Randomized phase II trial comparing two dose levels of thymoglobulin in patients undergoing unrelated donor hematopoietic cell transplant Journal Article
| Authors: | Bashir, Q.; Munsell, M. F.; Giralt, S.; de Padua Silva, L.; Sharma, M.; Couriel, D.; Chiattone, A.; Popat, U.; Qazilbash, M. H.; Fernandez Vina, M.; Champlin, R. E.; De Lima, M. J. |
| Article Title: | Randomized phase II trial comparing two dose levels of thymoglobulin in patients undergoing unrelated donor hematopoietic cell transplant |
| Abstract: | The optimal dose and schedule of thymoglobulin (ATG) for graft-versus-host disease prevention (GVHD) is unknown. We compared two doses of ATG (4.5 mg/kg and 7.5 mg/kg) in a Bayesian adaptively randomized fashion, and assessed whether ATG levels measured on days 0, 7, 14 and 28 were associated with clinical outcomes. Treatment success was defined as the patient being alive, engrafted, in remission and without acute GVHD at day 100. Twenty patients received ATG 4.5 mg/kg (n = 15) or 7.5 mg/kg (n = 5) with reduced-intensity conditioning followed by unrelated donor hematopoietic cell transplant. The first 10 patients were fairly randomized, but the next 10 patients were adaptively randomized to the arm with higher success rate (4.5 mg/kg arm in this trial). The posterior mean treatment success rates for the ATG 4.5 mg/kg and ATG 7.5 mg/kg arms were 0.73 and 0.45, respectively. The posterior probability that the success rate was greater in the 4.5 mg/kg arm than in the 7.5 mg/kg arm was 0.93. There was no difference in the overall survival (p = 0.607), relapse-free survival (p = 0.607), treatment-related mortality (p = 0.131) or incidence of acute (p = 0.303) or chronic GVHD (p = 0.999) between the two doses. ATG levels were not associated with clinical outcomes. Thus, our results favor the use of ATG 4.5 mg/kg over ATG 7.5 mg/kg in patients undergoing unrelated donor hematopoietic cell transplant with reduced-intensity conditioning regimens. © 2012 Informa UK, Ltd. |
| Keywords: | adult; cancer survival; clinical article; controlled study; treatment outcome; treatment response; aged; middle aged; survival rate; acute granulocytic leukemia; overall survival; fludarabine; drug dose comparison; comparative study; methotrexate; follow up; bortezomib; phase 2 clinical trial; randomized controlled trial; melphalan; hematopoietic stem cell transplantation; dose-response relationship, drug; cancer regression; engraftment; myelodysplastic syndrome; graft versus host reaction; transplantation conditioning; remission induction; cancer relapse; drug blood level; graft survival; tacrolimus; graft vs host disease; thymocyte antibody; recurrence free survival; graft-versus-host disease; antibody blood level; atg; antilymphocyte serum; hematopoietic cell transplant |
| Journal Title: | Leukemia and Lymphoma |
| Volume: | 53 |
| Issue: | 5 |
| ISSN: | 1042-8194 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2012-05-01 |
| Start Page: | 915 |
| End Page: | 919 |
| Language: | English |
| DOI: | 10.3109/10428194.2011.634039 |
| PROVIDER: | scopus |
| PUBMED: | 22023525 |
| PMCID: | PMC3894827 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2012" - "CODEN: LELYE" - "Source: Scopus" |
