Academic Journal
Impaired T- And NK-cell reconstitution after haploidentical HCT with posttransplant cyclophosphamide
| العنوان: | Impaired T- And NK-cell reconstitution after haploidentical HCT with posttransplant cyclophosphamide |
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| المؤلفون: | Rambaldi B., Kim H. T., Reynolds C., Rai S. C., Arihara Y., Kubo T., Buon L., Gooptu M., Koreth J., Cutler C., Nikiforow S., Ho V. T., Alyea E. P., Antin J. H., Wu C. J., Soiffer R. J., Ritz J., Romee R. |
| المساهمون: | Rambaldi, B, Kim, H, Reynolds, C, Rai, S, Arihara, Y, Kubo, T, Buon, L, Gooptu, M, Koreth, J, Cutler, C, Nikiforow, S, Ho, V, Alyea, E, Antin, J, Wu, C, Soiffer, R, Ritz, J, Romee, R |
| بيانات النشر: | American Society of Hematology US |
| سنة النشر: | 2021 |
| المجموعة: | Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| مصطلحات موضوعية: | CD16 antigen, CD4 antigen, CD56 antigen, cyclophosphamide, interleukin 15, killer cell immunoglobulin like receptor, methotrexate, mycophenolate mofetil, natural killer cell receptor NKG2A, programmed death 1 receptor, tacrolimus |
| الوصف: | Administration of posttransplant cyclophosphamide (PTCy) has significantly expanded the number of patients undergoing HLA-haploidentical hematopoietic cell transplantation (haplo-HCT). To examine immune reconstitution in these patients, we monitored T- and natural killer (NK)-cell recovery in 60 patients receiving bone marrow or peripheral blood stem cell (PBSC) grafts after haplo-HCT with PTCy and 35 patients receiving HLA-matched donor PBSC grafts with standard graft-versus-host disease (GVHD) prophylaxis. Compared with HLA-matched recipients, early T-cell recovery was delayed in haplo-HCT patients and skewed toward effector memory T cells with markedly reduced naive T cells. We found higher regulatory T (Treg)-cell/conventional T (Tcon)-cell ratios early after HCT and increased PD-1 expression on memory T cells. Within the haplo-HCT, patients who did not develop chronic GVHD (cGVHD) had higher PD-1 expression on central and effector memory CD41 Treg cells at 1 month after transplant. These findings suggest an immunologic milieu that promotes immune tolerance in haplo-HCT patients. NK cells were decreased early after haplo-HCT with preferential expansion of immature CD56brightCD162 NK cells compared with matched donor transplants. One month after transplant, mass cytometry revealed enrichment of immature NK-cell metaclusters with high NKG2A, low CD57, and low killercell immunoglobulin-like receptor expression after haplo-HCT, which partially recovered 3 months post-HCT. At 2 months, immature NK cells from both groups were functionally impaired, but interleukin-15 priming corrected these defects in vitro. Increased immature/ mature NK-cell ratios were associated with cytomegalovirus reactivation and increased incidence of cGVHD after haplo-HCT. These homeostatic imbalances in T- and NK-cell reconstitution after haplo-HCT reveal opportunities for early immune-based interventions to optimize clinical outcomes. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/33496734; info:eu-repo/semantics/altIdentifier/wos/WOS:000613791800002; volume:5; issue:2; firstpage:352; lastpage:364; numberofpages:13; journal:BLOOD ADVANCES; https://hdl.handle.net/10281/524262 |
| DOI: | 10.1182/bloodadvances.2020003005 |
| الاتاحة: | https://hdl.handle.net/10281/524262 https://doi.org/10.1182/bloodadvances.2020003005 |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.5665D5BF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1182/bloodadvances.2020003005 |
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