and cytokine levels were associated with acute GVHD (IL-7) or pattern of immune reconstitution (IL-15). However, it is not known whether recipients of lower-intensity conditioning or sirolimus-based GVHD prophylaxis have variable levels of these cytokines or whether such potential cytokine variability is associated with clinical outcome. To begin to address this, we measured multiple cytokine levels (MesoScale multiplex assay; current analysis restricted to IL-7 and IL-15 levels at day 0 of transplant) in recipients of low-intensity conditioning (Flu/Cy; total Cy dose, 1200 mg/m 2 ; see Table 1). Patients received GVHD prophylaxis consisting of cyclosporine plus shortcourse sirolimus (d2 through d14 post-SCT) at either standard-dose (n¼46; "SD Cohort") or high-dose (n¼20; "HD Cohort") (target trough level: 5-10 or 20-30 ng/ml, respectively). All patients received pre-emptive DLI consisting of rapamycin-resistant T cells (Fowler et al; Blood, 2013); however, in the current study, T cell manufacturing was reduced from 12 days to 6 days. Clinical outcomes (Table 1) were similar in SD and HD Cohorts, including: donor T cell and myeloid cell chimerism pre-DLI (d14 post-SCT) and post-DLI (d28 post-SCT), and incidence of classical acute GVHD. Remarkably, a wide range of IL-7 and IL-15 values were detected at day 0 of SCT in both SD and HD Cohorts
Aims: Our aim is to suggest that DAC has a favourable efficacy and safety profile as rescue therapy after AZA failure Methods: We report a short case series of 4 patients referred to our institution with s-AML occurring after MDS and MDS/MPN in accelerated phase treated with DAC following AZA failure used for MDS phase treatment. At the time of diagnosis, median age of patients was 73 (range 68-78), all patients were Intermediate-2 according to IPSS and they had RBC transfusion dependency. All patients underwent blood cell count samples, bone marrow biopsy and conventional cytogenetic assays to confirm diagnosis. Results: The 1 st patient was a 78-years-old woman with anemia (red blood cell transfusion dependency about 4-5 RBC units/month) and 15% of bone marrow blasts diagnostic for MDS-EB-2. Cytogenetic analysis showed a normal karyotype. She started treatment with azacytidine sc at 75 mg/sm/day for 7 days in 28-day cycles. After 11 courses the patient showed treatment failure with progression to AML (hyperleukocytosis WBC 150.000/microL, bone marrow blasts 40% and monosomy 8), thus she started treatment with decitabine iv at 20 mg/sm for 5 days in 28-day cycles plus hydroxyurea. A bone marrow biopsy done after 4 and 8 cycles showed 10% and 8% of blasts, respectively. After 9 th cycle she died due to chronic obstructive pulmonary disease worsening. The 2 nd patient was a 72-years-old man with thrombocytosis and anemia (red blood cell transfusion dependency about 1-2 RBC units/month) and 15% of bone marrow blasts diagnostic for MDS/MPN in accelerated phase. He started treatment with azacytidine sc at 75 mg/sm/day for 7 days in 28-day cycles. After 24 courses of azacytidine he showed progression to AML (bone marrow blasts 30% and fibrosis), thus he started decitabine iv at 20 mg/ sm for 5 days in 28-day cycles. After 1st cycle the patient obtained a transfusion indipendency lasted for the following 3 cycles. After 4 th cycle he developed pancytopenia, therefore a BM assay showed 50% of blasts. Finally the patient died for infectiuos complications. The 3 rd patient was a 68-years-old woman with a diagnosis of MDS-EB-2 (bone marrow blasts 15%), normal karyotype and a red blood cell transfusion dependency of about 1-2 RBC units/month. She started azacytidine sc at 75 mg/sm/day for 7 days in 28-day cycles. After 32 courses the disease progressed to AML (70% of blasts), thus she started therapy with decitabine 20 mg/sm for 5 days every 28 days achieving a partial response. At the end of 4th cycle she died due to cerebral hemorrhage. The 4 th patient was a 74-yearsold man treated with azacitidine (75 mg/sm for 7 days every 28 days) for a MDS-EB-2 (bone marrow blasts 10%, normal karyotype. He had a red blood cell transfusion dependency of about 1-2 RBC units/month). After 10 cycles of azacytidine he showed therapy failure with progression to AML (bone marrow blasts 80%), so he started decitabine 20 mg/sm for 5 days every 28 days, discontinued after 2 courses due to clinical worsening Summary/Conclusion: In this short mo...
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