bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal involvement in patients with non‐Hodgkin's lymphoma: Clinical and pathological features in 23 cases
Authors: Richards M. A. , Mootoosamy I. , Reznek R. H. , Webb J. A. W. , Lister T. A.
Published: February 2007

Twenty‐three cases of renal or perirenal involvement by non‐Hodgkin's lymphoma were identified from a restrospective review of computed tomography (CT) scans performed on patients at St Bartholomew's Hospital over an 8‐year period. The histology, clinical features and survival of these patients were examined.

Eighteen of the 23 patients had high grade histological subtypes according to the Kiel classification. The majority of cases were identified from scans performed at the time of presentation. In nine cases renal lymphoma was observed in the absence of detectable retroperitoneal lymphadenopathy. Staging was rarely altered by the finding of renal lymphoma as 21 of the 23 patients had involvement of other extranodal sites in addition to the kidney. Survival did not appear to be adversely affected by the presence of renal lymphoma at the time of initial diagnosis. During the same period no cases of renal involvement were identified in patients with Hodgkin's disease, although one patient had perirenal involvement.
Rearrangement of human T cell receptor β and γ chain genes in adult t cell leukemia/lymphoma
Authors: Ohshima K. , Yoshida T. , Kikuchi M. , Masuda Y. , Kimura N. , Satoh H.
Published: February 2007

We studied rearrangement of human T cell receptor genes (TCR) of Cβ, Cγ, Vγ and Jγ in 34 cases of adult T cell leukemia/lymphoma (ATLL), consisting of 29 cases with monoclonally integrated HTLV‐I proviral DNA (ATLL‐W) and five without monoclonal integration (ATLL‐O), in comparison with 12 cases of other peripheral T cell lymphomas (non‐ATLL).

All cases of both ATLL and non‐ATLL showed some rearrangement of T cell receptor genes (TCRs) of Cβ. Cγ, Vγ, or Jγ. Rearrangement of TCRβ was found in 28 of 29 cases of ATLL‐W, all cases of ATLL‐O. and eight of 12 cases of non‐ATLL. Rearrangement of TCRγ was observed in 21 of 22 cases of ATLL‐W. and in all cases of ATLL‐O and non‐ATLL. In TCRγ, rearrangement of Cγ was seen in six of 20 cases of ATLL‐W. none of three ATLL‐O cases and three of six cases of non‐ATLL. Vγ rearrangement occurred in 14 of 18 cases of ATLL‐W, one of two cases of ATLL‐O, and three of six cases of non‐ATLL. Rearrangement of Jγ, was found in 16 of 22 cases of ATLL‐W, two of five ATLL‐O cases, and six of seven non‐ATLL cases. Rearrangement was more frequent in ATLL‐W than in ATLL‐O and non‐ATLL. The incidence rate of rearrangement of Vγ families of Vγ1, Vγ2, and Vγ3 was nearly the same in each group, except for deletion of Vγ3, which was often observed in ATLL but was absent in non‐ATLL. These results indicate the usefulness of detection of TCR and HTLV‐I proviral DNA to differentiate ATLL from other T cell malignancies.
Human T‐cell lymphotropic virus type I (HTLV‐I) antibodies in pre‐diagnostic serum of patients with familial adult T‐cell leukemia/lymphoma (ATL)
Authors: Nomura Abraham M. Y. , Yanagihara Eugene T. , Blattner William A. , Ho Gloria Y. F. , Inamasu Melvin S. , Severson Richard K. , Nakamura Jeffrey M.
Published: February 2007

In a study of 7498 American men of Japanese ancestry in Hawaii, 26 incident cases of leukemia or non‐Hodgkin's lymphoma were identified after a follow‐up period of 19 years. Two of the cases, who were brothers, were diagnosed with adult T‐cell leukemia/lymphoma (ATL). Both of these brothers had human T‐cell lymphotropic virus type I (HTLV‐I) antibodies in their stored serum which were obtained 4 and 18 years before diagnosis. None of the 24 patients with other hematologic malignancies or the 26 matched controls were HTLV‐I antibody positive. This finding lends further support for a role of HTLV‐I in the etiology of adult T‐cell leukemia/lymphoma.
Combination of interferon and dexamethasone in refractory multiple myeloma
Authors: San Miguel J. F. , Moro M. , Bladé J. , Guerras L. , Hernandez J. , Jimenez‐Galindo R. , Ortega F. , Gonzalez M.
Published: February 2007

The present pilot study was designed to analyse the efficacy and toxicity of the association of interferon (IFN) and dexamethasone (Dx) in 32 resistant and relapsed myeloma patients. Among the evaluable cases. 15 (68 per cent) responded to treatment (32 per cent achieved an objective response—OR—and 36 per cent a partial response—PR—), the ‘remission’ status lasting for more than one year in six of them. Moreover, four out of the seven OR patients showed a reduction in B.M. plasma cells to < 5 per cent. Five out of 11 patients that were previously refractory to VBAD, that includes high dose dexamethasone (Dx), responded to IFN‐Dx. The protocol was generally well tolerated with only four patients discontinuing therapy due to adverse effects.

The present results show that the combination IFN + Dx is a promising therapeutic approach for patients with refractory myeloma.
Expression of differentiation and adhesion molecules in sporadic Burkitt's lymphoma
Authors: Aiello Antonella , Delia Domenico , Fontanella Enrico , Giardini Roberto , Rilke Franco , Porta Giuseppe Della
Published: February 2007

The phenotypic features of 44 cases of sporadic Burkitt's lymphoma (BL) were investigated by monoclonal antibodies (MoAbs). The majority of cases were positive for HLA‐DR (97 per cent), CD19 (100 per cent), CD20 (92 per cent) and CD37 (83 per cent) pan‐B markers, in accordance with the B‐cell derivation of the tumour; the B‐cell restricted markers CD21, CD22 and FMC7 reacted with 28 per cent, 66 per cent and 75 per cent of cases, respectively. Of the mantle zone B‐cell specific MoAbs, CD1c was always negative, whereas CD23 and 2.7 were positive with one and two cases, respectively. CD39 was weakly reactive on two specimens, one of which was CD23+. The germinal centre specific MoAbs CD10 and CD77 (Burkitt's lymphoma antigen) displayed a heterogeneous pattern of reactivity and allowed to identify 4 subgroups: CD10+/CD77+ (44 per cent), CD10+/CD77‐ (15 per cent), CD10‐/CD77+ (36 per cent) and CD10‐/CD77‐ (5 per cent). Of 15 cases tested for the expression of CD11a and CD18 lymphocyte‐function‐associated (LFA‐1) antigens and their ligand ICAM‐1 (CD54), seven were positive and six negative for the three markers, while the other two cases expressed alternatively the two molecules. Analysis of the putative normal BL cell counterpart, identified with the CD77 marker in normal lymphoid tissues, showed that all CD77+ B‐cells were constitutively CD11a+/CD18+, suggesting that BLs are likely to arise from a LFA‐1 positive B‐cell and may down‐regulate these molecules during neoplastic transformation.
PRESENCE OF EPSTEIN‐BARR VIRUS DNA IN NASAL LYMPHOMAS OF B AND ‘T’ CELL TYPE
Authors: Ho F. C. S. , Srivastava G. , Loke S. L. , Fu K. H. , Leung B. P. Y. , Liang R. , Choy D.
Published: February 2007

We studied 12 tumours from 11 Chinese patients with primary nasal lymphoma for presence of Epstein‐Barr Virus (EBV) DNA, using Southern‐blot analysis. These results were correlated with immunophenotype and T‐cell receptor (TcR) or immunoglobulin gene rearrangement patterns. EBV DNA was detected in all nine tumours with a ‘T’ phenotype, in both primary and secondary sites. When the structure of the viral genomic termini was studied using the EcoRI‐Dhet probe, a single clonal episomal band was demonstrated in five tumour samples, with one other case showing a biclonal pattern. However, none of these cases showed clonal rearrangement of TcRβ chain gene, and TcRγ rearrangement was found only in one. The lineage of these phenotypic ‘T’ lymphomas therefore require further studies for confirmation. Two out of three B‐lymphomas were also EBV DNA+; clonal EBV DNA was found in one. Their B‐lineage was confirmed by detection of clonal immunoglobulin gene rearrangements. The association of EBV with an increasing number of lymphomas of different types highlights the need for continued study into its role in oncogenesis.
HYBRID FORM OF HAIRY CELL LEUKEMIA AND CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Sun Tsieh , Susin Myron , Shevde Nirmala , Teichberg Saul
Published: February 2007

We report a case with mixed features of hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL), which may represent a hybrid form of these two entities. Hairy projections were demonstrated on leukemic cells in the peripheral blood. Surface marker studies of blood and spleen specimens by flow cytometry and immunohistochemistry showed immunophenotype characteristic of HCL, namely, monoclonal IgG‐kappa, positive reactions to CD 11c, CD 19, CD 20, CD 22, and HLA‐DR, but negative reactions to CD 3, CD 5, CD 7 and CD 10. The only atypical finding was the absence of CD 25. Immunogenotyping showed rearrangement of heavy‐chain and kappa light chain genes. Leukemic cells were also positive for tartrate‐resistant acid phosphatase (TRAP). A pseudosinus pattern was demonstrated in the spleen. However, the leukemic cells in the spleen showed atypical cytologic features. Clinically, the patient had generalized lymphadenopathy, high leukocyte counts, Coombs' negative hemolysis, hypoimmunoglobulinemia and IgG‐kappa monoclonal gammopathy, features more consistent with CLL than HCL. Although only CD 11c, CD 22, CD 25 and TRAP are characteristic for HLC and CD 5, characteristic for CLL, a panel of eight markers is recommended for the differential diagnosis of HCL, CLL and other low‐grade B‐cell neoplasms, which may share some common features, making a clear‐cut diagnosis difficult.
Non‐Hodgkin's lymphomas involving the female genital tract
Authors: Liang Raymond , Chiu Edmond , Loke S. L.
Published: February 2007

Thirteen female patients with lymphomas involving the genital tract were studied. Their median age was 50 years. There were three cases of stage I disease, one stage II and nine stage IV. The gastrointestinal tract was commonly involved in patients with disease in the ovary. The histology was mostly intermediate or high grade according to the Working Formulation. Immunophenotyping was performed in six patients and they were all B‐cell tumours. There appeared to have a strong association between gastrointestinal involvement and ovarian disease. All patients received combination chemotherapy with or without additional radiotherapy and the survival of patients with stage I and II disease appeared to be superior to those with stage IV disease. However, the difference observed did not reach statistical significance because of small patient number. It remains uncertain whether lymphomas of the female genital tract by itself carries a poorer prognosis than the nodal lymphomas of comparable stage and histology.
Failure of mithramycin to control the myeloid blast phase of chronic granulocytic leukemia: A report on nine patients and review of the literature
Authors: Johnson P. R. E. , Yin J. A. Liu , Narayanan M. N. , Geary C. G. , Love E. M. , Cinkotai K. I.
Published: February 2007

After reports of the successful use of mithramycin and hydroxyurea in the myeloid blast phase of chronic granulocytic leukemia, we treated nine patients according to the protocol devised by Koller and Miller (1986). There were no complete responses, but one patient had a partial response with a transient return to the chronic phase. Of the remaining eight patients, two experienced lessening of bone pains, and one a reduction in spleen size, but without hematological improvement. The regimen was associated with significant toxicity, and no overall survival advantage. We present a review of published data regarding the use of mithramycin in chronic granulocytic leukemia which supports the results in our series. The combination of mithramycin and hydroxyurea is largely ineffective in the blast phase of chronic granulocytic leukemia, but may be of value in the accelerated phase.
Prognostic value of serum beta 2 microglobulin in primary gastric lymphoma
Authors: Avilés Agustin , Díaz‐Maqueo José C. , Rodriguez Leticia , García Edna L. , Guzmán Renaldo , Talavera Alejandra
Published: February 2007

Sixty‐eight previously untreated patients with primary gastric non‐Hodgkin's lymphoma (NHL) available for analysis, were entered in a study in which the prognostic significance of serum beta 2 microglobulin levels were evaluated.

The serum beta 2 microglobulin was the most significant prognostic factor. Patients with high levels (> 3.5 μg/mL) had a relapse‐free survival (RFS) of 36 months, while the median RFS has not been reached in patients with normal levels (p<0.001). The 5‐year survival was 80 per cent for patients with normal levels, statistically significant when compared to patients with high levels: 38 per cent (p> 0.001).

Serum beta 2 microglobulin should be included in the initial staging of patients with primary extranodal NHL and patients with high levels should be treated more aggressively.
Severe legionella pneumophila infection in a patient with hairy cell leukemia in partial remission after a interferon treatment
Authors: Radaelli Franca , Langer Martin , Chiorboli Ornella , Proietti Daniela , Baldini Luca
Published: February 2007

Legionella pneumonia is an increasingly frequently reported complication in immunocompromised patients, particularly patients with hairy cell leukemia (HCL) in active phase. The most important predisposing factor seems to be the quantitative and qualitative defect of the monocytic‐macrophagic system characteristic of HCL. We report a case of severe Legionella pneumophila infection with multisystem involvement in a patient with HCL in stable partial remission obtained after therapy with interferon. In our patient recovery of a normal monocyte count did not protect against a legionella infection, indicating that this pathogen should always be sought in HCL patients even those in clinical and hematologic remission. Early diagnosis and appropriate treatment may reduce the mortality of this serious complication.
Radiotherapy as salvage treatment in patients with hodgkin's disease or non‐hodgkin's lymphoma relapsing after initial chemotherapy
Authors: Kirkove Carine , Timothy Adrian R.
Published: February 2007

The prognosis of relapsing Hodgkin's disease (HD) and high grade aggressive non‐Hodgkin's lymphoma (NHL) is generally poor since many of these patients fail to respond to second line chemotherapy. Radiation therapy has been reported as an effective but seldom used, alternative treatment. We have observed very encouraging results with salvage radiotherapy in a highly selected group of eight lymphoma patients (six with HD and two with high grade NHL), suffering mainly from nodal relapse. The literature on the use of radiation therapy after chemotherapy failures in HD and NHL is reviewed.
Sequential versus alternating chemotherapy for high grade non‐hodgkin's lymphomas: A randomized multicentre trial
Authors: Köppler H. , Pflüger K. H. , Eschenbach I. , Pfab R. , Birkmann J. , Zeller W. , Steinhauer E. U. , Gropp C. , Oehl S. , Lötzke E. , Kuhn H. , Drings P. , Gossmann H. H. , Lennert K. , Stein H. , Havemann K.
Published: February 2007

In a multicentre phase III trial 146 previously untreated patients with high grade non‐Hodgkin's lymphomas stage II–IV were randomized to receive either four cycles of CHOEP (cyclophosphamide 750 mg/m2 iv d 1, doxorubicin 50 mg/m2 iv d 1, vincristine 2 mg iv d 1, etoposide 100 mg/m2 iv d 3–5, prednisolone 100 mg po d 1–5) (treatment arm A), or four cycles of chemotherapy with hCHOP (cyclophosphamide 1200 mg/m2 iv d 1, doxorubicin 40 mg/m2 iv d 1 + 2, vincristine 2 mg iv d 1, prednisolone 100 mg po d 1–5) alternating with IVEP (ifosfamide 1500 mg/m2 iv d 1–5, vindesine 3 mg/m2 iv d 1, etoposide 120 mg/m2 iv d 3–5, prednisolone 100 mg po d 1–5) (treatment arm B). After four cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients in complete or partial remission without persisting extranodal disease. A complete response (CR) was seen in 124/146 patients (86 per cent) with 87 per cent CR in arm A versus 83 per cent CR in arm B. During a median follow‐up of 17 months (range 2–40) 30 patients relapsed (16 patients arm A, 14 patients arm B). The overall survival at 40 months is projected to be 71 per cent versus 70 per cent for arm A and B, respectively. Disease‐free survival is projected to be 68 per cent in arm A and 59 per cent in arm B at 40 months. So far, the differences in CR, survival and disease‐free survival are not statistically significant. Toxicity of all regimens was acceptable, however, with a significant morbidity and one treatment‐related death in patients > 70 years after hCHOP. Main side effects were mild nausea/vomiting, leukopenia and fever/infection associated with leukopenia.

In conclusion both treatment modalities produced high complete remission rates. A longer follow‐up will be needed to exclude differences in over‐all and disease‐free survival.
Treatment of terminal‐phase chronic myelogenous leukemia with intermediate‐dose cytarabine and hydroxyurea
Authors: Lazzarino M. , Morra E. , Brusamolino E. , Alessandrino E. P. , Orlandi E. , Pagnucco G. , Castagnola C. , Bernasconi P. , Merante S. , Bonfichi M. , Castelli G. , Canevari A. , Bernasconi C.
Published: February 2007

We used intermediate doses of Ara‐C (IDAra‐C) in the treatment of 15 patients with chronic myelogenous leukemia (CML) in blast crisis and, combined with hydroxyurea, in 20 CML patients in accelerated phase. Patients with blastic CML received intensive 5‐day courses of IDAra‐C 600 mg/m2 every 12 h as a 2‐h infusion. Of 15 patients, three achieved complete response (CR) and three partial response (PR), for an overall response rate of 40 per cent. All patients developed severe leukopenia and thrombocytopenia, and two died in hypoplasia. Except nausea and vomiting requiring medication, other nonhematologic toxicities were uncommon. Median response duration was 4 months (range 1 to 7 months). Survival was 5 months for responders and 1·5 months for nonresponders. Patients with CML in accelerated phase were treated with two‐day courses of IDAra‐C 600 mg/m2 every 12 h by 2‐h infusion, every two‐three weeks. Daily hydroxyurea 1–1·5 g/day was administered between courses. Of 20 patients, 15 (75 per cent) achieved a good PR with rapid improvement of the symptoms of disease acceleration. The median duration of response was 11 months (range 3 to 38 months); duration was over 24 months in five patients. The median survival from the start of IDAra‐C was 13 months for responders and 3·5 months for nonresponders. We conclude that IDAra‐C is an effective approach for CML in terminal phase. Its use in 5‐day induction courses for blast crisis CML has a response rate comparable to that achieved with high‐dose Ara‐C. In patients in accelerated phase, the combination of short courses of IDAra‐C with hydroxyurea is a well‐tolerated treatment able to improve substantially the clinical and hematologic symptoms of disease progression.
A pilot study of epirubicin and chlorambucil in the treatment of chronic lymphocytic leukemia (CLL)
Authors: Smith G. M. , Child J. A. , Milligan D. W. , McEvoy M. A. , Murray J. A.
Published: February 2007

In a pilot study of the combination of epirubicin and chlorambucil in the treatment of chronic lymphocytic leukemia (CLL), 10 patients with advanced or progressive disease were treated in four centres. Up to a total of 15 course in individual patients were given. Toxicity was relatively mild with nausea due to epirubicin being the most commonly reported side‐effect. One patient developed a probable septicemia during a period of neutropenia. In another patient who died from probable Pneumocystis carinii pneumonia (PCP) after only one course of therapy, death could not be regarded as necessarily treatment‐related. In seven previously untreated patients, one complete response and four partial remissions were seen. All three previously treated patients showed partial remissions
Quantitative study of KI‐67 antibody staining in 46 T‐cell malignant lymphomas using image analysis
Authors: Caulet S. , Brousset P. , Schoevaert D. , Chttal S. M. , Delsol G. , Audouin J. , Diebold J.
Published: February 2007

Image analysis with a SAMBA 2005 (ALCATEL‐TITN, Co) was used to quantify the Ki‐67 stained area percentage in 46 T‐cell malignant lymphomas (T‐ML), classified according to the updated Kiel classification. This parameter demonstrated correlation with the number of Ki‐67‐positive cellular profiles (r = 0.88, P < 0.001) and was more reproducible than cell counting.

A significant difference was found between low and high grade T‐ML (mean values ± SEM respectively of 10.20 ± 1.82 per cent and 25.63 ± 3.15 per cent). The most interesting findings were that: (1) AILD‐type T‐ML showed an intermediate proliferation rate (15.55 ± 2.72 per cent) between pleomorphic T‐ML with medium and with large cells (respectively 12.53 ± 3.64 per cent and 22.43 ± 3.46 per cent), both of which belong to the high grade malignancy group. This finding is in accordance with the poor prognosis of this subtype despite its classification in the low grade malignancy group. (2) Subclassification of the pleomorphic MLs according to the predominance of small, medium or large cells, demonstrated significant differences between these three subtypes. However, the great overlap of values between pleomorphic T‐ML with medium and with large cells, seems to indicate that the Subclassification of these two subtypes is less valid. (3) A wide range of values with overlap was observed in AILD‐type ML, in pleomorphic with medium or large cells and in lymphoblastic T‐ML: for these T‐ML with variable survival courses, the Ki‐67 area percentage, one parameter of proliferative activity, appears worth studying as a prognostic factor.
Recombinant human granulocyte macrophage colony stimulating factor following alternating non cross resistant chemotherapy in hodgkin's disease
Authors: Oza A. M. , Leahy M. , Dorey E. , Davis C. L. , Amess J. , Horton M. , Rohatiner A. Z. S. , Wrigley P. F. M. , Lister T. A.
Published: February 2007

Fourteen patients with Hodgkin's disease (two previously untreated, 12 following relapse or with refractory disease) were treated with a combination chemotherapy regimen comprising chlorambucil, vinblastine, procarbazine, prednisolone, etoposide, vincristine and adriamycin administered on days 1–8. Recombinant human granulocyte‐macrophage colony stimulating factor (rhGM‐CSF) (mammalian glycosylated, Sandoz Schering‐Plough) was administered after alternate cycles of chemotherapy from day 10 for 7 days by continuous intravenous (i.v.) infusion in 12 patients in a dose finding study (dose: 2 μg/kg/day in four patients. 4 μg/kg/day in four patients and 8 μg/kg/day in four patients) and by daily subcutaneous (s/c) injections in two patients (8 μg/kg/day). There was a rapid peripheral leucocytosis following the rhGM‐CSF, reaching a peak at 1–2 days in 12/14 patients. The initial leucocytosis was composed of neutrophils followed by a rise in immature myeloid cells. There was no difference observed in the duration or depth of the nadir following chemotherapy or in the rate of recovery of peripheral white cell counts between cycles with and without rhGM‐CSF in patients treated with 2 and 4 μg/kg/day. At the dose of 8 μg/kg/day, 3/6 patients had a shorter nadir duration in the cycle with rhGM‐CSF, compared with cycle without rhGM‐CSF. There was no difference in frequency of infection in cycles with and without rhGM‐CSF. Following chemotherapy, six patients achieved clinical remission, six partial remission and two had progressive disease.
Advances in the chemotherapy of gynecologic malignancies
Authors: Ozols Robert F.
Published: February 2007

Chemotherapy is playing an ever increasing role in the treatment of patients with the common gynecologic malignancies, including ovarian, cervical cancer, and endometrial cancer. Chemotherapy has its most defined role in the treatment of patients with ovarian cancer where virtually all patients will receive cytotoxic chemotherapy. There are four major areas of research in chemotherapy in gynecologic malignancies. In retrospective studies it has been demonstrated that dose intensity is an important factor in maximizing response rates. Clinical studies are now prospectively evaluating the importance of dose intensity, particularly with the new platinum analogue carboplatin. In addition, it has been demonstrated in endometrial cancer and cervical cancer that patients with poor prognostic features such as high grade tumours and large volume disease have a low probability of cure by standard modalities such as surgery and radiation. In this group of patients combined modality approaches are being evaluated. In addition, regional therapy, either in the form of intra‐arterial therapy for patients with cervical cancer or intraperitoneal therapy for patients with ovarian cancer, is being investigated.

The primary factor limiting the effectiveness of chemotherapy in gynecologic malignancies is the development of drug resistance. It has recently been demonstrated that several drugs such as taxol, ifosfamide. and hexamethylmelamine have activity in patients who have had previous treatment with platinum‐based compounds. In addition, the mechanism associated with the development of drug resistance in ovarian cancer have recently been identified. Clinical trials have been initiated with compounds such as buthionine sulfoximine in an attempt to specifically reverse resistance associated with alkylating agents and platinum compounds.
Effects of recombinant human interferon‐alpha, beta and gamma on the antiproliferative activity of cytarabine in K562 human myeloid leukemia clonogenic cells
Authors: Hassan H. T. , Tsiriyotis C. , Maurer H. R.
Published: February 2007

The effects of recombinant human interferon‐alpha, beta and gamma (IFN) on the antiproliferative activity of cytarabine (ara‐C) in K562 human myeloid leukemia clonogenic cells were studied in an agar capillary microassay. The addition of IFN‐alpha did not affect the antiproliferative activity of ara‐C in K562 cultures treated with low concentrations of ara‐C: 10–50 nM, whereas in those treated with high concentrations of ara‐C: 100–500 nM, IFN‐alpha significantly reduced the antiproliferative activity of ara‐C. The addition of 3 × 104 U/ml IFN‐alpha to ara‐C‐treated K562 cultures increased the IC50 of ara‐C on day 5 from 102 to 214 nM, i.e. ara‐C + IFN‐alpha was about twofold less potent than ara‐C alone. Low concentrations of IFN‐beta and IFN‐gamma did not affect the antiproliferative activity of ara‐C on K562 colonies, but high concentrations of these two interferons reduced the antiproliferative activity of ara‐C. The addition of 4 × 103 U/ml IFN‐beta or 104 U/ml IFN‐gamma increased the IC50 of ara‐C on day 5 to 304 nM or to 316 nM, respectively, i.e. ara‐C + IFN‐beta or IFN‐gamma was about threefold less potent than ara‐C alone. The significant reduction of the desired antiproliferative activity of ara‐C by the three interferons was reproduced in liquid suspension cultures of K562 cells on day 4 in the following order: IFN‐gamma > IFN‐beta > IFN‐alpha. The present negative interactions of the three interferons with ara‐C particularly at high concentrations, may caution against the clinical use of the combination of ara‐C and interferon in the treatment of myeloid leukemia patients.
The prognostic factors for peripheral T‐cell lymphomas
Authors: Liang Raymond , Loke S. L. , Chan A. C. L.
Published: February 2007

The peripheral T‐cell lymphomas of 50 patients were classified by histological type and tumour cell size, the latter as described by the Nebraska Group. There was no difference in the pattern of their clinical features among the various histological subtypes and their clinical outcome was similar. Cell size and other factors including sex, age, presence of B symptoms, sites of primary disease, histological subtypes according to the Japanese classification, lactate dehydrogenase level and presence of bulky disease did not appear to correlate with clinical outcome. However, patients with stage IV disease had significantly lower CR rate (9/29 versus 16/21, p = 0·01) and poorer survival at 3 years (p = 0·05) than those with stage I, II and III disease. Patients receiving COPP, the less intensive chemotherapy regimen, appeared to have poorer clinical outcome but the difference observed was not statistically significant because of the number of patients in each subgroup.
Angiocentric T‐cell lymphoma of the nose, paranasal sinuses and hard palate
Authors: Aviles Agustin , Rodriguez Leticia , Guzman Renaldo , Talavera Alejandra , Garcia Edna L. , Diaz‐Maqueo Jose C.
Published: February 2007

Sixty‐five cases of malignant lymphoma of the nose, paranasal sinuses and hard palate were retrospectively analysed to identify the presence or absence of angiocentric lesions. We observed that the 23 patients with angiocentric lesions had a worse prognosis with a shorter duration of response and also a shorter duration of survival, compared with 42 cases of malignant lymphoma of the same anatomical region but without angiocentric lesions. Patients with angiocentric lymphoma were associated with other bad prognostic factors such as elevated levels of lactic dehydrogenase and beta 2 microglobulin, local bone destruction and lymphopenia. Immunophenotyping studies showed that most patients with angiocentric lesions had T cell lymphomas (18 of 23, 78 per cent).

We believe that patients with angiocentric T cell lymphomas of the nose, paranasal sinuses and hard palate represent a distinctive clinico‐pathological entity with different clinical presentation and outcome. Patients with angiocentric T cell lymphomas had frequent relapse at extranodal sites and combined therapy should be considered as the initial therapeutic approach.
Acute myelogenous leukemia (AML) and diabetes insipidus (DI): Further association with monosomy 7
Authors: Slater S. E. , Maccallum P. K. , Birjandi F. , Gibbons B. , Lister T. A.
Published: February 2007

Diabetes insipidus (DI) is a rare complication of acute myelogenous leukemia (AML). Five of the six such cases described in the literature who had banded chromosomal studies performed had monosomy 7 and the sixth patient had del(7)(q22). A further case of AML complicated by DI in whom banded chromosomal studies revealed a complex karyotypic abnormality, including monosomy 7, is reported.

The association between monosomy 7 and DI in AML appears specific but the reason for this association remains unclear.
Mitoxantrone and intermediate‐dose cytosine arabinoside for poor‐risk acute leukemias: Response to treatment and factors influencing outcome
Authors: Sierra Jorge , Grañena Albert , Bosch Francesc , Carreras Enric , Martí Josep‐Maria , Urbano‐Ispizua Alvaro , Rovira Montserrat , Rozman Ciril
Published: February 2007

Mitoxantrone (MIT, 12 mg/m2, i.v. 5 days) and intermediate‐dose cytosine arabinoside (IDAC 1 g/m2/12 h, i.v. 3 days) was given to 43 patients with poor‐risk acute leukemias (AL). Moderate or severe toxicity was infrequent. The proportion of complete remissions (CR) in the main patient categories was as follows: 15/18 (85 per cent) in acute myeloid leukemia (AML) in the first relapse, 2/6 in ALL in the first relapse, 0/2 in AML in relapse after bone marrow transplantation (BMT), 2/7 in AML refractory to first‐line treatment (REFAL), and 1/6 in postmyelodysplastic (PMD‐AL) plus secondary AL (S‐AL). The mortality rate during induction was 23 per cent. Median duration of CR was 24 weeks.

The multivariate prognostic factor analysis on CR obtention showed that data concerning treatment for the first relapse and platelet count higher than the median of the series were favourable. On the contrary, PMD‐AL, S‐AL and REF‐AL were unfavourable situations. A percentage of marrow erythroblasts superior to the median was a favourable prognostic factor for survival. Finally, the duration of CR after MIT‐IDAC was directly related to the duration of previous CR.

In conclusion, MIT‐IDAC was highly effective to attain CR in AML in the first relapse. However, due to the poor long‐term results in these patients, additional measures are recommended after CR.
Cytophagic histiocytic panniculitis: A diagnostic dilemma
Authors: Cheah Phaik‐Leng , Looi Lai‐Meng , Tan Puay‐Eng , Bosco John , Kuperan Ponnudurai
Published: February 2007

Cytophagic histiocytic panniculitis (CHP) is a recently recognized entity that frequently poses a perplexing diagnostic problem. Although the classical case presents with a relapsing fever, subcutaneous nodules, pancytopenia and liver dysfunction, most patients have in addition a multitude of other manifestations which confuse the clinical picture. Notwithstanding the variable clinical course, the disease frequently terminates in fatal hemorrhage. Diagnosis is based on histological features. A lobular panniculitis with an infiltrate of cytologically benign cytophagocytic histiocytes in skin nodules is the sine qua non of CHP. Hence, a deep skin biopsy which includes subcutaneous fat is mandatory to establish the diagnosis. Published information regarding this newly described entity remains scarce and we report two cases of CHP, one occurring in a 30‐year‐old Kadazan man and another in a 17‐year‐old Chinese woman seen at the University Hospital, Kuala Lumpur. The latter case presented with exudative ascites, an unusual feature, possibly due to intra‐abdominal panniculitis. In addition, we record the development of cirrhosis in the same patient.
Association between atl and non‐hematopoietic neoplasms
Authors: Imamura Nobutaka , Inada Tominari , Tagya Yutaka , Yodoi Junji , Kuramoto Atsushi
Published: February 2007

A high incidence of multiple primary neoplasms has been observed in our patients with ATL in comparison to persons with other forms of hematologic malignancy who we have observed during the past 23 years (1963–1985). Five of 15 patients with ATL (33·3 per cent) have had at least one other associated neoplasm in comparison to only 44 of 1156 patients with other forms of hematological malignancy (3·8 per cent). The incidence figures for secondary neoplasms associated with the other hematologic malignancies were 4·3 per cent (16/370) for acute non‐lymphocytic leukemia (ANLL), 2·2 per cent (2/90) for acute lymphocytic leukemia (ALL), 4·8 per cent (1/21) for acute unclassifiable leukemia, 2·2 per cent (5/225) for chronic myelogenous leukemia, 4·7 per cent (2/43) for chronic lymphocytic leukemia, 5·9 per cent (8/136) for malignant monoclonal gammopathy and 3·7 per cent (10/271) for malignant lymphoma. The incidence of multiple neoplasms in patients with ATL in comparison to those with other hematological malignancies was statistically significant (p<0·01 or p<0·001). The neoplasms associated with ATL have been adenocarcinoma of the thyroid or stomach, and squamous cell carcinoma of the larynx, lip or lung. We identified ATL‐derived factor (ADF) in the cytoplasm of the secondary neoplasms of the ATL patients by means of indirect immunofluoroscopy and immunohistochemical techniques utilizing anti‐ADF antibody. We also identified ras p21 products in these neoplasms by means of p21 ras monoclonal antibody studies. The possibility that HTLV‐I was the cause of the secondary neoplasms thus was investigated. HTLV‐I provirus genome was not found in all the six cases of non‐ATL leukemic cells of the patients with anti‐HTLV‐I antibodies as determined by means of Southern blot analysis utilizing pX DNA probe. These findings suggest that there is some association between ATL cells and pre‐malignant cells through ADF or other unknown factors in the activation of ras oncogenes. Subsequent suppression of host immune defence mechanisms in ATL patients permits evolution of the secondary neoplasms.
Restriction of T cell receptor variable region in lymph nodes of adult T cell leukemia/lymphoma
Authors: Ohshima Koichi , Kikuchi Masahiro , Yoneda Satoshi , Kobari Shinichi , Sumiyosi Yoshiaki , Takeshita Morishige , Kimura Nobuhiro
Published: February 2007

Adult T cell leukemia/lymphoma (ATLL) is a mature T cell malignancy, especially derived from the CD4 positive T cell. To characterize the T cell, we examined the representation of T cell antigen receptor variable region, using the monoclonal antibodies [β V 5 (a), β V 5 (b), β V 6 (a), β V 8 (a), β V 12 (a), α V 2 (a), α‐β V (a)]. Clinicopathologically we classified the lymph nodes of patients with ATLL into three states (1) human T cell leukemia virus type I (HTLV‐I) associated lymphadenitis, reactive state; (2) incipient ATLL, early or pre‐neoplastic state; and (3) ATLL, neoplastic state. The lymph nodes of all three states were composed of unvarying CD4 positive T cells. Most of the lymph nodes with ATLL consistently presented α V 2 antigen, but no others. In HTLV‐I associated lymphadenitis, only a few cells reacted for α V 2, as in non‐specific lymphadenitis without ATLL features. One of three cases with incipient ATLL presented α V 2. The selective expression of T cell antigen receptor V region might be associated with the presence of HTLV‐I encoded superantigen, similar to human immunodeficiency virus (HIV).
Infiltration of eosinophils in Hodgkin's disease involved lymph nodes predicts prognosis
Authors: Enblad Gunilla , Sundstrom Christer , Glimelius Bengt
Published: February 2007

The number of infiltrating eosinophils were counted in tumour specimens from an unselected material of 140 cases of primary Hodgkin's disease (HD) and divided in three groups. Twenty‐six cases (19 per cent) showed heavy infiltration (>200 eosinophils/10 vision fields (VF)), 51 (36 per cent) moderate infiltration (11–200 eosinophils/10 VF and 63 virtually no infiltration (<10 eosinophils/10 VF). The eosinophilic infiltration was signifiantly more pronounced in the nodular sclerosis subtype. Cases with heavy infiltration had a significantly worse disease‐free survival compared to other cases. In a multivariate analysis, heavy eosinophilic infiltration was the most important factor for determining disease‐free survival in all patients and also when patients above and below 60 were analysed separately.
Potential role for low dose limited‐field radiation therapy (2 × 2 grays) in advanced low‐grade non‐Hodgkin's lymphomas
Authors: Ganem GéRard , Lambin Philippe , Socié GéRard , Girinsky ThéO , Bosq Jacques , Pico José Luis , Solal‐Céligny Philippe , Cosset Jean Marc
Published: February 2007

The purpose of this retrospective study was to evaluate the efficacy of low‐dose limited field radiation therapy (LDLRT) in low‐grade non‐Hodgkin's lymphoma (NHL) patients, in order to outline its possible role.

The rationale of the analysis was as follows: (1) there is no clear dose‐response relationship for radiation therapy (RT) in localized low‐grade non‐Hodgkin's lymphomas (LGNHL); (2) long‐term disease‐free survival can be achieved in advanced LGNHL with low‐dose (1.5‐2 Gy) fractionated total body irradiation; (3) moreover, some of our previous LGNHL patients stopped their conventional planned RT course for convenience after 5 to 7.5 Gy and remained free from local progression in irradiated volumes for a long period of time.

Patient selection criteria were the following: (1) patients with low‐grade NHL (LGNHL); (2) patients who received no other form of therapy concomitantly with LDLRT until evaluation of the response; (3) patients who received a planned dose of 4 Gy in two fractions and over 3 days in a limited field.

Out of 37 patients, 27 patients were fully evaluable. Twenty‐two patients had stage III or IV disease. The median logevity of the disease was 73 months. Twenty‐five patients had previously received chemotherapy (18 with anthracyclines).

Nineteen patients had received one LDLRT course only. Eight patients responding to the first LDLRT had received at least one subsequent LDLRT course.

After the first LDLRT course, an objective response in irradiated sites was observed in 24 of the 27 patients (89 per cent). Ten and 14 patients respectively demonstrated a complete response (CR) (37 per cent) and partial response (PR) (52 per cent). Freedom from progression in irradiated volumes for evaluable patients ranged from 4 to 35 months. Among the eight patients who received at least two LDLRT courses, a total of 20 different areas were irradiated, and 15 areas (75 per cent) showed a CR. Toxicity due to LDLRT was minimal.

In conclusion, low‐dose limited‐field RT resulted in a high proportion of responses in LGNHL. The mechanisms explaining this radioresponsiveness are poorly understood. However, the efficacy of LDLRT could have several clinical applications in the general management of patients with advanced LGNHL.
Transfection of the bcr/abl oncogene into factor‐dependent cells by electroporation: acquisition of autonomous proliferation
Authors: Takahashi Masuhiro , Furukawa Tatsuo , Tanaka Izumi , Ohsawa Yukiko , Nikkuni Kohji , Aoki Azusa , Goto Takao , Hashimoto Takao , Kishi Kenji , Koike Tadashi , Moriyama Yoshiaki , Shibata Akira
Published: February 2007

In order to clarify the function of P210 bcr/abl oncogene in leukemogenesis, IL‐3 dependent murine hematopoietic cell line, FDC‐P2, was transfected with the plasmid containing cDNA of P210 bcr/abl oncogene (pGD'210) or murine IL‐3 (pcDmIL3) by electroporation. Four out of five pGD'210 transfected clones as well as FDC‐P2 transfected with pcDmIL3, acquired autonomous proliferation (i.e. lost the requirement for IL‐3 supplementation). The expression of bcr/abl oncogene was weak in one clone, which remained dependent on IL‐3. Unlike pcDmIL3 transfectants, which secrete IL‐3 into the supernatant, IL‐3 was not demonstrated in the culture supernatant of pGD'210 transfected FDC‐P2. These findings suggest that P210 bcr/abl oncogene is directly associated with autonomous proliferation, which is the first process of leukemogenesis.
Salvage chemotherapy for relapsed and resistant lymphoma with a carboplatin containing schedule—epic
Authors: Richardson D. S. , Tighe M. , Cull G. , Johnson S. A. , Phillips M. J.
Published: February 2007

We have treated 11 patients with relapsed or resistant lymphoma with a combination of Etoposide, Prednisolone, Ifosfamide and Carboplatin (EPIC), obtaining complete responses in two patients and partial responses in four patients for an overall response rate of 54 per cent. The treatment was well tolerated with no toxic deaths and five patients were able to proceed to high dose therapy with autologous bone marrow transplantation (ABMT).
Multiple drug resistance, the MDR gene, and the law of maximum perversity as it applies to oncology: An hypothesis
Authors: Spiers A. S. D.
Published: February 2007

The so‐called Law of Maximum Perversity, generally stated, says that when more than one outcome is possible, that which is the more adverse is the outcome most likely to occur. In medical oncology, the most obvious expression of this law is the fact that all the neoplasms that are most sensitive to cytotoxic drugs and are most curable by chemotherapy, are rare and in numerical terms are not important as causes of cancer‐related deaths. Conversely, the most commonly encountered neoplasms that make up the bulk of oncologic practice and that cause over 90 per cent of cancer‐related deaths, are all relatively resistant to cytotoxic agents and are virtually never curable by chemotherapy administered in standard (i.e. non‐transplant) doses. It is postulated that the biological properties and the normal tissue distribution of the multidrug resistance (MDR) gene and its product p‐170 glycoprotein explain the observed incidences and distribution of tumours that are sensitive or insensitive to cytotoxic agents. The normal role of MDR is to protect cells from environmental carcinogens, and the tissues that are most at risk, and most richly supplied with MDR, will produce drug‐resistant neoplasms. Current attempts at MDR reversal may facilitate the treatment of some tumours that are resistant to multiple drugs but may cause severe toxic effects as a consequence of abrogating the largely unknown physiologic functions of P‐170.
Outcome of Hodgkin's disease in elderly patients
Authors: Diaz‐Pavon Jose Rodriguez , Cabanillas Fernando , Majlis Alejandro , Hagemeister Frederick B.
Published: February 2007

The outcome of Hodgkin's disease in elderly patients is a subject of controversy. We analysed retrospectively 31 cases of patients older than 60 years that received treatment according to current protocols. We observed a CR rate of 87 per cent and survival of 58 per cent with a median follow‐up of 58 months which is clearly better than most reported results in this age group. Although our population consists of only those entered on protocols it suggests that patients whose condition is adequate enough to allow them to receive standard therapy with a curative intent, have a similar outcome to that seen in younger patients.
Hepatosinusoidal leukaemia/lymphoma consisting of epstein‐barr virus‐containing natural killer cell leukaemia/lymphoma and T‐cell lymphoma; mimicking malignant histiocytosis
Authors: Ohshima Kohichi , Kikuchi Masahiro , Mizuno Shinichi , Akashi Koichi , Moriyama Kousei , Yoneda Satoshi , Takeshita Morishige , Shibata Takashi
Published: February 2007

Previously diagnosed cases of hepatosinusoidal T‐cell lymphoma and malignant histiocytosis (MH) may include lymphoid neoplasms of natural killer (NK) cell lineage associated with Epstein‐Barr virus (EBV). Such hepatosinusoidal neoplasms were found to demonstrate hepatomegaly but not lymphadenopathy, and all were diagnosed by a liver biopsy. Sixteen adult patients diagnosed with hepatosinusoidal leukaemia/lymphoma (six NK‐cell leukaemia/lymphomas [NKLLs], five instances of MH, three T‐cell malignant lymphomas [T‐MLs], and two adult T‐cell leukaemia/lymphomas [ATLLs] were examined for EBV by in situ hybridization, then were studied immunohistochemically and subjected to a DNA analysis. Among our five patients with MH, neoplastic cells showed T‐cells, but no histiocytic markers, and they were considered to have either a T‐cell or NK‐cell lineage. All NKLLs, MHs and T‐MLs, except for ATLLs accompanied by reactive hemophagocytic histiocytes, varied in number in each case. In situ hybridization revealed the presence of EBV in the nuclei of atypical cells in all of the six lymphoid neoplasms of NK‐cell lineage. Each case of MH and each T‐ML which represented EBV demonstrated no definite T‐cell or histiocytic markers. Patients with ATLL did not reveal EBV. In all patients with hemophagocytosis, EBV was present in the nuclei of the neoplastic lymphocytes, but not in the hemophagocytic cells. Finally, the 16 cases were reclassified into eight cases with EBV ‐containing NKLLs, six T‐MLs, and two ATLLs. In addition, no true histiocytic neoplasms were observed. The mechanism of hemophagocytosis may be therefore the production of lymphokines (macrophage‐activating factors) by neoplastic lymphocytes. EBV‐associated hepatosinusoidal leukaemia/lymphoma may thus contain a lymphoid neoplasm of NK‐cell lineage, which made it difficult to be distinguished from the previously designated malignant histiocytosis.