Summary:In an effort to improve the outcome of poor-risk lymphoma patients, we evaluated a novel regimen of tandem high-dose chemotherapy (THDC) with autologous stem cell transplantation. A total of 41 patients (median age 40 years, range 15-68 years) with poor-risk nonHodgkin's lymphoma and Hodgkin's disease were enrolled. THDC consisted of melphalan (180 mg/m 2 ) and escalating dose mitoxantrone (30-50 mg/m 2 ) (MMt) for the first conditioning regimen, and thiotepa (500 mg/m 2 ), carboplatin (800 mg/m 2 ), and escalating dose etoposide phosphate (400-850 mg/m 2 ), (ETCb) as the second regimen. In all, 31 patients (76%) completed both transplants, with a median time between transplants of 55 days (range 26-120). The maximum tolerated dose was determined as 40 mg/m 2 for mitoxantrone and 550 mg/m 2 for etoposide phosphate. The overall toxic death rate was 12%. Following high-dose chemotherapy, 10 of 24 evaluable patients (42%) were in CR. The two-year overall survival and event-free survival is 67% (95% CI, 52-81%) and 45%, (95% CI, 29-61%) for the 41 patients enrolled; and 69% (95% CI, 525-586%) and 48% (95% CI, 30-67%) for the 31 patients completing both transplants. This THDC regimen is feasible but with notable toxicity in heavily pretreated patients; its role in the current treatment of high-risk lymphoma remains to be determined. The majority of poor-risk lymphoma patients are not cured with conventional chemotherapy. High-dose chemotherapy (HDC) with peripheral blood progenitor cell support (PBPC) offers a survival advantage in such patients, but many still die from recurrent disease. 1 Strategies to improve survival in patients with poor risk, relapsed, or chemotherapy-resistant disease include intensified induction followed by HDC with PBPC support, 2-5 HDC with autografting and immunotherapy, 6 tandem HDC and autografting, [7][8][9][10][11][12] or sequential autologous and nonmyeloablative allogeneic transplantation.Tandem transplantation as a strategy to improve efficacy was demonstrated in myeloma by Barlogie et al 13 and Attal et al. 14 In an attempt to improve outcome in patients with high-risk lymphoma, our group examined the tolerability and efficacy of two regimens, first, mitoxantrone and melphalan (MMt) and second, etoposide, thiotepa, and carboplatin (ETCb), given in sequence with PBPC support in a program of tandem autologous transplantation. As first-line therapy for newly diagnosed poor-risk lymphoma, Corradini et al 15 reported favorable results using myeloablative doses of melphalan and mitoxantrone followed by autografting. Based on this report, we studied the utility and determined the maximum tolerated dose (MTD) of MMt given before the first transplant performed in our tandem autografting protocol for patients with poor-risk, resistant or relapsed disease.For our second autograft procedure, we devised a myeloablative conditioning regimen of ETCb. This combination derived from our experience with the high-dose combinations of cyclophosphamide, thiotepa, and carboplatin that we and o...

Previous studies have reported that tamoxifen use is associated with a decrease in mammographic breast density. This is a potentially valuable finding since mammographic sensitivity is limited by breast density. Anything that reduces breast density would theoretically enhance the sensitivity of mammography for the detection of breast cancer in women at an earlier stage when it is more curable. We performed a retrospective study investigating the potential effect of tamoxifen on breast density. The data for this retrospective study were collected from the records of 52 charts from a single medical oncologist. Patients with breast cancer were selected regardless of stage or age at the time of diagnosis or treatment, as long as their charts had records of bilateral mammograms. For each breast on each woman, both mediolateral oblique and craniocaudal views were reviewed independently by two radiologists on two separate occasions to obtain inter- and intraobserver variability. Two methods of classifying breast density were used: the Breast Imaging Reporting and Data System (BI-RADS), and measurements of percent density. Only age and menopausal status were found to be associated with breast density. There was no correlation between breast density and tamoxifen use (past or present). Our study shows no association between tamoxifen use and breast density. We confirm previous observations that breast density is inversely correlated with age and postmenopausal status.

Renal medullary carcinoma is a recently recognized epithelial malignant tumor arising in the renal parenchyma. The tumor is almost exclusive to young black patients with the sickle cell trait. Most patients present with metastatic disease and have a poor prognosis. An Hispanic woman with renal medullary carcinoma who initially responded to chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin and survived for 12 months is presented. The clinical, histologic, and radiologic features of this tumor are described, and chemotherapeutic regimens used in this disease are detailed. Treatment modalities have proved largely unsuccessful in the setting of advanced disease. Given the shared demographic, clinical, and radiographic features of these patients, awareness and early diagnosis may prove essential in improving survival.

Summary:The majority of poor-risk lymphoma patients are not cured with conventional chemotherapy. There is evidence for the superiority of single high-dose chemotherapy in such patients, but many still die from recurrent disease. Strategies to improve survival in these poor-risk patients include dose-intensification with high-dose chemotherapy and PBPC support, tandem autologous HDC with PBPC support, and autologous followed by non-myeloablative allogeneic transplantation. These more aggressive strategies are feasible and tolerable. Whether tandem transplantation will prove more effective than current single high-dose therapy in appropriately selected patients remains to be determined. Bone Marrow Transplantation (2001) 28, 529-535. Keywords: tandem transplantation; lymphoma; autologous; allogeneicThe majority of patients with lymphoma achieve remission with standard therapy. A small percentage of patients are refractory to initial therapy, and approximately one-third of patients with stage III-IV disease will relapse after achieving a complete response. Treatment of minimally responsive or refractory lymphoma patients remains a challenge. Single transplantation and the poor prognosis patientProspective randomized trials show single HDC with autologous transplantation to be superior to standard-dose chemotherapy for relapsed and resistant Hodgkin's disease, 1 for consolidative therapy of poor-risk B cell NHL in first remission 2 and for relapsed chemo-sensitive intermediate or high-grade NHL. 3 An update of the PARMA study reports an 8-year EFS of 36% and OS of 47% for these latter patients. 4 Fewer than 5% of patients with poor-risk NHL or HD who have induction failure and receive conventional salvage chemotherapy are alive at 5 years. NHL patients with induction failure who undergo HDC and autotransplantation have an overall survival at 5 years of 37%. 5 Data from the ABMTR show HD patients with induction Correspondence: DR CS Hesdorffer, Division of Medical Oncology, MHB 6N 435, 177 Ft. Washington Avenue, New York, NY 10032, USA failure who subsequently undergo HDC have progressionfree and overall survivals at 3 years of 38% and 50%, respectively. 6 Data by Sweetenham et al 7 from the EBMT are similar, reporting an actuarial 5-year OS rate of 36% and PFS rate of 32%.Allogeneic transplantation alone does not appear to offer a survival advantage over autologous transplant for lymphoma. 8,9 Studies suggest a graft-versus-lymphoma effect, but this has not translated into increased survival due to the high treatment-related mortality associated with allogeneic transplantation. Further prospective trials, randomized on the basis of HLA-identical donor availability, may provide more reliable data on this issue. 10 While salvage rates of 45-60% are achieved with HDC in patients with relapsed NHL and HD with good prognostic factors, adverse prognostic factors, such as relapse within 1 year of initial treatment, stage III/IV relapse or chemoresistance, portend a poorer outcome, with likely cure in less than 40%. The IP...