Preliminary results of the multicenter trial GPOH-HD 95 for the treatment of Hodgkin's disease in children and adolescents: analysis and outlook.

BACKGROUND: In 5 consecutive pediatric and adolescent Hodgkin's disease trials DAL-HD since 1978 the invasive diagnostic procedures and the radiotherapy have gradually been reduced and chemotherapy modified to minimize toxicity and the risk of late effects. Since 1982 the overall survival increased up to 95%. In this trial the possibility of reducing local radiation doses to 20 Gy in patients with good response to chemotherapy and omitting radiotherapy totally for patients with complete remission after chemotherapy was tested. PATIENTS AND METHODS: Over a period of 6 years, from August 1995 to July 2001, 1018 children and adolescents with Hodgkin's disease from Germany, Austria,Switzerland, the Netherlands, Sweden, Norway and Denmark were enrolled in this trial. The chemotherapy was equivalent to previous trial DAL-HD 90. The treatment group (TG) 1 (stages I and IIA) received 2 cycles OPPA for girls and 2 cycles OEPA for boys, TG2 (stages IIEA, IIB, IIIA) and TG3 (stages IIEB, IIIEA, IIIB, IV) received additional 2 or 4 cycles COPP respectively. In contrast to trial DAL-HD 90 boys in stage IIIB and IIIEB received OPPA instead of OEPA. The initial staging as well as the restaging for evaluating tumor volume reduction after chemotherapy was reviewed by the study center. Radiotherapy was planned accordingly: patients with complete remission after chemotherapy were not irradiated (21.9%); all other patients received local radiotherapy to the initially involved sites, depending on the tu-mor response. Patients with a partial remission of> 75 tumor regression were irradiated with 20 Gy (50AX), partial remission of< 75% with 30 Gy (4.1 %), and residual masses of > 50 ml were boosted up to 35 Gy (20.2 %). RESULTS: 36 tumor progressions and 49 relapses occurred over a period of 7 1/2 years (median followup 3 years, data deadline 12/19/02). Kaplan-Meier-analysis after 5 years showed a probability for event-free survival (pEFS) for all patients of 0.88 and for overall survival (pOS) of 0.97. For the total group the pDFS (disease free survival) was lower in 222 non irradiated patients than in the 758 irradiated patients (0.88 vs. 0.92,p - 0.049). But there was a difference between the individual treatment groups. In TG 1 there was no difference between nonirradiated and irradiated patients (0.97 vs. 0.94) and the non-ir-radiated patients showed a better trend. In TG 2, and in TG 2 and TG 3 combined, the pDFS was significantly worse for non irradiated patients in comparison with the irradiated patients (TG2:0.78 vs. 0.92; TG 2 +3:0.79 vs. 0.91). Compared to former DAL-HD trials the pOS stayed stable despite therapy reduction. CONCLUSIONS: A reduction of radiotherapy to 20 Gy for patients in all stages with good response to chemotherapy is possible without deterioration of the results. The omission of radiotherapy for patients in complete remission after chemotherapy is recommended only for patients in early stages (TG1). In future trials the possibility of a wider selection for chemotherapy alone for this group needs to be evaluated. In intermediate (TG2) and advanced (TG3) stages omission of radiotherapy for patients incomplete remission results in a lower pEFS, but the pOS is not significantly reduced. Only with knowledge of the long term effects of today's therapy we can give a satisfactory answer to the question whether in future trials the primary aim should be pEFS as high as possible due to front-line-therapy or reduction of late effects.

[Sentinel lymph node excision (SLNE) and positron emission tomography in the staging of stage I-II melanoma patients]. / Schildwächterlymphknotenexzision (SLKE) und Positronenemissionstomographie (PET).Staginguntersuchungen bei Melanompatienten in den klinischen Stadien I-II (nach DDG): Erfahrungen aus der Hautklinik Dortmund.

BACKGROUND AND OBJECTIVE: Sentinel lymph node excision (SLNE) and positron emission tomography (PET) were evaluated in the staging of 51 Stage I and II melanoma patients (staged according to the guidelines of the German Dermatological Society). PATIENTS/METHODS AND RESULTS: Tumor thickness ranged from 1.0 mm to 6.0 mm (median: 1.5 mm; mean: 2.07 mm). At least one sentinel lymph node (SLN) was excised in all patients; 80 SLN were excised from 69 lymphatic drainage areas. Positive SLN were detected in 6 patients (11.8%). Additional positive lymph nodes were not detected in any of these patients in the following complete lymph node dissection of the affected lymph node basin. Preoperative PET was performed in 40 patients and did not detect any of the micrometastases that were subsequently found by SLNE. During the follow up of 7-40 months (mean 21.9 months) 3 patients experienced tumor progression; 2 of 3 had a positive SLN. CONCLUSIONS: According to the current literature SLNE is recommended in primary tumors greater than 1 mm thickness. PET cannot be expected to give additional information in the staging of stage I-II patients.

[The significance of the autopsy--now and in the future]. / Die Bedeutung der Autopsie--heute und morgen.

The significance of the autopsy is reflected in the quality control of medical diagnosis and therapy, as well as in the social relevance of the autopsy findings for the individual, family and society in general ("individual" and social epidemiology). Contemporary statistics from research of the literature and internet will be presented and interpreted in a modern context. A pre-requisite for a quality control function is an adequately high autopsy rate, which should be a factor taken into consideration for the registration und certification of a clinic or hospital. There are some valuable studies cited which assess the significance of autopsy as a means of quality control in clinical surgery, oncology and general internal medicine. There is, on the other hand, a decline of autopsy rates worldwide, but especially in the Federal Republic of Germany since the beginning of the 90ties. In addition, the causes will be demonstrated and discussed briefly. The attitude of medical colleagues and health insurance companies, as well as public opinion and politics, all influence the significance of and attitude to the autopsy, including the readiness to create and maintain a transparent legal and cost-covering framework. A spectrum of the differing opinions, obtained from various discussions, will be given. In addition, the necessary legal and financial regulations to facilitate and sustain the autopsy service at a sufficiently high rate (at least 30%, based on statistical considerations) will be discussed in the context of desirable short- and long-term solutions.

High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The German-Austrian Pediatric Hodgkin's Disease Study Group.

PURPOSE: To further reduce therapy-related late effects in patients with pediatric Hodgkin's disease (HD) while maintaining the high cure rates achieved with vincristine, prednisone, procarbazine, and doxorubicin (OPPA) or OPPA/cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) chemotherapy and involved-field radiotherapy. The risk of testicular dysfunction was addressed by substituting etoposide for procarbazine (OEPA) in the induction therapy for boys. Radiation doses and fields were further reduced. PATIENTS AND METHODS: Three hundred nineteen boys and 259 girls younger than 18 years with previously untreated HD, enrolled onto the study between 1990 and 1995, were allocated to treatment group (TG)1 (early stages), TG2 (intermediate stages), or TG3 (advanced stages). All groups underwent two cycles of OEPA (boys) or OPPA (girls) for induction chemotherapy. TG2 and TG3 continued on additional two or four cycles, respectively, of COPP. Low-dose radiotherapy was given to the initially involved sites, ie, reduced involved fields. RESULTS: Initial response to OPPA or OEPA induction was virtually identical. Eight of 578 patients experienced early progression of HD. Thirty-seven relapses, three secondary tumors, and no secondary leukemias have been recorded, with a median follow-up duration of 5.1 years (maximum, 8.1 years). Thirteen of 578 patients died. The probability of 5-year event-free survival/overall survival is 91%/98% in the total group, 94%/97% with OPPA, and 89%/98% with OEPA induction therapy. Risk factor analysis showed two significant prognostic factors: histologic subtype NS2 and "B" symptoms. OEPA induction therapy, large mediastinal tumor, and age were not significant. Preliminary studies of testicular function indicate a lower risk of germ cell damage than previously documented with OPPA. CONCLUSION: OEPA is a satisfactory alternative to OPPA. Radiotherapy can be confined to involved sites when combined with appropriate chemotherapy. The DAL-HD-90 regimen represents a comprehensive treatment program for all stages of pediatric HD and offers a favorable benefit/risk ratio, combining excellent disease control, moderate acute toxicity, and reduced long-term toxicity.

[Multi-national therapy study for Hodgkin's disease in children and adolescents GPOH-DH 95. Interim report after 2 1/2 years]. / Multinationale Therapiestudie für den Morbus Hodgkin bei Kindern und Jugendlichen GPOH-HD 95. Zwischenbericht nach 2 1/2 Jahren.

Based on concepts of the successful German-Austrian pediatric Hodgkin studies DAL-HD 78 until-90, a new trial was initiated addressing the question whether radiotherapy can be further reduced or can be omitted in case of complete remission after initial chemotherapy, aiming at reduction of sequelae after radiotherapy, especially radiogenic second malignancies. In respect to CHEMOTHERAPY patients are stratified into 3 therapy groups (TG) according to stage and gender: 2 courses of OPPA (girls) or OEPA (boys) in TG1 (stage IA/B, IIA), and in addition 2 (TG2: stage IEA/B, IIEA, IIB, IIIA) or 4 (TG3: stage IIEB, IIIEA/B, IIIB, IVA/B) COPP courses. Boys with stage IIIB and IIIEB receive OPPA instead of OEPA. RADIOTHERAPY is administered according to response to chemotherapy independent of stage: patients with complete remission or minimal residues do not receive irradiation; patients with more than 75% tumor regression are irradiated to involved fields at a dose of 20 Gy. Doses of 30 or 35 Gy are given to regions with tumor regression below 75% or residual bulky tumor of > 50 ml, respectively. INTERIM RESULTS: From 8/95 till 1/98 we registered 385 patients under the age of 18 years from Germany, Austria, Switzerland, Sweden and the Netherlands. Therapy has been completed in 334 patients. Three patients with solitary nodular paragranuloma were treated with surgery only. Out of 331 patients 89 (26.9%) achieved a complete remission with chemotherapy. Tumor regression of more than 75% was seen in 193 (58.3%) patients and below 75% in 39 (11.8%) patients. Tumor progression during chemotherapy occurred in 1 (0.3%) patient. Response after chemotherapy was not evaluable for 9 (2.7%) patients. Radiotherapy was omitted in 91 (27.1%) patients: in TG1 50 of 142 (34%) patients, TG2 24 of 98 (24.5%) patients and TG3 18 of 94 (19.2%) patients. Initially involved regions were irradiated at a dose of 20 Gy in 164 of 334 (49.1%) patients. Doses up to 30 Gy or 35 Gy were given to 19 (5.7%) or 57 (17.1%) patients respectively. Events (tumor progression, relapse or death) occurred in 23 of 334 patients until now. The event-free survival rate is 0.91 at 2 1/2 years for all study patients and 0.89 for patients without radiotherapy. Six relapses occurred in 91 patients without radiotherapy. No relapse occurred in TG1 (n = 49), but in 5 of 24 TG2-patients, and in 1 of 18 TG3 patients without radiotherapy. As yet, the results are not significantly inferior compared with trial DAL-HD 82. Therefore this trial aiming at omitting radiation therapy in patients with complete remission after a short lasting chemotherapy will be continued. Longer follow up is necessary for final evaluations and conclusions.

Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin's disease.

PURPOSE: To determine the appropriate irradiation dose after four cycles of modern combination chemotherapy in nonbulky involved field (IF/BF) and noninvolved extended-field (EF/IF) sites in patients with intermediate-stage Hodgkin's disease (HD). MATERIALS AND METHODS: HD patients in stage I to IIIA with a large mediastinal mass, E stage, or massive spleen involvement were treated with two double cycles of alternating cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by EF irradiation in two successive trials (HD1 and HD5). In the HD1 trial (1983 to 1988), 146 patients who responded to chemotherapy were randomized to receive 20 Gy (70 patients) or 40 Gy (76 patients) of EF irradiation in all fields outside bulky disease sites. A cohort of 111 patients who fulfilled the same inclusion criteria in the subsequent trial HD5 (1988 to 1993) were treated with 30 Gy. Bulky disease always received 40 Gy. RESULTS: Freedom-from-treatment-failure (FFTF) and survival (SV) curves showed no differences between the 20-, 30-, and 40-Gy groups. However, acute toxicities were more frequent in the 40-Gy arm. Analysis of relapse patterns showed that 18 of 26 relapsing patients either failed to respond in initial bulky sites (n = 5) or had an extranodal relapse (n = 9) or both (n = 4). After 5 years, the cumulative risk for relapse in bulky sites is 10%, despite 40 Gy of radiation. CONCLUSION: Our results strongly suggest that there is no relevant radiotherapy dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4 months of modern polychemotherapy in patients with intermediate-stage HD. Relapse patterns indicate that patients destined to relapse need more systemic, rather than local, treatment. Based on our data, we conclude that 20 Gy is sufficient in EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy.

[Acute kidney failure in a recurrence of sarcoidosis at the height of summer]. / Akutes Nierenversagen bei Sarkoidose-Rezidiv im Hochsommer.

HISTORY AND FINDINGS: A 35-year-old woman with sarcoidosis, successfully treated 3 years previously, developed fatigue, nausea and loss of weight during a summer holiday in Italy where she was exposed to much bright sun. There had been no previous recurrence of the sarcoidosis. On return she was found to be in renal failure with marked hypercalcaemia. Physical examination merely revealed peasized non-tender submandibular and cervical lymph nodes, but was otherwise unremarkable. INVESTIGATIONS: Serum creatinine and calcium concentrations (3.8 mg/dl and 3.6 mmol/l) were markedly elevated. Computed tomography showed an enlarged submandibular lymph node, but no other organ abnormality. Biopsy of the salivary gland demonstrated recurrent sarcoidosis. TREATMENT AND COURSE: Calcium concentration became normal (2.4 mmol/l) within two weeks of treatment with methylprednisolone (100 mg daily for 3 days, followed by gradual reduction to 30 mg daily for 3 months, until discontinued slowly). Creatinine concentration, which had fallen to 1.5 mg/dl, was at the upper limit of normal (1.1 mg/dl) after 4 months and 0.8 mg/dl after 8 months. CONCLUSION: Marked exposure to UV light should be avoided in patients with a history of recent sarcoidosis, because it increases the formation of vitamin D3 precursors: In the case of recurrent sarcoidosis, these precursors are converted to 1,25 dihydroxyvitamin D3 in the sarcoidosis granulomas. This can lead to severe complications, such as hypercalcaemia and renal failure.

[Multicenter reticulohistiocytosis. Therapy with azathioprine and prednisolone]. / Die multizentrische Retikulohistiozytose. Therapie mit Azathioprin und Prednisolon.

A 86-year-old woman presented with a 3-month history of painless reddish nodules on fingers, nose and earlobes, together with polyarthralgia that had pre-existed for 9 months before. The diagnosis of multicentric reticulohistiocytosis was confirmed by histology. No underlying malignancy was found. On administration of systemic prednisolone and azathioprine the skin lesions resolved and the joint symptoms cleared up completely. Therapeutic aspects are discussed.

Hodgkin's disease in children: combined modality treatment for stages IA, IB, and IIA. Results in 356 patients of the German/Austrian Pediatric Study Group.

UNLABELLED: 356 children below 16 yrs of age with CS/PS IA, IB, and IIA were treated in the studies HD-78, HD-82, HD-85, HD-87, and OEPA-pilot 87 between June 1978 and Sept 1990. All patients received combined modality treatment (CMT) with 2 courses of chemotherapy (CT). In HD-78 and HD-82, the MOPP-derived drug combination OPPA (ADR instead of mechlorethamine) was applied. Extended-field radiotherapy (RT) was given in HD-78 using 36-40 Gy to involved-fields (IF) and 36-40 Gy vs. 18-20 Gy to adjacent fields. In HD-82 only IF-RT was applied using 35 Gy. When gonadotoxic effects of procarbazine (PC) in boys was detected in follow-up examinations, this drug was eliminated in studies HD-85 and HD-87 (OPA). Dosages of IF-RT were 35 Gy in HD-85 and 30 Gy in HD-87. With HD-87 a simultaneous pilot study was initiated to test the new combination OEPA (E = etoposide) together with 25 Gy IF-RT. RESULTS: (May 1993): Rates for event-free survival and survival are HD-78 (73 patients): 0.90 and 0.97 at 10 yrs; HD-82 (100 patients): 0.98 and 1.0 at 10 yrs; HD-85 (53 patients): 0.85 and 0.98 at 8 yrs; HD-87 (104 patients): 0.85 and 0.99 at 6 yrs; OEPA-pilot (26 patients): 0.96 and 0.96 at 5 yrs. No secondary leukemias, MDS, or solid tumors were observed in 14-yr observation time. After 2 OPPA, elevated FSH levels indicating impaired spermatogenesis were found in 29% of male patients. In contrast, after 2 OPA (without PC) only normal FSH levels were observed. In female patients, no gonadal dysfunction was found. Subclinical hypothyroidism was seen only after RT doses of > 30 Gy to the neck. Cardiomyopathies were not observed. CONCLUSION: 2 OPPA plus IF-RT using < 30 Gy can presently be considered optimal therapy for girls with localized HD. 2 OEPA plus 25 Gy IF-RT are being evaluated for boys in a phase III study (HD-90). In summary, there are good reasons to use CMT in early stages of HD in children, provided a highly effective CT of short duration and low long-term toxicity with low-dose IFI is applied.

Classification of Hodgkin's disease biopsies by a panel of four histopathologists. Report of 1,140 patients from the German National Trial.

First results from reviewing the diagnostic biopsies of Hodgkin's lymphomas (HL) are reported. Biopsies from 1,140 patients were evaluated by consensus diagnoses according to an extended classification of the British National Lymphoma Investigation. 95 of the recruited cases (8.3%) were omitted and not approved as Hodgkin's lymphoma. The remaining 1,045 biopsies were classified as follows: Lymphocytic predominance 31 (2.7%); Nodular sclerosis (NS) 660 (57.9%), Mixed cellularity (MC) 159 (13.9%); Lymphocytic depletion 8 (0.7%); unclassifiable Hodgkin's 148 (13.0%). The unproved Hodgkin's cases [95 (8.3%)] were divided into non-Hodgkin's lymphomas 32 (1.9%), uncertain due to inadequate techniques 32 (2.8%), borderline between Hodgkin's- and Non-Hodgkin's lymphoma 23 (2.0%). Major dissent on this question involved 17 cases (1.5%) and 1 case which was non-malignant. All unclassifiable, borderline or dissent cases were reassessed after the histologic techniques were improved, and immunophenotyping and clinical data reevaluated. The rate of agreement among the observers was about 81.6%, varying between 23.8% in grade 2 NS to 85.0% in both NS groups. Only 62.8% of all primary diagnoses were approved by the final diagnoses of the panel. Important differences in the classification of the British National Lymphoma Investigation concerns the NS-group and mainly its grade 2 subtype. MC was identical in both classifications. Clinico-pathologic correlation of actuarial survival times revealed a significantly worse outcome of MC vs NS, < 20% after 80 months observation. Only slightly significant better survivals were found in grade 1 vs grade 2 NS. Significant differences in unclear compared to all Hodgkin's, were found and the worst survival was in the NHL group.

Histopathological classification of Hodgkin's lymphomas. Results from the reference pathology of the German Hodgkin Trial.

Diagnostic biopsies of 1,140 previously untreated patients with Hodgkin's lymphoma from the German Hodgkin Therapy Trial were evaluated by a panel of 4 histopathologists. Each case was classified by consensus of the four according to an extended Rye-System including the diversifying of NS.HD and the unclassifiable cases. The interobserver agreement rate was 92.1% among the panel members regarding the final classification. Primary Hodgkin diagnosis was approved in 91.7% (1045/1140 cases). The distribution of the 1,140 cases within this system was (in %) as follows: 2.7 LP.HD, 57.9 NS.HD, 17.3 MC.HD, 0.7 LD.HD, 13 HD of unclassifiable subtypes, 6.3 of not certain HD, 1.9 Non-Hodgkin Lymphoma, 1 case of non malignancy. Grading of NS.HD into 2 subgroups according to the British classification differed conspicuously by 84.5% versus 15.5% and 71.6% versus 28.4% in British results. This divergency is explained by interobserver disagreement ranking from 43% to 85%.

[Borderline between Hodgkin and non-Hodgkin lymphomas with unfavorable clinical course: a clinical, histological and immunohistochemical analysis of 33 cases within the German Hodgkin Lymphoma Study]. / Grenzfälle zwischen Hodgkin- und Non-Hodgkin-Lymphomen mit ungünstigem klinischen Verlauf: Klinische, histologische und immunhistochemische Analyse von 33 innerhalb der Deutschen Hodgkin-Studie behandelten Fällen.

Reevaluation of diagnostic biopsies from 502 patients who entered the German Hodgkin Therapy trial was performed by a panel of four pathologists. Classification revealed 90% of unambiguous Hodgkin-lymphomas (HL), 1.6% of Non-Hodgkin-lymphomas (NHL) and 8.4% of cases difficult to evaluate, reflecting to the well-known problem of the border between these 2 groups of lymphoma. As these cases had the worst prognosis, a second attempt of reclassification, including immunohistochemical studies, was made, resulting in final classifying of 25% of these cases as NHL, 50% as HL, and 25% as further unclassifiable. The most common differential diagnostic problem was separating pleomorphic nodular sclerosing HL from large cell NHL's and HL with rather few Hodgkin- or Reed-Sternberg-cells from Lennerts lymphoma or angioimmunoblastic lymphadenopathy. Immunohistochemistry was helpful for the differential diagnostic decisions in these individual cases. A very high percentage of these problem cases had initially entered the trial as lymphocyte depleted HL, and the large majority of deaths came from the large cell NHL group.

Characterization of giant cells in Hodgkin's lymphomas by immunohistochemistry applied to randomly collected diagnostic biopsies from the German Hodgkin Trial.

A panel of 10 monoclonal antibodies reactive with formalin-resistant epitopes was applied to characterize the giant cells of the Reed-Sternberg, Hodgkin, and lacunar cell types in diagnostic biopsies from the German Hodgkin Trial. The 94 tissue samples examined had been sent to the Reference Center by 44 different laboratories which made the initial diagnoses. A board of four referees re-classified the primary diagnoses established by the 44 different histopathologists, providing subtyping of Nodular Sclerosis according to Bennett et al. (1985, 1989). Only cases with unequivocal agreement among the referees and which satisfied standards of fixation and embedding were included. Giant cells stained positively with: Ber-H2 in 92 per cent (81/88), LN-2 in 86.4 per cent (76/88), and DAKO-M1 in 72.2 per cent (64/88) of cases in which the lymphocyte predominance type was not included. Positive staining was quite rare with the other seven monoclonal antibodies. No significant difference in reactivity was revealed between giant cells of Reed-Sternberg, lacunar or Hodgkin cell types. Approximately one third of the cases were negative for at least one of the markers, Ber-H2, LN-2 or DAKO-M1. The lymphocytic and histiocytic cells in lymphocyte predominance Hodgkin's disease displayed a distinctive staining pattern with positivity for B-cell markers, whereas DAKO-M1 and Ber-H2 were predominantly negative. Finally, we found that randomly collected blocks of primary biopsies permit reliable immunostaining by this panel of monoclonal antibodies, since our results agree with results from the literature obtained from biopsies processed according to more uniform protocols for fixation and embedding.

An approach to reduce treatment and invasive staging in childhood Hodgkin's disease: the sequence of the German DAL multicenter studies.

UNLABELLED: From June 1978 through March 1987, 506 children under the age of 16, representing approximatively 70% of the children with Hodgkin's disease in West-Germany entered 3 consecutive multicenter studies at 68 centers. The general objective of these study sequence is to maximize the chance of cure while minimizing radiotherapy and chemotherapy as much as possible in a combined modality treatment concept. The purpose was also to reappraise the need for splenectomy and laparotomy and to define a staging policy which provides adequate evaluation of intraabdominal disease. Study II (HD-82) is described in detail. 203 protocol patients were enrolled between Dec. 1981 and Dec. 1984. Laparotomy was performed in 202 patients, but splenectomy only in 78 (38.4%) using an intraoperative decisional strategy, developed in Study I (HD-78). Patients were stratified according to stage into 3 groups (PS I/IIA, IIB/IIIA and IIIB/IV) receiving 2, 4 or 6 cycles of OPPA/COPP-chemotherapy. Radiotherapy was given only to the involved fields, the dose depending on the extent of chemotherapy (35, 30 or 25 Gy). RESULTS AND CONCLUSIONS: The event-free survival rates after 5 years are 96% (entire group), 99% (stage I/IIA), 96% (stage IIB/IIIA) and 90% (stage IIIB/IV). Thus, only involved field radiotherapy with reduced doses is needed, if a stage-dependent chemotherapy with 2, 4 or 6 cycles of OPPA/COPP is given. The strategy of selective splenectomy has proven very useful. Based on statistical analyses concerning abdominal involvement a clinical decisional strategy for selective laparotomy was developed. Further efforts are needed to reach a stepwise cautious and controlled narrowing-in on the therapy combining the lowest long-term toxicity with the highest chance of cure.

[Non-Hodgkin's lymphoma. Cytology and cytochemistry]. / Non-Hodgkin-Lymphome. Cytologie und Cytochemie.

Imprints of lymph nodes and tumor specimens from 442 patients with non-Hodgkin's lymphoma (NHL) were evaluated cytologically and cytochemically. With the exception of hairy cell leukemia, special forms of peripheral pleomorphic T-cell lymphoma, and lymph node plasmacytoma, all types of NHL of the Kiel classification were included in this study. The investigations were performed on slides stained with Pappenheim (May-Grünwald-Giemsa) or conventional cytochemical techniques for substrate and enzyme demonstration, such as periodic acid Schiff (PAS), neutral and acid non-specific alphanaphthyl acetate esterase, and acid and alkaline phosphatase. In certain cases further techniques for substrate and enzyme demonstration, including myeloperoxidase and naphthol AS-D chloroacetate esterase, were used. We combined the cytologic and cytochemical evaluation with an attempt to diagnose the type of lymphoma on imprints without prior knowledge of the histologic findings or clinical data, in other words, blind. At the same time, we attempted to distinguish the NHL from reactive lymph node lesions, nonlymphoid malignant tumors, and systemic diseases. For this purpose, 75 cases of lymphadenitis and 33 cases of nonlymphoid neoplasia were mixed with the NHL for a blind test. In the following we will summarize the results pertaining to the NHL only. Chronic lymphocytic leukemia of B type (B-CLL; n = 75) was cytologically characterized by the presence of so-called prolymphocytes and paraimmunoblasts and a predominance of lymphocytes. In our opinion, there are four main variants of B-CLL: small-cell ("mature") CLL, a type in which prolymphocytes are plentiful ("immature" CLL), LP immunocytoma-like ("basophilic") CLL, and a type of CLL with centrocyte-like lymphocytes ("B2-CLL"). B-CLL had no cytochemical profile of its own. The reproducibility of the diagnosis on imprints was 80%. In prolymphocytic leukemia of B type (B-PLL; n = 1) prolymphocytes and blast cells were plentiful. In the case studied, acid phosphatase activity was moderately strong (evident as granules distributed in a semicircular fashion and focally accumulated). In the blind test we diagnosed it only descriptively as an "acid phosphatase-rich lymphoma of low-grade malignancy with a high prolymphocyte and blast cell content". Chronic lymphocytic leukemia of T type (T-CLL) and prolymphocytic leukemia of T type (T-PLL) could not be distinguished with certainty in sections or imprints. There was also no strict delineation between T-CLL and T-PLL in blood smears. The T-CLL and T-PLL cases we evaluated (n = 4) belonged to the so-called helper cell type.(ABSTRACT TRUNCATED AT 400 WORDS)