| ||||
| ||||
Julie M. Vose, MD
Highlighting Thursday's session on hematologic malignancies were presentations on new diagnostic tools for Hodgkin's disease and new protocols for treatment of early-stage Hodgkin's disease. In addition, the results of one study suggest that young women treated for Hodgkin's disease be carefully monitored for breast cancer. A new study of high-risk patients with adult acute lymphoblastic leukemia found that they benefit from receiving an allogeneic transplant. Finally, another interesting presentation shed light on the nature of anaplastic large-cell lymphoma.
Anaplastic Large-Cell Lymphoma
Boulanger and colleagues, from the Institut Bergonie, Bordeaux, France, retrospectively identified 72 patients with anaplastic large-cell lymphoma (ALCL) to determine the clinical, immunologic, and histologic features of this infrequent entity and their relation to treatment response.[1] Extranodal sites of disease were present in 52% of the patients, with 18% having skin involvement. Tumor cell phenotype was B (28%), T (28%), and null (29%). Complete remission was obtained in 73% of the cases. The median survival for all patients was 73 months. The 5-year overall survival was 55%, and the 10-year survival was 45%. For overall survival, the multivariate analysis identified independent prognostic factors of negative immunostaining for CD45 (P .0032), localized stage (P =.0064), good performance status (P =.031), and hemoglobin level > 12 g/dL (P =.036). The investigators concluded that the prognosis for ALCL patients appears better than for similar patients with diffuse large-cell lymphoma.
BMT and Chemotherapy in Adult Acute Lymphoblastic Leukemia
Investigators from the Université Claude Bernard, Lyon, France, conducted a prospective study of allogeneic or autologous bone marrow transplantation (BMT) and chemotherapy in patients with adult acute lymphoblastic leukemia (ALL) who experienced their first remission. Patients aged 15-60 years with de novo ALL, except FAB L3, were randomized to induction with daunorubicin or zorubicin before CVP (cyclophosphamide, vincristine, and prednisone) therapy.[2] Patients aged 15-40 years who achieved a complete response (CR) and had an HLA-identical sibling went on to receive an allogeneic transplant as soon as possible. Other patients were randomized during the second consolidation course into the chemotherapy arm or autologous transplantation. The median age of the patients was 33 years.
Seventy-six percent of patients achieved a CR. There was no significant difference between the daunorubicin or zorubicin arms in terms of remission rate or survival. At 10 years, the overall disease-free survival is 30% and overall survival is 27%. The analysis was differentiated by standard vs low-risk patients. The high-risk patients were defined as those with Ph1+ ALL, a null phenotype, WBC > 30,000/mcl, age > 35 years, or requiring > 4 weeks to go into a CR.
In the allogeneic BMT study, the overall survival in the allogeneic arm was 46%, compared with 31% (P =.04) for the patients who had at least one sibling but no identical donor. The most marked effect was in the high-risk group with a 44% survival in the sibling transplant arm versus 11% in the control group (P =.009). For autologous BMT, the survival was 34% in the autologous arm, compared with 29% in the chemotherapy arm (P =.65). The conclusion of the study was that high-risk patients definitely benefited from receiving an allogeneic transplant.
FDG-PET as a Predictor for Survival in Hodgkin's Disease
The clinical use of positron emission tomography (PET) for detection and staging of malignant tumors is gaining ground. In a small study, Dr. de Wit and coworkers, of Hamburg, Germany, evaluated the utility of PET with the glucose analogue F-18-fluorodeoxyglucose (FDG-PET) to predict the outcome of patients with Hodgkin's disease (HD) after chemotherapy or chemoradiotherapy.[3]
Fifty whole-body FDG-PET scans were performed simultaneously with CT or MRI imaging of patients who underwent treatment. Of these patients, 33 had completed all of their therapy at the time the imaging was performed. The analysis of the true and false positive and false negative results was as follows:
True Pos False Pos True Neg False Neg PET 10 5 18 0 CT 7 16 7 3
For predicting disease recurrence, the overall accuracy of PET was 74%, with sensitivity of 91% and specificity of 69%. Overall accuracy of CT/MRI was 34%, with sensitivity of 72% and specificity of 23%. Thus, in patients with HD, FDG-PET seems to be an important addition to re-evaluation after therapy and may be more predictive of outcome than is standard CT or MRI scanning.
Breast Cancer After Cured Hodgkin's Disease
At Thursday's (September 16) session, Dr. B. Cutuli and colleagues reported their findings of patients who developed breast cancer after HD.[4] One hundred and nineteen patients treated for HD between 1960 to 1988 developed breast cancer at some time posttreatment. The median age of the patients at the time of diagnosis of the HD was 24 years, with 35% of the patients younger than 20 years at the time of treatment. Seventy-four of the patients had received radiation only, 2 had received chemotherapy only, and 43 had received chemotherapy and radiation therapy. The median time to development of breast cancer was 15 years, and the median age of the women at the time of breast cancer diagnosis was 41 years (13% of the patients were younger than 30 years). Fifty percent of the patients had axillary node involvement. The 5-year, disease-specific survival rate was 61%. Node-negative patients had a 5-year survival of 91%. The 5-year survival rates for patients with N1-3 and N>3 were 66% and 15%, respectively. This study demonstrated that patients treated with RT or combined modality therapy for HD at a young age have a high incidence of developing breast cancer, and many of them appear to have aggressive disease with axillary node involvement or metastatic disease. These patients should be monitored carefully with mammography starting at an early age and for prolonged periods of time after their successful therapy for HD.
Treatment of Early-Stage Hodgkin's Disease
Combined-modality therapy in early HD allows smaller field and lower dose of irradiation, which reduces the risk of relapse compared with radiation alone and can spare staging laparotomy. A. Baio and coworkers, of Pavia, Italy, presented their analysis of the efficacy and long-term toxicity of four cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) followed by limited radiotherapy.[5] Seventy-eight patients with clinical stage I (N=20) or clinical stage II (N=58) were treated with this protocol. The median age of the patients was 33 years, with 60% having mediastinal involvement and 12% having bulky disease. The median follow-up of the patients was 56 months. The complete response rate was 88% after the ABVD alone and 98% after both therapies. The 5-year relapse-free survival was 97%, with 2 of the 3 relapsing patients achieving only a partial response to ABVD. The 5-year overall survival was 98%. One patient died of disease progression, and 1 died of small-cell lung carcinoma. The long-term toxicity included pulmonary fibrosis with symptomatic disease in 2 cases, 1 case of dilated cardiomyopathy, and 5 cases of hypothyroidism requiring replacement therapy. This protocol appears to be an effective therapy for early-stage HD. However, patients will need to be followed for a longer time for possible relapse and other long-term complications.
Anthracycline-Related Leukemias After Breast Cancer Therapy
Anthracyclines used in the neoadjuvant and adjuvant treatment of breast cancer have been associated with secondary-acute leukemias (SAL). This is a cause for concern, and S. Delaloge and coworkers, Hôpital Saint Louis, France, evaluated data from eight international phase III trials (7383 patients), median follow-up of 37-160 months, for information on anthracycline-related acute leukemias.[6] Patients who received low doses of doxorubicin (< 50 mg/m2/cycle) or 4-epirubicin (< 50-60 mg/m2/cycle) had a 1/1,211 (0.08%) risk of SAL, compared with 26/6,172 (0.4%) for patients who received high-dose doxorubicin (> 60 mg/m2/cycle) or 4-epirubicin (> 100-120 mg/m2/cycle). These data suggest a dose-response relation for anthracycline-related leukemogenesis, which may be amplified by the number of cycles the patients received. Further analysis in prospective trails to evaluate this effect by total dose or dose intensity received should be encouraged.
References
- Boulanger V, Soubeyran P, de Mascarel I, et al. Anaplastic large cell lymphoma: Clinical features and prognosis in a retrospective series of 72 patients treated in a single institution. Abstracts and Proceedings of ECCO 10. Sept 12-16, 1999; Vienna, Austria. Abstract 1330.
- Fiere D, Degos L, Reiffers J, et al: Allogeneic, autologous bone marrow transplantation and chemotherapy in first remission of adult acute lymphoblastic leukemia. Prospective study LALA87. Abstracts and Proceedings of ECCO 10. Sept 12-16, 1999; Vienna, Austria. Abstract 1332.
- de Wit M, Bohuslavizki KH, Clausen M, et al. FDG-PET following treatment is a valid predictor for disease-free survival in Hodgkin's disease. Abstracts and Proceedings of ECCO 10. Sept 12-16, 1999; Vienna, Austria. Abstract 1333.
- Cutuli B, Borel C, Dhermain F, et al. Breast cancer after cured Hodgkin's disease. Abstracts and Proceedings of ECCO 10. Sept 12-16, 1999; Vienna, Austria. Abstract 1334.
- Baio A, De Vecchi P, Franchini P, et al. Analysis of efficacy and long-term toxicity in the treatment of early-stage Hodgkin's disease with four cycles of ABVD followed by limited radiotherapy. Abstracts and Proceedings of ECCO 10. Sept 12-16, 1999; Vienna, Austria. Abstract 1336.
- Delaloge S, Cvitkovic E, Cottu P, et al. Anthracycline-related leukaemias after breast cancer adjuvant/neoadjuvant treatment: Dose relationship? Abstracts and Proceedings of ECCO 10. Sept 12-16, 1999; Vienna, Austria. Abstract 1338.
|
