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V Zagonel

Publications and source records attributed to V Zagonel.

At least 55 records · Page 3Linked to original sources
PubMed1997

Rarity of microsatellite genomic instability in B-cell non-Hodgkin's lymphomas in hepatitis C virus-infected patients.

Several groups have emphasized the likely implication of the hepatitis C virus (HCV) in a fraction of B-cell non-Hodgkin's lymphomas. Since only a minority of patients with HCV infection and monoclonal mixed cryoglobulinaemia develop overt lymphoma, the identification of predisposing factors has relevant clinical implications. The replication error phenotype (RER+), as revealed by widespread microsatellite instability, is caused by defects in DNA mismatch repair genes, and has been frequently disclosed in subsets of B-cell lymphomas with underlying infection and chronic inflammation. We therefore investigated the occurrence of the RER+ phenotype in a series of eight consecutive B-cell NHLs in patients with chronic infection by HCV. A polymerase chain reaction-based assay was used to analyse an extended panel of 15 microsatellite loci. Microsatellite instability was not observed in six tumour samples in any locus; the two remaining cases showed instability at only one locus. Therefore genetic instability by defects in DNA mismatch repair genes should not represent the general mechanism predisposing to overt lymphoma in HCV-infected patients. Although a clearer definition of HCV-related B-cell disorders should better address future studies on genetic instability in larger series, we recommend additional oncogenetic pathways as the target of further research.

Adult↗
PubMed1997

Spectrophotometric detection of RT-PCR-amplified BCR/ABL fusion transcripts. A survey performed on archival hematologic slides.

We describe a method of spectrophotometric detection of BCR/ABL chimeric sequences amplified by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), enabling the use of archival hematologic slides as RNA sources. Multiplex PCR amplified b3a2, b2a2, and e1a2 break points of the BCR/ABL translocation and the normal ABL gene product. Assessment of sensitivity, performed on K562 cells, showed that the threshold approximated radioactive methods of detection (i.e., 1 positive cell in 1 x 10(6) negative cells for single round PCR and lower than 1 positive cell in 1 x 10(7) negative cells for nested PCR). Then, we assayed 38 different archival hematologic slides from 18 patients, including 11 cases of chronic myelogenous leukemia or chronic myelogenous leukemia-like disease, such as a case of myelofibrosis and a case of chronic neutrophilic leukemia, 6 cases of acute lymphoblastic leukemia, and 1 case of acute myelogenous leukemia. Amplification and spectrophotometric detection of BCR/ABL fusion messenger RNAs gave an unambiguous positive result in 24 (89%) of 27 expected positive slides, among which 17 (63%) were positive after a single PCR round. Concordant unambiguous results were obtained from 35 (92%) of 38 slides, as verified through parallel analyses of corresponding cryopreserved cells. Retrospective analysis on archival hematologic slides yielded identification of the presence or absence of the t(9;22) translocation and break point in 14 previously uncharacterized cases. The application of this method can help define the diagnosis of cases lacking other appropriate material and assist in the retrospective analysis of large patient series for which only smears are available.

Cell Line↗
PubMed1997

The role of eosinophils in the pathobiology of Hodgkin's disease.

BACKGROUND: Even though the presence of a prominent tissue eosinophilia represents a common histopathologic feature of Hodgkin's disease (HD), eosinophils have been mainly regarded as 'innocent' bystanders recruited and activated during the cellular reaction typical of HD. To evaluate the putative role of eosinophils or eosinophil-derived cytokines on tumor-cell regulation in HD, we have analyzed these cells for the functional expression of surface ligands (L) of the tumor necrosis factor (TNF) superfamily, whose specific receptors are known to transduce proliferation signals at the surface of Hodgkin (H) and Reed-Sternberg (RS) cells. MATERIALS AND METHODS: Eosinophils from peripheral blood of healthy donors and patients with HD, primary hypereosinophilic syndrome (HES), or secondary hypereosinophilia (HE), were purified by density gradient centrifugation and immunomagnetic depletion of residual granulocytes. RESULTS: By immunostaining and mRNA analysis, we were able to show that eosinophils from normal donors and patients with HD, HES, and HE express a number of receptors and ligands of the TNF superfamily, including CD40, CD40L, CD30L, CD95/Fas, CD95/FasL and 4-1BB. In addition, we provide evidence that cytokines regulating eosinophil proliferation and activation, i.e., interleukin (IL)-5, IL-3, and granulocyte-macrophage colony-stimulating factor, are able to enhance the cellular density of several TNF superfamily ligands and/or receptors at the surface of cultured eosinophils. Finally, we have shown that native CD40L and CD30L at the surface of purified eosinophils are functionally active and able to transduce proliferative signals on CD40+ and CD30+ target cells, including cultured H-RS cells. CONCLUSIONS: Our data suggest that eosinophils may act as important elements in the pathology of HD by providing cellular ligands for TNF-superfamily receptors (CD40, CD30, CD95/Fas) able to transduce proliferation and antiapoptotic signals at the surface of H-RS cells. The presence on eosinophils of receptors for TNF ligands expressed by activated T cells (i.e., OX40L, FasL, CD40L, 4-1BBL), also suggest that eosinophils may contribute to the deregulated network of interactive signals between H-RS cells, T cells, and other surrounding reactive cells.

Antigens, Neoplasm↗
PubMed1997

Human granulocyte-macrophage colony-stimulating factor supports the clonogenic growth of B-lineage acute lymphoblastic leukemias expressing myeloid antigens.

The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-6 on clonogenic growth of blast-cell progenitors from 19 immunologically defined CD10-positive B-lineage acute lymphoblastic leukemias (ALL) coexpressing (My+ALLs) or not (My-ALLs) myeloid antigens have been studied. Our results demonstrate that GM-CSF was able to support the clonogenic growth of blast cells from My+ALLs, being totally ineffective on My-All samples. Accordingly, both alpha and beta chains of GM-CSF receptor (R) were expressed by My+ALL blasts, as investigated by reverse-transcriptase polymerase chain reaction (RT-PCR). Colony cells from GM-CSF-stimulated My+ALL cultures displayed the same immunophenotype as primary leukemic cells at diagnosis (CD10+, CD19+, CD22+), and retained the expression of myeloid-associated antigens and of GM-CSF-R transcripts. Moreover, My+ALL blasts showed a preferential sensitivity to the growth-promoting activity of IL-3 and IL-6, as compared with My-ALL cells. In addition to rearrangements of the JH region of immunoglobulin genes, My+ALL cells showed aberrant rearrangements of gamma (three cases) and beta (two cases) T-cell receptor genes, as well as of bcr sequences (three cases). Our data, showing an unexpected cross-lineage response of My+ALLs to GM-CSF, and their preferential stimulation by IL-3 and IL-6, as compared with My-ALLs, further support the concept that My+ALLs represent a separate entity with unique biological features.

Adolescent↗
PubMed1996

Human eosinophils express functional CD30 ligand and stimulate proliferation of a Hodgkin's disease cell line.

The presence of a prominent tissue eosinophilia represents a typical histopathologic hallmark of Hodgkin's disease (HD). To evaluate the putative role of eosinophils on tumor cell regulation in HD, we have analyzed these cells for the functional expression of CD30 ligand (CD30L), a surface molecule able to transduce CD30-mediated proliferation signals on Hodgkin's (H) and Reed-Sternberg (RS) cells. The results demonstrate that circulating and tissue eosinophils from normal donors and patients with HD or hypereosinophilic syndrome (HES), display CD30L mRNA and express CD30L protein, as shown by immunostaining with a specific monoclonal antibody (M80) and with a biotinylated soluble CD30-Fc fusion protein. The surface density of CD30L on eosinophils from HD and HES patients was remarkably higher compared with healthy donors, probably reflecting a cytokine-mediated upregulation in these pathologic conditions. Accordingly, we provide evidence that cytokines regulating eosinophils proliferation and activation, ie, interleukin-5 (IL-5), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF), are able to enhance the cellular density of CD30L on purified eosinophils from normal subjects. Finally, we show that native CD30L on human eosinophils is a functionally active surface structure able to transduce proliferative signals on CD30+ target cells, including cultured H-RS cells. Our data suggest that eosinophils may not merely represent innocent bystanders, but rather act as important elements in the pathology of HD by contributing to the deregulated network of CD30/CD30L-mediated interactive signals between H-RS cells and surrounding reactive cells.

CD30 Ligand↗
PubMed1996

Validation of a multidimensional evaluation scale for use in elderly cancer patients.

BACKGROUND: Although aging is one of the most important risk factors for cancer, elderly patients tend to be excluded from cancer clinical trials, only on the basis of chronologic age. Performance Status (PS) has been used widely to select adult patients for entry into clinical trials, but it does not include a comprehensive evaluation of various age-related factors in the elderly. This study was designed to assess the reliability and validity of a multidimensional geriatric assessment protocol for elderly patients with cancer. METHODS: Thirty consecutive elderly patients (> or = 65 years), diagnosed with hematologic neoplasia or solid tumors and undergoing chemotherapy or radiotherapy, were given a specifically structured multidimensional questionnaire (MACE) three times during one week by two different physicians. MACE was intended to collect information on demographics, socioeconomic status, cognitive status, depression, physical performance, disability, and tumor characteristics. In parallel with MACE, information was collected by means of the Sickness Impact Profile (SIP). RESULTS: Both for inter-rater and test-retest reliability, the values of the intraclass correlation coefficient (ICC) were generally higher than 0.7. Disability, cognitive status, depressive symptoms, and the number of days spent in bed sick in the last two weeks were markedly correlated with the global, physical, and social SIP score. Disability alone explained 70% of the variance in the SIP global score, 83% of the variance in the SIP physical score, and 45% of the variance in the SIP psychosocial score. MACE proved to be applicable in a reasonable amount of time (around 30 minutes) for a medical oncology ward. CONCLUSIONS: These data indicate that this structured evaluation of functional status is feasible and reliable. MACE is therefore proposed as a clinical research tool to avoid arbitrary decisions on patient selection for enrollment in clinical trials, to favor uniform monitoring of treatment, and to allow a better comparison of results.

Aged↗
PubMed1996

Hepatitis C virus and non-Hodgkin's lymphomas.

Hepatitis C virus (HCV) seems to be the aetiologic agent of mixed cryoglobulinaemia, and as this 'benign' lymphoproliferative disorder can frequently develop into more aggressive haematological disorders, this study was undertaken to determine the prevalence of HCV infection in non-Hodgkin's lymphomas. 199 unselected subjects treated by three haematological centres in Northeast Italy were investigated for the presence of HCV infection. As controls, the prevalence of HCV infection was determined in a group of patients affected by other haematological malignancies (153 subjects) and in the general population of the same geographical area in the cohort study called the Dyonisos project (6917 subjects). The presence of anti-HCV antibodies was determined by a commercial kit and, in positive cases, by PCR amplification of the 5' untranslated region of the virus. The HCV genotype was also obtained by PCR amplification of the Core region with type-specific primers. The presence of serum cryoglobulins was determined in each case of NHL. HCV infection was significantly (P < 0.00000001) higher in patients with non-Hodgkin's lymphomas (28.0%) when compared with that of the general population (2.9%), and with the group of patients affected by other malignancies (3.1%). The prevalence is particularly high in low-grade (38.4%), as compared with intermediate (11.4%), or high-grade (15.2%) lymphomas. The presence of the virus is significantly (P < 0.000001) associated with the presence of detectable levels of cryoglobulins. On the basis of these findings. HCV seems to play an important role in the development of low-grade non-Hodgkin's lymphomas.

Adult↗
PubMed1996

Kaposi's sarcoma-associated herpesvirus DNA sequences in AIDS-related and AIDS-unrelated lymphomatous effusions.

Primary effusions presenting as the sole lymphoma localization are also known as body-cavity-based-lymphoma (BCBL), and have been shown to carry Kaposi's sarcoma herpesvirus (KSHV) DNA sequences. The aim of this study was a comparative analysis of the clinical, pathologic and molecular features of BCBL and lymphomatous effusions secondary to tissue-based lymphomas occurring both in the general population and in HIV-1-infected individuals. All the lymphomatous effusion samples (seven AIDS-related and nine AIDS-unrelated) were subjected to an identical multiparameter investigation, including collection of clinical data, analysis of morphology and immunophenotype, as well as the study of viral sequences and genetic lesions. In six cases defined as BCBL (four AIDS-related and two AIDS-unrelated), the patients exhibited exclusive or predominant involvement of the body cavities. BCBL tended to display indeterminate phenotypes (4/6), whereas all AIDS-related and AIDS-unrelated lymphomatous effusions secondary to tissue-based lymphomas consistently expressed B-cell phenotype. Detection of KSHV DNA sequences was restricted to cases of BCBL (3/4 AIDS-related and 1/2 AIDS-unrelated), whereas EBV association (3/4) and expression of EBV-encoded antigens (LMP-1, 2/3; EBNA-2, 1/3) were confined to the AIDS-related BCBL. Overall, our results confirm that both AIDS-related and AIDS-unrelated BCBL preferentially associate with peculiar clinical, immunophenotypic and molecular features among lymphomatous effusions and therefore should be singled out as a specific clinico-pathologic entity.

Adult↗
PubMed1996

CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues.

The CD30 ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and malignant tissues.

Antibodies, Monoclonal↗
PubMed1995

The expression of CD26 and CD40 ligand is mutually exclusive in human T-cell non-Hodgkin's lymphomas/leukemias.

CD26 and CD40 ligand (CD40L) are surface molecules on human activated T lymphocytes that play a critical role in the regulation of lymphopoiesis. Both molecules are expressed on a restricted fraction of human T-cell non-Hodgkin's lymphomas (NHL)/leukemias; however, little is known about their functional and/or clinical significance in these disorders. In this study, the pattern of expression of CD40L was compared with that of the CD26 molecule. A series of 67 human T-cell NHL/leukemias and a panel of leukemia/lymphoma T-cell lines were evaluated by immunohistochemistry, flow cytometry, and RNA studies. The overall frequency of CD26+ and CD40L+ samples was rather similar (25/67 [37%] v 18/67 [27%]). However, the majority of CD26-expressing cases clustered in the lymphoblastic lymphomas (LBL)/T-acute lymphoblastic leukemias (ALL; 12/23) and CD30+ anaplastic large-cell (ALC) lymphomas (5/8), whereas CD40L+ lymphomas included a large fraction of mycosis fungoides (11/21 [52%]). CD26 and CD40L coexpression was found only in 2 myocosis fungoides cases and 1 small lymphocytic lymphoma. Thus, the expression of the two antigens was mutually exclusive in almost all T-cell lymphomas/leukemias. Accordingly, lymphoma cell lines expressed either one of the molecules or the relative amounts of CD26 and CD40L were inversely proportional. In contrast, reactive T lymphocytes from patients with non-neoplastic T-cell expansions and in vitro activated CD3+ or CD4+ normal T cells were found to coexpress CD40L and CD26. Results of a multivariate analysis showed that the expression of CD26 in T-cell LBL/ALL patients was associated to a worse outcome in terms of survival, as compared with patients with CD26- tumors (P < or = .0001). Based on our results, it can be concluded that, (1) as opposed to activated or reactive normal T cells, the expression of CD26 and of CD40L is mutually exclusive in human T-cell lymphomas/leukemias; (2) expression of CD26 is restricted to aggressive pathologic entities, such as T-cell LBL/ALL and T-cell CD30+ ALC lymphomas, whereas CD40L is expressed on slow progressing diseases such as mycosis fungoides; and (3) within the T-cell LBL/ALL group of tumors, CD26 may identify a subset of poor prognosis patients.

Adolescent↗
PubMed1995

Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's disease cell lines.

CD40 is a member of the nerve growth factor receptor family, showing a significant homology to the Hodgkin's disease (HD)-associated antigen CD30 and is capable of transduce growth signals in a number of cell types. A series of 312 lymphoma samples, including 139 cases of HD, 32 cases of CD30+ anaplastic large cell (ALC) lymphomas, 141 cases of other non-Hodgkin's lymphomas (NHLs), and a panel of HD- or NHL-derived cell lines, were evaluated for CD40 expression by immunostaining of paraffin embedded sections, cell smears and flow cytometry. CD40 was strongly expressed with a highly distinct pattern of staining on Reed-Sternberg (RS) cells and variants in 100% (139/139) of HD cases, irrespective of their antigenic phenotype (T, B, non T-non B) and histologic subtype of HD. Conversely, CD40 was immunodetected on only one third (12/32; 37%) of ALC lymphoma cases and on 105 of 127 B-cell NHLs. The relative cell density of CD40 on HD cell lines (L-428, KM-H2, HDLM-2) as assessed by flow cytometry was significantly higher than on all other lymphoma cells analyzed. Engagement of CD40 by its soluble ligand (CD40L) enhanced both clonogenic capacity and colony cell survival of HD cell lines. Such effect was potentiated by interleukin-9 costimulation in KM-H2 cells. Finally, we have shown that in vitro rosetting of activated CD4+ T cells to HD cells (L-428) is mediated in part by the CD40/CD40L adhesion pathway. Our data indicate that CD40 is a useful antigen for immunodetection and identification of tumor cells in all subtypes of HD, and suggest that it may play a role in the regulation of RS cell expansion and the contact-dependent interactions of these cells with cytokine-producing T lymphocytes.

Animals↗
PubMed1995

CD30 (Ki-1)-positive anaplastic large-cell lymphomas in 13 patients with and 27 patients without human immunodeficiency virus infection: the first comparative clinicopathologic study from a single institution that also includes 80 patients with other human immunodeficiency virus-related systemic lymphomas.

PURPOSE: CD30 (Ki-1)-positive anaplastic large-cell lymphoma (Ki-1 ALCL) rarely has been described in patients with human immunodeficiency virus (HIV) infection. The purpose of this study was to characterize further the clinicopathologic features of Ki-1 ALCL in patients with HIV infection and, for the first time, to make a comparison with Ki-1 ALCL in patients without HIV infection. PATIENTS AND METHODS: From September 1987 to April 1993, 93 patients with HIV infection and systemic non-Hodgkin's lymphoma (NHL) were treated at the Cancer Center of Aviano, Italy; in 13 (14%), the diagnosis was of Ki-1 ALCL subtype. This group of patients was compared with the remaining 80 patients who had other HIV-related NHL and with another group of 27 patients with Ki-1 ALCL who were without a diagnosis of HIV infection. RESULTS: There was no case of a T-cell phenotype in the 13 HIV-positive Ki-1 ALCL patients, whereas there was such a phenotype in six of 27 (22%) HIV-negative Ki-1 ALCL patients. In regard to the general characteristics of the two groups with Ki-1 ALCL, more patients with stage IV, two or more extranodal sites at presentation, treatment-related leukopenia, and opportunistic infections as the cause of death were observed in the HIV-positive Ki-1 ALCL group. When these variables were compared with those of the other HIV-related NHL group, such differences were not present. CONCLUSION: Ki-1 ALCL is not a rare clinicopathologic entity among NHL in patients with HIV infection. The differences observed within the two Ki-1 ALCL groups of patients may be because of factors related to the HIV infection alone.

Adult↗
PubMed1995

Clinical Trials in Older Patients With Intermediate and High-Grade Lymphomas.

The number of studies concerning non-Hodgkin's lymphoma (NHL) in elderly patients has increased in the last few years. However, the effectiveness of treatments specifically devised for elderly patients with aggressive lymphoma must be determined despite a trend towards reduction of treatment-related death. Direct comparison of trial results is difficult since different age limits were set for the inclusion of patients on study, but we can confirm that the complete response rate decreases with increasing age. Comparison of results even among trials conducted on patients of the same age remains difficult due to the lack of homogeneity in prognostic factors related to the NHL as well as to associated comorbidity, mental status, physical activity and family and social status.

Journal Article↗
PubMed1995

Gastroduodenal involvement in staging of nodal non-Hodgkin lymphomas: a clinical and endoscopic prospective study of 235 patients.

OBJECTIVES: The gastrointestinal tract is often the site of involvement of non-Hodgkin lymphomas (NHL). The aim of this endoscopic prospective study was to verify the prevalence of the gastroduodenal involvement in patients in staging for NHL and to assess its impact on the choice of therapeutic strategies. METHODS: Two hundred and thirty-five consecutive patients were included in the study. Upper gastrointestinal endoscopy was performed, and biopsy samples were taken on every mucosal lesion and on macroscopically illness-free duodenal and gastric mucosa. The samples were submitted to histological examination, and the clinical stage of NHL was reevaluated. RESULTS: Sixty-one of the 235 patients exhibited histological involvement of gastric (40), duodenal (7), or both (14) mucosae. Endoscopic lesions were recorded in 51 patients, but the involved mucosa appeared macroscopically normal in 10 patients (16.3%). In 13 patients, the gastroduodenal involvement modified the clinical stage from I and II to III, indicating a different therapeutic approach. No difference was detected in the frequency of gastrointestinal involvement among the high, intermediate, and low grades of lymphoma malignancies. Thirty-five positive patients underwent a further endoscopic examination after the chemotherapy treatment. Although clinical remission was expected in all cases, 42.8% of them subsequently exhibited NHL. CONCLUSIONS: Upper digestive endoscopy plus biopsy sampling plays a necessary diagnostic role, not only when major clinical signs (hemorrhage) are present, but also in earlier stages of NHL (I and II), when a reevaluation of the therapeutic strategy may be indicated. In stages III and IV of illness, it may also prove useful in evaluating the efficacy of chemotherapy.

Biopsy↗
PubMed1994

Total body irradiation and prednimustine in chronic lymphocytic leukemia and low grade non-Hodgkin's lymphomas. A 9-year experience at a single institution.

BACKGROUND: The efficacy and toxicity of total body irradiation (TBI) in patients with chronic lymphocytic leukemia (CLL) and low grade non-Hodgkin's lymphomas (NHL) were evaluated. METHODS: Between January 1984 and September 1992, 81 consecutive patients, 40 affected with CLL and 41 with low grade NHL, with symptomatic Stage III and IV disease, were treated with TBI followed by prednimustine. TBI was given with a 6 MV linear accelerator, applying two opposite alternating fields, including total body, with two fractions of 15 cGy given per week (3-day interval). A total dose of 150 cGy was given over 5 weeks. Six to nine courses of prednimustine (100 mg/m2 orally for 5 consecutive days every 4 weeks) was administered 2 months after TBI treatment as consolidation therapy. RESULTS: Of 40 patients with CLL, 18 (Group I; median age 58.5 years) were younger than 65 years and 22 (Group II; median age 73 years) were older. The overall response rates were 78% in Group I and 91% in Group II, with a median response time of 16.5 and 16 months, respectively. Hematologic toxicity was 72% in Group I and 73% in Group II. It was reversible in all but one heavily pretreated patient who died of progressive anemia and thrombocytopenia after TBI alone. In the 40 patients with CLL, the response rate was 85%; there were 5 complete responses (CRs) (12.5%) and 29 partial responses (PRs) (72.5%). Of the 41 patients with NHL, 29 (Group I; median age 55 years) were younger than 65 years and 12 (Group II; median age 71.5) were older. The overall response rate in both groups was 83%, with median response times of 18.5+ and 14.5+ months for Groups I and II, respectively. Hematologic toxicity was 59% in Group I, whereas it was 50% in Group II. It was reversible in all patients. Overall, in the 41 patients with symptomatic Stage III and IV low grade NHL, the response rate was 82.8%; there were 10 CRs (24.3%) and 24 PRs (58.5%). The prednimustine regimen was generally well tolerated. CONCLUSIONS: In our experience, TBI given in a dose of 150 cGy in 10 fractions twice a week, followed by prednimustine, is an effective treatment for patients with CLL and patients with low grade NHL. This treatment also is effective in patients older than 65 years. The toxicity is acceptable, particularly when TBI and prednimustine are given as initial treatment. Pretreated patients should be monitored strictly.

Age Factors↗
PubMed1994

Expression of the c-kit receptor in human lymphomas is restricted to Hodgkin's disease and CD30+ anaplastic large cell lymphomas.

The product of the proto-oncogene c-kit is a transmembrane receptor protein that plays an important role in the regulation of normal and neoplastic hematopoiesis via the interaction with its specific ligand termed stem cell factor. To examine whether c-kit product is possibly involved in the pathogenesis of human lymphomas, we analyzed the expression of the c-kit protein in neoplastic cells from a variety of lymphoid tumors by immunostaining of lymph node frozen sections with the 17F11 antibody, detecting an extracellular epitope of the c-kit receptor, and of c-kit RNA by Northern blot hybridization. Of 24 nonHodgkin's lymphomas (NHL) of B- and T-cell phenotype, none expressed immunodetectable c-kit protein that was also not evidenced in lymphoid cells of reactive lymph nodes and normal tonsils. In contrast, c-kit protein was expressed by Reed-Sternberg cells and their mononuclear variants from 11 of 21 Hodgkin's disease (HD) cases, and in tumor cells from 11 of 16 cases of CD30+ anaplastic large cell lymphoma (ALCL). c-kit specific mRNA was also detected in lymph node tissues from HD and ALCL cases but not in neoplastic tissues from NHL other than ALCL. In addition, c-kit/CD30+ tumor cells were evidenced by flow cytometry in a patient displaying massive bone marrow involvement by ALCL. With the exclusion of lymphocyte predominance cases of HD that resulted c-kit expression and the other histologic subtypes of HD or the immunologic phenotype of tumor cells (B, T, nonB-nonT) in both HD and ALCL. The highly restricted expression of the c-kit product among human lymphomas to HD and ALCL provides a further biologic link between these two closely related lymphoma entities.

Hodgkin Disease↗