bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro chemosensitivity testing of leukemic cells: Prediction of response to chemotherapy in patients with acute non‐lymphocytic leukemia
Authors: Santini Valeria , Bernabei Pietro Antonio , Silvestro Luigi , Pozzo Orietta Dal , Bezzini Roberto , Viano Ilario , Gattei Valter , Saccardi Riccardo , Ferrini Pierluigi Rossi
Published: February 2007

The in vitro chemosensitivity to daunorubicin and cytosine arabinoside of blast cells derived from 35 patients affected by acute non‐lymphocytic leukemia was assessed by a semiautomated tetrazolium‐based colorimetric assay, by the use of p‐iodonitrotetrazolium violet. The results of the in vitro testing were then compared a posteriori to clinical outcome of patients, who followed a schedule of therapy which always included the drugs tested in vitro. Three dosages of drugs were employed to allow the determination of a dose‐response curve, which was obtained for all the patients. The data collected in INT assay correlated with the clinical sensitivity of patients, evaluated in terms of achievement of complete remission. For the dosage of ARA‐C 500 ng/ml it was possible to establish a significant cutoff between responders and non‐responders to therapy, while an acceptable distribution of sensitivity/resistance prediction was found for DNR 500 ng/ml and 5 μg/ml. Present results, together with rapid and easy execution of the test, encourage the use of INT assay in screening leukemic patients' sensitivity to antiblastic drugs before treatment or, in case of resistance to classical chemotherapy, in detecting individual sensitivity to alternative drugs.
Hairy cell leukemia—mediastinal involvement. A report of two cases and review of the literature
Authors: Malik S. T. A. , Amess J. , D'Ardenne A. J. , Lister T. A.
Published: February 2007

The clinical features of two patients with hairy cell leukemia involving the mediastinum are described. Both patients presented with acute chest pain 2‐3 months prior to diagnosis being made. In one patient mediastinal disease was recorded only by computerized tomography of the thorax. There was good response of mediastinal disease to alpha‐interferon in both patients, in spite of persisting bone marrow involvement with hairy cell leukemia.
Agnogenic myeloid metaplasia (AMM)—correlation of bone marrow lesions with laboratory data: A longitudinal clinicopathological study on 114 patients
Authors: Thiele Juergen , Zankovich Rudolf , Steinberg Thomas , Fischer Robert , Diehl Volker
Published: February 2007

A clinicopathological study was performed on 114 patients (46 male/68 female, median age 67 years) with the diagnosis of agnogenic myeloid metaplasia (AMM) respectively primary osteo‐myelofibrosis which was not preceded by any other or allied subtype of chronic myeloproliferative disorders. On admission patients revealed a striking variability of laboratory data as well as different histopathological features of initial bone marrow biopsies. For this reason discrimination was done into two groups based on bone marrow findings: group I patients (n = 46, 19 male/27 female) showed a hypercellular marrow without or only borderline (n = 24) to slight (n = 22) reticulin fibrosis and group II cases (n = 68, 27 male/41 female) displayed coarse bundles of collagen fibres (n = 18) frequently accompanied by osteosclerosis (n = 50). Statistical analysis of the corresponding initial hematological findings resulted in significant differences. These differences concerned also the complications occurring during the lengthy course of disease, which included a higher incidence of pancytopenia and severe marrow failure with hemorrhage and blast crisis in group II patients. However, overall survival time was not different in both groups. This may be related to the similarity of age distribution (64 resp. 65 years) and its significant association with arteriosclerotic vascular lesions. Consequently acute myocardial infarction and congestive heart failure were frequent causes of death in addition to infections due to marrow failure and blast crisis. Repeated bone marrow biopsies in 24 patients revealed an insidious transition from hypercellular lesions (group I) into advanced fibro‐osteosclerotic changes (group II) concurring with laboratory data. Therefore our discrimination into two groups of patients represents variable stages or static histological and corresponding hematologic features in the evolution of a dynamic disease process in AMM.
A risk factor for relapse in Hodgkin's disease: Female gender?
Authors: Jeffery G. M. , Colls B. M. , Robinson B. A. , Fitzharris B. M. , Atkinson C. H.
Published: February 2007

A retrospective study of 163 patients with Hodgkin's disease treated between 1969 and 1987 was performed to identify adverse prognostic factors. One hundred and thirty‐five patients (83 per cent) attained a complete remission and 42 (31 per cent) of these have relapsed (median follow‐up—43 months). Using multivariate analysis, no independent factors predicted for the event of relapse. However, analysis of disease‐free survival revealed that females fared significantly worse than males (p <0.05) and this was independent of other prognostic variables. Female sex has not been recognized as an independent prognostic factor predictive of inferior survival and inferior disease‐free survival.
T cells in follicular centroblastic/centrocytic (cleaved follicular centre cell) lymphomas at diagnosis, relapse and transformation
Authors: Swerdlow Steven H. , Habeshaw John A. , Murray Lesley J. , Stansfeld Alfred G.
Published: February 2007

Although T cells are often a prominent component of follicular (± diffuse) centroblastic/centrocytic (cleaved follicular centre cell—FCC) lymphomas (CB/cc/F±D), their evolution during the course of the disease and prognostic significance are uncertain. A total of 127 histopathologic and immunophenotypic studies from 77 patients with at least one histologic diagnosis of CB/cc/F±D were therefore retrospectively reviewed to address these questions. The proportion of T cells in each biopsy was analysed with reference to both histologic (diagnosis—Kiel and Lukes/Collins classification, presence of transformation, growth pattern, presence of residual mantle zones, biopsy sites) and clinical (biopsy date and number, treatment status) parameters. The actuarial survival for those patients whose first or second biopsy showed CB/cc/F±D and had immunophenotypic studies was also compared based on the proportions of T cells present.

Among the biopsies which were obtained from 0 to 153 months following diagnosis, the mean proportion of T cells was 25 ± 18 per cent. The only histopathologic group that showed a significantly different proportion of T cells were lymphomas of large cleaved FCC type (38 ± 20 per cent). Although the number of T cells present varied greatly between different patients and among different biopsies in the same patients, neither biopsy number nor treatment status affected the mean proportion of T cells in CB/cc/F±D. With the exception of those biopsies from 1 to 11 months following diagnosis, the interval time between diagnosis and biopsy also did not affect the number of T cells present. Finally, the proportion of T cells in the lymphomas could not be shown to be of prognostic importance.

Thus, the proportion of T cells in de novo CB/cc/F±D, at relapse or in transformation does not vary in a consistent fashion. Although extremely variable, the number of T cells present cannot be considered a feature of earlier or later disease and is not of demonstrable prognostic importance. Studies of specific subsets of T cells may provide more definite associations.
Hodgkin's disease in Hong Kong Chinese
Authors: Liang Raymond , Choi Peter , Todd David , Chan T. K. , Choy Damon , Ho Faith
Published: February 2007

A lower incidence of Hodgkin's disease in Orientals has been recognized. Although most Hong Kong Chinese came from the Guangdong province of China, the incidence of Hodgkin's disease in Hong Kong Chinese is 9.2 per cent which is more comparable to the low figure of 6 per cent in Japan than the 32 per cent incidence in Guangdong. If this discrepancy in the ethnically similar populations is confirmed, other etiological or promoting factors must be considered. Ninety‐two Hong Kong Chinese patients (54 males and 38 females) with Hodgkin's disease were reviewed. The median age was 34 years (range 5–79 years). The histology was lymphocyte predominant in nine (10 per cent), nodular sclerosing in 34 (37 per cent), mixed cellularity in 29 (31 per cent), lymphocyte depleted in nine (10 per cent) and unclassified in 11 (12 per cent). Seventeen per cent had stage Ia disease, 2 per cent Ib, 15 per cent IIa, 11 per cent IIb, 11 per cent IIIa, 9 per cent IIIb, 11 per cent IVa and 24 per cent IVb. Twenty‐five of them (27 per cent) were staged by laparotomy. Twelve patients (13 per cent) had bulky disease. Identical to the pattern observed in Caucasians, our patients had an apparent biomodal age distribution, a male predominance and similar distribution of histological subtypes according to the Rye classification. The absence of an early peak in young adulthood and the lower incidence of the nodular sclerosing subtype reported in the Japanese was not observed in our patients.

A variety of treatments were given to the 92 patients. Most of the patients with stage I–II disease received radiotherapy except for those with B symptoms, bulky disease or lymphocyte depleted histology, who received chemotherapy with or without radiotherapy. All patients with stage III–IV disease received chemotherapy with or without radiotherapy except for two patients with stage IIIa disease who had total nodal irradiation only. The multivariate analysis revealed that Ann Arbor staging was a significant independent factor determining the disease‐free survival of patients in complete remission and the overall survival of all patients. Age was the other independent variable significantly determining the overall survival.
Triple combination of retinoic acid + low concentration of cytosine arabinoside + hexamethylene bisacetamide induces differentiation of human aml blasts in primary culture
Authors: Hassan H. T. , Rees J. K. H.
Published: February 2007

Differentiation induction therapy provides an alternative therapeutic approach for patients with acute myeloid leukemia (AML) who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid (RA) + low concentration of cytosine arabinoside (Ara‐C) + hexamethylene bisacetamide (HMBA) on differentiation of blasts from 24 AML patients was studied. Non‐adherent mononuclear cells were seeded at a concentration of 5 × 105 cells per ml in 24‐well tissue culture plates containing RPMI 1640 culture medium with 20 per cent fetal calf serum and 10 per cent 5637‐conditioned medium and incubated with 10−6 M retinoic acid, 10−6 M cytosine arabinoside and or 2 mM hexamethylene bisacetamide for six days at 37 °C in a humidified incubator under 5 per cent CO2. Morphological, cytochemical and functional differentiation into mature cells were induced in blasts from 22 out of the 24 AML patients following exposure to the triple combination of 10−6 M RA + 10−6 M Ara‐C+2 mM HMBA in primary culture. These effective results justify a clinical trial of such triple combination for AML patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy.
Prognostic significance of flow cytometry studies in B‐cell non‐hodgkin lymphoma
Authors: Rehn Suzanne , Glimelius Bengt , Strang Peter , Sundström Christer , Tribukait Bernhard
Published: February 2007

The prognostic relevance of flow cytometric DNA measurements of lymph node biopsies in relation to histopathology according to the Kiel classification, stage, age and presence or absence of B‐symptoms was investigated in 106 patients with non‐Hodgkin lymphomas (NHL) of proven B‐cell type. Biopsies were taken at diagnosis before treatment. The mean proportion of cells in S‐phase was significantly lower in the 76 patients with a ‘low grade’ NHL (4.4 per cent) than in the 30 patients with a ‘high grade’ NHL (13.0 per cent) (p<0.0001). High S‐phase rates were associated with a poor prognosis within the whole material (p<0.01) and within the group of ‘high grade’ NHL (p<0.05). In the subgroup CB‐CC lymphomas of ‘low grade’ NHL, the prognostic value of the S‐phase rate was stronger than any other investigated parameter (p<0.05). In multivariate analyses, the S‐phase rate gave, in several subgroups, independent prognostic information, besides clinico‐pathological variables.
Acute myeloid leukemia in elderly adults
Authors: Tucker J. , Thomas A. E. , Gregory W. M. , Ganesan T. S. , Malik S. T. A. , Amess J. A. L. , Lim J. , Willis L. , Rohatiner A. Z. S. , Lister T. A.
Published: February 2007

One hundred and fifteen previously untreated adults aged over 60 years were referred to St Bartholomew's Hospital between 1978 and 1986 for management of acute myeloid leukemia (AML). Twenty‐seven patients received symptomatic or palliative treatment only because combination chemotherapy was considered inappropriate.

Eighty‐eight patients received intensive chemotherapy with curative intent. There was a 48 per cent ‘early death’ rate and a 24 per cent incidence of resistant disease; complete remission (CR) was achieved in 25 88 patients (28 per cent). By multivariate analysis, a blast count < 50 × 109/1 at presentation was the only factor predictive for achievement of CR whilst the latter and a presentation blast count <50 × 109/1 predicted for superior survival.

Treatment was often curtailed on account of unacceptable toxicity; only 2/88 patients received the planned six cycles of treatment. Two patients died in CR. Four patients are alive in first CR at 3–9 years from treatment; one is alive in second CR following meningeal relapse. Overall survival was significantly worse than that of a contemporaneous group of adults aged 15–59 years treated at this hospital, but duration of CR was comparable.

There are great difficulties involved in the intensive treatment of AML in elderly adults, but the major survival benefit gained by achieving CR should stimulate the search for better tolerated but still curative regimens.
Treatment of low‐grade non‐Hodgkin's lymphomas: Assessment of doxorubicin in a controlled trial
Authors: Lepage E. , Sebban C. , Gisselbrecht C. , Coiffier B. , Harousseau J. L. , Bryon P. A. , Boiron M.
Published: February 2007

From 1981 to 1984 a randomized clinical trial was conducted to evaluate the role of doxorubicin in low grade malignancy non‐Hodgkin's lymphoma (NHL). One hundred and thirteen patients were treated by an induction regimen including cyclophosphamide 400 mg/m2day 1 and 8, vincristine 1.4 mg/m2day 1 and 8, procarbazine 80 mg/m2day 1 to 14, prednisone 60 mg/m2day 1 to 5 (PCOP regimen) randomly associated to doxorubicin: 20 mg/m2day 1 and 8 (PACOP regimen). Maintenance therapy consisted of 12 monthly courses of chlorambucil 10 mg/m2for 5 days or association of cyclophosphamide 300 mg/m2for 3 days, vincristine 1.4 mg/m2day 1 and prednisone 60 mg/m2for 5 days. Complete response (CR) was obtained in 51 patients (45 per cent), in 30 patients after induction regimen and in 21 patients after maintenance therapy, without difference according to regimens. Bone marrow involvement (p=0.02) and number of involved nodal sites (p=0.001) were found to influence probability of achieving CR. The median time to progression was estimated to 39 months without difference between regimens. Median overall survival is not reached with a median follow‐up of 53 months. Multivariate regression analysis permits observation of negative influence on survival of three parameters: initial bone marrow involvement, age over 50 years and incomplete response to treatment. The initial adjunction of doxorubicin did not seem to influence the appearance of histologic progression.
Change in tumour cell‐lymphocyte interactions with age
Authors: Ghoneum Mamdooh , Grewal Iqbal S.
Published: February 2007

In the present study, we analysed the phenomenon of leukophagocytosis by tumour cells with respect to the age of the animal. Splenic leukocytes from C3H mice at different ages were depleted of macrophages and used as targets against tumour effector cells. Tumour cell lines P388D1, a macrophage lymphoma of mouse origin and LAZ‐559, a B cell lymphoma of human origin, were cultured with leukocytes at 37°C and 5 per cent CO2 for 4 h and the percentage of phagocytic tumour cells were examined in cytospin preparations. The results demonstrated that the phagocytic activity of P388D1 cells was 10, 6, 3 and 28 per cent against 1, 2, 6, and 35 week‐old mice respectively; while LAZ‐559 showed lower activity; 5, 3, 1·5 and 17 per cent against leukocytes of corresponding ages. Susceptibility of old leukocytes to phagocytosis could be detected as early as 30 min after culture with tumour cells, and increased with increasing incubation period. At 4 h, phagocytosis by tumour cells resulted in 38 and 29 per cent reduction in the leukocyte number postculture with P388D1 and LAZ‐559 cells respectively. We postulate that an age‐related decline in immune function is associated with increased level of phagocytic tumour cells, and that the loss of leukocytes may have adverse effects on the immune system.
RESIDUAL MEDIASTINAL WIDENING FOLLOWING THERAPY IN HODGKIN'S DISEASE
Authors: Orlandi Ester , Lazzarino Mario , Brusamolino Ercole , Caldera Daniela , Morra Enrica , Dore Roberto , Giulio Giuseppe Di , Bernasconi Carlo
Published: February 2007

The chest radiograms (CXR) of 102 patients with Hodgkin's disease presenting with mediastinal involvement at diagnosis were reviewed to assess the incidence and relevance of residual mediastinal abnormalities after therapy. All patients had completed planned treatment and had no evidence of persisting extramediastinum disease at restaging. Thirty‐nine cases (38 per cent) showed residual mediastinal widening at the end of therapy (minimal changes in nine and measurable changes in 30 cases). Neither presenting features nor treatment modality correlated with residual mediastinal mass on chest X‐ray. The isolated intrathoracic relapse rate was 11 per cent for patients with normal mediastinum following therapy, as compared with 20.5 per cent for those with residual widening; this difference did not reach statistical significance (p = 0.3). The persistence of mediastinal abnormalities was associated with a trend towards a higher risk of intrathoracic relapse for patients with initial bulky disease (p < 0.05) and for those with B symptoms (p = 0.07). Using thoracic CT scan for restaging (56 patients), the residual mediastinum rate rose to 70 per cent; the predictability of local relapse with this procedure was not greater than with conventional X‐ray study.
Secondary central nervous system involvement by non‐Hodgkin's lymphoma: The risk factors
Authors: Liang Raymond , Chiu Edmond , Loke S. L.
Published: February 2007

The risk of secondary central nervous system (CNS) was estimated in 833 cases of non‐Hodgkin's lymphoma diagnosed between January 1975 and December 1988. Fifty‐one of them had CNS disease (51/833, 6.1 per cent). No case of low grade lymphoma developed CNS disease. However, 6.5 per cent and 16.7 per cent of patients with intermediate and high grade lymphomas, respectively, had secondary CNS involvement. Stage IV disease and the presence of B symptoms were also associated with an increased risk of CNS disease.

Significantly higher incidence of CNS disease was seen in patients with lymphoma involving orbit (43 per cent), testis (40 per cent), peripheral blood (33 per cent), bone (29 per cent), nasal/paranasal sinuses region (23 per cent) and bone marrow (20 per cent). CNS prophylaxis is recommended to patients with an increased risk of CNS disease.
Management of advanced stage intermediate grade non‐Hodgkin's lymphomas
Authors: Liang Raymond H. S. , Chiu Edmond K. W. , Chan T. K. , Todd David , Loke S. L.
Published: February 2007

The treatment result of 271 cases of advanced stage intermediate grade lymphoma were reviewed. Ninety‐four patients received CHOP chemotherapy, 45 BACOP and 17 m‐BACOD. The clinical characteristics of the three groups of patients were comparable. Patients receiving CHOP had a complete response (CR) rate of 60 per cent, the disease‐free survival of CR patients was 31 per cent at 5 years. The overall survival following CHOP chemotherapy was 38 per cent at 5 years. The use of the BACOP or m‐BACOD regime did not appear to improve significantly the prognosis of these patients. Clinical staging, B symptoms, age and serum lactate dehydrogenase level were the most important independent prognostic factors.
Histopathological study of bone marrow biopsies in 30 cases of T‐cell lymphoma with clinical, biological and survival correlations
Authors: Caulet S. , Delmer A. , Audouin J. , Le Tourneau A. , Bernadou A. , Zittoun R. , Diebold J.
Published: February 2007

Forty‐five bone marrow (BM) biopsies have been studied in 30 T‐cell malignant lymphoma (ML). According to the updated Kiel classification, these ML comprised 12 low grade ML and 18 high grade ML. BM involvement was not significantly more frequent in low grade ML (41.6 per cent) than in high grade (33.3 per cent). This involvement was discovered in 85 per cent of the cases at the time of diagnosis. A correlation was found between BM and other visceral localizations for histological type in all cases. Infiltrates principally showed a nodular pattern in low grade and a diffuse pattern in high grade ML. Hematopoietic hyperplastic reaction was frequent (66.6 per cent) not correlated to involvement. Clinical staging showed extensive spreading. Our patients had an overall median survival of 40 months, worse in high grade ML (median: 19 months) than in low grade ML (41 months) but not statistically different (p = 0.25). Extranodal localizations are a significant criteria for poor prognosis (p = 0.018). Among them, BM involvement appears to be the most significant criteria (Cox model, p = 0.006). Patients with BM localization had a median survival of 9 months contrasting with 40 months in patients without BM localization (p = 0.007).

Thus, BM biopsy is useful for the diagnosis of patients with T‐ML and essential to establish the prognosis.
Salvage chemotherapy for non Hodgkin's lymphoma of unfavourable histology with a combination of ccnu and vinblastine
Authors: Palmieri G. , Lauria R. , Caponigro F. , Pagliarulo C. , Montesarchio V. , Nuzzo F. , Gridelli C. , Bianco A. R.
Published: February 2007

Twenty patients with relapsed or refractory, intermediate or high grade non Hodgkin's lymphoma were treated with a combination of CCNU and vinblastine. Complete responses occurred in four patients (20 per cent), partial responses in eight (40 per cent), for an overall response rate of 60 per cent. The regimen was more effective in patients with high grade lymphoma, absence of constitutional symptoms, better response to prior treatment. Duration of response was 4, 8, 16, 30 months for complete responders; 2, 2, 6, 6, 6, 8, 9, 14 months for partial responders. This combination regimen seems at least as effective as most of other regimens utilized in salvage treatment of non Hodgkin's lymphomas, with a very acceptable toxicity.
Heterogeneous expression of proto‐oncogenes in Hodgkin's disease derived cell lines
Authors: Jücker M. , Schaadt M. , Diehl V. , Poppema S. , Jones D. , Tesch H.
Published: February 2007

The expression of 20 proto‐oncogenes was analysed by Northern blotting in four cell lines derived from patients with Hodgkin's disease (L428, L540, CO and DEV) and compared to lymphoid and myeloid leukemia cell lines and normal hematopoietic cells. Expression of the proto‐oncogenes c‐myc, p53, c‐jun, pim‐1, lck, c‐syn, c‐raf and N‐ras were detected in Hodgkin's disease derived cell lines and in normal hematopoietic cells. Transcripts of the proto‐oncogene c‐met were detected in the Hodgkin's derived cell lines L428 and L540 but not in the lymphoid or myeloid leukemia cell lines or in tonsil cells, peripheral blood mononuclear cells and granulocytes. Expression of the proto‐oncogenes N‐myc and lck were observed in the Hodgkin's derived cell line CO which express T cell receptor genes and in the T cell lines JM and CEM. L428 cells and CO cells expressed aberrant transcripts of the c‐fes proto‐oncogene. Thus Hodgkin's disease derived cell lines are heterogenous in their expression pattern of proto‐oncogenes, expressing normal and aberrant transcripts of proto‐oncogenes which are not found in untransformed hematopoietic cells.
Clinical features associated with transformation of cerebriform T‐cell lymphoma to a large cell process
Authors: Greer John P. , Salhany Kevin E. , Cousar John B. , Fields James P. , King Lloyd E. , Graber Stanley E. , Flexner John M. , Stein Richard S. , Collins Robert D.
Published: February 2007

Some patients with cerebriform T‐cell lymphoma (CTCL) undergo morphologic transformation to a large cell lymphoma. From a series of 113 patients with CTCL, 22 patients were identified with transformed CTCL. Stages of involvement at diagnosis were: I (seven), II (four), III (four), IV (seven). Nine patients had transformation at the initial diagnosis while the median time from diagnosis to transformation in the other 13 patients was 16 months (range: 3 months–6 years). Thirteen had transformation extracutaneously: lymph nodes (eight), central nervous system (two), and other extranodal sites (three). T cell markers were identified in all cases; of 15 cases with complete phenotypes, there were eight T‐helper, three T‐suppressor, and four aberrant T phenotypes. Serology for human T‐leukemia virus‐I (HTLV‐I) was negative in eight patients tested. Median survival from diagnosis was 27 months compared to 53 months in 53 patients without transformation (p = 0.003). Despite combination chemotherapy in 12 patients following transformation, median survival after transformation was 12 months and only 7 months with extracutaneous disease. The likelihood of transformation could not be predicted by the initial histology, immunophenotype, or stage of disease.
Characterization of giant cells in Hodgkin's lymphomas by immunohistochemistry applied to randomly collected diagnostic biopsies from the german Hodgkin trial
Authors: Werner M. , Georgii A. , Bernhards J. , Hübner K. , Schwarze E. W. , Fischer R.
Published: February 2007

A panel of 10 monoclonal antibodies reactive with formalin‐resistant epitopes was applied to characterize the giant cells of the Reed‐Sternberg, Hodgkin, and lacunar cell types in diagnostic biopsies from the German Hodgkin Trial. The 94 tissue samples examined had been sent to the Reference Center by 44 different laboratories which made the initial diagnoses. A board of four referees re‐classified the primary diagnoses established by the 44 different histopathologists, providing subtyping of Nodular Sclerosis according to Bennett et al. (1985, 1989). Only cases with unequivocal agreement among the referees and which satisfied standards of fixation and embedding were included. Giant cells stained positively with: Ber‐H2 in 92 per cent (81/88), LN‐2 in 86.4 per cent (76/88), and DAKO‐M1 in 72.2 per cent (64/88) of cases in which the lymphocyte predominance type was not included. Positive staining was quite rare with the other seven monoclonal antibodies. No significant difference in reactivity was revealed between giant cells of Reed‐Sternberg, lacunar or Hodgkin cell types. Approximately one third of the cases were negative for at least one of the markers, Ber‐H2, LN‐2 or DAKO‐M1. The lymphocytic and histiocytic cells in lymphocyte predominance Hodgkin's disease displayed a distinctive staining pattern with positivity for B‐cell markers, whereas DAKO‐M1 and Ber‐H2 were predominantly negative.

Finally, we found that randomly collected blocks of primary biopsies permit reliable immunostaining by this panel of monoclonal antibodies, since our results agree with results from the literature obtained from biopsies processed according to more uniform protocols for fixation and embedding.
Necrotizing lymphadenitis: A review of clinicopathological, immunohistochemical and ultrastructural studies
Authors: Asano Shigeyuki , Akaike Yasushi , Jinnouchi Hirokazu , Muramatsu Takao , Wakasa Haruki
Published: February 2007

Necrotizing lymphadenitis (NEL) has been reported to be a reactive process described under differing terminology by Fujimoto et al. (1972), Kikuchi (1972), Wakasa et al. (1973) and other Japanese pathologists. Recently, this type of lymphadenitis has also been reported in America and Europe.

In Japan, NEL is observed more frequently in the northern area, however, no characteristic seasonal occurrence has been noted. The disease affects young females more than males, particularly from the third and fourth decades onwards. Common cold‐like symptoms, lymphadenopathy of the cervical region and leukopenia are characteristic clinical findings in the early stages.

Morphological features of the involved lymph nodes include the presence of numerous immunoblasts, histiocytes and macrophages, the latter with phagocytized nuclear debris derived from degenerated lymphocytes. However, granulocytes are generally absent. Tubular inclusions are observed ultrastructurally.

Immunohistochemical studies of peripheral blood using monoclonal antibodies have revealed that the helper/suppressor (Leu 3a/2a) ratio increases gradually with the clinical course because of a decrease in Leu 2a + cells. The pathogenesis of NEL is uncertain, but it has been speculated that there is cytolytic infection of lymphocytes by a virus or other organism, accompanied by secondary blastic transformation of suppressor T‐lymphocytes.
Hepatitis B infection in patients with lymphomas
Authors: Liang Raymond H. S. , Lok Anna S. F. , Lai C. L. , Chan T. K. , Todd David , Chiu Edmond K. W.
Published: February 2007

This paper reviewed the clinical characteristics and treatment outcome of 484 lymphoma patients with known hepatitis B status. Comparisons were made between the hepatitis B surface antigen positive and negative patients. Also, the effect of treatment for lymphomas, including cytotoxic chemotherapy, in the hepatitis B antigen positive patients were analysed. The hepatitis B status was determined in 484 Chinese lymphoma patients at the time of initial diagnosis. Hepatic complications occurring during therapy for lymphomas were analysed. Although our lymphoma patients had a similar prevalence of hepatitis B markers of 42 per cent, they had a strikingly higher positive rate of 22 per cent for hepatitis B surface antigen and a relatively lower positive rate of 20 per cent for antibody, as compared to the respective figures of 9.5 per cent and 33 per cent in the control population. The hepatitis B surface antigen positive patients were younger than the negative patients but their treatment outcomes were similar despite the higher incidence of hepatic complications (21 per cent) in the hepatitis B surface antigen positive patients during therapy for lymphomas. None of the clinical parameters analysed appeared to be useful in predicting the development of these complications which included fatal liver failure (5.7 per cent), icteric hepatitis (5.7 per cent) and anicteric hepatitis (9.5 per cent). The high prevalence of hepatitis B surface antigen in our lymphoma patients may be related to the immunosuppressive effect of lymphomas. There is no definite evidence to suggest that hepatitis B infection has an aetiological or promoting role in the pathogenesis of lymphomas. Hepatitis B infection has contributed to the high incidence of hepatic complications during therapy for lymphomas and possible ways of prevention need to be investigated.
The occurrence of variant Ph translocations in chronic myeloid leukemia (CML): A report of SIX cases
Authors: Kadam Pratibha R. , Nanjangud Gouri J. , Advani Suresh H.
Published: February 2007

Variants of Philadelphia chromosome (Ph) translocation were detected in six of 95 Ph positive chronic myeloid leukemia (CML) patients (6·3 per cent). Two of these patients showed a Ph variant of ‘simple’ type, involving chromosomes 10 and 12. In four patients, the variant Ph was of ‘complex’ type involving a third chromosome:chromosomes 1, 6, 7 and 12 in addition to 9 and 22. Two of these resulted in the occurrence of a ‘masked’ Ph. In addition to variant Ph translocations, variant breakpoints such as q12 (two patients) and q13 (one patient) on chromosome 22 were observed in another three patients with t(9;22).
CAVBP/DEP alternating chemotherapy for the treatment of intermediate and high grade non Hodgkin's lymphoma: Final results of a pilot study
Authors: Palmieri Giovannella , Caponigro Francesco , Iaffaioli Rosario Vincenzo , Contegiacomo Alma , Montesarchio Vincenzo , Lauria Rossella , Calderopoli Rita , Pagliarulo Clorindo , Gridelli Cesare , Bianco Angelo Raffable
Published: February 2007

Between May 1984 and September 1986, 40 patients with intermediate or high grade non Hodgkin's lymphoma were treated with a novel protocol, which alternated a conventional regimen consisting of cyclophosphamide, doxorubicin, vincristine, bleomycin, and prednisone (CAVBP) with a second chemotherapy regimen, including two drugs with newly discovered activity against lymphomas, such as cis‐platin, etoposide, and prednisone (DEP). Twenty‐one patients (52.5 per cent) achieved a complete response, 11 patients (27.5 per cent) had a partial response. Eight of the 21 complete responders (38 per cent) relapsed 5 to 24 months after completion of treatment. With a median follow‐up of over 40 months, 22 patients are alive, six with disease and three in a second complete response after salvage chemotherapy. Factors negatively associated with response included ‘B’ symptoms, advanced stage of disease, bulky tumour, poor performance status, number of extranodal sites of disease. ‘B’ symptoms, bulky tumour, and poor performance status were also negatively associated with survival. Toxicity was modest, with no treatment‐related deaths and only six cases of severe leukopenia. The results of this pilot study do not justify comparison of CAVBP/DEP with more efficacious regimens in prospective, randomized trials.
Primary and secondary cutaneous lymphomas in Hong Kong Chinese
Authors: Liang Raymond , Chiu Edmond , Loke S. L. , Chan T. K. , Todd David , Ho Faith
Published: February 2007

Sixty‐eight Hong Kong Chinese patients with cutaneous lymphomas were studied. There were 38 males and 30 females and their median age was 52 years. According to a staging system as proposed by the Mycosis Fungoides Cooperative Group, 48 (71 per cent) of the patients had disseminated stage IV disease. There were nine (13 per cent) cases of mycosis fungoides. The remaining cases were mostly intermediate or high grade non‐Hodgkin's lymphomas according to the Working Formulation. Immunophenotyping was performed in 23 cases and in 17 cases (74 per cent), T‐cell tumours were identified. Many of these T‐cell lymphomas were unclassifiable according to the Working Formulation and were either pleomorphic or immunoblasticlymphadenopathy‐like T‐cell lymphoma according to a modified system of the Japanese Lymphoma Study Group. A variety of therapies were given to these patients and those with stage IV disease had a significantly poorer survival. On the other hand, the histology, and immunophenotype did not appear to be useful in predicting prognosis.
Flow cytometric analysis of DNA ploidy in large cleaved cell lymphomas
Authors: Aine Risto , Lehtinen Tuula , Lehtinen Matti , Blanco Guillermo , Apaja‐Sarkkinen Meeri , Leinikki Pauli , Alavaikko Martti
Published: February 2007

The results of nuclear DNA content analysis of a series of 28 patients with large cleaved follicular centre cell non‐Hodgkin's lymphomas (NHL) are reported. DNA aneuploidy was found in 11 (39 per cent) cases. The DNA indices of the DNA‐aneuploid peaks ranged from 1.14 to 2.28. Seven (25 per cent) cases were tetraploid. DNA ploidy was not associated with prognosis. The percentage of S phase cells (SPF) ranged from 2.0 to 30.5 per cent (median 5.1 per cent). Lymphoma patients with SPF higher than 9.7 per cent had a worse survival rate than patients with lymphoma with less than 9.7 per cent S phase cells but the difference did not reach statistical significance. The results of the DNA ploidy and SPF were comparable to those of intermediate and high grade malignancy NHLs.
Cytokine expression in B‐cell non‐Hodgkin lymphomas
Authors: Merz H. , Fliedner A. , Lehrnbecher Th. , Sebald W. , Müller‐Hermelink H. K. , Feller A. C.
Published: February 2007

Cytokine expression of potentially active B‐cell growth factors (IL‐2, IL‐4, IL‐6) was investigated by means of mRNA‐expression in 29 cases of malignant non‐Hodgkin B‐cell lymphomas. Strong signals were found for IL‐4 and IL‐6 in two and five cases, respectively, whereas the majority of the remaining cases did not show any detectable mRNA‐signals for these growth factors. Comparing these results with those of the immunohisto‐chemistry, it could be demonstrated that at least in some of these cases the signal was due to an autocrine or paracrine phenomenon of the tumour cells.
Specific chromosomal changes in patients with acute nonlymphocytic leukemia from India
Authors: Kadam P. R. , Merchant A. A. , Advani S. H. , Nair C.
Published: February 2007

We analysed forty consecutive patients with acute nonlymphocytic leukemia (ANLL) using methotrexate cell synchronization and 24 h‐unstimulated cultures of bone marrow cells to determine the incidence of chromosomal aberrations and the association of specific anomalies with FAB morphological subtypes, in an Indian population. All patients demonstrated an abnormal karyotypic pattern. The specific chromosomal changes viz., t(9;22), t(8;21), t(15;17), t/del(11q), 12p‐ were found in M1(3/5), M2(8/15), M3(8/8), M4(1/1) M5(2/4) and M2Ba(1/1) (M2 with Basophilia) patients. Abnormalities of 11q were also noted in two M2 patients showing monocytic involvement. A translocation involving chromosomes 6 and 9 was seen in one patient with M1 and two patients with M2. An inv(16) was observed in M1 (one case), M2 (two cases) and M6 (one case). A del(16) was noted in an M4 case. Although t(9;22) is frequently associated with M1 patients, it was also detected in M2 (two patients) and M4 (one patient). Among all the FAB specific anomalies described above, t(8;21) and t(15;17) were observed only in M2 and M3 patients, respectively. Interestingly, one M2 patient had two independent clones, one with t(8;21) and t(9;11). Deletion or translocation involving 11q was found in a Ph positive M4 patient. New structural rearrangements such as t(1;7) (q32;q36) in association with t(8;21), and t(14;22) (q32;q11) in association with del(11)(q23) were detected in a M2 and a M5 patient, respectively. In conclusion, our studies have revealed that the incidence of FAB specific abnormalities viz., t(8;21); t(15;17), t(9;22), t/del(11q) and also other recurrent anomalies viz., ‐7/7q‐, +8 is much higher in our patients, as compared with other countries. This difference may be attributed to the influence of differential environmental exposure to unknown carcinogenic agents.
The value of the immunological subtypes and individual markers compared to classical parameters in the prognosis of acute lymphoblastic leukemia
Authors: Gómez E. , Miguel J. F. San , González M. , Orfao A. , Cañizo M. C. , Moraleda J. M. , Borrasca A. López
Published: February 2007

The value of the immunophenotypical subtypes and individual markers was compared with classical parameters in the prognosis of 150 patients with acute lymphoblastic leukemia (ALL).

Regarding the immunophenotype, common‐ALL had a better prognosis than T‐ALL in the children's group. However, in adults the situation was different since both null and T‐ALL patients had longer survival rates than the common/pre‐B group. Moreover, several individual markers add interesting prognostic information, either in ALL as a whole group or within the different immunophenotypes. Thus, the expression of CD 10 and TdT had a significantly favourable influence in the outcome of the whole series of patients; within the T‐ALL, those cases positive for CD10 also had a longer median survival (33 versus 17 months). In addition, in the common ALL patients group the expression of a relatively mature B marker—CD20—appeared to have a favourable prognosis (27 versus 13 months). Other non lineage specific markers, such as CD9 and CD38 did not seem to influence survival.

Regarding the more conventional parameters, our data suggest that the classical age prognostic classification in children (> 15 years) and adults can be improved using two cut‐off points at 11 and 35 years. Moreover, the multivariate analysis showed that this variable, together with FAB morphology and WBC counts were the best combination of parameters for predicting survival.

The present study shows that although the immunophenotype helps us in understanding the biological heterogeneity of ALL, having also prognostic implications, there are other clinical and hematological features that yield stronger prognostic information.
Short‐term remission induction and consolidation therapy for adult acute myelogenous leukemia
Authors: Battista R. , Bassan R. , D'Emilio A. , Dragone P. , Viero P. , Dini E. , Barbui T.
Published: February 2007

One hundred and ninety two adults (median age 44 years) withde novoor secondary (n= 17) acute myelogenous leukemia (AML) were managed with a maximum of six intended courses with adriamycin 25 mg/m2/d for three days, plus cytarabine 200 mg/m2/d and 6–thioguanine 200 mg/m2/d for seven days (short‐term therapy, STT). Twenty eight patients not in remission after the first course were given cytarabine 2 g/m2/bd for six days, a treatment that was highly toxic and gave a low CR rate. One hundred and twenty‐six patients overall (66 per cent) achieved a complete remission (CR), 117/164 (71 per cent) after one to three standard courses (median 1), and 9/28 (32 per cent) after high‐dose cytarabine. Median CR duration was 12 months. By multivariate analysis, younger age, blast count ≤ 50 × 109/L, andde novoAML were associated with a better outcome (p< 0.05). CR duration correlated favourably with FAB M3 morphology and total number (five or six) of cycles (p< 0.05). In patients receiving five or six total courses, median CR length resulted 15.5 months and leukemia‐free survival at 3 years 37 per cent. Therapy was curtailed in one fourth of CR patients because of unacceptable toxicity, and there were nine early deaths attributable to therapy‐related complications among 126 CR cases. STT may be a worthwhile form of treatment for patients withde novonon‐hyperleukocytic AML that are able to tolerate five or six consecutive induction‐like chemotherapy courses.
A simple, non‐invasive method of assessing the acute hemodynamic effects of doxorubicin
Authors: Clive Sally , Dawson Audrey , Bennett Bruce , Rawles John
Published: February 2007

Left ventricular stroke distance was measured by Doppler ultrasound in 10 doxorubicin‐treated and 10 control patients. Measurements were made 10 min, 2 h and 4 h after drug administration. Stroke distance (a linear analogue of stroke volume) increased significantly from 12.6 cm (S.D. 2.7) before and 12.5 cm (S.D. 2.7) 10 min after, to 13.6 cm (S.D. 2.8) 2 h after and 13.7 cm (S.D. 2.7) 4 h after doxorubicin (p < 0.05). Throughout the study period there were no significant changes in stroke distance in the control patients who were infused with similar fluid volumes, and no significant changes in heart rate or blood pressure in either group.

These observations confirm previous findings made by radionuclide ventriculography, a much more complex, expensive and hazardous technique, not amenable to repetition at short time intervals. The measurement of stroke distance by Doppler ultrasound is a convenient bedside method of assessing acute hemodynamic changes after doxorubicin or any drug affecting cardiac function. The method we describe is eminently suitable for investigating the cardiotoxicity of chemotherapeutic agents.
Chromosomal abnormalities in adult non‐endemic burkitt's lymphoma and leukemia: 22 new reports and a review of 148 cases from the literature
Authors: Kornblau Steven M. , Goodacre Angela , Cabanillas Fernando
Published: February 2007

Tumour cell karyotypes from patients with Burkitt lymphoma (BL) or Burkitt's type leukemia (ALL3) were studied for correlation with survival, bone marrow and cerebral spinal fluid involvement (CSF), human immunodeficiency virus (HIV) serology, and for recurrent cytogenetic abnormalities.

The records of 22 patients with BL from our institution and of 148 cases of BL and ALL3 reported in the literature with karyotypes were evaluated for clinical and cytological features.

Overall survival was only 28 per cent and 88 per cent of deaths occurred within the first nine months after diagnosis. Those who survived at least 18 months were unlikely to relapse. Age and gender did not significantly affect survival. Patients presenting with advanced Ann Arbor stage, bone marrow or CSF involvement had lower survival rates. The association of translocations involving chromosome band 8q24 with this disease is confirmed. Sixty‐two per cent of karyotypes had t(8;14)(q24;q32) translocations; the recognized variant translocations t(8;22)(q24;q11) and t(2;8)(p12;q24) affected 12 per cent and 9 per cent respectively. Seventeen percent had abnormal karyotypes but no classic translocation. Patients with variant translocations had the poorest survival rates, and those with the classic t(8;14)(q24;q32) did the best. Despite a small sample size, the variant translocation t(8;22)(q24;q11) appeared to occur at an increased frequency in the patients with AIDS. In the entire group, recurrent involvement of chromosome regions 1q2, 6q11–14 and 17pl suggests that alteration of genes at these loci, B Cell Growth Factor (BCGF) at 1q2 and p53 on 17p, may contribute to the development and progression of this tumour. Similarly, the frequent trisomies of chromosomes 7, 8, 12 and 18 may indicate an effect on tumour cell growth due to increased gene dosage. Trisomy 12 was found in eight tumours, five from patients with AIDS, suggesting that chromosome 12 has a site or gene whose allelic dosage is selected for in AIDS related lymphoma cells.

Cytogenetic studies of adult Burkitt lymphoma and leukemia suggest several likely loci for gene alterations that in conjunction with myc translocations can lead to tumorigenesis.
Etoposide, 6‐thioguanine and idarubicin, an oral combination regimen (ETI) for the induction treatment of acute leukemia
Authors: Ruutu Tapani , Elonen Erkki
Published: February 2007

Twenty patients with advanced acute leukemia (16 acute myeloid leukemia (AML), three myeloid blast crisis (BC) of chronic myeloid leukemia (CML), one acute lymphatic leukemia) were treated with a peroral regimen consisting of etoposide 80 mg/m2 and 6‐thioguanine 100 mg/m2 twice daily for 5 days, and idarubicin 15 mg/m2 once daily for 3 days (ETI). Two AML patients were in first relapse. All the other patients with acute leukemia had a later relapse or were refractory to primary or salvage treatment. One to six ETI cycles were given. Four AML patients achieved remission and one patient with BC of CML entered the second chronic phase. Clearing of the blood of leukemic cells was seen in seven additional patients. Infection was the most common complication, gastrointestinal toxicity was not a major problem. In conclusion, peroral ETI treatment has a marked antileukemic effect even in an advanced disease, and the toxicity is moderate and well acceptable.