Stage Hodgkin's Disease Research Articles

Radiation therapy in early stage Hodgkin's disease: long-term results and adverse effects.

Radiation therapy (RT) was the first treatment modality demonstrating cure of Hodgkin's disease. Long-term side-effects of this treatment, however, have become evident in the past few years. By reviewing the results of megavoltage radiotherapy as initial treatment in a consecutive series of 106 patients with early-stage Hodgkin's disease (HD), survival, relapse-free interval, salvage rate of relapsing cases, and incidence of second tumours were evaluated. Subtotal node irradiation was given to all patients with supradiaphragmatic disease, except for 15 patients with limited stage IA-IIA, who received mantle field treatment only. Inverted Y field irradiation was given to all seven patients with subdiaphragmatic disease. The median age was 32 years (range 14-77). The median follow-up was 140 months. The relapse-free interval of the patient population was 78% at 5 years and 72% at 10 years. The overall survival (OS) was 90% and 79%, respectively. Salvage therapy was successful in 26 of 30 relapsing patients. Twelve recurrences were located inside the treatment field. Sixteen patients (15%) developed second malignancies: cancer of the lung (two), ovary (two), cervix (one), colon (two), breast (three), stomach (one), skin (two), hypopharynx (one), and non-Hodgkin lymphoma (two). Eleven of these were located within the radiation field. Although RT is intended to be a curative treatment, up to 30% recurrences occur. Mortality was not determined by primary HD, but by second malignancies, which are likely related to treatment. New treatment strategies, aiming at long-term freedom from relapse without carcinogenic side-effects, are urgently needed.

Role of bone marrow examination in staging Hodgkin's disease: experience in México.

We assessed the value of bone marrow biopsy prospectively in a group of 91 individuals with Hodgkin's disease. The median age of our population was 29 years (range 4-87 years); 59 were males. Most patients (45%) had nodular sclerosing disease and most patients (44%) were in pathological stage II at diagnosis. The bone marrow biopsy showed infiltration by Hodgkin's disease in only three individuals (3.3%); two of these patients displayed constitutional symptoms and had been assigned to stage III before the biopsy. In one case, bone marrow biopsy was the diagnostic procedure, which was performed as part of the investigation of fever of unknown origin. Follow-up periods ranged between 1 and 117 months (median 16 months). All patients achieved complete remission, seven patients relapsed and four were given autologous stem cell transplants. The median survival of the whole group was 117 months, while the 3500-day survival was 76%. As bone marrow biopsy was the diagnostic procedure in one case, bone marrow biopsy was a useful staging procedure in only 2.2% of patients (two out of 90 patients). We suggest that bone marrow biopsy should be only be performed as a staging procedure in a selected subset of patients with Hodgkin's disease (clinical stage III, B symptoms, etc.).

New treatments for Hodgkin's disease.

Four of five patients with Hodgkin's disease (HD) will be cured with modern treatment strategies, depending on stage and risk factor profile. In early stage favorable HD, cure rates are greater than 90% with extended field (EF) irradiation, the standard treatment. However, the concept of EF irradiation therapy is being abandoned by most study groups because of the recognition of fatal long-term effects, especially the high rates of second solid tumors. Newer approaches include mild chemotherapy combined with involved field (IF) irradiation to control occult disease. Combined modality is the treatment of choice in early stages unfavorable (intermediate) HD, in which EF irradiation is substituted by IF irradiation. In the last three decades, because of the high relapse rates (30%-50%) after first-line polychemotherapy, the standard regimens were often modified. However, until recently, these efforts could not change the relatively poor outcome for patients with advanced stage disease. The introduction of a new dose-intensified regimen (BEACOPP) has significantly improved the prognosis for patients with advanced HD. Patients who relapse after radiation therapy alone for early stage HD have satisfactory results with combination chemotherapy and are not considered as candidates for high-dose chemotherapy with autologous stem cell transplantation. For patients with relapsed HD after combination chemotherapy, the data support the use of high-dose chemotherapy with autologous stem cell transplantation.

Interventions for early stage Hodgkin's disease in children.

Hodgkin's disease is one of the most curable cancers in children, particularly at the early stages. However it is not clear which combinations of treatment strategies are most effective at maintaining high cure rates and minimising long term harmful effects or sequelae of treatment. To assess the effects of radiotherapy, chemotherapy or combined radiotherapy and chemotherapy on relapse free survival and overall survival rates in children with early (stage I to IIA) Hodgkin's disease. We searched the Cochrane Library (issue 4, 2001), MEDLINE (1966 to July 2001), EMBASE, Cinahl, Cancer-CD and reference lists of relevant articles. We also handsearched six journals. Randomised controlled trials of involved field radiotherapy, extended field radiotherapy, anthracycline based chemotherapy regimens, or alkylating chemotherapy agents in children to 19 years of age with Hodgkin's disease. Trial eligibility and quality were assessed and study authors were contacted for additional information. Four trials involving 334 children were included. It was not possible to combine the outcomes as they covered different treatment regimens. The trials were of variable quality. One trial comparing radiotherapy alone showed no discernible difference in relapse free survival (relative risk 0.73, 95% confidence interval 0.49 to 1.09) or overall survival (relative risk 0.92, 95% confidence interval 0.79 to 1.07) between involved field and extended field radiotherapy. No discernible difference was found between involved field radiotherapy plus chemotherapy and extended field radiotherapy and chemotherapy (based on one small trial). In another trial, involved field radiotherapy plus chemotherapy appeared to increase relapse free survival compared to either involved field or extended field radiotherapy alone, although a discernible difference was found for overall survival. Extended field radiotherapy alone appeared to increase relapse free survival compared to extended radiotherapy plus chemotherapy (relative risk 0.34, 95% confidence interval 0.14 to 0.83) but no discernible difference was apparent for overall survival (based on one trial). There is little evidence from randomised controlled trials to evaluate the consensus approach of short course chemotherapy and local radiotherapy, although no discernible difference in survival was detected between involved field and extended field radiotherapy in one randomised trial.

The disappearance of prognostic factors in Hodgkin's disease

The purpose of this conceptual (and somewhat provocative) article is to analyse the reasons for the disappearance of prognostic factors in Hodgkin's disease (HD) and to explore the consequences for further research from a biometrical point of view. The very concept of prognostic factors is about to resolve in HD. Prognostic factors gradually loose their predictive power as treatment is successfully adapted to the disease burden. Freedom from treatment failure and overall survival curves of patients in early, intermediate and advanced stages of HD are superimposable with the best current treatment protocols of the German Hodgkin's Lymphoma Study Group. This disappearance of prognostic factors in HD necessitates a certain conceptual remodelling. It's time to think quantitatively and bivariately, and we need to (i) synthesise existing 'prognostic' factors into a quantitative measure of disease burden or severity; (ii) develop a quantitative measure of treatment strength and (iii) relate these two quantities in nomogram curves indicating how much treatment a patient with a given disease burden requires to have, say, a 85%, 90% and perhaps 95% expected chance of cure.

Prognostic factors and treatment outcome in patients with primary progressive and relapsed Hodgkin's disease

Depending on stage and risk factor profile, up to 95% of patients with Hodgkin’s disease (HD) at first presentation reach complete remission (CR; disappearance of all detectable clinical and radiographic evidence of disease) after standard treatment [1]. Depending on their initial treatment, those patients relapsing have different treatment options, including radiotherapy for localized disease in previously non-irradiated areas, conventional salvage chemotherapy, or high-dose chemotherapy (CT) followed by autologous stem cell transplantation (autoSCT) [2, 3]. Conventional CT is the treatment of choice for patients relapsing after initial radiotherapy for early stage HD. The survival of these patients is at least equal compared with advanced-stage patients initially treated with CT [4]. In contrast, patients with relapsed HD after primary CT generally have a poorer prognosis. The therapeutic options include salvage radiotherapy, salvage CT, and high-dose CT with autoSCT. More recently, new approaches such as sequential highdose CT, tandem high-dose CT, allogeneic (allo) SCT, or nonmyeloablative conditioning with allogeneic blood progenitor cell transplantation (‘mini-transplants’) have been investigated in relapsed HD [4–6]. Since more aggressive approaches are associated with increased toxicity, an accurate pretreatment prognostic assessment of patients is required to help selection of the most appropriate therapeutic regimen.

2-Deoxy-2-[F-18]Fluoro-D-Glucose Imaging with Positron Emission Tomography for Initial Staging of Hodgkin's Disease and Lymphoma

Purpose: To assess the accuracy of 2-Deoxy-2-[F-18] Fluoro-D-Glucose positron emission imaging (FDG-PET) for staging Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) compared to conventional staging (CS) and to evaluate the impact on patient management. Methods: Forty-five consecutive patients with lymphoma underwent whole-body FDG-PET imaging for initial staging. Discordant lesions were verified with biopsy or clinical follow-up. The impact on staging and management was reviewed retrospectively. Results: A total of 129 sites of disease were identified, and 88 of those were concordant. FDG-PET and conventional staging demonstrated 24 and 17 additional sites, respectively. FDG-PET correctly upstaged five patients and down-staged two patients (16% total), leading to a change in therapy in 6/45 (13%) patients. However, FDG-PET understaged three patients (7%), correctly staged by conventional staging modalities. Assuming that the addition of FDG-PET to conventional staging modalities is 100% accurate for staging lymphoma, the accuracy of FDG-PET alone was 91%, compared to 84% for conventional staging modalities. Conclusions: FDG-PET is a noninvasive and efficient imaging modality for staging patients with lymphoma and should be used in conjunction with conventional staging modalities, as they appear complementary. (Mol Imag Biol 2002;4:105–114)

Male gonadal dysfunction in patients with Hodgkin’s disease prior to treatment

Infertility after treatment of patients with Hodgkin's disease (HD) is considered as a side effect of alkylating agent containing chemotherapy regimens. To investigate whether gonadal failure is related primarily to the toxic effect of chemotherapy or rather to the disease itself, we investigated the fertility status before the onset of treatment. Semen quality and hormonal status were evaluated in 158 patients with first diagnosis of HD enrolled into trials of the German Hodgkin Lymphoma Study Group (GHSG). The median age of the patients was 28 years (range 16-52). Twenty patients (13%) were classified as early stage HD, 63 patients (40%) as intermediate stage, and 75 patients (47%)) as advanced stage according GHSG grading. Sixty-seven patients (42%) showed systemic symptoms. Semen analysis was performed according to WHO guidelines. Follicle-stimulating hormone (FSH) and luteinising hormone (LH) plasma levels were measured by specific double-antibody radio-immune-assay (RIA) methods. Prior to treatment, severe damage of fertility, i.e.. azoospermia and oligoasthenoteratospermia (OAT-syndrome) was found in 13 (8%) and 20 patients (13%), respectively. Thirty-eight patients (24%) had single, i.e., oligo-(O), astheno-(A) or teratospermia-(T), and 40 patients (26%) showed combined damages, i.e., OA, OT or AT. In 47 patients (30%) a normal sperm count was found. Thus, III patients (70%) showed semen abnormalities before the onset of treatment. In a multivariate analysis elevated ESR (P < 0.003) and advanced stage of disease (P < 0.01) could be distinguished as prognostic factors for severe damage of fertility. No correlation was found between pre-therapeutic gonadotropine levels and fertility status. Patients with HD have an increased risk for inadequate semen quality even prior to treatment. Infertility is more frequent in patients with elevated ESR and advanced stage of disease. This association demonstrates the predominant influence of the disease on fertility. Assuming HD is the major initial cause for infertility efforts should be made to identify new non-gonadal toxic chemotherapies to be able to regain fertility after effective therapy. Further investigations have to be performed to clarify mechanisms inducing fertility defects in patients with HD.

Prospective randomized trial in the treatment of early stage hodgkin's disease (ESHD) using involved field radiation therapy (IFRT) vs. subtotal nodal irradiation (STNI) after a short chemotherapy (CT) course

Prospective randomized trial in the treatment of early stage hodgkin's disease (ESHD) using involved field radiation therapy (IFRT) vs. subtotal nodal irradiation (STNI) after a short chemotherapy (CT) course

Asplenic-hyposplenic overwhelming sepsis: postsplenectomy sepsis revisited.

Absence of the spleen or splenic function predisposes individuals to risk of overwhelming infection. These infections are most often due to encapsulated organisms, especially pneumococcus, Haemophilus influenzae type b, and meningococcus, but any bacterial agent may cause the rapid onset of septicemia, meningitis, pneumonia, and shock characteristic of the asplenic-hyposplenic condition. The risk is greatest in infants and young children, but asplenic-hyposplenic adults also have an increased risk of infection. Prophylactic antibiotics and immunization with polyvalent pneumococcal, H. influenzae type b, and meningococcal vaccines have reduced the incidence of infections in asplenic-hyposplenic individuals, but even these measures have not eliminated the risk. Surgeons have adopted techniques to save as much splenic tissue as possible and some splenic functions, such as pitting red cells, have been preserved, but conservative surgery has not provided total protection against overwhelming infection. Therapies designed to interrupt the cascade of overwhelming sepsis have not yet been successful. In those cases in which the spleen is surgically removed, the underlying disease or condition leading to splenectomy influences the risk of sepsis. Splenectomy incidental to other operations, such as gastrectomy, results in the lowest risk for overwhelming infection, but this is still some 35-fold greater than the risk for overwhelming infections in the general population. In increasing order of risk, the other main indications for surgical removal of the spleen are idiopathic thrombocytopenia purpura, trauma, transplantation procedures, hereditary spherocytosis, staging Hodgkin's disease, portal hypertension with hypersplenism, and thalassemia. Pathologists should comment on the risk of overwhelming sepsis when spleens are processed as surgical specimens, and should carefully weigh all splenic tissue, including accessory spleens and splenic implants (splenosis), in autopsy cases with and without overwhelming sepsis.

A systematic overview of chemotherapy effects in Hodgkin's disease.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for Hodgkin's disease (HD) is based on 113 scientific reports including four meta-analyses, 44 randomised studies, 18 prospective studies and 40 retrospective studies. These studies involve 69,196 patients. The conclusions reached can be summarised into the following points: Chemotherapy is of utmost importance for the cure of HD. At early stages, extended field radiotherapy cures most patients. For the majority of patients with relapse after radiotherapy, chemotherapy is curative and the total proportion of cured early stage patients is 75-90%. Chemotherapy in addition to extended field radiotherapy reduces recurrences but does not improve long-term survival. In early stage HD with a large mediastinal mass and/or with systemic symptoms, combined treatment with chemotherapy and radiotherapy is recommended. It is likely that chemotherapy will play a greater role in the future in the treatment also of early stage patients in order to reduce late consequences from extended field radiotherapy. However, this conclusion remains to be better documented in the literature. At advanced stages, chemotherapy or a combination of chemotherapy and limited field radiotherapy are effective treatment options and, using the regimens available 10-20 years ago, 40-50% of the patients are cured. Based upon more favourable short-term (three to eight years) results of more recently developed regimens, it can be expected that today a higher proportion of the patients will become long-term survivors. Several chemotherapy regimens containing four to eight drugs are effective in HD. The best regimen considering both antitumour activity and acute and late side-effects is not known. The choice of regimen is probably best done after considering various pre-treatment factors such as the number of poor prognostic signs, concomitant diseases and individual preferences. The results of chemotherapy are more favourable in young than in elderly patients. The development of less toxic but still effective treatment programmes is therefore particularly important for the elderly. High dose chemotherapy with stem cell support is presently often used in patients who are chemotherapy induction failures, who relapse after a short initial remission or after a longer initial remission and treated initially with seven or eight drugs, or who have had multiple relapses. However, this use is based on data from uncontrolled or small controlled studies, not being fully convincing with respect to effect on survival. Persistent side-effects of treatment are common among long-term survivors, although most patients have an apparently normal life. The relative contributions of chemotherapy and radiotherapy to the persistent effects are not well documented.

Whole body positron emission tomography in the treatment of Hodgkin disease

In Hodgkin disease (HD), accurate assessment of the extent of disease is essential because it provides the basis for different treatment strategies. In addition to conventional imaging methods (CIM), positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) may permit reliable differentiation between lymphoma and nonmalignant tissue and thus improve determination of the stage of the disease. The aim of the current study was to assess the clinical value of FDG-PET for primary staging, treatment monitoring, and assessment in a suspected case of recurrent HD. Eighty-one patients with HD underwent 106 FDG-PET studies using a dedicated whole body PET ring scanner. In 25 patients PET was part of the primary staging, 63 PET studies were undertaken for treatment monitoring after the completion of treatment, and in 18 patients PET was performed in cases of suspected recurrence of HD. PET scans were compared with CIM and verified histologically and/or by follow-up evaluation (mean follow-up duration, 20.4 months). With regard to primary staging, in a patient to patient analysis, both PET scans and CIM were positive (i.e., showed pathologic foci indicative of HD) in 24 of 25 cases. In a staging-relevant lesion to lesion analysis, accuracy in the determination of the stage of disease was 96% for PET versus 56% for CIM. PET led to a lower stage classification in 28% and a higher stage classification in 12% of cases, compared with the stage assumed with CIM. With regard to treatment monitoring, PET showed an accuracy of 91% compared with 62% for CIM. The negative predictive value of PET was 96%. With regard to suspected recurrence, PET findings were true-positive in 10 of 12 PET scans and true-negative in 5 of 6 PET scans, resulting in accuracy of 83%, which compares favorably with the accuracy rate of 56% for CIM. It may be concluded that FDG-PET is capable of determining the stage of HD with great accuracy and is capable of correctly detecting manifestations of HD in treatment monitoring and cases of suspected recurrence, in which CIM occasionally result in equivocal findings. The results of the current study suggest that FDG-PET should become a routine tool in the staging/restaging of HD.

Treatment outcome in patients younger than 60 years with advanced stages (IIB-IV) of Hodgkin's disease: the Swedish National Health Care Programme experience.

Despite improved treatment results achieved in Hodgkin's disease (HD), only about 70% of patients with advanced stages are cured. The primary aim of this study was to evaluate the outcome of advanced stages (IIB-IVB) of HD in younger patients in an unselected population-based group of patients. The patients were recommended individualized treatment with respect to number of chemotherapy (CT) courses and post-CT radiotherapy (RT) based on pretreatment characteristics and tumour response. Secondly, we investigated if variables of prognostic importance could be detected. Between 1985-92, 307 patients between 17-59 yr of age (median 36) were diagnosed with HD in stages IIB-IVB in 5/6 health care regions in Sweden. Median follow-up time was 7.8 yr (1.3-13). Retrospectively, laboratory parameters were collected. In total, 267 (87%) patients had a complete response (CR). The overall and disease-free 10-yr survivals in the whole cohort were 76% and 67%, respectively. There was no difference in survival between the groups of patients who received 6 or 8 cycles of CT. Survival was not higher for patients in CR after CT when RT was added. For those in PR after CT, additional RT raised the frequencies of CR. A selected group of pathologically staged patients was successfully treated with a short course (2 cycles) of CT + RT. In univariate analyses survival was affected by age, stage IVB, bone-marrow involvement, B-symptoms, S-LDH, S-Alb and reaching CR or not after 2, 4 and 6 cycles of CT. In a multivariate analysis, age and reaching CR after 6 cycles of CT remained statistically significant. The lack of difference in survival between the groups of patients who received 6 versus 8 cycles of CT indicates a successful selection of patients for the shorter treatment. Reaching a rapid CR significantly affected outcome. Whether some patients need less CT than the generally recommended 8 courses can properly only be evaluated in a randomised study. Additional RT may play a role in successful outcome, particularly if residual tumours are present, but its precise role can also only be defined in prospectively randomised studies. Reaching CR after CT was the most important variable affecting survival besides age.

Biological markers may add to prediction of outcome achieved by the international prognostic score in Hodgkin's disease

The International Prognostic Score (IPS) identifies seven independent factors predicting progression-free and overall survival in advanced stage Hodgkin's disease (HD). The IPS is also applicable in limited disease. However, the IPS does not identify patients with a very poor prognosis. The aim of this study was to define biological markers which may add to the IPS in predicting outcome. One hundred forty-five patients (> 15 years) with HD of all stages and histopathology subgroups were included. In addition to factors included in the IPS, serum levels of CRP, sCD4, sCD8, sCD25, sCD30, sCD54, interleukin (IL)-10, beta2-microglobulin and thymidine kinase were analysed. The strongest predictors of a poor cause-specific survival (CSS) in univariate analyses were: increased serum levels of IL-10, sCD30 and CRP, anaemia, low levels of albumin (P < 0.001); stage IV (P = 0.003), age > or = 45 years (P = 0.006), increased serum levels of sCD25 (P = 0.010), low lymphocyte counts (P = 0.020). Serum IL-10 added prognostic information to that achieved by the IPS: patients with a high score and increased serum IL-10 had a very poor outcome with a five-year CSS of 38%. Patients with increased serum levels of sCD30 and a high score also had a poor outcome with a five-year CSS of 54%. Serum levels of IL-10 and sCD30 may add to IPS in prediction of outcome in HD, and should be validated in large, prospective studies.

Value of laparoscopic staging for Hodgkin disease.

Because of the potential for complications with laparotomy and splenectomy, and the widespread use of combination chemotherapy as first-line treatment, surgical staging is now performed in only 30% of patients with Hodgkin disease. Laparoscopic staging has rarely been reported. Three patients with the nodular sclerosis cell type of Hodgkin disease underwent laparoscopic staging. Mean operative time was 207 minutes. No conversion to laparotomy was necessary. There were no peri- or postoperative complications and no deaths. Mean blood loss was negligible. The pathologist deemed all liver and lymph nodes biopsies adequate for histologic analysis. Stage IA and IIA were confirmed in two patients: one patient with stage IIA was upstaged to IIIA after surgery. Performed by an experienced team, laparoscopy is the procedure of choice for abdominal staging of patients with Hodgkin disease.

Acute hematologic toxicity and practicability of dose-intensified BEACOPP chemotherapy for advanced stage Hodgkin's disease

Evidence is recently accumulating that the novel BEACOPP (bleomycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C), vincristine (O), procarbazine (P), prednisone (P)) chemotherapy is a highly effective treatment for advanced stage Hodgkin's disease. Two dose variants of BEACOPP are currently tested in a phase III randomized multicenter trial of the GHSG. To enable more extensive testing of BEACOPP we characterized its practicability regarding schedule adherence, acute hematotoxicity and need for supportive treatment. Data of 858 patients (6592 therapy cycles) from 184 participating institutions were evaluated. Planned total drug doses of the baseline variant (arm 1) were 80, 2400, 200, 5200, 11.2, 5600 and 4480 mg/m2 for B, E, A, C, O, P and P, respectively. Compared to arm 1, the doses of E, A and C in the dose-intensified variant (arm 2) were escalated by factor 2.0, 1.4, 1.92, respectively, using G-CSF assistance. Stepwise dose reductions were specified in case of dose-limiting toxicities. Both variants are given in eight three-weekly courses. Median dose adherence (dose actually given relative to planned arm 1 dose) in arm 1 was 1.0 for all drugs. Relative dose escalation of E, A, and C actually maintained in arm 2 was 1.83, 1.37 and 1.77 (medians), respectively, and 70% of patients maintained elevated dose levels throughout the entire treatment. Dose-limiting toxicities occurred in 25% of cycles in arm 2, most frequently due to leukocytopenia and thrombocytopenia. Time courses of leukocytes in arm 2 showed more severe but not more prolonged leukocytopenia compared with arm 1. WHO grades 3-4 infections were documented in 2.1% (arm 1) and 3.1% (arm 2) of all cycles. Erythrocytes were transfused in 61% (arm 1) and 28% (arm 2), platelets in < 1% (arm 1) and 6% (arm 2) of all cycles. Both BEACOPP schemes are practicable in a large multicenter setting. Despite increased hematotoxicity, moderate dose escalation is safe for the majority of the patients with G-CSF assistance and standard supportive treatment.

Hodgkin disease: prognostic factors and treatment strategies.

Depending on stage and risk factor profile, more than 80% of patients with Hodgkin disease (HD) will be cured with modern treatment strategies. In early-stage, favorable HD, extended field irradiation has been the standard treatment resulting in cure rates of greater than 90%. However, due to the recognition of fatal long-term effects, especially the high rates of second solid tumors, extended field irradiation therapy is now being abandoned by most study groups. Instead, mild chemotherapy for control of occult disease is combined with involved field irradiation. In early-stage, unfavorable (intermediate) HD, for which combined modality treatment is already the treatment of choice, extended field irradiation is replaced by involved field irradiation for the same reasons. A different situation is found in advanced HD. In this case, standard therapy consists of eight cycles of polychemotherapy. Until recently, modifications of the standard chemotherapy regimens had not changed the poor outcome of advanced-stage patients. The development of a new dose-intensified regimen (BEACOPP) now for the first time has significantly improved the prognosis of these patients. Patients who relapse following radiation therapy alone for early stage HD have satisfactory results with combination chemotherapy and are not considered candidates for high-dose chemotherapy with autologous stem cell transplantation. For patients with relapsed HD after combination chemotherapy, the current data support the use of high-dose chemotherapy with autologous stem cell transplantation.

HIV-associated Hodgkin's disease.

Hodgkin's disease (HD) appears to occur more frequently in people with HIV and within this population HD demonstrates a number of differences. In people with HIV, Epstein-Barr virus (EBV) is found more frequently in Reed-Sternberg cells and mixed cellularity and lymphocyte depleted histological subtypes predominate. Patients with HIV present with more advanced stage HD often with extranodal disease. The prognostic variables for HD in patients with HIV relate to the HIV rather than the HD. In people with HIV the response rates are lower, the relapse rates higher, the infectious complications more frequent and the overall survival worse than for HD in the general population.

Semen analysis and cryoconservation before treatment in Hodgkin's disease

The prophylaxis of the late effects of chemotherapy and radiotherapy has become one of the major concerns in the management of Hodgkin's disease (HD). Unlike other complications, male sterility could be managed by prior semen preservation (SP). To evaluate the semen quality of patients with HD and the outcome of insemination, we reviewed spermograms of patients who underwent SP before any treatment. The following criteria were necessary: 1) age > 16 and < 50; 2) HD of any stage; 3) informed about male sterility after HD treatment; 4) fully consenting. Such a proposal was made to 316 men, and 94 fulfilled the criteria. All patients underwent an initial chemotherapy. Mean age of the cohort was 27.5 years (range 16-48 years). Pretherapeutic staging of HD revealed 38 stage I (40%), 38 II (38%), 14 III (15%) and 4 IV (4%). Semen analysis before cryoconservation showed an overall 53% of normal or subnormal cases (50 cases). The analysis of semen quality and spermatozoid amount according to various parameters failed to find a correlation with stage, B symptoms, age, or biologic data (LDH, WBC, platelets, ESR). The use of cryopreserved semen was requested by 13 patients; 88 inseminations were performed leading to 9 pregnancies and 2 births. The low rate of success with cryopreserved semen in these cases suggests the need for a more careful design of non-toxic chemotherapy regimens in combined modality treatment.

Is the international prognostic score for advanced stage Hodgkin’s disease applicable to early stage patients?

BackgroundThe seven-factor International Prognostic Score (IPS) has been developed and verified for patients with advanced stage Hodgkin’s disease (HD). This report aims to assess the predictive power of the IPS for early stage HD patients. Patients and methodsData on patient characteristics, therapy and follow-up were available for 1424 adult patients in clinical stages I-IIIA treated for primary HD in two German Hodgkin’s Lymphoma Study Group (GHSG) trials (1988–1994). Patients with risk factors or in stage IIIA received chemo-radiotherapy (CMT; trial HD5); others received extended field radiotherapy (RT) alone (HD4). The IPS could be calculated for 712 HD5 and 249 HD4 patients (70%). The prognostic value of the IPS and its component factors was assessed using Cox proportional hazards regression. A search was made for additional factors which could add predictive power to the IPS. ResultsThe IPS identified 40% of the unfavourable early stage patients with an 8% lower disease-free survival at six years (hazard ratio 1.66, P = 0.0018). The factor ’low albumin’ was the only score component giving a significant individual contribution. Allowing for the IPS, extranodal involvement, particularly in stages IIB-IIIA, was associated with worse prognosis, but no further significantly prognostic factors were revealed. The IPS identified a similar hazard ratio in HD4, although here the effect was not significant. ConclusionsThe IPS for advanced HD has modest predictive ability in unfavourable early stage patients. Modification of the IPS for use with early stages may improve its prognostic power.