Table 7.
Clinical studies of evaluating the outcome of ETP-ALL.
| Study | Age of patients | Number of patients with ETP-ALL | Study details | Nature of study | Result | Remarks |
|---|---|---|---|---|---|---|
| Coustan-Smith et al. (6) | 0.5–18 years | 239 with T-ALL, 30 had ETP-ALL signature | Compared outcome between ETP-ALL and non-ALL treated with standard chemotherapy | Retrospective | 10-year OS 19% vs. 85%, 10-year EFS 22% vs. 69% (p < 0.0001), for ETP-ALL vs. non-ETP-ALL | Nil |
| Inukai et al. (12) | 1–18 years | 5 ETP-ALL patients | Compared outcome between ETP-ALL and non-ALL treated with pediatric protocol | Retrospective | 1. 4-year EFS 40% (ETP-ALL) vs. 70% (non-ETP-ALL), p = 0.0142. Overall survival not statistically different | Limited number of patients with ETP-ALL |
| Allen et al. (59) | 1–81 years | 7 ETP-ALL patients | Compared outcome of ETP-ALL and non-ETP-ALL treated with conventional chemotherapy | Retrospective | 1. Significantly higher relapse rates in pediatric ETP-ALL (HR = 11.63, p = 0.025)2. No difference in event-free and overall survival in all age group | 1. Limited sample size2. Heterogeneity of treatment regimen |
| Jain et al. (5) | 13–79 years | 15 ETP-ALL and 4 T-LBL with ETP-ALL phenotype | Compared outcome of ETP-ALL and non-ETP-ALL treated with augmented BFM or hyper-CVAD | Retrospective | Median OS 20 months vs. not reached (p = 0.008) | Allogenic stem cell transplant not routinely done for patients with CR1. |
| Patrick et al. (60) | 1–24 years | 35 patients with ETP-ALL | Compare outcome of ETP-ALL and non-ETP-ALL treated with UKALL 2003 protocol | Review of data from randomized control trial (UKALL 2003 trial) | Apparently inferior 5-year EFS and OS for ETP-ALL (76.7% vs. 84.6%, 82.4% vs. 90.9%) but not statistically significant | Adverse prognostic features of ETP-ALL might overcome by risk-adapted therapy with treatment intensification |
| Sayed et al. (61) | 1–18 years | 103 patients with T-ALL, 16.5% of them were ETP-ALL | Compared outcome of ETP-ALL vs. non-ETP-ALL treated with different protocol | Retrospective | Patients treated with the Total Therapy Study XIII protocol had a non-statistically significant inferior outcome for ETP: 70.8% vs. 76.6% (p = 0.67) | Adverse prognosis of ETP-ALL might be overcome by risk-adapted treatment intensification |
| Bond et al. (62) | Adult patients, median age 38.5 years | 47 ETP-ALL patients | Compared outcome of ETP-ALL vs. non-ETP-ALL treated with pediatric-inspired protocol, an early response-base intensification protocol | Analysis of data from GRAALL – 2003 study (prospective, phase II trial) and GRAALL – 2005 (prospective, randomized control trial) | 1. Non-statistically significantly inferior 5-year EFS and OS (59.6% vs. 66.5%) in ETP-ALL2. ETP-ALL had inferior 5-year OS without allogenic stem cell transplant (49.2% vs. 67.5%, p = 0.02) | 1. Early response-based intensification could improve outcome of ETP-ALL2. Allogenic stem cell transplant in CR1 could improve outcome of ETP-ALL |
| Brammer et al. (63) | 2–72 years | 16 patients with ETP-ALL | Analysis of outcome of different T-ALL subtypes and MRD status after allogenic stem cell transplant | Retrospective | Not statistically different in 3-year OS after allogenic SCT in CR1 (47% vs. 65%, p = 0.5) | 1. Allogenic SCT might overcome adverse prognosis of ETP-ALL2. Limited sample size |
| S. Fuhrmann et al (64) | 1–18 years | 493 T-ALL patients in total, 33 patients with ETP-ALL | Analysis of outcome of CD56 expression status in T-ALL from ALL-BFM 2000 trial | Analysis of data from prospective trial (AIEOP-BFM ALL 2000 study) | 1. Not statistically significantly different in event-free survival2. CD56 expression had inferior 5-year event-free survival (60% vs. 82%, p = 0.002%) and 5-year overall survival (60% vs. 85%, p = 0.003%) | 1. 30% of ETP-ALL express CD56 vs. 5.1% in non-ETP-ALL2. MRD-directed therapy improved outcome of ETP-ALL |
| Dunsmore et al (65) | 1–31 years | 1,596 patients with T-ALL, | Phase 3 RCT of nelarabine randomization in addition to escalating-dose methotrexate (MTX) plus pegaspargase (C-MTX) or high dose methotrexate | Randomized control trial | 1. No statistically significant impact on DFS (hazard ratio, 0.99; 95% CI, 0.59 to 1.67; P 5.981; p = 0.981).2. No significant difference in 5-year event-free survival (87% vs. 86.9%) and overall survival (93% vs. 92%) between ETP-ALL vs. non-ETP-ALL. | 92 patients with ETP-ALL taken off from the study protocol. Among them, 28 received allogenic hemopoietic stem cell transplant. This might contribute to improve outcome of ETP-ALL |
| Burns et al. (66) | 1–21 years | 123 T-ALL patients, 21 patients had ETP-ALL | Analysis of patients enrolled into DFCI 05-001 and DFCI 11-001 trial and identify prognostic factors of T-ALL | Analysis of data from phase III randomized controlled trials (DFCI 05-001 and DFCI 11-001 trial) | 1. ETP-ALL associated with higher rate of induction failure (33% vs. 5%, p = 0.008)2. Inferior 5-year event-free survival for ETP-All (54% vs. 87%, p = 0.006)3. Not statistically different in 5-year overall survival (85% vs. 92%, p = 0.31). | 1. Adverse prognosis of ETP-ALL could be overcome by treating with high-risk ALL regimen. |
| Morita et al. (17) | 13–78 years, median age 30 years | 171 T-ALL patients in total, 21 of them were ETP-ALL | Analysis of outcome of newly diagnosed near-ETP-ALL upon treatment of frontline chemotherapy with or without allo-SCT and effect of nelarabine | Retrospective | 1. CR rate of ETP was similar vs. near-ETP-ALL and non-ETP-ALL (83 vs. 79% vs. 91%)2. Inferior 5-year event-free survival of ETP-ALL vs. non-ETP-ALL (24% vs. 60%, p < 0.001) and 5-year overall survival (32% vs. 63%, p < 0.001)3. Allo-SCT improved 5-year EFS (36% vs. 18%, p = 0.03). | 1 .Allo-HSCT had a trend of better 5-year overall survival in ETP-ALL though not statistically significant (36% vs. 29%, p = 0.218)2. Allo-HSCT might improve outcome of ETP-ALL |
| Genesca et al. (67) | Adult T-ALL, mean age 33.5 years | 185 T-ALL patients in total, 34 of them were ETP-ALL | Analysis of clinic-biological, outcome, and prognostic features of PETHEMA and ALL-HR-2003 trials | Retrospective | 1. ETP-ALL significantly lower CR rate upon induction (77% vs. 94%, p = 0.005)2. ETP-ALL had lower MRD negative rate after day 35 induction (35% vs. 82%, p < 0.001, MRD < 0.1% as cutoff)3. Inferior overall survival at 4-year for ETP-ALL (36% vs. 49%, p = 0.037) | 1 .Higher rate of induction failure and slow MRD clearance for ETP-ALL2. The overall survival for patients with allo-SCT was lower in PETHEMA |
| Conter et al. (68) | 1–18 years | 139 treated with AIEOP R2006 study, 16 of them ETP-ALL. 201 T-ALL patients from AIEOP-BFM 2009 study, 33 of them were ETP-ALL | Analysis outcome of ETP-ALL patients treated with AIEOP-BFM protocol | Retrospective | 1. High rate of MRD positivity (cutoff 5 × 10−4): 85% at day 33 and day 78A2 .AIEOP-ALL R2006 study: 5-year event-free and overall survival (56.3% and 55.6%, respectively)3. AIEOP-BFM ALL 2009 study: 3-year event-free and overall survival (86.2%) | 1. Slow marrow response and MRD response for ETP-ALL2. Outcome of AIEOP-BFM ALL 2009 study not statistically different from non-ETP-ALL3 .More patients assigned to high-risk treatment protocol in AIEOP-BFM ALL 2009 study due to positive MRD4 .Improve outcome of ETP-ALL after treatment intensification |
| P. Quist-Paulsen et al. (69) | 1–45 years | A total of 278 T-ALL patients, 37 of them were ETP-ALL | Analysis of results of both pediatric and adult patients with ALL treated with NOPHO ALL 2008, a pediatric-inspired protocol | Prospective study of patients treated with NOPHO ALL 2008 protocol | 1 .Higher MRD at day 29 (0.3% vs. 0.04%, p = 0.001)2. Not statistically significantly different in relapse risk and overall survival | Most patients assigned to high-risk protocol or allo-SCT due to poor early MRD response |
EFS, Event-free survival; OS, Overall survival; HR, Hazard ratio; CR, Complete remission; RCT, Randomized-controlled trial; allo-HSCT, Allogenic hemopoietic stem cell transplant; MRD, Minimal residual disease.