scholarly journals AML with Myelodysplasia-Related Changes: Development, Challenges, and Treatment Advances

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 845
Author(s):  
Kristin L. Koenig ◽  
Kieran D. Sahasrabudhe ◽  
Audrey M. Sigmund ◽  
Bhavana Bhatnagar
Keyword(s):  
Myeloid Leukemia ◽  
Median Overall Survival ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Liposomal Daunorubicin ◽  
Remission Rates ◽  
Specific Subgroup ◽  
Biologic Subtype ◽  
Upfront Therapy ◽  
Acute Myeloid

Acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC) is a distinct biologic subtype of AML that represents 25–34% of all AML diagnoses and associates with especially inferior outcomes compared to non-MRC AML. Typically, patients with AML-MRC experience low remission rates following intensive chemotherapy and a median overall survival of merely 9–12 months. In light of these discouraging outcomes, it has become evident that more effective therapies are needed for patients with AML-MRC. Liposomal daunorubicin–cytarabine (CPX-351) was approved in 2017 for adults with newly diagnosed AML-MRC and those with therapy-related AML (t-AML), and remains the only therapy specifically approved for this patient population. Other studies have also demonstrated the efficacy of the hypomethylating agent (HMA) azacitidine as upfront therapy for AML-MRC patients, which, to date, is the most common treatment employed for patients unable to tolerate the more intensive CPX-351. HMAs and venetoclax combinations have also been evaluated, but additional studies utilizing these agents in this specific subgroup are needed before conclusions regarding their role in the therapeutic armamentarium of AML-MRC patients can be reached. Currently, many studies are ongoing in attempts to further improve outcomes in this historically ill-fated patient group.

Necrotizing Hemorrhagic Gastritis following Acute Myeloid Leukemia Induction with Midostaurin: An Unexpected Complication

2019 ◽  
Vol 143 (1) ◽  
pp. 65-68 ◽  
Author(s):  
Shai Shimony ◽  
Hilla Reiss Mintz ◽  
Yulia Shvartser Beryozkin ◽  
Avivit Shoham ◽  
Pia Raanani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Chemotherapy Regimen ◽  
Rare Complication ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Multikinase Inhibitor ◽  
Acute Myeloid ◽  
Count Recovery

Midostaurin is a tyrosine multikinase inhibitor approved for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) with mutated Fms-like tyrosine kinase-3. We describe a case report of a 49-year-old AML patient treated with an intensive chemotherapy regimen followed by midostaurin. After achieving complete remission with blood count recovery, he suffered from a serious, rare complication of necrotizing hemorrhagic gastritis with no evidence of infection or malignant infiltration, possibly associated with midostaurin therapy.

scholarly journals A Real World Study of Venetoclax Combined with Azacitidine in 64 Chinese Patients Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4414-4414
Author(s):  
Jiejing Qian ◽  
Jieyu Xu ◽  
Qing Hong ◽  
Yinjun Lou ◽  
Liping Mao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Chinese Patients ◽  
Combination Regimen ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Acute Myeloid

Abstract Background: Venetoclax combined with azacitidine has been demonstrated to have a favorable overall response rate and tolerable safety in acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. Methods: This study retrospectively recruited 64 Adults (≥18 years) with newly diagnosed AML ineligible for intensive chemotherapy who had received at least one cycle of treatment with venetoclax plus azacitidine. The primary endpoint was overall survival (OS). Secondary endpoints were remission rates. Safety was evaluated based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: The median age of the enrolled patients was 69 years. The median OS for the cohort was 15.5 months, with 21.2 months for complete responders as opposed to 13.3 months for those who did not achieve a complete response. 39 (60.9%) patients achieved composite complete remission (complete remission (CR) + CR with incomplete count recovery (CRi)) and 7/64 (10.9%) achieved morphologic leukemia-free state (MLFS) with a median follow-up time of 14.7 months. The median CR+CRi duration was 10.9 months. It is noteworthy that 43/64 (67.2%) patients achieved the best response after one cycle with a median time of 1.2 months. Normal karyotype (P=0.015) was significantly associated with extended OS in multivariate analysis, while higher white blood cell count (P=0.032), lower platelet count (p=0.018) and antifungal drug combination (P=0.013) were predictors of shortened OS in univariate analysis. Common grade 3/4 Adverse Events (AEs) included infection (68%) and hematological AEs consisting of neutropenia (93%), anemia (90%), leukopenia (86%), thrombocytopenia (77%) and febrile neutropenia (52%). The median neutropenia duration was 16 days. Conclusions: The novel venetoclax-azacitidine combination regimen showed prolonged survival period, promising efficacy, sound and rapid response, and superior tolerance in Chinese patients newly diagnosed AML. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals CNS Involvement in AML at Diagnosis is Rare and does not Affect Response or Survival: Data from 11 ECOG-ACRIN Trials

2021 ◽  
Author(s):  
Chezi Ganzel ◽  
Ju-Whei Lee ◽  
Hugo Fernandez ◽  
Elisabeth Paietta ◽  
Selina Luger ◽  
...  
Keyword(s):  
Survival Data ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Median Overall Survival ◽  
Newly Diagnosed ◽  
Cns Involvement ◽  
Systematic Data ◽  
Cns Disease ◽  
Significant Difference ◽  
Acute Myeloid

Central nervous system (CNS) involvement in newly diagnosed acute myeloid leukemia (AML) patients is rare and systematic data regarding outcome are scarce. This retrospective study summarized data from 11 consecutive ECOG-ACRIN clinical trials for newly diagnosed AML patients. 3240 patients with AML were analyzed and 36 (1.11%) were found to have CNS involvement at diagnosis. The incidence of CNS disease among the 5 studies with per protocol mandatory lumbar puncture (LP) was similar to the incidence among studies where LP was done at the discretion of the investigator (0.86% vs. 1.41%, p=0.18). There was no significant difference in the complete remission (CR) rate between patients with CNS involvement and those with other extramedullary disease (EMD) sites or those with no EMD (52.8% vs. 59.3-60%). The median overall survival (OS) of CNS-positive patients, other EMD or no EMD was 11.4, 11.3 and 12.7 months, respectively. There was no difference in OS between patients with CNS involvement and those with other EMD (HR 0.96, adjusted p=0.84) or no EMD (HR 1.19, adjusted p=0.44). In conclusion, the reported incidence of CNS involvement of newly diagnosed AML is low (1.1%), irrespective of whether an LP is mandatory or not. The presence of CNS disease at diagnosis does not appear, in and of itself, to portend for a poor prognosis for either achieving an initial CR or OS.

Decitabine Versus Intensive Chemotherapy for Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia

2019 ◽  
Vol 19 (5) ◽  
pp. 290-299.e3
Author(s):  
Eun-Ji Choi ◽  
Je-Hwan Lee ◽  
Han-Seung Park ◽  
Jung-Hee Lee ◽  
Miee Seol ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Acute Myeloid

Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses

2021 ◽  
Author(s):  
Kelly J. Norsworthy ◽  
Xin Gao ◽  
Chia-Wen Ko ◽  
E. Dianne Pulte ◽  
Jiaxi Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Strong Association ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Patient Level ◽  
Acute Myeloid

PURPOSE To explore trial-level and patient-level associations between response (complete remission [CR] and CR + CR with incomplete hematologic [CRi] or platelet [CRp] recovery), event-free survival (EFS), and overall survival (OS) in newly diagnosed acute myeloid leukemia (AML) trials of intensive chemotherapy. METHODS We identified data from eight randomized, active-controlled trials of intensive chemotherapy submitted to the US Food and Drug Administration for treatment of newly diagnosed AML (N = 4,482). Associations between trial-level odds ratios (ORs) for CR and CR + CRi or CRp, and hazard ratios (HRs) for EFS and OS were analyzed using weighted linear regression models. We performed patient-level responder analyses to compare OS by response using pooled data from all studies. RESULTS In trial-level analyses, association between HR for OS and OR for CR was moderate (R2 = 0.49; 95% CI, 0.05 to 0.86), as was the association with OR for CR + CRi or CRp (R2 = 0.48; 95% CI, 0.05 to 0.99). For OS versus EFS, a strong association was observed (R2 = 0.87; 95% CI, 0.47 to 0.98) when EFS definitions were harmonized across trials using raw data. In the patient-level responder analyses, patients who achieved CR had better OS compared with CRi or CRp responders (0.73; 95% CI, 0.64 to 0.84) and nonresponders (HR, 0.33; 95% CI, 0.31 to 0.37). CONCLUSION On a trial level, there is a moderate association between OS and CR rate. A strong association between EFS and OS was observed. However, CIs were wide, and results became moderate using alternative definitions for EFS. Patient-level analyses showed CR responders have better OS compared with CRi or CRp responders and nonresponders. A therapy in newly diagnosed AML with benefit in EFS or substantial benefit in CR rate would be likely to have an OS effect.

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