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Patients were classified according morphologic, immunophenotypic, and cytogenetic findings. Treatment protocols were similar between centers. For patients up to 60 years of age, the treatment protocol was adapted according to performance status and the presence of comorbidities (in particular, cardiac disorders). Briefly, the conventional chemotherapy consisted of daunorubicin (45-90 mg/m 2 per day for 3 days) and cytarabine (100-200 mg/m 2 per day for 7 days) or thioguanine, cytosine arabinoside, and daunorubicin as induction, 1 followed by 3 or 4 cycles of consolidation therapy with high doses of cytarabine (.1 g/m 2 per day). For patients who did not achieve complete remission (CR) after 1 course of chemotherapy, a second course was administered between days 28 and 35 after the end of the first course. CR was assessed by bone marrow examination on day 28 after each course of chemotherapy. For those who needed it, a postremission therapy based on autologous or allogeneic transplantation was performed. Patients older than 60 years were treated with low-dose cytarabine; a combination of etoposide, thioguanine, and idarubicin; or best supportive care. The local research ethics board of each participating center approved the study. Research was conducted in accordance with the Declaration of Helsinki.The baseline characteristics are summarized in supplemental Table 1. One hundred thirty patients were enrolled in Recife (northeast Brazil, 54%), and 111 patients were enrolled in Campinas (southeast Brazil, 46%). Baseline features were similar between centers. The median age was 47 years (range, 18-97 years) with 114 males (47%). Sixty-two patients (26%) were older than 60 years. Pretreatment bone marrow samples were analyzed by G-banding cytogenetics, of which 187 (78%) were successful. According to Medical Research Council trials, 2 patients were stratified as follows: favorable (30/187, 16%), intermediate (119/187, 64%), and adverse (38/187, 20%). Overall, 101 patients (42%) were cytogenetically normal. To test whether the samples without cytogenetics results were missing at random, the overall survival (OS) was evaluated for patients with and without cytogenetics data. The 5-year OS rate did not differ between patients with (18%) and without (23%) available cytogenetics data (P 5 .372). Additionally, the entire cohort was fully characterized for NPM1 and FLT3-ITD mutations. Details can be found in the supplemental Data, available on the Blood Web site.Out of 241 enrolled patients, 39 patients (16%) who started the induction treatment were lost to follow-up without assessment for CR. Of 202 evaluable patients, 115 (57%) achieved complete hematologic remission. CR rates according to the cytogenetic risk stratification were 33%, 64%, and 77% for adverse, intermediate, and favorable groups, respectively (P 5 .001). The logistic regression analysis revealed that age (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.93-0.98; P 5 .002) and cytogenetic risk stratification (OR, 0.41; 95% CI, 0.19-0.89; P 5 .024) wer...

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To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

in solid organ malignancies, including melanoma, ovarian, breast, and especially, colorectal cancers, where a higher degree of tumor-infiltrating lymphocytes (TIL) predicts improved survival independent of TNM (tumor, node, metastases) staging [1]. TIL have also shown prognostic value in various lymphoid hematological malignancies. In AML, evidence of immune modulation is seen in the "graft-versus-leukemia" effects post-allogeneic SCT together with promising preclinical activity of novel immune therapies. Furthermore, higher peripheral blood lymphocyte recovery after induction chemotherapy [2] and allogeneic SCT for AML [3] have predicted improved overall survival (OS). The prognostic significance of immune status at diagnosis has not been defined in AML. We therefore investigated whether degree of T lymphocyte infiltration within CN-AML diagnostic bone marrow trephines, which we have labeled the "leukemia-infiltrating lymphocyte" (LIL) index, had prognostic value.Patients diagnosed with CN-AML at an adult tertiary center between 2006 and 2013, treated with intensive chemotherapy and who had suitable stored, diagnostic bone marrow trephines were analyzed with institutional ethics approval. Trephines were formalinfixed, decalcified in EDTA, and processed through to paraffin. Immunostaining for pan-T cell marker, CD3, and cytotoxic markers, CD8 and Granzyme B (GB), was performed at the time of analysis using routine methods. CD4 immunostaining was attempted, however high levels of non-specific staining precluded quantitative analysis. Positive cells were quantified using FijiV C image analysis software (v1.48o) from photographs taken at 3200 magnification of three representative areas of each trephine, expressed as a percentage of total cells and averaged over the three images.The cohort included 53 patients (51% male, median age 51 years (range 19-78)) followed-up over a median of 25.9 months (range 0.17-102.6 months). Most patients (96%) had de novo AML, 47 patients (89%) achieved CR (29 (62%) of whom relapsed), 21 (40%) underwent allogeneic SCT (10 in second CR) and 20 (38%) died. From a mean of 13,768 cells per trephine analyzed, median CD3% was 4.64% (range 0.56-37.24%) (Fig. 1A,B), CD8% was 5.08% (range 0.43-43.5%) and GB% was 0.34% (range 0-10.11%). In univariate Cox regression analyses, significant risk factors for death were higher aspirate blast% (P 5 0.006), primary refractory disease (P 5 0.03), and relapse (P 5 0.04). Increasing age (P 5 0.093), FLT3-ITD positive(pos) (P 5 0.099), and CD3% (P 5 0.079) approached significance. Gender, preceding myelodysplastic syndrome, allograft, NPM1 mutation (NPM1 mut ), CD8%, and GB% were not significant. In Cox regression multivariate analyses, combining T cell numbers with the relevant univariate factors (i.e., P < 0.1), higher CD3 and CD8 were independent predictors of OS (CD3: hazard ratio (HR) 0.929 for death, 95% CI 0.870-0.992, P 5 0.029; CD8: HR 0.920, 95% CI 0.869-0.973, P 5 0.004). Patients were divided into quartiles to determine whether incremental d...

A high rate of hepatic, pancreatic and cardiac impairment by iron overload was demonstrated. Ferritin levels could not predict liver, heart or pancreas iron overload as measured by T2* magnetic resonance imaging. There was no correlation between liver, pancreas, liver and myocardial iron overload, neither between ferritin and fraction of labile plasma iron with liver, heart and pancreas T2* values.

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