Upfront Autologous Stem Cell Transplantation (SCT) Ameliorates the Prognostic Disadvantage of an Intermediate/High-Risk FLIPI Score in Patients with Advanced Follicular Lymphoma (FL): Evidence from Two Independent Data Sets.

The Follicular Lymphoma International Prognostic Index (FLIPI) is a useful predictor for the prognosis of patients with FL. It relies on a score consisting of age, stage, hemoglobin, LDH, and number of nodal sites involved at diagnosis, which defines 3 risk groups with different 5-year survival (5-y OS): Low risk (0–1 factor; 5-y OS >90%); intermediate risk (2 factors; 5-y OS 78%); and high risk (>2 factors; 5-y OS 53%). We hypothesized that SCT in first remission might improve the course of patients with advanced FL and high/intermediate risk FLIPI, thereby abrogating the prognostic impact of the FLIPI.

Methods: Consecutive patients from two independent data sets (Kiel/Hamburg = training sample (T); Heidelberg = validation sample (V)) who received upfront SCT for FL between 1990 and 2002 and had sufficient baseline information available to assess the FLIPI were analyzed retrospectively. SCT eligibility criteria were similar for both series and comprised first remission of advanced FL, age <60, and performance status <2. Patients were treated with sequential therapy comprising 2–8 cycles of a CHOP-like regimen for remission induction, Dexa-BEAM (T) or HAM (V) for stem cell mobilization, and TBI/CY or BEAM for myeloablation prior to SCT.

Results: 49 (T) and 57 (V) patients were eligible. Time from diagnosis to transplant was 9 (5–21) and 14 (5–116) months, respectively. The FLIPI assigned 40 (82%) and 36 (63%) patients to the high/intermediate risk group. With a median follow-up from SCT of 64 (12–134) or 62 (1–132) months, respectively, outcome data were similar in both samples. 5-y OS from diagnosis was 94% (T) and 90% (V) for the high/intermediate risk group vs. 83% (T) and 87% (V) for the low-risk group (p=0.09 and p=0.4). 5-year progression-free survival (PFS) was 62% (T) and 77% (V) vs. 71% (T) and 77% (V) (p=0.35 and p=0.73). Combining all patients (n=106) allowed for examination of each prognostic group separately. Differences in 5-y OS from diagnosis (90% for high risk, 93% for intermediate risk and 85% for low risk) or in 5-y PFS (60% for high risk, 75% for intermediate risk and 78% for low risk) were not statistically significant.

Conclusions: Upfront SCT abrogates the prognostic impact of the FLIPI by improving the outcome of intermediate/high-risk patients but not of low-risk patients. Therefore the FLIPI might be a useful tool to select patients for prospective trials on SCT in FL who may particularly benefit from this procedure.