{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:43:06Z","timestamp":1792446186256,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T00:00:00Z","timestamp":1589500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: T lymphocyte collection through leukapheresis is an essential step for chimeric antigen receptor T (CAR-T) cell therapy. Timing of apheresis is challenging in heavily pretreated patients who suffer from rapid progressive disease and receive T cell impairing medication. Methods: A total of 75 unstimulated leukaphereses were analyzed including 45 aphereses in patients and 30 in healthy donors. Thereof, 41 adult patients with Non-Hodgkin\u2019s lymphoma (85%) or acute lymphoblastic leukemia (15%) underwent leukapheresis for CAR-T cell production. Results: Sufficient lymphocytes were harvested from all patients even from those with low peripheral lymphocyte counts of 0.18\/nL. Only four patients required a second leukapheresis session. Leukapheresis products contained a median of 98 \u00d7 108 (9 - 341 \u00d7 108) total nucleated cells (TNC) with 38 \u00d7 108 (4 - 232 \u00d7 108) CD3+ T cells. Leukapheresis products from healthy donors as well as from patients in complete remission were characterized by high TNC and CD3+ T lymphocyte counts. CAR-T cell products could be manufactured for all but one patient. Conclusions: Sufficient yield of lymphocytes for CAR-T cell production is feasible also for patients with low peripheral blood counts. Up to 12\u201315 L blood volume should be processed in patients with absolute lymphocyte counts \u2264 1.0\/nL.<\/jats:p>","DOI":"10.3390\/cells9051225","type":"journal-article","created":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T10:53:59Z","timestamp":1589540039000},"page":"1225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Current Challenges in Providing Good Leukapheresis Products for Manufacturing of CAR-T Cells for Patients with Relapsed\/Refractory NHL or ALL"],"prefix":"10.3390","volume":"9","author":[{"given":"Felix","family":"Korell","sequence":"first","affiliation":[{"name":"Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Laier","sequence":"additional","affiliation":[{"name":"Institute of Clinical Transfusion Medicine and Cell Therapy (IKTZ), 89081 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Sauer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaya","family":"Veelken","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Hennemann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Luisa","family":"Schubert","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Sauer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Pavel","sequence":"additional","affiliation":[{"name":"Institute of Clinical Transfusion Medicine and Cell Therapy (IKTZ), 89081 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Mueller-Tidow","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dreger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1056\/NEJMoa1804980","article-title":"Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma","volume":"380","author":"Schuster","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene ciloleucel car t-cell therapy in refractory large B-cell lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2040620719841581","DOI":"10.1177\/2040620719841581","article-title":"Car T-cell therapy for B-cell lymphomas: Clinical trial results of available products","volume":"10","author":"Chavez","year":"2019","journal-title":"Ther. Adv. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1089\/hum.2016.097","article-title":"Chimeric antigen receptor T cell therapy targeting cd19-positive leukemia and lymphoma in the context of stem cell transplantation","volume":"27","author":"Schubert","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1002\/ijc.31147","article-title":"Chimeric antigen receptor transduced T cells: Tuning up for the next generation","volume":"142","author":"Schubert","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.tmrv.2016.03.001","article-title":"Car-T cell therapies from the transfusion medicine perspective","volume":"30","author":"Fesnak","year":"2016","journal-title":"Transfus. Med. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4108","DOI":"10.1182\/blood-2019-131399","article-title":"A characterization of bridging therapies leading up to commercial car T-cell therapy","volume":"134","author":"Hughes","year":"2019","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e026644","DOI":"10.1136\/bmjopen-2018-026644","article-title":"Treatment of patients with relapsed or refractory cd19+ lymphoid disease with T lymphocytes transduced by rv-sfg.Cd19.Cd28.4-1bbzeta retroviral vector: A unicentre phase i\/ii clinical trial protocol","volume":"9","author":"Schubert","year":"2019","journal-title":"BMJ Open"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1200\/JCO.2013.54.8800","article-title":"Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano classification","volume":"32","author":"Cheson","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e170580","DOI":"10.1001\/jamaoncol.2017.0580","article-title":"Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: A meta-analysis","volume":"3","author":"Berry","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_11","first-page":"3602","article-title":"Diffuse large B-cell lymphoma: 10 years\u2019 real-world clinical experience with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone","volume":"15","author":"Horvat","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/annonc\/mdj030","article-title":"Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: The British Columbia experience","volume":"17","author":"Savage","year":"2006","journal-title":"Ann. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1111\/trf.12506","article-title":"Unstimulated leukapheresis in patients and donors: Comparison of two apheresis systems","volume":"54","author":"Schulz","year":"2014","journal-title":"Transfusion"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"543531","DOI":"10.4061\/2010\/543531","article-title":"DNA damage induced by alkylating agents and repair pathways","volume":"2010","author":"Kondo","year":"2010","journal-title":"J. Nucleic Acids"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"222","DOI":"10.2174\/157436209789057502","article-title":"The inhibitory effect of cyclosporine a and prednisolone on both cytotoxic cd8+ T cells and cd4+cd25+ regulatory T cells","volume":"4","author":"Fei","year":"2009","journal-title":"Curr. Signal Transduct. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2165\/00003088-200544010-00003","article-title":"Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids","volume":"44","author":"Czock","year":"2005","journal-title":"Clin. Pharmacokinet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1002\/art.37966","article-title":"Glucocorticoids suppress T cell function by up-regulating microrna-98","volume":"65","author":"Davis","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_18","first-page":"625","article-title":"Effect of corticosteroids on the human immune response: Comparison of one and three daily 1 gm intravenous pulses of methylprednisolone","volume":"91","author":"Fan","year":"1978","journal-title":"J. Lab. Clin. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23002","DOI":"10.1038\/srep23002","article-title":"Effects of systemically administered hydrocortisone on the human immunome","volume":"6","author":"Olnes","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.omtm.2017.03.002","article-title":"Viral vector-based innovative approaches to directly abolishing tumorigenic pluripotent stem cells for safer regenerative medicine","volume":"5","author":"Mitsui","year":"2017","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1182\/blood.V91.1.347","article-title":"Impaired induction of the cd28-responsive complex in granulocyte colony-stimulating factor mobilized cd4 T cells","volume":"91","author":"Tanaka","year":"1998","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/phar.1900","article-title":"Chimeric antigen receptor T cells in hematologic malignancies","volume":"37","author":"Shank","year":"2017","journal-title":"Pharmacotherapy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1093\/cid\/cit684","article-title":"2013 IDSA clinical practice guideline for vaccination of the immunocompromised host","volume":"58","author":"Rubin","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","unstructured":"Lee, D.W., and Shah, N.N. (2020). Chapter 4\u2014Peri-car T-cell management. Chimeric Antigen Receptor T-Cell Therapies for Cancer, Elsevier."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1002\/cpt.1396","article-title":"Bispecific antibodies in the treatment of hematologic malignancies","volume":"106","author":"Duell","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s40262-017-0619-0","article-title":"Antibody-drug conjugates: Pharmacokinetic\/pharmacodynamic modeling, preclinical characterization, clinical studies, and lessons learned","volume":"57","author":"Hedrich","year":"2018","journal-title":"Clin. Pharmacokinet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1208\/s12248-016-9929-7","article-title":"Preclinical to clinical translation of antibody-drug conjugates using pk\/pd modeling: A retrospective analysis of inotuzumab ozogamicin","volume":"18","author":"Betts","year":"2016","journal-title":"AAPS J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6226","DOI":"10.1182\/blood-2012-01-400515","article-title":"Immunopharmacologic response of patients with b-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging cd19\/cd3-bispecific bite antibody blinatumomab","volume":"119","author":"Klinger","year":"2012","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1182\/blood-2015-11-679134","article-title":"Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia","volume":"127","author":"Fraietta","year":"2016","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1158\/1078-0432.CCR-15-1527","article-title":"The addition of the BTK inhibitor ibrutinib to anti-cd19 chimeric antigen receptor T cells (CART19) improves responses against mantle cell lymphoma","volume":"22","author":"Ruella","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7509","DOI":"10.1200\/JCO.2017.35.15_suppl.7509","article-title":"Cd19 car-T cells combined with ibrutinib to induce complete remission in CLL","volume":"35","author":"Gill","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_32","unstructured":"Hoffman, R.B., Heslop, H., and Weitz, J. (2018). Chapter T cell therapy of hematological diseases. Hematology: Basic Principles and Practice, Elsevier. [7th ed.]."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1111\/trf.14003","article-title":"Autologous lymphapheresis for the production of chimeric antigen receptor T cells","volume":"57","author":"Allen","year":"2017","journal-title":"Transfusion"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1111\/trf.14569","article-title":"Lymphocyte apheresis for chimeric antigen receptor T-cell manufacturing in children and young adults with leukemia and neuroblastoma","volume":"58","author":"Ceppi","year":"2018","journal-title":"Transfusion"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1038\/s41591-018-0201-9","article-title":"Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell","volume":"10","author":"Ruella","year":"2018","journal-title":"Nat. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/5\/1225\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:29:10Z","timestamp":1760174950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/5\/1225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,15]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["cells9051225"],"URL":"https:\/\/doi.org\/10.3390\/cells9051225","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,15]]}}}