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 <!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "http://jats.nlm.nih.gov/publishing/1.0/JATS-journalpublishing1.dtd"> <article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="research-article" dtd-version="1.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JHOR</journal-id>
      <journal-title-group>
        <journal-title>Journal of Hematology and Oncology Research</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2372-6601</issn>
      <publisher>
        <publisher-name>Open Access Pub</publisher-name>
        <publisher-loc>United States</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">JHOR-24-4962</article-id>
      <article-id pub-id-type="doi">10.14302/issn.2372-6601.jhor-24-4962</article-id>
      <article-categories>
        <subj-group>
          <subject>research-article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Hodgkin's Lymphoma In Low-Income Countries: Experience Of Togo</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Essohana</surname>
            <given-names>Padaro</given-names>
          </name>
          <xref ref-type="aff" rid="idm1849443644">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kodzovi</surname>
            <given-names>M C Womey</given-names>
          </name>
          <xref ref-type="aff" rid="idm1849443644">1</xref>
          <xref ref-type="corresp" rid="cor1">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Yao</surname>
            <given-names>Layibo</given-names>
          </name>
          <xref ref-type="aff" rid="idm1849440548">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kadara</surname>
            <given-names>R Adandodo</given-names>
          </name>
          <xref ref-type="aff" rid="idm1849443644">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hèzouwè</surname>
            <given-names>Magnang</given-names>
          </name>
          <xref ref-type="aff" rid="idm1849443644">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mensah</surname>
            <given-names>D I Kueviakoe</given-names>
          </name>
          <xref ref-type="aff" rid="idm1849440476">3</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1849443644">
        <label>1</label>
        <addr-line>Hematology Department, Campus University Hospital Center, University of Lomé, Togo</addr-line>
      </aff>
      <aff id="idm1849440548">
        <label>2</label>
        <addr-line>Hematology Laboratory, Sylvanus Olympio University Hospital Center, University of Lomé, Togo</addr-line>
      </aff>
      <aff id="idm1849440476">
        <label>3</label>
        <addr-line>Hematology Laboratory, Tsévié Regional Hospital Center, University of Lomé, Togo</addr-line>
      </aff>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Rada</surname>
            <given-names>M. Grubovic</given-names>
          </name>
          <xref ref-type="aff" rid="idm1849291684">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1849291684">
        <label>1</label>
        <addr-line>Macedonia, the Former Yugoslav Republic of</addr-line>
      </aff>
      <author-notes>
        <corresp id="cor1">Kodzovi M C Womey, Hematology Department, Campus University Hospital Center, University of Lomé, Togo. Email: <email>corcellar.womey@gmail.com</email></corresp>
        <fn fn-type="conflict" id="idm1842027204">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub" iso-8601-date="2024-03-04">
        <day>04</day>
        <month>03</month>
        <year>2024</year>
      </pub-date>
      <volume>4</volume>
      <issue>3</issue>
      <fpage>24</fpage>
      <lpage>30</lpage>
      <history>
        <date date-type="received">
          <day>05</day>
          <month>02</month>
          <year>2024</year>
        </date>
        <date date-type="accepted">
          <day>03</day>
          <month>03</month>
          <year>2024</year>
        </date>
        <date date-type="online">
          <day>04</day>
          <month>03</month>
          <year>2024</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>©</copyright-statement>
        <copyright-year>2024</copyright-year>
        <copyright-holder>Essohana Padaro, et al</copyright-holder>
        <license xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <self-uri xlink:href="http://openaccesspub.org/jhor/article/2085">This article is available from http://openaccesspub.org/jhor/article/2085</self-uri>
      <abstract>
        <p>While highly curable in developed countries, Hodgkin's lymphoma (HL), remains a significant challenge for resource-limited ones. This study aimed to describe the profile of HL in Togo. This was a retrospective, descriptive study conducted at the Clinical Hematology Department of the Campus University Hospital Center in Lomé, Togo. It focused on patient records diagnosed with HL between January 1, 2006, and December 31, 2022. Various variables such as age, gender, histological type of HL, Ann Arbor stage, prognostic classification, therapeutic protocol used, and patient outcomes were examined. The annual incidence of HL was 1.5 with a mean age of 38.7 years (range 12-63). Lymph node enlargement was the primary clinical sign (100%). Histologically, classical HL was found in 21 patients (87.5%). Staging was conducted for 16 (66.7%) patients, among whom 11 (66.7%) were at an advanced stage, and 6 (37.5%) had an unfavorable prognosis. The ABVD protocol was used in 13 patients (54.2%), receiving between 1 and 6 cycles. One patient achieved complete remission (4.1%), three deceased (12.5%), and 17 (71%) were lost to follow-up. Hodgkin's lymphoma prognosis remains unfavorable with low remission rates in Togo. Improving the technical facilities will ensure better management of this lymphoma.</p>
      </abstract>
      <kwd-group>
        <kwd>Hodgkin's lymphoma</kwd>
        <kwd>epidemiology</kwd>
        <kwd>Togo</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="3"/>
        <page-count count="7"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="idm1849288156" sec-type="intro">
      <title>Introduction</title>
      <p>First reported by Thomas Hodgkin from the Guy’s hospital in London in 1832, Hodgkin lymphoma are a family of unique lymphoma subtypes, in which the  nature of the neoplastic cell was enigmatic for many years <xref ref-type="bibr" rid="ridm1842508572">1</xref>. It’sremains a                distinct entity among lymphoproliferative neoplasms due to its biological                      characteristics <xref ref-type="bibr" rid="ridm1842575532">2</xref>. It is characterized by nodal infiltration within a reactive tissue by voluminous tumor cells called Reed-Sternberg (RS) cells, essential for                     diagnosis but not entirely specific. The nature of the Reed-Sternberg cell has long been debated, but it is now well-established that it’s a neoplasm derived from B cells, in which the unique cellular microenvironment plays an important role in accurate diagnosis and pathobiology. <xref ref-type="bibr" rid="ridm1842590724">3</xref>. The diagnosis of Hodgkin lymphoma in the modern era relies on an appropriate clinical setting, and morphological and immunophenotypic assessment <xref ref-type="bibr" rid="ridm1842508572">1</xref>. Clinical and biological data from the last          thirty years have distinguished two major entities in HL: classical HL and nodular lymphocyte-predominant HL <xref ref-type="bibr" rid="ridm1842369108">4</xref>. It is a rare pathology but highly curable with well-defined recommendations based on various prognostic classifications and initial response to treatments, combining different chemotherapy protocol (ABVD, BEACOPP) and radiotherapy  <xref ref-type="bibr" rid="ridm1842374220">5</xref>. In Togo, patients do not always have access to prognostic tools, which are crucial for treatment strategies. Hence, we conducted this study to describe the epidemiological, clinical, biological, and therapeutic aspects of patients diagnosed with HL, as well as their outcomes in a resource-limited country like  Togo. Additionally, this study aimed to assess the evolution of management, five years after the last one <xref ref-type="bibr" rid="ridm1842370764">6</xref>.</p>
    </sec>
    <sec id="idm1849289884" sec-type="methods">
      <title>Methods</title>
      <p>This was a retrospective, descriptive study involving patient records diagnosed with HL between                 January 1, 2006, and December 31, 2022, spanning a 16-year period. The study was conducted at the Clinical Hematology Department of CHU Campus in Lomé, Togo. The diagnosis of HL was based on histology from lymph node biopsy and/or immunohistochemistry. Staging included chest, abdominal and pelvis computed tomography and bone marrow biopsy in advanced stages. The Lugano Ann Arbor classification  <xref ref-type="bibr" rid="ridm1842352300">7</xref> was used to assess staging. The prognostic classifications used were the European Organization for Research and Treatment of Cancer (EORTC) <xref ref-type="bibr" rid="ridm1842326316">8</xref> for limited stages and the International Prognostic Score (IPS) <xref ref-type="bibr" rid="ridm1842325452">9</xref> for advanced stages.</p>
    </sec>
    <sec id="idm1849287940" sec-type="results">
      <title>Results</title>
      <p>In total, 24 records were included. HL accounted for 18.1% of lymphoid neoplasms (24/132) and 3.8% of malignant hematologic disorders (24/748) during the study period. The annual incidence was 1.5. The mean age of patients was 38.7 years (12-63), with a male predominance and a sex ratio of 1.7. <xref ref-type="fig" rid="idm1842427308">Figure 1</xref> describes the distribution of patients by age group.</p>
      <fig id="idm1842427308">
        <label>Figure 1.</label>
        <caption>
          <title> Distribution of patients according to age groups</title>
        </caption>
        <graphic xlink:href="images/image1.jpg" mime-subtype="jpg"/>
      </fig>
      <p>The main presenting circumstance of Hodgkin's lymphoma (HL) was lymph node enlargement, present in all patients (100%). Patients also exhibited night sweats (6/24), prolonged fever (6/24), fatigue (1/24), and persistent pruritus (1/24). Physical signs were predominantly characterized by lymph node enlargement, averaging 7cm (range 2-15). These were peripheral in 21 patients and cervical in 17. A quarter of the patients also presented with hepatomegaly, and four had splenomegaly.</p>
      <p>Histologically, classical HL constituted most histological types, diagnosed in 21 (87.5%) patients. <xref ref-type="table" rid="idm1842423708">Table 1</xref> illustrates the distribution of patients based on histology.</p>
      <table-wrap id="idm1842423708">
        <label>Table 1.</label>
        <caption>
          <title> Distribution of cases according to histological types</title>
        </caption>
        <table rules="all" frame="box">
          <tbody>
            <tr>
              <td> </td>
              <td>
                <bold>Numbers</bold>
              </td>
              <td>
                <bold>Percentage</bold>
              </td>
            </tr>
            <tr>
              <td>Classical HL</td>
              <td>21</td>
              <td>87,5</td>
            </tr>
            <tr>
              <td>Nodular sclerosis HL</td>
              <td>10</td>
              <td>41,6</td>
            </tr>
            <tr>
              <td>Mixed cellularity classical HL</td>
              <td>6</td>
              <td>25</td>
            </tr>
            <tr>
              <td>Lymphocyte-rich classical HL</td>
              <td>3</td>
              <td>12,5</td>
            </tr>
            <tr>
              <td>Lymphocyte-depleted classical HL</td>
              <td>1</td>
              <td>4,2</td>
            </tr>
            <tr>
              <td>Not specified</td>
              <td>1</td>
              <td>4,2</td>
            </tr>
            <tr>
              <td>Nodular lymphocyte predominant HL</td>
              <td>3</td>
              <td>12,5</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p>Sixteen patients underwent staging (66.7%). Among these patients, five (33.3%) were at an early stage at diagnosis, with two patients presenting a bulky mass, and eleven (67.7%) were at an advanced stage (<xref ref-type="fig" rid="idm1842363396">Figure 2</xref>). Adverse prognosis was observed in 37.5% of these patients (<xref ref-type="table" rid="idm1842361236">Table 2</xref>). Thirty-seven-point five percent (37.5%) of the included patients exhibited clinical signs of progression, and fifty-four percent (54%) showed biological signs of progression.</p>
      <fig id="idm1842363396">
        <label>Figure 2.</label>
        <caption>
          <title> Distribution of patients according to Ann Arbor (Lugano) classification</title>
        </caption>
        <graphic xlink:href="images/image2.jpg" mime-subtype="jpg"/>
      </fig>
      <table-wrap id="idm1842361236">
        <label>Table 2.</label>
        <caption>
          <title> Distribution of patients according to prognostic classification</title>
        </caption>
        <table rules="all" frame="box">
          <tbody>
            <tr>
              <td> </td>
              <td>
                <bold>Numbers</bold>
              </td>
              <td>
                <bold>Percentage</bold>
              </td>
            </tr>
            <tr>
              <td colspan="3">
                <bold>EORTC</bold>
                <bold>Classification</bold>
                <bold>(Limited</bold>
                <bold>stage),</bold>
                <bold>n=5</bold>
              </td>
            </tr>
            <tr>
              <td>Favorable</td>
              <td>4</td>
              <td>80</td>
            </tr>
            <tr>
              <td>Unfavorable</td>
              <td>1</td>
              <td>20</td>
            </tr>
            <tr>
              <td colspan="3">
                <bold>IPS</bold>
                <bold>Classification</bold>
                <bold>(Advanced</bold>
                <bold>stage),</bold>
                <bold>n=11</bold>
              </td>
            </tr>
            <tr>
              <td>Favorable</td>
              <td>3</td>
              <td>27,3</td>
            </tr>
            <tr>
              <td>Unfavorable</td>
              <td>8</td>
              <td>72,7</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p>In terms of treatment, the frontline protocol used was the combination chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Thirteen patients, accounting for a ratio of 54.2%, initiated this treatment. They received between 1 and 6 cycles. <xref ref-type="table" rid="idm1842335028">Table 3</xref> presents the outcomes of patients diagnosed with HL at the time of our study.</p>
      <table-wrap id="idm1842335028">
        <label>Table 3.</label>
        <caption>
          <title> Distribution of patients according to their outcome</title>
        </caption>
        <table rules="all" frame="box">
          <tbody>
            <tr>
              <td> </td>
              <td>
                <bold>Numbers</bold>
              </td>
              <td>
                <bold>Percentage</bold>
              </td>
            </tr>
            <tr>
              <td colspan="3">
                <bold>EORTC</bold>
                <bold>Classification</bold>
                <bold>(Limited</bold>
                <bold>stage),</bold>
                <bold>n=5</bold>
              </td>
            </tr>
            <tr>
              <td>Favorable</td>
              <td>4</td>
              <td>80</td>
            </tr>
            <tr>
              <td>Unfavorable</td>
              <td>1</td>
              <td>20</td>
            </tr>
            <tr>
              <td colspan="3">
                <bold>IPS</bold>
                <bold>Classification</bold>
                <bold>(Advanced</bold>
                <bold>stage),</bold>
                <bold>n=11</bold>
              </td>
            </tr>
            <tr>
              <td>Favorable</td>
              <td>3</td>
              <td>27,3</td>
            </tr>
            <tr>
              <td>Unfavorable</td>
              <td>8</td>
              <td>72,7</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
    </sec>
    <sec id="idm1849190004" sec-type="discussion">
      <title>Discussion</title>
      <p>In comparison to other malignant hematologic disorders, Hodgkin's lymphoma is relatively rare, as demonstrated by the prevalence found in our study. With approximately 1,500 new cases per year in France, Hodgkin's lymphoma accounts for only 10 to 15% of lymphomas and 0.5 to 1% of new cancer cases <xref ref-type="bibr" rid="ridm1842310868">10</xref>. In the United States, it represents 10% of all lymphomas <xref ref-type="bibr" rid="ridm1842309644">11</xref>. In Togo, although the                     incidence of Hodgkin's lymphoma is low, it is on the rise. While it was 0.65 new cases per year in a study conducted over a 20-year period by Padaro et al. <xref ref-type="bibr" rid="ridm1842370764">6</xref>, it is currently at 1.5. This increase could be attributed to an improvement in technical facilities and an increase in the number of pathologists,          making diagnosis more accessible. Hodgkin's lymphoma exhibits a bimodal distribution, with an initial peak in young adults (20-30 years) and a second peak in individuals over 60 years old <xref ref-type="bibr" rid="ridm1842303812">12</xref>. This                 bimodal incidence suggests that this pathology may stem from two distinct pathogenic processes: an infectious agent for young adults (EBV: Epstein Barr Virus) and a mechanism shared with other                   lymphomas for older patients <xref ref-type="bibr" rid="ridm1842301220">13</xref><xref ref-type="bibr" rid="ridm1842312524">14</xref>. In developing countries, Hodgkin's lymphoma predominantly affects a younger population. The average age of patients in our study aligns with this data, as do the findings of other sub-Saharan studies <xref ref-type="bibr" rid="ridm1842281988">15</xref><xref ref-type="bibr" rid="ridm1842278676">16</xref>. Hodgkin's lymphoma can also occur in children and                  adolescents, but it is rare before the age of 5 <xref ref-type="bibr" rid="ridm1842303812">12</xref>. In our study, the low proportion of children found is explained by the fact that the hematology department at CHU Campus primarily receives adults. Male predominance has also been noted in previous series <xref ref-type="bibr" rid="ridm1842309644">11</xref><xref ref-type="bibr" rid="ridm1842275004">17</xref><xref ref-type="bibr" rid="ridm1842286164">18</xref>.</p>
      <p>All patients presented with lymph node enlargement, predominantly peripheral and cervical. Indeed, at the time of diagnosis, most Hodgkin's lymphoma patients present with supradiaphragmatic                             lymphadenopathy. Patients frequently exhibit involvement of cervical, anterior mediastinal,                             supraclavicular, and axillary lymph nodes, while inguinal regions are less commonly affected. About a third of patients present systemic symptoms such as fever, night sweats, and weight loss <xref ref-type="bibr" rid="ridm1842263788">19</xref>.</p>
      <p>Classical HL is the most found subtype, accounting for nearly 90% of HL cases <xref ref-type="bibr" rid="ridm1842275004">17</xref><xref ref-type="bibr" rid="ridm1842286164">18</xref><xref ref-type="bibr" rid="ridm1842263788">19</xref>. The results of our study align with this.</p>
      <p>Only 16 patients (66.67%) underwent staging. This is mostly due to the patients' low socioeconomic status. Undergoing a scan cost approximately $133 USD, approximately 2.3 times the minimum wage during the study period ($58 USD). Long delays in specialized consultations, associated with                        diagnostic errors, and the difficulty in accessing the country's only public clinical hematology service account for the prevalence of advanced stages and poor prognoses in our study.</p>
      <p>The indicated first-line treatment in our study was the ABVD protocol with six cycles, due to the unavailability of PET-CT at CHU and radiotherapy, which could have reduced the number of chemotherapy cycles based on the therapeutic response to systemic treatment. Only one patient achieved complete remission, and 17 (71%) were lost to follow-up. This high rate of loss to follow-up and low rate of remission reflects the financial precariousness of patients, most of whom did not initiate or complete the treatment. Indeed, Hodgkin's lymphoma is a highly curable hematologic malignancy, and the ABVD protocol is a validated treatment supported by several studies. It is used in combined therapy with radiotherapy or as a single modality due to the late toxicity of radiotherapy <xref ref-type="bibr" rid="ridm1842260188">20</xref><xref ref-type="bibr" rid="ridm1842258604">21</xref><xref ref-type="bibr" rid="ridm1842255940">22</xref>. The BEACOPP protocol is another effective therapeutic alternative for advanced stages. However, it is more toxic, requiring additional supportive care and closer monitoring of hematological parameters <xref ref-type="bibr" rid="ridm1842252916">23</xref><xref ref-type="bibr" rid="ridm1842242100">24</xref><xref ref-type="bibr" rid="ridm1842240228">25</xref>, making it unfeasible in our practice setting. Therefore, therapeutic strategy in Hodgkin's lymphoma relies on effective risk stratification based not only on the Ann Arbor classification but also on certain prognostic factors <xref ref-type="bibr" rid="ridm1842352300">7</xref><xref ref-type="bibr" rid="ridm1842263788">19</xref>. Beyond the historical classifications of EORTC for limited stages and IPS for advanced stages <xref ref-type="bibr" rid="ridm1842326316">8</xref><xref ref-type="bibr" rid="ridm1842325452">9</xref>, which have long guided therapeutic choices, PET-CT has proven useful both in diagnostic performance <xref ref-type="bibr" rid="ridm1842237276">26</xref><xref ref-type="bibr" rid="ridm1842233460">27</xref><xref ref-type="bibr" rid="ridm1842227772">28</xref><xref ref-type="bibr" rid="ridm1842216828">29</xref> and in treatment <xref ref-type="bibr" rid="ridm1842213516">30</xref><xref ref-type="bibr" rid="ridm1842210348">31</xref>, leading to a modification in the therapeutic approach based on the response according to interim PET-CT after two cycles of chemotherapy. It is nowadays an indispensable tool for the effective management of Hodgkin's lymphoma.</p>
    </sec>
    <sec id="idm1849187196" sec-type="conclusions">
      <title>Conclusion</title>
      <p>Hodgkin's lymphoma is an infrequent lymphoma in our daily practice, even though its incidence is              increasing. Its diagnosis is straightforward, relying on histology coupled with immunohistochemistry. Although the treatment is well-defined by various international recommendations, it poses similar                 challenges for practitioners in resource-limited countries, including prolonged diagnostic delays  resulting in advanced disease and poor prognosis, inaccessibility to modern prognostic tools, and  difficulty accessing standard or innovative therapies. All these factors lead to a low remission rate. Improvement in technical facilities and better social coverage will likely enable a more effective management of Hodgkin's lymphoma in Togo.</p>
    </sec>
  </body>
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