5 research outputs found
Influence of mixed chimerism upon outcomes of allogeneic stem cell transplantation (allo-SCT) in patients with non-malignant diseases
Flow cytometric minimal residual disease monitoring in children with acute lymphoblastic leukemia treated by regimens with reduced intensity
191 consecutive unselected children with acute lymphoblastic leukemia aged from 1 to 16 years were enrolled in the study. Bone marrow samples were obtained at the time of initial diagnostics as well as at days 15 (n = 188), 36 (n = 191), and 85 (n = 187) of remission induction. Minimal residual disease (MRD) was assessed by 6β10-color flow cytometry. Flow cytometry data at day 15 allowed distinguishing three patients groups with significantly different outcome (p Λ 0.0001): 35.64 % patients with MRD < 0.1 % represented 5-year event-free survival (EFS) of 100 %; 48.40 % cases with 0.1 % β€ MRD< 10 % had EFS 84.6 Β± 4.2 %; 15.96 % patients with very high MRD (β₯ 10 %) belonged to group with poor outcome (EFS 56.7 Β± 9.0 %). At the end of remission induction (day 36) 36 children (18.85 %) with MRD higher than 0.1 % had significantly worse outcome compared to remaining ones (EFS 49.4 Β± 9.0 and 93.5 Β± 2.1 % respectively; p Λ 0.0001). From a clinical standpoint it is relevant to evaluate both low-risk and high-risk criteria. Multivariate analysis showed that day 15 MRD data is better for low-risk patients definition while end-induction MRD is the strongest unfavorable prognostic factor
Relation between genomic dna breakpoints in mll gene and treatment outcome in infants with acute leukemia
Π¦Π΅Π»Ρ: ΠΡΠ΅Π½ΠΈΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΡΠΎΡΠΊΠΈ ΡΠ°Π·ΡΡΠ²Π° Π² Π³Π΅Π½ΠΎΠΌΠ½ΠΎΠΉ ΠΠΠ Π³Π΅Π½Π° MLL Π½Π° ΠΏΡΠΎΠ³Π½ΠΎΠ· ΠΎΡΡΡΡΡ
Π»Π΅ΠΉΠΊΠΎΠ·ΠΎΠ² (ΠΠ) Ρ Π΄Π΅ΡΠ΅ΠΉ ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ Π³ΠΎΠ΄Π° ΠΆΠΈΠ·Π½ΠΈ.
ΠΠ΅ΡΠΎΠ΄Ρ: Π ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π±ΡΠ»ΠΎ Π²ΠΊΠ»ΡΡΠ΅Π½ΠΎ 68 Π΄Π΅ΡΠ΅ΠΉ ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ Π³ΠΎΠ΄Π° ΠΆΠΈΠ·Π½ΠΈ (29 ΠΌΠ°Π»ΡΡΠΈΠΊΠΎΠ² ΠΈ 39 Π΄Π΅Π²ΠΎΡΠ΅ΠΊ Ρ ΠΌΠ΅Π΄ΠΈΠ°Π½ΠΎΠΉ Π²ΠΎΠ·ΡΠ°ΡΡΠ° 4,8 ΠΌΠ΅Ρ.) Ρ MLL-ΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½ΡΠΌΠΈ ΠΎΡΡΡΡΠΌ Π»ΠΈΠΌΡΠΎΠ±Π»Π°ΡΡΠ½ΡΠΌ Π»Π΅ΠΉΠΊΠΎΠ·ΠΎΠΌ (ΠΠΠ) (n = 46), ΠΎΡΡΡΡΠΌ ΠΌΠΈΠ΅Π»ΠΎΠΈΠ΄Π½ΡΠΌ Π»Π΅ΠΉΠΊΠΎΠ·ΠΎΠΌ (ΠΠΠ) (n = 20) ΠΈ ΠΠ ΡΠΌΠ΅ΡΠ°Π½Π½ΠΎΠΉ Π»ΠΈΠ½Π΅ΠΉΠ½ΠΎΡΡΠΈ (n = 2).
Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ: 5-Π»Π΅ΡΠ½ΡΡ Π±Π΅ΡΡΠΎΠ±ΡΡΠΈΠΉΠ½Π°Ρ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΡ (ΠΠ‘Π) Π΄Π΅ΡΠ΅ΠΉ ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ Π³ΠΎΠ΄Π° ΠΆΠΈΠ·Π½ΠΈ Ρ ΠΠΠ, Π²ΠΊΠ»ΡΡΠ΅Π½Π½ΡΡ
Π² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ MLL-Baby, Ρ ΡΠΎΡΠΊΠΎΠΉ ΡΠ°Π·ΡΡΠ²Π° Π² ΠΈΠ½ΡΡΠΎΠ½Π΅ 11 ΠΠΠ Π³Π΅Π½Π° MLL (n = 29) Π±ΡΠ»Π° ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠΎ Π½ΠΈΠΆΠ΅, ΡΠ΅ΠΌ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² c Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ ΡΠΎΡΠ΅ΠΊ ΡΠ°Π·ΡΡΠ²Π°, Π½Π°ΡΠΈΠ½Π°Ρ Ρ ΠΈΠ½ΡΡΠΎΠ½Π° 7 ΠΏΠΎ ΡΠΊΠ·ΠΎΠ½ 11 (n = 17; 0,16 Β± 0,07 ΠΈ 0,38 Β± 0,14; p = 0,039), Π° ΠΊΡΠΌΡΠ»ΡΡΠΈΠ²Π½Π°Ρ Π²Π΅ΡΠΎΡΡΠ½ΠΎΡΡΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²Π° Π±ΡΠ»Π° Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π²ΡΡΠ΅ Π² Π³ΡΡΠΏΠΏΠ΅ Ρ ΡΠΎΡΠΊΠΎΠΉ ΡΠ°Π·ΡΡΠ²Π° Π² ΠΈΠ½ΡΡΠΎΠ½Π΅ 11 (0,74 Β± 0,09 ΠΈ 0,52 Β± 0,17; p = 0,045). Π ΡΠΎ ΠΆΠ΅ Π²ΡΠ΅ΠΌΡ ΠΌΠ½ΠΎΠ³ΠΎΡΠ°ΠΊΡΠΎΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ Π΅Π΄ΠΈΠ½ΡΡΠ²Π΅Π½Π½ΡΠΌ Π·Π½Π°ΡΠΈΠΌΡΠΌ ΡΠ°ΠΊΡΠΎΡΠΎΠΌ, ΡΠ²ΡΠ·Π°Π½Π½ΡΠΌ Ρ Π½Π΅Π±Π»Π°Π³ΠΎΠΏΡΠΈΡΡΠ½ΡΠΌ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΎΠΌ, ΠΎΡΡΠ°Π΅ΡΡΡ ΡΠΎΡ
ΡΠ°Π½Π΅Π½ΠΈΠ΅ ΠΌΠΈΠ½ΠΈΠΌΠ°Π»ΡΠ½ΠΎΠΉ ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΠΉ Π±ΠΎΠ»Π΅Π·Π½ΠΈ (ΠΠΠ) Π² ΡΠΎΡΠΊΠ΅ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΡ 4 ΠΏΡΠΎΡΠΎΠΊΠΎΠ»Π° MLL-Baby (ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ 5,994; 95%-ΠΉ Π΄ΠΎΠ²Π΅ΡΠΈΡΠ΅Π»ΡΠ½ΡΠΉ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π» 2,209β16,263; p < 0,001). Π£ 22 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠΠ ΡΠ²ΡΠ·ΠΈ ΠΌΠ΅ΠΆΠ΄Ρ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΎΠΌ ΠΈ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ ΡΠΎΡΠΊΠΈ ΡΠ°Π·ΡΡΠ²Π° Π² ΠΠΠ Π³Π΅Π½Π° MLL Π½Π΅ Π²ΡΡΠ²Π»Π΅Π½ΠΎ.
ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅: ΠΠ°Π»ΠΈΡΠΈΠ΅ ΡΠΎΡΠΊΠΈ ΡΠ°Π·ΡΡΠ²Π° Π² ΠΈΠ½ΡΡΠΎΠ½Π΅ 11 Π³Π΅Π½Π° MLL Ρ Π΄Π΅ΡΠ΅ΠΉ ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ Π³ΠΎΠ΄Π° ΠΆΠΈΠ·Π½ΠΈ Ρ ΠΠΠ, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
Π»Π΅ΡΠ΅Π½ΠΈΠ΅ ΠΏΠΎ ΠΏΡΠΎΡΠΎΠΊΠΎΠ»Ρ MLL-Baby, Π²Π΅Π»ΠΎ ΠΊ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠΎ Π±ΠΎΠ»Π΅Π΅ Π½ΠΈΠ·ΠΊΠΈΠΌ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΡΠΌ ΠΠ‘Π ΠΈ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΎΠΉ ΠΊΡΠΌΡΠ»ΡΡΠΈΠ²Π½ΠΎΠΉ Π²Π΅ΡΠΎΡΡΠ½ΠΎΡΡΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²Π°. ΠΠ΄Π½Π°ΠΊΠΎ Π² ΠΌΠ½ΠΎΠ³ΠΎΡΠ°ΠΊΡΠΎΡΠ½ΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΡΠΈΡΠΊΠ° ΡΡΠΎ Π½ΠΈΠ²Π΅Π»ΠΈΡΠΎΠ²Π°Π»ΠΎΡΡ ΡΠΎΡ
ΡΠ°Π½Π΅Π½ΠΈΠ΅ΠΌ ΠΠΠ Π² ΡΠΎΡΠΊΠ΅ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΡ 4. Π£ Π΄Π΅ΡΠ΅ΠΉ ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ Π³ΠΎΠ΄Π° ΠΆΠΈΠ·Π½ΠΈ Ρ ΠΠΠ Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·ΠΈ ΠΌΠ΅ΠΆΠ΄Ρ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ ΡΠΎΡΠΊΠΈ ΡΠ°Π·ΡΡΠ²Π° Π² ΠΠΠ Π³Π΅Π½Π° MLL ΠΈ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΎΠΌ Π½Π΅ Π²ΡΡΠ²Π»Π΅Π½ΠΎ.Aim: To evaluate the relation between genomic DNA breakpoints in MLL and translocation partner genes (TPG) and clinical parameters of infant AL.
Methods: 68 infants (29 boys and 39 girls with median age of 4.8 mo) with MLL-rearranged acute lymphoblastic leukemia (ALL) (n = 46), acute myeloid leukemia (AML) (n = 20) and mixed phenotype acute leukemia (MPAL) (n = 2) were included in the current study.
Results: 5-year EFS was significantly lower in patients with breakpoints in intron 11 (n = 29) in comparison to patients with breakpoint localized from intron 7 to exon 11 (n = 17) (0.16 Β± 0.07 vs 0.38 Β± 0.14, p = 0.039). While cumulative incidence of relapse was remarkably higher in the first group of patients (0.74 Β± 0.09 vs 0.52 Β± 0.17, p = 0.045). Although in Cox regression model including breakpoint location in intron 11 together with age, immunophenotype, initial white blood cell count, initial CNS involvement, type of MLL rearrangements, absolute blast number at day 8 of dexamethasone profase, minimal residual disease (MRD) at time point 4 (TP4) of MLL-Baby protocol, the only significant covariate was the presence of MRD at TP4 (HR 5.994, 95% CI 2.209β16.263, p < 0.001). In 22 AML patients there was not any correlation between breakpoint location and treatment outcome.
Conclusion: Breakpoints in intron 11 of MLL gene led to significantly worse outcome in infants with ALL, treated by MLL-Baby protocol, although this parameter was overcome by MRD-positivity at TP4. The latter was the only independent covariate in multivariate analysis. Our data provide additional information of molecular genetic features of MLL-rearranged infant AL