Published by: the National Cancer Insitute at: http://cancernet.nci.nih.gov
CITATIONS AND ABSTRACTS FROM THE NCI'S CANCERLIT DATABASE
Telomerase activity has been demonstrated in various types of cancers including lymphoid neoplasms. The tumour specificity of telomerase activity has been a subject of debate since the description of detectable enzymatic activity in non neoplastic tissues. We and others have demonstrated that such activity was present in non Hodgkin's lymphomas as well as in reactive hyperplastic lymph nodes and tonsils. However, we at the same time were surprised by the absence of telomerase activity in most cases of Hodgkin's disease. We have extended our previous study by adding additional cases and confirm that in the majority of cases, Hodgkin and Reed-Sternberg cells lack telomerase activity (only 2 cases positive out of 20). These results may indicate that the tumour cells of Hodgkin's disease evolve different pathways for maintaining the length of their telomeres during the process of becoming immortal.
Forty-eight autografted patients were studied after treatment with granulocyte-colony stimulating factor (G-CSF) and were compared with a historical series of 24 patients autografted with bone marrow (BM) without G-CSF. When the patients were divided on the basis of G-CSF administration, type of lymphoma and the source of hemopoietic stem cells, no significant difference was found in the median number of infused BM cells, duration of febrile episodes, platelet and hemoglobin recovery, or in the number of transfusions. The patients receiving peripheral blood (PB) + G-CSF had significantly shorter median durations of antibiotic therapy, hospital stay and polymorpho- nucleate (PMN) recovery. When the Hodgkin disease (HD) and non- Hodgkin lymphoma (NHL) cases were considered separately, a significa- nt difference between those receiving and those not receiving G-CSF was observed only in the HD group. The advantage offered by PB + G-CSF over BM + G-CSF was far more evident in the NHL group than in HD. It can be concluded that G-CSF improves the outcome of BM transplant in HD, and that the use of PB + G-CSF adds a further advantage; conversely, in NHL, PB + G-CSF is strikingly superior to BM + G-CSF, but the addition of G-CSF adds little advantage.
Twenty three HIV+ patients with cancer (2% of the infected populatio- n: 1100 patients) were treated at our Hospital between January 1987 and July 1997. Twelve patients (52%) had Kaposi's sarcoma (KS), five (22%) presented non Hodgkin lymphoma--B cell type (NHL), the remaining patients presented other non AIDS defining neoplasias. The patients with NHL presented, at the time of diagnosis, several infrequent localizations, poor tolerance to chemotherapy with a mean survival of 3 months. The patients with Kaposi sarcoma had neither positive response to recombinant Interferon alfa 2 nor to the etoposide regimens. A relatively high percentage (13%) of Hodgkin- disease (HL) was observed. Unlike previously consulted data, there was no apparent increased incidence of NHL. HIV+ patients with cancer who underwent conventional radiotherapy presented major toxicity and adverse effects not currently observed in non HIV+ patients.
Here we describe the case of a 14-year-old boy who underwent liver transplantation for post-Kasai biliary atresia when aged 4. Antirejection treatment consisted of prednisone and cyclosporine. At the age of 11 years the patient developed left cervical lymphadenopa- thy; the biopsy showed classical Hodgkin's disease(HD) of the mixed cellularity (MC) type. Neoplastic cells expressed CD30 and CD15, and were negative for CD45, CD20, CD3, CD43, and CD79a. Furthermore, they carried the EBV-related products LMP1 and EBER1/2. Treatment consisted of three cycles of adriamycin, bleomycin, vinblastine and DTIC (ABVD), followed by radiotherapy (2,000 cGys) on involved fields. At present, 42 months after the diagnosis of HD, the patient is still in complete remission. This is, to the best of our knowledge, the first reported case of classical HD following liver transplantation. The positivity of neoplastic cells for LMP1 and EBER1/2 indicates a possible role for immunosuppression in the development of the tumor, and whether a reduction in immunosuppressi- on might have influenced the course of the disease is open to question.
PURPOSE: A new regimen, MVC (mitoxantrone, vinblastine, and CCNU [lomustine]), was studied in advanced Hodgkin's disease. This regimen combines the most effective elements of previous regimens for poor-prognosis Hodgkin's disease and eliminates agents with unnecessary toxicities and marginal activity. Initially, patients with relapsed or refractory disease were entered, and after substantial activity was observed, patients with advanced-stage, newly diagnosed Hodgkin's disease were also treated. PATIENTS AND METHODS: Thirty-six relapsed or refractory patients were entered on this study. Prior treatment included radiotherapy alone (three patients), combined-modality treatment (n = 21), and single (n = 2) or multiple chemotherapy regimens (n = 10). Seventeen advanced-stage (bulky IIB-IVB) newly diagnosed Hodgkin's patients were also entered, with a median follow-up of 7 years. RESULTS: Thirty-two of 36 (88%) relapsed/refractory patients responded to MVC, with 18 partial responses (50%) and 14 complete responses (39%). Median complete response duration is 20 months (range, 2 to 108+ months). The median survival of all previously treated MVC patients is 28 months (range, 4 to 127+ months). Eleven of 32 previously treated MVC responders remain alive and disease-free at 12 to 127+ months, seven after autologous bone marrow transplantation (12 to 127+ months) and four after MVC without transplantation (31 to 113+ months). Thirteen of 17 advanced-stage, newly diagnosed Hodgkin's disease patients achieved a complete response and four achieved a partial response to MVC (100% response rate). Two complete response and all partial response patients have relapsed. Eight complete responses are ongoing at 11 to 114+ months. Three patients died in complete response at 11, 42, and 43 months. Median response duration has not been reached. DISCUSSION: MVC is a highly active regimen in relapsed and advanced-stage Hodgkin's disease, with outcome results comparable to other established regimens. Treatment is associated with myelosuppression but is otherwise well tolerated. MVC provides an effective alternati- ve regimen for newly diagnosed patients with Hodgkin's disease and an effective salvage regimen for patients previously treated with anthracyclines.
Immunotoxins (ITs) consisting of a cell-binding component and a potent toxin were developed as a new class of biological anti-tumor agents to improve adjuvant therapy. Hodgkin's lymphoma (HL) has been demonstrated to be an excellent target for ITs because high concentrations of lymphocyte activation markers such as CD25 and CD30 are expressed on Hodgkin and Reed-Sternberg (H-RS). Several ITs against these antigens have shown potent antitumor effects against H-RS cells in vitro and in different HL animal models. On the basis of its superiority in preclinical models, the anti-CD25 IT RFT5-SMPT- dgA was subsequently evaluated in a phase I study in patients with refractory Hodgkin's lymphoma. The IT was constructed by linking the monoclonal antibody (Moab) RFT5 via a sterically hindered disulfide linker (SMPT) to deglycosylated ricin A-chain (dgA). All 15 patients enrolled in this trial were heavily pretreated with a mean of five different prior therapies. The IT was administered intravenously over four hours on days 1-3-5-7 for total doses per cycle of 5, 10, 15, or 20 mg/m2. Side effects were reversible and related to the vascular leak syndrome (VLS), i.e. decrease in serum albumin, edema, weight gain, hypotension, tachycardia, myalgia, and weakness. In all three patients receiving 20 mg/m2 NCI toxicity grade III was observed. Thus, 15 mg/m2 is the maximal tolerated dose (MTD) of RFT5-SMPT-dgA. 50% of the patients developed human anti-ricin A-chain antibodies (HARA) and/or human anti-mouse antibodies (HAMA). Clinical results included two partial remissions (PR), one minor response (MR), three stable disease (SD) and nine progressive disease (PD). In an extension of the phase I trial, five additional patients have been treated at the MTD.
We performed a randomized clinical trial to assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with advanced Hodgkin's disease in complete remission (CR) after conventional chemotherapy. One hundred and thirty-five patients (stage IIIB-IV B) were initially treated with EBVD (epirubicin, bleomycin, vinblastine, dacarbazine). IF CR was achieved they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU three times a week for one year or no further treatment (control group). Clinical and laboratory characteristics at diagnosis were quite similar in both groups. After a median follow-up of 74.3 months (range 49 to 108), 61 out of 68 patients (91%; 95% confidence interval (CI): 76% to 97%) remain in first complete remission in the IFN-treated group compared to 38 out of 67 (58%; 95% CI: 49% to 71%) in the control group (p<.01). Overall survival was also better in the IFN treated group: 62 patients (92%; 95% CI: 82% to 97%) are alive free of disease at 7-years compared to 40 patients (67%, 95%: 55% to 76%) in the control group (p<.01). Toxicity secondary to IFN administration was mild and no dose modification was necessary during treatment. All patients received the planned dose of IFN. This was not an intent-to treat analysis. IFN administration as maintenance therapy was appears to be the only cause of improvement in outcome in these patients. We feel that IFN should be considered as maintenance therapy in patients with advanced Hodgkin's disease because this treatment improves the final outcome without the excessive toxicities of more aggressive therapeutic approaches such as bone marrow transplantation during first CR. We hope that IFN will be considered in future randomized clinical trials in order to define it's role in the treatment of Hodgkin's disease.
Tc-99m MIBI is used as a tumor imaging agent and has been proposed to measure p-glycoprotein function, which plays an important role in tumor multidrug resistance to chemotherapy. It has been reported that lung cancer and breast cancer with a high retention of Tc-99m MIBI have been more responsive to chemotherapy than tumors with low retention. Thus Tc-99m MIBI SPECT could be used as a measure of p glycoprotein function and consequently may serve as a predictor of the tumor's responsiveness to chemotherapeutic agents. Described here are two patients with lymphomas, one with non-Hodgkin's lymphoma and the other with Hodgkin's disease, who underwent Tc-99m MIBI thoracic SPECT before and after chemotherapy. The sequential studies demonstrated a reduction in tumor size and diminished tumor uptake in one patient and disappearance of tumor uptake after a course of chemotherapy in the other patient. The data suggest that elevated Tc-99m MIBI uptake in a tumor as a result of retention by p glycoprotein not only demonstrates mediastinal involvement of lymphomas but also may be used to forecast responsiveness to chemotherapy.
Thirty-five adult patients with high-risk HD (HD) defined by (1) Ann Arbor stage IV or bulky nodal disease (tumor/thorax ratio > 0.45) and (2) no or partial response (PR) (< 75%) to the initial 3 courses of ABVD, received an early intensive therapy with autologous stem cell transplantation (ASCT). Thirty patients were considered as partial responders and 5 as refractory to initial chemotherapy. Conditioning regimen consisted of chemotherapy alone (CBV in 11 patients before 1993, BEAM in 13 patients since 1993) followed by adjuvant radiother- apy: 40 Gy) on the initial sites of bulky disease, or 12 Gy total body irradiation plus 120 mg/kg cyclophosphamide in 11 patients with disseminated extra-nodal disease. All 30 patients in PR at the time of ASCT experienced prolonged complete remission (CR). One patient died in CR from an acute myocardial infarction 48 months after ASCT. Four out of the 5 patients with refractory disease at the time of ASCT experienced rapid progression of HD leading to death in 3 cases. After 6 years of CR post-ASCT, the last refractory patient died of myelodysplastic syndrome diagnosed 2 years after intensive therapy. With a median follow-up for surviving patients of 51 months (range: 11-111), the cumulative probability of 8-year overall survival is 75.6% for the entire group of patients, 94.1% for the chemosensitive ones, and 0% for the primary refractory (P < .0001). The cumulative probability of 8-year event-free survival is 79.9% for the entire group of patients, 94.1% for the chemosensitive ones, and 0% for the primary refractory (P < .0001). We conclude that early intensive therapy with ASCT is feasible in patients with high-risk HD and induces a high cure rate in chemosensitive patients. In primary refractory patients, new therapeutic approaches are warranted.
Hodgkin's disease primarily originating from the chest wall is very rare. A 48-year-old man was admitted to our hospital because of an abnormal shadow on a chest X-ray. Radiographic examinations suggested a neurogenic tumor located in the right second-intercostal space, and it was thus extirpated thoracoscopically. The tumor was thought to have arisen from the subpleural space, probably from a lymph node of the chest wall. The resected specimen measured 5.5 x 2.0 cm in size, and the pathological diagnosis was Hodgkin's disease of the diffuse lymphocyte predominant type. A clinical examination showed no other lesions in any other part of the body, including the bone marrow. Following surgery, adjuvant chemotherapy (COPP-ABVD) was given because of the possible scattering of malignant cells during surgery. To the best of our knowledge, this is the first report of Hodgkin's disease originating in the chest wall.
Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1. sCD106) were significantly elevated in patients with Hodgkin's disease (HD) (n = 101) compared to controls (n= 31) (P<0.0001). sVCAM-1 correlated with histology, stage, B-symptoms, and prognostic markers (sICAM-1, sCD30, sIL-2R, LDH). sVCAM-1, sICAM-1 and sCD30 added independent prognostic information for both disease-free and overall survival. 14 biopsies from 13 patients with HD were immunostained for VCAM-1 and ICAM-1. The vascular endothelium stained positive for VCAM-1 in 10/12 evaluable biopsies and for ICAM-1 in all evaluable biopsies. A stromal expression of both adhesion molecules precluded a precise evaluation of HRS-cells. This led us to investigate VCAM-1 (and ICAM-1) expression in six Hodgkin cell lines (HDLM-2, L428, L540, L591, DEV, KM-H2). Two cell lines stained positive for VCAM-1 (HDLM-2, L591). All cell lines stained positive for ICAM-1. sVCAM-1 is a new prognostic marker in HD; its predictive power equals or surpasses that of sCD30 and sICAM-1. Furthermore, two Hodgkin cell lines stained positive for VCAM-1. This indicates that VCAM-1 may be expressed by some HD tumour cells in vivo.
Autologous stem-cell transplantation has become a widely used therapy in Hodgkin's disease (HD). To appreciate the early and late risks associated with this procedure, its lethal toxicity and effects on the incidence of secondary cancers were studied. Data related to 467 French patients grafted from 1982 to 1995 for primary sensitive disease (PSD, 22%), primary refractory disease (PRD, 18%), first relapse (R1, 45%), or subsequent relapses (R2, 15%) were analyzed. Grafted patients (PSD, PRD, and R1; n = 393) were matched (3 controls for 1 case) on age, gender, clinical stage, B symptoms, and time at risk with 1179 conventionally treated patients issued from internati- onal databases. The proportional hazards (Cox) model was used to assess relative risks (RR). Among grafted patients, 8% died of toxicity related to the procedure, and 18 secondary cancers occurred leading to a 5-year cumulative incidence rate of 8.9%. In this series, risk factors for second cancer were age >/=40 years (RR = 3.73, P = .007) and the use of peripheral blood stem cells as source of graft (RR = 3.10, P = .03). Among grafted and matched ungrafted patients, risk factors for the development of secondary cancer were age >/=40 years (RR = 2.90, P < .001), relapse versus no relapse (RR = 5.22, P = .006), PRD versus other patients (RR = 3.86, P = .033), and grafted versus ungrafted patients (RR = 2.04, P = . 024). Solid tumors were more frequent in grafted than in ungrafted patients (RR = 5.19, P = .001) although the incidence of myelodysplasia and acute myeloid leukemia was similar in the two groups. We conclude that high-dose chemotherapy administered as first-line treatment or after relapse is associated with an acceptable toxic death rate. The risk of secondary myelodysplasia or acute myeloid leukemia is not significantly increased after autologous stem-cell transplantation for HD, whereas an increased risk of solid tumors exists. The peripheral blood stem-cell-associated risk of secondary cancer among grafted patients needs further investigations. Copyright 1998 by The American Society of Hematology.
CD25 and CD30 represent suitable target molecules for bispecific antibody (bimAb)-driven toxin delivery to lymphoid tumour cells. We describe two new anti-CD30/anti-saporin bimAbs (termed CD30 x sap1 and CD30 x sap2), produced by hybrid hybridomas, which react against non-cross-reactive epitopes of the saporin molecule, and compared their effect with a bimAb reacting with saporin and with CD25 (CD25 x sap1). In a protein synthesis inhibition assay these bimAbs were able to enhance saporin toxicity (IC50 = 8.5 x 10(-9) M in the absence of mAbs) with a similar activity: in the presence of 10(-9) M CD30 x sap1 bimAb the IC50 was 2.75 x 10(-11) M, whereas with CD30 x sap2 bimAb the IC50 was 6.5 x 10(-11) M and CD25 x sap1 bimAb displayed an IC50 of 3 x 10(-11) M (as saporin). The combined use of the two anti-CD30 bimAbs further increased cytotoxicity by 100-fold, resulting in an IC50 of 1.9 x 10(-13) M. A slightly less efficient improvement was obtained by combining the CD25 x sap1 bimAb with the CD30 x sap2 bimAb directed against a different toxin epitope (saporin IC50 to 7 x 10(-13) M). In contrast, no synergistic effect was observed using the combination of the anti-CD25 bimAb with the anti-CD30 bimAb reacting with the same epitope of saporin (IC50 = 4.5 x 10(-11) M). Analysis of FITC-saporin binding to L540 cells by flow cytometry demonstrated that the appropriate combinations of the two anti-CD30/anti-saporin bimAbs or of the anti-CD30/anti-saporin and anti-CD25/anti-saporin bimAbs had a cooperative effect on the binding of the ribosome-inactivating protein (RIP) to the cells, when compared with single bimAbs.
Explorative laparotomy with ensuing splenectomy in Hodgkin's disease is applied for the first time in the Stanford University in the late 60-ies. Opinions on the pros and cons of the method in terms of number of cases, complications and the like are largely dissenting. The analysis covers 153 patients with Hodgkin's disease subjected to splenectomy. Primary diagnosis is made on the ground of lymph node biopsy. Wide spreading of the disease, coincidence of diagnoses in different locations and complications are briefly discussed, with recommendations made concerning improvement of the organization of sample handling and correlation with the clinical findings.
We report two patients with Hodgkin's disease on chemotherapy, one with vincristine, the other with vinblastine, who were referred to the ENT department with a vocal fold palsy. These drugs are commonly used in the treatment of haematological malignancies, and head and neck sarcomas. Examination showed a unilateral immobile fold. No causative local pathology was identified, and they were otherwise thought to be achieving remission, but the development of a fold palsy suggested a poor response to treatment. One patient's palsy resolved following completion of chemotherapy, but the other patient's persists, despite an otherwise good response to the treatment. The vinca alkaloids are neurotoxic, usually causing a peripheral neuropathy, but cranial mononeuropathies are a rare side-effect. A total of 27 previous cases of vocal fold palsy have been reported with the use of the vinca alkaloids, and such a lesion should not be assumed to be due to advancing lymphoma.
The tumor cells in most cases of Hodgkin's disease (HD) have been recently recognized to originate from the B-cell lineage, but their precise differentiation stage is not fully clarified. Recently, we have reported that the histogenesis of B-cell lymphomas may be assessed by monitoring the expression pattern of BCL-6, a transcript- ion factor expressed in germinal center (GC) B cells, and CD138/ syndecan-1 (syn-1), a proteoglycan associated with post-GC, terminal B-cell differentiation. In this study, we have applied these two markers to the study of HD histogenesis. We have found that in nodular lymphocyte predominance HD (NLPHD) tumor cells consistently display the BCL-6(+)/syn-1(-) phenotype, indicating their derivation from GC B cells. Conversely, classic HD (CHD) is heterogeneous because the tumor cells of a fraction of CHD display the BCL-6(-)/ syn-1(+) phenotype of post-GC B-cells, whereas another fraction of CHD is constituted by a mixture of tumor cells reflecting the GC (BCL-6(+)/syn-1(-)) or post-GC (BCL-6(-)/syn-1(+)) phenotypes. BCL-6(-)/syn-1(+) tumor cells of CHD are mostly found surrounded by T cells expressing CD40L, consistent with the observation that CD40 signaling downregulates BCL-6 expression. These data indicate that tumor cells of NLPHD uniformly display a GC B-cell phenotype, whereas the phenotype of tumor cells of CHD appears to be modulated by the surrounding cellular background, particularly CD40L+ reactive T cells.
Hodgkin's disease is a common malignancy of the lymphoid system. Although the scarce Hodgkin and Reed-Sternberg (HRS) tumor cells in involved tissue synthesize major histocompatibility complex (MHC) class II and costimulatory molecules such as CD40 or CD86, it is unclear whether these tumor cells are operational antigen-presenting cells (APC). We developed an immunofluorescence-based assay to determine the number of MHC class II molecules present on the surface of single living HRS cells. We found that in fresh Hodgkin's disease lymph node biopsies, a subset of HRS cells express a substantial number of surface MHC class II molecules that are occupied by MHC class II-associated invariant chain peptides (CLIP), indicating deficient loading of MHC class II molecules with antigenic peptides. Cultured Hodgkin's disease-derived (HD) cell lines, however, were found to express few MHC class II molecules carrying CLIP peptides on the cell surface and were shown to generate sodium dodecyl sulphate (SDS)-stable MHC class II alphabeta dimers. In addition to showing deficient MHC class II antigen presentation in a subset of HRS cells, our results show that the widely used HD-cell lines are not ideal in vitro models for the disease. The disruption of MHC class II- restricted antigen presentation in HRS cells could represent a key mechanism by which these tumor cells escape immune surveillance.
The Epstein-Barr virus (EBV)-encoded latent membrane proteins, LMP1 and LMP2, are consistently expressed by the malignant Hodgkin/Reed- Sternberg (HRS) cells of EBV-associated Hodgkin's disease (HD). Cytotoxic T lymphocyte (CTL) responses to both of these proteins have been shown in the blood of EBV-seropositive individuals, yet in HD the apparent failure of the CTL response to eliminate HRS cells expressing LMP1 and LMP2 in vivo has given rise to the suggestion that HD may be characterized by the presence of defects in antigen processing/presentation or in CTL function. This study has used immunohistochemistry to show high-level expression of major histocompatibility complex (MHC) class I molecules by the HRS cells of EBV-associated HD and either low level or absence of expression of MHC class I molecules on HRS cells of EBV-negative tumors. In addition, HRS cells expressed high levels of transporter-associated proteins (TAP-1, -2), irrespective of the presence of latent EBV infection. These results suggest that global downregulation of MHC class I molecules does not account for the apparent ability of EBV-infected HRS cells to evade CTL responses, but may be important in the understanding of EBV-negative disease.We have also sequenced an epitope in LMP2A (CLGGLLTMV) that is restricted through HLA A2.1, a relatively common allele in Caucasian populations, and showed that this epitope is wild type in a small group of EBV-associated HLA A2.1-positive HD tumors. This result may be relevant to proposed immunotherapeutic approaches for EBV-positive HD patients that target CTL epitopes.
One hundred consecutive patients with malignant lymphoma treated with high-dose chemotherapy and autologous stem cell transplantation, followed at least 1 yr post-transplant, are reported, 68 with non-Hodgkin's lymphoma and 32 with Hodgkin's disease. At transplant, 23 patients were in first remission, 69 in later chemosensitive disease and 8 were chemotherapy resistant. Based on previous treatment and stem-cell source, the patients were subdivided into 3 cohorts: BMT1: bone-marrow harvest and transplant after > or =3 treatment regimens (38 patients); BMT2: bone marrow harvest and transplant after less than 3 treatment regimens (24 patients); PBSCT: peripheral-blood stem cell transplant (38 patients, 5 of these with CD34+ cell selected PBSC). The 4-yr survival and progression-free survival of all patients was 45 and 40%, respectively. Forty-one patients have died, 27 of lymphoma, evenly distributed in the cohorts. Fourteen treatment-related deaths occurred, 13 of these in the BMT1 cohort, significantly more than in the other cohorts (p=0.001). In univariate survival analysis cohort, age, disease status at transplant and number of previous treatment regimens were significant. In multivariate survival analysis cohort, age and sex were independently significant, women having a shorter survival. The patients transplanted with unselected PBSC had significantly shorter duration of pancytopenia and hospital stay than the otherwise comparable BMT2 patients, but their progression-free survival was identical. We confirm that high-dose therapy with autologous stem cell transplant from blood or bone marrow in not-too-heavily pretreated patients is a safe procedure but will cure only half the patients.
The aim of this study is to assess the risk of avascular osteonecros- is (AVN) of the femoral head in patients treated for Hodgkin's disease (HD), in relation to the type of treatment they have received. For this purpose, a cohort of 1391 patients treated for HD at University of Rome between 1972 and 1996 was divided into 2 groups according to their initial treatment. The first group contained 784 patients treated, at the onset of HD, either with chemotherapy (CT) containing steroids, combined in some cases with subdiaphragmatic radiotherapy (RT), or with subdiaphragmatic RT combined with CT without steroids. The second group was made up of 607 patients who had received, initially, supradiaphragmatic RT alone or supradiaphra- gmatic RT combined with CT without steroids. For the purpose of this study, only the 784 patients belonging to the first group were observed for the appearance of AVN, which occurred in 9 cases. The period of time which elapsed between the end of treatment and the radiological evidence of AVN ranged from 23 to 97 months, with an average of 35 months. Because the number of cases of AVN was so small, the pathogenesis of this complication could not be identified.
We describe a case of Hodgkin's disease with cervical lymphadenopathy which may easily be confused with a granulomatous process both radiologically and pathologically.
BACKGROUND: The use of inverted Y irradiation in the treatment of Hodgkin's disease with pelvic lymph node involvement can cause iatrogenic early menopause in young women as a result of ovarian exposure to radiation. Ovarian transposition protects the ovaries by removing them from the irradiation field. This surgical procedure, initially performed by laparotomy, can now be done by laparoscopy. METHODS: During the period July 1994 to April 1996, laparoscopic ovarian transposition was performed on 4 young women with Hodgkin's disease 1 week before inverted Y radiotherapy. The surgical procedure, complications, length of hospitalization, and hormonal, clinical, and biologic results were evaluated. RESULTS: The mean duration of hospitalization was 4 days, and there were no postoperat- ive complications. Iatrogenic menopause did not occur in any of the patients during the mean follow-up period of 20.75 months (range, 6-35 months; median, 20 months). CONCLUSIONS: Laparoscopy offers many advantages over laparotomy for ovarian transposition. This procedure, which can be performed without opening the abdominal wall, is highly efficient, requires only a short period of hospitalization, and leads to few postoperative complications. Laparoscopy is an attractive alternative to laparotomy for ovarian transposition in young women with advanced Hodgkin's disease who require pelvic radiotherapy.
Record linkage was carried out between the national Registry of AIDS and 13 Cancer Registries (CRs) covering, in 1991, about 15% of the Italian population. Observed and expected numbers of cancers and standardized incidence ratios (SIRs) were assessed in 6067 persons with AIDS, for a total of 25,759 person-years. Significantly increased SIRs were found for Hodgkin's disease [8.9, 95% confidence interval (CI) 4.4-16.0], in which seven of 11 cases were of mixed cellularity type; invasive carcinoma of the cervix uteri (15.5; 95% CI 4.0-40.1); and non-melanomatous skin cancer (3.0, 95% CI 1.3-5.9), in which five of eight cases were basal cell carcinoma. An excess was also seen for brain tumours, but this may be partly due to misdiagno- sis of brain non-Hodgkin's lymphoma or other brain diseases occurring near the time of the AIDS diagnosis. The risk for all cancer types, after exclusion of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), was approximately twice the general population risk. An increased SIR for Hodgkin's disease in persons with AIDS is thus confirmed, though it is many times smaller than that for NHL. An association with invasive carcinoma of the cervix is also shown at a population level. The excess of non-melanomatous skin cancer seems to be lower than in transplant recipients.
Modulation of Fas expression and function by CD40 ligation was investigated in the Fas-sensitive human Hodgkin's disease cell line HDLM2. The recombinant human trimeric soluble CD40L (sCD40L) protected this cell line from apoptosis induced by an agonistic Fas antibody at all concentrations tested. sCD40L also protected HDLM2 when added up to 2 h after Fas ligation. Apoptosis induced by a cell-permeable synthetic ceramide could not be prevented by sCD40L. Thus, CD40 ligation is likely to intervene in the early phases of the Fas signal transduction pathway. When CD40 ligation preceded Fas ligation, it rendered the cells refractory to Fas-induced apoptosis. sCD40L-mediated protection could not be attributed to reduction in surface Fas expression, increase in Bcl-2 levels or to increase in the levels of soluble Fas isoforms.
No abstract available.
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euchromatin: "the most active portion of the genome within the
cell nucleus".