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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_461"
                     title="Limited Benefit Seen in CML Drug, FDA Says"
                     score="0.014"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/18390?impressionId=1265750024139"
                     
      &lt;p&gt;WASHINGTON  --  Chronic myeloid leukemia (CML) patients who are resistant to imatinib (Gleevec) had a low response rate to treatment with omacetaxine (Omapro), according to Food and Drug Administration (FDA) reviewers.&lt;/p&gt;

&lt;p&gt;The FDA released its assessment of omacetaxine, made by ChemGenex Pharmaceuticals, in preparation for a meeting of an outside panel of oncology experts who will recommend whether the agency should approve the drug for imanitib-resistant CML patients with a Bcr-Abl T3151 mutation.&lt;/p&gt;
    &lt;p&gt;That meeting, original scheduled for Wednesday, was postponed when the federal government closed most Washington area offices because of snow. An FDA spokesman said no new date has been set.&lt;/p&gt;


&lt;p&gt;The agency does not have to follow the advice of its advisory panels, but it usually does.&lt;/p&gt;
&lt;p&gt;The Oncologic Drugs Advisory Committee will look at data from manufacturer ChemGenex&apos;s lone trial, which tested the safety and efficacy of subcutaneously administered omacetaxine in the target population.&lt;/p&gt;
&lt;p&gt;The trial divided 66 patients into disease stage cohorts of &quot;chronic phase,&quot; &quot;accelerated phase,&quot; or &quot;blast phase,&quot; and gave them 1.25 mg/m&lt;sup&gt;2&lt;/sup&gt; subcutaneous omacetaxine twice daily for 14 days every 28 days until hematologic response for induction therapy.&lt;/p&gt;
&lt;p&gt;If a patient achieved a complete hematologic response, hematologic improvement, or any cytogenetic response, the patient was transitioned to a maintenance does twice daily for seven days every 28 days.&lt;/p&gt;
&lt;p&gt;Researchers found: &lt;ul&gt; &lt;li&gt;For the chronic phase cohort of 40 patients, the major cytogenetic response rate was 15%, and the median duration of response was 7.7 months. &lt;/li&gt; &lt;li&gt;After a mean of nine months, 86% of the 49 chronic patients who were no longer controlling their diseases with imatinib had achieved a complete hematological response. &lt;/li&gt; &lt;li&gt;For the &quot;accelerated phase&quot; cohort of 16 patients, the major cytogenetic response rate was 6%, and the complete hematological response rate was 31%, with a median of duration of response of 22 weeks. &lt;/li&gt; &lt;li&gt;No patients responded in the more severe &quot;blast&quot; group, indicating omacetaxine works best among patients who are not as sick.&lt;/li&gt; &lt;li&gt;Overall, about 27% of patients achieved a major cytogenetic response, defined as absence of Bcr-Abl mutation in at least 35% of cells. About 18% of the patients had achieved a complete cytogenetic response, defined as all cells appearing to have lost the Bcr-Abl mutation.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;&quot;The response rate observed in the efficacy study was low,&quot; FDA reviewers concluded in documents released in advance of Wednesday&apos;s meeting.&lt;/p&gt;
&lt;p&gt;However, ChemGenex researchers said, &quot;These results demonstrate that omacetaxine is an effective and durable therapy with rapid onset of action for CML patients with the Bcr-Abl T315I mutation.&quot;&lt;/p&gt;
&lt;p&gt;The most common adverse events in the trial were thrombocytopenia, anemia, diarrhea, and neutropenia.&lt;/p&gt;
&lt;p&gt;The FDA reviewers cited a number of concerns with the ChemGenex study, noting that the company planned to enroll 100 patients but submitted efficacy data from only 66, and then continued to enroll additional patients after the prespecified data cutoff.&lt;/p&gt;
&lt;p&gt;Also, the reviewers said there is no commercially available test to detect the T3151 mutation. And, although it was a requirement of the study that the patients have a confirmed T3151 mutation, the mutation status of 35% of the patients in the trial was not confirmed.&lt;/p&gt;
&lt;p&gt;There are currently no approved drugs that have been found to be effective at treating CML patients with the T315I mutation.&lt;/p&gt;
&lt;p&gt;&quot;Omacetaxine offers an important therapeutic option for the treatment of CML patients who have the T315I mutation, a population that has a clear unmet medical need and no proven treatment options,&quot; ChemGenex researchers wrote in the company&apos;s briefing document.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_342"
                     title="Stem Cell Transplant Source Does Not Affect Long-Term Leukemia Outcomes (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/18220?impressionId=1265750024139"
                     
      Ten-year survival rates after allogeneic stem-cell transplant in leukemia patients were the same whether the cells came from donors&apos; bone marrow or peripheral blood, researchers conducting a randomized trial said.&lt;br&gt;
&lt;br&gt;Among 329 patients participating in the trial, overall survival was 49.1% for those receiving peripheral blood progenitor cell transplants versus 56.5% among those receiving bone marrow transplants (&lt;em&gt;P&lt;/em&gt;=0.27), reported Birte Friedrichs, MD, of Charite-Campus Benjamin Franklin in Berlin, Germany, and colleagues online in &lt;em&gt;Lancet Oncology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;There was also no significant difference over the long term in performance status, ability to work, hematopoietic function, development of bronchiolitis obliterans, or secondary malignancy rates.&lt;/p&gt;
&lt;p&gt;Ten-year leukemia-free survival rates were somewhat better with bone marrow transplant in patients with acute myeloid and acute lymphoblastic leukemia (AML, ALL) but the differences did not reach statistical significance. There was no apparent difference in disease-free survival for those with chronic myeloid leukemia (CML).&lt;/p&gt;
&lt;p&gt;But significantly more transplants involving peripheral blood progenitor cells led to chronic graft-versus-host disease (GVHD), seen in 73% of patients compared with 56% among those receiving bone marrow transplants (&lt;em&gt;P&lt;/em&gt;=0.021).&lt;/p&gt;
&lt;p&gt;As a result, significantly more patients receiving peripheral blood cell transplants were on immunosuppressant therapy five years postprocedure (26% versus 12%, &lt;em&gt;P&lt;/em&gt;=0.024).&lt;/p&gt;
&lt;p&gt;Noting that subgroup analyses did show notable differences in survival in patients with acute leukemias, Friedrichs and colleagues added, &quot;These data alone do not currently support the return to bone marrow transplantation for specific indications, but we believe that long-term data from other randomized trials should be collected.&quot;&lt;/p&gt;
&lt;p&gt;Patients in the study were participating in a parallel-group trial of the two transplant types, with transplants conducted from 1995 to 1999. Participants were adults up to age 55 with CML in second remission or newly diagnosed ALL or AML.&lt;/p&gt;
&lt;p&gt;Specific overall and leukemia-free survival rates for leukemia subtypes after 10 years were: &lt;ul&gt; &lt;li&gt;ALL: 32.9% overall and 28.3% disease-free with bone marrow transplant, 18.2% overall and 13.0% disease free with peripheral blood transplant (&lt;em&gt;P&lt;/em&gt;=0.071 and 0.12, respectively)&lt;/li&gt; &lt;li&gt;AML: 65.3% overall and 62.3% disease-free with bone marrow transplant, 52.3% overall and 47.1% disease-free with peripheral blood transplant (&lt;em&gt;P&lt;/em&gt;=0.24 and 0.16, respectively)&lt;/li&gt; &lt;li&gt;CML: 61.1% overall and 40.2% disease-free with bone marrow transplant, 56.8% overall and 48.5% disease-free with peripheral blood transplant (&lt;em&gt;P&lt;/em&gt;=0.81 and 0.60, respectively)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The failure to find significant differences may have been related to small patient numbers in these subgroups: 64 with AML, 19 with ALL, and 89 with CML.&lt;/p&gt;
&lt;p&gt;Transplant types were performed at equal rates in patients with AML and CML, but the randomization was unbalanced in ALL patients, with 15 of 19 receiving bone marrow transplants.&lt;/p&gt;
&lt;p&gt;Chronic GVHD was the most common cause of death in the study, killing nine patients (of whom six received peripheral blood progenitor cell transplants). Six patients died of recurrent leukemia. The remaining nine deaths were distributed among several causes including hemorrhage, bronchial cancer, suicide, and traffic accident.&lt;/p&gt;
&lt;p&gt;Patients with chronic GVHD after peripheral blood cell transplants were more likely to have skin, liver, and oral mucosal involvement compared with GVHD following bone marrow transplant, with relative risks ranging from 1.49 to 1.85.&lt;/p&gt;
&lt;p&gt;Factors significantly associated with better overall survival included a diagnosis of ALL (HR 2.90 versus other diagnoses, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), age of 40 or more (HR 1.55 versus age under 40, &lt;em&gt;P&lt;/em&gt;=0.009), and use of total body irradiation instead of a chemotherapy-only myeloablative regimen before transplant (HR 1.55, &lt;em&gt;P&lt;/em&gt;=0.014).&lt;/p&gt;
&lt;p&gt;The researchers noted that many of their findings, including the apparent benefit of preparative total body irradiation, were consistent with earlier studies.&lt;/p&gt;
&lt;p&gt;Limitations to the study included loss to follow-up of 26 patients, lack of detailed data on surviving participants&apos; quality of life, and changes in treatment since the study began.&lt;/p&gt;
&lt;p&gt;Friedrichs and colleagues noted that the introduction of tyrosine kinase inhibitors and new approaches to pretransplant conditioning have altered practice significantly.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;No external funding for the study was received.&lt;/p&gt;&lt;p&gt;No potential conflicts of interest were reported.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_167"
                     title="Stem Cells from Cord Blood Pass Early Test (CME/CE)"
                     score="-0.003"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/17998?impressionId=1265750024139"
                     
      The first reported clinical use of ex vivo-expanded stem cells from umbilical cord blood led to rapid engraftment in patients with high-risk acute leukemia, investigators found.&lt;br&gt;
&lt;br&gt;Activation of the Notch signaling pathway with a bioengineered protein led to a 164-fold increase in CD34+ cells. Infusion of the expanded stem-cell population into leukemia patients after myeloablation reduced the time to neutrophil recovery and the time to engraftment by 50%, according to a report published online in &lt;em&gt;Nature Medicine&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;After a mean follow-up of about a year, seven of 10 patients remained alive with no evidence of disease and with sustained complete engraftment, wrote Colleen Delaney, MD, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.&lt;br&gt;
&lt;br&gt;&quot;The real ground-breaking aspect of this research is that we have shown that you can manipulate stem/progenitor cells in the lab with the goal of increasing their numbers,&quot; Delaney said in a statement.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;When given to a person, these cells can rapidly give rise to white blood cells and other components of the blood system.&quot;&lt;/p&gt;
&lt;p&gt;Delayed engraftment after cord-blood transplantation is thought to result from an inadequate population of progenitor cells in the graft, the authors wrote. Delayed engraftment can lead to early transplant-related morbidity and mortality.&lt;/p&gt;
&lt;p&gt;Culture strategies that increase the number of viable progenitors would expand the applicability of cord-blood for transplantation.&lt;/p&gt;
&lt;p&gt;The phase I results reported by Delaney and colleagues had their origin in work begun more than a decade ago by co-investigator Irwin D. Bernstein, also of Fred Hutchinson. The Seattle group identified a potential role for the Notch signaling pathway in hematopoiesis by detecting the human &lt;em&gt;Notch 1&lt;/em&gt; gene in CD34+ human hematopoietic precursors. They subsequently demonstrated enhanced self-renewal of repopulating cells in response to retrovirus-mediated expression of an active form of Notch 1.&lt;/p&gt;
&lt;p&gt;Further study showed that activation of Notch receptors by immobilized Notch ligand had a profound effect on growth and differentiation of mouse marrow progenitor cells. Incubation of human cord-blood progenitors with immobilized ligand led to a 100-fold increase in CD34+ cells.&lt;/p&gt;
&lt;p&gt;&quot;Overall, these observations demonstrated that Notch signaling has a key regulatory role in hematopoiesis and suggest that Notch ligands will be useful reagents for improving ex vivo culture of stem/progenitor cells,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;As a prelude to the phase I clinical study, investigators cultured cord-blood CD34+ progenitors in the presence of immobilized Notch ligand for as long as three weeks, resulting in 138- to 163-fold expansion of the cell population. Validation studies of the culture system showed consistent expansion of the CD34+ population by more than 150-fold.&lt;/p&gt;
&lt;p&gt;When given to immunodeficient mice, ex vivo-expanded CD34+ cells resulted in repopulation with markedly enhanced kinetics and magnitude.&lt;/p&gt;
&lt;p&gt;The phase I study involved patients whose leukemia was in morphologic remission at the time of transplant. The patients ranged in age from 3 to 43.&lt;/p&gt;
&lt;p&gt;Myeloablative therapy consisted of whole-body irradiation, cyclophosphamide, and fludarabine. Each patient received one unmanipulated and one expanded cord-blood graft. All patients received standard prophylaxis for graft versus host disease (GVHD). Expansion of CD34+ cells prior to infusion averaged 164-fold.&lt;/p&gt;
&lt;p&gt;The median time to an absolute neutrophil count (ANC) &amp;#8805;100 cells/&amp;#181;L was nine days, compared with 19 days for a similar group of patients who received two unmanipulated cord-blood grafts.&lt;/p&gt;
&lt;p&gt;The median time to ANC &amp;#8805;500 cells/&amp;#181;L was 16 days in nine evaluable patients, compared with 26 days in patients who received two unmanipulated grafts.&lt;/p&gt;
&lt;p&gt;Nine of 10 patients had successful engraftment in an average of 14 days, whereas engraftment required an average of 28 days in patients who received unmanipulated cord-blood grafts.&lt;/p&gt;
&lt;p&gt;One patient had primary graft rejection. Peripheral blood analysis on day seven showed a predominance of donor-cell engraftment from the expanded-cell graft.&lt;/p&gt;
&lt;p&gt;Among evaluable patients, one had acute grade 3 GVHD, and all the others had acute grade 2 GVHD. In all cases patients responded to therapy. Three patients developed chronic limited GVHD, but no patient had chronic extensive GVHD.&lt;/p&gt;

&lt;p&gt;Results of the phase I study give reason for excitement about the potential for using cord blood-derived stem cells to treat leukemia, said Peter Emanuel, MD, director of the Winthrop P. Rockefeller Cancer Institute in Little Rock, Ark.&lt;/p&gt;
&lt;p&gt;&quot;Investigators from [Seattle] appear to have given us the next big leap forward in advances for stem cell transplants, that being the methods to culture cord blood in the laboratory so that the stem and immature cells will &apos;take root&apos; more rapidly when infused back into patients,&quot; said Emanuel, who was not involved in the study. &quot;This is significant for patient safety as it shortens the time period when they are at risk for life threatening infection.&quot;&lt;/p&gt;

&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The authors had no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_1521"
                     title="Antiviral Shows Promise in Acute Myeloid Leukemia"
                     score="-0.005"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/14230?impressionId=1265750024139"
                     
      HOUSTON, May 15 -- An antiviral drug that targets a growth-promoting oncogene led to stable disease or better response in all but two patients with relapsed or refractory acute myeloid leukemia in a small Canadian study. 
              &lt;p&gt;
              &lt;p&gt;Of 11 evaluable patients, three had major responses, two had blast responses, and four had stable disease when treated with ribavirin, Katherine L.B. Borden, Ph.D., of the University of Montreal, and colleagues reported online in &lt;em&gt;Blood&lt;/em&gt;. 
              &lt;p&gt;
              &lt;p&gt;Lack of effect on the eIF4E oncogene protein activity correlated with disease progression. 
              &lt;p&gt;
              &lt;p&gt;&quot;Ribavirin-induced relocalization of nuclear eIF4E to the cytoplasm and reduction of eIF4E levels were associated with clinical response,&quot; the authors said. &quot;Lack of response or relapse coincided with continued or renewed nuclear localization of eIF4E. 
              &lt;p&gt;
              &lt;p&gt;&quot;This first clinical study to target eIF4E in human malignancy demonstrates clinical activity and associated molecular responses in leukemic blasts.&quot; 
              &lt;p&gt;
              &lt;p&gt;The translation initiation factor eIF4E is elevated in about 30% of cancers, including the M4/M5 subtype of AML. 
              &lt;p&gt;
              &lt;p&gt;The factor&apos;s oncogenic potential arises from its ability to bind the 7-methyl guanosine cap (m&lt;sup&gt;7&lt;/sup&gt;G cap) on messenger RNA, selectively enhancing eIF4E-dependent nuclear mRNA export and translation, the authors explained. 
              &lt;p&gt;
              &lt;p&gt;Ribavirin mimics the m&lt;sup&gt;7&lt;/sup&gt;G cap, providing a rationale for using the antiviral agent to target eIF4E. To explore the rationale, investigators treated 11 patients with M4/M5 AML. Patients received ribavirin daily for as many as six 28-day cycles. 
              &lt;p&gt;
              &lt;p&gt;Assessment of response by the Cheson criteria occurred after 30 days. 
              &lt;p&gt;
              &lt;p&gt;One patient had a complete response and two had partial responses. The complete response and one partial response were associated with a marked decline in bone marrow blasts and restoration of normal hematopoiesis. 
              &lt;p&gt;
              &lt;p&gt;One patient with a blast response had decline from 60% blasts to 0% in peripheral blood and 95% to 29% in bone marrow, which persisted for 50 days. The second blast response was associated with a 66% decrease in blast count, lasting for 35 days. One patient with stable disease for 56 days had a 48% decline in blast count. 
              &lt;p&gt;
              &lt;p&gt;All of the patients had elevated levels of eIF4E prior to treatment with ribavirin. After treatment, 10 of the 11 patients had declines in eIF4E RNA levels that ranged from two- to 10-fold. 
              &lt;p&gt;
              &lt;p&gt;Neither cytogenetics nor mutations in &lt;em&gt;FLT3&lt;/em&gt; or &lt;em&gt;NPM&lt;/em&gt; predicted response. 
              &lt;p&gt;
              &lt;p&gt;Besides demonstrating ribavirin&apos;s ability to target eIF4E, the results suggested that nuclear localization of eIF4E and its mRNA export function contribute to the oncogene&apos;s transformation capacity, the authors said. 
              &lt;p&gt;
              &lt;p&gt;There was no significant treatment-related toxicity. 
              &lt;p&gt;
              &lt;p&gt;Because multiple proteins modulate eIF4E relocalization, future studies should focus on elucidating more information about the relocalization process, they added. 
              &lt;p&gt;
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;The study was funded by the Leukemia and Lymphoma Society. 
              &lt;p&gt;
              &lt;p&gt;Dr. Borden holds an equity position in Translational Therapeutics.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
        
    </recommendedItem>
    <recommendedItem id="20090101_19_2723"
                     title="FDA Staff Pan Data on AML Drug"
                     score="-0.005"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/15737?impressionId=1265750024139"
                     
      &lt;p&gt;An application to market clofarabine (Clolar) for treating acute myeloid leukemia (AML) in patients 60 and older has received a cool reception from FDA staff.&lt;/p&gt;
&lt;p&gt;The agency&apos;s staff review, released in advance of an Oncologic Drugs Advisory Committee meeting next week, was critical of the data submitted by the drug&apos;s manufacturer, Genzyme.&lt;/p&gt;
&lt;p&gt;It said the company failed to perform a randomized, controlled study in support of the application, against FDA&apos;s advice.&lt;/p&gt;
&lt;p&gt;The review also pointed out that the committee had voted down the only previous application for an AML drug in elderly patients  --  for tipifarnib (Zarnestra) in 2005  --  that was backed only by uncontrolled studies.&lt;/p&gt;
&lt;p&gt;Clofarabine is currently approved for treating acute lymphoblastic leukemia in patients up to age 21.&lt;/p&gt;
&lt;p&gt;Genzyme is seeking to expand the indication to include previously untreated older AML patients who have at least one unfavorable baseline prognostic factor, which would make them unlikely to respond to standard induction or other intensive chemotherapy.&lt;/p&gt;
&lt;p&gt;Genzyme relied mainly on data from a single-arm, phase II study with 116 patients to support its bid. Patients were newly diagnosed and had at least one unfavorable prognostic factor.&lt;/p&gt;
&lt;p&gt;That study showed that 45% of patients obtained complete remissions (with or without complete platelet recovery). Among those patients, median duration of response was one year.&lt;/p&gt;
&lt;p&gt;Overall median survival was 41 weeks. Those obtaining complete responses lived a median of 61 weeks.&lt;/p&gt;
&lt;p&gt;In their review, FDA staff said that at least 25% of patients in the study  --  perhaps as many as 41%  --  might have been good candidates for standard induction therapy.&lt;/p&gt;
&lt;p&gt;They noted that some study patients did, in fact, receive such treatment after the clofarabine study was over, with a 48% rate of complete responses.&lt;/p&gt;
&lt;p&gt;In addition, according to the review, &quot;the lack of a randomized study combined with the heterogeneous patient population regarding AML prognostic factors makes interpretation of the study results difficult.&quot;&lt;/p&gt;
&lt;p&gt;Minutes of a meeting held with Genzyme representatives in late 2007 indicated that FDA officials recommended a randomized controlled study, the review said.&lt;/p&gt;
&lt;p&gt;In the tipifarnib hearing in 2005, the committee had voted 7 to 4 to recommend against approval, and, as it usually does, the FDA followed the committee&apos;s advice.&lt;/p&gt;
&lt;p&gt;The committee will hear from Genzyme and agency staff on Sept. 1 at the start of a two-day meeting.&lt;/p&gt;
&lt;p&gt;It is also being asked to advise on safety and efficacy issues regarding three investigational cancer drugs: laromustine (Onrigin) for AML, romidepsin (Istodax) for cutaneous T-cell lymphoma, and pralatrexate (Folotyn) for peripheral T-cell lymphoma.&lt;/p&gt;
&lt;p&gt;The review for laromustine also raised concern about the application&apos;s reliance on single-arm studies and patient selection in those studies. Staff also plan to ask the committee for opinions on toxicities seen in the trial, including increased deaths when the drug was combined with cytarabine.&lt;/p&gt;
&lt;p&gt;Pralatrexate&apos;s efficacy data were questioned by FDA staff, who noted that, for half the patients identified as responders, two clinical raters disagreed on the initial assessment and a third rater had to break the tie. Confirmation of responses was spotty as well, according to the review.&lt;/p&gt;
&lt;p&gt;Specific voting questions on the four drugs were not released as of late Friday.&lt;/p&gt;

    </recommendedItem>
</recommendedContent>