Marrow fibrosis associated with a Philadelphia chromosome

Three patients had marked marrow fibrosis and an apparent Philadelphia (Ph) chromosome. Hematologic, cytogenetic, and molecular studies demonstrated the heterogeneity of such cases, including the first example of clinically typical myelofibrosis (MF) associated with a bcr gene rearrangement characteristic of chronic myelogenous leukemia (CML).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30164/1/0000548.pd

Younger adults with acute myeloid leukemia in remission for ≥3 years have a high likelihood of cure: The ECOG experience in over 1200 patients

We examined 1229 younger patients with acute myeloid leukemia who achieved CR1 on Eastern Cooperative Oncology Group trials. We defined late relapse as occurring after ≥3 years of CR1. With median follow-up of 11.3 years, there were 14 late relapses (1.1% of CR1 patients; 3.3% of 3-year CR1 patients). Eight achieved second CR and median overall survival after late relapse was 3.2 years. Most patients tested (9/11) had a normal karyotype at diagnosis; none had new cytogenetic abnormalities at relapse. Late relapse is rare and nearly all 3-year CR1 patients are cured. If late relapse occurs, outcomes are relatively favorable

Effects of poverty and race on outcomes in acute myeloid leukemia

To determine how patient race, ethnicity, and degree of poverty affect treatment and survival for acute myeloid leukemia (AML). A linked database of the Florida cancer registry and State inpatient and outpatient hospital data for 1998-2002 was queried. Effects of demographic and treatment characteristics on survival were explored using univariate and multivariate analyses methods. A total of 4659 patients with AML were identified. Over 50% of patients with AML were 70 years of age or older. African American (AA) patients were diagnosed at significantly younger ages than were whites (P < 0.001). In multivariate analysis, independent predictors of worse survival in AML were aged over 50 (hazard ratios [HRs]: 1.60, 2.15, 3.04, and 3.62 over the decade-cohorts, all P < 0.001), AA race (HR: 1.27, P < 0.001), being a former or current user of tobacco (HR: 1.13, P = 0.004 and HR: 1.28, P < 0.001, respectively), residing in an area with the highest poverty level (HR: 1.15, P = 0.007), and being covered only by Medicaid (HR: 1.23, P = 0.014). No differences in outcomes were observed related to gender or ethnicity. Receipt of chemotherapy was strongly associated with improved survival (HR: 0.59, P < 0.001). When only those patients who received and appeared to respond to treatment are included, AAs continued to demonstrate a worse outcome than Whites. AML disproportionately affects the elderly. AA patients and patients from poorer communities with AML have significantly worse survival. Interventions to provide earlier diagnosis in these patients as well as to improve overall outcomes are needed to address these disparities

Induction of CD8 T-cell-Ifn-gamma response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma

Large tumor burdens in advanced non-small-cell lung carcinoma (NSCLC) are thought to be immunosuppressive. To determine whether CD8-mediated immune responses could be elicited in stage IIIB/IV NSCLC patients, 14 subjects were immunized several times with allogeneic NSCLC cells transfected with CD80 (B7.1) and HLA-A1 or A2. Patients enrolled were matched or unmatched at the HLA A1 or A2 locus and their immune response compared. Immunization significantly increased the frequencies of interferon-gamma secreting CD8 T cells in all but one patient in response to ex vivo challenge with NSCLC cells. The CD8 response of matched and unmatched patients was not statistically different. NSCLC reactive CD8 cells did not react to K562. Clinically, five of 14 patients responded to immunization with stable disease or partial tumor regression. The study demonstrates that CD8 Ifn-gamma responses against nonimmunogenic or immunosuppressive tumors can be evoked by cellular vaccines even at advanced stages of disease. The positive clinical outcome suggests that nonimmunogenic tumors may be highly susceptible to immune effector cells generated by immunization

Allogeneic Vaccination With a B7.1 HLA-A Gene-Modified Adenocarcinoma Cell Line in Patients With Advanced Non–Small-Cell Lung Cancer

Purpose To determine the safety, immunogenicity, and clinical response to an allogeneic tumor vaccine for non–small-cell lung cancer, we conducted a phase I trial in patients with advanced metastatic disease. Patients and Methods We treated 19 patients with a vaccine based on an adenocarcinoma line (AD100) transfected with B7.1 (CD80) and HLA A1 or A2. Patients were vaccinated intradermally with 5 × 107 cells once every 2 weeks. Three vaccinations represented one course of treatment. If patients had complete response, partial response, or stable disease, they continued with the vaccinations for up to three courses (nine vaccinations). Immune response was assessed by a change between pre-study and postvaccination enzyme-linked immunospot frequency of purified CD8 T-cells secreting interferon-gamma in response to in vitro challenge with AD100. Results Four patients experienced serious adverse events that were unrelated to vaccine. Another four patients experienced only minimal skin erythema. All but one patient had a measurable CD8 response after three immunizations. The immune response of six surviving, clinically responding patients shows that CD8 titers continue to be elevated up to 150 weeks, even after cessation of vaccination. Overall, one patient had a partial response, and five had stable disease. Median survival for all patients is 18 months (90% CI, 7 to 23 months), with corresponding estimates of 1-year, 2-year, and 3-year survival of 52%, 30%, and 30%, respectively. HLA matching of vaccine, age, sex, race, and pathology did not bear a significant relation to response. Conclusion Minimal toxicity and good survival in this small population suggest clinical benefit from vaccination

A phase II trial of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin in the treatment of patients with locally advanced breast carcinoma

BACKGROUND Traditionally, primary surgical therapy is considered unsuitable for the treatment of patients with locally advanced breast carcinoma (LABC). Multiple reports have documented the efficacy of primary chemotherapy in this group of patients. The purpose of this study was to investigate the efficacy of a multimodality treatment program in reducing distant and local disease relapses in patients with LABC. METHODS Fifty‐five patients with large operable or inoperable Stage III breast carcinoma, median tumor greatest dimension 7 × 8 cm, were treated with neoadjuvant MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) to achieve maximum clinical response, followed by modified radical mastectomy, adjuvant MVAC for six courses, and chest wall radiation. Of these patients, 37 had Stage IIIA disease and 18 had Stage IIIB or inflammatory breast carcinoma. RESULTS Forty‐nine patients achieved overall responses to the neoadjuvant chemotherapy, including 16 complete clinical remissions. Histopathologic evaluation was performed for all patients; nine were pathologically free of disease and six had residual intraductal carcinoma only. After a median follow‐up of 47 months (range, 8‐76 months), 24 patients had relapsed: 6 locoregional and distant, and 18 distant only. The median disease free and overall survival have not been reached; the 5‐year disease free and overall survival rates are 51% and 63%, respectively. The number of lymph nodes with metastases was found to be an independent predictor of relapse in univariate and multivariate analyses. CONCLUSIONS This multidisciplinary approach produced an excellent local control rate and a respectable 5‐year distant relapse free rate. Axillary lymphadenectomy after primary chemotherapy provides crucial prognostic information, which can be important in planning multimodality treatment of patients with LABC. Cancer 1998;82:503‐11. © 1998 American Cancer Society. Neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin for patients with locally advanced breast carcinoma produces an excellent local control rate and a respectable 5‐year distant relapse free rate. Axillary lymph node involvement after the primary chemotherapy provides crucial prognostic information