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Hematology

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Acalabrutinib (Acp-196) In Relapsed Chronic Lymphocytic Leukemia, J. C. Byrd, B. Harrington, S. O'Brien, J. A. Jones, A. Schuh, S. Devereux, J. Chaves, W. G. Wierda, J. C. Barrientos, R. R. Furman, +20 Additional Authors Jan 2016

Acalabrutinib (Acp-196) In Relapsed Chronic Lymphocytic Leukemia, J. C. Byrd, B. Harrington, S. O'Brien, J. A. Jones, A. Schuh, S. Devereux, J. Chaves, W. G. Wierda, J. C. Barrientos, R. R. Furman, +20 Additional Authors

Journal Articles

Background Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors. Methods In this uncontrolled, phase 1-2, multicenter study, we administered oral acalabrutinib to 61 patients who had relapsed CLL to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib. Patients were treated with acalabrutinib at a dose of ...


Relationship Between Obesity And Clinical Outcome In Adults With Acute Myeloid Leukemia: A Pooled Analysis From Four Calgb (Alliance) Clinical Trials, J. J. Castillo, F. Mulkey, S. Geyer, J. E. Kolitz, W. Blum, B. L. Powell, S. L. George, R. A. Larson, R. M. Stone Jan 2016

Relationship Between Obesity And Clinical Outcome In Adults With Acute Myeloid Leukemia: A Pooled Analysis From Four Calgb (Alliance) Clinical Trials, J. J. Castillo, F. Mulkey, S. Geyer, J. E. Kolitz, W. Blum, B. L. Powell, S. L. George, R. A. Larson, R. M. Stone

Journal Articles

Obesity has been previously suggested as an adverse prognostic marker in patients with acute leukemia. To evaluate the relationship between obesity and clinical outcome, disease-free survival (DFS) and overall survival (OS), in patients with acute myelogenous leukemia (AML), including acute promyelocytic leukemia (APL), we performed a pooled analysis of four CALGB (Alliance) clinical trials. Our study included 446 patients with APL from CALGB 9710, and 1,648 patients between 18 and 60 years of age with non-APL AML from CALGB 9621, 10503, and 19808. Obesity was defined as BMI >/=30 kg/m(2) . Multivariate Cox proportional-hazard regression models were fitted ...


A Phase Ii Randomized Trial Comparing Standard And Low Dose Rituximab Combined With Alemtuzumab As Initial Treatment Of Progressive Chronic Lymphocytic Leukemia In Older Patients: A Trial Of The Ecog-Acrin Cancer Research Group (E1908), C. S. Zent, X. V. Wang, R. P. Ketterling, C. A. Hanson, E. N. Libby, J. C. Barrientos, T. G. Call, J. E. Chang, J. J. Liu, M. S. Tallman, +5 Additional Authors Jan 2016

A Phase Ii Randomized Trial Comparing Standard And Low Dose Rituximab Combined With Alemtuzumab As Initial Treatment Of Progressive Chronic Lymphocytic Leukemia In Older Patients: A Trial Of The Ecog-Acrin Cancer Research Group (E1908), C. S. Zent, X. V. Wang, R. P. Ketterling, C. A. Hanson, E. N. Libby, J. C. Barrientos, T. G. Call, J. E. Chang, J. J. Liu, M. S. Tallman, +5 Additional Authors

Journal Articles

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients requiring initial therapy are often older and frailer and unsuitable candidates for standard chemoimmunotherapy regimens. Shorter duration combination monoclonal antibody (mAb) therapy using alemtuzumab and rituximab has been shown to be effective and tolerable treatment for CLL. Standard dose anti-CD20 mAb therapy causes loss of CD20 expression by surviving CLL cells, which can be minimized by decreasing the mAb dose. We report a randomized phase II clinical trial enrolling older (>/= 65 years) patients (median age 76 years, n=31) with treatment naive progressive CLL. Patients received 8-12 weeks of standard subcutaneous alemtuzumab ...


Sotatercept (Ace-011) For The Treatment Of Chemotherapy-Induced Anemia In Patients With Metastatic Breast Cancer Or Advanced Or Metastatic Solid Tumors Treated With Platinum-Based Chemotherapeutic Regimens: Results From Two Phase 2 Studies, H. Raftopoulos, A. Laadem, P. J. Hesketh, J. Goldschmidt, N. Gabrail, C. Osborne, M. Ali, M. L. Sherman, D. Wang, J. Crawford, +3 Additional Authors Jan 2016

Sotatercept (Ace-011) For The Treatment Of Chemotherapy-Induced Anemia In Patients With Metastatic Breast Cancer Or Advanced Or Metastatic Solid Tumors Treated With Platinum-Based Chemotherapeutic Regimens: Results From Two Phase 2 Studies, H. Raftopoulos, A. Laadem, P. J. Hesketh, J. Goldschmidt, N. Gabrail, C. Osborne, M. Ali, M. L. Sherman, D. Wang, J. Crawford, +3 Additional Authors

Journal Articles

PURPOSE: Sotatercept may represent a novel approach to the treatment of chemotherapy-induced anemia (CIA). We report the results from two phase 2 randomized studies examining the use of sotatercept for the treatment of CIA in patients with metastatic cancer. METHODS: In study A011-08, patients with metastatic breast cancer were randomized to 2:2:2:1 to receive sotatercept 0.1, 0.3, or 0.5 mg/kg, or placebo, respectively, every 28 days. In study ACE-011-NSCL-001, patients with solid tumors treated with platinum-based chemotherapy received sotatercept 15 or 30 mg every 42 days. The primary endpoint for both studies was ...


Successful Pregnancy Outcome In Paroxysmal Nocturnal Hemoglobinuria (Pnh) Following Escalated Eculizumab Dosing To Control Breakthrough Hemolysis, R. Sharma, A. Keyzner, J. Liu, T. Bradley, S. L. Allen Jan 2015

Successful Pregnancy Outcome In Paroxysmal Nocturnal Hemoglobinuria (Pnh) Following Escalated Eculizumab Dosing To Control Breakthrough Hemolysis, R. Sharma, A. Keyzner, J. Liu, T. Bradley, S. L. Allen

Journal Articles

Pregnancy in women with paroxysmal nocturnal hemoglobinuria (PNH) is associated with increased maternal and fetal morbidity and mortality. There is limited published experience regarding therapy of PNH during pregnancy. We describe a case of a 30 year old female with hypoplastic myelodysplastic syndrome and PNH. After two years of treatment with eculizumab, she became pregnant. She developed breakthrough hemolysis at 20 weeks gestation. Pharmacokinetic and pharmacodynamic studies demonstrated a subtherapeutic eculizumab level with absence of complement blockade. Escalation of her eculizumab dose successfully controlled hemolysis and restored therapeutic eculizumab level and activity. She delivered a healthy baby at 36 weeks.


Phase Ii, Multicenter, Randomized Trial Of Cpx-351 (Cytarabine: Daunorubicin) Liposome Injection Versus Intensive Salvage Therapy In Adults With First Relapse Aml, J. E. Cortes, S. L. Goldberg, E. J. Feldman, D. A. Rizzeri, D. E. Hogge, M. Larson, A. Pigneux, C. Recher, G. Schiller, J. E. Kolitz, +3 Additional Authors Jan 2015

Phase Ii, Multicenter, Randomized Trial Of Cpx-351 (Cytarabine: Daunorubicin) Liposome Injection Versus Intensive Salvage Therapy In Adults With First Relapse Aml, J. E. Cortes, S. L. Goldberg, E. J. Feldman, D. A. Rizzeri, D. E. Hogge, M. Larson, A. Pigneux, C. Recher, G. Schiller, J. E. Kolitz, +3 Additional Authors

Journal Articles

BACKGROUNDCPX-351 is a liposome-encapsulated fixed-molar-ratio formulation of cytarabine and daunorubicin that exploits molar ratio-dependent drug-drug synergy to enhance antileukemic efficacy. METHODSThis phase II study randomized 125 patients 2:1 to CPX-351 or investigators' choice of first salvage chemotherapy. Patients with acute myeloid leukemia (AML) in first relapse after initial Complete Remission (CR) lasting 1 month were stratified per the European Prognostic Index (EPI) into favorable, intermediate, and poor-risk groups based on duration of first CR, cytogenetics, age, and transplant history. Control salvage treatment was usually based on cytarabine and anthracycline, often with 1 or more additional agents. Survival at 1 ...


Body Mass Index, Pam50 Subtype, And Outcomes In Node-Positive Breast Cancer: Calgb 9741 (Alliance), J. A. Ligibel, C. T. Cirrincione, M. Liu, M. Citron, J. N. Ingle, W. Gradishar, S. Martino, W. Sikov, R. Michaelson, W. T. Barry, +6 Additional Authors Jan 2015

Body Mass Index, Pam50 Subtype, And Outcomes In Node-Positive Breast Cancer: Calgb 9741 (Alliance), J. A. Ligibel, C. T. Cirrincione, M. Liu, M. Citron, J. N. Ingle, W. Gradishar, S. Martino, W. Sikov, R. Michaelson, W. T. Barry, +6 Additional Authors

Journal Articles

BACKGROUND: Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors. METHODS: CALGB 9741 was a randomized trial of dose density and sequence of chemotherapy for node-positive breast cancer. All patients received doxorubicin, cyclophosphamide, and paclitaxel, dosed by actual body weight. Height and weight at diagnosis were abstracted from patient records, and the PAM50 assay was performed from archived specimens using the NanoString platform. Relationships between body mass index (BMI), PAM50, and recurrence-free and overall survival (RFS and OS) were evaluated using proportional hazards regression, adjusting for number ...


Acute Myeloid Leukemia Ontogeny Is Defined By Distinct Somatic Mutations, R. C. Lindsley, B. G. Mar, E. Mazzola, P. V. Grauman, S. Shareef, S. L. Allen, A. Pigneux, M. Wetzler, R. K. Stuart, B. L. Ebert, +9 Additional Authors Jan 2015

Acute Myeloid Leukemia Ontogeny Is Defined By Distinct Somatic Mutations, R. C. Lindsley, B. G. Mar, E. Mazzola, P. V. Grauman, S. Shareef, S. L. Allen, A. Pigneux, M. Wetzler, R. K. Stuart, B. L. Ebert, +9 Additional Authors

Journal Articles

Acute myeloid leukemia (AML) can develop after an antecedent myeloid malignancy (secondary AML [s-AML]), after leukemogenic therapy (therapy-related AML [t-AML]), or without an identifiable prodrome or known exposure (de novo AML). The genetic basis of these distinct pathways of AML development has not been determined. We performed targeted mutational analysis of 194 patients with rigorously defined s-AML or t-AML and 105 unselected AML patients. The presence of a mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 was >95% specific for the diagnosis of s-AML. Analysis of serial samples from individual patients revealed that these mutations occur early ...


Targeting Mutant Braf In Relapsed Or Refractory Hairy-Cell Leukemia, E. Tiacci, J. H. Park, L. De Carolis, S. S. Chung, A. Broccoli, S. Scott, F. Zaja, S. Devlin, K. R. Rai, M. S. Tallman, +31 Additional Authors Jan 2015

Targeting Mutant Braf In Relapsed Or Refractory Hairy-Cell Leukemia, E. Tiacci, J. H. Park, L. De Carolis, S. S. Chung, A. Broccoli, S. Scott, F. Zaja, S. Devlin, K. R. Rai, M. S. Tallman, +31 Additional Authors

Journal Articles

Background BRAF V600E is the genetic lesion underlying hairy-cell leukemia. We assessed the safety and activity of the oral BRAF inhibitor vemurafenib in patients with hairy-cell leukemia that had relapsed after treatment with a purine analogue or who had disease that was refractory to purine analogues. Methods We conducted two phase 2, single-group, multicenter studies of vemurafenib (at a dose of 960 mg twice daily) - one in Italy and one in the United States. The therapy was administered for a median of 16 weeks in the Italian study and 18 weeks in the U.S. STUDY: Primary end points were ...


Management Of Adverse Events Associated With Idelalisib Treatment: Expert Panel Opinion, S. E. Coutre, J. C. Barrientos, J. R. Brown, S. De Vos, R. R. Furman, M. J. Keating, D. Li, S. M. O'Brien, J. M. Pagel, A. D. Zelenetz, +3 Additional Authors Jan 2015

Management Of Adverse Events Associated With Idelalisib Treatment: Expert Panel Opinion, S. E. Coutre, J. C. Barrientos, J. R. Brown, S. De Vos, R. R. Furman, M. J. Keating, D. Li, S. M. O'Brien, J. M. Pagel, A. D. Zelenetz, +3 Additional Authors

Journal Articles

Idelalisib is a first-in-class selective, oral, phosphatidylinositol 3-kinase delta (PI3Kdelta) inhibitor approved for the treatment of several types of blood cancer. Idelalisib has demonstrated significant efficacy and a tolerable safety profile in clinical trials. However, the US prescribing information contains a black box warning for fatal and/or severe diarrhea or colitis, hepatotoxicity, pneumonitis and intestinal perforation. An expert panel was convened to review the pathology of these treatment-emergent adverse events (TEAEs) to propose key management tools for patients receiving idelalisib therapy. This article provides an overview of idelalisib TEAEs reported in clinical trials, and a summary of the panel ...


In Support Of A Patient-Driven Initiative And Petition To Lower The High Price Of Cancer Drugs, A. Tefferi, K. Rai, A. I. Schafer, C. Schiffer, M. A. Sekeres, L. L. Siu, F. M. Stewart, M. Thompson, J. M. Vose, P. H. Wiernik, +109 Additional Authors Jan 2015

In Support Of A Patient-Driven Initiative And Petition To Lower The High Price Of Cancer Drugs, A. Tefferi, K. Rai, A. I. Schafer, C. Schiffer, M. A. Sekeres, L. L. Siu, F. M. Stewart, M. Thompson, J. M. Vose, P. H. Wiernik, +109 Additional Authors

Journal Articles

No abstract provided.


Feasibility And Cardiac Safety Of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (Neo) Adjuvant Therapy For Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer, I. E. Krop, T. M. Suter, C. T. Dang, L. Dirix, G. Romieu, C. Zamagni, M. L. Citron, M. Campone, N. Xu, M. Smitt, L. Gianni Jan 2015

Feasibility And Cardiac Safety Of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (Neo) Adjuvant Therapy For Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer, I. E. Krop, T. M. Suter, C. T. Dang, L. Dirix, G. Romieu, C. Zamagni, M. L. Citron, M. Campone, N. Xu, M. Smitt, L. Gianni

Journal Articles

Purpose Trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC). Patients and Methods Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) >= 55% received (neo) adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without trastuzumab. T-DM1 ...


Long-Term Follow-Up Of Mcl Patients Treated With Single-Agent Ibrutinib: Updated Safety And Efficacy Results, M. L. Wang, K. A. Blum, P. Martin, A. Goy, R. Auer, B. S. Kahl, W. Jurczak, R. H. Advani, J. C. Barrientos, S. Rule, +14 Additional Authors Jan 2015

Long-Term Follow-Up Of Mcl Patients Treated With Single-Agent Ibrutinib: Updated Safety And Efficacy Results, M. L. Wang, K. A. Blum, P. Martin, A. Goy, R. Auer, B. S. Kahl, W. Jurczak, R. H. Advani, J. C. Barrientos, S. Rule, +14 Additional Authors

Journal Articles

Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy. We report the updated safety and efficacy results from the multicenter, open-label phase 2 registration trial of Ibrutinib (median 26.7-month follow-up). Patients (N = 111) received oral ibrutinib 560 mg once daily, and those with stable disease or better could enter a long-term extension study. The primary end point was overall response rate (ORR). The median patient age was 68 years (range, 40-84), with a median of 3 prior therapies (range, 1-5). The median treatment duration was ...


Identification And Characterization Of Distinct Il-17f Expression Patterns And Signaling Pathways In Chronic Lymphocytic Leukemia And Normal B Lymphocytes, B. Sherry, P. Jain, P. Y. Chiu, L. Leung, S. L. Allen, J. E. Kolitz, K. R. Rai, J. Barrientos, S. Liang, R. Hawtin, N. Chiorazzi Jan 2015

Identification And Characterization Of Distinct Il-17f Expression Patterns And Signaling Pathways In Chronic Lymphocytic Leukemia And Normal B Lymphocytes, B. Sherry, P. Jain, P. Y. Chiu, L. Leung, S. L. Allen, J. E. Kolitz, K. R. Rai, J. Barrientos, S. Liang, R. Hawtin, N. Chiorazzi

Journal Articles

Chronic lymphocytic leukemia (CLL) is characterized by a progressive accumulation of B lymphocytes. T cell abnormalities are a common feature of CLL and contribute to impaired immune function in these patients. T cells are ineffective in eliminating the leukemic clone and may actually promote tumor growth and survival. Previous work from our laboratory documented elevated circulating levels of IL-17A-producing Th17 cells in CLL patients as compared to healthy age-matched control subjects. These high circulating Th17 levels associated with better prognostic markers and significantly longer overall survival, even among patients whose clones used unmutated IGHVs (U-CLL). Recent studies suggest that Th17 ...


Therapeutic Potential Of New B Cell-Targeted Agents In The Treatment Of Elderly And Unfit Patients With Chronic Lymphocytic Leukemia, K. R. Rai Jan 2015

Therapeutic Potential Of New B Cell-Targeted Agents In The Treatment Of Elderly And Unfit Patients With Chronic Lymphocytic Leukemia, K. R. Rai

Journal Articles

Chronic lymphocytic leukemia (CLL), the most common adult leukemia in the Western world, is primarily a disease of the elderly, with most patients >= 65 years of age and having at least one major comorbidity. Aggressive chemoimmunotherapy regimens recommended to achieve remission and improve survival in young, fit patients are often poorly tolerated in elderly and/or less physiologically fit ("unfit") patients, necessitating alternative treatment options. Although patient age, fitness, and comorbidities are key considerations in the selection of a treatment regimen, historically, clinical trials have been limited to young, fit patients by virtue of the ethical concerns associated with potential ...


Management Of Chronic Lymphocytic Leukemia In The Elderly, J. C. Barrientos Jan 2015

Management Of Chronic Lymphocytic Leukemia In The Elderly, J. C. Barrientos

Journal Articles

No abstract provided.


Phase Ii Double-Blind Placebo-Controlled Randomized Study Of Armodafinil For Brain Radiation-Induced Fatigue, B. R. Page, E. G. Shaw, L. Lu, D. Bryant, D. Grisell, G. J. Lesser, D. C. Monitto, M. J. Naughton, S. R. Savona, M. D. Chan, +3 Additional Authors Jan 2015

Phase Ii Double-Blind Placebo-Controlled Randomized Study Of Armodafinil For Brain Radiation-Induced Fatigue, B. R. Page, E. G. Shaw, L. Lu, D. Bryant, D. Grisell, G. J. Lesser, D. C. Monitto, M. J. Naughton, S. R. Savona, M. D. Chan, +3 Additional Authors

Journal Articles

BACKGROUND: Common acute-term side effects of brain radiotherapy (RT) include fatigue, drowsiness, decreased physical functioning, and decreased quality of life (QOL). We hypothesized that armodafinil (a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy) would result in reduced fatigue and sleepiness for patients receiving brain RT. METHODS: A phase II, multi-institutional, placebo-controlled randomized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT, from whom we obtained estimates of variability for fatigue, sleepiness, QOL, cognitive function, and treatment effect. RESULTS: From September 20, 2010, to October 20, 2012, 54 ...


The Bruton Tyrosine Kinase Inhibitor Ibrutinib With Chemoimmunotherapy In Patients With Chronic Lymphocytic Leukemia, J. R. Brown, J. C. Barrientos, P. M. Barr, I. W. Flinn, J. A. Burger, A. Tran, F. Clow, D. F. James, K. Rai, S. O'Brien, +2 Additional Authors Jan 2015

The Bruton Tyrosine Kinase Inhibitor Ibrutinib With Chemoimmunotherapy In Patients With Chronic Lymphocytic Leukemia, J. R. Brown, J. C. Barrientos, P. M. Barr, I. W. Flinn, J. A. Burger, A. Tran, F. Clow, D. F. James, K. Rai, S. O'Brien, +2 Additional Authors

Journal Articles

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naive previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT ...


Introduction: Moving Beyond Chemotherapy, F. Muggia, E. Teplinsky Jan 2015

Introduction: Moving Beyond Chemotherapy, F. Muggia, E. Teplinsky

Journal Articles

Epithelial ovarian cancer and related cancers arising in extrauterine Mullerian epithelium are generally chemosensitive—particularly to the platinum drugs, cisplatin and carboplatin, that form the backbone of first-line treatments upon diagnosis even at early stages. Doublets of platinums with paclitaxel have represented the standard-of-care since the late 1990s, with further notable advances taking place by intraperitoneal administration (in Gynecologic Oncology Group studies) after optimal surgical cytoreduction is achieved, and by divided doses of paclitaxel (in a Japanese GOG study). Adding another agent to improve on these results has otherwise proven to be quite challenging. Nevertheless, continued forays into introducing ‘targeted ...


Romidepsin In Peripheral And Cutaneous T-Cell Lymphoma: Mechanistic Implications From Clinical And Correlative Data, S. E. Bates, R. Eisch, A. Ling, D. Rosing, M. Turner, S. Pittaluga, H. M. Prince, M. H. Kirschbaum, S. L. Allen, R. L. Piekarz, +15 Additional Authors Jan 2015

Romidepsin In Peripheral And Cutaneous T-Cell Lymphoma: Mechanistic Implications From Clinical And Correlative Data, S. E. Bates, R. Eisch, A. Ling, D. Rosing, M. Turner, S. Pittaluga, H. M. Prince, M. H. Kirschbaum, S. L. Allen, R. L. Piekarz, +15 Additional Authors

Journal Articles

Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third-line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients ...


Tamibarotene In Patients With Acute Promyelocytic Leukaemia Relapsing After Treatment With All-Trans Retinoic Acid And Arsenic Trioxide, D. Sanford, F. Lo-Coco, M. A. Sanz, E. Di Bona, S. Coutre, J. K. Altman, M. Wetzler, S. L. Allen, F. Ravandi, H. Kantarjian, J. E. Cortes Jan 2015

Tamibarotene In Patients With Acute Promyelocytic Leukaemia Relapsing After Treatment With All-Trans Retinoic Acid And Arsenic Trioxide, D. Sanford, F. Lo-Coco, M. A. Sanz, E. Di Bona, S. Coutre, J. K. Altman, M. Wetzler, S. L. Allen, F. Ravandi, H. Kantarjian, J. E. Cortes

Journal Articles

Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m2 /d) during induction and for up to six cycles of consolidation. The ...


Integrating Targeted Drugs With Taxanes And Platinums: Opportunities And Challenges, D. Kudlowitz, E. Teplinsky, F. Muggia Jan 2015

Integrating Targeted Drugs With Taxanes And Platinums: Opportunities And Challenges, D. Kudlowitz, E. Teplinsky, F. Muggia

Journal Articles

In ovarian cancer, multiple attempts to adjust the standard taxane/platinum doublet by adding cytotoxic therapy or varying scheduling, dosage, and delivery have been met with limited success. Alternative methods to improve the grim prognosis of ovarian cancer, including molecular therapies, are currently under investigation. Efforts have been made to study tyrosine kinase inhibitors (including imatinib and pazopanib), Src kinase inhibitors and histone deacetylase inhibitors (HDACi) in combination with taxanes/platinums in order to improve efficacy. Unfortunately, while many pre-clinical and early phase clinical trials argue that the utilization of these molecular targets may enhance survival, only modest benefit has ...


Augmenting Nf-Kappab In Poor-Risk Cll: A General Paradigm For Other Cancers?, D. Tuveson, K. R. Rai Jan 2015

Augmenting Nf-Kappab In Poor-Risk Cll: A General Paradigm For Other Cancers?, D. Tuveson, K. R. Rai

Journal Articles

No abstract provided.


Egfr And Her2: Is There A Role In Ovarian Cancer?, E. Teplinsky, F. Muggia Jan 2015

Egfr And Her2: Is There A Role In Ovarian Cancer?, E. Teplinsky, F. Muggia

Journal Articles

Advanced ovarian cancer carries a grim prognosis and development of targeted therapies to improve outcomes has become an active area of research in this disease. The epidermal growth factor receptor (EGFR) and HER2/neu have shown to be overexpressed in ovarian cancer and there have been several clinical trials evaluating anti-EGFR and HER2 therapies in ovarian cancer. Unfortunately, the drugs have shown minimal efficacy and more recent work has now focused on identifying mechanisms of resistance and alternative ways of targeting these pathways. This review will discuss the currently published trials with anti-EGFR and HER2 agents in ovarian cancer and ...


Ighv1-69 B Cell Chronic Lymphocytic Leukemia Antibodies Cross-React With Hiv-1 And Hepatitis C Virus Antigens As Well As Intestinal Commensal Bacteria, K. K. Hwang, A. M. Trama, D. M. Kozink, S. L. Allen, K. R. Rai, R. Catera, X. J. Yan, C. C. Chu, N. Chiorazzi, B. F. Haynes, +12 Additional Authors Jan 2014

Ighv1-69 B Cell Chronic Lymphocytic Leukemia Antibodies Cross-React With Hiv-1 And Hepatitis C Virus Antigens As Well As Intestinal Commensal Bacteria, K. K. Hwang, A. M. Trama, D. M. Kozink, S. L. Allen, K. R. Rai, R. Catera, X. J. Yan, C. C. Chu, N. Chiorazzi, B. F. Haynes, +12 Additional Authors

Journal Articles

IGHV1-B-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently use IGHV1-69 gene segments, we hypothesized that IGHV1-69 B-CLL precursors may contribute to the gp41 B cell response during HIV-1 infection. To test this hypothesis, we rescued 5 IGHV1-69 unmutated antibodies as heterohybridoma IgM paraproteins and as recombinant IgG(1) antibodies from B-CLL patients, determined their antigenic specificities and analyzed BCR sequences. IGHV1-69 B-CLL antibodies were enriched for reactivity with HIV-1 envelope gp41, influenza, hepatitis C virus E2 protein ...


Outcomes Of Temporary Interruption Of Rivaroxaban Compared With Warfarin In Patients With Nonvalvular Atrial Fibrillation, M. W. Sherwood, J. D. Douketis, M. R. Patel, J. P. Piccini, A. S. Hellkamp, Y. Lokhnygina, A. C. Spyropoulos, G. J. Hankey, D. E. Singer, R. C. Becker, +4 Additional Authors Jan 2014

Outcomes Of Temporary Interruption Of Rivaroxaban Compared With Warfarin In Patients With Nonvalvular Atrial Fibrillation, M. W. Sherwood, J. D. Douketis, M. R. Patel, J. P. Piccini, A. S. Hellkamp, Y. Lokhnygina, A. C. Spyropoulos, G. J. Hankey, D. E. Singer, R. C. Becker, +4 Additional Authors

Journal Articles

Background During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. Methods and Results In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including ...


Prognostic And Biologic Significance Of Dnmt3b Expression In Older Patients With Cytogenetically Normal Primary Acute Myeloid Leukemia, C. Niederwieser, J. Kohlschmidt, S. Volinia, S. P. Whitman, K. H. Metzeler, A. K. Eisfeld, K. Maharry, P. Yan, J. E. Kolitz, C. D. Bloomfield, +17 Additional Authors Jan 2014

Prognostic And Biologic Significance Of Dnmt3b Expression In Older Patients With Cytogenetically Normal Primary Acute Myeloid Leukemia, C. Niederwieser, J. Kohlschmidt, S. Volinia, S. P. Whitman, K. H. Metzeler, A. K. Eisfeld, K. Maharry, P. Yan, J. E. Kolitz, C. D. Bloomfield, +17 Additional Authors

Journal Articles

DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (60 years) adults with primary, cytogenetically normal acute myeloid leukemia (CN-AML). Patients were dichotomized into high versus low expressers using median cut. Outcomes were assessed in the context of known CN-AML prognosticators. Gene and microRNA expression, and DNA methylation profiles were analyzed using microarrays and MethylCap-sequencing, respectively. High DNMT3B expressers had fewer complete remissions (CR; P=0.002) and shorter disease-free (DFS; P ...


Igm Myeloma Or Waldenstrom's Macroglobulinemia Is The Big Question?, V. R. Bhatt, S. Murukutla, M. Naqi, S. Pant, S. Kedia, T. Terjanian Jan 2014

Igm Myeloma Or Waldenstrom's Macroglobulinemia Is The Big Question?, V. R. Bhatt, S. Murukutla, M. Naqi, S. Pant, S. Kedia, T. Terjanian

Journal Articles

ABSTRACT: Although critical from therapeutic and prognostic perspectives, differentiating IgM Myeloma (MM) from Waldenstrom's macroglobulinemia (WM) is fraught with failure. WM can usually be distinguished from IgM MM by the lymphoplasmacytic versus pure plasmacytic morphology, absent versus present lytic bone lesions, and immunophenotypic findings. However, all these features have their own limitations; hence, it requires constant vigilance and periodic re-evaluation. Here we describe a case of a 70-year-old woman initially diagnosed as smoldering IgM MM, who eventually turned out to have WM.


Validation Of Zap-70 Methylation And Its Relative Significance In Predicting Outcome In Chronic Lymphocytic Leukemia, R. Claus, D. M. Lucas, A. S. Ruppert, K. E. Williams, D. Weng, K. Patterson, M. Zucknick, J. C. Barrientos, K. R. Rai, J. C. Byrd, +13 Additional Authors Jan 2014

Validation Of Zap-70 Methylation And Its Relative Significance In Predicting Outcome In Chronic Lymphocytic Leukemia, R. Claus, D. M. Lucas, A. S. Ruppert, K. E. Williams, D. Weng, K. Patterson, M. Zucknick, J. C. Barrientos, K. R. Rai, J. C. Byrd, +13 Additional Authors

Journal Articles

ZAP-70 methylation 223 nucleotides downstream of transcription start (CpG+223) predicts outcome in chronic lymphocytic leukemia (CLL), but its impact relative to CD38 and ZAP-70 expression or immunoglobulin heavy chain variable region (IGHV) status is uncertain. Additionally, standardizing ZAP-70 expression analysis has been unsuccessful. CpG+223 methylation was quantitatively determined in 295 untreated CLL cases using MassARRAY. Impact on clinical outcome vs CD38 and ZAP-70 expression and IGHV status was evaluated. Cases with low methylation (0.90). Thus, ZAP-70 CpG+223 methylation represents a superior biomarker for TT and OS that can be feasibly measured, supporting its use in risk-stratifying ...


Gas6 Expression Identifies High-Risk Adult Aml Patients: Potential Implications For Therapy, S. P. Whitman, J. Kohlschmidt, K. Maharry, S. Volinia, K. Mrozek, D. Nicolet, S. Schwind, H. Becker, J. E. Kolitz, C. D. Bloomfield, +11 Additional Authors Jan 2014

Gas6 Expression Identifies High-Risk Adult Aml Patients: Potential Implications For Therapy, S. P. Whitman, J. Kohlschmidt, K. Maharry, S. Volinia, K. Mrozek, D. Nicolet, S. Schwind, H. Becker, J. E. Kolitz, C. D. Bloomfield, +11 Additional Authors

Journal Articles

Emerging data demonstrate important roles for the TYRO3/AXL/MERTK receptor tyrosine kinase (TAM RTK) family in diverse cancers. We investigated the prognostic relevance of GAS6 expression, encoding the common TAM RTK ligand, in 270 adults (n=71 aged <60 >years; n=199 aged >= 60 years) with de novo cytogenetically normal acute myeloid leukemia (CN-AML). Patients expressing GAS6 (GAS6+), especially those aged >= 60 years, more often failed to achieve a complete remission (CR). In all patients, GAS6+ patients had shorter disease-free (DFS) and overall (OS) survival than patients without GAS6 expression (GAS6-). After adjusting for other prognostic markers, GAS6+ predicted CR ...