bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic heterogeneity displayed by T‐NON Hodgkin's lymphoma (T‐NHL) cells dispersed from diagnostic lymph node biopsies
Authors: Jones D. B. , Wright D. H. , Paul F. , Smith J. L.
Published: February 2007

In this communication we present the results of the study of the surface antigen expression of cells dispersed from 19 fresh lymph node biopsies. All cases subsequently received a histological diagnosis of T‐cell lymphoma (T‐NHL). The monoclonal antibody (Mab) panel employed for surface staining of viable cells contained reagents reactive with the sheep red blood cell receptor (OKT11) and T3‐receptor associated determinants (UCHT1, OKT3) and a range of surface antigens found on subsets of T‐cells. These antibodies are characterized according to their CD group as allocated by the First and Second Monoclonal Antibody Workshops. Cells were also stained with Mabs reactive with MHC class II subregion products. All 19 cases displayed marked heterogeneity for both pan‐T‐cell and T‐subset antigens. An observation which is significant in terms of the routine diagnosis of T‐NHL and with regard to the rational classification of node‐based tumours of T‐cell origin

Unlike resting peripheral blood T‐cells, MHC class I1 subregion products were expressed on most of the cases examined though Tu22, directed towards a monomorphic determinant of HLA‐DQ, stained fewer cells than other antibodies. Aberrant expression of MHC class I1 on lymphoma cells may reflect the activation of the tumour population.
Lymphohistiocytosis: A multi‐factorial syndrome of macrophagic activation clinico‐pathological study of 38 cases
Authors: Goldberg J. , Nezelof C.
Published: February 2007

Lymphohistiocytosis (LH) is defined by a widespread infiltrate of non‐malignant lymphocytes and macrophages, involving principally the liver, spleen and central nervous system and associated with a severe lymphoid atrophy

For this histological study, 38 juvenile cases of LH were selected and reviewed. Morphological and histochemical studies revealed that the macrophages were activated. They appeared to be OKM1, OKT9 and HLADr positive and showed a patent or occult erythro and thrombocytophagocytosis. Comparatively, most of the lymphoid cells did not bear any immunoglobulin and did not label with a wide panel of monoclonal antibodies including T3, T4, T6, T8, T11

The review of the clinical and biological data of these 38 cases suggests that LH does not represent a single entity but can be regarded as a non‐specific response to various causes. Three different conditions associated with LH can be isolated

The first group consists of patients in whom the disease is characterized by an early onset, high familial incidence and an inevitably fatal course. This category contains the largest number of cases (29 out of 38) and corresponds to the classic description of Familial Erythrophagocytic Reticulosis by Farquhar and Claireaux

The second group includes mainly male patients and children over 2 years old. Inheritance is not a predominant feature. The course of the disease is comparatively long. A viral infection was present in three of the seven cases. This category shares many of the clinico‐pathological features of the Virus Hemophagocytic Syndrome and is presumably related to a chronic and latent viral infection

A third group can be identified on the basis of the presence of pigmentation abnormalities and immunodeficiency disorders probably associated with cytoskeletal abnormalities. This group includes Chediak‐Higashi disease and Griscelli's disease

The fact that some genetic factors and immunodeficiency disorders are present in these three groups is probably significant and suggests that LH is a condition brought about by multiple factors—of which the common denominator is an apparent activation of the Mononuclear Phagocytic System.
An investigation of Ki‐1 positive large cell lymphoma with antibodies reactive with tissue macrophages
Authors: Jones D. B. , Gerdes J. , Stein H. , Wright D. H.
Published: February 2007

The diagnosis of true histiocytic lymphoma (THL) represents one of the most difficult and controversial areas of lymph node pathology. Recently, Stein et al. (1985) have demonstrated that a series of tumours presenting with morphological and immunocytochemical features, previously considered as being indicative of THL, share antigenic markers with Reed‐Sternberg and mononuclear Hodgkin's cells and, therefore, may be derived from lymphocytes, rather than histiocytes. In this study we have re‐investigated some of these cases with a panel of monoclonal antibodies variously reactive with macrophages. Although all cases contain a heavy infiltrate of reactive histiocytes the tumour populations are negative for histiocyte antigens.
DNA‐abnormality in hairy cell leukemia
Authors: Arrenbrecht Stefan , Heider Sonia
Published: February 2007

Spleen and light density peripheral blood leukocytes of 10 hairy cell leukemia (HCL) patients and total leukocytes of one patient and blood donor cells were stained quantitatively for cellular DNA. The DNA content of single cells was measured by flow cytometry (FC) and compared to the DNA content of sheep cells admixed as an internal control

Eight of eleven patients (72 per cent) showed deviations from blood donor DNA content. Two female patients showed increased cellular DNA content, the six male patients had hypodiploid cells. Chromosomal aberrations are therefore likely to exist in the majority of HCL patients

Separation of HCL cells into sheep erythrocyte rosette and non rosette forming cells revealed similar DNA abnormalities in both cell populations, suggesting that the leukemia encompasses cells with B and with T markers.
Cytosine arabinoside in the management of recurrent leukaemia
Authors: Ganesan T. S. , Barnett M. J. , Amos R. J. , Piall E. M. , Aherne G. W. , Man A. , Lister T. A.
Published: February 2007

A Phase II study of high dose cytosine arabinoside (ara‐C) with different schedules in patients with recurrent acute myelogenous leukaemia (AML) and myeloid blast crisis of chronic myeloid leukaemia has been conducted at St. Bartholomew's Hospital. Ara‐C was infused continuously for seven days at a dose of 100–200 mgs/m2 daily from day 1 with 1–2 g/m2 (3 h infusions) twice daily from day 2 for six days

Nineteen patients with acute myelogenous leukaemia and four patients with myeloid blast crisis of chronic myeloid leukaemia (CML) were treated. Complete remission was achieved in 4/19 patients with AML and in a further four patients an antileukaemic effect was observed. There were eight early deaths and three patients failed to show any response to therapy. All four patients with myeloid blast crisis of CML failed to respond to the treatment

Toxicity was considerable with gastro‐intestinal and hepatotoxicity being the most serious problems

Pharmacokinetic studies revealed that mean basal levels achieved with continuous infusion prior to high‐dose ara‐C were 102 ng/ml and peak levels were of the order of 104 ng/ml. The considerable toxicity of the regimen, without clinical advantage over less intensive programmes, resulted in its termination.
Treatment‐related leukemia in Hodgkin's disease: A multi‐institution study on 75 cases
Authors: Brusamolino E. , Papa G. , Valagussa P. , Mandelli F. , Bernasconi C. , Marmont A. , Bonadonna G. , Tura S. , Bosi A. , Mango G. , Mazza P. , Rossi E. , Leoni F. , D'Onofrio G. , D'Arcangelo E.
Published: February 2007

Hematological and cytogenetic characteristics of 75 cases of therapy‐related acute non lymphoid leukemia (t‐ANLL) occurring in Hodgkin's disease (HD) are analysed in this multi‐institution study. Combined radio and chemotherapy had been given in 88 per cent of patients, either as adjuvant (44 per cent) or as salvage modality (44 per cent). Radiotherapy alone and chemotherapy alone had been given in 3 per cent and 9 per cent respectively. Eighty per cent of patients were in remission of HD and 71 per cent off‐therapy while developing leukemia. The median latent time from remission of HD to leukemia was 34 months. The myeloblastic variety of leukemia accounted for 43 per cent of total cases; the myelomonocytic and monocytic for 17 per cent and 4 per cent, the promyelocytic and erythroblastic variants for 5 per cent and 7 per cent of t‐ANLL. Twenty four per cent of cases were unclassifiable; one of these was TdT‐positive. Dysplastic features of erythrocytic line were invariably present with circulating erythroblasts; defects of granulocytes, circulating megathrombocytes and micromegakaryocytes were also present. Bone marrow hypoplasia and marked fibrosis were documented in 47 per cent and 30 per cent of cases. Preleukemia heralded overt leukemia in 73 per cent of cases; 37 per cent had refractory anemia with no excess of blasts; 16 per cent of preleukemias were unclassifiable. Cytogenetics revealed chromosome abnormalities in 83 per cent of cases; 72 per cent presented chromosome 5 and/or 7 monosomy or partial deletion (5q‐ or 7q‐) of the long arm (94 per cent in the combined modality therapy group). In 3 cases, a pure monosomy 7 was observed; in none 5q‐alone. Response rate to conventional therapy was 14 per cent; low and high‐dose cytarabine were of little benefit. Long‐term CR (28+ and 16+ months) was achieved in 2 cases with allogeneic bone marrow transplantation (BMT) as first‐line therapy. A better knowledge of t‐ANLL in HD and new therapies, including BMT, may improve the prognosis of this late complication of intensive HD treatment.
Gastrointestinal lymphoma in Chinese: A retrospective analysis
Authors: Liang R. , Todd D. , Chan T. K. , Ng R. P. , Ho F. C. S.
Published: February 2007

Eighty‐four Chinese patients with gastrointestinal lymphoma were reviewed. There were 45 gastric and 39 intestinal lymphomas. The median age was 45 years and the male to female ratio 1.14:1. Diffuse histiocytic (60 per cent) or diffuse large cell (53.5 per cent) lymphoma comprised a majority of the cases. A high incidence of gastrointestinal bleeding at presentation was observed in our patients. According to a modified staging classification, a larger proportion of patients with intestinal lymphoma had advanced disease (Stage III and IV) than those with gastric lymphoma (82 per cent versus 55 per cent, p < 0.02) and gastric lymphoma carried a better prognosis. The modified staging classification used in this study appeared to stratify better the patients into 2 sub‐groups of localized (Stage I and II) and advanced (Stage III and IV) disease, which correlated very well with the prognosis. Good treatment results were obtained following intensive therapy in our patients with localized disease (Stage I and II). The poorer treatment results of patients with advanced disease (Stage III and IV) call for better chemotherapy regimens and earlier diagnosis. Surgical resection of the primary gastrointestinal lesion is recommended to prevent haemorrhage and perforation following chemotherapy, which occurred in 38 per cent of our patients whose gastrointestinal lesions were not resected.
Large cell transformation of subclinical small lymphocytic leukemia/lymphoma: A variant of richter's syndrome
Authors: Strauchen James A. , May Michael M. , Crown John
Published: February 2007

The authors report three cases of diffuse aggressive non‐Hodgkin's lymphomas (large cell, two; mixed small and large cell, one) arising in association with clinically silent small lymphocytic proliferations involving bone marrow, and lymph nodes. Immunologic marker studies suggested origin from a common B cell clone in two cases; in one case the large cell lymphoma lacked detectable surface markers. Some cases of diffuse aggressive lymphomas of adults may arise by large cell transformation of clinically silent small lymphocytic proliferations, a process akin to Richter's syndrome.
Non‐hodgkin's lymphoma of unfavourable histology: A multivariate analysis of factors predicting the response to chop
Authors: Pereira Arturo , Cervantes Francisco , Montserrat Emilio , Llebaria Carlos , Rozman Ciril
Published: February 2007

Forty‐eight patients withde novonon‐Hodgkin's lymphoma (NHL) of unfavourable histology received CHOP as first‐line chemotherapy. A complete remission (CR) was achieved in 64.5 per cent patients. Overall 4‐year projected survival was 48 per cent with a median follow‐up of 40.5 months. Two pretreatment characteristics, high LDH serum levels and bulky abdominal disease, were negatively associated with survival at the proportional hazards regression model and were used to calculate each patient's relative‐risk. Such analysis allowed to identify two prognostic subgroups according to their outcome to CHOP. Firstly, a high‐risk subgroup that showed an 8 per cent CR rate, most patients dying within the first year after diagnosis. Secondly, a low‐risk subgroup that showed an 83.5 per cent CR rate and a 4‐year projected survival of 66 per cent. From the above results two major conclusions can be drawn: (1) the CHOP combination is an effective treatment for unfavourable NHL patients with a low relative‐risk and (2) new therapeutic approaches should be explored for NHL patients with a high relative‐risk at diagnosis.
VAD chemotherapy—toxicity and efficacy—in patients with multiple myeloma and other lymphoid malignancies
Authors: Anderson H. , Scarffe J. H. , Lambert M. , Smith D. B. , Chan C. C. , Chadwick G. , McMahon A. , Chang J. , Crowther D. , Swindell R.
Published: February 2007

Thirty‐three patients with multiple myeloma (11 untreated, 15 refractory and seven relapsed patients) have received vincristine and adriamycin infusion therapy with oral dexamethasone (VAD). The median number of courses received was five. In addition 16 patients with lymphoid malignancy have received a median of four courses of VAD.

Three patients who relapsed after VAD have received further VAD therapy making 52 patient treatments assessable for toxicity. Ten per cent had nausea, 4 per cent vomiting, 4 per cent total alopecia, 25 per cent constipation, 33 per cent paraesthesiae, 8 per cent proximal myopathy, 33 per cent dyspepsia, 23 per cent proven bacteraemia, and 19 per cent chest infections. Infections were not usually associated with neutropenia. Shingles was seen in four patients with myeloma, but none of the patients with lymphoid malignancy.

The response rate in myeloma was 9/11, for previously untreated patients, 3/7 for relapsed, and 8/15 for refractory patients. Responses have been seen in other lymphoid malignancies—1/2 patients with relapsed acute lymphoblastic leukaemia had a complete remission. Two out of seven patients with chronic lymphocytic leukaemia achieved a partial remission, and a further three had a clinical improvement. Three out of six patients with non‐Hodgkin lymphoma and one patient with macroglobulinaemia achieved a partial remission.
Follicular non‐Hodgkin's lymphoma in Hong Kong Chinese: A retrospective analysis
Authors: Liang Raymond , Todd David , Chan T. K. , Ng R. P. , Choy D. , Loke S. L. , Ho F. C. S.
Published: February 2007

Follicular lymphoma is relatively rare in Hong Kong Chinese. Fifty‐two patients with follicular lymphoma were reviewed. The histology was nodular lymphocytic poorly differentiated (NLPD) in 75 per cent, nodular mixed (NM) in 21 per cent and nodular histiocytic (NH) in 4 per cent. Our patients appeared to have a higher proportion of NLPD and a lower proportion of NM lymphoma than the western series. Fifty patients were analysed excluding the two patients with NH lymphoma. They had a median age of 50 and a male to female ratio of 0.92. Seventy‐two per cent of them presented with asymptomatic lymph node enlargement. Twenty per cent had B symptoms and 32 per cent bulky tumour. Twelve per cent had stage I disease, 2 per cent stage II, 30 per cent stage III and 56 per cent stage IV. A high incidence of bone marrow involvement (48 per cent of all patients) was found.

All seven stage I‐II patients responded to involved‐field radiotherapy alone and none of them has relapsed. The 43 stage III‐IV patients were treated with chemotherapy without deferral and a majority of them received CVP (51.1 per cent) or chlorambucil alone (34.9 per cent). The complete response rate of stage III‐IV patients was 81 per cent and 26 per cent of the complete responders relapsed. The 5‐years disease‐free survival (DFS) and overall survival of all patients (stage III and IV) were 50 per cent and 65 per cent respectively. The DFS curve showed a pattern of continuous relapses. Stage III patients appeared to have a better complete response rate, a lower relapse rate and superior disease‐free survival than stage IV patients but the differences did not reach statistical significance. However, the overall survival of stage III patients was significantly better than stage IV patients (p < 0.02). Other factors including sex, age, presence of bulky tumour, B symptoms, histologic subtypes and the chemotherapeutic regimes did not significantly affect their prognosis.
Molecular analysis of Hodgkin's disease‐derived cell lines
Authors: Tesch Hans , Jücker Manfred , Falk Martin H. , Bornkamm Georg W. , Jones David B. , Diehl Volker
Published: February 2007

Three Hodgkin's disease‐derived cell lines were analysed for the organization of immunoglobulin and T cell receptor genes, for the expression of the interleukin 2 (IL‐2) receptor gene, and for the cellular oncogene c‐myc. All three cell lines have characteristic genotypic markers of lymphoid cells and can be classified as immature lymphoid cells with respect to the incomplete expression of their antigen receptor genes. This immature genotype is in contrast to the expression of activation antigens Ki‐1 (CD 30), IL‐2 receptor (CD 25), and HLA‐DR. The results obtained are in agreement with studies obtained from primary Hodgkin's lymphomas, which are activated by as yet unknown mechanisms.
Angiofollicular lymph node hyperplasia associated with myelofibrosis case report and immunologic marker studies
Authors: Bleiweiss Ira J. , Dumitrescu Otilia L. , Jagirdar Jaishree
Published: February 2007

A case of angiofollicular lymph node hyperplasia (AFH) (hyaline vascular type) of the mediastinum associated with myelofibrosis is reported with immune marker studies. We hypothesize that the myelofibrosis is more than a mere coincidence since other myeloproliferative disorders have been observed in conjunction with AFH. Immunohistochemistry on cryostat sections of lymph node using the biotin‐avidin fluorescence technique showed the presence of numerous T helper cells and very few T suppressor/cytotoxic cells in the parafollicular areas. Concentric rings of lymphocytes showed the phenotype of mantle zone lymphocytes (i.e. IgM, IgD positivity), while the germinal centres were ill‐formed as shown by Leu 14 (a Pan B cell marker) staining. By electron microscopy, follicular dendritic reticulum cells were readily found. The above findings suggest an abnormality of germinal center formation.
Low field strength magnetic resonance imaging of bone marrow in acute leukaemia
Authors: Richards M. A. , Webb J. A. W. , Malik S. , Jewell S. E. , Amess J. A. L. , Lister T. A.
Published: February 2007

The accuracy of low field strength (0.08 Tesla) magnetic resonance imaging (MRI) of bone marrow for the detection of acute leukaemia in adults has been assessed by comparison with bone marrow biopsy results. Spin lattice relaxation time (T1) measurements from patients were compared with those from 90 volunteers. Eighteen patients were studied at the time of diagnosis of leukaemia. Bone marrow T1 was prolonged in all cases. One of two patients with refractory anaemia with excess of blasts in transformation (RAEBt) had prolonged bone marrow T1, the other had normal T1. T1 at the time of diagnosis for patients with acute leukaemia or RAEBt correlated with the cellularity and blast cell count in the marrow. None of the 17 patients who were studied when in long‐term remission of leukaemia had prolonged marrow T1.

Serial studies were undertaken in five of the newly diagnosed patients. An increase in bone marrow T1 was observed in each of four patients studied seven days after the start of treatment, at a time when they showed a decrease in leukaemic cells on peripheral blood examination. T1 measurements made 3 weeks after the commencement of chemotherapy were similar to pretreatment values and did not reflect the reduction in leukaemic infiltration observed on bone marrow needle aspirate. The implications and possible explanations for these findings are discussed.
Intensive chemotherapy for acute non‐lymphoblastic leukemia after primary myelodysplastic syndrome
Authors: Martiat Philippe , Ferrant Augustin , Michaux Jean‐Louis , Sokal Gérard
Published: February 2007

Twenty‐five patients with a primary myelodysplastic syndrome (MDS) transformed into acute non‐lymphoblastic leukaemia (ANL) were treated with intensive chemotherapy. A complete remission (CR) was obtained in six patients (24 per cent). In five of these six patients two courses of chemotherapy were needed to achieve CR. In eight patients chemotherapy cleared the bone marrow of blasts, but the aplasia was fatal. A partial effect on bone marrow blasts was seen in four patients and no effect in another six. Eleven patients (44 per cent) died from the consequences of chemotherapy‐induced cytopenia. A short interval between MDS and transformation into ANL was associated with a better chance of achieving complete remission. Age, karyotype, type of MDS, peripheral blood or bone marrow findings had no influence on the result of chemotherapy. The median survival from start of treatment was 5 months (range 0.5–24 months). In the patients who achieved a CR, the median duration of the remission was 7 months (range 3–12 months). The poor response rate, the short duration of the remissions and the high treatment‐related mortality suggest that current intensive anti‐leukemic chemotherapy in ANL after primary MDS is of limited benefit.
Diagnostic features and survival in typical and prolymphocytoid variants of chronic lymphocytic leukemia
Authors: Scott Colin Stephen , Stark Allistair N. , Head Christine , Roberts Bryon E.
Published: February 2007

Diagnostic features were evaluated with regards to survival in 203 cases of typical and prolymphocytoid chronic lymphocytic leukemia. Excluding 27 (13 per cent) patients with second malignancies, survival analyses indicated that the prognostic factors with greatest significance were age at presentation (< 65 years and 65 years or more: p = 0.0004), proportions of prolymphocytoid cells (< 10 per cent and 10 per cent or more: p < 0.0001 age corrected) and surface immunoglobulin (SIg) density (weak and more than weak: p = 0.001 age corrected). In contrast, sex, absolute numbers of prolymphocytoid cells, SIg light chain type and FMC7 expression were not prognostically significant. These observations suggest that the recognition and delineation of prolymphocytoid CLL variants by morphological and immunophenotypic criteria, although important in diagnostic terms, may have less relevance with respect to prognosis and patient management.
Angiotropic large cell lymphoma (ALCL): Morphological, immunohistochemical and genotypic studies with analysis of previous reports
Authors: Domizio P. , Hall P. A. , Cotter F. , Amiel S. , Tucker J. , Besser G. M. , Levison D. A.
Published: February 2007

The entity ‘angioendotheliomatosis proliferans systemisata’ was first described 28 years ago as a cutaneous small vessel neoplasm of presumed endothelial origin. Since then, 101 similar cases have been reported under a variety of different names, most with systemic as well as cutaneous lesions, and a lymphoid histogenesis of the tumour cell is now favoured. Review of these cases has shown a characteristic clinical presentation with predominant neurological and dermatological features, although the diagnosis was made at autopsy in 53 per cent of patients. Most therapeutic regimens have proved ineffective with a median survival of 5 months from date of clinical presentation. Aggressive combination chemotherapy can produce complete and lasting remission and a partial response to steroids is sometimes seen. We have examined a case of this condition showing unusual clinical features. Immunohistochemical studies confirm the lymphoid origin of the tumour cells with B cell phenotype. Antigen receptor gene rearrangement studies indicate the presence of the same clonal population of B cells in multiple sites. We suggest that the term ‘angioendotheliomatosis proliferans systemisata’ should be dropped and support the use of ‘angiotropic large cell lymphoma’ to describe this unusual condition.
Malignant lymphoma in Hawaii‐Japanese: A retrospective morphologic survey
Authors: Yanagihara Eugene T. , Blaisdell Richard K. , Hayashi Takuji , Lukes Robert J.
Published: February 2007

A retrospective morphologic survey (1973–1983) of 146 cases of malignant lymphoma among the Hawaii‐Japanese (migrant Japanese and their offspring) was conducted to determine whether differences in the incidence and cytologic types of malignant lymphoma exist when compared to those of native Japanese (lifetime residents of Japan). The age‐adjusted incidence rates for malignant lymphoma among the Hawaii‐Japanese were similar to rates for U.S. whites. However, higher rates for follicular centre cell (FCC) lymphoma with a follicular pattern were observed in the Hawaii‐Japanese population when compared with rates for native Japanese.

On the basis of the cytologic types of the Lukes–Collins classification, non‐Hodgkin's lymphomas among the Hawaii‐Japanese resembled those of Western countries, rather than those of Japan. B‐cell lymphomas predominated (72 per cent), while T‐cell types comprised 23 per cent of cases. Follicular centre cell types were encountered most often (59 per cent), and the small cleaved FCC subtype was the most common (30 per cent). The high degree of follicularity (29 per cent) was at variance with the consistently low rates reported in Japan. This may be explained, in part, by higher rates of nodal lymphomas among the Hawaii‐Japanese. Of the T‐cell lymphomas, diffuse large cell types (T‐cell immunoblastic sarcoma, T‐IBS), often with cytologic pleomorphism, were relatively frequently encountered (16 per cent), and comprised 15 per cent of non‐Hodgkin's lymphomas; this observation necessitates special clinical and epidemiologic consideration in view of the large Japanese migration to Hawaii from HTLV‐I endemic regions of southern Japan. No registered cases of non‐Hodgkin's lymphoma or of Hodgkin's disease were documented in Hawaii‐Japanese subjects under the age of 15 years.

The age‐adjusted incidence rates for Hodgkin's disease among the Hawaii‐Japanese were similar with those of native Japanese. Nodular sclerosis was the most frequent histologic subtype. The difficulty in distinguishing between Hodgkin's disease and non‐Hodgkin's lymphoma, particularly when immunologic cell surface markers are not available, is addressed.

Low rates for chronic lymphocytic leukemia among the Hawaii‐Japanese were confirmed. Not one well‐documented case was identified in the 11‐year period surveyed.
A monoclonal antibody 1A6 to T‐cell recognizes a common antigen expressed on lymphocytes from normal and leukemic patients, and inhibits nk cell activity
Authors: Togashi Hiroyuki , Ghoneum Mamdooh , Takasugi Mitsuo , Kasai Kiyoshi , Mugishima Hideo , Billing Ronald , Terasaki Paul. I.
Published: February 2007

A new monoclonal antibody (MAB), IA61gG2a, has been derived from Balb/c mice after immunization with T‐cell chronic lymphocytic leukemia (T‐CLL). This monoclonal antibody, 1A6 was tested on normal human peripheral blood cells, leukemia patient's cells and leukemia‐lymphoma cell lines. The results demonstrated that this antibody reacts with normal human T and B cells, but not with erythrocytes, granulocytes or platelets. Further examinations showed 10/11 leukemic patient cell types were positive with 1A6. In contrast, many leukemia‐lymphoma cell lines were negative (14/17), i.e. T and B leukemia lymphoma cell lines, non‐T and non‐B leukemia cell lines as examined by complement mediated cytotoxicity test and immunofluorescence test. Other prominent characteristics of 1A6 MAB have been demonstrated, which include inhibition of myeloid colony formation (CFU‐C) and suppression of human natural killer cell cytotoxicity (NKCC). These results suggest that 1A6 is a common marker for normal T, B, NK cells and leukemic patients cells having T and B cell origin, but 1A6 antigen is not expressed on many leukemia lymphoma cell lines. Therefore, it could be useful for studying malignant transformation of lymphoid cells.
Treatment of refractory acute myeloid leukemia with mAMSA and VP 16‐213 in combination: Results of a clinical phase I/II study
Authors: Hiddemann Wolfgang , Urbanitz Dieter , Preusser Peter , Achterrath Wolf , Büchner Thomas
Published: February 2007

Twenty patients with refractory AML were treated with mAMSA and VP 16–213 in combination to assess the toxicity and anti‐leukemic activity of the two‐drug regimen. Refractoriness was defined according to the response to induction therapy consisting of 6‐thioguanine, cytosine arabinoside and daunorubicin (TAD9) and the duration of the preceding remission. Patients were eligible for AMSA/VP 16–213 if they were primary non‐responders against two TAD9 induction courses, had early relapses within the first six months, were non‐responders to one additional TAD9 course at later relapses or were at second or subsequent relapses. Therapy consisted of a five‐day course of mAMSA 210 mg/m2/d on days 2, 3 and 4. VP 16–213 was applied on days 1 and 5 by a 1‐h infusion of 100 mg/m2 followed by a 23 h infusion, the dosage of which was escalated in three steps from 110 mg/m2 over 200 mg/m2 to 230 mg/m2 in subsequent patients.

Even at the highest dose of VP 16–213, toxicity was mild to moderate except for mucositis of grade III after two cycles and severe intrahepatic cholestasis in one case. Four of the 20 patients died within the first three weeks after the onset of treatment and were not evaluable for the assessment of antileukemic efficacy. From the remaining 16 patients five achieved partial remissions while no complete remission was obtained. Four of the five PR occurred in the eight patients with primary TAD9 resistance.

These data indicate that AMSA/VP 16–213 reveals a moderate toxicity only, and that the combination may not be completely cross‐resistant with TAD9. The overall anti‐leukemic activity is limited however, and seems inferior compared to other presently available salvage regimens in refractory AML.
Absent clinical effects of retinoic acid and isoretinoin treatment in the myelodysplastic syndrome
Authors: Hast Robert , Laurén Sten Axdorph Lillemor , Reizenstein Peter
Published: February 2007

Ten patients with the myelodysplastic syndrome (eight with anemia, two with granulocytopenia, four with thrombocytopenia) were given etretinate (ER) and retinoid acid (RA). No correlation was seen between the RA effect in vitro and its clinical effect. No effect was seen of the ER‐treatment or of the RA‐treatment on anemia, thrombocytopenia or the abnormal karyotype seen in three patients. In three of eight patients given RA a decreased blast cell percentage in the bone marrow was seen, and in two of these there was also a normalization of the in vitro bone marrow cell colony formation. We found no clinical effect of ER and only a minimal one of RA.
Cytogenetics and their prognostic value in childhood and adult acute lymphoblastic leukemia (ALL) excluding L3
Authors: Fenaux P. , Lai J. L. , Morel P. , Nelken B. , Taboureau O. , Deminatti M. , Bauters F.
Published: February 2007

Cytogenetic analysis was made at diagnosis in 174 cases of ALL (101 children less than 20 years and 73 adults), excluding Burkitt's ALL (L3). In 11 children (11 per cent) insufficient material was obtained. In the remaining 90, 50 (56 per cent) had a normal karyotype, 20 (22 per cent) a hyperdiploid karyotype, five (6 per cent) a hypodiploid karyotype, 12 (13 per cent) had a translocation (including seven cases of t(1;19)) and three had a pseudodiploid karyotype without translocation. Ninety‐eight per cent of patients reached complete remission (CR). Median actuarial CR duration was not attained, was 50 months, 13 months and 11 months respectively in patients with hyperdiploid, normal, hypodiploid karyotype and in patients with a translocation, the difference between subgroups being significant. In a Cox model, cytogenetics were the strongest factor predicting CR duration (p= 0.03) followed by leukocytes (p= 0.04), whereas the presence of ‘bulky disease’ had a borderline value (p= 0.077). Of note was that 9/17 (53 per cent) patients with a hypodiploid karyotype or a translocation had no ‘risk factors’ before cytogenetic analysis.

In adults, cytogenetic analysis was unsuccessful in 15 (20 per cent) of patients. In the remaining 58 cases, 19 (33 per cent) had a normal karyotype, 15 (26 per cent) had a hyperdiploid, one (2 per cent) had a hypodiploid karyotype, 19 (33 per cent) had a translocation (including 12 t(9;22)), and four (7 per cent) had a pseudodiploid without translocation. 73 per cent patients reached CR. Median actuarial DFS was 12.5 months. No significant differences in CR rate and CR duration were seen between cytogenetic groups, but median CR duration was slightly longer in patients with a normal karyotype (17 months) and shorter in patients with t(9; 22) (8.5 months). Only 3/12 of the latter had major risk factors before cytogenetic analysis. Cytogenetic analysis is important in ALL, especially in patients with otherwise standard risk factors, as it may reveal unexpected translocations or hypodiploidy, which may require a therapeutic reinforcement.
Malignant lymphomas of follicular centre cell origin in man. VII. Prognostic features in small cleaved cell lymphoma
Authors: Stein Richard S. , Greer John P. , Cousar John B. , Hendey Gregory W. , Wehner John H. , Flexner John M. , Collins Robert D.
Published: February 2007

To extend the clinical‐pathologic description of small cleaved cell lymphoma (SCCL), we reviewed the records of 106 patients with SCCL who were treated in accordance with a policy of watchful waiting and palliative therapy. Median age was 58 years. A pure diffuse pattern was seen in only 16 per cent of cases. Stage III or IV disease was present in 85 per cent of patients; marrow involvement was noted in 60 per cent of patients. ‘B’ symptoms were present in 25 per cent of patients.

By univariate analysis, age > 60, diffuse pattern, stage IV disease, involvement of liver, lung, pleura, or g‐1 tract, ‘B’ symptoms, surface heavy chain IgM or IgM‐D, and LDH > 200 IU/dl were found to be significantly associated with a poor prognosis. Marrow involvement, increased (5–25 per cent) transformed (non‐cleaved) cells, and surface light chain had no prognostic significance.

By multivariate analysis, only age >60, stage IV disease, and LDH > 200 IU/dl were prognostically significant. For patients with all three unfavourable prognostic features, median survival was only 11 months. For patients with age ± 60, stage I, II, or III disease, and LDH ± 200 IU/dl, median survival was not reached at 180 months. Recognition of prognostic features in indolent lymphoma can help clarify whether the results of treatment protocols represent true advances or the mere selection of favourable patients.
Refractory acute lymphocytic leukemia: Response to aclacinomycin a and VP‐16‐213
Authors: Rowe Jacob M. , Chang Alex Y. C. , Bennett John M.
Published: February 2007

Twelve patients with acute lymphoblastic leukemia (ALL) were treated with aclacinomycin A (60 mg/m2/day for five days) and VP‐16‐213 (100 mg/m2/day). All were heavily pretreated and had relapsed or were refractory to primary or subsequent treatment. Eight patients were refractory to reinduction therapy given for first, second, third or fourth relapse. One patient was treated in third relapse; one in second relapse (after a short second remission) and two in first relapse—one with the Ph1 chromosome, after a four‐month remission, and one patient who relapsed while receiving consolidation therapy. Four patients (33 per cent) responded, three entered complete remission (25 per cent), and one a partial remission (8 per cent). Two of the patients treated for refractoriness to reinduction therapy went into complete remission. Side effects from this treatment were similar to the conventional DAT regimen (daunorubicin, cytosine arabinoside, thioguanine), although the gastrointestinal toxicity and mucositis appeared to be more severe in this study population. One of the patients had severe ventricular arrhythmias which contributed to her death. The complete remission rate (25 per cent) in this group of very heavily pretreated ALL patients warrants further studies to evaluate these preliminary findings.
Prognostic implications of cell kinetics, histopathology and pathologic stage in non‐Hodgkin's lymphomas
Authors: Silvestrini R. , Costa A. , Giardini R. , Boracchi P. , Del Bino G. , Marubini E. , Rilke F.
Published: February 2007

Cell kinetics ([3H]‐thymidine labelling index, [3H]‐Thy LI) were determined on pathologic lymph nodes from 175 untreated adult patients. [3H]‐Thy LI significantly differed in low‐grade and high‐grade malignancy groups according to the Kiel classification (median values, 1.8 per cent and 10.4 per cent, respectively) and in low, intermediate, high grade according to the Working Formulation (median values: 1.7 per cent, 4.8 per cent and 14.2 per cent, respectively) but was unrelated to pathologic stage or patient's age. Cell kinetics, histo‐pathology, pathologic stage and patient's age were significant discriminants of 6‐year survival. Multivariate analysis was performed by Cox's proportional hazard model to investigate the role of [3H]‐Thy LI after making allowance for the other prognostic factors. When [3H]‐Thy LI was added to the model, a large increase (chi square = 29.94) contributed by the cell kinetic variable in identifying patients at different risk was revealed.
Oral idarubicin in the treatment of acute myelogenous leukaemia and the blast phase of chronic myeloid leukaemia
Authors: Malik S. T. A. , Tucker J. , Rohatiner A. Z. S. , Brace W. , Lister T. A.
Published: February 2007

Fourteen patients with poor‐risk acute myelogenous leukaemia (AML) and five patients with accelerated phase/blast crisis chronic myeloid leukaemia (CML) were treated with 3 days of oral idarubicin (25 mg/m2/day). No complete remissions or return to chronic phase CML were observed. A fall in the peripheral blast count was seen in all patients with the first cycle of treatment, and with subsequent cycles in CML patients, but all responses were transient, with eventual reemergence of peripheral blasts. In some patients, there was a clear cut improvement in symptoms such as bone and splenic pain. Five of the AML patients and all of the CML patients were treated as out‐patients. In this group of patients oral idarubicin was found to be a useful drug for palliative treatment.
Phase 2 study of mitozantrone in combination with chlorambucil and prednisolone for relapsed and refractory non‐Hodgkins lymphoma
Authors: Jones L. , Cotter F. E. , Lord D. , Newland A. C.
Published: February 2007

Thirty‐six patients with non‐Hodgkin's lymphoma (NHL) (comprising patients with refractory or relapsed disease and eight elderly, unfit patients with de novo disease) were treated with mitozantrone, chlorambucil and prednisolone on an out‐patient basis. Fifteen patients had low grade (LG) disease, five patients intermediate grade (IG) disease and 16 patients high grade (HG) disease and 31/36 had stage IV disease. All elderly patients had IG or HG disease. The regimen was well‐tolerated. After six courses of chemotherapy, there was a 69 per cent response rate with 33 per cent in complete remission. The median duration of remission was 15 months. The overall 3‐year projected survival was 38 per cent; 27 per cent for LG disease and 47 per cent for HG and IG disease. Responses did not appear durable for either HG or LG disease unless CR was achieved early on. Three of the eight patients treated de novo (mean age 71 years) have survived, disease‐free, between 28 and 38 months from entry. This study indicates that mitozantrone‐based regimens have promising activity in NHL and require further evaluation. The low toxicity combined with worthwhile remissions make this an attractive first‐line option for elderly patients.
Immunophenotype of blast cells in acute myeloid leukemia may be a useful predictive factor for outcome
Authors: Tucker J. , Dorey E. , Gregory W. M. , Simpson A. P. F. , Amess J. A. L. , Lister T. A. , Horton M. A.
Published: February 2007

The immunophenotype of peripheral blood blast cells was tested in 92 patients with acute myeloid leukemia (AML), who were diagnosed and treated at single centre, St Bartholomew's Hospital, from 1978‐1987 with a standard adriamycin, cytosine arabinoside and 6‐thioguanine regimen. Immunological analysis involved standard fluorescence flow cytometry and utilized 31 monoclonal antibodies to known myeloid antigens (of CD groups 11b, 11c, 13, 14, 15, 16, w17, 31, w32, 33, 34, 35 and 36), a number of relatively less well studied antibodies with potential specificity for AML, and a series of control antibodies to T and B lymphocytes, platelets, erythrocytes and of widespread distribution (CD45, leucocyte common; HLA‐DR). The results highlighted a number of antibodies with wide myeloid reactivity, in addition to CD13 and 33 (present in 66 per cent and 76 per cent of cases, respectively), which may be of immunodiagnostic use. A number of correlations between AML cell immunophenotype and FAB morphology subtype were found; in particular five antibodies (CD11c, 10.1, Tu3, CD15 and CD16), of both predominant granulocytic and monocytic reactivity, reacted with cells of AML‐M5 subtype (p<0.05). There was no significant correlation between immunophenotype and clinical and pathological features at presentation. Correlation with clinical outcome was not a prominent feature, in contrast to some reports based on multicentre data. However, of particular note was the strong association between early death (at less than 2 months) and the coexpression of Leucocyte Function Associated (LFA) antigens, CD11b and 11c, on patient's blast cells (p=0.003). The relationship was independent of clinical features and persisted even if AML‐M5 cases were excluded. The significance of this latter finding is unclear, but may be related to the known role of CD11b and 11c LFA antigens in the cellular response to infection.
The myelotoxicity of carboplatin is influenced by the time of its administration
Authors: Kerr D. J. , Lewis C. , O'Neil B. , Lawson N. , Blackie R. G. , Newell D. R. , Boxall F. , Cox J. , Rankin E. M. , Kaye S. B.
Published: February 2007

Previous studies have demonstrated that there are circadian rhythms in susceptibility to a range of commonly used cytotoxic drugs. In this study we have compared the pharmacokinetics and myelotoxicity of carboplatin administered at 18.00 and 06.00 in random order in patients with advanced ovarian carcinoma. Carboplatin treatment at 06.00 is associated with significantly greater thrombocytopenia than at 18.00 (platelet nadir 95 000 versus 180 000, p < 0.05). There was no pharmacokinetic difference in the patients' handling of ultra‐filterable platinum therefore it is possible that there is an intrinsic rhythm of susceptiblity of bone marrow to carboplatin.
The relation between hypocholesterolemia and degree of maturation in acute myeloid leukemia
Authors: Zyada L. E. , Hassan H. T. , Rees J. K. H. , Ragab M. H.
Published: February 2007

Plasma cholesterol concentrations were determined in 83 acute myeloid leukemia patients. Mean plasma cholesterol concentration (± S.D.) at the time of diagnosis was 2·91 mmol/L(± 1·13). The percentage of AML patients having hypocholesterolemia was 90·4 per cent. The lowest cholesterol levels were observed in the poorly differentiated FAB subtypes of acute myeloid leukaemia: AMyL(M1) and AMoL(M5a). The results showed that the initial hypocholesterolemia in acute myeloid leukemia is significantly related to the degree of both cytological and cytochemical maturation of leukemic blast cells at diagnosis. The degree of maturation at diagnosis has been shown to be related to prognosis in favour of more differentiated subtypes of acute myeloid leukemia. Also, hypocholesterolemia has been shown in several epidemiological studies to be related to an increased mortality from human cancer. Therefore, the degree of maturation may serve as a link between hypocholesterolemia and the increased mortality from human cancer.
Conversion of high grade lymphoma tumor cell line to intermediate grade with tpa and bryostatin 1 as determined by polypeptide analysis on 2D gel electrophoresis
Authors: Al‐Katib Ayad , Mohammad Ramzi M. , Mohamed Anwar N. , Pettit George R. , Sensenbrenner Lyle L.
Published: February 2007

A high‐resolution two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) was used for total cellular polypeptide mapping of two established lymphoma cell lines; MANCA, a Burkitt's line representing a high grade lymphoma (HGL) and WSU‐NHL (nodular histiocytic lymphoma) representing an intermediate grade lymphoma (IGL). Gels were digitized and analysed with an image scanning computer using the Elsie 4 system. Polypeptide mapping revealed striking similarities in 1100 polypeptide spots in both types. However, three polypeptides were unique to HGL (Molecular mass/isoelectric point (Mr/PI): 39/4·4, 35/5·6, 33/4·8), and one to IGL (95/4·7). In order to investigate the kinetics of expression of these polypeptides, the two cell lines were treated with two protein kinase C (PKC) activators, tumour promoting 12‐O tetradecanoylphorbol 13‐acetate (TPA) and bryostatin 1. 2D‐PAGE of the treated cells revealed that the HGL line loses its unique polypeptides and expresses a new one. The new polypeptide has the same Mr and PI as that unique to the untreated IGL (95/4·7). TPA or bryostatin 1 treatment of the IGL line for 72 h induced no significant changes. Our data show a unidirectional change from HGL to IGL, supporting the clinical notion that HGL is less differentiated than IGL. It also shows the similarity in the mode of action of bryostatin 1 and TPA in inducing these polypeptide changes.
Inducible lymphokine‐activated killer (LAK) cell activity in the peripheral blood of patients with relapsed/refractory non‐Hodgkin's lymphoma (NHL)
Authors: Zamkoff Kenneth W. , Watman Nora P. , Duggan David B. , Poiesz Bernard J. , Gottlieb Arlan J.
Published: February 2007

Therapy with recombinant interleukin‐2 (rIL‐2) induces clinical response in a significant number of patients with refractory malignant disease. Very few patients with non‐Hodgkin's lymphoma (NHL) have been treated with rIL‐2. The present study sought to determine if peripheral blood mononuclear cells (PBM) from patients with relapsed/refractory non‐Hodgkin's lymphoma could be induced in vitro to generate LAK cell activity. PBM from 28 patients with relapsed/refractory NHL were incubated for 7 days in rIL‐2 to determine their ability to lyse the LAK cell sensitive Daudi cell line. The PBM from all patients were able to generate LAK activity after in vitro incubation in rIL‐2. Approximately one third of the patients' PBM samples generated less activity than activity generated in the PBM sample from normal control donors. However, two‐thirds of patient samples were able to generate activity equal to or greater than that of the controls. The degree of LAK activity generated by the patients' PBM did not correlate either with histologic subtype or amount of prior chemotherapy. The amount of LAK activity an individual generated (control or patient) tended to remain stable over time.