Hemophagocytic syndrome in a case of splenic large B-cell lymphoma.

A case of splenic large B-cell lymphoma with hemophagocytic syndrome is reported. The difficulties of diagnosis are emphasized especially when peripheral lymph nodes or bone marrow lymphomatous infiltration are not present. Diagnostic criteria for hemophagocytic syndrome and their relationship with the pathogenesis of the disease are also stressed.

[Clinical usefulness of the immunophenotypic study of circulating lymphocytes in leukemic lymphoproliferative diseases]. / Considerazioni sulla utilità clinica dello studio immunofenotipico dei linfociti circolanti nelle malattie linfoproliferative leucemizzate.

The immunophenotypes (IF) on peripheral lymphocytes of 24 B-CLL in different stage, 2 PLL and 14 leukemic B-non Hodgkin lymphomas were investigated. As regard to B-CLL and PLL, the results are similar to those reported so far. In stage A and B of B-CLL the IF appear less variable than in advanced stages where a decrease of CD21+ and an increase of both CD25+ and CD38+ lymphocytes were observed. In the lymphocytic, small cleaved cell lymphomas and splenic lymphomas, the peripheral IF correspond to the theoretical ones of respective lymphoma tissues. On the contrary they disagree in three cases of large cells, mixed small and cleaved cell, immunoblastic lymphomas. These features are discussed.

Probability of cure in elderly Hodgkin's disease patients.

BACKGROUND: Elderly Hodgkin's disease patients have a poor prognosis. The question arises whether these patients need aggressive treatment or a palliative strategy. So far, as a consequence of the scarcity of trials designed for them, useful information can be obtained only by retrospective analyses. METHODS: We retrospectively studied clinical data from 567 patients recorded from 1982 to 1989 in the Piemonte Hodgkin's Disease Register (PHDR). The 65 patients over 65 years of age were compared to younger ones. We analyzed the role of disease independently of confounding variables, mainly inadequacy of staging and/or treatment, comorbidity and toxicity. RESULTS: In the elderly comorbidity was as high as 35%. Forty elderly patients (60%) entered a suboptimal plan with a low degree of aggressivity, which was different from the usual PHDR protocol. Elderly patients also had a high proportion of subsequent protocol interruptions (25%). Chemotherapy dose intensity was negatively affected by advanced age (p < 0.01 after both 3 and 6 courses of chemotherapy). Toxic deaths were significantly higher in elderly patients than in younger ones (14% vs 1%; p < 0.05). CR rates, overall survival (OS), disease-specific survival (DSS) and event free survival (EFS) were all significantly influenced by age (p < 0.01). Relapse-free survival (RFS) in patients achieving CR did not differ according to age class (77% vs 60%; p = ns). RFS was better in elderly patients entering the PHDR protocols than in those following an alternative plan (75% vs 54%; p = 0.04); however, elderly patients treated according to PHDR guidelines showed a higher incidence of toxic deaths than those treated less aggressively (23% vs 8%). The two groups had similar EFS (36% vs 24%; p = ns). CONCLUSIONS: Elderly patients who achieve CR can have good RFS and cure is possible, but the toxic cost of conventional strategies is unacceptable and selected strategies still must be found.

The discriminating analysis in the differential diagnosis of monoclonal gammopathies.

The clinical diagnosis is not always easy in monoclonal gammopathies. Therefore we used discriminating analysis to obtain diagnosis statistically sure. The parameters considered were kappa-lambda ratio, marrow plasma cells percentage and labeling index, CD3, CD4, CD8 lymphocytic absolute values. The plasma cells percentage and their labeling index make the differential diagnosis between MM and MGUS or SMM and MGUS feasible and quite correct. Additional immunological parameters should be used for the diagnosis between SMM and MM.

Kappa/lambda ratio on peripheral blood lymphocytes and bone marrow plasma cell labeling index in monoclonal gammopathies.

Bone marrow plasma cell labeling index (L.I.), kappa/lambda ratio, CD4+ and CD8+ subpopulations were studied in patients with smoldering multiple myeloma (SMM), active myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). The loss of the light chain isotype suppression (LCIS) and a high labeling index (L.I.) allowed us to distinguish all MM patients from SMM patients. On the contrary, a low L.I. and a normal kappa/lambda ratio were found in most kappa and lambda MGUS. A significant difference in the kappa/lambda ratio was noted between MGUS and K-SMM. A significant decrease in CD4+ and a significant increase in CD8+ were not observed in patients with LCIS. The kappa/lambda ratio together with the plasma cell L.I. could be useful parameters for distinguishing active MM from SMM, especially in the cases with a border line L.I.

Isolation and characterization of the major serum albumin adduct formed by aflatoxin B1 in vivo in rats.

Aflatoxin B1 (AFB1) was shown to react primarily with one or more lysine residues in serum albumin (SA), accounting for more than half of the total binding to this protein. The radioactivity associated with SA following administration of [U-14C]AFB1 to rats was cleared with a half-life of 2.5 days, which is not significantly different from the half-life of unmodified albumin in the normal rat. The product isolated from a Pronase digest of in vivo-modified SA was identical by chromatographic retention time and u.v. and mass spectroscopy to the synthetic product obtained by the acylase-catalyzed deacetylation of the reaction product of N alpha-acetyl-L-lysine with 8,9-dihydro-8,9-dibromo-AFB1. The latter was characterized by u.v., fluorescence, 500 MHz 1H-n.m.r. and fast atom bombardment mass spectrometry. The spectral data strongly support a structure in which the terminal dihydrofuran ring of AFB1 has been converted to a pyrrolinone ring. It is proposed that the initial adduct is formed by condensation of the dialdehyde tautomer of 8,9-dihydro-8,9-dihydroxy-AFB1, with the epsilon-amino group of lysine, to form a Schiff base, and that the Schiff base undergoes an Amadori rearrangement to an alpha-amino ketone. The pyrrolinone ring is formed by condensation of the amino group with the remaining aldehyde to yield the final product. The purified product was relatively stable but was shown to decompose significantly under the conditions used to isolate it from modified SA.

Primary brain malignant non-Hodgkin lymphoma: report of a case treated with chemotherapy in combination with radiotherapy.

Primary brain lymphomas are usually treated with surgery in combination with radiotherapy, whereas only a few cases have been treated with chemotherapy. We describe a case of a 68-year-old man with an immunoblastic primary cerebral lymphoma first treated with surgery and radiotherapy and subsequently with chemotherapy consisting of cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). In this case immunological study of the peripheral blood and cerebrospinal fluid (CSF) lymphocytes confirmed that a primary brain lymphoma may be an intrinsic cerebral neoplasm with different forms of spreading within the central nervous system (CNS). The period of survival of our patient is equivalent to that of patients treated with radiotherapy alone or in combination with surgery. This suggests the need for further investigation in this field.

4-Chloro-6-methoxyindole is the precursor of a potent mutagen (4-chloro-6-methoxy-2-hydroxy-1-nitroso-indolin-3-one oxime) that forms during nitrosation of the fava bean (Vicia faba).

Fava beans (Vicia faba) upon treatment with nitrite under simulated gastric conditions, form a direct-acting bacterial mutagen, comparable in specific activity to the most potent known mutagens for several strains of Salmonella typhimurium. The precursor of the mutagen was isolated and identified as 4-chloro-6-methoxyindole by u.v., i.r., m.s. and n.m.r. The precursor was dechlorinated with NaBH4 and PdCl2 as the catalyst and the product obtained from this reaction was identified as 6-methoxyindole. Since synthetic 4-chloro-6-methoxyindole was not available, structure activity studies were conducted on substituted indoles. Nitrosation of 4-chloroindole closely follows the results for nitrosation of 4-chloro-6-methoxyindole. The major product of nitrosation of 4-chloroindole is 4-chloro-2-hydroxy-N1-nitroso-indolin-3-one oxime. Thus, it appears that the major nitrosation product of 4-chloroindole and of 4-chloro-6-methoxyindole is a stable alpha-hydroxy N-nitroso compound. This is the first reported case of stable alpha-hydroxy N-nitroso compounds. In the presence of N-(1-naphthyl)ethylenediamine dihydrochloride (NEDD), the alpha-hydroxy N-nitroso compound rearranges to an aromatic diazonium ion which couples with the diamine to form an azo dye. Studies on nitrosation kinetics indicate that the nitrosation of indoles are relatively fast reactions. Both the structural and rate studies give strong support to the hypothesis that intragastric nitrosation of fava beans yield the putative gastric carcinogen in the high-risk area in Colombia.

Lymphocyte populations and T cell subpopulations in blood of patients with non-Hodgkin lymphomas.

Lymphocytic populations and T cell subsets were studied in the blood of patients with nonleukemic non-Hodgkin lymphoma. A statistically significant decrease of both the T lymphocytes and the OKT4-, OKT8-binding cells was detected in low-grade malignant lymphomas (LGML). A significant decrease of the T cell population and of the OKT4-binding cells was also found in high-grade malignant lymphomas (HGML); in these, the OKT8-binding cells were not lowered. The amount of the circulating B lymphocytes was not found to be altered both in HGML and in LGML.

Spontaneous complete remission of CLL. Report of a case studied with monoclonal antibodies.

A case of complete spontaneous remission of CLL in a 76-year-old woman is reported. Despite the complete remission, the study of the peripheral blood T lymphocytic subsets by the aid of monoclonal antibodies has showed, however, that the ratio between helper-induced and suppressor cytotoxic T cells is still impaired (0.81) as we can see in overt B-CLL. The cause of the remission and its possible connection with the imbalanced distribution of the T lymphocytic subsets is discussed.

Qualitative and quantitative characterization of mutagens in commercial beef extract.

Two mutagenic compounds have been isolated and purified from commercial beef extract. These two compounds have chemical, chromatographic, spectroscopic and biological behavior indistinguishable from those of the two known mutagens 2-amino-3-methyl-imidazo-[4,5-f]-quinoline and 2-amino-3,8-dimethyl-imidazo-[4,5-f]-quinoxaline.

Chemotherapy of advanced non-Hodgkin lymphomas: a report of 35 cases.

Thirty-five patients with stage III and IV non-Hodgkin lymphomas, classified according to Lennert have been treated by combination chemotherapy (CVP). Total remission (complete plus partial) was obtained in 68.5% of the cases and complete remission in 28.5%; 73% of the favorable types and 55% of the unfavorable histologic types achieved tumor response: the difference was not statistically significant, perhaps because of the limited number of cases. Median survival was 14 months for the unfavorable histologic types and 28 months for the favorable types; longer survivals were obtained in patients who achieved complete remission. CHOP regimen after CVP in patients refractory to this type of treatment was not satisfactory in our patients.

Monoclonal immunoproliferative disorder of B-lymphocytes IgD/lambda changing from chronic lymphocytic leukaemia to myeloma and plasmacytic leukaemia pattern.

An immunoproliferative disorder with M component IgD/lambda and a strong decrease of the other Ig classes in the serum is reported. The peculiarity of this disorder consists in the shift from a predominant chronic lymphocytic leukaemic pattern, at the beginning, to a true myeloma with plasmacytic leukaemia IgD/lambda several months later. The possibility of the removal, in this case, of the initial precocious block with derepression or 'switch on' in transformation of the malignant lymphocyte clone and, consequently, change of a type of malignant lymphoma into another more evoluted and more malignant type is discussed.