Avascular osteonecrosis in patients treated for Hodgkin's disease

Abstract: The aim of this study is to assess the risk of avascular osteonecrosis (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 supradiaphragmatic 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.     

Lomustine, etoposide, vindesine, and dexamethasone (CEVD) in Hodgkin's lymphoma refractory to cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD): a multicenter trial of the German Hodgkin Study Group

Thirty-two patients with advanced Hodgkin's lymphoma resistant to cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were treated with a salvage chemotherapy regimen consisting of lomustine, etoposide, vindesine, and dexamethasone (CEVD). Twenty-seven patients were treated because of primary resistance to COPP/ABVD, and five patients were treated in early relapse (less than 12 months) after COPP/ABVD-induced complete remission. Fourteen patients (44%) achieved complete remission, and four patients achieved partial remission, with an overall response rate of 56%. Two partial responders achieved complete remission after additional radiotherapy. Four of five patients in early relapse after COPP/ABVD achieved complete remission. Consolidation radiotherapy was given for only one complete responder. Median duration of complete remission is greater than 10 months, and median survival is greater than 26 months. The treatment was well-tolerated. The main side effects were leukopenia, thrombocytopenia, mild nausea/vomiting, and cushingoid side effects. CEVD is a very active and well-tolerated salvage chemotherapy regimen in patients with Hodgkin's disease resistant to or relapsing after COPP and ABVD.     

Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome

The appropriate therapy for limited-stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is unclear. In contrast to classical Hodgkin lymphoma (CHL), chemotherapy is often omitted; however, it is unknown whether this impacts the risk of relapse. Herein, we compared the outcome of patients with limited-stage NLPHL treated in an era in which ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy was routinely incorporated into the primary therapy to an earlier era in which radiotherapy (RT) was used as a single modality. Using the British Columbia Cancer Agency Lymphoid Cancer Database, 88 patients with limited-stage NLPHL (stage 1A/1B or 2A, nonbulky disease < 10 cm) were identified. Treatment followed era-specific guidelines: before 1993, (n = 32) RT alone; and 1993 to present (n = 56), ABVD-like chemotherapy for 2 cycles followed by RT with the exception of 14 patients who received ABVD chemotherapy alone. Most patients were male (75%) with stage I disease (61%). In an era-to-era comparison, the 10-year time to progression (98% vs 76% P = .0074), progression-free survival (91% vs 65% P = .0024), and OS (93% vs 84%, P = .074) favored the ABVD treatment era compared with the RT alone era. Treating limited-stage NLPHL similarly to CHL may improve outcome compared with the use of radiation alone.     

Treatment of early-stage Hodgkin's disease with four cycles of ABVD followed by adjuvant radio-therapy: analysis of efficacy and long-term toxicity

BACKGROUND AND OBJECTIVES. The use of combined modality therapy in early-stage Hodgkin's disease can spare staging laparotomy and reduces the risk of relapse compared to radiation alone. This paper reports on the efficacy and long-term events of a combined modality approach consisting of a brief course of chemotherapy followed by adjuvant radiotherapy, without laparotomy, in early-stage Hodgkin's disease. DESIGN AND METHODS. This study included 78 patients with Hodgkin's disease (20 in stage I and 58 in stage II); 60% had mediastinal enlargement (12% had bulky disease) and 5% had subdiaphragmatic disease. Their median age was 33 years (range: 15-64) and median follow-up 60 months. The treatment program consisted of four cycles of ABVD followed by adjuvant radiation to involved sites (43 patients) or involved and contiguous sites of disease (35 patients); radiation doses ranged from 30 to 36 Gy to uninvolved and involved sites, respectively; bulky disease received up to 44 Gy. Gonadal function in women was assessed by hormonal tests and evaluation of menses; young men were given the opportunity to have their semen cryopreserved. RESULTS. The treatment program was completed in a median of 6.2 months (range: 5-10). The complete remission rate was 88% after 4 courses of ABVD and 98.7% after adjunctive RT. The 5-year relapse-free survival was 97% and overall survival 98%; three patients died, one of disease progression and two of small cell lung carcinoma. Long-term events included three cases of pulmonary fibrosis with symptomatic interstitial disease, one case of dilated cardiomyopathy with cardiac failure (all had received mediastinal radiation) and four cases of dysthyroidism. Fertility was preserved in young women, with three subsequent normal pregnancies. Second neoplasms included two small cell lung carcinomas and one breast carcinoma. INTERPRETATION AND CONCLUSIONS. In early-stage Hodgkin's disease, four cycles of ABVD followed by adjuvant radiotherapy produced a 5-year overall survival of 98%. Prolonged monitoring for therapy-related long term complications is mandatory in these potentially curable patients.     

Stage I-III Hodgkin's Disease: Outcome and Pattern of Failure Following Treatment with Radiation Therapy and Chemotherapy in a Modern Era

Purpose: To analyse the long term outcome, pattern of failure and treatment related complications after radiation therapy (RT) with or without chemotherapy for stage I—III Hodgkin's disease (HD).

Material and methods: Detailed records from 86 patients with stage I—III HD treated between 1989 and 1998, were retrospectively reviewed. Seventeen patients with favourable stage I-IIA were treated with RT alone, and the remaining 69 patients with combined modality treatment (CMT). Patients treated with RT received extended-field or subtotal nodal irradiation (STNI) to a total dose of 36–54 Gy, and patients with CMT, received involved-field irradiation to a lower doses, 26–40 Gy. The median follow-up time was 50 months (range 16–180).

Results: The 10-year overall survival (OS) for the whole group was 96% (SE 2%), 100% for stage I, 95% for stage II and 100% for stage III patients. Of potential prognostic factors analysed for statistical significance, only the response to chemotherapy (p = 0.0393) was found to influence significantly OS rates. Twelve patients (13.9%) relapsed. Salvage treatment was effective in 10 of the 12 relapsed patients. The 10-year freedom from treatment failure (FFTF) was 79% (SE 6%). Although 8 (9.6%) of the 83 surviving patients developed late effects that could represent toxicity from the treatment, no patient died of late complications.

Conclusions: RT alone for favourable early stage HD attains good survival rates with a modest treatment related morbidity. For patients with unfavourable stage II and stage III HD, CMT with limited RT provides a good to excellent prognosis.     

Comparison between hybrid MOPPABV and ABVD chemotherapy protocols for Hodgkin’s lymphoma in public hospitals of the largest South American city—a retrospective 14-year study

The behavior of Hodgkin’s lymphoma (HL) is different in developing countries, perhaps due to differences in epidemiology and population access to health care. We performed a retrospective study comparing the efficacy of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPPABV) versus adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy protocols as first-line therapy for HL in a Brazilian population. A hundred and eighty-six HL patients were retrospectively analyzed regarding their first-line treatment with MOPPABV and ABVD at two public hospitals in São Paulo, Brazil. Eligible patients were either previously untreated or at first relapse after being treated with only radiotherapy with confirmed HL diagnosis. At a median follow-up of 9 years, complete remission is 89.5 and 85.9 (P?=?0.3), overall survival 93.8% and 89.6% (P?=?0.68), disease-free survival 85.6% and 81.6% (P?=?0.41), and relapse ratios 20.9% and 26.4% (P?=?0.17) for ABVD and MOPPABV, respectively. Extended-field radiation therapy postchemotherapy was mostly used in the MOPPABV group. There were three cases of secondary neoplasm (colon adenocarcinoma, myeloid chronic leukemia, and non-Hodgkin’s lymphoma), all associated with MOPPABV. ABVD and MOPPABV protocols as first-line treatment for HL resulted in similar therapeutic outcomes and did not influence overall survival, disease-free survival, and relapse ratio. MOPPABV was related to a higher risk of secondary malignancy and, therefore, ABVD should be considered a better option for HL therapy. These findings corroborate recent data in literature.     

Therapeutic implications of mediastinal involvement in advanced Hodgkin's disease

47 patients with advanced Hodgkin's disease (stage IIIB or IV) and mediastinal involvement, treated during the period 1969-78 and followed till death or from 36 to 126 months after initiation of therapy, were analysed. All 47 patients had received combination chemotherapy (MOPP or equivalent regimens). 20 had also received additional radiotherapy to mediastinum (and in some cases to other involved areas as well). The 2 treatment groups did not differ significantly with regard to the more important prognostic factors. Both in the case of stages IV and IIIB patients in the group treated with combination chemotherapy alone, remissions were significantly more often only partial, the frequency of relapse and of treatment failure was significantly higher, and relapse-free survival was significantly poorer than in the group treated with additional radiotherapy. Furthermore, survival from Hodgkin's disease and crude survival including all causes of death were significantly better for patients treated with combination chemotherapy plus mediastinal irradiation. Consequently, for patients with advanced Hodgkin's disease and mediastinal involvement a combined approach including radiotherapy as well as combination chemotherapy would seem advisable.     

Combined modality (ABVD plus radiotherapy) versus radiotherapy in the management of early stage (IIA) Hodgkin's disease with mediastinal involvement.

The aim of this study was to establish whether combined modality treatment (ABVD plus radiotherapy) can reduce the risk of relapse in Hodgkin's disease patients with mediastinal involvement, as compared to radiotherapy alone. The results obtained suggest that one course of ABVD before irradiation can reduce the incidence of relapse. These findings, however, should be considered preliminary and need to be confirmed in larger studies.     

Critical value of laparotomy with splenectomy in stage III Hodgkin's disease as restaging procedure after chemotherapy

38 patients with stage III Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first line chemotherapy which included MOPP, ABVD, or both. 28 patients were judged to be in clinical complete remission (CR) and 10 were resistant or had relapsed. Among patients in CR, 27 (96%) were confirmed to be in pathological CR; among patients resistant or relapsed, 9 (90%) were confirmed to have disease in the abdomen or retroperitoneum. The therapy for patients in clinical remission before laparotomy consisted of TNI or sTNI in 19 patients, mediastinal radiation in 6 patients and no further therapy in the remaining 3 patients. No significant differences were seen in survival and relapse-free survival between those patients treated by extensive and those treated by local radiotherapy or no further therapy. Instead, among those patients who received extensive radiotherapy 3 developed acute non-lymphoid leukemia (ANLL). The therapy for this group of patients consisted of further chemotherapy in 7 who had concomitant liver involvement and TNI in the remaining 3 who had the disease confined to the spleen and/or lymph nodes. Among these patients, only 3 obtained CR; 2 with radiation and 1 who was resistant to MOPP, with ABVD. This study leads us to re-consider the role of laparotomy in stage III HD which should be used as non-routine procedure only in selected patients without poor prognostic factors who may be cured by radiotherapy alone. In patients resistant to chemotherapy, an early evaluation of disease in the abdomen may be useful for a better salvage treatment.     

A prospective clinical trial comparing chemotherapy,radiotherapy and combined therapy in the treatment of early stage Hodgkin‘s disease with bulky disease

We performed a randomized clinical trial to assess the usefulness and toxicity of combined therapy compared with chemotherapy and radiotherapy in the treatment of early stage Hodgkin‘s disease with bulky disease as an adverse prognostic factor. Three-hundred and seven patients were enrolled into the study. They were randomized to receive either radiotherapy (extended field, generally mantle, 3500 cGy), or chemotherapy (adriamycin, bleomicin, vinblastine and dacarbazine: ABVD, 6 monthly) cycles or combined therapy (three cycles of ABVD, followed by irradiation therapy and three more cycles of chemotherapy). The median follow-up duration from start of treatment was 11.4 years. Complete response rates were similar in the three arms: 83% for radiotherapy (95% confidence interval [CI] 67–92%), 80% for chemotherapy (CI 69–88%) and 87% for combined therapy (CI 74–94%). However, disease-free survival and overall survival were better in the patients treated with combined therapy. At 12 years 76% (CI 51–93%) of the patients treated with combined therapy remained alive in the first complete remission compared with 42% (CI 26–61%) in patients treated with radiotherapy and 48% (CI 31–57%) in patients who had received chemotherapy alone (P < 0.01). Improvement in overall survival was also evident at 12 years: 88% (CI 59–93%) in those who had received combined therapy, compared with 53% (CI 36–67%) in the radiotherapy arm and 59% (CI 35–67%) in the chemotherapy group. Acute toxicity was more frequent in patients treated with combined therapy, but no death related treatment was observed in the three groups. Late toxicity was similar in the three treatment groups. Combined therapy with extended field radiotherapy and six cycles of chemotherapy is an effective treatment of patients with early stage bulky Hodgkin‘s disease compared with chemotherapy or radiotherapy alone.     

Results of three courses of adriamycin, bleomycin, vindesine, and dacarbazine with subtotal nodal irradiation in 189 patients with nodal Hodgkin’s disease (stage I, II and IIIA)

Aim of the study. To evaluate in a prospective trial three courses of an ABVD-like chemotherapy (CT) regimen given before radiation therapy (RT) (subtotal nodal irradiation (STNI)) in favorable stage Hodgkins disease (HD). The efficacy, risk factors and medium-term toxicities are reported. Patient characteristics. Stage I or II with at least one of the following factors, mediastinal involvement, histological type 3, age > 40 years, ESR rate > 50 mm, or stage IIIA. 189 patients with newly diagnosed HD were treated between 01/86 and 01/94 (stage I, n = 33; stage II, n = 129, stage IIIA, n = 27). Three courses of an ABVD-like regimen (adriamycin 25 mg/m², bleomycin 10 mg, vindesine 2 mg/m² and dacarbazine 250 mg/m² day 1 and 8) were given before STNI at 36/40 grays. At diagnosis, prognostic factors were distributed as follows: B symptoms (n = 54), bulky mediastinum (n = 41), hemoglobin < 12 g/dl (n = 37), ESR > 50 (n = 65), age > 45 (n = 24). Results. After chemotherapy, 90% had an objective response (partial response > 75%) and 98% were in complete remission (CR) at the end of RT. Three patients had primary refractory disease and 13 patients (7%) relapsed, 3 at the initial site, 4 at previously uninvolved sites and 6 at both. With a median follow-up of 60 months, 170 patients are in 1st CR, 5 in 2nd or greater CR and 11/14 patients have died from HD. Bulky mediastinum (p = 0.009), age > 45 years (p = 0.03) and ESR >50 mm (p = 0.05) were adverse prognostic factors for survival. Bulky mediastinum (p = 0.009) was the only prognostic factor for freedom from progression. Toxicities. Two patients died from treatment related toxicity and one patient died with an osteogenic sarcoma. No secondary leukemia has so far been detected. 24 pregnancies were reported. Cardiopulmonary toxicity was always < grade 1 (WHO) in 95 patients evaluated. Two patients over 45 years old had a myocardial infarction. Conclusion. With an acceptable medium-term toxicity, this treatment achieved 85% survival at 5 years.     

Increasing interdependency of prognosis- and therapy-related factors in Hodgkin's disease

Two subsequent series of patients with Hodgkin's disease (HD) treated according to different therapeutic plans were compared: the study made it possible to analyze the role played by therapy in influencing the individual importance of a group of well-known prognostic factors. Study 1 concerned 667 patients treated in the period 1971-1979 without special measures for mediastinal bulky disease and with four-drug chemotherapy regimens (MOPP, COPP, ABVD) for stage B or IV. Study 2 included 220 patients treated between 1980 and 1984 with combined sandwich chemoradiotherapy when mediastinal bulk was present, and with eight-drug alternating chemotherapy regimens for stages B or IV (MOPP/ABVD, CcVPP/ABVD). Distribution of epidemiologic and clinical characteristics as well as staging accuracy were comparable in the two series. Only sex, serum albumin at onset and success or failure in achieving complete remission showed the same ability to discriminate survival in both studies. Age, stage and histology retained a reduced role in Study 2, where it was found they could be handled as binary variables, i.e. more or less than 50 years of age, stage IV or other stages, lymphocyte depletion histotype or other types. The influence of B symptoms on survival was sharply decreased in patients treated with alternating chemotherapy regimens, whereas combined sandwich therapy showed a truly leveling effect on the role of mediastinal bulk, which has to be considered a very unfavorable factor with other treatments. In HD the evaluation of clinical findings with respect to their impact on prognosis is crucial for validating and graduating the staging process, and for matching the intensity of the therapy to the needs of the patient. The ongoing evolution in the roles of single prognostic factors due to therapy needs periodic reevaluation for proper adjustments of therapeutic strategies.     

A population-based study of the outcome for patients with first relapse of Hodgkin's lymphoma

BACKGROUND: Our aims were to evaluate the response to salvage treatment in relation to initial treatment and to evaluate prognostic factors at the time of relapse in an unselected population of relapsing patients with Hodgkin's lymphoma (HL). PATIENTS AND METHODS: In total, 124 patients younger than 60 yr of age with initial diagnosis of HL in Sweden relapsed between 1985 and 1995. RESULTS: Fifty-eight patients relapsed after initial treatment with radiotherapy (RT) only, 62 after combination chemotherapy (CT), of whom 30 had received additional involved-field RT, and four after a short course of CT followed by extended-field RT. For 37 patients among the 58 relapsers after initial RT treated according to the recommendations of the National guidelines, the 5-yr Hodgkin-specific survival (HLS) was 85%, overall survival (OS) 73% and event-free survival (EFS) 62%, which is not inferior to survival in patients with primarily advanced stages. It was poorer in the 21 patients who initially had received RT only, even though they had been recommended for more extensive treatment. For patients initially treated with a full course (6-8 cycles) of CT the 5-yr HLS was 60%, OS 58% and EFS 22%. Bulky disease and age at diagnosis strongly affected survival in a multivariate analysis. CONCLUSIONS: Patients initially treated with RT who relapse have a favourable outcome, provided they have been treated according to the recommendations of the guidelines at the time of diagnosis. Initially bulky disease and, as a consequence, additional RT as part of the initial treatment negatively affect survival at relapse in patients initially treated with a full course of CT.     

The addition of radiotherapy to chemotherapy does not improve outcome of early stage Hodgkin’s lymphoma patients: a retrospective long-term follow-up analysis of a regional Italian experience

We retrospectively reviewed 139 stage I–II HL patients who were diagnosed and followed up in an Italian northern region (Liguria) from 1995 to 2007, and who received either chemotherapy (CT) alone (mainly doxorubicin, bleomycin, vinblastine, and dacarbazine; ABVD) or a combined modality treatment (chemotherapy + radiotherapy, CT + RT). The two therapeutic groups were comparable for clinical and histologic features. Complete remission rate after CT + RT was higher than what was achieved with CT alone (96% vs. 84%, respectively, p = 0.03). Relapse rate (12%) was the same in both groups and disease-free survival curves were comparable (82% and 83%, p = 0.47). The overall survival of the two therapeutic groups is comparable. No second tumors have been reported among patients receiving chemotherapy alone, whereas a second neoplasia has been diagnosed in four patients (in two cases possibly radiotherapy related) in the CT + RT group (5%, p = 0.09) In conclusion, our retrospective study shows that CT + limited RT is an effective and well-tolerated option for early stage Hodgkin’s lymphoma, even if the use of RT is associated with a certain risk of developing a second tumor. However, four to six courses of ABVD can lead to similar, optimal, long-term disease control without exposing patients to the risk of a second neoplasia.     

Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) salvage of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP)-resistant advanced Hodgkin's disease

Thirty-nine patients with advanced Hodgkin's disease were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Thirty-one of these patients had previously failed to respond to MOPP (mechlorethamine, vincristine, prednisone, and procarbazine) treatment (29 patients) or to CCVPP (lomustine, cyclophosphamide, vincristine, procarbazine, and prednisone) treatment (two patients). Twenty-seven patients were considered evaluable: eight (30%) achieved complete remission (CR), two (7%) achieved partial remission (PR), and 17 (63%) had no response. All of the complete responders are still in continuous unmaintained CR, while 14 of the 19 partial responders and nonresponders have died. The overall median survival was 21 months; it was 16 months for partial responders and nonresponders. The remaining eight patients had ABVD substituted to MOPP early in treatment, because of allergy to procarbazine: six patients achieved CR and two achieved PR. Our results are in keeping with the literature data and confirm the effectiveness of ABVD as primary and salvage treatment in advanced Hodgkin's disease.     

Absence of treatment-induced second neoplasms after ABVD in Hodgkin''s disease

One of the most serious complications of successful treatments for Hodgkin's disease is an increased incidence of acute nonlymphocytic leukemia (ANLL) and other malignancies. A retrospective analysis carried out on 1032 consecutive patients with Hodgkin's disease admitted to our Institute between 1965 and 1978 and treated with radiotherapy (RT) or chemotherapy or both modalities revealed that within 10 yr from initial therapy. ANLL was documented in 3% of patients, and over a comparable period of time 7.9% of patients developed other malignancies. ANLL was observed only in patients treated with chemotherapeutic regimens containing alkylating agents and/or procarbazine either alone (2.3%) or associated with RT (4%). Other second tumors were documented in patients given RT with or without chemotherapy. No second malignancies were observed in patients given ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) with or without RT. The incidence of ANLL was higher in patients given chemotherapy as salvage treatment upon relapse following primary irradiation (6.1%) compared to patients initially treated with combined modality (1.5%). The difference, however, failed to reach statistical significance. Since our analysis supports the evidence of a major role played by alkylating agents, procarbazine, and RT in inducing second malignancies, regimens not containing there drugs or their administration through treatments of different intensity warrant careful consideration.     

No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy

When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality.     

Salvage chemotherapy with ABVD in MOPP-resistant Hodgkin's disease

Fifty-five consecutive patients with advanced recurrent Hodgkin's disease resistant to MOPP chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone) were given ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine). In 54 patients evaluable for response, complete remission after pathologic restaging was seen in 59% and partial remission in 13%. Fifteen of 29 patients (52%) showing disease progression during primary MOPP treatment achieved complete remission after ABVD. The median time to complete response was 3 months. The median duration for complete remission was 17 months, and 38% of patients who attained complete remission have remained alive and continuously disease free at 5 years from start of ABVD treatment. The median survival of complete responders was more than 60 months. Toxic manifestations were moderate, aside from pronounced vomiting in more than half of patients. These results indicate that ABVD is an effective salvage regimen for MOPP-resistant Hodgkin's disease.     

Acute leukaemia in patients treated for Hodgkin''s disease

Fourteen acute non-lymphoid leukaemias (ANLL) were identified among 947 consecutive patients with Hodgkin's disease (HD) treated in five collaborating centres in Italy between January 1969 and December 1979. Leukaemia developed 12-118 months after the diagnosis of HD and was always preceded by a pre-leukaemic phase. The karyotype of the leukaemic cells was studied in nine of the 14 patients and was abnormal in seven cases. Bone marrow agar cultures were performed in five of the 14 patients and were abnormal in every case. The actuarial risk of developing ANLL at 10 years was 6.2% for combined therapy, 4.8% for salvage therapy and 2.2% for chemotherapy alone. No case of ANLL was documented among 136 patients treated with radiotherapy alone. One patient developed acute promyelocytic leukaemia following treatment with ABVD and radiotherapy. Both univariate and multivariate analyses seem to demonstrate that the induction therapy modality is a significant variable in development of secondary acute leukaemia. The recognition of a significant risk of ANLL in patients treated for HD should create changes in treatment policy.     

Treatment of Hodgkin's disease using the German Study Group protocol. Personal experience and results

The article present an evaluation (02/1999) of the study of primary treatment of Hodgkin's disease (HD) according to the third generation of the German Hodgkin's Disease Study Group (GHSG), and our experience with this treatment strategy. HD7 study of early stages HD showed better results (fewer relapses) for combined chemo and radiotherapy than for radiotherapy alone (2x ABVD + extended field radiotherapy compared to extended field radiotherapy alone). HD8 study of intermediate stage HD did not show any difference between chemotherapy 2x (COPP + ABVD) combined with radiotherapy extended field, or involved field. Due to the long-term consequences (especially secondary neoplasm), in the current (fourth) generation protocol extended field radiotherapy in early and intermediate stage HD has been replaced by a combination of lesser toxic chemotherapy and involved field radiotherapy. HD9 study of advanced HD. The standard treatment at present of COPP/ABVD (A) was compared with the new chemotherapeutic regimen, BEACOPP baseline (B) and escalated (C). The first evaluation of this study (1996) showed better results in the case of BEACOPP. The latest evaluation showed significantly better results for the escalated version. This is best illustrated by the low percentage of disease progression (C 2%, B 8%, A 12%, p < 0.05). Therefore, DHSG is considered to be the new standard for treatment of advanced stage HD. OUR RESULTS: Between 1995-1998, 54 patients with primary HD were treated at the FN Královaké Vinohrady, Prague according to the third generation GHSG protocol. Of these, 5 patients (9%) according to HD7, 14 (26%) according to HD8 and 35 patients (65%) according to HD9. Our results correspond to those of the whole GHSG, but they can not be statistically evaluated because of the small number of patients involved.