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Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial.

التفاصيل البيبلوغرافية
العنوان: Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial.
المؤلفون: Naik S; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA. swati.naik@stjude.org., Li Y; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Talleur AC; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Selukar S; Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA., Ashcraft E; Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA., Cheng C; Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA., Madden RM; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Mamcarz E; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Qudeimat A; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Sharma A; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Srinivasan A; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Suliman AY; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Epperly R; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Obeng EA; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Velasquez MP; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Langfitt D; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Schell S; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Métais JY; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Arnold PY; Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA., Hijano DR; Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA., Maron G; Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA., Merchant TE; Department of Radiation Oncology, St Jude Children's Research Hospital, Memphis, TN, USA., Akel S; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Leung W; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Gottschalk S; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA., Triplett BM; Department of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA. brandon.triplett@stjude.org.
المصدر: Journal of hematology & oncology [J Hematol Oncol] 2024 Jun 27; Vol. 17 (1), pp. 50. Date of Electronic Publication: 2024 Jun 27.
نوع المنشور: Clinical Trial, Phase II; Journal Article
اللغة: English
بيانات الدورية: Publisher: Biomed Central Country of Publication: England NLM ID: 101468937 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-8722 (Electronic) Linking ISSN: 17568722 NLM ISO Abbreviation: J Hematol Oncol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Biomed Central, 2008-
مواضيع طبية MeSH: Killer Cells, Natural*/transplantation , Killer Cells, Natural*/immunology , Transplantation, Haploidentical*/methods , Hematopoietic Stem Cell Transplantation*/methods , Hematopoietic Stem Cell Transplantation*/adverse effects , Transplantation Conditioning*/methods , Memory T Cells* , Hematologic Neoplasms*/therapy, Humans ; Female ; Male ; Child ; Adolescent ; Child, Preschool ; Graft vs Host Disease/prevention & control ; Graft vs Host Disease/etiology ; Infant ; Young Adult ; Adult ; Treatment Outcome ; Graft vs Leukemia Effect
مستخلص: Background: Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated with acute and long-term adverse effects. We used a CD45RA-depleted haploidentical graft for adoptive transfer of memory T cells combined with NK-cell addback and hypothesized that maximizing the graft-versus-leukemia (GVL) effect might allow for reduction in intensity of conditioning regimen.
Methods: In this phase II clinical trial (NCT01807611), 72 patients with hematological malignancies (complete remission (CR)1: 25, ≥ CR2: 28, refractory disease: 19) received haploidentical CD34 + enriched and CD45RA-depleted hematopoietic progenitor cell grafts followed by NK-cell infusion. Conditioning included fludarabine, thiotepa, melphalan, cyclophosphamide, total lymphoid irradiation, and graft-versus-host disease (GVHD) prophylaxis consisted of a short-course sirolimus or mycophenolate mofetil without serotherapy.
Results: The 3-year overall survival (OS) and event-free-survival (EFS) for patients in CR1 were 92% (95% CI:72-98) and 88% (95% CI: 67-96); ≥ CR2 were 81% (95% CI: 61-92) and 68% (95% CI: 47-82) and refractory disease were 32% (95% CI: 11-54) and 20% (95% CI: 6-40). The 3-year EFS for all patients in morphological CR was 77% (95% CI: 64-87) with no difference amongst recipients with or without minimal residual disease (P = 0.2992). Immune reconstitution was rapid, with mean CD3 and CD4 T-cell counts of 410/μL and 140/μL at day + 30. Cumulative incidence of acute GVHD and chronic GVHD was 36% and 26% but most patients with acute GVHD recovered rapidly with therapy. Lower rates of grade III-IV acute GVHD were observed with NK-cell alloreactive donors (P = 0.004), and higher rates of moderate/severe chronic GVHD occurred with maternal donors (P = 0.035).
Conclusion: The combination of a CD45RA-depleted graft and NK-cell addback led to robust immune reconstitution maximizing the GVL effect and allowed for use of a submyeloablative, TBI-free conditioning regimen that was associated with excellent EFS resulting in promising long-term outcomes in this high-risk population. The trial is registered at ClinicalTrials.gov (NCT01807611).
(© 2024. The Author(s).)
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فهرسة مساهمة: Keywords: CD45RA depletion; Graft-versus-leukemia; Haploidentical; Immune reconstitution; Memory T cell; NK cell; Non-TBI regimen; Pediatric hematological malignancies; T-cell depletion; Transplantation
سلسلة جزيئية: ClinicalTrials.gov NCT01807611
تواريخ الأحداث: Date Created: 20240627 Date Completed: 20240628 Latest Revision: 20240630
رمز التحديث: 20240630
مُعرف محوري في PubMed: PMC11212178
DOI: 10.1186/s13045-024-01567-0
PMID: 38937803
قاعدة البيانات: MEDLINE
الوصف
تدمد:1756-8722
DOI:10.1186/s13045-024-01567-0