Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial.
J Hematol Oncol
; 17(1): 50, 2024 Jun 27.
Article
de En
| MEDLINE
| ID: mdl-38937803
ABSTRACT
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% CI72-98) 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).Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cellules tueuses naturelles
/
Transplantation de cellules souches hématopoïétiques
/
Tumeurs hématologiques
/
Conditionnement pour greffe
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Greffe haplo-identique
/
Cellules T mémoire
Limites:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
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Infant
/
Male
Langue:
En
Journal:
J Hematol Oncol
Sujet du journal:
HEMATOLOGIA
/
NEOPLASIAS
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique
Pays de publication:
Royaume-Uni