DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma.

Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. Tumor-specific cytotoxic CD8+ and CD4+ T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte-monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.

These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support.

PURPOSE-The threat of smallpox resulting from bioterrorist action has prompted a reassessment of the level of immunity in current populations. METHODS-We have examined the magnitude and duration of antiviral antibody immunity conferred by smallpox vaccination in 246 participants of the Baltimore Longitudinal Study of Aging.Of this population, 209 subjects were vaccinated one or more times 13 to 88 years before this evaluation, and stored serum samples were available at various intervals after vaccination. An additional 8 subjects who had documented childhood smallpox infection and 29 subjects with no history of infection or vaccination were included. We quantified the total vaccinia IgG and neutralizing antibody titers in each of these subgroups of participants over time.RESULTS-Vaccinated participants maintained antivaccinia IgG and neutralizing antibody titers above 3 natural logs essentially indefinitely. The absolute titer of antivaccinia antibody was only slightly higher after multiple vaccinations. In 97% of the participants, no decrease in vaccinia-specific antibody titers was noted with age over a follow-up period of up to 88 years. Moreover, Baltimore Longitudinal Study of Aging participants who survived active smallpox infections in their youth retained antivaccinia antibody titers that were similar to the levels detected in vaccinated subjects.CONCLUSION-These data suggest that multiple or recent vaccinations are not essential to maintain vaccinia-specific antibody responses in human subjects. Scarce vaccine supplies should be applied first to individuals who have not previously been vaccinated. KeywordsAging; BLSA; Biodefense; Smallpox; Vaccination; Vaccinia The vaccinia virus vaccine has been used to prevent smallpox disease and control its spread since the late 18 th century. Routine vaccination with vaccinia was discontinued over 30 years ago in many countries. [1][2][3][4][5][6][7][8] Despite the worldwide eradication of smallpox in 1977, the potential re-emergence of this disease from bioterrorist action has prompted international health care NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript authorities to reassess the level of immunity in current populations and to evaluate the risks and benefits of revaccination programs.Given that the majority of Americans under the age of 35 years have never been vaccinated against smallpox and the great majority of those over 35 have not received booster vaccinations since the early 1970s, immunity to smallpox is considered to be low to nonexistent in today's population. In the past, primary vaccination of individuals with vaccinia was believed to confer dependable protection for at least 5 years, with increasing protection achieved with subsequent revaccinations. 1,2 However, a major question posed today is whether those individuals vaccinated 40 or more years ago would be protected in the event of smallpox exposure. This may be a critical question because the availability of smallpox vaccines is limited and currently inade...

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The results of treatment of 198 patients with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) for Hodgkin's disease were analyzed after a median of 14 years of follow-up. Throughout the period of follow-up, 103 patients have remained continuously free of disease. Review of biopsy specimens of 43 patients originally classified as Hodgkin's disease, lymphocyte-depleted type, revealed that ten of these patients actually had diffuse immunoblastic or large cell non-Hodgkin's lymphomas. Of the 188 patients with Hodgkin's disease, 157 achieved a complete response (CR) (84%), and 66% of them (101 patients) have remained disease-free more than 10 years from the end of treatment. Absence of B symptoms and receiving higher doses of vincristine were factors associated with a higher CR rate and longer survival. Patients entering complete remission in five cycles or less had significantly longer remissions than those requiring six or more cycles. Forty-eight percent of the Hodgkin's disease patients have survived between 9 and 21 years (median, 14 years) from the end of treatment. Nineteen percent of the CRs have died of intercurrent illnesses, free of Hodgkin's disease.

Two recent reports of the same combination chemotherapy program, cyclophosphamide, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, bleomycin, and prednisone (ProMACE-CytaBOM), in similar subsets of patients with advanced-stage aggressive-histology lymphoma used two different methods to report the actual dose-intensity (DI) data. One method treats DI as a property of a particular cycle of treatment within the entire population that received that cycle. The other treats DI as a characteristic of a particular patient's entire treatment course. We have applied both methods to the same set of data and provide evidence that the latter method is preferable for at least two reasons: (1) it more accurately reflects actual DI by clearly incorporating the duration of the actual treatment course and, thus, can be used to compare the administration of same or related regimens to distinct patient populations; and (2) it allows assignment of a numerical value to an individual patient's treatment course or a group of patients' treatment courses such that DI can be examined for its impact on treatment outcome just like any other prognostic factor. The observed differences in treatment outcome between the Southwest Oncology Group (SWOG) and National Cancer Institute (NCI) studies are not clearly related to differences in distribution of clinical prognostic factors in the two study populations. The differences in methods of reporting DI prohibit evaluation of the influence of dose-related variables on outcome in the two studies. Adoption of a standard method of calculating and reporting DI data would facilitate evaluation of the prognostic significance of DI.

When patients with aggressive lymphoma present with intraabdominal disease, a stable residual mass is frequently detected radiographically at the time of the clinical complete remission. To discern the optimal management for this clinical problem, we reviewed 241 patients with aggressive lymphoma treated at the National Cancer Institute (NCI) from 1977 to 1986. Seventy-two/241 patients (30%) had an abdominal mass at diagnosis and 29/72 (40%) were left with a radiographically detectable residual mass at clinical complete remission. The likelihood of a residual mass was much higher for patients with bulky disease (P2 less than .0003) (two-tailed test [P2]). Twenty-nine patients had radiologically stable residual masses after therapy, and of 22 (76%) with pathologic evaluations, 21 had negative specimens (95%) and one was positive (5%). None of the patients with negative pathologic evaluation has relapsed in the abdominal site (median follow-up, 31 months). Seven patients were observed clinically without laparotomy: five are alive, without evidence of disease, at 2 to 9 years; two relapsed with disseminated disease within 2 months of chemotherapy. Initial tumor size and size of the residual mass did not correlate with residual disease, since residual masses identified by radiographic examination did not usually harbor viable lymphoma cells. Aspiration cytology was negative for residual tumor in 15/16 cases. One negative result was not confirmed at laparotomy, presumably due to sampling error. The one positive aspiration was followed by a negative laparotomy, possibly due to subsequent tumor necrosis. Restaging laparotomy has a low yield. In most patients with aggressive lymphoma who have otherwise completely responded to carefully administered full-dose combination chemotherapy, stable residual abdominal masses can be closely followed clinically without surgical exploration.