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- Inaba, Hiroto, et al.
(författare)
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Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia : a retrospective international study
- 2015
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 126:13, s. 1575-1584
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Tidskriftsartikel (refereegranskat)abstract
- Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age <= 18 years) with non-Down syndrome de novo AMKL diagnosed from 1989 to 2009. Patients with AMKL (median age 1.53 years) comprised 7.8% of pediatric AML. Five-year event-free (EFS) and overall survival (OS) were 43.7% +/- 2.7% and 49.0% +/- 2.7%, respectively. Patients diagnosed in 2000 to 2009 were treated with higher cytarabine doses and had better EFS (P = .037) and OS (P = .003) than those diagnosed in 1989 to 1999. Transplantation in first remission did not improve survival. Cytogenetic data were available for 372 (75.9%) patients: hypodiploid (n = 18, 4.8%), normal karyotype (n = 49, 13.2%), pseudodiploid (n = 119, 32.0%), 47 to 50 chromosomes (n = 142, 38.2%), and >50 chromosomes (n=44, 11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: +21 (n = 106, 28.5%), +19 (n = 93, 25.0%), +8 (n = 77, 20.7%). Losses occurred in 65 patients (17.5%): -7 (n = 13, 3.5%). Common structural chromosomal aberrations were t(1; 22)(p13; q13) (n = 51, 13.7%) and 11q23 rearrangements (n = 38, 10.2%); t(9; 11)(p22; q23) occurred in 21 patients. On the basis of frequency and prognosis, AMKL can be classified to 3 risk groups: good risk-7p abnormalities; poor risk-normal karyotypes, -7, 9p abnormalities including t(9;11)(p22;q23)/MLL-MLLT3, -13/13q-, and -15; and intermediate risk-others including t(1;22)(p13;q13)/OTT-MAL (RBM15-MKL1) and 11q23/MLL except t(9;11). Risk-based innovative therapy is needed to improve patient outcomes.
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| 4. |
- Pui, Ching-Hon, et al.
(författare)
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Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia : A Retrospective Multinational Study
- 2019
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 37:10, s. 770-779
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials.PATIENTS AND METHODS: This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome.RESULTS: With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly ( P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction.CONCLUSION: MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogeneic transplantation did not significantly improve outcome overall and, in particular, for patients who achieved MRD-negative status after induction.
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| 5. |
- van Weelderen, Romy E., et al.
(författare)
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Measurable residual disease and fusion partner independently predict survival and relapse risk in childhood KMT2A-rearranged acute myeloid leukemia : a study by the international Berlin-Frankfurt-Münster study group
- 2023
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 41:16, s. 2963-2974
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged (KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease.Methods: A total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (≥0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS).Results: The high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P < .0001), CIR (59.7% v 35.2%; P < .0001), and OS (49.2% v 70.5%; P < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P < .0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P < .0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P = .016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P = .00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS.Conclusion: EOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.
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| 6. |
- van Weelderen, Romy E., et al.
(författare)
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Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia
- 2024
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 8:12, s. 3200-3213
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive international consensus on the cytogenetic risk-group stratification of KMT2A-rearranged (KMT2A-r) pediatric acute myeloid leukemia (AML) is lacking. This retrospective (2005-2016) International Berlin-Frankfurt-Münster Study Group study on 1256 children with KMT2A-r AML aims to validate the prognostic value of established recurring KMT2A fusions and additional cytogenetic aberrations (ACAs) and to define additional, recurring KMT2A fusions and ACAs, evaluating their prognostic relevance. Compared with our previous study, 3 additional, recurring KMT2A-r groups were defined: Xq24/KMT2A::SEPT6, 1p32/KMT2A::EPS15, and 17q12/t(11;17)(q23;q12). Across 13 KMT2A-r groups, 5-year event-free survival probabilities varied significantly (21.8%-76.2%; P < .01). ACAs occurred in 46.8% of 1200 patients with complete karyotypes, correlating with inferior overall survival (56.8% vs 67.9%; P < .01). Multivariable analyses confirmed independent associations of 4q21/KMT2A::AFF1, 6q27/KMT2A::AFDN, 10p12/KMT2A::MLLT10, 10p11.2/KMT2A::ABI1, and 19p13.3/KMT2A::MLLT1 with adverse outcomes, but not those of 1q21/KMT2A::MLLT11 and trisomy 19 with favorable and adverse outcomes, respectively. Newly identified ACAs with independent adverse prognoses were monosomy 10, trisomies 1, 6, 16, and X, add(12p), and del(9q). Among patients with 9p22/KMT2A::MLLT3, the independent association of French-American-British-type M5 with favorable outcomes was confirmed, and those of trisomy 6 and measurable residual disease at end of induction with adverse outcomes were identified. We provide evidence to incorporate 5 adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine the risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcomes and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs.
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