Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment-refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients. Median age at diagnosis was 65 years. Best response to HMAs was complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%). Additionally, 8.5% experienced hematologic improvement. Median OS was 6.7 months (95% confidence interval, 6.1-7.3). As expected, OS differed significantly by best response, with patients achieving CR and CRi having a median OS of 25.3 and 14.6 months, respectively. In multivariate analysis, the presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates, whereas the presence of >5% circulating blasts and >20% bone marrow blasts were associated with decreased OS. A significant subset of RR-AML patients (16%) achieved CR/CRi with HMAs and experienced a median OS of 21 months. Outside of a clinical trial, HMAs represent a reasonable therapeutic option for some patients with RR-AML.

Summary. In this study, we used multiparameter flow cytometry to quantify minimal residual disease (MRD) in 165 serial bone marrow samples from 40 patients diagnosed with acute lymphoblastic leukaemia (ALL) who underwent allogeneic stem cell transplantation (allo-SCT) from siblings (n ¼ 34) or unrelated donors (n ¼ 6). Samples were prospectively taken from 24 patients before starting the conditioning regimen, at days +30, +60 and +90 and subsequently every 2-3 months. Samples from 16 patients in complete remission (CR) after allo-SCT were taken at least twice. Six of 24 patients harboured MRD (0AE2-10% of mononuclear cells) at transplant and 18 were negative. Estimated disease-free survival for the MRD+ and MRDgroups at transplant was 33AE3% and 73AE5% respectively (P ¼ 0AE03). During follow-up, increasing MRD levels were detected in nine patients, a finding that preceded marrow relapse by 1-6 months. Two patients with stable low MRD levels remained in CR. When we used flow cytometry to test the effect of donor leucocyte infusions (DLI) in six patients, we observed that the only sustained remission was achieved when DLI was applied prior to overt relapse. We conclude that MRD by flow cytometry can rapidly assess tumoral burden before transplant to predict outcome, and can be clinically useful for the timing of DLI for increasing levels of leukaemia after transplant.

We hypothesize that the use of the individual patient ex vivo pharmacological profiles may help to guide a personalized treatment selection.

Intestinal decolonization with aminoglycosides is associated with a reduction in crude mortality and KPCKP infections at 180 days after initiating treatment.

Summary:(CGVHD), older age, use of methotrexate (MTX) as prophylaxis for GVHD and low levels of serum immunoglobulin (Ig). 5,6 Classical management of these patients To describe clinical outcome with first line immunosuppression therapy for obstructive airways disease includes bronchodilators (aerosolised ␤-agonists), antiinfectious prophylaxis, Igs replacement, and immunosup-(OAD) after allogeneic BMT, we have retrospectively examined 20 long-term survivors affected by OAD. All pressive agents such as prednisone (PRD), AZT or CsA. Despite aggressive treatment, the mortality rate is over 50% patients had normal pulmonary function test (PFTs) before BMT. OAD was defined as FEV1 less than 80%, (ranging from 21 to 100%), in most published series, 7,8 significantly higher than in comparable cohorts without OAD. FER less than 80%, maximum midexpiratory flow rate of 50% vital capacity (MMFR) less than 65%, orComplexity in the management of these patients is due largely to the lack of standardised approaches and the fact residual volume greater than 120. Prednisone (n = 4), CsA (n = 8) and azathioprine (n = 8) have been used as that the effectiveness of specific regimens has never been established. Furthermore, there are no well-defined first-line immunosuppression agents. Mean follow-up was 65 months (range 15-142). We identified three catresponse criteria and consequently the optimal duration of immunosuppression therapy remains uncertain. egories of patients according to response to treatment: complete (n = 6, 30%), partial (n = 6, 30%) or noIn this retrospective study we analysed 20 patients affected by OAD from 275 patients who underwent allogeneic response (n = 8, 40%). Age, FEV1, time of onset after BMT, Karnofsky index or immunosuppression modality BMT at a single institution over a 12 year period and had had long-term follow-up. Presence of risk factors was do not seem to be related to subsequent response. However, patients with low values of MMFR and high values assessed. The aims of the study were to analyse the patterns of pulmonary function evolution over the treatment period, of RV at the beginning of therapy are likely to show poor response. In the complete response group, normaland evaluate the role of different immunosuppression regimens in clinical outcome. isation of PFTs is achieved within the first months of treatment (median 6 months ranging from 3 to 9 months), suggesting that prolonged therapy is not advantageous and could increase morbidity and morPatients and methods tality if there are no other signs of CGVHD. Keywords: obstructive airways; immunosuppression; Patients BMT Between May 1981 and July 1995, allogeneic bone marrow transplantation was performed on 275 patients at the University Hospital Reina Sofia. Of these patients 225 who Respiratory complications after BMT, both early (occurring survived more than 3 months after BMT and were at risk within the first 3 months) and late, affect 40-60% of of developing OAD were included in this study. Patient patients and are the major cause of mo...

ex vivo expansion protocols, OX40 blocking might be crucial to optimize the use of Treg to prevent GVHD.

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-neg) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph-neg adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15-60 years (y) with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation, were assigned to receive delayed consolidation and maintenance therapy up to 2y in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95%CI) cumulative incidence of relapse (CIR), overall survival (OS) and event-free survival (EFS) probabilities for the whole series were 43%±7%, 49%±7% and 40±6%, respectively, with CIR and OS rates of 45±8% and 59±9% for patients assigned to chemotherapy and of 40±12% and 38±11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph-neg adult ALL patients up to 60y with adequate MRD response after induction and consolidation. Better post-remission alternative therapies are especially needed for patients with poor MRD clearance. ClinicalTrials.gov (NCT01540812)

The combination of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-Ida) is widely used in relapsed/refractory acute myeloid leukaemia (AML). We retrospectively analysed the results of 259 adult AML patients treated as first salvage with FLAG-Ida or FLAG-Ida plus Gentuzumab-Ozogamicin (FLAGO-Ida) of the Programa Español de Tratamientos en Hematología (PETHEMA) database, developing a prognostic score system of survival in this setting (SALFLAGE score). Overall, 221 patients received FLAG-Ida and 38 FLAGO-Ida; 92 were older than 60 years. The complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 51%, with 9% of induction deaths. Three covariates were associated with lower CR/CRi: high-risk cytogenetics and t(8;21) at diagnosis, no previous allogeneic stem cell transplantation (allo-SCT) and relapse-free interval <1 year. Allo-SCT was performed in second CR in 60 patients (23%). The median overall survival (OS) of the entire cohort was 0·7 years, with 22% OS at 5-years. Four independent variables were used to construct the score: cytogenetics, FLT3-internal tandem duplication, length of relapse-free interval and previous allo-SCT. Using this stratification system, three groups were defined: favourable (26% of patients), intermediate (29%) and poor-risk (45%), with an expected 5-year OS of 52%, 26% and 7%, respectively. The SALFLAGE score discriminated a subset of patients with an acceptable long-term outcome using FLAG-Ida/FLAGO-Ida regimen. The results of this retrospective analysis should be validated in independent external cohorts.