bluuebunny/crossref_metadata_2025 huggingface dataset:
Follicular mantle zone cell subpopulations detected by monoclonal antibody SN3
Authors: Barcos M. , Pollard C. , Fukukawa T. , Seon B. K.
Published: February 2007

A monoclonal antibody, SN3, has been prepared against a cell membrane fraction of the pre‐B leukemic cell line NALM‐1. By radioimmunoassay, SN3 reacted with four of four non‐T/non‐B, two of two pre‐B and one of three leukemic B cell lines. The reagent was unreactive, however, with established leukemic T and myelomonocytic cell lines or normal B cell lines. On immunohistochemical assays on frozen sections of nine reactive lymph nodes and three spleens, SN3 showed a preferential binding to 50–95 per cent mantle zone (MZ) cells and 5–20 per cent interfollicular or red pulp B‐lymphocytes. This was uninhibited by pre‐incubation with heterologous anti‐HLA‐DR or anti‐δ reagents. SN3 was unreactive with normal germinal centre (GC), epidermal or Langherhans cells but did react with less than 1 per cent thymic B‐lymphocytes. In eight follicular small cleaved cell lymphomas tested SN3 exhibited three patterns of reactivity: (1) peripheral follicular, (2) combined peripheral and central follicular, and (3) combined follicular and interfollicular. Three follicular lymphomas were essentially SN3‐. In three diffuse small lymphocytic lymphomas, SN3 showed patchy areas of reactivity unassociated with proliferation centres. In four diffuse B‐cell lymphomas (one mixed small and large cell, two large non‐cleaved cell, and one small non‐cleaved (Burkitt) cell), SN3 reactivity was uniformly distributed in the majority (60–90 per cent) of the cells. SN3 was unreactive with one diffuse B‐large cell lymphoma, three nodal T‐cell lymphomas and three cases of mycosis fungoides. The findings indicate that (1) SN3 detects an antigen that is present in subpopulations of normal MZ cells, (2) the antigen is also detected in GC cells undergoing lymphomatous transformation but is not readily detected in normal GC cells, and (3) the antigen is also expressed in subpopulations of diffuse B‐ but not T‐cell lymphomas.
Glucose‐6‐phosphatase activity of reed‐sternberg and hodgkin cells
Authors: Pangalis Gerassimos A. , Tsavaris Nikolaos B.
Published: February 2007

The glucose‐6‐phosphatase (G‐6‐Pase) enzyme cytochemical reaction was successfully applied on lymph node imprints, after introducing the appropriate modifications related to fixation and to composition of the substrate solutions. Using this method we studied the G‐6‐Pase cytochemical profile on lymph node imprint preparations from 30 patients with Hodgkin's disease. Three cases had the histologic subtype of lymphocyte predominance, 14 the modular sclerosis, 11 the mixed cellularity and two the lymphocyte depleted. A strong G‐6‐Pase positivity was found in the Reed‐Sternberg (RS) and Hodgkin cells of the mixed cellularity type, while the RS and Hodgkin cells of the other subtypes were less positive. The rest of the cell population present were G‐6‐Pase negative, with the exception of plasma cells which exhibited a strong G‐6‐Pase cytoplasmic positivity. We concluded from our study that RS and Hodgkin cells resemblance to plasma cells and therefore they may be of B‐cell origin. In addition it appears that RS and Hodgkin cells express different functional properties in the various histologic subtypes of the disease.
The role of eosinophil in regulation of granulopoiesis
Authors: Gardner Renee V. , Tebbi Cameron K. , Chervinsky David , McGarry Michael
Published: February 2007

An association between eosinophilia and neutropenia has been observed in a number of clinical conditions. To probe the role of eosinophils in granulopoiesis, marrow and peritoneal eosinophils, obtained from Schistosoma mansoni‐infected mice, were separated and purified. Normal bone marrow cells were cultured in semisolid culture medium in concentrations ranging from 5 × 104 to 5 × 105, with and without added eosinophils. To examine whether high prostaglandin E (PGE) content of eosinophils affects granulopoiesis, idomethacin was added to duplicate marrow cultures containing eosinophils. The addition of eosinophils to normal syngeneic marrow culture caused a significant inhibition of granuloyte‐macrophage colony formation (CFU‐GM) in culture. This suppressive effect was reversible upon addition of indomethacin. These findings suggest that eosinophils, in vitro, are capable of inhibition of granulopoiesis. The reversal of this effect by indomethacin indicates that this suppression may be prostaglandin mediated.
Hypoplastic acute leukemia: Review of 70 cases with multivariate regression analysis
Authors: Berdeaux Donald H. , Glasser Lewis , Serokmann Ruth , Moon Thomas , Durie Brian G. M.
Published: February 2007

Between 1971 and 1984, 22 of 190 adult patients (11·6 per cent) with acute leukemia seen at the University of Arizona had hypocellular acute leukemia (HAL), defined as lymphoblasts or myeloblasts (plus atypical promyelocytes) of ≧30 per cent, but marrow cellularity of the core biopsy or clot section of ≧50 per cent based on a 1000 point count. These 22 patients with HAL plus the 48 previously published patients with well documented HAL (combined series of 70 patients) were evaluated in detail with multivariate analysis. The median leukocyte count was 2700/μL, hemoglobin of 8μ2g/dl, and platelet count 63000/μL. Circulating blasts were noted in 27 of 52 patients (52 per cent). Twenty‐seven of 34 patients (79 per cent) had abnormal cytogenetics. The overall median survival was 8 months (range: 0·1–48). The median survival for the 22 patients managed with supportive care alone was 4 months, 6 months for the 16 patients treated with non‐aggressive induction therapy, and 13 months for the 32 patients treated with aggressive induction therapy (p<0·02 versus other categories). Multivariate analysis confirmed that aggressive induction therapy was a major favourable prognostic factor (p=0·016). Multivariate analysis of the aggressively induced patients revealed that younger patients (≧65; p=0·04) and patients with no AHD (p=0·09) lived longer. Thus, aggressive remission induction can be attempted in HAL and appears to contribute to prolonged survival especially under age 65 years.
Non‐secretory multiple myeloma: A report of 13 cases with a review of the literature
Authors: Smith David B. , Harris Martin , Gowland Eric , Chang James , Scarffe J. Howard
Published: February 2007

The clinical features of 13 patients with non‐secretory myloma from a series of 172 consecutive multiple myelomas are presented. The non‐secretors survived significantly longer that the secretors, median 46 months versus 21 months (p<0·01). Non‐secretory myeloma was associated with a higher incidence of neurological presentation, minimal lytic bone disease, a lower median percentage of plasma cells in the marrow and a lower incidence of hypogammaglobulinaemia. The median survival of the non‐secretors with minimal lytic bone lessions was 74 months compared to 21 months for those with extensive bone disease. The superior survival of non‐secretors is thus thought to be due to earlier presentation possibly as a result of a tendency to form symptomatic local tumours

Retrospective immunoperoxidase staining of stored tissue was performed in nine cases. In only one of these was a monoclonal immunoglobulin not detected indicating that true ‘non‐production’ is rare. In four patients who produced a biochemically detectable paraprotein during the course of their disease and in whom immunoperoxidase data was available the immunoglobulin was of the same type. Immunoperoxidase staining may help in the initial diagnosis of non‐secretory myeloma but did not contribute any prognostic information.
The myelodysplastic syndrome—a practical guide
Authors: Hamblin T. J. , Oscier D. G.
Published: February 2007

The term ‘myelodysplastic syndrome’ (MDS) is of recent coinage but neatly describes a well‐recognized group of conditions. In the past they have been confusingly classified by a variety of terms from ‘refractory anaemia’ to ‘pre‐leukaemia’. There have been several excellent reviews (Galton, 1984, 1986; Francis and Hoffbrand, 1985; Jacobs, 1985) which comprehensively cover the history and development of MDS as a concept and describe recent advances both in diagnosis and treatment and in the understanding of the pathogenesis. The purpose of this paper is not to rival these reviews in exhaustive detail, but to present a practical guide to the diagnosis and management of MDS as it presents to the working physician. In doing this we draw heavily on experience of 238 cases of MDS seen in our own unit in the past 6 years.
In vitro production of granulocyte–macrophage colony‐stimulating activity by murine bone marrow and spleen following vinblastine administration IN VIVO
Authors: Williams Douglas E. , Chervinsky David S. , Orsini Frank R. , Tebbi Cameron K. , Fitzpatrick John E.
Published: February 2007

The production of granulocyte–macrophage colony‐stimulating activity (CSA) by isolated murine femur shafts, non‐dispersed bone marrow and spleens was assessed following administration of Vinblastine (VLB). These organs were removed from 2 h to 10 days post‐VLB and allowed to condition endotoxin‐free medium for 48 h. CSA activity was assessed using a soft agar cloning system. The data demonstrate that CSA elaboration was maximal 24 h post‐VLB, corresponding to the nadir of bone marrow GM‐CFC, and 6 h after splenic reached a minimum. No relationship between peripheral blood granulocyte count or serum endotoxin levels were observed.
Peripheral blood stem cell autografting
Authors: Bell A. J. , Hamblin T. J. , Oscier D. G.
Published: February 2007

Transplantation of haemopoietic stem cells provides a means whereby patients with malignant disease may be treated with increased doses of chemotherapy or chemoradiotherapy. Until recently, the bone marrow has been the sole source of these cells. However, haemopoietic progenitors can also be demonstrated in the blood and it has been known for more than twenty years that peripheral blood mononuclear cells are capable of repopulating the marrow in animals. This phenomenon has recently been reproduced in man. The use of peripheral blood rather than bone marrow for autologous stem cell rescue may have advantages in terms of ready access, availability in patients with compromised pelvic bone marrows, a lower risk of tumour contamination and more rapid granulocyte and immune recovery. However, clinical experience with peripheral blood stem cell autografting is still very small. This review discusses the characteristics of circulating stem cells, the methods by which they can be collected and stored and the information which has come from recent studies of their transplantation in man.
Immunoprecipitation of the interleukin‐2 receptor from Hodgkin's disease derived cell lines by monoclonal antibodies
Authors: Schwarting R. , Gerdes J. , Ziegler A. , Stein H.
Published: February 2007

The nature of Hodgkin and Reed‐Sternberg (H–RS) cells and their normal counterpart remains a matter of controversy. Our recent investigations have suggested that H–RS‐cells derive from certain activated lymphocytes of either B or T cell origin. In keeping with this concept, we were able to demonstrate that in the majority of cases of Hodgkin's disease the interleukin‐2 receptor (IL2‐R) was detectable on H–RS‐cells by three monoclonal antibodies (anti‐Tac, Tü69 and ACT‐1) with the sensitive alkaline phosphatase anti‐alkaline phosphatase (APAAP) tissue staining procedure. In extension of these studies, we precipitated IL2‐R antigen from two established permanent cell lines (L540 and L591) derived from patients with Hodgkin's disease. Although these cell lines are different in nature, in that the L540 line shows rearrangement for the T cell receptor beta chain gene and the L591 line displays rearrangement for immunoglobulin genes (gamma heavy and lambda light chain), the antigen precipitated by monoclonal antibodies against IL2‐R exhibited a molecular weight of approximately 53 kd on the L591 line and 58 kd on the L540 line. Thus, these data strongly support the view that the labelling of H–RS‐cells in tissue sections for IL2‐R was not merely due to cross‐reactivities of the two anti‐IL2‐R antibodies with a determinant of an unrelated structure but represents true IL2‐R molecules.
Opec chemotherapy (vincristine, prednisolone, etoposide and chlorambucil) for refractory and recurrent Hodgkin's disease
Authors: Barnett M. J. , Man A. M. , Richards M. A. , Waxman J. H. , Wrigley P. F. M. , Lister T. A.
Published: February 2007

Fifteen adults with refractory or recurrent Hodgkin's disease were treated with a combination of: vincristine, prednisolone, etoposide and chlorambucil (OPEC). All had previously received mustine, vinblastine, procarbazine and prednisolone (MVPP) and seven had subsequently been treated with alternative regimens. Responses were achieved in four, but complete remission in only one. Toxicity was considerable and five died of treatment related complications. Only two are alive (one in complete remission) more than three years after therapy. The toxicity of the OPEC regimen outweighed its benefit in this group of poor prognosis patients.
Leu M‐1 antigen: Comparative expression in hodgkin's disease and T cell lymphoma
Authors: Strauchen J. A. , Breakstone B.
Published: February 2007

Expression of the granulocyte antigen Leu M‐1 is characteristic of Reed–Sternberg cells and the related mononuclear cells of Hodgkin's Disease. Leu M‐1 has been proposed as a specific immunological marker for Hodgkin's Disease which may be otherwise difficult to distinguish both morphologically and immunologically from non Hodgkin's lymphomas of peripheral T‐cell type. In the present study the comparative expression of Leu M‐1 in Hodgkin's Disease and peripheral T cell lymphoma was studied in a series of 43 cases including 25 cases of Hodgkin's Disease and 18 cases of immunologically documented peripheral T cell lymphoma. Leu M‐1 staining by avidin‐biotin‐peroxidase complex technique in acetone fixed frozen sections was observed in 22 of 25 cases of Hodgkin's Diseases, (2 of 3 cases of lymphocyte predominant Hodgkin's Disease and 1 case of mixed cellularity were negative) and in 4 of 18 cases of peripheral T cell lymphoma. The pattern of staining in the peripheral T cell lymphomas was indistinguishable from that observed in Hodgkin's Disease in 2 of the cases. Leu M‐1 staining appears to be of limited diagnostic value in the differential diagnosis of Hodgkin's Disease and T cell lymphoma. Absence of Leu M‐1 staining in frozen tissue however, makes a diagnosis of Hodgkin's Disease (with the exception of the lymphocyte predominant form) unlikely.
Long‐term results of treatment of patients with follicular lymphomas
Authors: Kalter S. , Holmes L. , Cabanillas F.
Published: February 2007

The management of patients with follicular lymphoma is controversial, particularly in those with follicular small cleaved cell (FSCC) or nodular poorly differentiated lymphoma (NPDL). Some advocate no treatment until symptoms arise, while others prefer to treat with intensive combination regimens and others with single agents. We reviewed the long‐term effects of two types of combination chemotherapy on relapse‐free survival and survival on 91 patients (88 were stages III–IV) who had received no previous chemotherapy. Those patients with FSCC lymphoma obtaining a complete remission had a significantly longer median survival than did those obtaining a partial remission (13 years versus 2 years). An adriamycin‐containing regimen appeared to be the key factor in obtaining a complete remission in FSCC after taking into consideration prognostic factors. Not only was the complete response rate significantly higher for patients receiving adriamycin, but so too was the median survival and relapse‐free survival. BCG immunotherapy appeared to be important in preventing relapse in some of the complete responders with NPDL who received adriamycin.
Reliability and consistency of bone marrow assessments of complete remission in acute myelogenous leukaemia
Authors: Birkhead B. G. , Salt D. , Jackson R. R. P.
Published: February 2007

An experiment is described which was designed to investigate the level of variability in the assessment of bone marrow remission in Acute Myelogenous Leukaemia (AML). The inter‐rater reliability and individual consistency of three haematologists at St Bartholomew's Hospital, London, are analysed using their assessments of cellularity, percent blast cells and marrow status for fifty bone marrow samples.
Lymph node architecture in Hodgkin's disease: Evidence for the role of the composite nodule in nodular sclerosing Hodgkin's disease
Authors: Van Parys G. , De Wolf‐Peeters C. , Van Den Oord J. J. , Desmet V. J.
Published: February 2007

The presence or absence of composite nodules, corresponding to recently described structural and functional units in the human reactive lymph node, was investigated in 22 lymph nodes involved by Hodgkin's disease using in situ immuno‐ and enzymehistochemical techniques

In 10/13 cases of nodular sclerosing subtype, typical composite nodules composed of adjacent B‐ and T‐domains and surrounded by a rim of high endothelial venules were recognized. In association with these venules, a concentrical rim of fusiform shaped Alk Phase+ fibroblastic reticulum cells was observed

Reed‐Sternberg cells and their morphological variants were exclusively found in the T‐area of these composite nodules

In 5/6 cases of mixed cellularity Hodgkin's disease, B lymphoid follicles were apparent. No vascular relationship with the tumourally involved areas was noticed

In the remaining cases, including all cases of lymphocytic depletion Hodgkin's disease only scattered B cell clusters were recognized

Our observations indicate the persistence of an organoid structure, i.e. the composite nodule in nodular sclerosing Hodgkin's Disease (HD).
Chromosomal abnormalities in non‐hodgkin lymphoma with peripheral t‐cell type: Effect of HTLV‐I infection
Authors: Sanada Isao , Ishii Toshinori , Matsuoka Masao , Kumagai Etsuko , Nishimura Hiromichi , Yamaguchi Kazunari , Takatsuki Kiyoshi
Published: February 2007

Cytogenetic studies were done in lymph node and peripheral leukemic cells from sixteen patients with non‐Hodgkin lymphoma with peripheral T‐cell type. Ten patients were positive for human T‐cell leukemia virus I (HTLV‐I) proviral DNA in tumour cells and six were negative. The former group had a higher tendency for leukemic conversion and poorer prognosis than the latter. However, no definite difference on the numerical and structural chromosomal abnormalities between these two groups was found. The most frequent chromosome abnormalities: 14p +, 14q+ and No. 6 abnormalities were detected in both groups. These results may indicate that HTLV‐I does not play a specific role in chromosome abnormalities of non‐Hodgkin lymphoma with peripheral T‐cell type.
Peripheral T‐cell lymphoma: A clinicopathologic study of 42 cases
Authors: Weisenburger Dennis D. , Linder James , Armitage James O.
Published: February 2007

We analysed the clinical and pathologic features of 42 patients with immunologically confirmed peripheral T‐cell lymphoma. The median age was 60 years and the male to female ratio was 1:1. A prior lymphoprolifera‐tive or autoimmune disorder was present in 14 per cent of the patients. Signs of advanced disease were usually present from the onset, such as B symptoms (55 per cent), generalized lymphadenopathy (57 per cent), stage III/IV disease (62 per cent), and elevated levels of serum lactate dehydrogenase (68 per cent). Primary extranodal disease (14 per cent), hepatomegaly (12 per cent), splenomegaly (12 per cent), lung/pleural involvement (12 per cent), skin involvement (21 per cent), and bone marrow involvement (28 per cent) were uncommon. Lymphocytopenia was present in 64 per cent of the patients, and none of nine patients tested were serologically positive for human T‐cell leukemia/lymphoma virus (HTLV‐I) infection. Among 38 patients receiving combination chemotherapy, 20 (53 per cent) achieved a complete remission. The actuarial median survival of all patients was 17 months. Age greater than 60 years and stage III/IV disease predicted a poor clinical outcome, whereas the large cell histological subtype predicted a favourable outcome. Prospective clinical studies using uniform treatments and a uniform histologic classification scheme are needed to confirm these findings.
Auer rods in the acute myeloid leukemias: Frequency and methods of demonstration
Authors: Jain N. C. , Cox C. , Bennett J. M.
Published: February 2007

One hundred and twenty‐five cases of acute myeloid leukemia (AML) were reviewed for the presence of Auer rods by two peroxidase methods. The percentage of Auer rods recognized by Wright‐Giemsa (WG) staining was 20·8% but three times higher by peroxidase staining techniques using either benzidine base as a substrate (PO method) or 3,3′‐diaminobenzidine as a substrate (DAB method). Both PO and DAB methods were equally sensitive in identifying Auer rods, the higher percentage being in FAB types M2 and M4 and lower in M1, M3, and MSB, with none in MSA. Cell counts of at least 100 cells were as accurate as counting cells up to a total of 1000 consecutive blasts.
Allogeneic and autologous bone marrow transplantation for acute leukemia and malignant lymphoma: Current status
Authors: Petersen F. B. , Buckner C. Dean
Published: February 2007

The current status of autologous and allogeneic marrow transplantation for acute leukemias and malignant lymphoma is reviewed and compared to the current status of conventional chemotherapy. Based on the reviewed literature, it is concluded that marrow transplantation and conventional chemoradiotherapy are not mutually exclusive and that for most young patients with acute hematological malignancies the question is not if, but rather when to intervene with a marrow transplant treatment. Thus marrow transplantation and conventional chemoradiotherapy can work as complimentary units in the complex therapeutic approach needed to cure most patients with hematological malignancies.
Bone marrow transplantation—The Marsden experience
Authors: Helenglass G. , Lakhani A. , Powles R. , Nandi A. , Zuiable A. , Gore M. , Forgeson G. , Treleaven J. , Milliken S. , Millar J.
Published: February 2007

Allogeneic bone marrow transplantation (BMT) was first successful at the Royal Marsden Hospital in 1973 and although the programme was initially centred around treating aplastic anaemia, we soon applied the technique to acute leukaemia. Since then we have undertaken approximately 500 bone marrow transplants. This short review will cover some aspects of our programme.
The potential value of very intensive therapy with autologous bone marrow rescue in the treatment of malignant lymphomas
Authors: Gribben J. G. , Hudson B. Vaughan , Linch D. C.
Published: February 2007

Autologous bone marrow transplantation (ABMT) following intensive therapy regimes is being used increasingly in relapsed lymphomas. To date no randomised studies have been performed to ascertain the value of this form of therapy. We describe here our experience of ABMT in both Hodgkin's disease and Non‐Hodgkin's Lymphoma and review the situations in which we believe future randomised studies should be based.
Experience with the portacath
Authors: Lambert Mark E. , Chadwick Gill A. , McMahon Ann , Scarffe J. Howard
Published: February 2007

Fifty Portacaths have been inserted in patients undergoing prolonged outpatient chemotherapy, most for haematological disease. Twenty‐one are still working at a median duration of 12 months (range 1‐27) and a further 15 were functioning normally at the time of the patients death (median survival 6 months). Four functioning Portacaths have been removed, three suspected of causing septicaemia and one believed erroneously to have occluded.

Ten have ceased to function and nine of these have been removed. The causes of these failures are nearly all avoidable and are discussed in detail; many occurred early in our experience. With careful attention to detail and with management by trained and interested staff, the Portacath is a safe and reliable device for intermittent vascular access.
Report of the third U.K. national meeting: East of Scotland and Newcastle lymphoma group
Authors: Leonard R. C. F. , Allan N. C.
Published: February 2007

At a meeting of the East of Scotland and Newcastle Lymphoma Group papers were presented from the major U.K. groups and from North America. The themes focused on the clinical management of poor prognosis non‐Hodgkin's lymphoma, and the identification and treatment of bad risk Hodgkin's disease.
Rearranging antigen‐receptor genes in enriched reed‐sternberg cell fractions of Hodgkin's disease
Authors: Cossman Jeffrey , Sundeen James , Uppenkamp Michael , Sussman Eileen , Wahl Larry , Coupland Robert , Lipford Edward , Raffeld Mark
Published: February 2007

Molecular genetic analysis of rearranging antigen‐receptor genes in non‐Hodgkin's lymphomas has revealed the clonality and lineage in the majority of cases. In an analogous approach, we sought to apply gene rearrangement analysis to Hodgkin's disease to understand better the clonality and origin of this disorder. However, the putative neoplastic cell of Hodgkin's disease, the Reed‐Sternberg cell and its variants, is extraordinarily rare in most cases of Hodgkin's disease. On the average, Reed‐Sternberg cells and variants represent 0.1 per cent of total cell suspensions of nodular sclerosing Hodgkin's disease. As this frequency is below the minimum threshold of sensitivity of the Southern blot assay, we attempted to enrich for Reed‐Sternberg cells before DNA extraction and analysis. Using either elutrition or Percoll density gradient centrifugation, we were able to enrich the percentage of Reed‐Sternberg cells and variants to above 1 per cent in five cases of nodular sclerosing Hodkin's disease. In three of these cases, immunoglobulin gene rearrangements were identified, but no T cell receptor gene rearrangements were seen. No rearrangements were detected in unseparated cells or in the Reed‐Sternberg cell‐depleted fractions. In addition, the L428 Hodgkin's disease cell line was found to have one rearranged and one deleted heavy‐chain gene, a rearranged β gene, a rearranged λ gene, and a single rearranged β allele. No rearrangements of the Tγ gene were found in L428. Taken together, these findings indicate that clonal cell populations are present in Hodgkin's disease and suggest the possibility of a clonally expanded lymphoid cell in this disorder.
Clonal antigen receptor gene rearrangements and epstein‐barr viral DNA in tissues of Hodgkin's disease
Authors: Weiss Lawrence M. , Warnke Roger A. , Sklar Jeffrey
Published: February 2007

In an initial survey of 16 cases of Hodgkin's disease, tissues from one case of nodular sclerosing Hodgkin's disease, a recurrence with numerous Reed‐Sternberg cells, demonstrated faint heavy‐ and light‐chain immunoglobulin gene rearrangements. Analysis of seven additional similar cases with extremely numerous Reed‐Sternberg cells revealed that six of these seven cases contained clonally rearranged heavy‐ or light‐chain genes. In addition, the original biopsy specimen from the index case (obtained two years prior to the recurrence) had the same pattern of rearrangements of the immunoglobulin genes. In contrast, a germline configuration was observed for the β T cell receptor gene in all cases.

These cases of Hodgkin's disease were also investigated for the presence of Epstein‐Barr viral (EBV) genomes by Southern and slot‐blot DNA hybridization analysis. Tissues from four of the 21 case studied showed evidence of EBV DNA sequences. Uninvolved lymphoid tissue from two of the positive cases failed to demonstrate viral DNA. To assess clonality of the cells containing the EBV genomes, the tissues positive for EBV DNA were also hybridized with a restriction fragment probe for the terminal sequences of the EBV genome. By this analysis three of the four cases demonstrated a clonal population of EBV‐infected cells.
A review and interpretation of cytogenetic abnormalities identified in Hodgkin's disease
Authors: Cabanillas Fernando
Published: February 2007

The nature of the cell which gives origin to Hodgkin's disease remains unclear after years of intensive investigation. Cytogenetic data, which are very scarce in Hodgkin's disease, could contribute information which might help elucidate this problem. Review of our own data and others shows that the most frequent abnormalities in this disorder involve chromosomes 14q in 35 per cent of cases, 11q in 32 per cent, 6q in 32 per cent, and 8q in 18 per cent. The most common breakpoint in chromosome 14 occurred at 14q32 where the IgH chain genes reside thus suggesting that in these cases the cell of origin might be a B lymphocyte. The 11q and 6q structural abnormality have also been frequently seen in lymphoid disorders such as ALL and large cell lymphoma. Of interest also is the fact that in a certain type of childhood pre‐B cell acute lymphoblastic leukemia which shows cytogenetic abnormalities on 11q23, aberrant myeloid and monocytic markers are seen. This suggests that in Hodgkin's disease a similar phenomenon might occur which could help to explain why the Reed‐Sternberg cell expresses myeloid‐monocytic antigens such as Leu M‐1.
The management of early‐stage aggressive non‐Hodgkin's lymphoma
Authors: Horwich A. , Catton C. N. , Quigley M. , Easton D. , Brada M.
Published: February 2007

Sixty‐one patients with stage I or II non‐Hodgkin's lymphoma of aggressive histological subtype were treated at The Royal Marsden Hospital between 1972 and 1984. The overall 5‐year survival probability was 69 per cent (60 per cent continuously relapse‐free). The 5‐year survival probability was 80 per cent for stage I disease and 55 per cent in stage II (p = 0.05). Survival was significantly higher in non‐bulky than bulky presentations (85 per cent versus 44 per cent at 5 years, p = 0.003). There was no significant 2‐year survival difference between those treated initially with chemotherapy and those treated with radiotherapy alone (65 per cent versus 83 per cent), however chemotherapy had been employed predominantly in patients with adverse presentations. The 2‐year survival in 41 patients treated initially with doxorubicin‐containing chemotherapy combinations was 76 per cent. Combined modality treatments should be considered especially in patients with stage II or bulky disease.
Severe lung toxicity with a weekly low dose chemotherapy regimen in patients with non‐Hodgkin's lymphoma
Authors: Quigley M. , Brada M. , Heron C. , Horwich A.
Published: February 2007

Nineteen patients in poor prognostic subgroups of aggressive non‐Hodgkin's lymphoma (NHL) were treated with weekly chemotherapy consisting of low dose mitoxantrone and cyclophosphamide alternating with bleomycin and vincristine together with continuous oral prednisolone. Six patients developed pneumonitis which was severe in five patients. This occurred at total bleomycin doses of < 50 U/m2 and cyclophosphamide < 1875 mg/m2. The 31 per cent incidence of pneumonitis following low dose bleomycin suggests an increased susceptibility to drug‐induced pulmonary damage in non‐Hodgkin's lymphoma.
Correlation between histology and immunophenotype in a series of 322 cases of non‐Hodgkin's lymphoma
Authors: Smith J. L. , Jones D. B. , Bell A. J. , Wright D. H.
Published: February 2007

The non‐Hodgkin's lymphomas (NHL) are a heterogeneous group of lymphoid neoplasms displaying a wide variation in cell morphology, histological patterns, immunological phenotype and prognosis. In this paper we compare the results of phenotypic investigation of 322 tissue biopsies with the histology based on the Kiel classification. Immunological analysis revealed that 81 per cent of these tumours were of B cell origin. 12 per cent of T cell origin and the remaining 7 per cent could not be characterized as representing either cell lineage. This last group included a number of cases which had received a histological diagnosis of true histiocytic lymphoma. The original morphological diagnosis, based on routine haematoxylin and eosion sections correlated with the immunologically determined phenotype in 86 and 93 per cent of the T‐ and B‐cell cases respectively. The B cell tumours were phenotypically heterogenous with respect to immunoglobulin (Ig) heavy chain and B lymphocyte subset marker expression. IgG was most often found associated with NHL of cb/cc histology and a small subgroup of lymphocytic NHL. IgA expression was uncommon and occurred in combination with IgD and G in three cases and alone in two cases of NHL. The most common immunoglobulin isotype expressed was IgM this isotype occurred with IgD most often in lymphocytic and centrocytic NHL and less often in tumours of cb/cc histology. Whilst greater than 90 per cent of the lymphocytic NHLs expressed the CD5 antigen, between 20 and 75 per cent of B‐cell tumours of other histologies also expressed this epitope. The CD10 antigen and the epitope recognized by the monoclonal reagent FMC7 were widely distributed on tumour cells from all histologies. TdT expression commonly regarded as a marker for immature cells was found in one case of follicle centre cell lymphoma. All cases of T cell NHL displayed marked heterogeneity for both pan T and T subset antigens which is significant in terms of the routine diagnosis of T NHL and with regard to the rational classification of node based T NHL. Unlike resting peripheral blood T cells, MHC class II, OKT 10 and CD25 epitopes were expressed reflecting activation of tumour populations.

The cases in which a T‐ or B‐cell lineage was not determined in the initial biopsy were subsequently re‐examined in paraffin section using CD45R monoclonal reagents. These antibodies have been shown to assist the determination of cell lineage in paraffin section. Following this analysis five cases were shown to represent atypical Ig negative B cell lymphomas and three showed membrane positivity with T cell markers. Four cases remained unclassified and in these the original histological diagnosis of histiocytic lymphoma would seem appropriate.
Failure of lithium to reduce period of neutropenia during induction therapy of acute myeloid leukemia
Authors: Scarffe J. Howard , Chang James
Published: February 2007

Fifty‐four patients treated with daunorubicin, cytosine arabinoside and thioquanine for acute myeloid leukemia were randomly assigned to recieve oral lithium carbonate 1200 mg daily or no lithium. The duration of neutropenia (<0.5 × 109/L) was similar between controls (median 22.5 days) and patients treated with lithium (median 24 days). The number of remissions, relapse‐free survival and survival were similar for the lithium treated and control groups of patients. There was no apparent clinical efficacy in the use of lithium to reduce the period of neutropenia in patients undergoing remission induction therapy for acute myeloid leukemia.
Lomustine, vindesine and bleomycin (LVB) used in the treatment of relapsed advanced Hodgkin's disease. A prospective study on behalf of the east of Scotland and Newcastle lymphoma group (ESNLG)
Authors: Lennard A. L. , Proctor S. J. , Dawson A. A. , Allan N. C. , Prescott R. J. , Parker A. C. , Leonard R. C. F. , Angus B. , Dobson C. , Ritchie G. L. , Lucraft H. H. , Scott S.
Published: February 2007

Sixty‐three patients with relapsed advanced Hodgkin's disease were treated with lomustine (CCNU), vindesine and bleomycin (LVB). Age range was 17–72 years, with 38 males and 25 females. Thirty patients achieved complete remission (CR) with a median duration of 24 + months (range 3–55). Nineteen continue in unmaintained CR. CR rates were highest for those patients who relapsed > 6 months after first line treatment and for those at second or subsequent relapse. CR rates were higher in those with nodal only relapse.

Twenty‐seven patients were non‐responders and six were partial responders. These 33 patients were subsequently changed to alternative chemotherapeutic regimes and 26 failed to respond to any therapy and have since died. Only one patient is in unmaintained complete remission.

The regimen was well tolerated by patients, and easy to administer. It produced no serious episodes of toxicity.

We conclude that LVB is of value in the management of relapsed advanced Hodgkin's disease especially in chronic relapsing patients, and where relapse occurs > 6 months after first line treatment. We are presently unsure whether it offers any advantage over reintroduction of first line treatment in the latter group.
Morphological, immunophenotypical and isoenzymatic profiles of human leukemia cells and derived T‐cell lines
Authors: Drexler Hans G. , Minowada Jun
Published: February 2007

Six monoclonal leukemia cell lines (MOLT 12‐17) were established from three patients with acute leukemia. Two of the patients' samples were of the T‐ALL type, the third had morphological, isoenzymatic and immunological features of AMoL. The cell lines resulting from these original cells displayed distinct, but stable marker profiles. A comparison between primary cells and resulting cell lines showed that the cell lines established from patients with T‐ALL (MOLT 12, 13, 14 and MOLT 16, 17) expressed similar phenotypes and isoenzyme patterns, but were different in a few specific aspects. The changes suggest a modulation of marker expression in vitro or an arrest at a more immature stage of differentiation than the original cells. The cell line MOLT 15 established from the case of AMoL exhibited a quite discordant profile when compared to the primary sample: the cells lacked all previously found myelomonocytic antigens and a monocyte‐specific esterase isoenzyme, but expressed the T‐cell associated CD7 antigen and had rearrangements and RNA transcripts of the T‐cell receptor β and γ chain genes. This striking discrepancy between the patient's malignant cells and the corresponding cell line suggests that subpopulation selection had occurred in culture.
Chronic lymphocytic leukemia (CLL) in younger adults: A retrospective study of 133 cases
Authors: De Rossi Giulio , Mandelli Franco , Covelli Alfredo , Luciani Matteo , Martelli Maurizio , Resegotti Luigi , Alberti Antonio , Cajozzo Aurelio , Derriu Luigi , De Biasi Raffaele , Broccia Giorgio , Abbadessa Antonio , Caronia Francesco , Leone Pietro
Published: February 2007

Clinical and biological data have been evaluated, using both univariate and Cox's multivariate statistical analyses, in a series of 133 Chronic Lymphocytic Leukemia (CLL) patients with a mean age of 46.6 years (range 31‐50).

In univariate analyses, anemia (Hb < 13 g/dl), peripheral blood (PB) lymphocytosis (> 40 × 109/1) and bone marrow (BM) lymphocytosis (> 80 per cent) were shown to be of significant prognostic value.

Multivariate analysis, through a forward stepwise procedure, showed that the most important and independent variable is the BM lymphocytosis. These results are different from those obtained in previous studies and particularly in a recent identical study performed by the same Cooperative Group on 1777 patients with a mean age of 64.2 years (Mandelliet al., 1987).

No significance can be demonstrated in stratifying this series of younger patients according to different staging methods (Raiet al., 1975; Binetet al., 1981b; Mandelliet al., 1987). Therefore this population of CLL patients, with less than 50 years of age, has risk factors quite different from classical CLL.

The results of the present study show that the diagnostic approach to B‐CLL in younger adults must be more complete: using the common diagnostic criteria, established staging systems appear to be inadequate in this series of younger patients.
Leucocyte common antigen in the differential diagnosis of Hodgkin's disease
Authors: Strauchen James A.
Published: February 2007

The utility of immunohistochemical staining for leukocyte common antigen (LCA) in the differential diagnosis of Hodgkin's disease was studied in a series of 42 cases of Hodgkin's and non‐Hodgkin's lymphoma and compared with Leu M‐1, a proposed marker for Reed‐Sternberg cells. LCA staining of neoplastic cells was absent in 23 of 24 cases of Hodgkin's disease but present in 16 of 18 cases of non‐Hodgkin's lymphoma including eight of 10 cases with pleomorphic Reed‐Sternberg‐like cells. Leu M‐1, in contrast was present in 14 of 24 cases of Hodgkin's disease, but also in five of 18 cases of non‐Hodgkin's lymphoma including five of 10 cases with pleomorphic Reed‐Sternberg‐like cells. Immunohistochemical staining for LCA appears useful in the differential diagnosis of Hodgkin's disease and appears to be a better discriminant than Leu M‐1.
Retrovirus‐associated adult T‐cell leukemia‐lymphoma: An epidemiologic study of five cases among Hawaii‐born offspring of migrant Japanese
Authors: Yanagihara Eugene T. , Nakamura Jeffrey , Kimura Lucille , Oishi Noboru
Published: February 2007

Adult T‐cell leukemia‐lymphoma (ATLL) is a distinct clinicopathologic entity etiologically linked to HTLV‐I infection. We have identified five cases of retrovirus‐associated ATLL among Hawaii‐born first generation offspring (nisei) of migrant Japanese. Four patients were offspring of migrant Japanese (issei) who emigrated to Hawaii from Okinawa, an HTLV‐I endemic area. The fifth patient was born of parents who emigrated to Hawaii from Fukushima and Miyagi prefectures, HTLV‐I nonendemic areas. Epidemiologic implications and family studies with regard to HTLV‐I antibody testing of the index cases are discussed. The high rate of HTLV‐I antibody seropositivity among family members and relatives indicates that the risk of acquiring HTLV‐I infection and of developing ATLL persists long after migration. Documentation of ATLL among offspring of Japanese immigrants to Hawaii is an important observation because it confirms the potential for long latency between putative exposure to virus and the development of overt disease. Changing marriage patterns among the Hawaii‐Japanese may weaken the risk of vertical virus transmission to the descendents of migrants from southern Japan, while increasing the risk to children born of mixed marriages. In addition, blood products derived from high‐risk donors will constitute a continuing hazard if they are not subject to screening.
Philadelphia chromosome without breakpoint cluster region rearrangement in a case of Lennert's lymphoma of suppressor phenotype
Authors: Terjanian Terenig , Blick Mark B. , Shtalrid Mordechai , Manning John T. , Trujillo Jose M. , Cabanillas Fernando
Published: February 2007

A 60‐year‐old woman presented with diffuse lymphadenopathy. Diagnostic and staging work‐up showed that the patient had diffuse small cleaved cell lymphoma (diffuse poorly differentiated lymphocytic lymphoma) with associated histiocytes (lymphoepithelioid cell lymphoma) by the Kiel classification system. Immunohistologic staining showed a T suppressor cell tumour phenotype. Cytogenetic studies revealed the Philadelphia chromosome (Ph1). On DNA studies, the breakpoint cluster region (BCR) gene was not rearranged suggesting that the Ph1 involvement was not identical to that seen in chronic myelogenous leukemia (CML). This case is presented because of the rarity of Ph1 in lymphoid malignancies, particularly in those of T‐cell origin, and because of its potentially adverse implications.
Identification of peanut agglutinin binding glycoproteins restricted to Hodgkin's disease‐derived cell lines
Authors: Flavell D. J. , Jones D. B. , Wright D. H.
Published: February 2007

Peanut agglutinin (PNA) binding glycoproteins from four Hodgkin's desease (HD)‐derived cell lines and a variety of cell lines/peripheral blood cells representative of the lymphoid and myeloid lineages were identified by probing nitrocellulose membranes of SDS‐PAGE separated NP40 solubilized cellular glycoproteins with [125I]‐labelled PNA. The two Hodgkin's cell lines Ho and L428 demonstrated the most heterogeneous glycoprotein profiles each expressing 15 PNA binding glycoproteins, respectively. The two remaining Hodgkin's lines Co and L591 expressed only four glycoproteins each and these were all also commonly expressed by Ho and L428.

Comparative analysis with all other cell types studied revealed the expression of five glycoproteins restricted to Ho (gp42, gp40, gp38, gp24 and gp22) and six restricted to L428 (gp180, gp75, gp40, gp38, gp24 and gp22). Four of these, gp40, gp38, gp24 and gp22 were commonly expressed by both Ho and L428. Of cell lines of myeloid lineage studied only the erythroleukemia cell line K562 expressed detectable glycoproteins also expressed by some of the Hodgkin's cell lines (gp 110, gp96, gp50 and gp45). Only one glycoprotein, gp20 expressed by Ho was also commonly expressed by normal peripheral blood granulocytes.

This limited study has thus succeeded in demonstrating for the range of cell types studied, that some glycoproteins with terminal d‐galactose β (1 → 3) N‐acetyl galactosamine oligosaccharide sequences are apparently restricted to two of the HD cell lines. Moreover, the heterogeneous glycoprotein profiles obtained for the HD cell lines Ho and L428 suggests that galactosylation processes in these two cell lines is aberrant.
In vitro chemosensitivity testing of leukemic cells: Development of a semiautomated colorimetric assay
Authors: Bernabei Pietro Antonio , Santini Valeria , Silvestro Luigi , Pozzo Orietta Dal , Bezzini Roberto , Viano Ilario , Gattei Valter , Saccardi Riccardo , Ferrini Pierluigi Rossi
Published: February 2007

A rapid chemosensitivity assay was developed, employing the human continuous leukemic cell lines HL 60, K 562, FLG 29.1. This automated colorimetric assay is based on the characteristic of viable, metabolically active cells to cleave p‐iodonitrotetrazolium violet (INT) into a red formazan derivative, whose optical density is readable at 492 nm by an automated microtiter‐plate reader photometer.

A linear relationship was found between the viable cell number and the optical density of INT cleaved by the cellular samples. Dead cells did not reduce INT and did not interfere with the formazan derivative generation and the photometric reading.

Leukemic cell lines were also tested for INT formazan derivative generation after exposure to antileukemic drugs at various concentrations, representative of plasma levels obtainable in vivo. A dose‐dependent inhibition was detected, with different sensitivity patterns, related both to the drugs and to the different cell lines. A significant correlation between the viable cell number and the amount of tetrazolium salt cleaved was also demonstrated after drug exposure. INT assay allows the processing of a great number of samples and gives the opportunity to screen several drugs, saving time and yielding fully reliable results.
Determination of proliferative fractions detected by immunohistochemistry with the monoclonal antibodies to bromodeoxyuridine and Ki‐67 in malignant lymphomas
Authors: Kawauchi Kiyotaka , Sato Yuichi , Furuya Takashi , Watanabe Shaw
Published: February 2007

The stainability of proliferating cells with monoclonal antibodies to both bromodeoxyuridine (BrdU) and Ki‐67 were compared in 22 malignant lymphomas and six related conditions.

A significant correlation was observed (r = 0.78) between the positivities of proliferating cells determined using these two monoclonal antibodies. The growth fractions determined with the antibodies were usually related to the histologic classification, but labelling index was more varied in diffuse large cell type lymphoma. BrdU labelling was well correlated with the Working Formulation, and more useful as a prognostic indicator. On the other hand, Ki‐67 was useful for broad recognition of cell proliferative ability.