The University of Chicago experience with a reduced intensity allogeneic peripheral blood stem cell transplant preparative regimen using fludarabine, cyclophosphamide, and antithymocyte globulin (ATG) in pts with a hematologic malignancy

Abstract

6626 Background: Non-myeloablative preparative regimens have been used extensively in alloSCT. We hypothesized that a novel preparative regimen, fludarabine, cyclophosphamide, ATG, could result in hematopoetic engraftment, disease control, and low toxicity. Methods: Patients (pts) received fludarabine 30 mg/m2/d on d –9, -8, -7, -6, -5, cyclophosphamide 2gm/m2/d on day –5, and ATG 10 mg/m2/d on day –5, -4, -3, -2. Stem cells were from full HLA matched sibling donors. GVHD prophylaxis included tacrolimus 0.03 mg/kg/d starting day -4, to reach a level of 5–15ng/ml, and tapered to discontinue by day +90. Mycophenylate mofetil 1mg PO bid was started on day +1 and continued until day +60. T cell subsets were analyzed by flow cytometry, Results: 17 pts were treated on this study from June 1999 to October 2001. (3 AML, 1 MDS, 5NHL, 3 HD, 2MM, 2CLL/SLL, 1CMML) Median age was 60 yrs, (24–67). Pts had a median of 3 prior chemo regimens (0–5), including 5 with a prior autoSCT. Median ECOG PS was 1 (0–1). Median hospitalization was 21d (15–77). Median days to ANC>500 was 14 (0–21) and median days to plt>100 was 13 (0- not reached). Two deaths occurred prior to d100, both due to sepsis (d23, d61). No pt had acute GVHD. 3/17 pts had extensive chronic GVHD (2 liver, 1colon) Median donor chimerism at d30 was 67.5%, at d100 was 75%. Best response: CR 8pts, PR 2pts, SD 3 pts, PD 3pts. One pt died at d21 with RD. Median PFS of pts with SD, PR, or CR was 5.13 mos (2.6 –50+). Three pts had DLI after PD. (1 HD pt had no GVHD, but had PD; 1 NHL pt had grIV gut GVHD, died of sepsis d39 w/RD; 1MM pt had grIII liver GVHD, achieved a CR lasting 2 yrs) Data from T-cell subset analysis is available on 7 / 17 pts. At d33, pts with a CR or PR had more IL2-producingCD8+ (12.02 vs 3.20, p=0.0034), CD4+ (126.64 vs. 38.92, p=0.0294), and CD3+ (138.66 vs 42.11, p=0.02) T cells/μL.Conclusions: This regimen was well tolerated by this older group of heavily pretreated pts, but median donor chimerism was only 75% at d100. The numbers of T cells producing Th1 cytokines at d33 was higher in pts with a good clinical response. No significant financial relationships to disclose.