Venetoclax combined with homoharringtonine, cytarabine and aclacinomycin as induction therapy in newly diagnosed Chinese acute myeloid leukaemia patients: A multicentre phase II study.

TBC1D16 predicts chemosensitivity and prognosis in adult acute myeloid leukemia (AML) patients

Recurrent Gene Mutations in Pediatric Patients with AML By Targeted Sequencing ―the Jccg Study, JPLSG AML-05―

FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.

We previously reported the clinical, pathological and molecular genetic findings of a series of adult acute myeloid leukaemia (AML) patients with ocular extramedullary myeloid leukaemia (EML) (Ohanian et al, 2018). In response, Dr. Paydas took exception to our assertion that ocular EML is uncommon. The differences between our study and the studies cited by Dr. Paydas appear to reflect differences in patient age and geography. While the overall incidence of EML in AML patients of all ages is about 9%, its incidence in children may reach as high as 40% (Ohanian et al, 2013). At our institution, over a period of 12 years, 7% (252/3764) of adult AML patients demonstrated EML; 10 patients with EML (4%) had ocular involvement. Thus, at our institution, the overall incidence of ocular EML in adult AML patients is 10 out of 3,724 (0·3%) (Ohanian et al, 2018). Of the 10 cases of ocular AML that we reported, 4 were therapy-related, and 2 de novo AML showed the t(8;21)(q22;q22) (Ohanian et al, 2018). In contrast, most ocular EML cases reported in children represent extramedullary involvement by de novo AML, and the most common cytogenetic abnormality is t(8;21)(q22;q22), which has been identified in up to 100% (9/9) of cases (Schwyzer et al, 1998). In the Western world, ocular EML is uncommon in AML patients of all ages (Bisschop et al, 2001). In a recent retrospective analysis of 3240 AML patients in the United States ranging in age from 15 (Ganzel et al, 2016) to 86 years (Rowe et al, 2004), 769 (23·7%) evaluable patients had clinical evidence of EML at diagnosis, none of which were ocular (Ganzel et al, 2016). Compared to those without EML, patients with EML were generally younger and predominantly male, consistent with the literature (Cavdar et al, 1989; Bisschop et al, 2001). In a Dutch study of 477 children with AML, 25% had EML, none of which were ocular (Bisschop et al, 2001). The incidence of ocular EML appears much higher in children in Africa (Davies & Owor, 1965; Schwyzer et al, 1998) and the Middle-East than in the Western hemisphere (Cavdar et al, 1989). In a study from Uganda, among 8 children with granulocytic sarcoma, 6 demonstrated orbital involvement, 4 of which were confirmed by biopsy (Davies & Owor, 1965). In a South African study of 88 children of African descent with AML, 15 (17%) had EML, 9 with ocular involvement, although biopsy results were not provided (Schwyzer et al, 1998). Similarly, a 20-year retrospective study reported that 33/133 Turkish children with AML presented with ocular symptoms (exophthalmos, chemosis, orbital masses), 12 (36%) with biopsy-proven EML (Cavdar et al, 1989). These authors reported an association between paediatric ocular EML, lower socioeconomic status and defects in delayed hypersensitivity testing, suggesting T-cell deficiency (Cavdar et al, 1989). It is difficult to determine the true incidence of ocular EML in particular, and of EML in general. Many of the reported cases of ocular EML were based solely on physical examination and were not biopsy-proven, which may overestimate its incidence. On the other hand, because baseline and follow-up imaging studies are not currently standard practice in AML management, it is likely that EML is under-reported. Several small prospective studies using positron emission tomography (PET) or PET/computed tomography (CT) imaging in AML patients either before induction chemotherapy or at relapse have demonstrated that many EML cases are undetectable by physical examination alone. A pilot study of 10 AML patients who underwent PET or PET/CT imaging before induction chemotherapy identified EML in 40%, involving meninges, pericardium, abdomen, testes and lymph nodes (Buck et al, 2008). A larger study of 26 AML patients who underwent PET imaging before induction chemotherapy demonstrated that PET imaging detected EML in twice as many patients as physical examination alone (65% vs. 31%) (Cribe et al, 2013). In 10 patients with newly diagnosed or relapsed AML with known EML, PET/CT imaging detected new sites of EML in 60% of patients (Ohanian et al, 2013). The results of these studies provide a rationale for baseline imaging in AML to help establish the true incidence of EML, and possibly change the current practice of monitoring only bone marrow responses to AML therapy. MO and LA wrote the manuscript. CT reviewed and approved the manuscript.

Feasibility of Allogeneic Hematopoietic Cell Transplantation Among High-Risk AML Patients in First Complete Remission: Results of the Transplant Objective from the SWOG (S1203) Randomized Phase III Study of Induction Therapy Using Standard 7+3 Therapy or Idarubicin with High-Dose Cytarabine (IA) Versus IA Plus Vorinostat

Prognostic Significance of Intracellular Survivin in Myeloid Blast Cells As an Inhibitor of Apoptosis in Egyptian Adult Acute Myeloid Leukemia (AML) Patients

Comparative effectiveness of busulfan/cyclophosphamide versus busulfan/fludarabine myeloablative conditioning for allogeneic hematopoietic cell transplantation in acute myeloid leukemia and myelodysplastic syndrome

Subnormal Vitamin D Levels Are Associated with Adverse Outcome In Newly-Diagnosed Similarly-Treated Adult Acute Myeloid Leukemia (AML) Patients.

Identification of Relapse Risk Using a Multiparameter Flow Cytometry-Based Detection of Minimal Residual Disease in Adult Patients with Acute Myeloid Leukemia at ELN Intermediate-Risk

RUNX3 Expression Is an Independent Prognostic Factor in Cytogenetically Abnormal Adult Acute Myeloid Leukemia (AML) Patients with Wild-Type FLT3.

Venetoclax (VEN) combined with hypomethylating agents (HMA) decitabine or azacitidine is used for adult acute myeloid leukaemia (AML), but its application in paediatric, adolescent and young adult (AYA) AML lacks prospective studies. We performed a retrospective chart review of paediatric and AYA AML patients treated with HMA + VEN at Cincinnati Children's Hospital Medical Centre. Twenty-seven patients received 30 HMA + VEN treatment courses for relapsed/refractory (R/R, n = 21) or newly diagnosed (n = 9) AML due to ineligibility for intensive chemotherapy. The R/R cohort had high-risk cytomolecular genetic alterations and prior extensive treatments, with 50% (n = 9) of relapse patients (n = 18) having undergone haematopoietic stem cell transplantation (HSCT). Venetoclax treatment using the 400 mg adult exposure-equivelant dosing (AED) had a median duration of 21 days (range 7-30 days). Grade 3-4 toxicities included neutropenia (90%), anaemia (64%), thrombocytopenia (64%) and febrile neutropenia (44%). The overall complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 73% (77% minimal residual disease [MRD] negativity <0.1%), with 60% undergoing HSCT. Among newly diagnosed patients (n = 9), 89% achieved CR/CRi (78% MRD negativity) and 78% proceeded to HSCT. The R/R cohort (n = 21) showed a 67% CR/CRi rate (71% MRD negativity), with 52% undergoing HSCT. These findings support the safety and efficacy of HMA + VEN in paediatric/AYA AML, indicating it as a viable option for patients unfit for intensive chemotherapy. Further studies are necessary to determine optimal venetoclax dosing, chemotherapy combinations and pharmacokinetics in this population.

Venetoclax Combined with Daunorubicin and Cytarabine (DAV) As Induction Therapy in De Novo Young Adult Acute Myeloid Leukemia

Frequency and Prognostic Impact of NUP98/NSD1 Translocations in Adult AML and MDS Patients

Venetoclax Combined with Three-Day Multi-Frequency Decitabine (DEC3-VEN) in the Treatment of Adult Patients with <i>De Novo</i> Acute Myeloid Leukemia

Validation of the 2022 European Leukemianet Risk Stratification of Acute Myeloid Leukemia (AML)