An international collaboration was set up to prospectively evaluate the role of allogeneic transplantation for adults with acute lymphoblastic leukemia (ALL) and compare autologous transplantation with standard chemotherapy. Patients received 2 phases of induction and, if in remission, were assigned to allogeneic transplantation if they had a compatible sibling donor. Other patients were randomized to chemotherapy for 2.5 years versus an autologous transplantation. A donor versus no-donor analysis showed that Philadelphia chromosome-negative patients with a donor had a 5-year improved overall survival (OS), 53% versus 45% (P ‫؍‬ .01), and the relapse rate was significantly lower (P < .001). The survival difference was significant in standard-risk patients, but not in high-risk patients with a high nonrelapse mortality rate in the highrisk donor group. Patients randomized to chemotherapy had a higher 5-year OS (46%) than those randomized to autologous transplantation (37%; P ‫؍‬ .03). Matched related allogeneic transplantations for ALL in first complete remission provide the most potent antileukemic therapy and considerable survival benefit for standard-risk patients. However, the transplantation-related mortality for highrisk older patients was unacceptably high and abrogated the reduction in relapse risk. There is no evidence that a single autologous transplantation can replace consolidation/maintenance in any risk group. This study is registered at http:// clinicaltrials.gov as NCT00002514. (Blood.

The international acute lymphoblastic leukemia (ALL) study was designed to prospectively define the optimal therapy for adults 60 years of age or younger with newly diagnosed ALL. All patients received identical induction therapy, and 91% achieved complete remission (CR). Patients 50 years of age or younger with a compatible sibling were assigned to undergo allogeneic transplantation; the others were randomly assigned to autologous transplantation or to consolidation/maintenance therapy for 2.5 years. Patients who did not achieve CR after induction had an overall survival rate of 5% compared with 45% for patients who achieved CR. Factors at diagnosis predictive of overall survival and diseasefree survival were age (P ‫؍‬ .001), white blood cell count less than 30 ؋ 10 9 /L for B lineage or less than 100 ؋ 10 9 /L for T lineage (P ‫؍‬ .001) and immunophenotype, T lineage versus B lineage (P ‫؍‬ .001). The data demonstrate that achieving CR with induction therapy is indispensable for long-term survival in adult patients with ALL. Furthermore, with a response rate greater than 90%, the induction regimen was highly efficacious as remissioninducing therapy. This large database has validated several previously identified independent prognostic factors in ALL, such as age, white blood cell count at presentation, cytogenetics, and immunophenotype. However, the achievement of CR within 4 weeks does not appear to be an independent prognostic factor. (Blood. 2005;106:3760-3767)

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and B M from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 X I O 5 mononuclear cells. lmmunostained tumor cells were detected in 9.8% (1 3/133) PBSC specimens from 9/48 (1 8.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < ,005). IGH-DOSE chemotherapy followed by autologousH marrow infusion appears to be an effective treatment for some patients with locally advanced or metastatic breast cancer.I4 However, using sensitive immunocytochemical techniques, tumor cells can be observed in histologically normal bone marrow (BM) in 20% to 45% of patients with operable disease and in 20% to 70% of patients with metastatic breast cancer.'-* As a result, many patients who have multiple bone or BM metastases have not been considered eligible for autologous BM transplantation (BMT).Recently, peripheral blood stem collections (PBSC) have been used as an alternative to BM for hematopoietic support in patients with breast cancer or hematologic malignancies who have BM Several studies examining patients with neuroblastoma and lymphoma"-I3 suggest that PBSC collections are less likely to contain tumor cells than BM and thus may provide a less contaminated source of hematopoietic stem cell support after high-dose chemotherapy.The incidence and quantity of tumor cell contamination of PBSC collections in breast cancer patients has not been widely inve~tigated.'~,'' We prospectively examined the incidence of tumor cell contamination in paired samples of PBSC and BM collections from 48 advanced-stage breast cancer patients using a highly sensitive immunocytochemical technique. To determine whether these tumor cells were capable of clonogenic growth in vitro, tumor cell-specific clonogenic assays were performed on 58 BM or PBSC collections. MATERIALS AND METHODS Patient population andparticipating centers.Patients with histologically documented locally advanced or metastatic adenocarcinoma of the breast who were enrolled on high-dose chemotherapy programs at the participating treating institutions were eligible for this study. This protocol was approved by the Institutional Review Board for Human Investigation and each patient gave written in-The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/1 O5 mononuclear cells (range 0.33 to 2.0/105) compared with 22.9/105 mononuclear cells in BM (range 1 to 3,000/105, P < .0001). In culture experiments, clonogenic tumor colonies grew in 21 /26 immunocytochemically po...

Thirty-six patients with metastatic melanoma were entered into a study of the therapeutic efficacy of adoptive immunotherapy with high-dose interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells. Thirty-two patients who received all components of the therapy are evaluable for response, and all patients are evaluable for toxicity. Sites of disease included lung, liver, subcutaneous nodules, and intra-abdominal metastases. One complete response (CR) and five partial responses (PRs) resulted from treatment (19% response rate). The median response duration was 5 months, with the durable CR continuing at 31+ months and one durable PR continuing for 13 months. Sites of response included lung, liver, subcutaneous nodules, and lymph nodes. Response, response duration, or site of response did not correlate with the total dose of IL-2 administered, rebound lymphocytosis, or the number of LAK cells infused. Toxicity included hypotension, fluid retention with a "capillary leak syndrome" in most patients, and transient multiorgan dysfunction that resolved promptly after the completion of therapy. Adverse cardiac events occurred in 16% of patients, with one myocardial infarction leading to a death. This study confirms the activity of the initial IL-2/LAK cell regimen in metastatic melanoma reported by Rosenberg et al, supporting the concept of adoptive immunotherapy as an important new treatment approach for this disease.

Bone marrow transplantation now is a common procedure done throughout the world. Cooperative groups have assumed a major role in conducting clinical trials. A standardized approach defining basic standards of care will assure uniformity of management, better interpretation of data, and continued progress in the care of the patient who has had a bone marrow transplantation. Basic research and clinical trials are ongoing to define better methods for the treatment and prevention of graft-versus-host disease and hepatic veno-occlusive disease.