Adult T -cell leukaemia/lymphoma (ATL) is an aggressive disease associated with human T-cell lymphotropic virus type-I (HTLV-I) with heterogeneous clinical presentation and outcomes, described in Southern Japan, Europe, Caribbean and previously on Pacific coast of South America including Peru (EHA 2001, abst. 304). Shimoyama’s ATL classification (BHJ1991:79) includes four types: acute, lymphomatous, chronic and smoldering; recently a new clinical type cutaneous had been described (BJD2005:152). Herein we show our experience in ATL in our institution between October 1997 and May 2005 All our 55 cases shown positivity to HTLV-I Western Blot test; immune-histopathology, blood smears and flow cytometry showed mature T-cell lymphocyte. Median age at diagnosis 61 years old (range 23–84), female/male ratio: 1.2. Thirty-one (56%) patients had ECOG status performance at diagnosis ≥ 2. Clinical types: acute (n=26), lymphomatous (n=22), smouldering (n=2), cutaneous (n=5) with no chronic type observed. Median haemoglobin diagnosis was 12.1 g/dl (range 6.9–17), median albumin was 3.2 g/dl (range 1.8 – 4.9), median beta-2 microglobulin was 4.6 g/dl (range 1.5 – 16.9), median globulin was 2.7 g/dl (range 1.5 – 8.2) and DHL was 796 UI/ml (range 331 – 13000). Twenty-five per cent (9/36) debuted with hypercalemia (acute type=7, lymphomatous=2). Acute ATL showed median leukocytes of 48,900 cell/mm3 (range 6830–259,000). IPI risk score was: low (n=6), low intermediate (n=7), high intermediate (n=16) and high (n=27). Treatment for acute ATL was based on acute leukaemia and lymphoma regimens without any response but one, interestingly this patient was treated with Fludarabine 25 mg/mt2 day 1–5 each 28 day for 6 cycles and got complete remission. Twenty-one over 24 lymphomatous ATL type were evaluable for treatment response: overall response 38% (9/24) with 26% complete response. Smouldering and cutaneous ATL types received mainly topic treatments. Stratify analysis for IPI, DHL, beta-2 microglobulin, globulin and albumin for acute and non-acute ATL did not show any statistic difference. Median overall survival was: acute type (2.0 months DE 0.2), lymphomatous type (10.2 months DE 3.6), smouldering type (17.2 months) and cutaneous type (36.2 months DE 19.5) (Log Rank 30,76 p=0.0) ATL persist is a poor prognostic peripheral T-lymphocytic malignancy with bad clinical and therapeutically outcomes mainly in the acute type. Cutaneous type seems to be less aggressive. Figure Figure
Background Acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) represents a broad and complex group of diseases characterized by involvement of the myeloid lineage on hematopoiesis with remarkable variability on clinical presentation, genes mutations, karyotype and molecular abnormalities. Precise characterization on AML/MDS biology is important and the identification of the pathogenic mutated genes is relevant for risk stratification and therapy strategy, mainly for those patients in which targeted therapies is a must. Among pathogenic mutated genes in AML/MDS; TP53 is associated with lower response and high mortality rates. The cumulated number of mutated genes is associated with bad clinical outcomes as well. Aims To explore the frequency and impact of mutated genes on clinical outcomes in a cohort of Peruvian patients diagnosed with AML/MDS studied at diagnosis. Methods In this report we showed 31 consecutive AML/MDS cases treated at three medical centers in Lima (Clínica Delgado, Clínica Anglo Americana and INEN) from January 2016 until July 2020. Information available at diagnosis was: clinical, karyotype, molecular PCR panel, Illumina TruSight Myeloid Sequencing (TSM) panel which include 53 genes involved on oncogenesis, therapy regimen, response to treatment and overall survival (OS). Results A total of 31 cases were studied. F/M ratio 0.55 (11/20), median age 62 years (range 16-87), number of cases by disease were AML=23 and MDS=8. Among the 26 available karyotypes, the abnormal vs diploid karyotype ratio was 0.18 (4/22). Ad hoc PCR panel were positive in just 5 cases among 30 studies available, for FLT3-ITD(n=2), CBFB-MYH11(n=1), NPM1(n=1) and AML-ETO (n=1). In the TSM analysis, median number of pathogenic mutated genes was 3 (range 0-15). Most common (≥18%) pathogenic mutated genes wereBCOR (n=11; 35,5%), CUX1 (n=7; 22,6%) , DNMT3 (n=7; 22,6%), RAD21(n=6; 19,4%), and STAG2 (n=6; 19,4%)with different rates compare with other series (figure 1). Response rate were as follow: 58,1% complete (18/31), 9,7% partial (3/31), 19,3% non-response (6/31) and 12,9% non-evaluable (4/31). The estimated median OS was 36,67 months for the entire cohort, the 1 and 3-years OS rates were 69,9% and 62,2% respectively. For AML and MDS cases median OS was not reached, 1-year OS rates were 68,6% and 72,9% respectively, 3-years OS rates were 54,9% and 72,9% respectively (Log Rank 0,071 p=0,79). MutatedTP53was detected in 5 cases (MDS=3 and AML=2) with no therapy response in 4 and all of them had already dead; median OS for mutatedTP53cases was 3,53±0,43 months; 1-year OS rates for non-mutated vs mutatedTP53cases were 80,2% and 20% respectively, 3-year OS rates for cases with non-mutated vs mutatedTP53were 70,2% and 20% respectively (Log Rank 14,6 p<0,0001) (figure 2). The median OS for mutatedBCORwas not reached; 1-year OS rates for non-mutated vs mutatedBCORwere 77,4% and 52,6% respectively; 3-year OS rates for non-mutated vs mutatedBCORwere 64,5% and 52,6% respectively (Log Rank 0,09 p=0,76). The medians OS were not reached for <3 and ≥3 pathogenic mutated genes cases, 1-year OS rates were 92,3% and 53,5% respectively and 3-years OS rates were 73,8% and 53,5% respectively (Log Rank 1,98 p=0,159). The median OS for ≥4 pathogenic mutated genes cases was 11,93±2,5 months, 1-year OS for <4 and ≥4 were 88,9% and 42,4% respectively and 3-years OS for <4 and ≥4 were 71,1% and 42,4% respectively (Log Rank 3,293 p=0,07). Ad-hoc composite analysis for cases of <4 vs ≥4±mutated-TP53showed medians OS not reached and 9,87±2,9 months respectively; 1-year OS rates were 100% and 40,8% and 3-years OS were 75,0% and 40,8% respectively (Log Rank 9,10 p=0,003)(figure 3). Conclusion NGS for LMA/MDS is an important tool for diagnosis, assessment and risk stratification in our serie of cases. Only 5 over 53 genes were detected in ≥ 18% of casesBCOR, CUX1, DNMT3, RAD, and STAG. TP53 was related with a high therapy failure response and short OS. Number of pathogenic mutated genes ≥3 or ≥4 by TSM showed tendencies for shorter OS. A composite analysis for patients with 4 mutated genes with or without mutated-TP53showed significant shorter OS. Further studies with mature data and more cases are warrant to propose genetics characterization and risk stratification by NGS in Peruvian AML/MDS cases. Disclosures No relevant conflicts of interest to declare.
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