Summary:We have performed a prospective study to evaluate early chimerism and its kinetics after allogeneic peripheral blood stem cell transplantation among 68 patients who received a reduced-intensity conditioning (RIC) regimen with fludarabine plus melphalan (n ¼ 40) or busulphan (n ¼ 28). Chimerism was analyzed by polymerase chain reaction amplification of short tandem repeats in unfractionated (UF) and/or fractionated nucleated cells from bone marrow and peripheral blood (PB). All of the patients showed initial donor engraftment and no patient presented primary or secondary graft failure. In UF samples, the probability of achieving stable complete donor chimerism (CDC) in PB within the first 6 months was 70% on day +30, 85% on day +100 and 95% on day +180. CDC in granulocytes was observed in nearly all cases from day +30 onwards. CDC in T cells, however, differed among melphalan and busulphan recipients during the first 3 months (100 vs 0% on day +30 and 93 vs 20% on day +90, respectively). In multivariate analysis, the only significant variable associated with the achievement of early CDC was having received more than two lines of chemotherapy pretransplant (Po0.02). No correlation was found between the rate of achieving early CDC and the occurrence of acute graft-versus-host disease (GVHD) or disease progression post-transplant. In multivariate analysis, the only variable that influenced the incidence of disease progression posttransplant was the development of chronic extensive GVHD (Po0.05). In conclusion, a state of CDC is readily obtained within the first 6 months after our RIC protocols. Donor myeloid engraftment occurs rapidly in all cases, while early T-cell CDC is more common in more immunosuppressed hosts and, perhaps, in melphalan recipients.
Summary:Two patients with disseminated mantle-cell lymphoma relapsed 24 and 13 months, respectively, after high-dose chemotherapy and autologous stem cell transplantation (autoSCT). Both patients had an HLA-identical sibling and received an allogeneic stem cell transplant (alloSCT) 32 and 18 months after autologous transplant, after conditioning with fractionated 12 Gy total body irradiation plus cyclophosphamide 120 mg/kg. They are both alive and in complete remission 24 months after transplant. Both patients have developed chronic graftversus-host disease and their Karnofsky performance status is 90%. AlloSCT may offer a useful approach in a subgroup of patients with mantle-cell lymphoma who have relapsed after autologous transplantation. Bone Marrow Transplantation (2000) 26, 677-679.
1244 Poster Board I-266 Allogeneic stem cell transplantation (SCT) is the only curative treatment for chronic lymphocytic leukemia (CLL). Advanced age, extensive prior therapy, lack of response to treatment, and T-cell depletion of the graft are poor prognostic factors which have been identified in many studies. Beta-2 microglobulin (B2M) has important prognostic value in patients treated with chemotherapy or chemoimmunotherapy, but has been scarcely investigated in the context of allogeneic SCT. In two studies (Khouri et al. Cytotherapy 2002; Sorror et al. J Clin Oncol 2008) no correlation was found between B2M and transplant outcome. Against this background, we analyzed the influence of B2M and other prognostic parameters in 32 patients (median age 50 yrs [range, 29-63], 20 males) who received an allogeneic SCT in our institution between 1991 and 2006. Interval between diagnosis and transplantation was 44 months (range, 6-116). Median number of prior therapies was 2 (range, 1-6). Six patients had previously received an autologous SCT. Most patients had adverse biologic features (high ZAP-70 expression, unmutated IGHV, poor cytogenetics). Serum B2M was increased (≥2.5 mg/L) in 13 out of 29 patients prior to transplant. Creatinine levels and glomerular filtration rate were normal. Median follow-up after transplantation was 7 years (range, 1.8- 16.9). The relapse risk (RR) at 5 and 10 years was 5 % (95% CI, 0-14%) and 23% (95% CI, 2-44), respectively. At one and 10 years the cumulative non-relapse mortality (NRM) was 34% (95% CI, 17-51) and 38% (95% CI, 20-55), respectively. Five and 10-year progression free survival (PFS), event free survival (EFS) and overall survival (OS) were 85% (CI, 66-100) and 65% (CI, 35-94), 58% (CI, 40-76) and 40% (CI, 19-62), and 62% (CI, 45-79) and 57% (CI, 38-75). In the univariate analysis, factors associated with a higher NRM were prior autologous SCT (p=0.006), chemorefractory disease (p=0.04), and high serum B2M levels at the time of SCT (p=0.03). Parameters associated with EFS and OS were high B2M levels (p=0.001 and p=0.002), prior autologous SCT (p<0.001 and p=0.001), and number of prior lines of chemotherapy (≤ 1 vs. ≥ 2) (p=0.018 and p=0.042). In the multivariate analysis, prior autologous SCT (RR=4.4, CI: 1.2-16.3; p=0.02) and chemorefractory disease (RR=3.82, CI: 1.06-13.7; p=0.04) were associated with a higher NRM whereas B2M at the time of SCT was a strong independent factor associated with EFS (RR=5.34, CI: 1.7-16.6; p=0.004) and OS (RR=6.20, CI: 1.6-23; p=0.006). The figure shows the impact of B2M on survival after allogeneic SCT. In contrast, IGHV mutational status, high ZAP-70 expression, > 30% bone marrow infiltration, and disease status (CR vs. no CR) at the time of SCT were not associated with outcome. In summary, this study indicates that, as in patients treated with chemo or chemoimmunotherapy, B2M is a strong predictor of clinical outcome in patients with CLL submitted to allogeneic SCT. Disclosures No relevant conflicts of interest to declare.
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