DLI results in complete remissions in a high percentage of patients with relapsed chronic-phase CML. Complete remissions are observed less frequently in patients with advanced CML and acute leukemia. GVHD and pancytopenia occur commonly; GVHD is highly correlated with response.

Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or hearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistant to conventional-dose cisplatin-based therapies.

Three hundred twenty-five women with metastatic adenocarcinoma of the breast who had failed one prior chemotherapeutic regimen for advanced disease were randomized to receive 14 mg/m2 of mitoxantrone or 75 mg/m2 of doxorubicin intravenously (IV) every 3 weeks. Enrollment was closed on October 31, 1984, after 165 patients were randomized to mitoxantrone and 160 patients to doxorubicin. Patients randomized to the two treatment groups were compared for response rate, duration of response, time to progression or death, time to treatment failure (TTF), and survival. The response rate to mitoxantrone was 20.6%, to doxorubicin 29.3% (P = .07). The median response duration was 151 days for the mitoxantrone group and 126 days for the doxorubicin group (P = .16). The median TTF was 70 days in the mitoxantrone group and 104 days in the doxorubicin group (P = .36). The median survival of patients initially randomized to receive mitoxantrone was 273 days; for doxorubicin 268 days (P = .40). There were three responses among 77 patients crossed over to mitoxantrone after initial treatment with doxorubicin. The major dose-limiting toxicity for both drugs was leukopenia. There was significantly less severe and less frequent toxicity with mitoxantrone administration. Severe nausea and vomiting occurred in 9.5% of mitoxantrone patients and 25.3% of doxorubicin patients (P less than .001). The incidence of severe stomatitis and mucositis was 0.6% in the mitoxantrone group and 8.4% in the doxorubicin group (P = .001). Severe alopecia occurred in 5.1% of mitoxantrone patients and 61.0% of doxorubicin patients (P less than .001). A life-table comparison of the cumulative dose to the development of a cardiac event showed that mitoxantrone had significantly less cardiotoxicity than doxorubicin (P = .0005). This study demonstrates that mitoxantrone is active as a single agent in the treatment of metastatic breast cancer. Compared with doxorubicin it appears to be marginally less active and significantly less toxic. We conclude that mitoxantrone can be used alone or with other standard drugs to palliate the symptoms of metastatic breast cancer, especially in settings where drug toxicity is an important consideration.

Summary:with median survivals of 3.0 and 10.5 months for nonHodgkin's lymphoma (NHL) and Hodgkin's disease (HD), respectively. 1Increasing numbers of patients have received autologous stem cell transplants (ASCT) for hematologic maligPotential benefits of allogeneic bone marrow transplantation (alloBMT) over ASCT include lack of graft tumor nancies. Since only a fraction of these patients are cured, physicians are more frequently faced with the contamination and the presence of a graft-versus-tumor effect. The graft-versus-leukemia effect is well established dilemma of how to manage relapse post-transplant. Potential advantages of allogeneic transplantation in alloBMT. 2 There is a significantly lower incidence of leukemia relapse in patients who undergo alloBMT com-(alloBMT) over ASCT include lack of graft tumor contamination and presence of a graft-versus-tumor effect.pared to patients who receive autografts. Evidence of a graft-versus-lymphoma effect has also been demonstrated For this reason, patients who relapse after ASCT are often considered candidates for allogeneic bone marrow in patients who received alloBMT for treatment of lymphoid malignancies. 3 Therefore, there is a theoretical benefit transplantation. However, there is limited knowledge on the outcome of alloBMT in patients who relapse after for patients who relapse after ASCT to receive subsequently an alloBMT. However, there is limited data on ASCT. We retrospectively analyzed the outcome of 20 patients with malignant lymphoma (n = 14) and AML the outcome of patients who undergo alloBMT for relapse after ASCT. (n = 6) who underwent alloBMT after failing an ASCT. The median age was 30 (17-41) years and the intervalThe purpose of this study was to evaluate therapy-related toxicities, long-term survival, and hematopoietic stem cell from ASCT to alloBMT was 10.5 (2-25) months. Seventeen patients died between 0.3 to 11 months (median engraftment in patients with hematologic malignancies who underwent alloBMT for progressive disease after ASCT. 2.0) after alloBMT, all due to BMT-related toxicities. Three patients remain alive and free of disease at 1.1, and 2.5 years after alloBMT. Sixteen of the 18 evaluable patients (89%) developed grade II-IV acute Materials and methods GVHD. Patients undergoing alloBMT after ASCT have a very high treatment-related mortality and incidence of Study cohort grade II-IV acute GVHD. Alternative treatments with salvage chemotherapy, radiation or investigationalWe retrospectively analyzed consecutive patients who underwent alloBMT after failing an ASCT for hematologic approaches should be considered in patients who relapse after ASCT.malignancies, from 1988 to 1995, at the following institutions: University of Texas Health Science Center at San Keywords: BMT; relapse; second transplant; lymphoma; leukemia Antonio (San Antonio, TX), Vanderbilt University (Nashville, TN), University of Oklahoma Health Science Center (Oklahoma City, OK), University of California at Los Angeles School of Medicine (Los Angeles, CA), and High-...

Summary:The objective of this study was to describe the outcome of allogeneic stem cell transplantation (alloSCT) in a series of patients with B cell chronic lymphocytic leukemia (B-CLL). Twenty-three B-CLL patients were transplanted between 1988 and 1997 using stem cells from a related (n = 20) or an unrelated donor (n = 3). The median age of the patients was 46 years, and the median number of prior chemotherapy regimens received was two. At transplantation, 14 patients had chemorefractory disease and 12 of these were refractory to fludarabine. The preparative regimens included total body irradiation (TBI) in 22 of the 23 cases. All patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporine and methotrexate. Twenty patients (87%) achieved a complete remission (CR). The incidence of grade II-IV acute GVHD was 54%. Fourteen (61%) patients are alive and disease-free, including two with unrelated donors, at a median of 26 months (range, 9-115 months). Nine patients (39%) have died, one of whom had progressive B-CLL. The only favorable prognostic factor for failure-free survival (FFS) and overall survival (OS) after alloSCT was the use of a cyclophosphamide/TBI rather than an etoposide/ cyclophosphamide/TBI regimen (P = 0.03). The projected 5-year FFS, OS, and relapse rates after alloSCT were 65% (95% CI, 48-88%), 62% (95% CI, 43-88%), and 5% (95%, CI 0-13%), respectively. These findings demonstrate the potential of high-dose therapy and alloSCT for inducing and maintaining a remission in patients with advanced or chemorefractory B-CLL. The low relapse rate may be due to an allogeneic graft-versus-leukemia effect. Bone Marrow Transplantation (2000) 25, 717-722.