Evidence map›Paper›PMID 38937803›Full record

Trial reportJournal of hematology & oncology2024

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

Swati Naik, Ying Li, Aimee C Talleur, Subodh Selukar, Emily Ashcraft, Cheng Cheng, Renee M Madden, Ewelina Mamcarz, Amr Qudeimat, Akshay Sharma and 16 more

Registry-linked trialAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Journal of hematology & oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01807611 (Haploidentical Donor Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation With a TLI Based Conditioning Regimen in Patients With Hematologic Malignancies), which is not on this map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01807611 phase2completednot on this map

Haploidentical Donor Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation With a TLI Based Conditioning Regimen in Patients With Hematologic Malignancies

TypeinterventionalSponsorSt. Jude Children's Research HospitalRan2013 to 2021Enrolled82ConditionsLeukemia, LymphomaArmsTotal Lymphoid Irradiation, Fludarabine, Cyclophosphamide, Thiotepa, Melphalan
3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Chronic graft-versus-host disease.Nature reviews. Disease primers · 2026
    Review
  6. Article
  7. Article
  8. Review
  9. Review
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  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Swati NaikDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA. swati.naik@stjude.org.
Ying LiDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Aimee C TalleurDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Subodh SelukarDepartment of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA.
Emily AshcraftDepartment of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA.
Cheng ChengDepartment of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA.
Renee M MaddenDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Ewelina MamcarzDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Amr QudeimatDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Akshay SharmaDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Ashok SrinivasanDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Ali Y SulimanDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Rebecca EpperlyDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Esther A ObengDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
M Paulina VelasquezDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Deanna LangfittDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Sarah SchellDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Jean-Yves MétaisDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Paula Y ArnoldDepartment of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
Diego R HijanoDepartment of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.
Gabriela MaronDepartment of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.
Thomas E MerchantDepartment of Radiation Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
Salem AkelDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Wing LeungDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Stephen GottschalkDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
Brandon M TriplettDepartment of Bone Marrow Transplantation & Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA. brandon.triplett@stjude.org.

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9M
NCI NIH HHS P30 CA021765
6 · The paper itself

Abstract

backgroundRelapse 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.

methodsIn 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.

resultsThe 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).

conclusionThe 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).

Indexed as

Hematologic NeoplasmsHematopoietic Stem Cell TransplantationKiller Cells, NaturalMemory T CellsTransplantation ConditioningTransplantation, HaploidenticalAdolescentAdultChildChild, PreschoolFemaleGraft vs Host DiseaseGraft vs Leukemia EffectHumansInfantMaleCD45RA depletionGraft-versus-leukemiaHaploidenticalImmune reconstitutionMemory T cellNK cellNon-TBI regimenPediatric hematological malignanciesT-cell depletionTransplantation

Identifiers

PMID38937803
PMCPMC11212178

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.