bluuebunny/crossref_metadata_2025 huggingface dataset:
Purine degradative enzymes in circulating malignant cells of patients with chronic B cell neoplasia
Authors: Ho Anthony D. , Knauf Wolfgang , Ganeshaguru Kanagabasai , Hunstein Werner , Hoffbrand A. V.
Published: February 2007

Previous reports have shown that the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and ecto‐5'‐nucleotidase (5'NT), play an important role in the normal development of lymphocytes and that investigations of these enzymes are of value in defining subsets of lymphoid malignancies of T‐cell origin. Pharmacological inhibition of one of these enzymes has been found to be an effective treatment for a few lymphatic neoplasia. We have studied the activities of the above enzymes in the circulating malignant cells of 25 patients with B‐chronic lymphatic leukemia (B‐CLL), four patients with B prolymphocytic leukemia (PLL), seven patients with leukemic centrocytic lymphoma (CC), 18 patients with hairy cell leukemia (HCL) and 16 patients with immunocytoma (IC). For comparison, the blasts of nine patients with ‘common’ acute lymphatic leukemia (cALL) and normal T (n = 12) and B (n = 8) cells were simultaneously investigated. Despite morphologic similarity, the leukemic cells of the chronic B cell malignancies demonstrate different enzyme patterns. B‐CLL is characterized by very low activities of all the enzymes ADA, PNP and 5'NT. In the cells of HCL the highest values of PNP are found. The leukemic cells of IC are characterized by low levels of ADA but moderate levels of PNP and high levels of 5'NT. Thus some of the entities of B malignancies show typical enzyme patterns which might be of importance in defining maturation stages of the disease. The differences in these enzyme patterns can also be made use of in therapy with enzyme inhibitors such as deoxycoformycin.
A comparison of bone marrow findings in patients with acquired immunodeficiency syndrome (aids) and aids related conditions
Authors: Namiki T. S. , Boone D. C. , Meyer P. R.
Published: February 2007

Bone marrow biopsies and smears were examined from 70 patients with acquired immunodeficiency syndrome (AIDS) or AIDS related conditions: 32 patients with AIDS; 9, at risk, group patients with B‐cell lymphoma; 22 patients with AIDS related complex (ARC) and 7, at risk, group patients with idiopathic thrombocytopenic purpura (ITP). The first three groups showed similarity with respect to frequency of nonspecific findings: hypo and hypercellularity, marrow damage, lymphoid aggregates, histiocytosis, plasmacytosis and features of myelodysplasia. AFB and fungal organisms were present in the biopsies of 17 per cent of AIDS and 18 per cent of ARC patients. The organisms were associated with bone marrow granulomas or histiocytosis, peripheral lymphopenia and anemia. Only one out of 9 biopsies in patients with previous diagnoses of lymphoma showed involvement of the marrow. One case each of Hodgkin's disease and non‐Hodgkin's lymphoma were discovered incidentally among the 22 biopsies from ARC patients without a previous diagnosis of lymphoma. Except for those presenting with ITP alone, bone marrow changes are similar in patients with AIDS and AIDS related conditions.
Acute leukemia with coexpression of lymphoid and myeloid phenotypes
Authors: Gupta A. Das , Advani S. H. , Nair C. N. , Gopal R. , Saikia T. , Kumar M. S. Ashok , John B. , Dhond S. R.
Published: February 2007

A multiparameter analysis of 706 cases of acute leukemia (AL) over a two‐year period revealed only six cases (0·86 per cent) with coexpression of lymphoid and myeloid phenotypes. In three cases, expression of both lymphoid and myeloid markers by the majority of the blast cells suggested a ‘biphenotypic’ pattern while in the remaining three cases, the lymphoid and myeloid phenotypes were seggregated into two morphologically distinct populations of blast cells indicating a ‘biclonal’ distribution. The poor response to anti‐acute lymphoblastic leukemia therapy in five of these six cases underlines the bad prognostic significance of Co‐expression of lymphoid and myeloid phenotypes in AL. The incidence of ‘mixed lineage’ phenotype in the present series appears very low.
Management of stage I–II diffuse aggressive non‐hodgkin's lymphoma of the waldeyer's ring: Combined modality therapy versus radiotherapy alone
Authors: Liang R. , Ng R. P. , Todd D. , Choy D. , Khoo R. K. K. , Ho F. C. S.
Published: February 2007

Twenty five patients with stage I and II diffuse aggressive non‐Hodgkin's lymphoma of the Waldeyer's ring were reviewed. There were 19 patients with diffuse histiocytic, 4 diffuse lymphocytic poorly differentiated and 2 diffuse mixed lymphoma. Their median age was 51 years. There were 12 males and 13 females. Eight patients had stage I, and 17 had stage II disease. There was a significantly higher incidence of involvement of the left side of the Waldeyer's ring compared to the right (p = 0.0251). Fifteen patients received radiotherapy alone, and ten had radiotherapy and chemotherapy. The median durations of follow‐up were 42 (range 8–162) and 44 (range 8–97) months respectively. All patients had complete remission but 9 patients (36 per cent) subsequently had relapse of their lymphomas. Stomach was the commonest site of relapse (44 per cent). The disease free survival and overall survival at 5 years were 59 per cent and 57 per cent respectively. Higher relapse rate was observed in the radiotherapy alone group (60 per cent) as compared to the combined modality therapy group (0 per cent). Patients who received combined modality therapy had significantly superior 5 years disease free survival (100 per cent versus 32 per cent, p <0.01) and overall survival (81 per cent versus 40 per cent, p <0.05). After radiotherapy alone, patients with stage II disease appeared to have a high relapse rate than those with stage I disease (70 per cent versus 40 per cent) but the difference did not reach statistical significance due to small sample sizes. The histological subtypes did not appear to affect their prognosis. All patients with stage I and II diffuse aggressive non‐Hodgkin's lymphoma of the Waldeyer's ring should have gastrointestinal barium studies at initial staging, and a prospective randomised study on these patients comparing radiotherapy alone and combined modality therapy should be performed.
The prognostic significance of X‐ray changes at presentation and reassessment in patients with multiple myeloma
Authors: Smith David B. , Scarffe J. Howard , Eddleston Brian
Published: February 2007

The relationship between presenting skeletal X‐ray findings and survival in multiple myeloma was assessed in 172 consecutive patients treated at this institute. All patients were investigated, treated and followed up according to one protocol. The shortest survival was seen in those with normal X‐rays (3‐year actuarial 11 per cent) and the longest in those with minimal lytic changes (3‐year actuarial 44 per cent). Patients with osteoporosis alone and those with extensive lytic lesions had intermediate survivals of 32 per cent and 33 per cent respectively. Of the other major prognostic features only anaemia demonstrated a significant correlation with X‐ray findings in terms of survival (p < 0.001) suggesting that those with normal X‐rays may have a more diffuse marrow involvement accounting for their poor prognosis.

The response on bone X‐rays in 102 patients who completed nine cycles of chemotherapy was also analysed. Patients with evidence of healing had a 3‐year actuarial survival of 37 per cent, those with progression 36 per cent and those with stable X‐rays 65 per cent (p < 0.01).

Normal bone X‐rays at presentation and radiological evidence of healing following therapy appear to be bad prognostic signs in multiple myeloma.
Treatment of early chronic lymphocytic leukemia: Intermittent chlorambucil versus observation
Authors: Shustik C. , Mick R. , Silver R. , Sawitsky A. , Rai K. , Shapiro L.
Published: February 2007

The effect of early therapy on the course of chronic lymphocytic leukemia (CLL) has not been established. Fifty‐nine patients with indolent Rai stage I and II CLL were randomized to receive intermittent chlorambucil once a month or to receive no treatment. The two groups were comparable in entry characteristics. At 5 years from randomization there was no significant difference in survival between the two groups although the proportion of patients exhibiting active disease 5 years after randomization is 70 per cent in the untreated group and 55 per cent in the treated group. In this study, early treatment of CLL with intermittent chlorambucil did not result in a survival advantage for patients with indolent stage I and II CLL.
CHOP and COPBLAM chemotherapy for diffuse large cell non‐Hodgkin's lymphomas: A retrospective comparison
Authors: Gerhartz Heinrich H. , Thiel Eckhard , Hiller Erhard , Nerl Christoph , Kolb Hans J. , Wilmanns Wolfgang , Huhn Dieter ,   All the authors are members of the Munich Lymphoma Study Group
Published: February 2007

Between 1979 and 1985 61 consecutive patients with non‐Hodgkin's lymphomas of unfavourable histology (mostly diffuse large cell lymphomas subclassified according to Kiel nomenclature) were treated in our departments by either the CHOP‐ (n = 34) or the COPBLAM‐regimen (n = 27). A retrospective analysis revealed that prognostic variables, excluding primary central nervous system (CNS)‐involvement (n = 5), were equally distributed between both groups. Remission rates were significantly higher in the COPBLAM treated patients as compared with the CHOP treated group (85 per cent versus 38 per cent CR, P = 0.001) even when cases with primary CNS‐disease were excluded. The survival curve did not reach a plateau in CHOP treated cases, whereas 85 per cent of the COPBLAM treated group reached a plateau by 15 months. The mean observation time, however, was shorter in the COPBLAM treated group (37 versus 30 months, respectively).

It is concluded that the COPBLAM regimen is superior to the CHOP‐protocol in inducing complete responses in aggressive non‐Hodgkin's lymphomas. Longer follow‐ups are needed to definitely show if this corresponds to an increased proportion of ‘cures’.
Comparative analysis of [3H]‐thymidine labelling index and monoclonal antibody Ki‐67 in non‐Hodgkin's lymphomas
Authors: Veneroni S. , Costa A. , Motta R. , Giardini R. , Rilke F. , Silvestrini R.
Published: February 2007

The relation between the [3H]‐thymidine labelling index (3H‐Thy LI), which evaluates the S‐phase cells, and the monoclonal antibody Ki‐67 (MoAb Ki‐67), which recognizes a nuclear antigen expressed during the cell cycle, was defined in 35 non‐Hodgkin's lymphomas (NHL). Significantly higher median values of [3H]‐Thy LI and Ki‐67‐positive cells were observed for high‐grade than for low‐grade malignancy tumours according to the Kiel classification, but with wide and overlapping values for the two morphologic subgroups. A significant correlation was observed between [3H]‐Thy LI and Ki‐67‐positive cells (P < 0.0001; r = 0.62). However, the ratio between the two cell kinetic variables on individual tumours was not constant. It sharply increased with decreasing [3H]‐Thy LI values and was much higher in low‐grade NHL than in high‐grade NHL. Follow‐up studies are needed to establish the role of the tumour growth fraction as evaluated by MoAb Ki‐67 as a prognostic indicator in NHL.
Retinoic acid alone and in combination with cytosine arabinoside induces differentiation of human myelomonocytic and monoblastic leukaemic cells
Authors: Hassan H. T. , Rees J. K. H.
Published: February 2007

The effect of retinoic acid (RA) alone and in combination with cytosine arabinoside (Ara‐C) on differentiation of fresh human myeloid leukaemic cells from patients with AML was studied. Cells from six patients: three with acute myelomonocytic leukaemia AMMoL and three with acute monoblastic leukaemia AMoL with a percentage of blasts > 70, were treated in an in vitro primary suspension culture with retinoic acid (10−7 M), cytosine arabinoside (100 ng/ml) or both in combination. Non‐adherent mononuclear cells were seeded at a concentration of 5 × 105 cells/ml in RPMI 1640 culture medium supplemented with 20 per cent fetal bovine serum and 10 per cent (PHA‐LCM) phytohaemagglutinin leucocyte conditioned medium and incubated for 6 days at 37°C in a humidified incubator containing 5 per cent CO2 in air. Morphological and functional differentiation into terminal mature elements was induced in all leukaemia cells of the six patients following exposure to the combination of both agents. These results suggest the potential usefulness of the combination of a differentiating agent (retinoic acid) and an antileukaemic drug (cytosine arabinoside) in the treatment of acute myeloid leukaemias: AMMoL and AMoL. This combination warrants a clinical trial.
Blood lymphocyte characteristics as predictors of prognosis in chronic lymphocytic leukemia of B‐cell type
Authors: Kimby E. , Mellstedt H. , Nilsson B. , Björkholm M. , Holm G. , Lindemalm C. , Tribukait B.
Published: February 2007

The prognostic information of blood lymphocyte characteristics and clinical findings was assessed in 62 patients with chronic lymphocytic leukemia of B cell type. Bivariate and multivariate survival analyses were performed using age, Rai stage, surface membrane immunoglobulin (smIg) isotype pattern of the leukemic clone, total lymphocyte counts, numbers of proliferating lymphocytes and T cell subpopulations. Rai stages III and IV, high numbers of blood lymphocytes in S‐phase (S+) and smμ isotype were found to be partly independent factors predicting short therapy‐free survival. Patients with a smμ+leukemic cell clone had a shorter therapy‐free and total survival compared to those with smμ+/δ+and smδ+leukemic cells. Moreoever, patients with high numbers of blood S+lymphocytes had a shorter therapy‐free and total survival compared to those with few S+cells. These prognostic variables were valid also in patients with a low tumour burden (Rai stages 0, I and II) and may thus be of clinical importance as a guideline for therapeutic intervention.
Allogeneic bone marrow transplantation in 24 patients with multiple myeloma reported to the ebmt registry
Authors: Gahrton G. , Tura S. , Flesch M. , Gratwohl A. , Gravett P. , Lindeberg A. , Lucarelli G. , Michallet M. , Reiffers J. , Ringdén O. , Nikoskelainen J. , Van Lint M. T. , Vernant J.‐P. , Zwaan F. E.
Published: February 2007

Twenty‐four patients with multiple myeloma received an allogeneic bone‐marrow graft from HLA‐compatible sibling donors (n = 23), or a twin donor (n = 1). Eighteen patients are alive, 1‐36 months post bone‐marrow transplantation (median 14 months). Ten of these patients had no signs of multiple myeloma as judged by immunoglobulins in serum, light chains in urine, or the percentage of plasma‐cells in bone‐marrow aspirate. Bone lesions on X‐ray were mainly unchanged. Six patients died from transplant‐related complications 3 weeks to 5 months post transplantation. One of these patients had severe acute graft‐versus‐host disease (aGVHD). In other patients aGVHD was a minor problem. Allogeneic bone‐marrow transplantation appears to be a promising method for treatment of a selected group of patients with multiple myeloma.
Immunogenotyping in Hodgkin's disease
Authors: Griesser Henrik , Mak Tak W.
Published: February 2007

This review presents and discusses the immunogenotypic findings in 112 cases of Hodgkin's disease (HD) and eight Hodgkin's cell lines. Clonal rearrangements of the T cell receptor γ and β chain, as well as immunoglobulin heavy and light chain genes, are detected in the majority of nodular sclerosis and lymphocytic depletion subtypes. Together with the recent immunophenotypic data, these findings are in favour of the view that HD is a disease of activated lymphoid cells. Further investigations will be necessary to characterize the morphology and immunophenotype of the clonally rearranged cell population which seems not to be confined to the Sternberg‐Reed and Hodgkin cell in every case. Prospective clinical studies including the genotype of HD cases have to be done in order to address the question of whether or not distinctive immunogenotypic profiles correlate with the clinical course of this lymphoproliferative disorder.
In vitro analysis of cell populations involved in Hodgkin's disease lesions and in the characteristic T cell immunodeficiency
Authors: Ford Richard J. , Rajaraman Chitra , Lu Ming , Blick Mark
Published: February 2007

Hodgkin's disease (HD) is an aggressive human lymphoproliferative disease that displays a curious pleomorphic histopathologic appearance unlike that of any of the common non‐Hodgkin's lymphomas (NHL). Although the bizarre giant cells of the HD lesion, the Reed‐Sternberg cells (RSC) and mononuclear variant Hodgkin's cells (HC), have been considered to be malignant cells, little objective evidence supports this conclusion. We have studied the proliferative characteristics of T cell as well as RSC and HC‐enriched populations from HD lesions, and found the majority of the proliferative activity in the T cell populations. RSC‐enriched populations not only showed little spontaneous proliferation, but also did not respond to a variety of cytokine growth factors in vitro, suggesting that these cell populations are not actively growing cells. Further molecular studies to identify possible monoclonal T or B cell populations in HD lesions, using a TCR β chain probe and IgH probes respectively on Southern blot analysis, revealed no evidence of monoclonal lymphoid cell populations.

Additional studies on the characteristic T cell immunodeficiency in HD were also undertaken. Our previous studies had associated a decrement in IL‐2 production with this defect. Our studies now show that an intrinsic T cell abnormality exists when HD patients' T cells are stimulated with agonistic MAb that can optimally activate and stimulate IL‐2 production in normal control T cells.
Prognostic factors in decision‐making in the clinical management of Hodgkin's disease
Authors: Hagemeister Fredrick B.
Published: February 2007

At the beginning of this conference, Dr Ford asked whether or not Hodgkin's disease was a malignancy. Most physicians would agree that, regardless of whether this question can be answered on a molecular level, Hodgkin's disease certainly behaves like a malignancy, and clinically fits criteria necessary to call it one. It grows without control locally, comprising vital organs. It ‘metastasizes’, infiltrates organs, and causes organ dysfunction. Patients afflicted with the disease have a shortened life span without proper therapy, as demonstrated by DeVita in his original publication describing the benefits of MOPP chemotherapy (nitrogen mustard, vincristine, procarbazine, prednisone) (DeVita et al., 1970). However, it can progress very slowly, with 50 per cent of untreated patients with stage III or IV disease dead at one year, but 10 to 15 per cent alive at five years. Therefore, in its clinical behaviour, Hodgkin's disease certainly qualifies as a malignant disorder, despite the fact that we do not have the molecular means of calling it one.
Induction of plasmacytoid and hairy cell features by phorbol esters (TPA) in B‐lymphoma cells: Attempted correlation with disease activity
Authors: Gazitt Yair , Leizerowitz Rachel , Polliack Aaron
Published: February 2007

Mononuclear cells concentrated from the blood of 16 non‐Hodgkin's lymphoma (NHL) patients in the leukemic phase, were exposed to 10 ng/ml of TPA in an attempt to induce differentiation. Immunoglobulin (Ig) secretion, surface markers (SmIg, GP‐70), tartrate resistant acid phosphatase (TRAP) and surface features were followed for up to six days in vitro. TPA induced ‘hairy cell’ like features in NHL cells as defined by cell morphology, ultrastructure, cell surface markers and the presence of TRAP. Unlike the results obtained in patients with CLL, cells from different patients at the same stage of disease reacted in a similar way. Differences were evident between NHL mononuclear cells obtained from patients in partial remission and active disease when compared with those derived from patients in complete remission. In the former group, NHL cells were maximally induced by TPA to secrete Ig and higher proportions of TRAP positive cells. In addition hairy cell features as seen by light and scanning electron microscopy were also more pronounced. TPA also induced the maximal expression of SmIg and GP‐70 in cells derived from patients in this group. Patients with NHL in leukemic phase in complete remission did not express surface membrane GP‐70 before or after TPA treatment while SmIg was expressed to some degree before TPA treatment and further induced following treatment with TPA. GP‐70 appears to be a more reliable marker for follow‐up of NHL patients than any other marker studied here.
Management of localized non‐Hodgkin's lymphoma: The experience at St. Bartholomew's hospital 1972–1985
Authors: Richards M. A. , Gregory W. M. , Hall P. A. , Dhaliwal H. S. , Fernandez J. , Stansfeld A. G. , Jones A. E. , Lister T. A.
Published: February 2007

A retrospective study of 202 patients with clinical stage I and II non‐Hodgkin's lymphoma managed at St. Bartholomew's Hospital between 1972 and 1985 was conducted. Patients were treated either with radiotherapy alone, radiotherapy and adjuvant chemotherapy, or chemotherapy (with or without adjuvant radiotherapy). At the onset of the study it was intended that all patients with localized NHL should be treated with involved field radiotherapy and adjuvant ‘CVP’. As it became apparent that this was inadequate for some patients and too toxic for others a flexible approach was later adopted. Treatment selection depended on age, volume, distribution of disease and histological subtype.

The actuarial 5 year overall survival for the whole group was 70 per cent. Death from lymphoma after 5 years was very rare. Increasing age and high grade histology were highly significant adverse prognostic factors by multivariate analysis. The results for patients with high grade and low grade histology were therefore analysed separately, as was the outcome for patients presenting with either gastrointestinal or skin lymphomas.

During the latter part of the study period intensive chemotherapy was given as the initial treatment to patients with high grade histology and bulky, or stage II disease. Twenty out of 24 patients so treated achieved complete remission and only one has relapsed to date. These results are encouraging and probably explain the absence of a difference in prognosis between patients with stage I and IE disease and those with stage II and IIE disease observed over the whole period of the study.

Remission was achieved in the overwhelming majority of patients with low grade histology for whom radiotherapy was selected as primary therapy. Duration of remission was better in patients who received adjuvant chemotherapy than in those treated with radiation alone, but no difference in overall survival was observed between these groups. Neither stage nor the presence of a follicular histological pattern correlated with prolonged survival in patients with low grade histology.
Lymphoplasmacytoid and small cell centrocytic non‐Hodgkin's lymphoma—A retrospective analysis from St Bartholomew's hospital 1972–1986
Authors: Richards M. A. , Hall P. A. , Gregory W. M. , Dhaliwal H. S. , Stansfeld A. G. , Amess J. A. L. , Lister T. A.
Published: February 2007

Lymphoplasmacytoid (1pc) and small cell centrocytic (scc) lymphoma are the two major sub‐types of diffuse low grade non‐Hodgkin's Lymphoma (NHL) within the Kiel classification. The presentation features and outcome for all 112 patients with these diagnoses (60 lpc, 52 scc) managed at St Bartholomew's Hospital between 1972 and 1986 are presented. The outcome for these patients is compared with that for patients with follicular and high grade lymphomas managed at this hospital during the same period.

Nineteen of the 112 patients had localized (stages I–IIE) disease. In 18 of these cases the primary site of disease was extranodal, the gastrointestinal tract being involved in 12 cases. The survival for patients with localized disease was excellent. Eighteen are currently alive with median follow‐up of 8 years.

Ninety‐three patients had advanced disease. A high incidence of splenomegaly, hepatomegaly, bone marrow and peripheral blood involvement was observed in both histological subgroups. A monoclonal paraprotein band was detected in the serum of nearly 50 per cent of patients with advanced lpc lymphoma.

Patients with advanced disease were treated with either chlorambucil or cyclophosphamide, vincristine and prednisolone (CVP). The outcome was similar for both histological groups.

Survival for these patients was poor (median 40 months) with less than 20 per cent surviving 5 years. Advanced age, elevated aspartate transaminase and failure to respond to treatment were identified by multivariate regression analysis as adverse prognostic factors.
Cyclosporin associated demyelination following allogeneic bone marrow transplantation
Authors: Lind M. J. , McWilliam L. , Jip J. , Scarffe J. H. , Morgenstern G. R. , Chang J.
Published: February 2007

Neurological complications associated with cyclosporin administration are well documented. However their histopathological basis are ill‐understood. We describe below a case of demyelination following cyclosporin administration to a patient following allogeneic bone marrow transplantation.
Treatment of acute myeloid leukemia in the elderly: A clinical dilemma
Authors: Copplestone J. A. , Smith A. G. , Osmond C. , Oscier D. G. , Hamblin T. J.
Published: February 2007

Fifty‐four patients representing all the cases of acute myeloid leukemia in patients aged over 60 years, presenting to three adjacent hospitals, were studied. Only 26 of the 54 patients were considered suitable for remission induction with intensive combination chemotherapy which produced seven complete remissions (CR) (26 per cent). Eighteen of the 54 patients survived longer than three months—11 of these had received remission induction chemotherapy (five CRs), two low dose cytarabine, one vincristine and vitamin A and four supportive treatment alone. By six months all the patients who had received supportive treatment had died.

Patients who received intensive chemotherapy spent 77 per cent of the first 90 days in hospital and half died in hospital. Patients receiving differentiating agents or supportive care spent more time at home (37 per cent. 34 per cent of the first 90 days, respectively) but had shorter overall survival.

Assessment of clinical characteristics in an attempt to predict response to treatment and survival indicated that poor performance status and the presence of infection were the most important factors. Analysis was limited by the statistically small number in the group.

At present there is no reliable method of predicting which patients will respond well to treatment with intensive chemotherapy. The clinical dilemma is whether to treat more intensively to benefit a minority, or to use supportive treatment to allow more time to be spent at home albeit with a shorter overall survival.
Pulsed high dose oral prednisolone in relapsed or refractory multiple myeloma
Authors: Norfolk D. R. , Child J. A.
Published: February 2007

Seventeen unselected patients with relapsed or refractory multiple myeloma were treated with oral prednisolone 60 mg per m2 for five consecutive days with nine‐day treatment‐free intervals. Of the fourteen patients who completed at least six courses of treatment there were five good responses (Chronic Leukemia–Myeloma Task Force Criteria), five partial responses and four failures. Median survival (all seventeen patients) was between 19 and 20 months. Eight patients achieved plateau phase (median duration 9 months). Eleven patients showed improved performance status and four became free of transfusion support. The commonest side‐effect was bacterial pulmonary infection. Peptic ulceration occurred in two patients despite prophylactic ranitidine. Other steroid‐related side‐effects were mild and well tolerated. This study provides further evidence for the efficacy of higher dose steroid regimens in relapsed or refractory myelomatosis and confirms that durable remissions may be achieved. Responders show a gratifying improvement in quality of life and are spared the many toxicities of combination cytotoxic chemotherapy. Further studies of high dose steroid regimens in first‐line therapy, especially in patients with bone marrow suppression, are clearly merited.
Is the Hodgkin cell A T‐ or B‐lymphocyte? recent evidence from geno‐ and immunophenotypic analysis and in‐vitro cell lines
Authors: Drexler Hans G. , Jones David B. , Diehl Volker , Minowada Jun
Published: February 2007

The cellular derivation of Hodgkin (H) and Reed‐Sternberg (RS) cells remains a controversial issue. A large body of conflicting results in the literature led to a variety of discordant speculations. The application of immunophenotyping, molecular biology and tissue culture provided additional means for investigations on the nature of H‐RS cells. Using immunoenzymatic staining with monoclonal antibodies (McAbs) at the single cell level, H‐RS cells from many, albeit not all cases, were shown to be positive for T‐ and/or B‐cell markers; none of the cases were labelled by anti‐myeloid or anti‐monocyte/macrophage McAbs. A common feature of the otherwise heterogeneous immunoprofile is the expression of activation and proliferation antigens besides HLA‐DR class II antigen and the X‐hapten.

Clonal rearrangements of T‐cell receptor or immunoglobulin chain genes were found in 22 per cent of cases. The low frequency of positive samples might be due to the commonly low number of H‐RS cells in the total population which can lay below the threshold of sensitivity for genotypic analysis.

Several cell lines containing H‐RS‐like cells have been established. These cell lines have geno‐ and immunophenotypic characteristics of T‐ or B‐cells, but lack properties of myeloid cells or monocytes/macrophages.

In the absence of evidence in support of an origin from monocytes/macrophages or other non‐lymphoid cells the here reviewed data, which are based on geno‐ and immunophenotypic analysis of fresh and cultured H‐RS cells, provide a lead to a lymphoid derivation of H‐RS cells.
Rapid and complete hemopoietic reconstitution following combined transplantation of autologous blood and bone marrow cells. A changing role for high dose chemo‐radiotherapy?
Authors: Gianni A. M. , Bregni M. , Siena S. , Villa S. , Sciorelli G. A. , Ravagnani F. , Pellegris G. , Bonadonna G.
Published: February 2007

The role of high dose chemo‐radiotherapy with autologous bone marrow transplantation in the treatment of neoplasia remains to be clearly defined. Because of the iatrogenic morbidity, mortality and high cost of the supportive care required during the post‐transplantation period of prolonged marrow aplasia, intensive therapy remains a sophisticated procedure lacking proper evaluation in clinical trials. We report here that when autologous bone marrow cells are supplemented with a small number of peripheral blood nucleated cells collected after prior myelosuppressive chemotherapy, complete hematological recovery is so prompt that myeloid toxicity appears no longer the major limiting factor of high‐dose chemo‐radiotherapy. The increased therapeutic index made possible by the procedure will allow us to address the issue of whether intensive cytoreductive therapy can be useful as initial treatment of selected tumors with curative intent.
A phase 1a clinical trial of LYM‐1 monoclonal antibody serotherapy in patients with refractory b cell malignancies
Authors: Hu Eddie , Epstein Alan L. , Naeve Gregory S. , Gill Indraini , Martin Sue , Sherrod Andy , Nichols Peter , Chen David , Mazumder Amitabha , Levine Alexandra M.
Published: February 2007

Ten patients with refractory B cell lymphomas were treated with weekly intravenous infusions of escalating doses of murine monoclonal antibody (MoAb) LYM‐1 over four weeks. LYM‐1 is a recently developed IgG2a murine MoAb that recognizes a polymorphic HLA‐Dr antigen on surfaces of normal and malignant B cells but does not bind to any other normal tissues. MoAb LYM‐1 has several advantages for serotherapy, since the antigen it recognizes is not shed from the cell surface and does not modulate in response to MoAb therapy. Furthermore, in vitro studies have indicated significant anti‐tumour activity against lymphoma cell lines. In the current trial, dose‐dependent levels of free LYM‐1 were detected in the serum of all patients, but penetration of extravascular tumour tissues was poor. No significant toxicity or human anti‐mouse antibody responses were observed in any patient. Clinical responses were minor and appeared to correlate with the number of infiltrating T cells seen in the initial lymphoma specimens. LYM‐1 appears to be well‐tolerated and has demonstrated several potential advantages as a therapeutic agent in patients with lymphoma. The mechanism of anti‐tumour effect and plans for further clinical studies are discussed.
Terminal transferase positive acute myeloid leukemia: Immunophenotypic characterization and response to induction therapy
Authors: Coco Francesco Lo , Lopez Manuela , Pasqualetti Daniela , Montefusco Enrico , Cafolla Arturo , Monarca Bruno , Sgadari Cecilia , De Rossi Giulio
Published: February 2007

A quantitative evaluation of terminal deoxynucleotidyl transferase (TdT) was performed using a highly sensitive enzyme immunoassay (EIA) in 72 previously untreated patients with acute myeloid leukemia (AML). Biological analysis of the leukemic cells included in all cases cytochemistry, search for Ph' chromosome and immunophenotyping with both anti‐lymphoid and anti‐myeloid monoclonal antibodies (MoAbs). Thirteen AML cases (18 per cent) were considered TdT + by EIA. According to the FAB classification, almost all of them (12 out of 13) were within the M1 and M2 subgroups. A mixed lymphoid‐myeloid phenotype was observed in one of the 13 TdT + cases, while in none of the others were lymphoid features detected. Nine of the 10 EIA TdT + cases studied in parallel were TdT positive with the conventional immunofluorescence assay. All patients received standard protocol chemotherapy and in 61 (13 TdT +, 48 TdT − ) the response to induction treatment was analysable. Only 3/13 TdT + patients (23 per cent) achieved a complete remission (CR), while in the TdT – group 38 patients had a CR (79 per cent) and 10 were resistant (p<0.01). It is suggested that the incidence, biological interest and prognostic significance of TdT + AML should encourage the routine and more accurate search for this marker in all patients with AML.
Peripheral T‐cell lymphoma presenting as hemophagocytic syndrome
Authors: Chan Eric Y. T. , Pi David , Chan George T. C. , Todd David , Ho Faith C. S.
Published: February 2007

Three patients with peripheral T‐cell lymphoma presenting with pyrexia, wasting, hepatosplenomegaly and pancytopenia in the absence of myelophthisic lymphomatous involvement are reported. Early in the course of the disease when there was no significant lymphadenopathy, these cases created enormous diagnostic confusion. Although the clinical features were suggestive of malignant histiocytosis (MH), marrow findings showed phagocytic histiocytes which did not appear atypical, and the criteria for diagnosis of MH could not be satisfied. Lymph node enlargement was detected only after 14, 5, and 8 weeks from the onset of symptoms, and the diagnosis of T‐lymphoma was then made on lymph node biopsies. Treatment with multiple agent chemotherapy was attempted. Two patients died 3 days and 11 weeks after treatment was started and the third was lost to follow‐up. In contrast with most of the cases reported in the literature, our cases show that a reactive hemophagocytic syndrome can be an early and prominent manifestation of an underlying T‐cell lymphoma. Differentiation from other causes of hemophagocytic syndrome can be difficult and lack of histological proof of malignancy in the initial stage often delays definitive diagnosis and treatment.
Multicentre randomized therapeutic trial for advanced centrocytic lymphoma: Anthracycline does not improve the prognosis
Authors: Meusers P. , Engelhard M. , Bartels H. , Binder T. , Fülle H. H. , Görg K. , Gunzer U. , Havemann K. , Kayser W. , König E. , König H. J. , Kuse R. , Löffler H. , Ludwig W.‐D. , Mainzer K. , Martin H. , Pralle H. , Schoppe W. D. , Staiger H. J. , Theml H. , Zurborn K. H. , Zwingers Th. , Lennert K. , Brittinger G.
Published: February 2007

Within a multicentre observation study on non‐Hodgkin lymphomas (NHL) diagnosed according to the Kiel classification advanced stages III and IV of centrocytic (CC) lymphoma exhibited the worst prognosis among lymphomas of low‐grade malignancy with a 5‐year survival probability of less than 10 per cent. Treatment had been solely expectative and palliative with treatment results showing a prognostic superiority of patients achieving partial and complete remissions over non‐responders. Therefore, a randomized multicentre study was initiated to compare the remission‐inducing potential of the COP regimen (Bagleyet al., 1972) with that of the more intensive adriamycin‐containing CHOP regimen (McKelveyet al., 1976).

From 91 newly diagnosed CC lymphomas 63 fulfilled randomization criteria with 37 patients assigned to the COP regimen and 26 patients to the CHOP regimen. Between the COP‐ and CHOP‐treated patients no significant differences could be demonstrated with respect to initial clinical parameters, rate of complete (41 per cent versus 58 per cent) or partial remissions (43 per cent versus 31 per cent), median overall survival probability (32 versus 37 months), relapse‐free survival (10 versus 7 months) and rates of relapse (73 per cent versus 67 per cent) and death (57 per cent versus 50 per cent).

It can be concluded that CC lymphoma is a typical lymphoma of low‐grade malignancy with its inability to reach stable remissions while the demonstration of identical survival probabilities for patients with complete and partial remissions constitutes a unique feature of this lymphoma entity. These observations prove advanced CC lymphoma to represent an incurable neoplastic disease under conventional therapeutic approaches.
Primary intestinal lymphoma of Ki‐1 large cell anaplastic type with mesenteric lymph node and spleen involvement in a renal transplant recipient
Authors: Audouin J. , Le Tourneau A. , Diebold J. , Reynes M. , Tabbah I. , Bernadou A.
Published: February 2007

A laparotomy performed for an occlusive syndrome, disclosed the presence of an ileal lymphoma in a renal graft recipient, 17 years after a first renal transplant. Mesenteric lymph node and spleen involvement were associated. The morphology of the large cells, the type of infiltration of the lymph node simulating metastatic carcinoma or malignant histiocytosis were highly suggestive of a new type of high grade malignancy lymphoma recently described which is called ‘large cell anaplastic ML’. The immunolabelling study confirmed this diagnosis, demonstrating the following phenotype CD4, CD25 (TAC), CD30 (Ki‐1), OKT 9 (transferrin receptor), EMA and HLA DR positivity. The tumour cells were negative for the other T, B and histiomono‐cytic markers. This case, of a large cell anaplastic Ki‐1 positive lymphoma, expressing CD4, in a renal graft recipient shows that high grade ML in such patients are not all of the B cell type.
LONG‐TERM EFFECTS OF PARENTERAL DICHLOROMETHYLENE BISPHOSPHONATE (CL2MBP) ON BONE DISEASE OF MYELOMA PATIENTS TREATED WITH CHEMOTHERAPY
Authors: Merlini Giampaolo , Parrinello Giuseppe Attardo , Piccinini Lino , Crema Francesca , Fiorentini Maria L. , Riccardi Alberto , Pavesi Franco , Novazzi Francesco , Silingardi Vittorio , Ascari Edoardo
Published: February 2007

Data on the long‐term treatment of myeloma bone disease with bisphosphonates are scanty. In a prospective pilot trial we evaluated the effect of long‐term parenteral administration of dichloromethylene bisphosphonate (Clodronate), in addition to standard chemotherapy, in 30 patients with active myeloma bone disease. Patients were treated with a mean of 4 courses (range 2–8) of Clodronate: 300 mg/day i.v. for seven days followed by 100 mg/day i.m. for 10 days, administered at a mean interval of 4 months (range 3–6). The median follow‐up was 24 months (range 8–36). Clodronate reduced bone pain rapidly and significantly, and reduced the mean values of the biochemical indices of bone resorption to within normal limits; these effects were maintained throughout the follow‐up. In three hypercalcemic episodes serum calcium became normal after 2–5 days of treatment with Clodronate. No toxic or side effects were noticed. The occurrence of skeletal morbidity in patients treated with Clodronate was compared with that observed in the control group of myeloma patients treated with chemotherapy only: Clodronate provided a significant reduction (p < 0.001) in severe bone pain as well as in the incidence of new osteolytic lesions and pathological fractures (p<0.001). Supportive Clodronate therapy contributes significantly in controlling the progression of myeloma bone disease.
Significance of common acute lymphoblastic leukemia antigen (cALLA) positive cells in bone marrow of children off therapy in complete remission
Authors: Self S. E. , Morgan S. , Grush O. , La Via M. F.
Published: February 2007

Bone marrows from 21 children with acute lymphoblastic leukemia in complete remission (CR) and off therapy for 14 months to 10 years were examined by flow cytometry with a panel of monoclonal antibodies. Significant percentages of cALLA + cells of low fluorescence intensity were present up to 9 years after CR. These results emphasize the need to interpret flow cytometry results in light of the findings that low intensity cALLA + cells represent a normal population of immature, non‐malignant lymphoid cells.
Normal B cell compartment in chronic lymphatic leukemia
Authors: Pluta A. , Górski A. , Nowaczyk M. , Modlińska M.
Published: February 2007

In contrast to normal B lymphocytes, CLL cells express CD5 antigen believed to be a T cell marker. We have assessed normal and malignant B cell compartments in CLL patients with the aid of two‐colour immunofluorescence techniques (CD5‐TRITC, DR‐FITC). No clear correlation was found between progression of disease and parameters studied. However, there was a tendency for a diminution of normal B cells in advanced stages of disease.
Long‐term follow‐up of patients receiving salvage chemotherapy for intermediate and high grade non‐Hodgkin's lymphomas
Authors: Liang Raymond H. S. , Chiu Edmond K. W. , Chan T. K. , Todd David , Ng Ronald P. , Ho Faith F. C. , Loke S. L.
Published: February 2007

This is an analysis of the long‐term follow‐up data of 99 patients receiving HOAP‐Bleo, IMVP‐16 and PAC as salvage chemotherapy for refractory or relapsed intermediate or high grade non‐Hodgkin's lymphomas. Most of the patients received HOAP‐Bleo or PAC following failure of initial chemotherapy and IMVP‐16 was used mainly for HOAP‐Bleo failures. The longest follow‐up time of the surviving patients was 108 months. Twenty‐two and 29 per cent of the patients survived beyond 2 years following HOAP‐Bleo and PAC respectively. The treatment outcome following IMVP‐16 was worst with a 2‐year survival of only 5 per cent, as it was used mainly following HOAP‐Bleo failures. Although the prognosis of these refractory or relapsed cases are poor, salvage treatment is still worthwhile as a small proportion of these patients may have long‐lasting remissions and occasional patients may be cured. Newer approaches such as autologous bone marrow transplantation should be compared with current salvage chemotherapy regimens.
Ifosfamide and mitoxantrone (I‐M) in relapsed and refractory high grade non‐Hodgkin's lymphoma and Hodgkin's disease
Authors: Dovey G. J. , Child J. A. , Simmons A. V. , Barnard D. L. , Parapia L. , Morgan M. , Fletcher J. , Parker D. , Norfolk D. R. , Stone J. , Stuart N. S. A. , Tucker J.
Published: February 2007

Fifty‐five patients, initially diagnosed as having advanced high grade non‐Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first‐line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three‐weekly intervals. Of 32 patients with NHL evaluable for response, 10 (31 per cent) achieved complete remission and five partial remission, giving an overall response rate of 47 per cent. Two patients subsequently went on to bone marrow transplant (BMT)—one allogeneic and the other autologous. Of 17 patients with HD evaluable for response, six (35 per cent) achieved complete remission and six partial remission, giving an overall response rate of 71 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. Given the need to offer alternative treatment of patients in these categories, this combination (I‐M) is clearly of value in relapsed patients especially where therapeutic options are limited because of previous multi‐drug treatment.
Factor X‐activating procoagulant in normal and malignant breast tissue
Authors: El‐Baruni Khaled , Taylor Irving , Roath Stuart , Francis John L.
Published: February 2007

Factor X‐activating activity (FXAA) was determined by a chromogenic assay in normal and malignant breast tissue. FXAA was found in all tissue (n = 38) irrespective of pathology, and the activity of normal tissue was similar to that of tumours. FXAA correlated with tissue hemoglobin in normal breast (p<0.02) but not in tumours. FXAA was markedly reduced by aluminium hydroxide, barium citrate, anti‐human factor VII, DFP, PMSF and phospholipase C, but was unaffected by iodoacetamide and mercuric chloride. It is concluded that FXAA is a serine protease with the properties of a tissue factor‐factor VII complex. FXAA occurs in normal and malignant breast tissue, although the ‘normal’ activity may be an artefact of the homogenization process.
Decrease in clonogenic tumour cells in bone marrow aspirates from multiple myeloma patients due to the incorporation of cyclophosphamide into treatment with vincristine, adriamycin and methyl prednisolone
Authors: Bell J. B. G. , Millar B. C. , Montes‐Borinaga A. , Joffe J. K. , Cunningham D. , Mansi J. , Treleaven J. , Viner C. , McElwain T. J.
Published: February 2007

A study of 32 patients receiving cyclophosphamide (CY) and verapamil (VER) in addition to the drug combination vincristine, adriamycin and methyl prednisolone (VAMP) was made in which the clinical response and growth of clonogenic myeloma cells (MY‐CFUc) from bone marrow aspirates were compared. At presentation, MY‐CFUc were grown from 72 per cent (23/32) of the patients. After treatment with CY‐VAMP or VERCY‐VAMP, MY‐CFUc were grown from 25 per cent (8/32) of patients of whom only 50 per cent responded clinically. The overall clinical response rate for patients receiving CY‐VAMP and VERCY‐VAMP was 64 per cent (9/14) and 72 per cent (13/18) respectively of whom 14 per cent in each group achieved complete remission.

There was no concomitant increase in normal tissue toxicity as measured by granulocyte–macrophage colony (GM‐CFUc) formation. Comparison of these data with our previous study of patients receiving VAMP alone, suggests that the addition of CY to the regimen may increase the tumour cell kill. Further clinical studies will determine whether there is a significant increase in the complete remission rate.