Abstract
Introduction
T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) originate from the common T-cell precursors and are formally differentiated by bone marrow blast count with less than 25% considered as T-LBL. ALL treatment protocols are successfully applied with quite similar long-term results in both entities. Dose intense chemotherapy is proposed to be the best option. RALL is conducting a prospective multicenter trial in the treatment of Ph-negative adult ALL patients based on the opposite approach - non-intensive but non-interruptive treatment (NCT01193933). T-LBL pts were included in the study.So we decided to define whether the difference in response rate and long-term results exists in T-ALL and T-LBL patients treated according to RALL-2009 protocol.
Patients and Methods
The therapy was unified for all Ph-negative ALL pts, but in T-cell ALL/LBL autologous hematopoietic stem cell transplantation (auto-HSCT) after non-myeloablative BEAM conditioning was scheduled as late intensification (+3-4 mo of CR) followed by prolonged 2 years maintenance. From Jan 2009, till Jul 2016, 30 centers enrolled 107 T-ALL/LBL pts. Median age was 28 years (15-54 y), 34 f / 73 m; early T-cell (TI/II) phenotype was verified in 56 (52.3%), mature (T-IV) - in 10 (9.4%), thymic (TIII, CD1a+) ALL - in 41 pts (38.3%). T-lymphoblastic lymphoma (T-LBL= <25% b/m blasts) was diagnosed in 22 pts (20,5%). We divided the analyzed population into 3 groups: < 5% b/m blasts, with 5-24%, ≥25%. Pts' characteristics according to the b/m involvement are depicted in Table 1. Autologous HSCT was performed in 35, allogeneic-in 7 pts. The analysis was performed in July 2016.
Results
As it's shown in Table 1 the patients with T-LBL disregarding the % of blasts cells (<5% or 5-24%) have much less initial WBC and LDH levels, more frequent mediastinum involvement, less frequent CNS disease in comparison with T-ALL patients. There were no patients with pro-T-subtype (T1) T-LBL comparing with 42% of patients with pro-T-ALL. Mature T-subtype was slightly more frequent (4/22 vs 6/85) (p=0,1) in T-LBL. Total CR rate in 97 available for analysis patients was 87,6% (n=85), induction death was registered in 5,1% (n=5), resistance-in 7,2% (n=7). All induction deaths occurred in T-ALL patients, resistant cases were registered much more frequently (p=0,01) in T-LBL with less than 5% of blast cells than in T-ALL (3/10 vs 4/85). Only 35 of 85 (41,2%) CR pts underwent autologous HSCT due to logistics problems and refusals. Auto-HSCT was done at a median time of 6 mo from CR and pts proceeded to further maintenance. We compared 5-y disease-free survival (DFS) and probability of relapse (RP) in transplanted pts and those who survived in CR ≥ 6 months (land-mark) receiving only chemotherapy. This analysis was carried out in 2 cohorts of patients: T-LBL (<5%; 5-24%) and T-ALL (≥25%). Land-mark analysis demonstrated the essential benefit of auto-HSCT only for T-ALL patients: DFS from time of transplantation was 95% and from land-mark for chemotherapy group - 61% (p=0,005), RP-5% vs 30% (p=0,02). But in T-LBL pts there were no benefit of autologous HSCT over chemotherapy (DFS -100% vs 86%, RP-0% vs 14%, p=0,3). At 5 years overall survival (OS) for the whole T-ALL/T-LBL group constituted-66%, DFS-76%. There were no differences in OS (77% vs 66%, p=0,8) and in DFS (87% vs 74%, p=0,7) in T-LBL and T-ALL.
Conclusions
Our data demonstrate that non-intensive, but non-interruptive treatment approach is effective as in T-ALL so in T-LBL. T-LBL patients had no induction mortality but more frequently were reported as having resistant disease on RALL-2009 protocol. Auto-HSCT after BEAM conditioning followed by maintenance provided substantial benefit only for patients with T-ALL, but not T-LBL.
Table 1 Clinical characteristics and treatment outcome in T-ALL and T-LBL patients Table 1. Clinical characteristics and treatment outcome in T-ALL and T-LBL patients
Disclosures
No relevant conflicts of interest to declare.
Excessive proliferation and impaired function of primitive hematopoietic cells in bone marrow due to senescence post chemotherapy in a T cell acute lymphoblastic leukemia model
