Abstract
Background:
The Early T-cell precursor (ETP) variant of acute lymphoblastic lymphoma/leukemia (ALL) is a recognized high risk variant, recognized by the absence of CD1a, with aberrant myeloid antigen expression (CD13, CD33, CD117, and CD34), and frequent absence of CD4 or CD8. Treatment intensification may improve outcome in this subset. We undertook a multi-center retrospective analysis to explore clinical features, treatment exposure, and outcomes in ETP ALL as compared to non-ETP variants.
Methods
Adult T-ALL/T-LBL cases were compiled from 3 high volume cancer centers between the years 2003-2015. Data collected included patient demographics, tumor characteristics (white count at diagnosis, flow cytometry, FISH, cytogenetics, bone marrow involvement), treatment regimens and patient outcomes. ETP cases were defined as definite (CD1a-/CD8-/myeloid+) or probable (CD1a unk/CD8-/myeloid+, or CD1a-/myeloid+ with CD4+ and/or CD8+). All other cases were defined as non-ETP. Demographic data were compared using independent t-test assuming non-equal variance. OS and PFS were calculated from diagnosis and compared by Kaplan Meier and log-rank testing.
Results
Among 95 cases, 33 met criteria for definite/probable ETP (35%). OS and PFS data were indistinguishable between these groups (p=0.24, p=0.34), and were subsequently analyzed as a single group.
Within the ETP group, no factors were associated with OS, including histology (CD1a+ vs unk, CD3cyt vs CD3sur, CD5dim vs CD5+, CD1a+/13+ vs CD1a+/13-, or CD13, CD33, CD117, CD34, & TdT status), marrow blast burden, peripheral blast burden, white blood cell count (wbc), hemoglobin (hgb), platelet count (plt), cytogenetics/FISH status, chemotherapy choice, or allogeneic transplant (in CR1 or at any time). With regards to PFS, only the inclusion of asparaginase with induction was associated with outcome (p=0.009), while all other covariates failed to show any significance.
The ETP group was compared with the non-ETP subset (table 1). ETP were more likely to abuse marijuana, possibly reflecting unrecognized pesticide exposure, and were more likely to abnormalities of chrom 5 & 7. ETP trended towards lower response and higher rate of relapse, with lower PFS. Comparison of OS was not significant, likely related to small numbers (5y OS 37% vs 22%, figure 1). Non-ETP failed to show PFS benefit with frontline asparaginase, otherwise no treatment differences were apparent.
Conclusions
In this muti-center cohort we were able to identify and characterize ETP cases, confirming poor outcomes. Improvement in PFS among ETP patients treated with frontline asparaginase warrants attention and prospective confirmation. Unfortunately, OS remains poor independent of treatment or receipt of allogeneic transplant, suggesting a critical need remains for development and study novel therapies.
| ETP | Non-ETP | p-value | |
|---|---|---|---|
| Median Age | 37.45 | 34.74 | 0.42 |
| Male | 82% | 66% | 0.89 |
| FamilyHx of Lymph/Leuk | 21% | 8% | 0.112 |
| FamilyHx of Ca | 42% | 25% | 0.09 |
| THC | 24% | 5% | 0.021 |
| P blasts | 40% | 28% | 0.158 |
| >25% M blasts | 30% | 55% | 0.0571 |
| WBC | 78.45 | 76.55 | 0.948 |
| wbc>100 | 24% | 24% | 0.995 |
| Hgb | 10.72 | 11.78 | 0.148 |
| hgb<12 | 67% | 47% | 0.097 |
| plt | 151.59 | 138.66 | 0.644 |
| Chrom 5/7 | 40% | 7% | 0.005 |
| Remission | 61% | 79% | 0.096 |
| Relapse | 76% | 58% | 0.073 |
| OS | 27.00 | 22.00 | 0.595 |
| PFS | 13.00 | 17.00 | 0.048 |
| PFS Asp | |||
| ETP (asp no vs yes) | 12 | 59 | 0.009 |
| non-ETP (asp no vs yes) | 17 | 15 | 0.777 |
| ETP | Non-ETP | p-value | |
|---|---|---|---|
| Median Age | 37.45 | 34.74 | 0.42 |
| Male | 82% | 66% | 0.89 |
| FamilyHx of Lymph/Leuk | 21% | 8% | 0.112 |
| FamilyHx of Ca | 42% | 25% | 0.09 |
| THC | 24% | 5% | 0.021 |
| P blasts | 40% | 28% | 0.158 |
| >25% M blasts | 30% | 55% | 0.0571 |
| WBC | 78.45 | 76.55 | 0.948 |
| wbc>100 | 24% | 24% | 0.995 |
| Hgb | 10.72 | 11.78 | 0.148 |
| hgb<12 | 67% | 47% | 0.097 |
| plt | 151.59 | 138.66 | 0.644 |
| Chrom 5/7 | 40% | 7% | 0.005 |
| Remission | 61% | 79% | 0.096 |
| Relapse | 76% | 58% | 0.073 |
| OS | 27.00 | 22.00 | 0.595 |
| PFS | 13.00 | 17.00 | 0.048 |
| PFS Asp | |||
| ETP (asp no vs yes) | 12 | 59 | 0.009 |
| non-ETP (asp no vs yes) | 17 | 15 | 0.777 |
Shah:Acetylon: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PLexus Communications: Honoraria; Pharmacyclics: Speakers Bureau; Rosetta Genomics: Research Funding; Seattle Genetics: Research Funding. Kota:Pfizer: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding. Hathaway:OnQ Health: Research Funding.
