Journal article
A phase II multicenter rabbit anti-thymocyte globulin trial in patients with myelodysplastic syndromes identifying a novel model for response prediction
Haematologica (Roma), Vol.99(7), pp.1176-1183
07/2014
DOI: 10.3324/haematol.2012.083345
PMCID: PMC4077078
PMID: 24488560
Abstract
Immune dysregulation is a mechanism contributing to ineffective hematopoiesis in a subset of myelodysplastic syndrome patients. We report the first US multicenter non-randomized, phase II trial examining the efficacy of rabbit(r)-anti-thymocyte globulin using 2.5 mg/kg/day administered daily for 4 doses. The primary end point was hematologic response; secondary end points included duration of response, time to response, time to progression, and tolerance. Nine (33%;95% confidence interval=17%-54%) of the 27 patients treated experienced durable hematologic improvement in an intent-to-treat analysis with a median time to response and median response duration of 75 and 245 days, respectively. While younger age is the most significant factor favoring equine(e)-anti-thymocyte globulin response, treatment outcome on this study was independent of age (P=0.499). A shorter duration between diagnosis and treatment showed a positive trend (P=0.18), but International Prognostic Scoring System score (P=0.150), karyotype (P=0.319), and age-adjusted bone marrow cellularity (P=0.369) were not associated with response classification. Since activated T-lymphocytes are the primary cellular target of anti-thymocyte globulin, a T-cell expression profiling was conducted in a cohort of 38 patients consisting of rabbit and equine-antithymocyte globulin-treated patients. A model containing disease duration, CD8 terminal memory T cells and T-cell proliferation-associated-antigen expression predicted response with the greatest accuracy using a leave-one-out cross validation approach. This profile categorized patients independent of other covariates, including treatment type and age using a leave-one-out-cross-validation approach (75.7%). Therefore, rabbit-anti-thymocyte globulin has hematologic remitting activity in myelodysplastic syndrome and a T-cell activation profile has potential utility classifying those who are more likely to respond (NCT00466843 clinicaltrials.gov).
Details
- Title: Subtitle
- A phase II multicenter rabbit anti-thymocyte globulin trial in patients with myelodysplastic syndromes identifying a novel model for response prediction
- Creators
- Rami S Komrokji - Moffitt Cancer CenterAdam W Mailloux - Moffitt Cancer CenterDung-Tsa Chen - Moffitt Cancer CenterMikkael A Sekeres - Cleveland ClinicRonald Paquette - UCLA Medical CenterWilliam J Fulp - Moffitt Cancer CenterChiharu Sugimori - Ishikawa Prefectural Central HospitalJennifer Paleveda-Pena - Moffitt Cancer CenterJaroslaw P Maciejewski - Cleveland ClinicAlan F List - Moffitt Cancer CenterPearlie K Epling-Burnette - Moffitt Cancer Center
- Resource Type
- Journal article
- Publication Details
- Haematologica (Roma), Vol.99(7), pp.1176-1183
- DOI
- 10.3324/haematol.2012.083345
- PMID
- 24488560
- PMCID
- PMC4077078
- ISSN
- 0390-6078
- eISSN
- 1592-8721
- Grant note
- I01 CX000114 / CSRD VA P30 CA076292 / NCI NIH HHS
- Language
- English
- Date published
- 07/2014
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297326002771
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