Showing papers by "Elias Anaissie published in 2006"
TL;DR: A subset of cases with a predominating myeloid gene expression signature had more favorable baseline characteristics and superior prognosis to those lacking this signature, suggesting that this signature is linked to disease progression.
1,012 citations
TL;DR: The data suggest that altered transcriptional regulation of genes mapping to chromosome 1 may contribute to disease progression, and that expression profiling can be used to identify high-risk disease and guide therapeutic interventions.
867 citations
TL;DR: When incorporated into high-dose therapy for myeloma, thalidomide increased the frequency of complete responses and extended event-free survival at the expense of added adverse effects without improving overall survival.
Abstract: Background High-dose therapy with melphalan can prolong survival among patients with multiple myeloma We assessed whether the addition of thalidomide, which has activity against advanced and refractory myeloma, would further improve survival Methods Between October 1998 and February 2004, 668 patients with newly diagnosed multiple myeloma received two cycles of intensive melphalan-based chemotherapy, each supported by autologous hematopoietic stem-cell transplantation A total of 323 were randomly assigned to receive thalidomide from the outset until disease progression or undue adverse effects, and 345 did not receive thalidomide The primary end point was the five-year event-free survival rate Secondary end points were complete response and overall survival Results After a median follow-up of 42 months among survivors, the thalidomide and control groups had rates of complete response of 62 percent and 43 percent, respectively (P<0001), and five-year event-free survival rates of 56 percent and 44 percent (P = 001) The five-year rate of overall survival was approximately 65 percent in both groups (P = 090) Median survival after relapse was 11 years in the thalidomide group and 27 years in the control group (P = 0001) Severe peripheral neuropathy and deep-vein thrombosis occurred more frequently in the thalidomide group than in the control group Conclusions When incorporated into high-dose therapy for myeloma, thalidomide increased the frequency of complete responses and extended event-free survival at the expense of added adverse effects without improving overall survival (ClinicalTrialsgov number, NCT00083551)
716 citations
TL;DR: Mucositis appeared to reduce exposure but did not significantly affect mean total posaconazole exposure (AUC and Cmax) at steady state, and this reduction could be overcome by increasing the total dose and dosing frequency.
Abstract: The pharmacokinetics of posaconazole oral suspension in neutropenic patients undergoing high-dose chemotherapy and stem cell transplantation were evaluated, and the association of plasma posaconazole exposure with the presence and severity of oral mucositis was explored in this nonrandomized, open-label, parallel-group, multiple-dose pharmacokinetic study. Thirty patients were enrolled and received one of three regimens (group I, 200 mg once daily; group II, 400 mg once daily; group III, 200 mg four times daily) for the duration of neutropenia. The mean total exposure for day 1, as shown by the area under the concentration-time curve from 0 to 24 h (AUC0-24), was 1.96 mg · h/liter in group I and was 51% higher in group II and in group III. Increases in AUC0-24 and maximum plasma concentration (Cmax) in groups II and III were dose related. The AUC0-24 and Cmax values on day 1 were similar between groups II and III. There was interpatient variability of up to 68% in the pharmacokinetic values for our study population. Steady state was attained by days 5 to 6. Average steady-state plasma posaconazole trough values were 192, 219, and 414 ng/ml in groups I, II, and III, respectively. The AUC0-24 and apparent oral clearance increased by increasing dose and dosing frequency. Mucositis appeared to reduce exposure but did not significantly affect mean total posaconazole exposure (AUC and Cmax) at steady state (P = 0.1483). Moreover, this reduction could be overcome by increasing the total dose and dosing frequency. Posaconazole was safe and well tolerated.
143 citations
TL;DR: TT2 (without thalidomide) improved OS of patients without CAs; those with CAs benefited from posttransplantation consolidation chemotherapy, proving the validity of a melphalan dose-response effect in myeloma.
130 citations
TL;DR: Increased pre-transplant BMIS and smoking are significant predictors of severe infection after myeloablative chemotherapy followed by ASCT in myeloma patients.
Abstract: We evaluated the risk factors for infection of 367 consecutive myeloma patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT). Examination of bone marrow iron stores (BMIS) prior to ASCT was used to evaluate body iron stores. Other variables included age, sex, active smoking, myeloma remission status, severity of mucositis and duration of severe neutropenia post-ASCT (<100 absolute neutrophils counts (ANC)/microl). Median age was 56 years; 61% of patients were males. 140 episodes of severe infections occurred in 116 patients, including bacteremia (73), pneumonia (40), severe colitis (25) and bacteremia with septic shock (two). The infection incidence per 1,000 days at risk was 45.2. Pre-ASCT risk factors for severe infection by univariate analysis were increased BMIS (OR=2.686; 95% CI 1.707-4.226; P<0.0001), smoking (OR=1.565; 95% CI 1.005-2.437; P=0.0474) and male gender (OR=1.624; 95% CI 1.019-2.589; P=0.0414). Increased BMIS (OR=2.716; 95% CI 1.720-4.287; P<0.0001) and smoking (OR=1.714; 95% CI 1.081-2.718; P=0.022) remained significant by multivariate analysis. Duration of ANC <100 micro/l (OR=1.129; 95% CI 1.039-1.226; P=0.0069 and OR=1.127; 95% CI 1.038-1.224; P=0.0045 by both univariate and multivariate analysis, respectively) was the only post-ASCT risk factor for infection. Increased pre-transplant BMIS and smoking are significant predictors of severe infection after myeloablative chemotherapy followed by ASCT in myeloma patients.
111 citations
TL;DR: It is concluded that BSA dosing of melphalan results in wide variations in themg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kgmelphalan dose have the greatest risk for severe OM following Mel-ASCT.
Abstract: Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.
89 citations
TL;DR: Mucosa is the most common site of CoNS colonization and is the likely source of coagulase-negative staphylococci bacteremia in cancer patients.
35 citations
TL;DR: The IRF-D is a simple, inexpensive and widely available test that can predict marrow recovery several days before ANC⩾100/μl, and is validated in a group of 117 myeloma patients and 99 patients with various disorders undergoing ASCT with different conditioning regimens.
Abstract: The duration of neutropenia (absolute neutrophil count (ANC) ⩽100/μl) identifies cancer patients at risk for infection. A test that precedes ANC⩾100/μl would be of clinical value. The immature reticulocyte fraction (IRF) reflects erythroid engraftment and hence a recovering marrow. We evaluated the IRF as predictor of marrow recovery among 90 myeloma patients undergoing their first and second (75 patients) melphalan-based autologous stem cell transplantation (Mel-ASCT). The time to IRF doubling (IRF-D) preceded ANC⩾100/μl in 99% of patients after the first Mel-ASCT by (mean±s.d.) 4.23±1.96 days and in 97% of the patients after the second Mel-ASCT by 4.11±1.95 days. We validated these findings in a group of 117 myeloma patients and 99 patients with various disorders undergoing ASCT with different conditioning regimens. We also compared the time to hypophosphatemia and to absolute monocyte count⩾100/μl to the time to ANC⩾100/μl. These markers were reached prior to this ANC end point in 55 and 25% of patients but were almost always preceded by IRF-D. We conclude that the IRF-D is a simple, inexpensive and widely available test that can predict marrow recovery several days before ANC⩾100/μl.
22 citations
TL;DR: Five-year Rc appears to be an important prerequisite for prolonged subsequent overall survival in multiple myeloma and initial quality of response or having received the scheduled tandem transplantations did not affect post-5-year survival.
Abstract: Background Complete response has been considered a surrogate for favorable long-term outcome in multiple myeloma. Data on the impact of the duration of response on prognosis are lacking. Patients and Methods Of the 899 patients enrolled in Total Therapy trials (Total Therapy 1, N=231; Total Therapy 2, N=668), 254 survived for > 5 years. The prognostic impact of continuous (Rc) versus discontinuous (Rd) 4-year remission after 5-year survival was examined along with laboratory features present at baseline and at 5 years. Results Most baseline prognostic features were evenly distributed among Rc and Rd groups; however, a greater proportion of Rc patients were enrolled in Total Therapy 2 (60%) compared with Rd (19%; P Conclusion Five-year Rc appears to be an important prerequisite for prolonged subsequent overall survival.
18 citations
TL;DR: F-MEL-VTD was remarkably well tolerated, permitting total MEL dose escalation to > 200mg/m 2 in 13 of 22 patients, without incurring grade >2 stomatitis in the majority of patients.
TL;DR: With longer follow-up of 53mo on TT2, EFS remains superior among patients randomized toTHAL; post-relapse survival is no longer inferior among those randomized to THAL; THAL benefited a high-risk subgroup with >2 standard risk factors, whereas no significant `difference has yet emerged among genetically defined subgroups.
TL;DR: Safety profile supports continuing study to define the optimal dose for prevention of severe OM, and single dose velafermin at 0.03mg/kg is may be active in reducing CT induced severe OM in AHSCT pts.
Abstract: 6537 Background: Oral mucositis (OM) is a commonly occurring side effect of high-dose chemotherapy (HDCT) in patients (pts) undergoing autologous hematopoietic stem cell transplant (AHSCT). Velafer...
TL;DR: S serum GMI is validated as an excellent surrogate endpoint for the outcome of invasive aspergillosis among patients with hematological cancer and has important implications for patient care and for the design of clinical trials of mould-active antifungal agents.
University of Arkansas for Medical Sciences1, Albany Medical College2, University of Texas Health Science Center at San Antonio3, Mayo Clinic4, Duke University5, University of Maryland, Baltimore6, University of Alabama at Birmingham7, Harvard University8, New York University9, University of Tennessee Health Science Center10, Long Beach Memorial Medical Center11, Ankara University12, Hacettepe University13, Roswell Park Cancer Institute14, University of Wisconsin-Madison15, University of California, Irvine16, University of Colorado Denver17, University of Southern California18, Tufts University19, Yeshiva University20, University of Mississippi21, University of Cologne22, Carlos III Health Institute23, University of Massachusetts Medical School24, University of Aberdeen25, University of Manchester26, Radboud University Nijmegen27, Université de Montréal28, Indiana University29, University of Paris30, Virginia Commonwealth University31, Texas Tech University Health Sciences Center32, Case Western Reserve University33, University of Florida34, University of Kentucky35, LSU Health Sciences Center Shreveport36, National Institutes of Health37, San Antonio Military Medical Center38, University of Pittsburgh39, City of Hope National Medical Center40, University of Miami41, St. Jude Children's Research Hospital42, University of Texas MD Anderson Cancer Center43, Karolinska Institutet44, St. Vincent's Health System45, University of Texas Medical Branch46, Federal University of Rio de Janeiro47, University of Illinois at Chicago48, Ochsner Medical Center49, University of Iowa50, Wayne State University51, McMaster University52, Charité53, University of Pennsylvania54, Georgetown University55, George Washington University56, Children's National Medical Center57, University of Cincinnati58, University of Sydney59, University of Milan60, Katholieke Universiteit Leuven61, Rowan University62
TL;DR: This paper aims to provide a history of single-cell myeloma in the clinic and some of the mechanisms leading to cell death and its Kessler’s disease progression.
Abstract: Received 6 September 2006; accepted 6 September 2006;electronically published 13 September 2006Author affiliations are listed at the end of the textReprints or correspondence: Dr Elias J Anaissie, MyelomaInstitute for Research and Therapy, University of Arkansasfor Medical Sciences, 4301 W Markham, Slot 816, LittleRock, AR 72205 (anaissieeliasj@uamsedu)
01 Jan 2006
TL;DR: In MM and related plasma cell dyscrasias, FDG-PET or PET/CT imaging are useful and reliable techniques for assistance in the diagnosis by identifying optimal sites for biopsy, for staging and restaging the tumor, for detecting extramedullary disease, and for monitoring response to treatment.
Abstract: In MM and related plasma cell dyscrasias, FDG-PET or PET/CT imaging are useful and reliable techniques for assistance in the diagnosis by identifying optimal sites for biopsy, for staging and restaging the tumor, for detecting extramedullary disease, and for monitoring response to treatment. They are equally effective in secretory or nonsecretory disease, with the latter developing with an increasing frequency during the course of the disease, causing difficulty in monitoring disease response or progression.
TL;DR: It is suggested that exercise in combination with prophylactic epoetin alfa therapy benefits patients by reducing the number of RBC and platelet transfusions and theNumber of attempts at and number of days of stem cell collection.
Abstract: 8605 Background: Epoetin alfa increases hemoglobin levels and reduces the need for RBC transfusions in diverse groups of patients with cancer-related anemia. Interest in other potential benefits le...
TL;DR: In addition to the strong association between neutrophil recovery and IA response, the critical role of immunity in IA is supported by common development of IRIS, spontaneous resolution of IA and response to immunomodulatory therapies.
TL;DR: OS and EFS survival of myeloma patients treated with chemotherapy ± thalidomide is not affected by VTE development, and a survival benefit associated with anticoagulation therapy in multiple myel cancer patients is supported.
University of Arkansas1, Cornell University2, Wake Forest University3, Fred Hutchinson Cancer Research Center4, Scripps Health5, Virginia Commonwealth University6, Oregon Health & Science University7, Cleveland Clinic8, Northwestern University9, Temple University10, University of Kansas11, University of Rochester12, Duke University13, University of Pennsylvania14, University of Miami15, University of Massachusetts Amherst16
TL;DR: HD-DTPACE is an effective, well-tolerated salvage regimen for AR-MM and could be cycled rapidly in heavily pre-treated patients, with excellent hematopoietic recovery.