Acute myeloid leukemia with inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2): Study of 61 patients treated with intensive protocols

Abstract

IntroductionInv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms.ObjectiveThe aim of this study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017.MethodsIn this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed.ResultsSixty‐one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One‐ and 4‐year CIR were 52% and 56%. One‐ and 4‐year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, P = .017).ConclusionInv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.

Unified classification and risk-stratification in Acute Myeloid Leukemia

“…Furthermore, this model demonstrates that a key differentiator between sAML1 and sAML2 is response to induction chemotherapy, with 43.7% of sAML2 group patients not attaining CR as compared to 26% in sAML1 (Fisher’s Exact test p = 0.002). Consistent with prior findings, adverse outcomes in TP53/complex and inv(3) are explained by highly chemoresistant disease and relapse-related mortality 14 , 23 . These observations were also observed in the AMLSG cohort (Supplementary Fig.…”

“…Cox multi-state models 22 , 23 were used to estimate the transition covariate coefficients across six clinical endpoints (Alive (received induction chemotherapy) → Alive in CR; Alive → Death no CR; Alive in CR → Alive in Relapse; Alive in CR → Death in CR; Alive in Relapse → Death in Relapse) for the following 4 models: (1) AML Classes; (2) ELN 2017 ; (3) Proposed risk score; (4) AML Classes, demographic and clinical parameters. For detailed information on the coefficients please refer to: https://www.aml-risk-model.com/calculator…”

“…2b, Supplementary Figs. [22][23][24][25][26][27][28][29]. These findings provide a rationale for the development of a risk stratification schema that is based on class membership and FLT3 ITD status, thus offering the opportunity to unify classification to risk stratification and importantly link a biological definition of disease ontology to clinical presentation and outcomes.…”

“…For the development of a personalized risk calculator we consider 3201 intensively treated patients from the AML NCRI and AMLSG cohorts. For each patient,cytogenetic findings and mutations in the panel of 32 genes were considered to derive class assignment, ELN 2017 and proposed risk scores.Cox multi-state models22,23 were used to estimate the transition covariate coefficients across six clinical endpoints (Alive (received induction chemotherapy) → Alive in CR; Alive → Death no CR; Alive in CR → Alive in Relapse; Alive in CR → Death in CR; Alive in Relapse → Death in Relapse) for the following 4 models: (1) AML Classes; (2) ELN 2017 ; (3) Proposed risk score; (4) AML Classes, demographic and clinical parameters. For detailed information on the coefficients please refer to: https://www.aml-risk-model.com/calculator…”

Unified classification and risk-stratification in Acute Myeloid Leukemia

“…Furthermore, this model demonstrates that a key differentiator between sAML1 and sAML2 is response to induction chemotherapy, with 43.7% of sAML2 group patients not attaining CR as compared to 26% in sAML1 (Fisher’s Exact test p=0.002). Consistent with prior findings, adverse outcomes in TP53/complex and inv(3) are explained by highly chemoresistant disease and relapse-related mortality 14,23 . These observations were also observed in the AMLSG cohort (S.Figure 31) (S.Table 9).…”