Dataset Information

Hybrid Email and Outpatient Clinics to Optimize Maintenance Therapy in Acute Lymphoblastic Leukemia.

ABSTRACT: Acute lymphoblastic leukemia treatment includes an outpatient (OP)-based 2-year maintenance therapy (MT). Over an 8-year period, patients were transited from only OP to a hybrid e-clinic/OP-clinic model. Electronic and patient-held medical records of acute lymphoblastic leukemia patients 1 to 18 years old during MT were used to analyze demographics, drug doses, treatment response and cost. A survey evaluated family satisfaction with the hybrid service. Four hundred and seventy-eight children, all with at least 1 year of MT from March 13, 2014 to March 24, 2022 were grouped into 4 treatment eras, representing the transition from all OP (era 1) to the current hybrid MT practice (era 4). Cohort demographics were similar across all eras. With transition to era 4, OP visits decreased to a third (16 to 18/48 visits). Practice optimization in era 2 resulted in higher MT dose intensity in subsequent eras (era 1: median 82% [interquartile range, 63 to 97]; era 2: 93% [73 to 108]; era 3: 88% [68 to 106]; era 4: 90% [74 to 114], P <0·0001), with no differences in absolute neutrophil count or neutropenia-related toxicity ( P =0.8). The hybrid service reduced MT expenses by ~50% and families (133/156, 85%) reported being very satisfied. Our experience indicates that a hybrid model is feasible, effective and less burdensome for patients and families.

SUBMITTER: Mungle T

PROVIDER: S-EPMC10756697 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Hybrid Email and Outpatient Clinics to Optimize Maintenance Therapy in Acute Lymphoblastic Leukemia.

Mungle Tushar T Mahadevan Ananya A Das Parag P Mehta Amit K AK Gogoi Manash P MP Jana Bishwaranjan B Ghara Niharendu N Ghosh Debjani D Saha Vaskar V Krishnan Shekhar S

Journal of pediatric hematology/oncology 20231212 1

Acute lymphoblastic leukemia treatment includes an outpatient (OP)-based 2-year maintenance therapy (MT). Over an 8-year period, patients were transited from only OP to a hybrid e-clinic/OP-clinic model. Electronic and patient-held medical records of acute lymphoblastic leukemia patients 1 to 18 years old during MT were used to analyze demographics, drug doses, treatment response and cost. A survey evaluated family satisfaction with the hybrid service. Four hundred and seventy-eight children, al ...[more]

PMID: 38096154

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Project description:Maintenance therapy (MT) with oral methotrexate (MTX) and 6-mercaptopurine (6-MP) is essential for the cure of acute lymphoblastic leukemia (ALL). MTX and 6-MP interfere with nucleotide synthesis and salvage pathways. The primary cytotoxic mechanism involves the incorporation of thioguanine nucleotides (TGNs) into DNA (as DNA-TG), which may be enhanced by the inhibition of de novo purine synthesis by other MTX/6-MP metabolites. Co-medication during MT is common. Although Pneumocystis jirovecii prophylaxis appears safe, the benefit of glucocorticosteroid/vincristine pulses in improving survival and of allopurinol to moderate 6-MP pharmacokinetics remains uncertain. Numerous genetic polymorphisms influence the pharmacology, efficacy, and toxicity (mainly myelosuppression and hepatotoxicity) of MTX and thiopurines. Thiopurine S-methyltransferase (encoded by TPMT) decreases TGNs but increases methylated 6-MP metabolites (MeMPs); similarly, nudix hydrolase 15 (encoded by NUDT15) also decreases TGNs available for DNA incorporation. Loss-of-function variants in both genes are currently used to guide MT, but do not fully explain the inter-patient variability in thiopurine toxicity. Because of the large inter-individual variations in MTX/6-MP bioavailability and metabolism, dose adjustments are traditionally guided by the degree of myelosuppression, but this does not accurately reflect treatment intensity. DNA-TG is a common downstream metabolite of MTX/6-MP combination chemotherapy, and a higher level of DNA-TG has been associated with a lower relapse hazard, leading to the development of the Thiopurine Enhanced ALL Maintenance (TEAM) strategy-the addition of low-dose (2.5-12.5 mg/m2/day) 6-thioguanine to the 6-MP/MTX backbone-that is currently being tested in a randomized ALLTogether1 trial (EudraCT: 2018-001795-38). Mutations in the thiopurine and MTX metabolism pathways, and in the mismatch repair genes have been identified in early ALL relapses, providing valuable insights to assist the development of strategies to detect imminent relapse, to facilitate relapse salvage therapy, and even to bring about changes in frontline ALL therapy to mitigate this relapse risk.

Dataset Information

Hybrid Email and Outpatient Clinics to Optimize Maintenance Therapy in Acute Lymphoblastic Leukemia.

Publications

Hybrid Email and Outpatient Clinics to Optimize Maintenance Therapy in Acute Lymphoblastic Leukemia.

Similar Datasets

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