Hgb level, MCV and platelet count and patient characteristics
A total of 328 newly diagnosed MM patients were enrolled in this study, of whom 180 were males and 148 were females; the median age was 63 years (range from 31 to 84). Table 1 shows the baseline characteristics and treatment specifics of the patients. According to the results of the routine peripheral blood examinations at the time of diagnosis, 72 patients (22.0%) had WBC counts lower than normal (4×109/L), 197 patients (60.1%) had an Hgb level lower than 100 g/L, 84 patients (25.6%) had a MCV higher than normal (99.1fL) and 128 patients (39.0%) had a Plt count lower than 150×109/L.
Table 1
Baseline characteristics of all patients
Baseline characteristics | N = 328 |
Age(y), median, (range) | 63 (31–84) |
Male, n (%) | 180 (54.9) |
D-S, n (%) | |
IA + 2A + 2B | 59 (18.0) |
3A | 212 (64.6) |
3B | 57 (17.4) |
ISS, n (%) | |
1 | 101 (30.8) |
2 | 102 (31.1) |
3 | 125 (38.1) |
R-ISS, n(%) | n = 292 |
1 | 33 (11.3) |
2 | 175 (59.9) |
3 | 84 (228.8) |
Hgb(g/L), median, (range) | 94 (42–161) |
Plt, median, (range) | 170 (23–597) |
WBC, median, (range) | 5.1 (1.5–36.6) |
MCV (fL), median, (range) | 95.2 (72.1-112.3) |
Hematopoietic score, n (%) | |
0 | 93 (28.4) |
1 | 103 (31.4) |
2 | 90 (27.4) |
3 | 42 (12.8) |
LDH (u/L), median, (range) | 188 (79-5785) |
Cr (umol/L), median, (range) | 86 (33-1033) |
Bone marrow plasma cells %, median, (range) | 27 (10–99) |
Therapy received, n (%) | |
PAD | 38 (11.6) |
PCD | 214 (65.2) |
PTD | 23 (7.0) |
PD | 53 (16.2) |
ASCT, n (%) | 43 (13.1) |
Abbreviations: DS, Durie-Salmon Staging; ISS, International Staging System; R-ISS, Revised International Staging System; Hgb, hemoglobin; Plt, platelet; WBC, white blood cell; MCV, mean corpuscular volume; LDH, lactate dehydrogenase; Cr, creatinine; PD, bortezomib, dexamethasone; PCD, bortezomib, dexamethasone, cyclophosphamide; PAD, bortezomib, dexamethasone, adriamycin; PTD, bortezomib, dexamethasone thalidomide; ASCT: Autologous hematopoietic stem cell transplantation. |
A MCV > 99.1fL was common in patients with a Hgb level < 100 g/L (34% vs 13%) and bone marrow plasma cells percentage > 30% (31% vs 21%), age ≥ 70 years (37% vs 23%), Plt < 150×109/L (36% vs 19%) and high-risk RISS (35% vs 21% vs 21%). A Hgb level < 100 g/L was most common in patients aged ≥ 70 years (74% vs 57%) and was also common in patients with Plt counts < 150×109/L (81% vs 47%), bone marrow plasma cells percentage > 30% (69% vs 52%), renal insufficiency (sCr > 177umol/L) (79% vs 56%), high-risk Durie-Salmon stage (81% vs 61% vs 36%), ISS stage (79% vs 65% vs 32%), R-ISS (83% vs 55% vs 18%) stage and elevated red blood cell volumes(80% vs 53%). A Plt count < 150×109/L was common in patients with Hb < 100g/L (52% vs 19%), MCV > 99.1fL (55% vs 34%), bone marrow plasma cells percentage > 30% (50% vs 30%), serum LDH > normal level (62% vs 33%), high-risk Durie-Salmon stage (49% vs 41% vs 22%), ISS stage (51% vs 33% vs 30%) and RISS stage (57% vs 33 % vs 24%) (Supplementary Table 1).
Hematopoietic Score And Patient Survival
The median duration of follow-up was 32.2 months, the median PFS time was 33.3 months (95%CI: 23.6–43.0), and the estimated 3-year and 5-year PFS rates were 48.0% and 31.0%, respectively. The median OS was 60.5 months (95%CI: 54.1–66.9), and the estimated 3-year and 5-year OS rates were 70.4% and 50.3%, respectively. The patient’s age, bone marrow plasma cell percentage, serum LDH level, Durie-Salmon stage and RISS stage significantly affected patient PFS (P < 0.05) (Table 2, Supplementary Table 2). Moreover the patient’s age, Durie-Salmon stage, ISS stage, RISS stage, bone marrow plasma cell percentage, and serum creatinine and LDH levels had significant effects on OS (P < 0.05) (Table 3, Supplementary Table 2).
Table 2
Univariable and multivariable analysis for PFS
Univariable analysis | | Multivariable analysis |
Variable | HR (95%CI) | P value | | Variable | HR (95%CI) | P value |
Age ≥ 70 years | 1.55 (1.10–2.18) | 0.013 | | Age ≥ 70 years | 1.43 (0.99–2.06) | 0.057 |
D-S 3B vs 1-3A | 1.50 (1.03–2.17) | 0.032 | | Hematopoietic score 2–3 vs 0–1 | 1.64 (1.19–2.26) | 0.003 |
ISS 3 vs 1–2 | 1.26 (0.93–1.70) | 0.138 | | Plasma cells > 30% | 1.54 (1.12–2.12) | 0.008 |
R-ISS 3 vs 1–2 | 1.57 (1.12–2.20) | 0.009 | | | | |
WBC < 4×109/L | 0.93 (0.64–1.34) | 0.694 | | | | |
Hgb < 100g/L | 1.24 (0.91–1.67) | 0.173 | | | | |
MCV > 99.1fL | 1.58 (1.14–2.18) | 0.005 | | | | |
Plt < 150×109/L | 1.59 (1.18–2.14) | 0.002 | | | | |
Hematopoietic score 2–3 vs 0–1 | 1.75 (1.30–2.35) | < 0.001 | | | | |
Plasma cells > 30% | 1.76 (1.31–2.36) | < 0.001 | | | | |
Cr > 177umol/L | 1.34 (0.93–1.93) | 0.119 | | | | |
LDH > 245u/L | 1.88 (1.33–2.66) | < 0.001 | | | | |
Abbreviations: HR, hazard ratio; CI, confidence interval; D-S, Durie-Salmon Staging; ISS, International Staging System; R-ISS, Revised International Staging System; WBC, white blood cell; Hgb, hemoglobin; MCV, mean corpuscular volume; Plt, platelet; Cr, creatinine; LDH, lactate dehydrogenase. |
Table 3
Univariable and multivariable analysis for OS
Univariable analysis | | Multivariable analysis |
Variable | HR (95%CI) | P value | | Variable | HR (95%CI) | P value |
Age ≥ 70 years | 1.76 (1.18–2.62) | 0.005 | | Age ≥ 70 years | 1.67 (1.11–2.48) | 0.013 |
D-S 3B vs 1-3A | 2.58 (1.73–3.84) | < 0.001 | | LDH > 245u/L | 1.95 (1.31–2.90) | 0.001 |
ISS 3 vs 1–2 | 2.00 (1.40–2.85) | < 0.001 | | Hematopoietic score 2–3 vs 0–1 | 1.60 (1.11–2.31) | 0.011 |
R-ISS 3 vs 1–2 | 2.51 (1.70–3.71) | < 0.001 | | Plasma cells > 30% | 1.81 (1.26–2.60) | 0.001 |
WBC < 4×109/L | 0.84 (0.54–1.32) | 0.451 | | Cr > 177umol/L | 2.15 (1.44–3.21) | < 0.001 |
Hgb < 100g/L | 1.58 (1.08–2.31) | 0.018 | | | | |
MCV > 99.1fl | 1.83 (1.25–2.67) | 0.001 | | | | |
Plt < 150×109/L | 1.78 (1.25–2.53) | 0.001 | | | | |
Hematopoietic score 2–3 vs 0–1 | 2.03 (1.43–2.89) | < 0.001 | | | | |
Plasma cell > 30% | 1.97 (1.38–2.81) | < 0.001 | | | | |
Cr > 177umol/L | 2.42 (1.63–3.59) | < 0.001 | | | | |
LDH > 245u/L | 2.25 (1.53–3.30) | < 0.001 | | | | |
Abbreviations: PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; D-S, Durie-Salmon Staging; ISS, International Staging System; R-ISS, Revised International Staging System; WBC, white blood cell; Hgb, hemoglobin; MCV, mean corpuscular volume; Plt, platelet; Cr, creatinine; LDH, lactate dehydrogenase. |
Based on univariable analysis, MCV and platelet counts significantly affect the patient's PFS, while Hgb, MCV and platelet counts significantly affect the patient's OS (Tables 2, 3, and Supplementary Table 2). The median PFS was 38.7 months for patients with Hgb levels ≥ 100 g/L and 26.5 months for Hgb levels < 100 g/L (P = 0.173), and the median OS was 64.8 and 56.8 months, respectively (P = 0.018). The median PFS was 38.1 months for patients with MCV ≤ 99.1fL and 23.3 months for patients with MCV > 99.1fL (P = 0.005), and the median OS times were 63.1 and 46.2 months, respectively (P = 0.001). Additionally, the median PFS was 42.8 months for patients with Plt counts ≥ 150×109/L and 24.1 months for patients with Plt counts < 150×109/L (P = 0.002), and the median OS times were not reach (NR) vs 51.1 months(P = 0.001), respectively. Each of the above three indicators was assigned a score of 1 to generate the hematopoietic score. The integral values were 0, 1, 2, and 3, and the score significantly affected both PFS and OS (P < 0.001) (Tables 2, 3 and Fig. 1A, 1B). Overall, 93 (28.4%), 103 (31.4%),90 (27.4%) and 42 (12.8%) patients had scores of 0, 1, 2 and 3, respectively; the median PFS times were 38.7 months, 55.9 months, 23.9 months and 16.7 months, respectively (P < 0.001), and the median OS times were NR, 64.8 months, 53.6 and 33.2 months, respectively (P < 0.001). The median PFS was 43.1 months in patients who had a hematopoietic score from 0 to 1, and the estimated 3-year and 5-year PFS rates were 54.5% and 37.6%, respectively. In patients with a score of 2–3, the median PFS was only 23.5 months, with estimated 3-year and 5-year PFS rates of 37.3% and 20.6%, respectively (P < 0.001) (Fig. 2A, Table 1, Supplementary Table 2). The median OS was NR for patients who had a hematopoietic score from 0 to 1, and the estimated 3-year and 5-year OS rates were 78.8% and 56.6%, respectively. In contrast, the median OS of patients who had a score of 2 to 3 was only 31.4 months, with estimated 3-year and 5-year OS rates of 58.0% and 40.7%, respectively (P < 0.001) (Fig. 2B, Table 2, Supplementary Table 2).
Cox proportional hazards model was used for multivariate analysis. The factors that enter the PFS analysis include age, R-ISS stage, bone marrow plasma cell ratio, and hematopoietic score; factors that enter OS analysis include age, ISS stage, serum creatinine and LDH levels, bone marrow plasma cell percentage and hematopoietic score. The results suggested that hematopoietic score (2–3 vs 0–1, HR, 1.64; P = 0.003) and plasma cell percentage (> 30%, HR, 1.54; P = 0.008) were independent prognostic predictors of PFS; The patient’s age (> 70 years, HR, 1.67; P = 0.013), serum LDH (> 245u/L, HR, 1.95; P = 0.001), serum creatinine level (> 177umol/L, HR, 2.15; P < 0.001), hematopoietic score (2–3 vs 0–1, HR, 1.60; P = 0.011) and bone marrow plasma cells percentage (> 30%, HR, 1.81; P = 0.001) were independent prognostic predictors of OS (Tables 2, 3).