European LeukemiaNet-defined primary refractory acute myeloid leukemia: the value of allogeneic hematopoietic stem cell transplant and overall response

Abstract

We sought to appraise the value of overall response and salvage chemotherapy, inclusive of allogeneic hematopoietic stem cell transplant (AHSCT), in primary refractory acute myeloid leukemia (prAML). For establishing consistency in clinical practice, the 2017 European LeukemiaNet (ELN) defines prAML as failure to attain CR after at least 2 courses of intensive induction chemotherapy. Among 60 consecutive patients (median age 63 years) correspondent with ELN-criteria for prAML, salvage was documented in 48 cases, 30/48 (63%) being administered intensive chemotherapy regimens and 2/48 consolidated with AHSCT as first line salvage. 13/48 (27%) attained response: CR, 7/13 (54%), CRi, 2/13 (15%), MLFS, 4/13 (31%). The CR/CRi rate was 9/48 (19%), with CR rate of 7/48 (15%). On univariate analysis, intermediate-risk karyotype was the only predictor of response (44% vs 17% in unfavorable karyotype; P = 0.04). Administration of any higher-dose (>1 g/m2) cytarabine intensive induction (P = 0.50), intensive salvage chemotherapy (P = 0.72), targeted salvage (FLT3 or IDH inhibitors) (P = 0.42), greater than 1 salvage regimen (P = 0.89), age < 60 years (P = 0.30), and de novo AML (P = 0.10) did not enhance response achievement, nor a survival advantage. AHSCT was performed in 12 patients with (n = 8) or without (n = 4) CR/CRi/MLFS. 1/2/5-year overall survival (OS) rates were 63%/38%/33% in patients who received AHSCT (n = 12) vs 27%/0%/0% in those who achieved CR/CRi/MLFS but were not transplanted (n = 5), vs 14%/0%/0% who were neither transplanted nor achieved CR/CRi/MLFS (n = 43; P < 0.001); the median OS was 18.6, 12.6 and 5.6 months, respectively. Although CR/CRi/MLFS bridged to AHSCT (n = 8), appeared to manifest a longer median OS (20 months), vs (13.4 months) for those with no response consolidated with AHSCT (n = 4), the difference was not significant P = 0.47. We conclude AHSCT as indispensable for securing long-term survival in prAML (p = 0.03 on multivariate analysis), irrespective of response achievement.

Venetoclax‐based therapy for relapsed or refractory acute myeloid leukaemia following intensive induction chemotherapy

“…The oral selective Bcl‐2 inhibitor venetoclax in combination with HMA represents the most significant improvement for treating elderly and unfit patients with newly diagnosed AML with significant increase in OS and CR rates 18,19 and in the R/R AML setting, compelling evidence supports the addition of venetoclax to intensive salvage chemotherapy with reported CR/CRi rates of ~70% 20,21 . Reportedly, for prAML patients, median OS for those offered supportive care is only ~3.5 months and for those treated with intensive cytoreductive therapy, the median OS is ~7 months 7,8,11,22–24 . Even if AHSCT remains indispensable for long term OS, the relapse rates post‐AHSCT remain very high 11,22,24 .…”

Serum proteomics screening intercellular adhesion molecule-2 improves intermediate-risk stratification in acute myeloid leukemia

“…In general, the intensity and type of treatment for AML patients are adjusted according to the risk status, and standard chemotherapy is considered reasonable for favorable-risk AML, whereas allogeneic hematopoietic stem cell transplantation is used for adverse-risk AML. 23 For intermediate-risk AML, bone marrow transplantation and chemotherapy are commonly used after the first complete remission, but it is still controversial which method can improve the prognosis of patients. 24 New molecular markers have been shown to affect prognosis and have been included in the revision of the ELN classification.…”

Acute lymphoblastic leukemia with clonal evolution due to delay in chemotherapy: A report of a case

“…Parents of the patient informed that during this time the patient did not undergo any special therapeutic intervention and for supportive reasons 7 units of whole blood and 10 units of random donor platelets. Accordingly, the patient was found to be severely anemic and severely thrombocytopenic with peripheral blood film demonstrating more than 90% blast cells, also 2A; second clone showed 46, XY with del [7] (q22; q36) del (p22; p24), as shown in Figure 2B; and the third clone of cells showed 46, XY, as shown in Figure 2C. The patient did not respond to chemotherapy and died within 1 week of induction chemotherapy (HyperCVAD-A).…”

“…Accordingly, bone marrow analysis was repeated and demonstrated morphological and immunophenotypic features consistent with previous bone marrow analysis. Repeated cytogenetic analysis revealed presence of three different clones of blast cells: one clone showed 46, XY with del (p22; p24) t (11;14) (p15.3; q11.2) as shown in Figure 2A ; second clone showed 46, XY with del [ 7 ] (q22; q36) del (p22; p24), as shown in Figure 2B ; and the third clone of cells showed 46, XY, as shown in Figure 2C . The patient did not respond to chemotherapy and died within 1 week of induction chemotherapy (HyperCVAD‐A).…”

“…Spontaneous clonal evolution results in emergence of clones of neoplastic cells that transforms a previously well‐controlled disease to one that is unresponsive to available therapeutic modalities [ 6 ]. It is very obvious that at cellular and molecular levels, there are many factors, sill unexplored, that take part in intercellular signaling and thus lead to clonal evolution [ 7 ].…”