No Differences in the Treatment Outcome in T-Cell Acute Lymphoblastic Leukemia/Lymphoma Regarding the Initial Bone Marrow Blasts Count: Results of the Russian Acute Lymphoblastic Leukemia (RALL) Study Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5149-5149
Author(s):  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Andrey N. Sokolov ◽  
Larisa A. Kuzmina ◽  
Sergey Bondarenko ◽  
...  

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.

2017 ◽  
Vol 39 (2) ◽  
pp. 81-89 ◽  
Author(s):  
Keizo Horibe ◽  
Keiko Yumura-Yagi ◽  
Tooru Kudoh ◽  
Shinichiro Nishimura ◽  
Megumi Oda ◽  
...  

2017 ◽  
Vol 1 (20) ◽  
pp. 1760-1772 ◽  
Author(s):  
Xavier Cahu ◽  
Julien Calvo ◽  
Sandrine Poglio ◽  
Nais Prade ◽  
Benoit Colsch ◽  
...  

Key Points BM niches differentially support T-ALL. BM niches differentially protect T-ALL cells from chemotherapy.


Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 174-179 ◽  
Author(s):  
CH Pui ◽  
FG Behm ◽  
B Singh ◽  
MJ Schell ◽  
DL Williams ◽  
...  

Abstract Presenting features of 120 consecutive children with T-cell acute lymphoblastic leukemia (ALL), representing 15% of all patients diagnosed as having ALL during the study period, were analyzed to determine relationships with treatment outcome. Patients' ages ranged from 1.7 to 18.8 years (median, 10.3 years) and their leukocyte counts from 1.7 to 1,070 x 10(9)/L (median, 100 x 10(9)/L). Central nervous system (CNS) leukemia was present in 12.5% of the cases, a mediastinal mass in 61%, and L2 lymphoblast morphology in 32%. A relatively high proportion of cases, 26%, had normal karyotypes at presentation. Of the cases tested, membrane CD1 expression was found in 38% of cases, CD3 in 33%, CD4 in 50%, CD5 in 94%, CD8 in 55%, and CD10 in 35%. Four presenting features were found to confer an increased risk of treatment failure: age greater than or equal to 15 years, L2 lymphoblast morphology, abnormal karyotype, and membrane CD3 expression. This study illustrates the heterogeneity of presentations of childhood T-cell ALL and suggests that the relative importance of risk factors in ALL differs according to immunophenotype and treatment strategy.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4652-4652
Author(s):  
Aining Sun ◽  
Wenjuan Wang ◽  
Guanghua Chen ◽  
Wu Depei ◽  
Suning Chen ◽  
...  

Abstract Abstract 4652 Objective This study was purposed to analyze the mutations of JAK1 in bone marrow cells from adult patients with newly-diagnosed T cell acute lymphoblastic leukemia (T-ALL). Methods The entire coding sequence of JAK1 in bone marrow mononuclear cells (MNCs) from 40 adult T cell ALL patients were screened by polymerase chain reaction (PCR) and direct sequencing, then the clinical features of JAK1 mutation positive patients were analyzed. Results JAK1 mutations were identified in 5%(2/40) patients, one is point mutation, the other is insertion mutation, resulting in changes in amino acid sequences, and the two types of mutations are different from those mutations found before. Conclusion The JAK1 mutations were found in about 5% newly-diagnosed T cell acute lymphoblastic leukemia, which was lower than those report abroad. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1439-1439 ◽  
Author(s):  
Hamilton L. Gimenes-Teixeira ◽  
Guilherme A. dos Santos ◽  
Dalila L. Zanette ◽  
Priscila S Scheucher ◽  
Luciana Correa Oliveira de Oliveira ◽  
...  

Abstract Abstract 1439 T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy of immature T cells that accounts about 15% of pediatric and 25% of adult ALL cases. In the last years, several clinical and laboratory features have been described as prognostic markers; nevertheless, with intensification of therapy most of them have lost their predictive value. MicroRNA (miRNA) expression analysis has proved to be an useful tool for identifying specific subsets of cancer patients with relevant cytogenetic, laboratorial and clinical features. The aim of the present study was to determine if miRNAs may be useful markers in T-ALL. First, we performed a supervised analysis comparing the miRNA expression profile of T-ALL blasts from 36 T-ALL/CD56− and 12 T-ALL/CD56+. We selected CD56 as prognostic marker based on our previous report showing that the disease-free survival (DFS) of T-ALL/CD56+ patients was of 28.5 months compared to 69.8 in the CD56− group. Also patients tended to be older and to present normal platelet counts in the T-LLA/CD56+ group. We used the Taqman MicroRNA Assay Human Panel (Applied Biosystems) to perform a screening of 164 knowledge mature miRNA sequences using specific primers and probes according to manufacturer instructions. Total RNA input was normalized based on the geometric means of Ct values obtained from four endogenous RNAs. All reactions were run in duplicate and a coefficient of variation greater than 5% was used as an exclusion factor (seven miRNAs were excluded). The fold change was calculated using comparative 2−δCt method. We have identified a set of 14 miRNAs differentially expressed, of which miR-374 and miR-221 best distinguished T-ALL/CD56+ from T-ALL/CD56− blasts. Based on this profile, we selected miR-221 and miR-374 as potential markers and quantified their expression in the same samples using RQ-PCR. Patients were stratified as high and low expression using the median value as cut off. We detected a significant association between the miR-221 high expression and poorer treatment outcome. On the contrary, miR-374 expression levels were not associated with treatment outcome. We evaluate the impact of age, white blood cell counts, CD56 and miR221 expression on overall survival (OS). Age and miR-221 were the only ones found to be significant. The estimate 5-year OS (mean and confidence interval 95%) was of 67.0 ± 10.3% in the group of patients expressing miR-221 below the cut-off value, whereas this value was of 28.5 ± 14.5% in the alternative group. Even among T-ALL/CD56− patients, the higher expression of miR-221 was significantly associated with poorer outcome. Our data suggest that miR-221 play an important role in T-ALL and its regulation may represent a potential therapeutic intervention. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 99 (6) ◽  
pp. 1077-1087 ◽  
Author(s):  
Tanja Rezzonico Jost ◽  
Chiara Borga ◽  
Enrico Radaelli ◽  
Andrea Romagnani ◽  
Lisa Perruzza ◽  
...  

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