Evidence map›Paper›PMID 19744131›Full record

Trial reportBritish journal of haematology2009

A phase I/II study of the safety and efficacy of the addition of sirolimus to tacrolimus/methotrexate graft versus host disease prophylaxis after allogeneic haematopoietic cell transplantation in paediatric acute lymphoblastic leukaemia (ALL).

Michael A Pulsipher, Donna A Wall, Michael Grimley, Rakesh K Goyal, Kenneth M Boucher, Patricia Hankins, Stephan A Grupp, Nancy Bunin

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of haematology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02177760 (Sirolimus in Prevention of aGVHD in Maternally Engrafted), which is not on this map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.3field-weighted citation impact, top 7% of its field
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.

NCT02177760 phase2withdrawnnot on this mapstarted 2014, after this paper: background citation

Sirolimus in Prevention of aGVHD in Maternally Engrafted (TME) Severe Combined Immunodeficiency (SCID) Infants Receiving Unconditioned Hematopoietic Stem Cell Transplant (HSCT)

TypeinterventionalSponsorUniversity of California, San FranciscoRan2014 to 2015Enrolled0ConditionsSevere Combined Immunodeficiency, Transplacental Maternal Engraftment, Stem Cell TransplantArmsSirolimus
3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Prevention and Treatment of Acute Graft-versus-Host Disease in Children, Adolescents, and Young Adults.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2020
    Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Sirolimus pharmacokinetics in early postmyeloablative pediatric blood and marrow transplantation.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2013
    Article
  11. Article
  12. Is pimecrolimus cream (1%) an appropriate therapeutic agent for the treatment of external ear atopic dermatitis?Medical science monitor : international medical journal of experimental and clinical research · 2012
    Article
  13. Strategies to prevent EBV reactivation and posttransplant lymphoproliferative disorders (PTLD) after allogeneic stem cell transplantation in high-risk patients.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2011
    Review
  14. High-risk pediatric acute lymphoblastic leukemia: to transplant or not to transplant?Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2011
    Review
  15. Review
  16. Should methotrexate plus calcineurin inhibitors be considered standard of care for prophylaxis of acute graft-versus-host disease?Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2010
    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

8 authors at 6 institutions in 2 countries.

Michael A PulsipherDivision of Hematology/Blood and Marrow Transplant, Primary Children's Medical Center, University of Utah School of Medicine, Salt Lake City, UT 84132-2408, USA. michael.pulsipher@hsc.utah.edu
Donna A Wall
Michael Grimley
Rakesh K Goyal
Kenneth M Boucher
Patricia Hankins
Stephan A Grupp
Nancy Bunin
Children's Hospital of Philadelphia · USChildren's Hospital of Pittsburgh · USHuntsman Cancer Institute · USMethodist Children’s Hospital · USPrimary Children's Hospital · USUniversity of Manitoba · CA

Funding

USE OF mTOR INHIBITORS IN B CELL LEUKEMIAR01CA102646 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI GRUPP, STEPHAN A. · 2005 to 2009
$1.6M
Determinants of Relapse Risk After BMT for ALLR01CA116660 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI GRUPP, STEPHAN A. · 2007 to 2011
$1.5M
NCI NIH HHS CA102646NCI NIH HHS CA1116660NCI NIH HHS R01 CA102646NCI NIH HHS R01 CA116660
6 · The paper itself

Abstract

Sirolimus has been shown to have activity against human acute lymphoblastic leukaemia at serum levels used for immunosuppression. We hypothesized that the addition of sirolimus to a tacrolimus/methotrexate graft-versus-host disease (GVHD) prophylaxis regimen would decrease relapse after haematopoietic stem cell transplantation and initiated a phase I/II study to demonstrate safety, feasibility, and efficacy. The study cohort included 18 patients in high-risk (HR) first complete remission (CR1), 16 in HR CR2, 17 in intermediate risk (IR) CR2, and 12 in CR3+. The 2-year event-free survival (EFS) of the cohort was 66% (standard error 6.4). EFS of risk groups was 74%, 81%, 44% and 46% for CR1, IR CR2, HR CR2 and CR3+ patients respectively, and did not differ by stem cell source. Cumulative incidence of acute GVHD grade II-IV and III-IV was 38% and 21% respectively, while the cumulative incidence of chronic GVHD was 32%. Cumulative incidence of transplant-related mortality and relapse was 10% and 25% respectively. Significant toxicities included veno-occlusive disease [seven patients (11%)], transplant-associated microangiopathy (three patients), and idiopathic pneumonitis (one patient). In summary, sirolimus-based GVHD prophylaxis can be given safely in this population and early survival results are promising. A phase III trial to test whether sirolimus decreases relapse and improves outcome after transplantation for ALL is ongoing.

Indexed as

AdolescentChildChild, PreschoolEpidemiologic MethodsFemaleGraft SurvivalGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansImmunosuppressive AgentsInfantMaleMethotrexatePrecursor Cell Lymphoblastic Leukemia-LymphomaRecurrenceSirolimusImmunosuppressive AgentsMethotrexateSirolimusTacrolimus

Identifiers

PMID19744131
PMCPMC2888481
OpenAlexW1979916062

What OpenQuestion holds

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Read underepoch 390

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.