Clinical Factors Associated with Long-Term Complete Remission versus Poor Response to Chemotherapy in HIV-Infected Children and Adolescents with Kaposi Sarcoma Receiving Bleomycin and Vincristine: A Retrospective Observational Study
Identifieur interne : 000417 ( Pmc/Curation ); précédent : 000416; suivant : 000418Clinical Factors Associated with Long-Term Complete Remission versus Poor Response to Chemotherapy in HIV-Infected Children and Adolescents with Kaposi Sarcoma Receiving Bleomycin and Vincristine: A Retrospective Observational Study
Auteurs : Nader Kim El-Mallawany [États-Unis] ; William Kamiyango [Malawi] ; Jeremy S. Slone [États-Unis] ; Jimmy Villiera [Malawi] ; Carrie L. Kovarik [États-Unis] ; Carrie M. Cox [États-Unis] ; Dirk P. Dittmer [États-Unis] ; Saeed Ahmed [Malawi, États-Unis] ; Gordon E. Schutze [États-Unis] ; Michael E. Scheurer [États-Unis] ; Peter N. Kazembe [Malawi] ; Parth S. Mehta [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2016.
Abstract
Kaposi sarcoma (KS) is the most common HIV-associated malignancy in children and adolescents in Africa. Pediatric KS is distinct from adult disease. We evaluated the clinical characteristics associated with long-term outcomes. We performed a retrospective observational analysis of 70 HIV-infected children and adolescents with KS less than 18 years of age diagnosed between 8/2010 and 6/2013 in Lilongwe, Malawi. Local first-line treatment included bleomycin and vincristine plus nevirapine-based highly active anti-retroviral therapy (HAART). Median age was 8.6 years (range 1.7–17.9); there were 35 females (50%). Most common sites of presentation were: lymph node (74%), skin (59%), subcutaneous nodules (33%), oral (27%), woody edema (24%), and visceral (16%). Eighteen (26%) presented with lymphadenopathy only. Severe CD4 suppression occurred in 28%. At time of KS diagnosis, 49% were already on HAART. Overall, 28% presented with a platelet count < 100 x 109/L and 37% with hemoglobin < 8 g/dL. The 2-year event-free (EFS) and overall survival (OS) were 46% and 58% respectively (median follow-up 29 months, range 15–50). Multivariable analysis of risk of death and failure to achieve EFS demonstrated that visceral disease (odds ratios [OR] 19.08 and 11.61, 95% CI 2.22–163.90 and 1.60–83.95 respectively) and presenting with more than 20 skin/oral lesions (OR 9.57 and 22.90, 95% CI 1.01–90.99 and 1.00–524.13 respectively) were independent risk factors for both. Woody edema was associated with failure to achieve EFS (OR 7.80, 95% CI 1.84–33.08) but not death. Univariable analysis revealed that lymph node involvement was favorable for EFS (OR 0.28, 95% CI 0.08–0.99), while T1 TIS staging criteria, presence of cytopenias, and severe immune suppression were not associated with increased mortality. Long-term complete remission is achievable in pediatric KS, however outcomes vary according to clinical presentation. Based on clinical heterogeneity, treatment according to risk-stratification is necessary to improve overall outcomes.
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DOI: 10.1371/journal.pone.0153335
PubMed: 27082863
PubMed Central: 4833299
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Slone</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Pediatrics, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Texas Children’s Cancer and Hematology Centers, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Texas Children’s Cancer and Hematology Centers, Houston, Texas</wicri:regionArea></affiliation></author><author><name sortKey="Villiera, Jimmy" sort="Villiera, Jimmy" uniqKey="Villiera J" first="Jimmy" last="Villiera">Jimmy Villiera</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Baylor College of Medicine Children’s Foundation Malawi, Lilongwe, Malawi</addr-line></nlm:aff><country xml:lang="fr">Malawi</country><wicri:regionArea>Baylor College of Medicine Children’s Foundation Malawi, Lilongwe</wicri:regionArea></affiliation></author><author><name sortKey="Kovarik, Carrie L" sort="Kovarik, Carrie L" uniqKey="Kovarik C" first="Carrie L." last="Kovarik">Carrie L. Kovarik</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania</wicri:regionArea></affiliation></author><author><name sortKey="Cox, Carrie M" sort="Cox, Carrie M" uniqKey="Cox C" first="Carrie M." last="Cox">Carrie M. Cox</name><affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Department of Pediatrics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois</wicri:regionArea></affiliation></author><author><name sortKey="Dittmer, Dirk P" sort="Dittmer, Dirk P" uniqKey="Dittmer D" first="Dirk P." last="Dittmer">Dirk P. Dittmer</name><affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Ahmed, Saeed" sort="Ahmed, Saeed" uniqKey="Ahmed S" first="Saeed" last="Ahmed">Saeed Ahmed</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Baylor College of Medicine Children’s Foundation Malawi, Lilongwe, Malawi</addr-line></nlm:aff><country xml:lang="fr">Malawi</country><wicri:regionArea>Baylor College of Medicine Children’s Foundation Malawi, Lilongwe</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, Texas</wicri:regionArea></affiliation></author><author><name sortKey="Schutze, Gordon E" sort="Schutze, Gordon E" uniqKey="Schutze G" first="Gordon E." last="Schutze">Gordon E. Schutze</name><affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, Texas</wicri:regionArea></affiliation></author><author><name sortKey="Scheurer, Michael E" sort="Scheurer, Michael E" uniqKey="Scheurer M" first="Michael E." last="Scheurer">Michael E. Scheurer</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Pediatrics, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Texas Children’s Cancer and Hematology Centers, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Texas Children’s Cancer and Hematology Centers, Houston, Texas</wicri:regionArea></affiliation></author><author><name sortKey="Kazembe, Peter N" sort="Kazembe, Peter N" uniqKey="Kazembe P" first="Peter N." last="Kazembe">Peter N. Kazembe</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Baylor College of Medicine Children’s Foundation Malawi, Lilongwe, Malawi</addr-line></nlm:aff><country xml:lang="fr">Malawi</country><wicri:regionArea>Baylor College of Medicine Children’s Foundation Malawi, Lilongwe</wicri:regionArea></affiliation></author><author><name sortKey="Mehta, Parth S" sort="Mehta, Parth S" uniqKey="Mehta P" first="Parth S." last="Mehta">Parth S. Mehta</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Pediatrics, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Texas Children’s Cancer and Hematology Centers, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Texas Children’s Cancer and Hematology Centers, Houston, Texas</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Kaposi sarcoma (KS) is the most common HIV-associated malignancy in children and adolescents in Africa. Pediatric KS is distinct from adult disease. We evaluated the clinical characteristics associated with long-term outcomes. We performed a retrospective observational analysis of 70 HIV-infected children and adolescents with KS less than 18 years of age diagnosed between 8/2010 and 6/2013 in Lilongwe, Malawi. Local first-line treatment included bleomycin and vincristine plus nevirapine-based highly active anti-retroviral therapy (HAART). Median age was 8.6 years (range 1.7–17.9); there were 35 females (50%). Most common sites of presentation were: lymph node (74%), skin (59%), subcutaneous nodules (33%), oral (27%), woody edema (24%), and visceral (16%). Eighteen (26%) presented with lymphadenopathy only. Severe CD4 suppression occurred in 28%. At time of KS diagnosis, 49% were already on HAART. Overall, 28% presented with a platelet count < 100 x 10<sup>9</sup>/L and 37% with hemoglobin < 8 g/dL. The 2-year event-free (EFS) and overall survival (OS) were 46% and 58% respectively (median follow-up 29 months, range 15–50). Multivariable analysis of risk of death and failure to achieve EFS demonstrated that visceral disease (odds ratios [OR] 19.08 and 11.61, 95% CI 2.22–163.90 and 1.60–83.95 respectively) and presenting with more than 20 skin/oral lesions (OR 9.57 and 22.90, 95% CI 1.01–90.99 and 1.00–524.13 respectively) were independent risk factors for both. Woody edema was associated with failure to achieve EFS (OR 7.80, 95% CI 1.84–33.08) but not death. Univariable analysis revealed that lymph node involvement was favorable for EFS (OR 0.28, 95% CI 0.08–0.99), while T<sub>1</sub> TIS staging criteria, presence of cytopenias, and severe immune suppression were not associated with increased mortality. Long-term complete remission is achievable in pediatric KS, however outcomes vary according to clinical presentation. Based on clinical heterogeneity, treatment according to risk-stratification is necessary to improve overall outcomes.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Orem, J" uniqKey="Orem J">J Orem</name></author><author><name sortKey="Otieno, Mw" uniqKey="Otieno M">MW Otieno</name></author><author><name sortKey="Remick, Sc" uniqKey="Remick S">SC Remick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Y" uniqKey="Chang Y">Y Chang</name></author><author><name sortKey="Cesarman, E" uniqKey="Cesarman E">E Cesarman</name></author><author><name sortKey="Pessin, Ms" uniqKey="Pessin M">MS Pessin</name></author><author><name sortKey="Lee, F" uniqKey="Lee F">F Lee</name></author><author><name sortKey="Culpepper, J" uniqKey="Culpepper J">J Culpepper</name></author><author><name sortKey="Knowles, Dm" uniqKey="Knowles D">DM 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27082863</article-id><article-id pub-id-type="pmc">4833299</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0153335</article-id><article-id pub-id-type="publisher-id">PONE-D-15-55806</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Vaccination and Immunization</subject><subj-group><subject>Antiviral Therapy</subject><subj-group><subject>Antiretroviral Therapy</subject><subj-group><subject>Highly-Active Antiretroviral Therapy</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Vaccination and Immunization</subject><subj-group><subject>Antiviral Therapy</subject><subj-group><subject>Antiretroviral Therapy</subject><subj-group><subject>Highly-Active Antiretroviral Therapy</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Public and Occupational Health</subject><subj-group><subject>Preventive Medicine</subject><subj-group><subject>Vaccination and Immunization</subject><subj-group><subject>Antiviral Therapy</subject><subj-group><subject>Antiretroviral Therapy</subject><subj-group><subject>Highly-Active Antiretroviral Therapy</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Oncology</subject><subj-group><subject>Cancers and Neoplasms</subject><subj-group><subject>Sarcomas</subject><subj-group><subject>Kaposi Sarcoma</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Pediatrics</subject></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Diagnostic Medicine</subject><subj-group><subject>Signs and Symptoms</subject><subj-group><subject>Edema</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Pathology and Laboratory Medicine</subject><subj-group><subject>Signs and Symptoms</subject><subj-group><subject>Edema</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Diagnostic Medicine</subject><subj-group><subject>Signs and Symptoms</subject><subj-group><subject>Lesions</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Pathology and Laboratory Medicine</subject><subj-group><subject>Signs and Symptoms</subject><subj-group><subject>Lesions</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Oncology</subject><subj-group><subject>Cancer Treatment</subject><subj-group><subject>Chemotherapy</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Clinical Medicine</subject><subj-group><subject>Clinical Oncology</subject><subj-group><subject>Chemotherapy</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Oncology</subject><subj-group><subject>Clinical Oncology</subject><subj-group><subject>Chemotherapy</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Pharmaceutics</subject><subj-group><subject>Drug Therapy</subject><subj-group><subject>Chemotherapy</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Anatomy</subject><subj-group><subject>Lymphatic System</subject><subj-group><subject>Lymph Nodes</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Anatomy</subject><subj-group><subject>Lymphatic System</subject><subj-group><subject>Lymph Nodes</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Oncology</subject><subj-group><subject>Cancer Treatment</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Clinical Factors Associated with Long-Term Complete Remission versus Poor Response to Chemotherapy in HIV-Infected Children and Adolescents with Kaposi Sarcoma Receiving Bleomycin and Vincristine: A Retrospective Observational Study</article-title><alt-title alt-title-type="running-head">Long-Term Outcomes in Pediatric Kaposi Sarcoma</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>El-Mallawany</surname><given-names>Nader Kim</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib><contrib contrib-type="author"><name><surname>Kamiyango</surname><given-names>William</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Slone</surname><given-names>Jeremy S.</given-names></name><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Villiera</surname><given-names>Jimmy</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kovarik</surname><given-names>Carrie L.</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cox</surname><given-names>Carrie M.</given-names></name><xref ref-type="aff" rid="aff006"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dittmer</surname><given-names>Dirk P.</given-names></name><xref ref-type="aff" rid="aff007"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ahmed</surname><given-names>Saeed</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref><xref ref-type="aff" rid="aff008"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Schutze</surname><given-names>Gordon E.</given-names></name><xref ref-type="aff" rid="aff008"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Scheurer</surname><given-names>Michael E.</given-names></name><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kazembe</surname><given-names>Peter N.</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mehta</surname><given-names>Parth S.</given-names></name><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Department of Pediatrics, Division of Hematology, Oncology, and Hematopoietic Stem Cell Transplantation, New York Medical College, Valhalla, New York, United States of America</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Department of Pediatrics, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Baylor College of Medicine Children’s Foundation Malawi, Lilongwe, Malawi</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Texas Children’s Cancer and Hematology Centers, Houston, Texas, United States of America</addr-line></aff><aff id="aff005"><label>5</label><addr-line>Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America</addr-line></aff><aff id="aff006"><label>6</label><addr-line>Department of Pediatrics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, United States of America</addr-line></aff><aff id="aff007"><label>7</label><addr-line>Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America</addr-line></aff><aff id="aff008"><label>8</label><addr-line>Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Gao</surname><given-names>Shou-Jiang</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Southern California Keck School of Medicine, UNITED STATES</addr-line></aff><author-notes><fn fn-type="conflict" id="coi001"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: NKE WK JV CLK CMC SA PNK PSM. Performed the experiments: NKE WK JV CLK. Analyzed the data: NKE JSS MES PSM. Contributed reagents/materials/analysis tools: NKE JSS CLK SA DPD MES. Wrote the paper: NKE JSS DPD GES MES PNK PSM.</p></fn><corresp id="cor001">* E-mail: <email>nader.el-mallawany@bcm.edu</email></corresp></author-notes><pub-date pub-type="epub"><day>15</day><month>4</month><year>2016</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>11</volume><issue>4</issue><elocation-id>e0153335</elocation-id><history><date date-type="received"><day>28</day><month>12</month><year>2015</year></date><date date-type="accepted"><day>28</day><month>3</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 El-Mallawany et al</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>El-Mallawany et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="pone.0153335.pdf"></self-uri><abstract><p>Kaposi sarcoma (KS) is the most common HIV-associated malignancy in children and adolescents in Africa. Pediatric KS is distinct from adult disease. We evaluated the clinical characteristics associated with long-term outcomes. We performed a retrospective observational analysis of 70 HIV-infected children and adolescents with KS less than 18 years of age diagnosed between 8/2010 and 6/2013 in Lilongwe, Malawi. Local first-line treatment included bleomycin and vincristine plus nevirapine-based highly active anti-retroviral therapy (HAART). Median age was 8.6 years (range 1.7–17.9); there were 35 females (50%). Most common sites of presentation were: lymph node (74%), skin (59%), subcutaneous nodules (33%), oral (27%), woody edema (24%), and visceral (16%). Eighteen (26%) presented with lymphadenopathy only. Severe CD4 suppression occurred in 28%. At time of KS diagnosis, 49% were already on HAART. Overall, 28% presented with a platelet count < 100 x 10<sup>9</sup>/L and 37% with hemoglobin < 8 g/dL. The 2-year event-free (EFS) and overall survival (OS) were 46% and 58% respectively (median follow-up 29 months, range 15–50). Multivariable analysis of risk of death and failure to achieve EFS demonstrated that visceral disease (odds ratios [OR] 19.08 and 11.61, 95% CI 2.22–163.90 and 1.60–83.95 respectively) and presenting with more than 20 skin/oral lesions (OR 9.57 and 22.90, 95% CI 1.01–90.99 and 1.00–524.13 respectively) were independent risk factors for both. Woody edema was associated with failure to achieve EFS (OR 7.80, 95% CI 1.84–33.08) but not death. Univariable analysis revealed that lymph node involvement was favorable for EFS (OR 0.28, 95% CI 0.08–0.99), while T<sub>1</sub> TIS staging criteria, presence of cytopenias, and severe immune suppression were not associated with increased mortality. Long-term complete remission is achievable in pediatric KS, however outcomes vary according to clinical presentation. Based on clinical heterogeneity, treatment according to risk-stratification is necessary to improve overall outcomes.</p></abstract><funding-group><award-group id="award001"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000200</institution-id><institution>United States Agency for International Development</institution></institution-wrap></funding-source><award-id>674-A-00-10-00093-00</award-id><principal-award-recipient><name><surname>Ahmed</surname><given-names>Saeed</given-names></name></principal-award-recipient></award-group><award-group id="award002"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100007197</institution-id><institution>U.S. Public Health Service</institution></institution-wrap></funding-source><award-id>CA019014</award-id><principal-award-recipient><name><surname>Dittmer</surname><given-names>Dirk P.</given-names></name></principal-award-recipient></award-group><award-group id="award003"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100004677</institution-id><institution>ConocoPhillips</institution></institution-wrap></funding-source></award-group><award-group id="award004"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100007197</institution-id><institution>U.S. Public Health Service</institution></institution-wrap></funding-source><award-id>CA190152</award-id><principal-award-recipient><name><surname>Dittmer</surname><given-names>Dirk P.</given-names></name></principal-award-recipient></award-group><award-group id="award005"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100007197</institution-id><institution>U.S. Public Health Service</institution></institution-wrap></funding-source><award-id>CA192744</award-id><principal-award-recipient><name><surname>Dittmer</surname><given-names>Dirk P.</given-names></name></principal-award-recipient></award-group><funding-statement>Financial support for the pediatric HIV-associated malignancy and oncology program was provided by a grant from the United States Agency for International Development through the Tingathe Program via cooperative agreement number 674-A-00-10-00093-00 and philanthropic contributions to purchase chemotherapy from ConocoPhillips. The Kamuzu Central Hospital pathology laboratory and Kaposi sarcoma research at the University of North Carolina Project-Malawi are supported by public health service grants CA019014, CA190152, and CA192744. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="3"></fig-count><table-count count="3"></table-count><page-count count="17"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>The dataset has been uploaded to Dryad at the following DOI: doi:<ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.5061/dryad.75tn6">10.5061/dryad.75tn6</ext-link>.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>The dataset has been uploaded to Dryad at the following DOI: doi:<ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.5061/dryad.75tn6">10.5061/dryad.75tn6</ext-link>.</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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