Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma.

Purpose: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma (MCL).

Patients And Methods: Patients with indolent and MCL were eligible. Bortezomib was given at a dose of 1.

Differential expression patterns of c-REL protein in classic and nodular lymphocyte predominant Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) is characterized by numerical gains of the short arm of chromosome 2. The high frequency of 2p overrepresentation including REL, particularly in the nodular sclerosis subtype suggests that constitutive activation of nuclear factor kappaB/REL is a hallmark of Reed-Sternberg (RS) cells. The aim of this study was to investigate c-Rel protein expression patterns in cHL and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) cases by immunohistochemical analysis.

Promising activity of the proteasome inhibitor bortezomib (VELCADE) in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma: ASH poster session 517-II.

Dr. O'Connor delivered the following material as a poster at the 2003 American Society of Hematology meeting highlighting results from his work with bortezomib in the treatment of non-Hodgkin's and mantle cell lymphoma. A full publication of his results will appear later this year.

Semi-parametric estimation of the binormal ROC curve for a continuous diagnostic test.

Not until recently has much attention been given to deriving maximum likelihood methods for estimating the intercept and slope parameters from a binormal ROC curve that assesses the accuracy of a continuous diagnostic test. We propose two new methods for estimating these parameters. The first method uses the profile likelihood and a simple algorithm to produce fully efficient estimates.

Construct validity of the posttraumatic stress disorder checklist in cancer survivors: analyses based on two samples.

The measurement of posttraumatic stress disorder (PTSD) is critically important for the identification and treatment of this disorder. The PTSD Checklist (PCL; F. W.

The NHL-15 protocol for aggressive non-Hodgkin's lymphomas: a sequential dose-dense, dose-intense regimen of doxorubicin, vincristine and high-dose cyclophosphamide.

Background: The NHL-15 protocol is a novel, dose-intense, dose-dense, sequential chemotherapy program developed to improve outcome in advanced, aggressive non-Hodgkin's lymphomas.

Patients And Methods: The phase II NHL-15 protocol comprised: (i) induction [doxorubicin 60 mg/m(2) i.v.

Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease.

To determine whether combined modality therapy (CMT) is superior to chemotherapy (CT) alone, 152 untreated Hodgkin disease patients with clinical stages (CSs) IA, IB, IIA, IIB, and IIIA without bulk disease were prospectively randomized to 6 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) alone or 6 cycles of ABVD followed by radiation therapy (RT) (3600 cGy: involved field for 11 patients, modified extended field for the rest). Of 76 patients randomized to receive RT, 65 actually received it, and 11 did not (4 progressed, 1 had bleomycin toxicity, 6 refused). For ABVD + RT, the complete remission (CR) percentage was 94% and no major response, 6%.

Adverse prognostic significance of CD20 positive Reed-Sternberg cells in classical Hodgkin's disease.

The prognostic significance of CD20 positive classical Hodgkin's disease (cHD) is uncertain. All cHD cases referred to the Memorial Sloan-Kettering Cancer Center (MSKCC) were retrospectively identified (5/92-11/00); the samples were immunostained, and clinical data ascertained. Cases were re-reviewed without knowledge of clinical outcome.

An update on the management of relapsed and primary refractory Hodgkin's disease.

With the use of combined modality therapy for early stage disease and a risk-adapted approach for advanced stage disease, nearly 90% of patients with Hodgkin's lymphoma are cured with initial therapy. However, in patients who have primary refractory or relapsed disease, high-dose therapy and autologous stem cell transplantation is the best curative option. The use of peripheral blood progenitor cells has decreased transplant related mortality to less than 3%; but long-term progression-free survival as increased minimally.

Quantifying and comparing the accuracy of binary biomarkers when predicting a failure time outcome.

The positive and negative predictive values are standard measures used to quantify the predictive accuracy of binary biomarkers when the outcome being predicted is also binary. When the biomarkers are instead being used to predict a failure time outcome, there is no standard way of quantifying predictive accuracy. We propose a natural extension of the traditional predictive values to accommodate censored survival data.

Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a triplet (CAG) expansion mutation. The length of the triplet repeat is the most important factor in determining age of onset of HD, although substantial variability remains after controlling for repeat length. The Venezuelan HD kindreds encompass 18,149 individuals spanning 10 generations, 15,409 of whom are living.

Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin's disease.

Prospective randomized studies have determined that high dose therapy and autologous stem cell transplantation (ASCT) is the standard treatment for patients with chemosensitive relapsed Hodgkin's disease (HD); however, the role of this approach in patients with primary refractory disease has been controversial. This report is an integrated analysis of 75 consecutive patients with biopsy-confirmed primary refractory HD, who were treated with high dose chemoradiotherapy (HDT) and ASCT at the Memorial Sloan Kettering Cancer Center. The patients underwent conventional dose cytoreductive chemotherapy followed by HDT and ASCT.

Quantifying and comparing the predictive accuracy of continuous prognostic factors for binary outcomes.

The positive and negative predictive values are standard ways of quantifying predictive accuracy when both the outcome and the prognostic factor are binary. Methods for comparing the predictive values of two or more binary factors have been discussed previously (Leisenring et al., 2000, Biometrics 56, 345-351).

Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma.

Patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) who achieve complete response (CR) before autologous stem cell transplantation (ASCT) generally have better outcomes than those who achieve only partial response (PR). We investigated whether adding rituximab to the ifosfamide-carboplatin-etoposide (ICE) chemotherapy regimen (RICE) could increase the CR rate of patients with DLBCL under consideration for ASCT. Thirty-six eligible patients were treated with RICE, and 34 received all 3 planned cycles.

Small sample estimation of relative accuracy for binary screening tests.

Comparing the accuracy of two screening tests is ideally achieved by administering both tests as well as a gold standard test to all study subjects. In practice, a more ethical screen positive study design is often used, one that requires gold standard determination only for subjects that screen positive on either test under investigation. Although it is not possible to quantify the absolute accuracy of each test with such a design,the relative accuracy of the tests can be estimated.

Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis.

Purpose: To assess the safety and efficacy of intensive methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma (PCNSL).

Patients And Methods: Twenty-eight patients received induction chemotherapy using high-dose systemic methotrexate (3.5 g/m2) and cytarabine (3 g/m2 daily for 2 days).

Progressive disease following autologous transplantation in patients with chemosensitive relapsed or primary refractory Hodgkin's disease or aggressive non-Hodgkin's lymphoma.

To determine the outcome of patients with chemosensitive relapsed or primary refractory Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL) whose disease progresses after autologous stem cell transplantation (ASCT), we reviewed the records of 82 patients with HD and 139 patients with NHL transplanted between 1993 and 2000. Disease progression occurred in 25 patients with HD and 66 patients with NHL, with median times to progression (TTP) of 3.8 and 5.

Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma.

Background: In the era of highly active antiretroviral therapy (HAART), standard-dose chemotherapy for human immunodeficiency virus (HIV)-associated diffuse large B-cell lymphoma is becoming the standard of care. In contrast, the safety and efficacy of intensive regimens have not been established for Burkitt lymphoma (BL), a highly aggressive lymphoma for which moderate-dose chemotherapy is substandard in the HIV-negative population.

Methods: To evaluate the feasibility of intensive chemotherapy in HIV-associated BL, the authors retrospectively reviewed 14 HIV-positive adults with BL treated at their center between 1988 and 2000.

Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma.

Despite advances in the management of aggressive non-Hodgkin's lymphoma, the treatment of relapsed and primary refractory disease remains a major challenge. High-dose chemotherapy or radio-chemotherapy followed by autologous or allogeneic stem cell transplantation (SCT) is a potentially curative treatment approach; however, the applicability of this approach is restricted to patients responding to second-line chemotherapy. Thus, second-line therapy must be both efficacious and without stem cell or organ toxicity that would compromise the ability to proceed to SCT.

Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma.

Second-line chemotherapy followed by high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) cures less than half of the patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Prognostic models capable of predicting outcome are essential. In 3 sequential clinical trials, conducted from January 1993 to August 2000, we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease.

Rituximab for aggressive non-Hodgkin's lymphomas relapsing after or refractory to autologous stem cell transplantation.

Purpose: The median survival for aggressive non-Hodgkin's lymphomas relapsing after or refractory to high-dose therapy and autologous stem cell transplantation therapy is 6.2 months. In these cases, there is limited salvageability with the use of conventional therapy.

Risk-adapted therapy for relapsed and refractory lymphoma using ICE chemotherapy.

At Memorial Sloan Kettering Cancer Center, New York, we have treated over 400 patients with ICE chemotherapy after failure of upfront anthracycline-based therapy with a response rate of 72% in aggressive non-Hodgkin's lymphoma (NHL) and 84% in Hodgkin's disease. Utilizing this database, we have identified pretreatment prognostic markers capable of predicting the quality of response (complete response vs partial response vs failure) to second-line cytoreductive ICE chemotherapy and consequently autologous stem cell transplantation. We have shown that in aggressive NHL, patients achieving a complete response have superior survival when compared to those achieving only a partial response.

Sample size calculations for comparative studies of medical tests for detecting presence of disease.

Technologic advances give rise to new tests for detecting disease in many fields, including cancer and sexually transmitted disease. Before a new disease screening test is approved for public use, its accuracy should be shown to be better than or at least not inferior to an existing test. Standards do not yet exist for designing and analysing studies to address this issue.

Palliative care for people with late-stage Huntington's disease.

Huntington's disease provides a unique model to examine issues of long-term and palliative care for a younger and more mobile population who remain institutionalized longer than other nursing home residents. A lack of community-based alternatives for young families, and the need for highly complex care planning encourage long term care placement mid-way in the disease process. Despite the need for a body of knowledge specific to environmental enrichment and therapeutic strategies for improving quality of life for people in the later stages of Huntington's disease, there is no published data in the neurological or rehabilitation literature.

Cyclophosphamide/fludarabine (CF) is active in the treatment of mantle cell lymphoma.

The purpose of this study was to determine the efficacy and toxicity of the cyclophosphamide and fludarabine (CF) regimen in patients with newly diagnosed and relapsed/refractory mantle cell lymphoma (MCL). Thirty patients with pathologically confirmed MCL were treated with the CF regimen. Ten (33%) had no prior therapy, six (20%) had one previous regimen, and 14 (47%) received two or more prior regimens.