately 15-20%.     

Factors modulating the sensitivity of the relaxation to the loading conditions in rat cardiac muscle

The load sensitivity of the relaxation phase was studied in rat papillary muscle, with isotonic afterloaded contractions and stretches applied after the peak of isometric twitches.The tension decay occurred earlier in isotonic than in isometric contractions. When a central region of the preparation was marked with small stainless steel pins, a lengthening of this region could be shown during relaxation of isometric (fixed end) contractions. This lengthening was earlier and faster in isotonic afterloaded contractions. Therefore the sensitivity of relaxation to load or length changes could be described in the context of the general mechanism of relaxation which takes into account the non uniform behaviour of the muscle and the internal movement during contractions.Interventions which decelerate the activation decay rate had different effects on the load dependence of relaxation. Caffeine addition and substitution of strontium for calcium abolished the load sensitivity while a temperature reduction had no influence on it.     

Familial partial monosomy 7 and myelodysplasia: different parental origin of the monosomy 7 suggests action of a mutator gene

Two sisters are reported, both with a myelodysplastic syndrome (MDS) associated with partial monosomy 7. A trisomy 8 was also present in one of them, who later developed an acute myeloid leukemia (AML) of the M0 FAB-type and died, whereas the other died with no evolution into AML. Besides FISH studies, microsatellite analysis was performed on both sisters to gather information on the parental origin of the chromosome 7 involved in partial monosomy and of the extra chromosome 8. The chromosomes 7 involved were of different parental origin in the two sisters, thus confirming that familial monosomy 7 is not explained by a germ-line mutation of a putative tumor-suppressor gene. Similar results were obtained in two other families out of the 12 reported in the literature. Noteworthy is the association with a mendelian disease in 3 out of 12 monosomy 7 families, which suggest that a mutator gene, capable of inducing both karyotype instability and a mendelian disorder, might act to induce chromosome 7 anomalies in the marrow. We postulate that, in fact, an inherited mutation in any of a group of mutator genes causes familial monosomy 7 also in the absence of a recognized mendelian disease, and that marrow chromosome 7 anomalies, in turn, lead to MDS/AML.     

Localization of neurons projecting into the extrinsic penile smooth musculature of the pig: an experimental study on the retractor penis muscle

The aim of this study was to locate in male pigs the sensory and autonomic ganglia innervating the retractor penis muscle (RPM), which was taken as an experimental model of the genital smooth musculature. The retrograde neuronal tracers horseradish peroxidase (HRP), Fast Blue (FB), and diamidino yellow (DY) were injected into the bulbopenile portion of the left RPM. The tracers highlighted a different affinity for the neuronal structures, although labelled cells supplying the RPM were generally found in bilateral dorsal root ganglia (DRGs, S1-S3), in bilateral paravertebral ganglia (PaGs, L2-S3), and in the left and right caudal mesenteric ganglia (CMGs). The mean number of labelled FB cells was 795 (range, 645-952) in DRGs, 16046.25 (range, 10226-18742) in PaGs, and 635.25 (range, 333-786) in CMGs. The mean diameter of pseudounipolar DRG cells was 60-75 microm, while the multipolar neurons of PaGs and CMGs had dimensions varying between 20-50 microm and 20-30 microm, respectively.     

Histologic and immunohistochemical findings in the differential diagnosis of chronic lymphocytic leukemia of B-Cell type and lymphoplasmacytic/lymphoplasmacytoid lymphoma

Summary 114 cases of malignant lymphoma consisting chiefly of lymphocytes were classified by histology as chronic lymphocytic leukemia of the B-cell type (B-CLL) or lymphoplasmacytic/lymphoplasmacytoid lymphoma (LP immunocytoma) and investigated with the immunoperoxidase-bridge (PAP) method for the presence of heavy and light immunoglobulin chains. Fifteen cases were excluded because they showed a completely negative reaction, which might have been an artifact. Of the remaining 99 cases, 46 revealed polyclonal immunoglobulin-positive plasma cells only and could be clearly classified as B-CLL. In 33 cases there were a moderate or large number of plasma cells or plasmacytoid cells with monoclonal intracytoplasmic positivity. Two heavy chain classes were demonstrated in three other cases, and both light chain types were detected in one case. These 37 cases were finally classified as LP immunocytoma. Ten cases contained only a few monoclonal plasmacytoid cells and were interpreted as borderline cases between B-CLL and LP immunocytoma. Six cases have not yet been clarified — there was an inexplicable discrepancy between their histology and immunostaining.In LP immunocytoma, the heavy chain class demonstrated most often was the chain (27 cases). Light chains of the type were about 2.5 times as common as chains.The differential diagnostic criteria for distinguishing B-CLL from LP immunocytoma are discussed and compared. PAS-positive tumor cells are an almost definite criterion of LP immunocytoma. At present, a critical evaluation of the results of PAP immunostaining is the most reliable way to clearly distinguish B-CLL from LP immunocytoma.Supported by the Kind-Philipp-Stiftung