Advanced Hodgkin disease with large mediastinal involvement can be treated with eight cycles of chemotherapy alone after a major response to six cycles of chemotherapy: a study of 82 patients from the Groupes d'Etudes des Lymphomes de l'Adulte H89 trial.

BACKGROUND: The prognostic impact of large mediastinal involvement (mediastinum/thorax [M/T] ratio > 0.33) in advanced Hodgkin disease (HD) and the optimal treatment with chemotherapy or combined treatment remains controversial. METHODS: Among 533 assessable patients with Ann Arbor Stage IIIB/IV HD included in the H89 trial, 82 had large mediastinal mass defined on chest X-ray. All patients received induction with six cycles of chemotherapy (mechlorethamine, vincristine, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine or doxorubicin, vinblastine, bleomycin, procarbazine, prednisone); then complete and good partial responders were randomized between two consolidation treatments: 2 cycles of the same chemotherapy or (sub)total lymph node irradiation. RESULTS: Among 82 patients with an M/T ratio greater than 0.33, 48 were very large (ratio > 0.45). A large mediastinal mass was associated with supradiaphragmatic disease, younger age, histologic nodular sclerosis, and different sex ratio compared with other H89 trial patients. Biologic parameters and prognostic factors were similar for both groups. Although the major response rate to induction chemotherapy (after 6 cycles) was lower for patients with large mediastinal mass (78% vs. 86%), the 5-year overall survival rate (80% vs. 79%) and event free survival rate (59% vs. 61%) were similar (P = 0.64 and 0.3, respectively). The outcome was the same for patients (74%) with a large mediastinal mass randomized to 1 of the 2 consolidation arms. Analysis of progression showed that 68% (21 of 31) of failures occurred early during treatment and involved the mediastinum in 86% of the cases. CONCLUSIONS: For patients with large mediastinal mass and advanced HD who achieved a major response of at least 75% after 6 cycles of chemotherapy, a consolidation radiation therapy can be replaced by 2 additional cycles of chemotherapy.

Pathologic and clinical features of 77 Hodgkin's lymphoma patients treated in a lymphoma protocol (LNH87): a GELA study.

Between 1987 and 1993, 77 of 2855 lymphomas included in the LNH87 protocol of the GELA as non-Hodgkin lymphoma (NHL) and reviewed by a panel of pathologists had a diagnosis changed to Hodgkin lymphoma (HL). Some of these lymphomas had been initially interpreted as anaplastic large-cell lymphoma Hodgkin-like (ALCL-HL subtype). The purpose of this study was to analyze the histologic pitfalls initially encountered, to define more clearly the diagnostic criteria of lymphomas placed in the gray zone around HL, and to follow the survival of these 77 patients affected with HL and initially treated with NHL regimens. The 77 cases of HL were reviewed by three hematopathologists and immunostained with a large panel of antibodies, including CD30, CD15, CD3, CD20, CD45, CD43, LMP-1, EMA, BNH-9, TiA1, and ALK1. Each case was classified according to the Lukes-Rye system and the British National Lymphoma Investigation (BNLI) grading. The initial clinical presentation of patients was analyzed, and the overall and event-free survival rates of the 77 patients were estimated. Among the 77 HLs, 46 were misinterpreted as NHL by primary individual pathologists (12 as ALCL, 8 as ALCL-HL, 12 as peripheral T-cell lymphoma (PTCL), 6 as B-cell lymphoma, and 8 as unclassifiable NHL). The other 31 cases had been first considered by the panel as consistent with ALCL-HL (n = 18) or with PTCL (n = 13) and were changed later in view of an immunophenotype concordant with HL. Fifty-five percent of the patients completed the full NHL treatment. The 5-year event-free and overall survival rates were 54% and 77%, respectively. The current results indicate that lymphomas initially called ALCL-HL should not be regarded as a variant of ALCL, but as HL. The clinical consequences of misdiagnoses seem to be a lower event-free survival rate compared with that of classical HL, probably because of more relapses of initially inappropriately treated HL.

Myelodysplasias and leukemias after autologous stem cell transplantation for lymphoid malignancies.

The incidence of secondary myelodysplastic syndromes and acute leukemia (MDS/AL) was reported for 395 patients autografted for Hodgkin's disease (HD) (n = 96) and non-Hodgkin's lymphoma (NHL) (n = 299) between 1987 and 1998. Eleven patients developed secondary MDS/AL (crude rate at 2.8%) including two lymphoblastic AL cases. The mean time of occurrence was at 32 months after autologous stem cell transplantation (ASCT) and 71 months after diagnosis. The estimated actuarial incidence at 10 years was at 6.3% (+/-4%). Karyotyping revealed complex chromosomal aberrations in only one patient, and two translocations [t(8;21) and t(8;16)]. No features of topoisomerase II inhibitor-related leukemia were found. Only one patient had received ASCT in first remission. The remaining 10 patients had received multiple courses of chemotherapy before stem cell collection and four had relapsed after ASCT and before the occurrence of secondary MDS/AL. Five of 11 patients had received localized radiotherapy and five others received TBI in their conditioning regimen. Ten patients died despite chemotherapy and/or supportive care and only one patient is alive and well after genoidentical allogeneic transplantation. We suggest a cumulative leukemogenic role of pre-ASCT radiation and chemotherapy in the occurrence of these secondary MDS/AL more than the high-dose therapy itself.

Development of metastases in malignant melanoma is associated with an increase in the plasma L-dopa/L-tyrosine ratio.

In this prospective study we evaluated a new biochemical approach in which the plasma ratio of the melanin precursors L-dopa and L-tyrosine serves as a marker of metastatic dissemination in malignant melanoma. Control values (11.20 x 10(-5) +/- 2.92 x 10(-5)) were determined. The L-dopa/L-tyrosine ratio was evaluated in the plasma of 90 patients with malignant melanoma (stage I/II, n = 33; stage III, n = 33; stage IV, n = 24) classified according to the tumour/node/metastasis (pTNM) classification. A total of 106 samples were studied. Serial measurements were performed in eight stage III-IV patients. The L-dopa/L-tyrosine ratio was significantly elevated in melanoma patients with clinical stage III (15.23 x 10(-5) +/- 3.34 x 10(-5)) compared with stage I (10.88 x 10(-5) +/- 2.52 x 10(-5)). Stage IV patients showed a significant increase in the plasma L-dopa/L-tyrosine ratio (45.73 x 10(-5) +/- 61.75 x 10(-5)) compared with the other groups. The ratio was higher for those with two rather than one metastatic site and markedly higher for those with widespread metastases. The development of metastases was associated with an increase in plasma L-dopa, a decrease in plasma L-tyrosine and a significant increase in the plasma L-dopa/L-tyrosine ratio. These data suggest that the plasma L-dopa/L-tyrosine ratio reflects the tumour burden and correlates with the progression of malignant melanoma.

Hodgkin's disease in 35 patients with HIV infection: an experience with epirubicin, bleomycin, vinblastine and prednisone chemotherapy in combination with antiretroviral therapy and primary use of G-CSF.

BACKGROUND: The optimal therapeutic approach for patients with Hodgkin's disease and human immunodeficiency virus infection (HD-HIV) is unknown. In an attempt to improve the results previously obtained with EBV (epirubicin, bleomycin and vinblastine) without G-CSF (Cancer 1994; 73: 437-44), in January 1993 we started a trial using chemotherapy (CT) consisting of EBV plus prednisone (EBVP), concomitant antiretroviral therapy (zidovudine, AZT or dideoxinosyne, DDI), and G-CSF. PATIENTS AND METHODS: Up to August, 1997, 35 (30 M/5 F) consecutive previously untreated patients (median age 34, range 21-53 years) with HD-HIV were enrolled in the European Intergroup Study HD-HIV. Their median performance status was 1 (range 1-3). At diagnosis of HD, 26% of the patients had AIDS, 90% had B symptoms at HD presentation and 83% had advanced-stage HD. Patients received E 70 mg/m2 i.v. on day 1, B 10 mg/m2 i.v. on day 1, V 6 mg/m2 i.v. on day 1 and P 40 mg/m2 p.o. from day 1 to day 5 (EBVP). Courses were repeated every 21 days for six cycles. AZT (250 mg x 2/day), or DDI (200 or 300 mg x 2/day) if AZT had been previously used, were given orally from the beginning of CT. G-CSF was given at the dose of 5 mcg/kg/day s.c. from day 6 to day 20 in all cycles. RESULTS: An overall response rate of 91% was observed. There were 74% complete responses (CR) and 17% partial responses (PR). Toxicity was moderate, with grade 3-4 leukopenia and thrombocytopenia in 10 (32%) and three (10%) patients, respectively. The median number of administered cycles was 6 (range 3-6). Twenty-three of 35 patients received AZT and nine patients received DDI. Three (8%) patients had opportunistic infections (OI) during or immediately after CT. The median CD4+ cell count was 219/mm3 (6-812) at HD diagnosis and 220/mm3 (2-619) after the end of combined therapy, and these numbers remained unchanged. Ten of 26 (38%) patients who achieved CR relapsed. Twenty-three patients died of HD progression alone or in association with OI, being the cause of death in 48% and 9% of patients respectively. The median survival was 16 months, with a survival rate of 32% and a disease-free survival of 53% at 36 months. CONCLUSIONS: The combined antineoplastic and antiretroviral treatment is feasible, but HD in HIV setting is associated with a more adverse prognosis than in the general population. Although the CR rate obtained was satisfactory, the relapse rate was high. Furthermore, comparison of the results of our two consecutive prospective studies demonstrated no overall improvement in the current trial with respect to the CR rate and survival.

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 Hodgkin's 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 01/89 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 EST > 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.

Effect of granulocyte colony-stimulating factor administration in elderly patients with aggressive non-Hodgkin's lymphoma treated with a pirarubicin-combination chemotherapy regimen. Groupe d'Etudes des Lymphomes de l'Adulte.

PURPOSE: Results of a multidrug chemotherapy regimen consisting of cyclophosphamide, pirarubicin, teniposide, and prednisolone (CTVP) plus subcutaneous granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma (NHL) are reported. PATIENTS AND METHODS: Between January and December 1992, 46 previously untreated patients older than 69 years with intermediate- and high-grade NHL received cyclophosphamide 750 mg/m2, teniposide 75 mg/m2, pirarubicin 50 mg/m2 day 1, and prednisolone 40 mg/m2 days 1 to 3. G-CSF, 5 micrograms/kg/day, was administered from day 4 up to day 14 or when the absolute neutrophil count reached 5 x 10(9)/l. Six cycles were scheduled every 3 weeks. RESULTS: Grade 3 or grade 4 neutropenia complicated 22% and 26% of chemotherapy cycles, respectively. Fever or/and clinical infection were observed in 4% and 14% of cycles. One toxic death related to a septic shock occurred. Eight cycles (4%) were delayed with a median duration of 7 days. Administered median dose intensity was 93.5%. Objective response rate was 74% and 46% of the patients achieved a complete response. The 2-year overall survival and event-free survival rates were 47% and 28%. CONCLUSION: In comparison with a previous group of patients treated with CTVP, G-CSF allows delivery of chemotherapy with a reduced neutropenia-induced morbidity in an outpatient setting in elderly patients with aggressive NHL without modifying response rate or survival.

[Right coronary artery issuing from the pulmonary artery: review of the literature apropos of a case]. / Coronaire droite née de l'artère pulmonaire: revue de la littérature à propos d'une nouvelle observation.

A new case of right coronary artery abnormally issued from the pulmonary trunk is reported. The patient was an asymptomatic young man in whom a continuous cardiac murmur was discovered by chance and an angiographic examination disclosed the coronary abnormality. A review of the literature yielded 37 cases of this anomalous origin which was either isolated, as in the case reported here, or associated with another congenital or acquired cardiopathy. The diagnosis may be suspected on the presence of a continuous murmur in an usually asymptomatic subject and is confirmed by angiography. The abnormality is generally well tolerated owing to an inter-coronary collateral circulation resulting in retrograde perfusion of the right coronary artery from the left coronary artery. This good tolerance explains why an isolated abnormality of that type is often discovered belatedly, in contrast with the anomalous origin of the left coronary artery from the pulmonary trunk, which is usually revealed at birth by clinical signs of acute coronary insufficiency. However, the likelihood of either cardiac failure due to the left-to-right shunt in elderly people or, chiefly, acute myocardial ischaemia by coronary steal with a risk of sudden death in young people makes it imperative in such cases to perform reimplantation surgery.

Necrobiotic xanthogranuloma with myeloma. A case report.

Necrobiotic xanthogranuloma is a newly recognized cutaneous manifestation associated with paraproteinemia. Necrobiotic xanthogranuloma is distinctive clinically by yellowish-red nodular lesions, often ulcerated, with predilection for the periorbital area and ocular involvement. Histologically, it is characterized by the combination of inflammatory xanthogranulomas together with areas of necrobiosis. These skin lesions are associated with a dysglobulinemia and preceded the development of an IgG lambda myeloma in a previous patient. Hyperlipidemia may be found in some patients. A case of necrobiotic xanthogranuloma is reported, occurring in a 46-year-old man and associated with an IgG kappa myeloma.