RESUMEN
The prognostic significance of the length of internal tandem duplication (ITD) insertions in mutant FLT3 genes in acute myeloid leukemia (AML) is controversial. We conducted a retrospective study to evaluate the correlation between the ITD base-pair (bp) insertion length and clinical outcomes. The mutational status of the FLT3 gene was evaluated in 402 of 467 consecutive AML patients treated at the University of Maryland Greenebaum Comprehensive Cancer Center between 2013 and 2020; 77 had FLT3-ITD mutations. Patients were divided into three cohorts based on bp insertion length (<30 (0−33rd percentile), 30−53 (34th−66th percentile),and >53 (>66th percentile)). The median overall survival (OS) of patients was 16.5 months (confidence interval (CI) 7.3-NA), 18.5 months (CI 7.3-NA), and 21.9 months (CI 19.1-NA) (p = 0.03) for the <30, 30−53, and >53 bp insertion length cohorts, respectively. The adjusted median event-free survival (EFS) for the ITD insertion lengths >30, 30−53, and >53 bp was 11.1 months (CI 2.8−16.5), 5.2 months (CI 2.9−12.6), and 9.1 months (CI 5.4-NA) (p = 0.5), respectively. Complete remission (CR) rates were 64% (<30 inserted bp), 55% (30−53 inserted bp), and 79% (>53 inserted bp) (p = 0.23). For patients treated with gilteritinib and midostaurin, the unadjusted median OS was not statistically significantly different between cohorts.
RESUMEN
There is a deficiency of real-world data on the impact of combining venetoclax (VEN) with hypomethylating agents (HMAs) in newly diagnosed acute myeloid leukemia (AML) patients. We conducted a single-center, propensity-adjusted retrospective cohort study to compare composite complete remission (CCR) rates, median overall survival (m-OS) and median event-free survival (m-EFS). A total of 170 adult AML patients were treated with first-line azacitidine (AZA) or decitabine (DEC) +/- VEN. Median age was 71 years and 99 (58%) were male. Median follow-up in HMA and HMA-VEN groups was 79 and 21 months. Treatments included AZA alone (n=35, 21%), DEC alone (n=84, 49%), AZA-VEN (n=24, 14%) and DEC-VEN (n=27, 16%). VEN improved CCR rates to HMAs overall (52% vs. 27%, P<0.05) and to AZA (54% vs. 10%, P<0.05), but not to DEC (43% vs. 32%, P=0.35); it did not improve OS, and only improved EFS for AZA (10.5 vs. 3.8 months, P<0.05). CCR rates were lower with AZA than with DEC (13% vs. 33%, P<0.05), but OS and EFS were not different statistically. CCR rates did not differ for AZA-VEN vs. DEC-VEN (CCR: 58% vs. 52%, P=0.66), but OS and EFS were longer for AZA-VEN (m-OS: 12.3 vs. 2.2 months, P<0.05; m-EFS: 9.2 vs. 2.1 months, P<0.05). Our analysis showed that combining VEN with AZA in newly diagnosed AML patients improved outcomes, but combining VEN with DEC did not. AZA-VEN was associated with improved outcomes compared to DEC-VEN. Further studies are needed to test the benefit of combining VEN with DEC.
RESUMEN
Acute myeloid leukemia (AML) is the common type of acute leukemia in adults. Definitive prognostic significance of variants of unknown significance lacks for many commonly mutated genes, including the isocitrate dehydrogenase 1 (IDH1) synonymous single nucleotide polymorphism (SNP) variant c.315C>T. In this retrospective cohort study of 248 AML patients at the University of Maryland Greenebaum Comprehensive Cancer Center, we show that the IDH1 c.315C>T SNP, previously reported to be associated with poor prognosis by other studies with conflicting data, does not confer worse prognosis, with a median overall survival (OS) of 17.1 months compared to 15.1 months for patients without this SNP (P=0.57). The lack of negative effect on prognosis by IDH1 SNP c.315C>T is consistent with the absence of amino acid alteration (p.Gly105Gly).
RESUMEN
PURPOSE OF REVIEW: Rare malignancies developing from lymphocyte precursor cells, lymphoblastic leukemia (LBL), and acute lymphoblastic lymphoma (ALL) have historically been viewed as different manifestations of the same disease process. This review examines data on their epidemiology, genetics, clinical presentation, and response to treatment while highlighting areas of similarity and divergence between these two clinical entities. RECENT FINDINGS: Pediatric-type ALL chemotherapy regimens, compared to both lymphoma-type chemotherapy and adult-type ALL regimens, have led to improved outcomes for children, adolescents, and young adults with ALL. BCR-ABL-targeting tyrosine kinase inhibitors (TKIs) have improved outcomes in Philadelphia chromosome-positive (Ph +) ALL and in rare cases of Ph + LBL. Newer therapies including blinatumomab, inotuzumab, CAR-T therapy, and nelarabine have improved outcomes in selected cases of ALL and have an emerging role in the management of LBL. Better understanding of ALL and LBL biology allows for the development of therapies that target immunophenotypic or genetic features found in subsets of both diseases. Novel therapies are leading to improved outcomes in Ph + and relapsed and refractory disease.