Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD-free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3(+) cells ≥ 50 × 10(6)/kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.

Prognostic relevance of serum beta2 microglobulin in patients with follicular lymphoma treated with anthracycline-containing regimens. A GISL study.

BACKGROUND AND OBJECTIVES: Although serum beta2 microglobulin (beta2 M) is an easy parameter to measure, and over-expressed in a large number of lymphoproliferative diseases, its prognostic value has been largely underestimated. The present study examined the influence of beta2M levels on overall survival (OS) of patients with follicular lymphoma (FL). DESIGN AND METHODS: The prognostic role of beta2M was evaluated in 236 patients with FL identified from the databases of the Gruppo Italiano per lo Studio dei Linfomi (GISL) and treated with anthracycline-based regimens from 1993 to 2003. RESULTS: Elevated serum beta2M levels were found in 82 patients (35%). According to multivariate logistic regression analysis, elevated beta2M levels were associated with elevated lactate dehydrogenase (LDH) (p=0.021), age (p=0.029), and number of involved nodal areas (p<0.001). The percentage of elevated beta2M levels increased progressively with increasing FLIPI scores (17%, 38%, and 63% in the low-, intermediate-, and high-risk groups, respectively). Five-year OS was 61% (95% CI, 47-73%) and 89% (95% CI, 82-93%) for patients with elevated vs normal beta2M levels respectively (p<0.001). Cox regression analysis showed that beta2M level had an independent and stable prognostic value (HR=3.0; 95%CI, 1.6-5.7). In a multivariate analysis the impact of beta2M level on survival was independent of FLIPI score, with a HR of 2.94 (95% CI, 1.54-5.62). INTERPRETATION AND CONCLUSIONS: Our results demonstrate that in patients treated in the pre-rituximabera, beta2M level was an independent prognostic marker in addition to FLIPI score. We thus suggest that beta2M be routinely assessed and tested in future prognostic studies of FL patients treated with combination chemotherapy and anti-CD20 agents.