RESUMO
PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS: Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS: Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION: Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.
Assuntos
Compostos de Anilina , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Mutação , Pirazinas , Tirosina Quinase 3 Semelhante a fms , Humanos , Tirosina Quinase 3 Semelhante a fms/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Pirazinas/uso terapêutico , Adulto , Compostos de Anilina/uso terapêutico , Idoso , Sequências de Repetição em Tandem , Adulto Jovem , Neoplasia Residual , Inibidores de Proteínas Quinases/uso terapêutico , Quimioterapia de Manutenção , Duplicação GênicaRESUMO
This case presents an unusual manifestation of cutaneous chronic graft-vs-host disease (cGVHD) mimicking psoriasis along Blaschko's lines. Such a presentation may pose a particular challenge to providers as it is quite rarely reported, and, therefore, it is possibly misdiagnosed. cGVHD may mimic psoriasis and should be considered in any patient previously transplanted even with a previous history of psoriasis. A Blaschkoid pattern of cGVHD is unusual and may be the manifestation of an immune reaction unveiling a previously masked mosaicism.