Data from patients at 13 university hospitals in South Korea were collected retrospectively between December 2005 and May 2013. All patients were treated with thalidomide-containing chemotherapy and then underwent ASCT. Patients who were treated with an induction chemotherapy regimen without thalidomide or those who underwent tandem ASCT were excluded. The thalidomide combination induction chemotherapy consisted of thalidomide (fixed oral dose of 50 to 100 mg on days 1 to 28) plus intravenous (IV) dexamethasone (20 mg/m² or oral on days 1 to 4 and days 15 to 18) every 4 weeks (TD), cyclophosphamide (fixed oral dose of 150 mg on days 1 to 4 every 4 weeks) plus TD (CTD), doxorubicin (9 mg/m² IV rapid infusion on days 1 to 4) plus TD (TAD) every 4 weeks, and thalidomide plus vincristine 4 mg/m² IV infusion on days 1 to 4, 9 mg/m² doxorubicin IV rapid infusion on days 1 to 4, and 20 mg/m² dexamethasone IV or oral on days 1 to 4, 9 to 12, and 17 to 20 (VAD) every 4 weeks. Only four patients were treated with this thalidomide plus VAD regimen. Low-dose aspirin was used to prevent thrombosis during induction chemotherapy. A total of 221 patients who achieved PR or better underwent ASCT with high-dose melphalan (100 to 200 mg/m²).

Progression-free survival (PFS) and overall survival (OS) were estimated using clinical parameters in all patients, including age, sex, hemoglobin, platelet count, ALC, β2MG, serum albumin, LDH, cytogenetic risk, ISS score, response before ASCT, and inflammatory score. A conventional chromosomal study was performed in 204 patients and FISH including t(11;14), t(4;14), 13q deletion, 17p deletion, t(14;16), tri 1q, and t(14;20) were also performed in more than 100 patients. The cytogenetic risk, which was determined by conventional cytogenetics or FISH, was divided into standard, intermediate, and high risk. Standard risk included normal cytogenetics and hyperdiploidy, t(11;14), and t(6;14). Intermediate risk included t(4;14), 13q deletion, and hypodiploidy; and high risk included 17p deletion, t(14;16), and t(14;20) [19,21-23]. Each inflammatory factor of ALC level < 1.0 × 10⁹/L, β2MG level > 3.5 mg/L, serum albumin < 3.5 g/dL, and LDH level above normal was defined as a combined abnormal inflammatory factor, and the sum of these abnormal factors was analyzed. Responses before and after ASCT were assessed according to the International Myeloma Working Group uniform response criteria [24].

We investigated independent prognostic factors associated with survival using the listed clinical and laboratory parameters. PFS was defined as the duration from the start date of induction chemotherapy to the date of disease progression, relapse, or death from any cause after ASCT. OS was calculated from the date of diagnosis to the date of death from any cause or the final follow-up date. Survival probabilities were calculated according to the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards regression model was used for the multivariate analysis of independent prognostic factors of survival. Information about the baseline medical status and treatment modalities was collected from the medical records. Approval for this study was obtained from each Institutional Review Board.

The median age of the 232 patients was 57 years (range, 33 to 77), and the male to female ratio was 1.09:1. The median serum monoclonal protein level was 2.4 g/dL (range, 0.0 to 9.8), the median hemoglobin level was 10.1 g/dL (range, 4.2 to 15.4), and the median platelet count was 196.5 × 10⁹/L (range, 37.0 to 454.0). Standard cytogenetic risk was found in 173 patients (74.6%), intermediate risk in 39 (16.8%), and high risk in 20 (8.6%). The frequencies of the combined abnormal inflammatory factors of 0, 1, 2, 3, and 4 were found in 64 (27.6%), 75 (32.3%), 67 (28.9%), 18 (7.8%), and five (2.2%) patients, respectively. Other clinical and laboratory characteristics are summarized in Table 1.

The response rates achieved before and after ASCT were as follows: complete response (CR) or stringent CR in 81 (34.9%) and 142 (60.2%) patients, very good partial response (PR) in 61 (26.3%) and 47 (20.3%), PR in 79 (34.1%) and 32 (13.8%), and < PR in seven (3.1%) and five (2.3%). The median follow-up duration was 24.5 months (range, 6.9 to 108.9). The median PFS was 31.93 months (range, 25.1 to 38.8), and the median OS was not reached during the follow-up (Fig. 1).

The following factors in the univariate analysis were associated with a greater than 2-year PFS (Table 2): low β2MG (< 3.5 mg/L vs. ≥ 3.5 mg/L, 74.8% vs. 54.5%, p = 0.022), normal LDH (normal vs. abnormal, 67.4% vs. 50.5%, p = 0.009), low cytogenetic risk (standard vs. intermediate vs. high, 68.5% vs. 48.5% vs. 61.5%, p = 0.018), and having fewer than two combined abnormal inflammatory factors (< 2 vs. ≥ 2, 72.1% vs. 53.3%, p = 0.004) (Fig. 2A). The following factors were associated with a greater than 2-year OS (Table 2): higher hemoglobin level (< 10 g/dL vs. ≥ 10 g/dL, 84.6% vs. 96.1%, p = 0.042), higher platelet count (< 100 × 10⁹/L vs. ≥ 100 × 10⁹/L, 48.5% vs. 93.1%, p < 0.001), lower β2MG (< 3.5 mg/L vs. ≥ 3.5 mg/L, 98.7% vs. 84.7%, p < 0.001), normal LDH (normal vs. abnormal, 91.6% vs. 69.5%, p < 0.001), lower cytogenetic risk (standard vs. intermediate vs. high, 92.1% vs. 90.3% vs. 83.8%, p = 0.028), lower ISS (I, II, and III, 98.0%, 90.3%, and 83.8%, respectively; p = 0.024), and having fewer than two combined abnormal inflammatory factors (< 2 vs. ≥ 2, 98.1% vs. 81.1%, p < 0.001) (Fig. 2B). The survival curves of 2-year PFS and OS according to the inflammatory factors (Fig. 2A and 2B) are compared to 2-year PFS and OS according to ISS in Fig. 2C and 2D. The factors correlated with longer survival in the univariate analysis were included in a multivariate analysis, excluding β2MG and LDH because they were already included as abnormal inflammatory factors. ISS was also excluded from the multivariate analysis because β2MG and albumin were already included as abnormal inflammatory factors. In the multivariate analysis, abnormal inflammatory factors (< 2) was the only independent prognostic factor for superior PFS (relative risk [RR], 0.618; 95% confidence interval [CI], 0.409 to 0.933; p = 0.022), and platelet count > 100 × 10⁹/L, and fewer than two abnormal inflammatory factors were the only independent prognostic factors for greater OS (RR, 4.793; 95% CI, 1.897 to 11.839; p = 0.001 and RR, 0.263; 95% CI, 0.113 to 0.612; p = 0.002, respectively) (Table 3).