hoejdosisbehandling-autolog-stamcelletransplantation (LH Indholdsside)

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      <HtmlField Name="PageContent"><![CDATA[<h2>Definition<a href="https://hematology.dk/filer/vejledninger/diverse/Rekommandationer_for_stamcellemobilisering_h%C3%B8st_og_HDT_2018.pdf" data-type="other-reference" data-value="Rekommandationer for stamcellemobilisering/høst og højdosis kemoterapi med autolog stamcelletransplantation hos voksne. Udarbejdet af udvalg under Dansk Hæmatologisk Selskab 2018" data-url="https://hematology.dk/filer/vejledninger/diverse/Rekommandationer_for_stamcellemobilisering_h%C3%B8st_og_HDT_2018.pdf" title="Rekommandationer for stamcellemobilisering/høst og højdosis kemoterapi med autolog stamcelletransplantation hos voksne. Udarbejdet af udvalg under Dansk Hæmatologisk Selskab 2018">1</a></h2>
<ul>
    <li>H&oslash;jdosisbehandling med autolog stamcelletransplantation er en ressourcekr&aelig;vende terapi, som tilbydes&nbsp;udvalgte patienter med malign sygdom ved universitetssygehusene p&aring; 6 h&aelig;matologiske centre i Danmark </li>
    <li>Lymfompatienterne skal have sygdom, som er f&oslash;lsom for kemoterapi
    <ul>
        <li>Det vil sige, at man opn&aring;r en behandlingseffekt efter et begr&aelig;nset antal cytostatikabehandlinger med konventionelle doser cytostatika (induktionsbehandling) </li>
        <li>Desuden skal der foreligge dosis-respons-forhold mellem cytostatikadosis og kr&aelig;ftdr&aelig;bende effekt </li>
    </ul>
    </li>
    <li>H&oslash;jdosisbehandling er etableret praksis for:
    <ul>
        <li>Ubehandlede myelomatosepatienter under 65 &aring;r, hvor man dog kan g&aring; op til 70 &aring;r ved god almentilstand og ingen v&aelig;sentlig komorbiditet&nbsp;<a href="%20" title="Child JA, Morgan GJ, Davies FE et al, Medical Research Council adult Leukemia Working Party. High dose chemotherapy with hematopoietic stem cell rescue for multiple myeloma. N Engl J Med 2003;348: 1875-1883" data-url="reference-link" data-value="Child JA, Morgan GJ, Davies FE et al, Medical Research Council adult Leukemia Working Party. High dose chemotherapy with hematopoietic stem cell rescue for multiple myeloma. N Engl J Med 2003;348: 1875-1883" data-type="journal-reference" data-value-piped="Child JA, Morgan GJ, Davies FE et al|Medical Research Council adult Leukemia Working Party. High dose chemotherapy with hematopoietic stem cell rescue for multiple myeloma|N Engl J Med|2003|348|1875-1883">2</a></li>
        <li>Patienter med Mantle celle lymfom og ved visse T-cellelymfomer - her&nbsp;indg&aring;r autolog transplantation som&nbsp;1. linjebehandling <a href=" " data-type="journal-reference" data-value="Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E, Nordic Lymphoma Group., Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.. Blood 2008;112: 2687-93" data-value-piped="Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E, Nordic Lymphoma Group.|Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.|Blood|2008|112|2687-93|18625886" data-url="reference-link" data-pubmedid="18625886" title="Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E, Nordic Lymphoma Group., Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.. Blood 2008;112: 2687-93">3</a><sup>,</sup><a href="%20" title="d´Amore F, Relander T, Lauritzen GE et al, Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol 2012;30: 3093-3099" data-url="reference-link" data-value="d´Amore F, Relander T, Lauritzen GE et al, Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol 2012;30: 3093-3099" data-type="journal-reference" data-value-piped="d´Amore F, Relander T, Lauritzen GE et al|Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01|J Clin Oncol|2012|30|3093-3099">4</a>&nbsp;</li>
        <li>Udvalgte&nbsp;patienter med h&oslash;j-risiko malignt&nbsp;<a href="~/link.aspx?_id=25FC45605F1346C39C26A9873007A244&amp;_z=z">non-Hodgkins lymfom</a> og Hodgkins sygdom, som udvikler recidiv efter 1. linjebehandling&nbsp;eller progredierer under prim&aelig;rbehandlingen (refrakt&aelig;r sygdom) <a href="%20" title="Vose JM, Zhang M-J, Rowlings PA et al, Autologous transplantation for diffuse aggressive non-Hodgkin´s Lymphoma in patients never achieving remission:a report from the autologous blood and marrow transplant registry. J Clin Oncol 2001;19: 406-413" data-url="reference-link" data-value="Vose JM, Zhang M-J, Rowlings PA et al, Autologous transplantation for diffuse aggressive non-Hodgkin´s Lymphoma in patients never achieving remission:a report from the autologous blood and marrow transplant registry. J Clin Oncol 2001;19: 406-413" data-type="journal-reference" data-value-piped="Vose JM, Zhang M-J, Rowlings PA et al|Autologous transplantation for diffuse aggressive non-Hodgkin´s Lymphoma in patients never achieving remission:a report from the autologous blood and marrow transplant registry|J Clin Oncol|2001|19|406-413">5</a><sup>,</sup><a href="%20" title="Moskowitz CH, Kewelramani T, Nimer SD et al, Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin´s disease. Br J Haematol 2004;124: 645-652" data-url="reference-link" data-value="Moskowitz CH, Kewelramani T, Nimer SD et al, Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin´s disease. Br J Haematol 2004;124: 645-652" data-type="journal-reference" data-value-piped="Moskowitz CH, Kewelramani T, Nimer SD et al|Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin´s disease|Br J Haematol|2004|124|645-652">6</a>&nbsp;</li>
    </ul>
    </li>
    <li>Ved blandt andet&nbsp;<a href="~/link.aspx?_id=46FEE007B346407FBF2B7E5DB46C6492&amp;_z=z">testikelkr&aelig;ft</a> og amyloidose<a href=" " data-type="journal-reference" data-value="Dispenzieri A, Kyle RA, Lacy MQ, Therneau TM, Larson DR, Plevak MF, Rajkumar SV, Fonseca R, Greipp PR, Witzig TE, Lust JA, Zeldenrust SR, Snow DS, Hayman SR, Litzow MR, Gastineau DA, Tefferi A, Inwards DJ, Micallef IN, Ansell SM, Porrata LF, Elliott MA, Gertz MA, Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study.. Blood 2004;103: 3960-3" data-value-piped="Dispenzieri A, Kyle RA, Lacy MQ, Therneau TM, Larson DR, Plevak MF, Rajkumar SV, Fonseca R, Greipp PR, Witzig TE, Lust JA, Zeldenrust SR, Snow DS, Hayman SR, Litzow MR, Gastineau DA, Tefferi A, Inwards DJ, Micallef IN, Ansell SM, Porrata LF, Elliott MA, Gertz MA|Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study.|Blood|2004|103|3960-3|14739213" data-url="reference-link" data-pubmedid="14739213" title="Dispenzieri A, Kyle RA, Lacy MQ, Therneau TM, Larson DR, Plevak MF, Rajkumar SV, Fonseca R, Greipp PR, Witzig TE, Lust JA, Zeldenrust SR, Snow DS, Hayman SR, Litzow MR, Gastineau DA, Tefferi A, Inwards DJ, Micallef IN, Ansell SM, Porrata LF, Elliott MA, Gertz MA, Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study.. Blood 2004;103: 3960-3">7</a>&nbsp;er h&oslash;jdosisbehandling fortsat at betragte som eksperimentel behandling ved recidiv </li>
    <li>Enkelte b&oslash;rn med onkologiske diagnoser inkluderes i kliniske protokoller, som indeholder h&oslash;jdosisbehandling</li>
</ul>
<h2>Procedure</h2>
<ul>
    <li>Behandlingen indeb&aelig;rer, at patienten f&aring;r h&oslash;je doser med knoglemarvstoksiske medikamenter </li>
    <li>F&oslash;r selve behandlingen h&oslash;stes h&aelig;matopoietiske stamceller (CD34-positive celler)&nbsp;fra perifert blod ved hj&aelig;lp af afereseteknik
    <ul>
        <li>Efter en mobiliserings-kemoterapi og 4-5 dages behandling med granulocyt-kolonistimulerende faktor bliver h&oslash;st (aferese) af&nbsp;stamceller udf&oslash;rt ved brug af afereseudstyr, n&aring;r m&aelig;ngden af CD34-positive celler i perifert blod er tilstr&aelig;kkelig h&oslash;jt</li>
        <li>F&oslash;r aferese f&aring;r patienten indlagt centralt dobbeltl&oslash;bet venekateter, hvor fuldblod bliver trukket ud via det ene ben, og hvor fuldblod minus&nbsp;stamceller&nbsp;returneres til patienten via det andet ben</li>
        <li>Efter ca. 3-4 timer, n&aring;r 2,5-3 gange patientens blodvolumen er blevet&nbsp;behandlet i aferesemaskinen, er der h&oslash;stet et stamcelleprodukt, som indeholder 0,5-6 % CD34-positive celler</li>
    </ul>
    </li>
    <li>Stamcellerne fryses ned og opbevares ved -180 &deg;C </li>
    <li>2-3 d&oslash;gn efter h&oslash;jdosisbehandlingen, n&aring;r cytostatika-koncentrationen er under knoglemarvstoksisk niveau, t&oslash;s patientens stamceller op, for derefter at blive reinfunderet intraven&oslash;st via et anlagt centralt venekateter</li>
    <li>Stamcellerne finder tilbage til knoglemarven, hvor der er specielle receptorer for disse celler</li>
    <li>Knoglemarvsregeneration
    <ul>
        <li>Proliferation, differentiering og modning af de enkelte cellelinjer finder sted, mens patienten er i en aplasiperiode med&nbsp;um&aring;leligt lavt&nbsp;antal modne&nbsp;leukocytter i det&nbsp;perifere blod </li>
        <li>I denne periode er der stor infektionsrisiko, og de fleste patienter har cytostatikabivirkninger, ofte fra slimhinder i GI-kanalen (stomatitis/mucositis) og behov for bredspektret antibiotisk behandling samt blod- og trombocyttransfusioner</li>
    </ul>
    </li>
    <li>Som f&oslash;lge af knoglemarvsregeneration vil de h&aelig;matologiske blodv&aelig;rdier som regel stige efter ca. 10-14 dage, og knoglemarvsfunktionen normaliseres almindeligvis to til tre uger efter reinfusionen af stamcellerne</li>
</ul>
<h2>Overlevelse</h2>
<ul>
    <li>H&oslash;jdosisbehandling med autolog stamcellest&oslash;tte &oslash;ger median overlevelsestid for myelomatosepatienter med&nbsp;ca. 24&nbsp;m&aring;neder <a href="%20" title="Child JA, Morgan GJ, Davies FE et al, Medical Research Council adult Leukemia Working Party. High dose chemotherapy with hematopoietic stem cell rescue for multiple myeloma. N Engl J Med 2003;348: 1875-1883" data-url="reference-link" data-value="Child JA, Morgan GJ, Davies FE et al, Medical Research Council adult Leukemia Working Party. High dose chemotherapy with hematopoietic stem cell rescue for multiple myeloma. N Engl J Med 2003;348: 1875-1883" data-type="journal-reference" data-value-piped="Child JA, Morgan GJ, Davies FE et al|Medical Research Council adult Leukemia Working Party. High dose chemotherapy with hematopoietic stem cell rescue for multiple myeloma|N Engl J Med|2003|348|1875-1883">2</a>, men har ikke kurativt potentiale ved&nbsp;<a href="~/link.aspx?_id=FEA337568D6743A3B6DAE50693FED1CA&amp;_z=z">myelomatose</a> </li>
    <li>Ved malignt lymfom og&nbsp;<a href="~/link.aspx?_id=17C7F13511584F368A3FC390D88772CD&amp;_z=z">Hodgkins lymfom</a> har behandlingen kurativt potentiale, og der er ogs&aring; god dokumentation for, at den mediane overlevelsestid forl&aelig;nges&nbsp;<a href=" " data-type="journal-reference" data-value="Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E, Nordic Lymphoma Group., Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.. Blood 2008;112: 2687-93" data-value-piped="Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E, Nordic Lymphoma Group.|Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.|Blood|2008|112|2687-93|18625886" data-url="reference-link" data-pubmedid="18625886" title="Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E, Nordic Lymphoma Group., Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.. Blood 2008;112: 2687-93">3</a><sup>,</sup><a href="%20" title="d´Amore F, Relander T, Lauritzen GE et al, Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol 2012;30: 3093-3099" data-url="reference-link" data-value="d´Amore F, Relander T, Lauritzen GE et al, Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol 2012;30: 3093-3099" data-type="journal-reference" data-value-piped="d´Amore F, Relander T, Lauritzen GE et al|Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01|J Clin Oncol|2012|30|3093-3099">4</a><sup>,</sup><a href="%20" title="Vose JM, Zhang M-J, Rowlings PA et al, Autologous transplantation for diffuse aggressive non-Hodgkin´s Lymphoma in patients never achieving remission:a report from the autologous blood and marrow transplant registry. J Clin Oncol 2001;19: 406-413" data-url="reference-link" data-value="Vose JM, Zhang M-J, Rowlings PA et al, Autologous transplantation for diffuse aggressive non-Hodgkin´s Lymphoma in patients never achieving remission:a report from the autologous blood and marrow transplant registry. J Clin Oncol 2001;19: 406-413" data-type="journal-reference" data-value-piped="Vose JM, Zhang M-J, Rowlings PA et al|Autologous transplantation for diffuse aggressive non-Hodgkin´s Lymphoma in patients never achieving remission:a report from the autologous blood and marrow transplant registry|J Clin Oncol|2001|19|406-413">5</a><sup>,</sup><a href="%20" title="Moskowitz CH, Kewelramani T, Nimer SD et al, Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin´s disease. Br J Haematol 2004;124: 645-652" data-url="reference-link" data-value="Moskowitz CH, Kewelramani T, Nimer SD et al, Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin´s disease. Br J Haematol 2004;124: 645-652" data-type="journal-reference" data-value-piped="Moskowitz CH, Kewelramani T, Nimer SD et al|Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin´s disease|Br J Haematol|2004|124|645-652">6</a>&nbsp;</li>
    <li>H&oslash;jdosisbehandling kan have kurativt potentiale ved sarkom og testikelkr&aelig;ft ved recidiv og afpr&oslash;ves med henblik p&aring; dette </li>
    <li>I disse grupper kan prognosen betragtes som relativt god, hvis patienten er i live 18 m&aring;neder efter en s&aring;dan behandling </li>
    <li>For andre kr&aelig;fttyper er der begr&aelig;nset dokumentation for effekt af h&oslash;jdosisbehandling</li>
    <li>Den procedure-relaterede mortalitet ved h&oslash;jdosisbehandling&nbsp;er under 5 %</li>
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