Multivariable analysis results of studies included in this analysis
| No. . | Reference . | n . | Variables included in multivariable models . | HR for PFS . | HR for OS . | Other variables significant on multivariable analysis . | |||
|---|---|---|---|---|---|---|---|---|---|
| Unmutated IGHV . | High-risk FISH . | Unmutated IGHV . | High-risk FISH . | PFS . | OS . | ||||
| IGHV only | |||||||||
| 1 | 6 | 84 | — | — | — | — | — | ||
| 2 | 5 | 47 | — | — | — | — | — | ||
| 3 | 8 | 307 | ZAP-70, IGHV | 2.5 | — | Zap-70, IGHV | — | ||
| 4 | 9 | 303 | Age, Rai stage, CD49d, ZAP-70, IGHV | — | 6.5 | Rai stage, β2M, CD49d, IGHV | Age, CD49d, IGHV | ||
| 5 | 10 | 262 | IGHV, ZAP-70, CD38 | 2.5 | — | IGHV, ZAP-70, CD38 | — | ||
| 6 | 11 | 337 | — | — | — | — | — | ||
| 7 | 12 | 224 | — | — | — | — | — | ||
| FISH only | |||||||||
| 8 | 7 | 325 | LDH, WBC, Binet stage, FISH | — | 2.9 (del11q) | — | LDH, WBC, Binet stage, FISH | ||
| 8.1 (del17p) | |||||||||
| 9 | 13 | 231 | β2M, morphology, FISH | 4.7 (del11q) | — | β2M, morphology, FISH | — | ||
| Both IGHV and FISH (OS only) | |||||||||
| 10 | 14 | 325 | CD38, Age, IGHV, FISH, LDH, WBC count | 2.9 | 1.8 (del11q) | IGHV, FISH, age, LDH, WBC | |||
| 8.2 (del17p) | |||||||||
| 11 | 15 | 205 | Stage, IGHV, FISH, Sex, CD38, morphology | 6.9 | 2.0 (del11q) | Stage, IGHV, FISH | |||
| 3.3 (del17p) | |||||||||
| 12 | 16 | 1948 | Age, sex, stage, ECOG performance status, CBC, lymphocyte count, LDH, TK, β2M, ZAP-70, CD38, IGHV, FISH | 1.9 | 1.4 (del11q) | Age, sex, ECOG performance status, β2M, TK, IGHV, FISH | |||
| 6.0 (del17p) | |||||||||
| Both IGHV and FISH (PFS only) | |||||||||
| 13 | 17 | 351 | CCL3, stage, CD38, IGHV, FISH | NS | 2.4 (del11q) | CCL3, stage, CD38, FISH | |||
| 2.4 (del17p) | |||||||||
| 14 | 18 | 930 | LDH, LN number and size, IGHV, FISH | 10.7 | 1.9 (del11q) | LDH, LN number and size, IGHV, FISH | |||
| 2.1 (del17p) | |||||||||
| 15 | 19 | 384 | CLL vs MBL, IGHV, NOTCH1, FISH | 3.9 | 1.5 (del11q) | CLL, IGHV | |||
| 16 | 20 | 3490 | NOTCH1, SF3B1, TP53, IGHV, FISH | 3.7 | 1.4 (del11q) | IGHV, SF3B1, TP53 | |||
| Both IGHV and FISH (PFS and OS) | |||||||||
| 17 | 21 | 706 | Age, CD38, ZAP70, FISH, IGHV, β2M and GFR-adjusted β2M | NS | 3.3 (del11q or del17p) | NS | 3.7 (del17p or del11q) | FISH, GFR-adjusted β2M | Age, FISH, GFR-adjusted β2M |
| 18 | 22 | 482 | Age, WBC, IGHV, karyotype, FISH, t(14;18) | 4.8 | NS | NS | 5.2 (del17p) | WBC, IGHV | Age, WBC, t(14;18) |
| 19 | 23 | 2487 | Rai stage, IGHV, ALC, CD38, ZAP-70, FISH | 2.8 | 1.3 (del11q or del17p) | 2.8 | 2.9 (del11q or del17p) | Stage, ALC, CD38, IGHV | CD38, FISH |
| 20 | 24 | 252 | LPL expression, age, gender, Binet stage, IGHV, FISH, CD38 | 2.4 | 1.4 (del11q) | 1.9 | 0.9 (del11q) | CD38, IGHV | Age, stage, IGHV, FISH, LPL expression |
| 2.0 (del17p) | 4.6 (del17p) | ||||||||
| 21 | 25 | 255 | SNP, IGHV, FISH | — | — | 1.8 | 1.5 (del11q or del17p) | — | SNP |
| 22 | 26 | 1154 | CD38, age, LDT, IGHV, FISH, ZAP-70 | 3.3 | NS | 2.7 | NS | Age, LDT, CD38, IGHV | |
| 23 | 27 | 620 | Age, sex, ALC, β2M, stage, CD38, lymph node regions, ZAP-70, year of diagnosis, therapy | 3.1 | 2.0 (del11q) | 2.0 | 2.1 (del17p) | β2M, IGHV, FISH | Age, sex, β2M, stage, IGHV, FISH |
| 24 | 28 | 292 | LDH, sex, β2M, IL-10 SNP, IGHV | 2.0 | — | 2.1 | — | Sex, LDH, β2M, IL-10 SNP, IGHV | Stage, IL-10 SNP, IGHV |
| 25 | 29 | 265 | Age, Binet Stage, Sex, CD38, FISH, telomere length, TP53/NOTCH1/SF3B1 mutation | — | 2.1 (del11q) | — | 1.2 (del11q) | CD38, genetic profile, telomere length, FISH | Age, stage, CD38, genetic profile, telomere length |
| 26 | 30 | 311 | LAIR1 expression, IGHV, Binet stage, CD49d | 2.7 | 2.0 (del11q or del17p) | — | — | LAIR1, stage, IGHV | — |
| 27 | 31 | 1274 | age, stage, integrated cytogenetic and mutational model, IGHV | — | — | 1.6 | — | — | Age, stage, IGHV, integrated cytogenetic and mutational model |
| 28 | 32 | 949 | Stage, β2M, FISH, ZAP-70, IGHV, NOTCH1, SF3B1, CIRS | NS | NS | — | NS | Stage, β2M, ZAP-70 | Stage, β2M, ZAP-70, CIRS |
| 29 | 33 | 468 | Rai stage, ALC, β2M, CD38, gene profile, IGHV, FISH | 2.6 | 1.7 (del11q or del17p) | — | — | Rai stage, ALC, β2M, progression-risk score | — |
| 30 | 34 | 288 | Array CGH, IGHV | 5.6 | - | 6.6 | 3.5 (del17p)* | Array CGH, IGHV | |
| 31 | 35 | 1160 | SF3B1, NOTCH1, IGHV, TP53, FISH, sex, age, CD38, ZAP-70 | 3.0 | 1.5 (del11q) | 2.2 | 2.2 (del17p)† | SF3B1, IGHV, FISH | SF3B1, TP53, age, CD38 |
| No. . | Reference . | n . | Variables included in multivariable models . | HR for PFS . | HR for OS . | Other variables significant on multivariable analysis . | |||
|---|---|---|---|---|---|---|---|---|---|
| Unmutated IGHV . | High-risk FISH . | Unmutated IGHV . | High-risk FISH . | PFS . | OS . | ||||
| IGHV only | |||||||||
| 1 | 6 | 84 | — | — | — | — | — | ||
| 2 | 5 | 47 | — | — | — | — | — | ||
| 3 | 8 | 307 | ZAP-70, IGHV | 2.5 | — | Zap-70, IGHV | — | ||
| 4 | 9 | 303 | Age, Rai stage, CD49d, ZAP-70, IGHV | — | 6.5 | Rai stage, β2M, CD49d, IGHV | Age, CD49d, IGHV | ||
| 5 | 10 | 262 | IGHV, ZAP-70, CD38 | 2.5 | — | IGHV, ZAP-70, CD38 | — | ||
| 6 | 11 | 337 | — | — | — | — | — | ||
| 7 | 12 | 224 | — | — | — | — | — | ||
| FISH only | |||||||||
| 8 | 7 | 325 | LDH, WBC, Binet stage, FISH | — | 2.9 (del11q) | — | LDH, WBC, Binet stage, FISH | ||
| 8.1 (del17p) | |||||||||
| 9 | 13 | 231 | β2M, morphology, FISH | 4.7 (del11q) | — | β2M, morphology, FISH | — | ||
| Both IGHV and FISH (OS only) | |||||||||
| 10 | 14 | 325 | CD38, Age, IGHV, FISH, LDH, WBC count | 2.9 | 1.8 (del11q) | IGHV, FISH, age, LDH, WBC | |||
| 8.2 (del17p) | |||||||||
| 11 | 15 | 205 | Stage, IGHV, FISH, Sex, CD38, morphology | 6.9 | 2.0 (del11q) | Stage, IGHV, FISH | |||
| 3.3 (del17p) | |||||||||
| 12 | 16 | 1948 | Age, sex, stage, ECOG performance status, CBC, lymphocyte count, LDH, TK, β2M, ZAP-70, CD38, IGHV, FISH | 1.9 | 1.4 (del11q) | Age, sex, ECOG performance status, β2M, TK, IGHV, FISH | |||
| 6.0 (del17p) | |||||||||
| Both IGHV and FISH (PFS only) | |||||||||
| 13 | 17 | 351 | CCL3, stage, CD38, IGHV, FISH | NS | 2.4 (del11q) | CCL3, stage, CD38, FISH | |||
| 2.4 (del17p) | |||||||||
| 14 | 18 | 930 | LDH, LN number and size, IGHV, FISH | 10.7 | 1.9 (del11q) | LDH, LN number and size, IGHV, FISH | |||
| 2.1 (del17p) | |||||||||
| 15 | 19 | 384 | CLL vs MBL, IGHV, NOTCH1, FISH | 3.9 | 1.5 (del11q) | CLL, IGHV | |||
| 16 | 20 | 3490 | NOTCH1, SF3B1, TP53, IGHV, FISH | 3.7 | 1.4 (del11q) | IGHV, SF3B1, TP53 | |||
| Both IGHV and FISH (PFS and OS) | |||||||||
| 17 | 21 | 706 | Age, CD38, ZAP70, FISH, IGHV, β2M and GFR-adjusted β2M | NS | 3.3 (del11q or del17p) | NS | 3.7 (del17p or del11q) | FISH, GFR-adjusted β2M | Age, FISH, GFR-adjusted β2M |
| 18 | 22 | 482 | Age, WBC, IGHV, karyotype, FISH, t(14;18) | 4.8 | NS | NS | 5.2 (del17p) | WBC, IGHV | Age, WBC, t(14;18) |
| 19 | 23 | 2487 | Rai stage, IGHV, ALC, CD38, ZAP-70, FISH | 2.8 | 1.3 (del11q or del17p) | 2.8 | 2.9 (del11q or del17p) | Stage, ALC, CD38, IGHV | CD38, FISH |
| 20 | 24 | 252 | LPL expression, age, gender, Binet stage, IGHV, FISH, CD38 | 2.4 | 1.4 (del11q) | 1.9 | 0.9 (del11q) | CD38, IGHV | Age, stage, IGHV, FISH, LPL expression |
| 2.0 (del17p) | 4.6 (del17p) | ||||||||
| 21 | 25 | 255 | SNP, IGHV, FISH | — | — | 1.8 | 1.5 (del11q or del17p) | — | SNP |
| 22 | 26 | 1154 | CD38, age, LDT, IGHV, FISH, ZAP-70 | 3.3 | NS | 2.7 | NS | Age, LDT, CD38, IGHV | |
| 23 | 27 | 620 | Age, sex, ALC, β2M, stage, CD38, lymph node regions, ZAP-70, year of diagnosis, therapy | 3.1 | 2.0 (del11q) | 2.0 | 2.1 (del17p) | β2M, IGHV, FISH | Age, sex, β2M, stage, IGHV, FISH |
| 24 | 28 | 292 | LDH, sex, β2M, IL-10 SNP, IGHV | 2.0 | — | 2.1 | — | Sex, LDH, β2M, IL-10 SNP, IGHV | Stage, IL-10 SNP, IGHV |
| 25 | 29 | 265 | Age, Binet Stage, Sex, CD38, FISH, telomere length, TP53/NOTCH1/SF3B1 mutation | — | 2.1 (del11q) | — | 1.2 (del11q) | CD38, genetic profile, telomere length, FISH | Age, stage, CD38, genetic profile, telomere length |
| 26 | 30 | 311 | LAIR1 expression, IGHV, Binet stage, CD49d | 2.7 | 2.0 (del11q or del17p) | — | — | LAIR1, stage, IGHV | — |
| 27 | 31 | 1274 | age, stage, integrated cytogenetic and mutational model, IGHV | — | — | 1.6 | — | — | Age, stage, IGHV, integrated cytogenetic and mutational model |
| 28 | 32 | 949 | Stage, β2M, FISH, ZAP-70, IGHV, NOTCH1, SF3B1, CIRS | NS | NS | — | NS | Stage, β2M, ZAP-70 | Stage, β2M, ZAP-70, CIRS |
| 29 | 33 | 468 | Rai stage, ALC, β2M, CD38, gene profile, IGHV, FISH | 2.6 | 1.7 (del11q or del17p) | — | — | Rai stage, ALC, β2M, progression-risk score | — |
| 30 | 34 | 288 | Array CGH, IGHV | 5.6 | - | 6.6 | 3.5 (del17p)* | Array CGH, IGHV | |
| 31 | 35 | 1160 | SF3B1, NOTCH1, IGHV, TP53, FISH, sex, age, CD38, ZAP-70 | 3.0 | 1.5 (del11q) | 2.2 | 2.2 (del17p)† | SF3B1, IGHV, FISH | SF3B1, TP53, age, CD38 |
β2M, serum β2-microglobulin; CCL3, chemokine ligand 3; CGH, comparative genomic hybridization; ECOG, Eastern Cooperative Oncology Group; GFR, glomerular filtration rate; FISH, fluorescence in situ hybridization; HR, hazard ratio; IGHV, immunoglobulin heavy-chain variable region gene mutation status; LAIR1, leukocyte-associated immunoglobulin-like receptor 1; LDH, lactate dehydrogenase; LPL, lipoprotein lipase; MBL, monoclonal B-cell lymphocytosis; OS, overall survival; PFS, progression-free survival; SNP, single-nucleotide polymorphism; TK, serum thymidine kinase; WBC, white cell count.
del17p identified by array CGH also.
TP53 mutation included with del17p.