Prognosis of older patients with newly diagnosed AML undergoing antileukemic therapy: A systematic review

Qin, Hao; Foroutan, Farid; Han, Mi Ah; Devji, Tahira; Nampo, Fernando Kenji; Mukherjee, Sudipto; Alibhai, Shabbir M.H.; Rosko, Ashley; Sekeres, Mikkael A.; Guyatt, Gordon; Brignardello‐Petersen, Romina

doi:10.1371/journal.pone.0278578

Cited by 3 publications

(1 citation statement)

References 107 publications

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“…AML is an aggressive, heterogeneous disease that can present in all age groups with an overall poor prognosis [ 3 ]. Increasing age correlates with incidence, with the highest rates observed in people over 75 [ 4 , 5 ]. Due to the intensity of standard chemotherapies, the cure rate for patients older than 60 years is only 5–15% [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML

James

Curd

Ashworth

et al. 2023

IJMS

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In vivo models of acute myeloid leukemia (AML) are low throughput, and standard liquid culture models fail to recapitulate the mechanical and biochemical properties of the extracellular matrix-rich protective bone marrow niche that contributes to drug resistance. Candidate drug discovery in AML requires advanced synthetic platforms to improve our understanding of the impact of mechanical cues on drug sensitivity in AML. By use of a synthetic, self-assembling peptide hydrogel (SAPH) of modifiable stiffness and composition, a 3D model of the bone marrow niche to screen repurposed FDA-approved drugs has been developed and utilized. AML cell proliferation was dependent on SAPH stiffness, which was optimized to facilitate colony growth. Three candidate FDA-approved drugs were initially screened against the THP-1 cell line and mAF9 primary cells in liquid culture, and EC50 values were used to inform drug sensitivity assays in the peptide hydrogel models. Salinomycin demonstrated efficacy in both an ‘early-stage’ model in which treatment was added shortly after initiation of AML cell encapsulation, and an ‘established’ model in which time-encapsulated cells had started to form colonies. Sensitivity to Vidofludimus treatment was not observed in the hydrogel models, and Atorvastatin demonstrated increased sensitivity in the ‘established’ compared to the ‘early-stage’ model. AML patient samples were equally sensitive to Salinomycin in the 3D hydrogels and partially sensitive to Atorvastatin. Together, this confirms that AML cell sensitivity is drug- and context-specific and that advanced synthetic platforms for higher throughput are valuable tools for pre-clinical evaluation of candidate anti-AML drugs.

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Section: Introductionmentioning

confidence: 99%

Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML

James

Curd

Ashworth

et al. 2023

IJMS

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Real-world practice-based prognostic model for higher-risk myelodysplastic syndromes treated with azacitidine monotherapy: The Kyoto prognostic scoring system

et al. 2023

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The Outcome of Outpatient Intermediate and High Dose Cytarabine Consolidation Chemotherapy in Patients with Acute Myeloid Leukemia. The Experience of King Fahad Specialist Hospital in Dammam, Saudi Arabia

Khalid Ahmed,

Alsaeed,

Kanfer

et al. 2024

J Stem Cell Ther Transplant

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Background: Adult patients with Acute Myeloid Leukemia (AML) have traditionally been hospitalized for the duration of intensive consolidation chemotherapy until blood count recovery to avoid complications. Recently, there has been a trend to shift the care of AML patients treated with intensive chemotherapy from inpatient to outpatient settings to reduce treatment costs and save beds. Methods and materials: A retrospective study of AML patients who received cytarabine consolidation chemotherapy between the 1st of August 2016 and the 31st of December 2023 at King Fahad Specialist Hospital in Dammam, Saudi Arabia was performed. Results: Over a period of 7 years and 4 months, 62 patients received a total of 127 cycles of intensive consolidation chemotherapy at outpatient setting. At diagnosis: 12 patients had extramedullary disease, and 17 patients had adverse cytogenetic abnormalities. Following the 127 cycles of chemotherapy, 38 episodes of febrile neutropenia were encountered, and 46 hospital admissions were required. No complications were encountered following 62.2% of the cycles of consolidation therapy and no early mortality due to intensive consolidation therapy was reported. Out of 62 patients studied, 36 patients underwent various forms of hematopoietic stem cell transplantation. Disease relapses were encountered in 24 patients and the 5-year incidence of relapse for the entire group of patients was 42%. The 5-year leukemia-free survival for the: entire study patients, transplanted patients, and non-transplanted patients were: 43%, 38%, and 50% respectively. The 5-year overall survival for the: entire study patients, transplanted patients, and non-transplanted patients were: 44%, 34%, and 65% respectively. At the end of follow-up: 37 patients (59.68%) were alive, 24 patients (38.71%) were dead, and the fate of 1 patient (1.61%) was unknown as the patient moved to another hospital. Conclusion: Administration of intensive consolidation chemotherapy for patients with AML at outpatient setting is safe, feasible, and cost-effective. The incidence of infectious complications was relatively low. No early treatment-related mortality due to intensive consolidation therapy was encountered. Outpatient administration of intensive consolidation therapy can save beds, reduce hospital costs, and is associated with short-term and long-term outcomes that are comparable to inpatient administration of consolidation therapy.

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Prognosis of older patients with newly diagnosed AML undergoing antileukemic therapy: A systematic review

Cited by 3 publications

References 107 publications

Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML

Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML

Real-world practice-based prognostic model for higher-risk myelodysplastic syndromes treated with azacitidine monotherapy: The Kyoto prognostic scoring system

The Outcome of Outpatient Intermediate and High Dose Cytarabine Consolidation Chemotherapy in Patients with Acute Myeloid Leukemia. The Experience of King Fahad Specialist Hospital in Dammam, Saudi Arabia

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