Table 1.
Clinical, immunophenotypic, and molecular features of 86 cases of T-PLL
| Parameter | Distribution | Statistically significant correlations |
|---|---|---|
| Clinical features | ||
| Median age at diagnosis, y (range) | 62 (46-83) | Age > 62 y associated with shorter OS (P = .018; for >65 y P = .024) |
| Male patients, no. (%) | 45 (52.3) | — |
| Median presenting WBC count, ×109/L (range) | 40 (1.6-621) | Higher initial WBC correlated with shorter OS (P< .001); only 1 patient presented with leukopenia and 1 with normal lymphocyte counts |
| Median peak WBC count, ×109/L (range) | 179 (1.9-799) | Higher peak WBC correlated with shorter OS (P = .039, ≤/> median) |
| Median pretreatment LDT, mo (range)* | 8.57 (1->79) | Shorter LDT correlated with poor outcome; P < .001 when grouped (% surviving, median OS) as indolent (81.1%, 63.5 mo), intermediate (75.9%, 38.8 mo), and aggressive (43%, 17.5 mo) |
| Outcome | — | Median follow-up: 25.9 mo (range: 1-116.1 mo); at last follow-up, 5 patients (median age: 63 y) were in CR after therapy |
| Deaths from disease, no. (%) | 68 (79.1) | — |
| Median OS, mo† | 27.4 | — |
| 5-y survival rate, % | 21.0 | — |
| Cytogenetic features | ||
| (inv14)(q11;q32.1) or t(14;14)(q11;q32.1)/total cases analyzed (%) | 24/60 (40.0) | Detection of 14q32 alterations by conventional karyotype correlated with TCL1 protein expression (P = .027); 9/24 cases with inv14/t(14;14) had low TCL1 |
| Trisomy 8 or isochromosome 8q/total cases analyzed (%) | 21/60 (35.0) | Detection of chr 8 abnormalities by conventional karyotype correlated with inv14/t(14;14) (P < .001), del11q22–23 (P = .004), sTCR+ (P = .027) |
| −11 or deletion 11q22-23/total cases analyzed (%) | 20/60 (33.3) | Correlated with detection of 14q32 alterations (P < .001) |
| −17 or isochromosome 17q or deletion 17p/total analyzed cases | 8/60 (13.3) | — |
| Immunophenotypic features | ||
| TCL1 protein | — | Higher TCL1 correlated with shorter OS (P = .029), higher presenting WBC counts (P = .03), shorter pretreatment LDT (P = .03) |
| Absent, no. (%) | 19/82 (23.2) | — |
| Low positive, no. (%) | 15/82 (18.3) | — |
| Strong positive, no. (%) | 48/82 (58.5) | — |
| sTCR/sCD3+ (%) | 67/82 (81.7) | sTCR expression correlated with shorter OS (P < .001) and CD45RAnegative phenotype (P = .016); no sTCRγ/δ+ cases were detected |
| pAKT, no. with score 0 (%), 1 (%), 2 (%) | 12 (40), 15 (50), 3 (10) | pAKT correlated with inferior OS (P = .02), high presenting WBC (P = .002), and short pretreatment LDT (P = .013) |
| CD4+CD8− (%) | 50/81 (61.7) | Correlated with higher age (P = .008), CD26negative/dim (P = .021) |
| CD4+CD8+ (%) | 28/81 (34.6) | Correlated with younger age (P = .008), better OS (P = .027) in sTCR+ group |
| CD4−CD8+ (%) | 3/81 (3.7) | — |
| CD4−CD8− (%) | 0/81 (0) | 5 cases CD4dimCD8−; all 8 CD4dim/negative cases have absent pLAT (P = .04) |
| CD45RA+RO− (%); CD45RA+RO+ (%) | 15 (20.5); 8 (11.0) | CD45RA+ tumors had lower pAKT (P = .02), lower presenting WBC (P = .006), and better OS (P = .06; for RA+RO+ subset P = .04) |
| CD45RA− RO+ (%); CD45RA− RO− (%) | 44 (60.3); 6 (8.2) | CD45RA−CD45RO+ showed a trend toward inferior OS (P = .08); CD45RA−CD45RO− phenotype correlated with low CD25 (P = .03), low CD26 (P = .007), and high SHP1/2 (P = .01) |
| SHP1/2, no. with score 0 (%), 1 (%), 2 (%) | 9 (20), 10 (22), 26 (58) | SHP1/2 expression (IHC) correlated with lower pLCK expression (IHC, P = .05); the 9 cases negative for SHP1/2 had better OS (P = .01) |
| pLAT, no. with score 0 (%), 1 (%), 2 (%)‡ | 4 (17), 10 (44), 9 (39) | pLAT detection (IHC) correlated with pLCK (P = .005), low pAKT (P = .04), and higher peak WBC count (P = .03) |
| pLCK, no. with score 0 (%), 1 (%), 2 (%)‡ | 15 (48), 9 {29), 7 (23) | pLCK detection (IHC) correlated with younger age (P = .02) and pLAT (P = .005) |
| pZAP70, no. with score 0 (%), 1 (%), 2 (%) | 13 (41), 8 (25), 11 (34) | pZAP70 (IHC) correlated with CD25dim/negative (FACS, P = .02) and younger age (P = .012); correlated with better OS (P = .026) in the sTCR+ group |
| CD25, no. with score 0 (%), 1 (%), 2 (%)§ | 44 (58), 14 (18), 18 (24) | FACS level correlated with lower peak WBC count (P = .012) and pAKT absence (P < .001) |
| CD26, no. with score 0 (%), 1 (%), 2 (%)§ | 10 (24), 6 (14), 26 (62) | CD26 level (FACS) correlated with CD25 (P = .01) and CD38 (P = .017) |
| CD38, no. with score 0 (%), 1 (%), 2 (%)§ | 20 (35), 13 (23), 24 (42) | As above (CD26) |
| CD69, no. with score 0 (%), 1 (%), 2 (%) | 6 (24), 11 (44), 8 (32) | CD69 expression (IHC) correlated with pAKT (P = .04), lower pLAT (P = .02) |
sTCR indicates surface T-cell receptor alpha/beta detected by flow cytometry; —, not applicable; IHC, detected by paraffin immunohistochemical staining; and FACS, detected by flow cytometry.
*
LDT scoring as described in “Methods.”
†
OS is disease-specific survival from the time of diagnosis with censoring of unrelated deaths (1 case) or losses to follow-up (1 case).
‡
pLCK+ and pLAT+ tumor cells were often found as clusters in bone marrow sections.
§
These scores use the following cutoffs: 0 (≤10% cells), 1 (>10%-50% cells), and 2 (>50% cells), as determined by flow cytometry.