{"id":5621,"date":"2021-05-21T01:58:30","date_gmt":"2021-05-20T23:58:30","guid":{"rendered":"https:\/\/meddists.com\/learn\/clinical\/hematology\/bone-marrow-transplantation\/"},"modified":"2021-05-27T23:11:26","modified_gmt":"2021-05-27T21:11:26","slug":"stem-cell-transplantation","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/hematology\/stem-cell-transplantation\/","title":{"rendered":"Stem cell transplantation"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><div class=\"intro\">Stem cell transplantation (SCT) involves eliminating the patient\u2019s hemopoietic and immune system by chemotherapy and\/or radiotherapy and replacing it with stem cells either from another individual or with a previously harvested portion of the patient\u2019s own hemopoietic stem cells.<\/div><\/p>\n\n\n<span class=\"block-heading\" id=\"header_1\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">HLA system<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_1\">\n\n\n<p class=\"wp-block-paragraph\">Stands for <strong>human leukocyte antigen<\/strong> system; highly polymorphic, coding for the MHC complexes.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>MHC I are found on every nucleated cell (self-presenting antigen) &#8211; HLA-A, HLA-B, HLA-C<\/li><li>MHC II are found on antigen-presenting cells &#8211; HLA-DR, HLA-DQ, HLA-DP<\/li><li>MHC III are soluble components &#8211; HSP70, TNF<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_2\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Classification<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_2\">\n\n<\/span><span class=\"block-heading\" id=\"header_3\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">According to the source<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_3\">\n\n\n<ul class=\"wp-block-list\"><li>Bone marrow transplantation (BMT)<\/li><li>Peripheral blood stem cell (PBSC) transplantation<\/li><li>Umbilical cord transplantation<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_4\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">According to the donor<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_4\">\n\n\n<figure class=\"wp-block-table is-style-stripes\"><table class=\"pure-table\"><thead><tr><th><\/th><th>Autologous<\/th><th>Allogenic<\/th><\/tr><\/thead><tbody><tr><td><strong>Donor types<\/strong><\/td><td>From self<\/td><td>Synergenic (identical twins)<br>HLA-matching siblings<br>Haploidentical (parent to child)<br>Unrelated HLA-matching donor<br>Umbilical cord blood<\/td><\/tr><tr><td><strong>Indications<\/strong><\/td><td>Lymphomas, MM, amyloidosis<\/td><td>AML, ALL, CML, MDS, lymphomas, MM, myelofibrosis<br>Hemoglobinopathies, PNH, aplastic anemia<\/td><\/tr><tr><td><strong>Conditioning<\/strong><\/td><td>Myeloablative<br>Lymphoablative<\/td><td>Myeloablative<br>Reduced-intensity<br>Non-myeloablative<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n<\/span><span class=\"block-heading\" id=\"header_5\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Steps<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_5\">\n\n\n<ul class=\"wp-block-list\"><li><strong>Collection<\/strong><ul><li>PBSC collection is preferred nowadays.<ul><li>The donor is given <strong>G-CSF<\/strong> to stimulate the growth of granulocytes, and <strong>plerixafor<\/strong> to reduce their adhesion to the bone marrow and mobilize them to the peripheral blood.<\/li><li>The donor is then connected to a cell separator machine through a double-lumen cannula; the machine collects the mononuclear cells while RBCs are pumped back into the donor.<\/li><li>It may take up to a week to complete the process.<\/li><\/ul><\/li><li>Bone marrow collection<ul><li>~500mL of bone marrow can be harvested from the pelvis under general anesthesia.<\/li><\/ul><\/li><\/ul><\/li><li><strong>Stem cell processing<\/strong><ul><li>RBCs are removed, mononuclear cells are concentrated.<\/li><li>In some cases, T-cells are removed (to avoid GVHD).<\/li><li>Chemotherapy and monoclonal antibodies can be used to remove residual cells (in an autologous collection).<\/li><\/ul><\/li><li><strong>Conditioning<\/strong><ul><li>Eradicates the patient\u2019s hemopoietic and immune system malignant cells, as well as prevents rejection.<\/li><li>Myeloablative conditioning, total-body irradiation + chemotherapy (cyclophosphamide, etoposide).<\/li><li>Lymphoablative conditioning includes anti-thymocyte globulin and alemtuzumab (anti-CD52).<\/li><li>Non-myeloablative conditioning does not completely destroy the patient&#8217;s hematopoietic system, using low-dose chemotherapy.<\/li><\/ul><\/li><li><strong>Transplantation<\/strong><ul><li>Engraftment is usually quicker following PBSC transplantation compared with BMT<\/li><\/ul><\/li><li><strong>Post-transplant engraftment and immunity<\/strong><\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_6\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Autologous transplantation<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_6\">\n\n\n<p class=\"wp-block-paragraph\">Possible in case that the cells of the marrow are not affected by the primary disease. It is not considered a &#8220;true&#8221; transplantation, as transplantation refers to implantation of foreign tissues. It&#8217;s a way to &#8220;reset&#8221; the adaptive immune system.<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li><strong>Collection<\/strong><ol><li>Preparation (treat all infections, make sure patient is in remission)<\/li><li>Chemotherapy (cyclophosphamide, etoposide), G-CSF administration<\/li><li>When WBC begins rising, administer plerixafor<\/li><li>Perform collection (plasmapheresis)<\/li><li>Process and store in liquid nitrogen<\/li><\/ol><\/li><li><strong>Conditioning<\/strong><ul><li>Very high-dose chemotherapy +- radiotherapy<\/li><\/ul><\/li><li><strong>Transplantation<\/strong><ol><li>36 hours after chemo has finished, thaw and infuse the stem cells<\/li><li>Prophylactic therapy (G-CSF, heparin, antimicrobial agents)<\/li><li>RBC, PLT transfusions (ONLY FILTERED, IRRADIATED BLOOD PRODUCTS!)<\/li><\/ol><\/li><li><strong>Post-transplant engraftment and immunity<\/strong><ol><li>The engraftment is evident within 2 weeks, but the reserve remains impaired for 1-2 years.<\/li><li>Profound immunodeficiency for 3-12 months with low T-helper count.<\/li><li>Frequent checks up to 100 days after the transplantation; additional evaluation with imaging + lab tests.<\/li><\/ol><\/li><\/ol>\n\n\n<\/span><span class=\"block-heading\" id=\"header_7\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Allogenic transplantation<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_7\">\n\n\n<p class=\"wp-block-paragraph\">The major complications include infections and GVHD, as well as high mortality. In many cases, used directly as &#8220;graft-vs-leukemia&#8221; treatment (although umbilical blood is not good for this purpose).<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_8\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Donor\u2013recipient HLA-matching<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_8\">\n\n\n<p class=\"wp-block-paragraph\">The different resolutions used can help determine the outcome of the transplantation based on the differences between the donor&#8217;s and the recipient&#8217;s HLAs. If both the donor and recipient are completely the same:<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>HLA-A, B, C matching is 6\/6<\/li><li>HLA-A, B, C, DR matching is 8\/8<\/li><li>HLA-A, B, C, DR, DQ matching is 10\/10<\/li><li>HLA-A, B, C, DR, DQ, DP matching is 12\/12<\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">A minimum of 7\/8 matching is required; the higher the better.<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_9\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Steps in allogenic transplantation<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_9\">\n\n\n<ol class=\"wp-block-list\"><li>Conditioning<\/li><li>Transplantation<\/li><li>Monitoring and managing the GVHD, infections<\/li><li>Supportive treatment (fluids, antimicrobial treatment)<\/li><li>Monitoring chimerism using PCR or FISH (checking if both donor&#8217;s blood cells are in the circulation). Ideally, we want full donor chimerism = only donor cells in the circulation.<\/li><li>Immune suppression<\/li><li>RBC, PLT transfusions (ONLY FILTERED, IRRADIATED BLOOD PRODUCTS! note the new blood group!)<\/li><li>Close follow-up for the next year, although relapse may occur even after 10 years.<\/li><\/ol>\n\n\n<\/span><span class=\"block-heading\" id=\"header_10\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Immune suppression<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_10\">\n\n\n<ol class=\"wp-block-list\"><li><strong>Conventional drugs (1st phase)<\/strong><ol><li>Steroids (Prednisone: 0.1-10 mg\/kg)<\/li><li>Azathioprine (1mg\/kg)<\/li><li>Cyclophosphamide (10mg\/kg)<\/li><li>Methotrexate (0.2mg\/kg)<\/li><\/ol><\/li><li><strong>Calcineurin inhibitors (2nd phase)<\/strong><ol><li>Cyclosporin A (2-10mg\/kg)<\/li><li>Tacrolimus<\/li><li>Sirolimus<\/li><li>Gusperimus<\/li><\/ol><\/li><li><strong>Purine and pyrimidine antagonists<\/strong><ol><li>Azathioprine = Imuran<\/li><li>Mycophenolate<strong> <\/strong>mofetil = CellCept<\/li><li>Sodium-brequinar (highly lymphocyte specific)<\/li><\/ol><\/li><li><strong>Monoclonal antibodies<\/strong><ol><li>Anti-IL2, anti-TNF<\/li><li>Anti-IL2R (anti-TAC)<\/li><li>Anti-CD3 (OKT3)<\/li><li>Anti-CD4<\/li><li>Anti-LFA1, anti-ICAM1 (experimental)<\/li><\/ol><\/li><li><strong>CAR-T cells<\/strong><\/li><\/ol>\n<\/span><div id=\"the_titles\" style=\"display:none;\"><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">HLA system<\/h3><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Classification<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">According to the source<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">According to the donor<\/h4><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Steps<\/h3><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Autologous transplantation<\/h3><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Allogenic transplantation<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Donor\u2013recipient HLA-matching<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Steps in allogenic transplantation<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Immune suppression<\/h4><\/div>","protected":false},"excerpt":{"rendered":"<p>HLA system Stands for human leukocyte antigen system; highly polymorphic, coding for the MHC complexes. MHC I are found on every nucleated cell (self-presenting antigen) &#8211; HLA-A, HLA-B, HLA-C MHC II are found on antigen-presenting cells &#8211; HLA-DR, HLA-DQ, HLA-DP MHC III are soluble components &#8211; HSP70, TNF Classification According to the source Bone marrow [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":4472,"menu_order":8,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-5621","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.9 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Stem cell transplantation &#8211; Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/hematology\/stem-cell-transplantation\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/hematology\\\/stem-cell-transplantation\\\/\",\"url\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/hematology\\\/stem-cell-transplantation\\\/\",\"name\":\"Stem cell transplantation &#8211; 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