A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study

Abstract

A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy þ Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36 ± 4%, respectively. Disease status (relapse o12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N ¼ 36): OS 58%, EFS 45%; one adverse factor (intermediate, N ¼ 54): OS 37%, EFS 31%; two or three adverse factors (poor, N ¼ 43): OS 12%, EFS 12% (Po10 À4 , P ¼ 0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

Influence of molecular subgroups on outcome of acute myeloid leukemia with normal karyotype in 141 patients undergoing salvage allogeneic stem cell transplantation in primary induction failure or beyond first relapse

“…In contrast, patients with an unfavorable genotype showed a significantly shorter CR, including a remission of less than six months in 39% of patients who would have been regarded as primary refractory by many groups. 10,35,36 Moreover, the FLT3-ITD + subgroup was characterized by a higher number of patients with circulating blasts, and a higher leukemia burden in BM. As compared to the favorable genotype, OS and LFS after HSCT beyond CR1 were clearly inferior among patients showing an unfavorable genotype at time of diagnosis.…”

“…4 Recently, the favorable genotype was shown to maintain a good prognosis in relapsed and refractory AML after gemtuzumab-ozogamicin based therapy, 8 whereas FLT3-ITD retained its negative prognostic value in two series of relapsed patients which both included a limited number of patients receiving salvage alloHSCT. 9,10 Here, we present the results of a large cohort of patients who had all received the FLAMSA-RIC regimen before alloHSCT for CN-AML, either in PIF or beyond CR1. The study aimed to further evaluate the role of the most common molecular aberrations in this setting, and to determine the efficacy of FLAMSA-RIC based alloHSCT in clinically and molecularly defined patient subgroups.…”

5‐Azacytidine treatment for relapsed or refractory acute myeloid leukemia after intensive chemotherapy

“…The most important predictors of response to salvage chemotherapy are age, karyotype, duration of first remission, and history of previous hematopoietic stem cell transplantation (HSCT) [3]. On the other hand disease status (relapse < 12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for overall survival (OS) and event free survival [4]. In R=R patients, the main goal is to achieve a CR since patients who could proceed to allogenic HSCT whilst in CR are likely to have the best chances to achieve long-term OS [5].…”

Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation

“…2,5 This negative impact also exists in the setting of relapse; patients harboring the FLT3-ITD mutation have a significantly worse outcome in first relapse compared with those without the mutation. [6][7][8] Several novel agents targeting the FLT3 kinase have shown promising activity in patients with AML and mutated FLT3.…”