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Sarah Waheed,
Alan Mitchell,
Saad Usmani,
Joshua Epstein,
Shmuel Yaccoby,
Bijay Nair,
Rudy Van Hemert, Edgardo Angtuaco,
Tracy Brown,
Twyla Bartel,
James McDonald,
Elias Anaissie,
Frits van Rhee,
John Crowley,
Bart Barlogie
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ABSTRACT: Background. Multiple myeloma causes major morbidity resulting from osteolytic lesions that can be detected by metastatic bone surveys. Magnetic resonance imaging and positron emission tomography can detect bone marrow focal lesions long before development of osteolytic lesions.Design and Methods: Using data from patients enrolled in Total Therapy 3 for newly diagnosed myeloma (N=303), we analyzed associations of these imaging techniques with baseline standard laboratory variables assessed before initiating treatment. Of 270 patients with complete imaging data, 245 also had gene expression profiling data. Results. Osteolytic lesions detected on metastatic bone surveys correlated with focal lesions detected by magnetic resonance imaging and positron emission tomography, although, in two-way comparisons, focal lesion counts based on both magnetic resonance imaging and positron emission tomography tended to be greater than those based on metastatic bone survey. Higher numbers of focal lesions detected by magnetic resonance imaging and positron emission tomography were positively linked to high serum concentrations of C-reactive protein, gene-expression-profiling-defined high risk, and the Proliferation molecular subgroup. Positron emission tomography focal lesion maximum standardized unit values were significantly correlated with gene-expression-profiling-defined high risk and higher numbers of focal lesions detected by positron emission tomography. Interestingly, four genes associated with high-risk disease (related to cell cycle and metabolism) were linked to counts of focal lesions detected by magnetic resonance imaging and positron emission tomography. Conclusions. Collectively, our results demonstrate significant associations of all three imaging techniques with tumor burden and, especially, disease aggressiveness captured by gene-expression-profiling-risk designation. (clinicaltrials.gov identifier: NCT00081939).
Haematologica 06/2012; · 6.42 Impact Factor
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ABSTRACT: A 55-year-old immunocompetent man presented with headache, nausea, progressive bilateral upper lid ptosis, and diplopia. Examination showed bilateral asymmetric upper lid ptosis with limited adduction and elevation of both eyes. Cranial magnetic resonance imaging revealed enhancing intra-axial and extra-axial midbrain lesions. Blood and cerebrospinal fluid were positive for cryptococcal antigen and cerebrospinal fluid fungal cultures grew Cryptococcus neoformans. Treatment with liposomal amphotericin B and flucytosine resulted in complete resolution of his neurological deficits and lesions on neuroimaging. Patients with cryptococcal meningitis may rarely present with bilateral cranial nerve III dysfunction.
Survey of Ophthalmology 08/2011; 57(3):284-91. · 2.35 Impact Factor
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Twyla B Bartel,
Jeff Haessler,
Tracy L Y Brown,
John D Shaughnessy,
Frits van Rhee,
Elias Anaissie,
Terri Alpe, Edgardo Angtuaco,
Ronald Walker,
Joshua Epstein,
John Crowley,
Bart Barlogie
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ABSTRACT: F18-fluorodeoxyglucose positron emission tomography (FDG-PET) is a powerful tool to investigate the role of tumor metabolic activity and its suppression by therapy for cancer survival. As part of Total Therapy 3 for newly diagnosed multiple myeloma, metastatic bone survey, magnetic resonance imaging, and FDG-PET scanning were evaluated in 239 untreated patients. All 3 imaging techniques showed correlations with prognostically relevant baseline parameters: the number of focal lesions (FLs), especially when FDG-avid by PET-computed tomography, was positively linked to high levels of beta-2-microglobulin, C-reactive protein, and lactate dehydrogenase; among gene expression profiling parameters, high-risk and proliferation-related parameters were positively and low-bone-disease molecular subtype inversely correlated with FL. The presence of more than 3 FDG-avid FLs, related to fundamental features of myeloma biology and genomics, was the leading independent parameter associated with inferior overall and event-free survival. Complete FDG suppression in FL before first transplantation conferred significantly better outcomes and was only opposed by gene expression profiling-defined high-risk status, which together accounted for approximately 50% of survival variability (R(2) test). Our results provide a rationale for testing the hypothesis that myeloma survival can be improved by altering treatment in patients in whom FDG suppression cannot be achieved after induction therapy.
Blood 06/2009; 114(10):2068-76. · 9.90 Impact Factor
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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.
FDG-PET or PET/CT imaging are also useful techniques for detecting occult infection in patients with hematologic malignancies,
for finding the source of infection, and for documenting response to treatment of infection, even in the setting of severe
immunosuppression. The information gained by FDG-PET or PET/CT related to infectious disease often contribute to changes in
patient management.
The presence of a high number of focal lesions, especially with cytogenetic abnormalities or chromosome 13 deletions, and/or
the presence of extramedullary tumor, identifies patients at high risk with poor long-term prognosis who will need aggressive
monitoring and treatment.
Failure to achieve normalization of FDG-PET or PET/CT images after treatment identifies patients at high risk for early relapse.
Progression of disease on treatment is a poor prognostic sign identifying patients in need of immediate intervention.
10/2006: pages 283-302;
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ABSTRACT: To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy.
A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period.
With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones.
AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.
Journal of Clinical Oncology 09/2005; 23(22):5217-23. · 18.37 Impact Factor
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Athanasios B-T Fassas,
Firas Muwalla,
Tanya Berryman,
Riad Benramdane,
Lija Joseph,
Elias Anaissie,
Rajesh Sethi,
Raman Desikan,
David Siegel,
Ashraf Badros,
Amir Toor,
Maurizio Zangari,
Christopher Morris, Edgardo Angtuaco,
Sajini Mathew,
Carla Wilson,
Aubrey Hough,
Sami Harik,
Bart Barlogie,
Guido Tricot
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ABSTRACT: Involvement of the central nervous system (CNS) by multiple myeloma, as defined by the detection of malignant plasma cells in the cerebrospinal fluid in the presence of suggestive symptoms, is considered extremely rare. We report on the characteristics of 18 such patients diagnosed and treated at the University of Arkansas over the last 10 years for an overall incidence of approximately 1%. Their evaluation revealed association of CNS involvement with unfavourable cytogenetic abnormalities (especially translocations and deletion of the chromosome 13), high tumour mass, plasmablastic morphology, additional extramedullary myeloma manifestations and circulating plasma cells. The presence of these features should alert clinicians to the possibility of CNS involvement. The outcome of these patients was extremely poor despite the use of aggressive local and systemic treatment including autologous stem cell transplants. Given this universally poor prognosis, the application of allogeneic transplants should be studied in this clinical setting.
British Journal of Haematology 05/2002; 117(1):103-8. · 4.94 Impact Factor
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Athanasios B.-T. Fassas,
Firas Muwalla,
Tanya Berryman,
Riad Benramdane,
Lija Joseph,
Elias Anaissie,
Rajesh Sethi,
Raman Desikan,
David Siegel,
Ashraf Badros,
Amir Toor,
Maurizio Zangari,
Christopher Morris, Edgardo Angtuaco,
Sajini Mathew,
Carla Wilson,
Aubrey Hough,
Sami Harik,
Bart Barlogie,
Guido Tricot
[show abstract]
[hide abstract]
ABSTRACT: Involvement of the central nervous system (CNS) by multiple myeloma, as defined by the detection of malignant plasma cells in the cerebrospinal fluid in the presence of suggestive symptoms, is considered extremely rare. We report on the characteristics of 18 such patients diagnosed and treated at the University of Arkansas over the last 10 years for an overall incidence of approximately 1%. Their evaluation revealed association of CNS involvement with unfavourable cytogenetic abnormalities (especially translocations and deletion of the chromosome 13), high tumour mass, plasmablastic morphology, additional extramedullary myeloma manifestations and circulating plasma cells. The presence of these features should alert clinicians to the possibility of CNS involvement. The outcome of these patients was extremely poor despite the use of aggressive local and systemic treatment including autologous stem cell transplants. Given this universally poor prognosis, the application of allogeneic transplants should be studied in this clinical setting.
British Journal of Haematology 03/2002; 117(1):103 - 108. · 4.94 Impact Factor
