Antithymocyte globulins have been used in the setting of unrelated SCT in order to prevent both graft rejection and GVHD. We designed a RIC regimen with fludarabine and high-dose THY (25 mg/kg) for patients (pts) undergoing unrelated SCT, an association that contributed to 100% engraftment in pts submitted to haploidentical related SCT after a chemotherapy-alone RIC regimen (

Biol Blood Marrow Transplant 2003;9:633–642 and 2005;11:399–400
). We used this combination since, when accrual began, most of our patient/donor pairs were being HLA-typed in class I by low resolution and only DRB1 was being evaluated at the allele level. A total of 28 pts (15 females and 13 males) with a median age of 37.5 years and the diagnoses of acute leukemia (AL) (n=14), myelodysplastic syndrome (MDS) (n=6) and chronic myeloid leukemia (CML) (n=8) were treated. Fourteen pts had early disease (CML 1st chronic phase, AL 1st CR or untreated MDS) and another 14 pts had more advanced disease. Seventeen pts were transplanted with bone marrow and 11 pts received PBPC from unrelated donors with known antigen or allele mismatches in 13 cases. The RIC regimen consisted of Ara-C 2gm/m2 D-8, fludarabine 30 mg/m2/day D-8 to D-4, THY 5 mg/kg/day plus prednisolone 2 mg/kg/day D-9 to D-5, and melphalan 70 mg/m2/day D-3 and D-2. GVHD prophylaxis consisted of mycophenolate mofetil plus cyclosporine. All pts had prompt engraftment. There were transitory acute side effects from THY: fever (n=13), skin rash (n=8), hypotension (n=7), diarrhea (n=4) and shortness of breath (n=2). The most frequent infectious complication was CMV reactivation, which occurred in 12 pts (2 with interstitial pneumonia). A significant number of pts initiated IV antibiotics very early pre-transplant (median, D-5), which was likely due to THY toxicity and not to infection. Five pts (17.8%), all with advanced disease, died within the first 100 days post-transplant. The 5 year probability of acute and chronic GVHD was 33.1% and 44.6%, respectively. Pts not developing any form of GVHD had a higher incidence of relapse (44.4% VS 14.3%, p=0.01). The 5 year probability of overall survival (OS) and disease free survival (DFS) was 48.7% and 45.4%, respectively. The pts with early disease had a better 5 year OS and DFS than those with advanced disease (OS - 71.4% VS 23.8%, p=0.001; DFS - 64.3% VS 23.8%, p=0.02). Pts with chronic GVHD also had superior 5 year probability of OS and DFS than those without this complication (OS - 88.9% VS 40.0%, p=0.02; DFS - 88.9% VS 34.3%, p=0.01). This RIC regimen permitted 100% engraftment with low incidence of acute and chronic GVHD. Six pts had limited chronic GVHD and 4 pts developed mild to moderate extensive chronic GVHD, without the need for long-term treatment. Since cyclosporine was discontinued until day 60 and mycophenolate mofetil was tapered until day 180, we hypothesize that this may have contributed for the emergence of controllable GVHD with a concomitant graft-versus leukemia effect, thereby compensating for the early in vivo donor T-cell depletion mediated by high dose THY. As a result, the incidence of relapse was comparable to that observed in other studies where lower doses of THY were given.

Topics:
graft-versus-host disease, hematopoietic stem cell transplantation, thymoglobulin, conditioning (psychology), brachial plexus neuritis, graft-versus-host disease, chronic, transplantation, cyclosporine, fludarabine, mycophenolate mofetil

Disclosures: Higher dose of Thymoglobulin.

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2006, The American Society of Hematology
2006
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