Carfilzomib combined with rituximab, ifosfamide, carboplatin, and etoposide for relapsed or refractory DLBCL.

The CORAL study highlighted the need to develop novel salvage regimens in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) previously treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Carfilzomib (CFZ) can overcome rituximab chemotherapy resistance in lymphoma preclinical models by targeting the ubiquitin-proteasome system. We conducted an investigator initiated, single-center, open-label, prospective phase 1 study evaluating the safety and efficacy of CFZ in combination with rituximab, ifosfamide, carboplatin, and etoposide (C-R-ICE) in high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) eligible patients with R/R DLBCL (NCT01959698).

Spatiotemporal assessment of immunogenomic heterogeneity in multiple myeloma.

Spatial heterogeneity is a common phenomenon in metastatic solid tumors and an evolving concept in multiple myeloma (MM). The interplay between malignant plasma cells (PCs) and the microenvironment has not yet been analyzed in MM. For this purpose, we performed bone marrow aspirates and imaging-guided biopsies of corresponding lesions in newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) patients.

Ofatumumab plus HyperCVAD/HD-MA induction leads to high rates of minimal residual disease negativity in patients with newly diagnosed mantle cell lymphoma: Results of a phase 2 study.

Background: Ofatumumab is a humanized type 1 anti-CD20 monoclonal antibody. Preclinical studies show improved complement-mediated cytotoxicity (CMC) compared to rituximab in mantle cell lymphoma (MCL). This study evaluates the safety and efficacy of combining ofatumumab with HyperCVAD/MA (O-HyperCVAD) in newly diagnosed MCL.

Low 25(OH) vitamin D3 levels are associated with adverse outcome in newly diagnosed, intensively treated adult acute myeloid leukemia.

Background: Several studies have suggested that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in patients with acute myeloid leukemia (AML).

Methods: Vitamin D levels were evaluated in 97 consecutive, newly diagnosed, intensively treated patients with AML. MicroRNA expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome.

Phase II trial of clofarabine and daunorubicin as induction therapy for acute myeloid leukemia patients greater than or equal to 60 years of age.

We designed a phase II study evaluating the upfront combination of clofarabine and daunorubicin in acute myeloid leukemia (AML) patients≥60 years old. The median age of the 21 patients was 69 (range 60-85) years. Fourteen patients (67%) had unfavorable risk features.

Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia.

Purpose: To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML).

Patients And Methods: We analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), and overall survival (OS) among patients classified into the four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse) separately for 818 younger (age < 60 years) and 732 older (age ≥ 60 years) patients.

Image cytometry-based detection of aneuploidy by fluorescence in situ hybridization in suspension.

Cytogenetic abnormalities are important diagnostic and prognostic criteria for hematologic malignancies. Karyotyping and fluorescence in situ hybridization (FISH) are the conventional methods by which these abnormalities are detected. The sensitivity of these microscopy-based methods is limited by the abundance of the abnormal cells in the samples and therefore these analyses are commonly not applicable to minimal residual disease (MRD) stages.

Monoallelic and biallelic deletions of 13q14.3 in chronic lymphocytic leukemia: FISH vs miRNA RT-qPCR detection.

Deletion of 13q14.3 (del(13q)) is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL) and implies a favorable prognosis. We explored the feasibility of detecting del(13q) by real-time quantitative polymerase chain reaction (PCR) for miR-15a and miR-16-1, whose loci are located in the deleted region.

Is obesity a prognostic factor for acute myeloid leukemia outcome?

Obesity adversely affects outcome in pediatric acute lymphocytic leukemia and acute myeloid leukemia (AML). We asked if obesity, measured by body mass index (BMI), affected outcome in 329 adult AML patients treated with high-dose cytarabine and idarubicin-containing regimens administered according to actual body weight. Age ≥ 60, unfavorable karyotype, secondary AML, and positive smoking status had adverse impact on overall survival in a multivariate analysis, while BMI did not.

Smoking adversely affects survival in acute myeloid leukemia patients.

Smoking adversely affects hematopoietic stem cell transplantation outcome. We asked whether smoking affected outcome of newly diagnosed acute myeloid leukemia (AML) patients treated with chemotherapy. Data were collected on 280 AML patients treated with high-dose cytarabine and idarubicin-containing regimens at Roswell Park Cancer Institute who had smoking status data at diagnosis.

Phase 1 study of arsenic trioxide, high-dose cytarabine, and idarubicin to down-regulate constitutive signal transducer and activator of transcription 3 activity in patients aged <60 years with acute myeloid leukemia.

Background: Constitutive activation of signal transducer and activator of transcription-3 (STAT3) was detected in blasts from approximately 50% of patients with acute myeloid leukemia (AML) and was correlated with an adverse outcome. In vitro treatment of AML blasts with arsenic trioxide (ATO) down-regulated STAT3 activity within 6 hours associated with a reduced viability within 48 hours.

Methods: A phase 1 clinical trial to evaluate the biologically effective dose and/or the maximally tolerated dose (MTD) of ATO in vivo in conjunction with high-dose cytarabine (Hidac) and idarubicin (Ida) in patients with AML aged <60 years was conducted.

Myeloid blastic transformation of myeloproliferative neoplasms--a review of 112 cases.

Blastic transformation of myeloproliferative neoplasms (MPN) is still poorly understood. We describe a cohort of 23 Roswell Park Cancer Institute (RPCI) patients and 89 additional cases from the English literature for whom biologic features were described. We initially compared our 23 patients to the 89 cases from the literature.

A GOG 210 aCGH study of gain at 1q23 in endometrioid endometrial cancer in the context of racial disparity and outcome.

The goal of this study was to identify recurrent regions of genomic gain or loss in endometrial cancer of the endometrioid type in the context of racial disparities in mortality for this disease. Array comparative genomic hybridization (aCGH) analysis was performed on 80 frozen primary tumors from the Gynecologic Oncology Group (GOG)-210 bank using the RPCI 19K BAC arrays. The 80 patients included 20 African American (AA) Stage I, 20 White (W) Stage I, 20 African American (AA) Stage IIIC/IV, and 20 White (W) Stage IIIC/IV.

Efficacy of lenalidomide in patients with chronic lymphocytic leukemia with high-risk cytogenetics.

Patients with chronic lymphocytic lymphoma (CLL) with high-risk cytogenetics [del(11q)(q22.3) or del(17p)(p13.1)] have limited therapeutic options and their prognosis remains poor.

Treating octogenarian and nonagenarian acute myeloid leukemia patients--predictive prognostic models.

Background: Treating the octogenarian and nonagenarian patients who have acute myeloid leukemia (AML) with intensive chemotherapy is controversial. Several models to predict outcome were proposed, including the use of a comorbidity index. However, it is unclear whether the Charlson comorbidity index (CCI) or the hematopoietic cell transplant comorbidity index (HCTCI) is more sensitive.

Metachronous and synchronous presentation of acute myeloid leukemia and lung cancer.

Smoking is associated with both acute myeloid leukemia (AML) and lung cancer. We therefore searched our database for concomitant presentation of AML and lung cancer. Among 775 AML cases and 5225 lung cancer cases presenting to Roswell Park Cancer Institute between the years January 1992 and May 2008 we found 12 (1.

Central review of cytogenetics is necessary for cooperative group correlative and clinical studies of adult acute leukemia: the Cancer and Leukemia Group B experience.

The Cancer and Leukemia Group B has performed central review of karyotypes submitted by institutional cytogenetics laboratories from patients with acute myeloid (AML) and acute lymphoblastic (ALL) leukemia since 1986. We assessed the role of central karyotype review in maintaining accurate, high quality cytogenetic data for clinical and translational studies using two criteria: the proportion of karyotypes rejected (i.e.

Therapy-related myelodysplastic syndrome and acute myeloid leukemia following treatment of acute myeloid leukemia: possible role of cytarabine.

Therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/t-AML) have been reported only rarely following treatment of AML. We report five patients treated for de novo AML who developed t-MDS/t-AML, all with chromosome 7 abnormalities, including -7, del(7)(q22q36) and del(7)(p11.22p22).