Background. Alpha‐interferon and dexamethasone are each effective in patients with multiple myeloma and have a combined inhibitory effect on the in vitro growth of myeloma colonies. The effect of combined therapy in newly diagnosed patients is unknown. Methods. Fifty‐one consecutive patients with previously untreated multiple myeloma of low tumor mass received primary therapy with 3 million units (mu)/m2/day of interferon administered subcutaneously for 20 days and 20 mg/m2 of dexamethasone given orally each morning for 4 days beginning on days 1, 9, and 17. Courses were repeated after a rest period of 14 days. Results were compared with those of similar patients who received primary treatment with dexamethasone alone in the same dose regimen. Results. The response rate was similar: 57% for patients treated with interferon‐dexamethasone and 48% for those treated with dexamethasone alone. Remission and survival times of both groups were identical. Twenty‐nine percent of patients resistant to interferon‐dexamethasone and 19% of patients resistant to dexamethasone responded subsequently to either standard melphalan‐prednisone or to a cyclophosphamide‐vincristine‐doxorubicin‐dexamethasone combination. These regimens were also effective in one third of patients with disease relapse despite interferon. Conclusion. In this nonrandomized study of previously untreated patients with multiple myeloma, the addition of interferon in a dose of 3 mu/m2/day to dexamethasone achieved results similar to those with dexamethasone alone. Copyright © 1993 American Cancer Society

Few effective regimens are available for patients with advanced multiple myeloma resistant to or relapsing after both alkylating agents and VAD. We treated 52 patients with advanced and refractory multiple myeloma with the combination of cyclophosphamide (3.0 g/m2) and etoposide (900 mg/m2) followed by GM‐CSF at a daily dose of 0.125 mg/m2 until recovery of granulocytes. 42% of patients responded with a median time of 19 d for recovery of granulocytes to 0.5 x 109/1 and a 4% mortality rate. Eight responding patients received a second myeloablative treatment supported by either autologous bone marrow (six patients) or blood stem cells (two patients). The median survival time for all patients was 11 months and the median remission time for responding patients was 8 months. The combination of cyclophosphamide and etoposide provided an effective rescue treatment for many patients with advanced multiple myeloma resistant to conventional therapies. This programme also allowed early marrow or blood stem cell collection in support of subsequent myeloablative therapy for selected patients. Copyright © 1993, Wiley Blackwell. All rights reserved

Purpose: In recent years, increasing numbers of patients with asymptomatic multiple myeloma have been diagnosed by chance and followed without any therapy. Those at risk for early or late disease progression should be distinguished in order to prevent complications. This study defined prognostic factors that would predict the need for early treatment. Patients and Methods: We followed 95 patients with asymptomatic multiple myeloma without chemotherapy between 1974 and 1991. Magnetic resonance imaging (MRI) of the spine was conducted in 23% of patients with normal radiographs. An increase in serum myeloma protein to more than 50 g/L or new lytic bone lesions justified the institution of chemotherapy. Response to treatment and survival were assessed, and prognostic factors were defined for early or late disease progression by standard techniques. Results: The median time to progression in all patients was 26 months. The 25 patients with either a lytic bone lesion, or both serum peak greater than 30 g/L and Bence Jones proteinuria, had the shortest median time to progression of 10 months; the 27 patients without any harmful factor remained stable for a median of 61 months. MRI confirmed bone or marrow disease in half of the patients with normal radiographs and may assist in the prognostic staging. Despite the markedly different times of disease stability, the response rates and survival after chemotherapy were similar for all groups of patients. Conclusion: Among asymptomatic patients with multiple myeloma, the extent of disease at diagnosis and the subsequent rate of disease evolution were major factors in the total survival time. These patients are a markedly heterogeneous group who may benefit from different approaches to treatment according to defined risk factors. © 1993.

Sixty-eight patients with Waldenstrom's macroglobulinemia were treated either with fludar-abine (28 patients) or 2-chlorodeoxyadenosine (40 patients) and responding patients were followed without further treatment. Both programs were well tolerated and myelosuppression was moderate but reversible. Overall, 35 patients responded including 93% of previously untreated patients, 83% of those relapsing off therapy, 48% of patients with primary refractory disease and 15% of those treated during refractory relapse. With a median follow up of 18 months, only two of 15 previously untreated patients have relapsed whereas the median remission duration and survival of previously treated patients were 38 and 43 months respectively. Fludarabine and 2-chlorodeoxyadenosine are both highly active agents against Waldenstrom's macroglobulinemia, especially when administered early in the disease course. © 1993 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Summary— Collecting duct carcinoma (CDC) is a recently recognised histological variety of renal carcinoma (RC) considered to arise from the epithelium of the collecting ducts. Diagnosis of this entity depends on well defined gross and microscopic criteria and is supported by a characteristic immunostaining pattern. The clinical features of these patients, the natural course of the disease and its response to treatment have not been clearly established. Between 1980 and 1990 we treated 12 patients (median age 43 years, range 16–62) with collecting duct carcinoma of the kidney. In addition to being relatively young, each patient had a strong family history of associated malignancies. Survival was short (median 22 months) and 11 patients presented with locally advanced or metastatic disease. © 1993 British Journal of Urology

Multiple myeloma is a disseminated malignant neoplasm usually derived from a single clone of plasma cells. Patients with myeloma have diverse signs such as anemia, hypercalcemia, uremia, pathologic fractures, and recurrent infections. Extraosseous manifestations are found in less than 5% of patients with multiple myeloma. They can arise in any tissue, and their presence has been associated with more aggressive disease. The purpose of this assay is to illustrate the imaging findings of extraosseous myeloma and heighten awareness of this unusual manifestation of multiple myeloma.

purpose: To assess the response rate, remission duration, and survival of patients with Waldenström's macroglobulinemia treated with the adenine nucleoside analogue fludarabine. patients and methods: Twenty-eight patients with Waldenström's macroglobulinernia, of whom only 2 were previously untreated, received fludarabine at a dose of 20 to 30 mg/m2 intravenously daily for 5 days (20 patients) or 30 mg/m2 intravenously daily for 3 days (8 patients). Treatment was continued until maximum response was achieved. Responding patients were followed with no further treatment until relapse. results: Ten patients responded (36%), including the 2 previously untreated patients and 8 of 26 patients (31%) who were resistant to prior therapies. Uninaintained remissions lasted for a median of 38 months. There were no fatalities associated with this treatment. Previously untreated patients and those with a primary resistant disease of relatively short duration were more likely to benefit from this treatment. conclusion: Fludarabine is an effective salvage agent for the treatment of patients with resistant Waldenström's macroglobulinemia. Further investigations of fludarabine in untreated patients and in combination with other active agents are warranted. © 1993.

Fludarabine monophosphate (fludarabine) was initially discovered to have significant activity in indolent lymphoma and chronic lymphocytic leukemia (CLL). The major clinical experience with fludarabine is in previously treated patients with CLL. In such patients the complete and partial response rate (CR + PR) is over 50%. These results were obtained with 5-day schedules of fludarabine 25 to 30 mg/m2/d. Subsequent schedules have explored once-a- week fludarabine and a 3-day schedule every 4 weeks. These strategies, in particular the once-a-week schedule, have obtained inferior results. The addition of prednisone has not been associated with an improvement in response rate or survival. The application of fludarabine to previously untreated patients demonstrated a CR + PR rate of 75% to 80%. The addition of prednisone did not improve the response rate or survival in this group of patients. A significant concern in patients with CLL treated with fludarabine is a decrease in the CD4 and CD8 counts. Despite median posttreatment counts of approximately 200 CD4 lymphocytes/μL, the incidence of infections in patients in remission off therapy is low. Major clinical activity has been demonstrated with fludarabine in Waldenstrom's macroglobulinemia, in which more than one third of refractory patients achieve a CR or PR. Responding patients with anemia or thrombocytopenia have a marked improvement in blood counts. The duration of response has been long (>30 months) in most responders. The early activity of fludarabine as a single agent in phase I/II studies in indolent lymphoma subsequently has been confirmed by a number of investigators. Fifty percent to 60% of patients with follicular lymphomas respond to fludarabine as a single agent. A number of these responses are complete despite the patients having received extensive prior treatment. A number of combination programs are being developed in CLL and indolent lymphoma. The combination of fludarabine with doxorubicin and prednisone has been developed and is being studied in phase I/II clinical trials. In addition, combinations of fludarabine and cytarabine with or without cisplatin based on elegant preclinical pharmacokinetic rationales have been applied to CLL with impressive cytoreductive activity but significant myelosuppression. A new combination of fludarabine, mitoxantrone, and dexamethasone has been developed for use in lymphoma. Phase I studies demonstrated a high response rate, especially in follicular lymphomas, with a number of patients achieving complete remission. Subsequent phase II studies demonstrate a response rate of 89% in patients with indolent lymphoma. The enhancement of the formation of the triphosphate form of cytarabine in acute myelogenous leukemia blast cells has led to the study of fludarabine and cytarabine in previously treated patients with acute leukemia. The promising results in these patients have led to the application of the fludarabine and cytarabine combination in frontline patients with poor-risk disease and, subsequently, in those with better-risk disease. Results equivalent or superior to traditional combinations have been obtained. The same regimen has been applied to myelodysplastic syndrome patients with a response rate of over 50%. The addition of granulocyte colony-stimulating factor to fludarabine and cytarabine to enhance the cytotoxicity of cytarabine on acute myelogenous leukemia and myelodysplastic syndrome has further improved the response rate. These drugs have now been combined with Idarubicin (Adria Laboratories, Columbus, OH). Fludarabine has been demonstrated to have a marked impact on the inhibition of repair of DNA damage subsequent to radiation and exposure to cytotoxic substances such as cisplatin. These biologic effects have been used to develop clinical protocols exploring the combinations of fludarabine/cisplatin with or without cytarabine and fludarabine/radiation therapy. The expanding use of fludarabine in hematologic malignancies is related to its wide range of biochemical actions. Further use in combinations is anticipated.

Purpose: To evaluate the role of serum β2-microglobulin (β2M) in the prognosis of patients with Hodgkin's disease. Patients and Methods: One hundred sixty previously untreated patients with Hodgkin's disease had serum β2M levels determined before initiation of treatment. Serum β2M was tested for its correlation with known prognostic factors for patients with Hodgkin's disease. These variables, including β2M, were correlated with complete remission (CR) rate and time to treatment failure (TTF). Univariate and multivariate analyses were performed. Results: Serum β2M levels greater than 2.5 mg/L were found in 29% of patients. Such elevation was more common in patients with more advanced-stage disease. Elevated serum β2M was an independent and powerful factor in the prediction of lower response rate and shorter TTF. Its impact appeared to be more significant in patients with advanced disease. Conclusion: Serum β2M appears to correlate with tumor stage in patients with Hodgkin's disease and elevated serum levels of this polypeptide predict a less favorable prognosis.

Purpose: To assess prospectively the role of magnetic resonance (MR) imaging in the staging of patients with a solitary bone plasmacytoma (SBP). Patients and Methods: Twelve consecutive patients with an apparent SBP underwent MR imaging of both the primary tumor and the thoracic and lumbosacral spine to seek additional foci of marrow involvement that might have been undetected by standard skeletal survey. All patients received megavoltage irradiation (total dose, 40 Gy) to the primary lesion. Results: MR imaging of the thoracic and lumbosacral spine showed additional foci of marrow replacement in four of 1 2 patients, with signal characteristics identical to those of the primary tumor. In all four patients, the abnormal protein persisted at greater than 50% of the pretreatment value following radiation treatment. In contrast, the myeloma protein disappeared or was reduced by greater than 50% in five of the six patients with secretory disease and without additional marrow abnormalities. One of four patients progressed to multiple myeloma 10 months after diagnosis with new lesions on conventional radiographs in the same areas as detected previously by MR imaging. Conclusion; Four of 12 patients considered to have a SBP by standard criteria may have been understaged, because MR imaging showed additional marrow abnormalities consistent with myeloma. MR imaging of the spine may contribute to the initial staging of SBP, especially since some patients may be cured with radiotherapy. © 1993 by American Society of Clinical Oncology.

Forty patients with multiple myeloma received thiotepa (750 mg/m2), busulfan (10 mg/kg), and cyclophosphamide (120 mg/kg) (TBC) followed by autologous bone marrow or blood stem cell support. Granulocyte-Colony stimulating factor (G-CSF) was administered to accelerate hematopoietic recovery. Sixty-five percent of all patients responded to this treatment. Eighty-eight percent of patients transplanted in partial remission had a further reduction of the myeloma and 53% achieved a complete remission. Forty-eight percent of patients with refractory myeloma responded. All responding patients transplanted during partial remission or with primary refractory myeloma remain free of progression for a period of 4 to 24 months posttransplant, but the remission duration of patients treated in refractory relapse was short (4 months). Five of 24 patients transplanted with marrow and none of 16 receiving blood stem cells died of treatment-related complications. Use of blood stem cells resulted in more rapid granulocyte and platelet recovery. We conclude that TBC is an effective, relatively well tolerated, preparative regimen for patients with multiple myeloma. © 1993 by The American Society of Hematology.

Twenty-three consecutive patients with Waldenström macroglobulinemia were studied with magnetic resonance (MR) imaging of the spine and computed tomography (CT) of the abdomen and pelvis. MR imaging studies included sagittal T1-weighted and gradient-recalled-echo sequences performed with and without contrast material enhancement. Marrow involvement was identified with MR imaging in 21 of 23 (91%) patients. Diffuse involvement was noted in 13 patients (56%), and a variegated pattern in eight (35%). CT demonstrated enlarged nodes in 10 of 23 (43%) patients. Correlation of MR imaging patterns and presence of adenopathy at CT with standard laboratory values for Waldenström macroglobulinemia revealed an association of the diffuse MR imaging pattern of marrow involvement and the presence of enlarged nodes at CT with more advanced disease. MR imaging of the spine and CT are reliable means of evaluation of disease status in Waldenström macroglobulinemia. They may be employed as additional means in the staging of Waldenström macroglobulinemia and may be helpful in the follow-up of patients with this rare hematologic malignancy.

Objective: To evaluate the activity of 2-chlorodeoxyadenosine (2CdA) in the treatment of patients with Waldenstrom macroglobulinemia. ■ Design: Uncontrolled phase II trial. ■ Setting: Tertiary, referral cancer center. ■ Patients: Twenty-nine consecutive, symptomatic patients with Waldenstrom macroglobulinemia, of whom 9 were previously untreated. ■ Intervention: 2-Chlorodeoxyadenosine was administered as a continuous intravenous infusion at a dose of 0.1 mg/kg body weight per day for 7 days. Only two courses of 2CdA were given and responding patients were then followed without further treatment. ■ Measurements and Main Results: A total of 17 (59%) patients responded, including all of those who were newly diagnosed and 40% of those who had failed previous therapies. Treatment was well tolerated except for one death in a patient who had presented with severe pancytopenia. With a median follow-up of 7 months, only one responding patient has relapsed. ■ Conclusion: 2-Chlorodeoxyadenosine is a nucleoside analog that was effective in most patients with Waldenstrom macroglobulinemia and was associated with little toxicity.