BACKGROUNDSeveral studies have suggested that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in patients with acute myeloid leukemia (AML).METHODSVitamin D levels were evaluated in 97 consecutive, newly diagnosed, intensively treated patients with AML. MicroRNA expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome.RESULTSThirty‐four patients (35%) had normal 25(OH) vitamin D3 levels (32‐100 ng/mL), 34 patients (35%) had insufficient levels (20‐31.9 ng/mL), and 29 patients (30%) had deficient levels (<20 ng/mL). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse‐free survival (RFS) compared with normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European Leukemia Network genetic group, and white blood cell count retained their statistical significance for RFS. Several microRNAs and SNPs were associated with 25(OH) vitamin D3 levels, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with a lower complete remission rate (P = .0442) and with shorter RFS (P = .0058) and overall survival (P = .0011).CONCLUSIONSIt remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve outcomes for patients with AML. Cancer 2014;120:521–529. © 2013 American Cancer Society.

e18018 Background: AD occurring in the setting of MDS is challenging to recognize and incorporate into the treatment plan. We assessed the clinical presentations, laboratory abnormalities and outcome of patients with MDS and AD. Methods: Records of MDS patients treated at Roswell Park Cancer Institute between 2007 and 2010 were reviewed (n=123). Results: AD was identified in 10 MDS patients (8.1%): 70% were males, median age was 60.6 years (41-75). AD manifested as seronegative polyarthritis in 2, bronchiolitis obliterans in 2, Hashimoto’s thyroiditis in 2, and 1 (10%) for each of rheumatoid arthritis, systemic lupus, polymyalgia rheumatica, Sjogren syndrome and relapsing polychondritis. Laboratory autoimmune markers were: anti nuclear antibodies in 2, rheumatoid factor in 2, anti-double stranded DNA in 1 and anti phospholipid syndrome with thrombosis in 1. Corticosteroids were the most common used treatment for AD (60%). Regarding the MDS diagnosis; 50% had refractory anemia with excess of blasts-1 and -2, 20% refractory anemia with ring sideroblasts, 10% for each of chronic myelomonocytic leukemia, refractory anemia and MDS/myeloproliferative neoplasm. Normal cytogenetics were noted in 70% of patients, 20% with complex karyotype and 10% had monosomy 7. Hypomethylating agents were used to treat MDS in 80% of patients and in one case were associated with concomitant improvement of AD. Overall survival from diagnosis with MDS was 54 months (6-127). Conclusions: Our experience with one patient and review of the literature suggest that both AD and MDS could benefit from treatment with hypomethylating agents. This warrants a prospective clinical trial.

Our objective was to recognize the association of autoimmune diseases (AD) in patients with myelodysplastic syndromes (MDS) and understand how this association could affect prognosis and management of both diseases. We describe our cohort of 10 patients and 34 patients reported in the English literature in addition to ten cohort studies. Interestingly, four cases showed improvement in AD after 5-azacitidine treatment. The mechanism(s) of the association between AD and MDS are discussed. Treatment could be targeted against AD, MDS or both, though based on recent reports, treating MDS with hypomethylating agents alone could improve the associated AD.

Blastic plasmacytoid dendritic cell neoplasm is an extremely rare hematopoietic tumor that accounts for less than 1% of acute myeloid leukemias. The mean age at diagnosis is 61-67 years and rare pediatric cases have been documented. Here we report a case …

Obesity adversely affects outcome in pediatric acute lymphocytic leukemia and acute myeloid leukemia (AML). We asked if obesity, measured by body mass index (BMI), affected outcome in 329 adult AML patients treated with high-dose cytarabine and idarubicin-containing regimens administered according to actual body weight. Age ≥ 60, unfavorable karyotype, secondary AML, and positive smoking status had adverse impact on overall survival in a multivariate analysis, while BMI did not. We conclude that high BMI should not be a barrier to administer high-dose cytarabine-containing regimens for AML induction.

6592 Background: MRD measured by FC and polymerase chain reaction are independent prognostic indicators for pediatric and adult ALL with significant cost benefit for the former. METHODS We queried our ALL database between 1995 to 2009 for newly diagnosed untreated patients (pts) age ≥17 years, karyotype and FC at diagnosis, week (wk) 8 (range 7-9) and wk 16 (range 15-17) post diagnosis. Pts were treated on or per Cancer and Leukemia Group B protocols. The gating strategy used a series of Boolean regions that best defined the diagnostic abnormal population based on its expression patterns; for B-ALL CD 5, CD 10, CD 19 and kappa before 2003 and CD10, CD19, CD34, and CD38 after 2003, and for T-ALL CD 5, CD 10, CD 19 and CD 34 throughout. The same regions were applied to the post induction samples, and the number of residual events was determined. MRD positivity (+) was defined as >0.01% of the gated population. RESULTS 79 ALL pts with a median age of 52 years (range, 19-80), including 44 males:35 females were analyzed. All pts achieved complete remission; median follow-up was 20 months (mos) (range: 4.9 to 148.7), and 42 (52%) pts relapsed. 64 (81%) pts had B lineage, 6 (8%) had bi-phenotypic and 9 (11%) had T cell phenotype. Karyotype: 2 had favorable, 35 intermediate and 40 adverse karyotype; 2 were not available. The median white blood cell count was 8.97 x 109/L (range 0.6-493.98); 32 (40.5%) pts underwent transplantation (SCT) in first remission. In multivariate analysis MRD+ at 8 wks was associated with inferior progression-free survival (PFS) [40.2 vs. 2.3 mos; 95% confidence interval (CI) 4.6 to not reached (NR) vs. 0.92 to 40.016] (P=0.0080) but not overall survival (OS). MRD+ at 16 wks was associated with both inferior PFS [22.1 vs. 5 mos; 95% CI 12.7 to NR vs. 2.9 to 8.7 (P=0.0001)] and OS (46.2 vs. 14.3 mos; 95% CI 19.7 to NR vs. 10.41 to 26.283) (P=0.0029)]. In pair-wise comparison those who were MRD negative at wk 16 did not benefit from SCT compared to the non SCT group. CONCLUSIONS MRD+ by FC at wk 16 following induction was predictive of inferior survival and identified a subgroup of pts who benefitted from SCT. Pts with MRD negativity by FC at wk 16 did not benefit from SCT.

Smoking adversely affects hematopoietic stem cell transplantation outcome. We asked whether smoking affected outcome of newly diagnosed acute myeloid leukemia (AML) patients treated with chemotherapy. Data were collected on 280 AML patients treated with high-dose cytarabine and idarubicin-containing regimens at Roswell Park Cancer Institute who had smoking status data at diagnosis. Patients' gender, age, AML presentation (de novo vs. secondary), white blood cell (WBC) count at diagnosis, karyotype and smoking status (never vs. ever) were analyzed. Among the 161 males and 119 females with a median follow-up of 12.9 months, 101 (36.1%) had never smoked and 179 (63.9%) were ever smokers. The proportion of patients between never and ever smokers was similar to respect to age, AML presentation, WBC count at diagnosis or karyotype based on univariate analysis of these categorical variables. Never smokers had a significantly longer overall survival (OS) (60.32 months) compared to ever smokers (30.89; p = 0.005). In multivariate analysis incorporating gender, age, AML presentation, WBC count, karyotype and smoking status as covariates, age, karyotype and smoking status retained prognostic value for OS. In summary, cigarette smoking has a deleterious effect on OS in AML.

Esta investigación tuvo como objetivos determinar la influencia de calcio, cobre y boro sobre losparámetros de crecimiento, a nivel in vitro, de plantas de banano y su comportamiento en el desarrollode la Sigatoka negra. Para el estudio se diseñaron ocho tratamientos con diferentes combinaciones yconcentraciones de los tres elementos en estudio, a partir de los cuales se prepararon los medios decultivo, en los que fueron sembrados los propágulos. Se empleó un testigo constituido por el medio MScomercial. Se evaluaron semanalmente los diferentes parámetros agronómicos de las vitroplántulas,durante 45 días. Posteriormente, se tomaron discos de hojas y se realizaron inoculaciones dirigidas conconidias y con concentrado crudo tóxico de M. fijiensis, evaluándose los daños. En los análisisestadísticos se observó diferencias estadísticas entre los tratamientos y el control al evaluarse losdiferentes parámetros agronómicos estudiados. Las evaluaciones realizadas con conidias nopresentaron diferencias estadísticas a pesar de que los tratamientos (T3, T4, T5, T6, T7 y T8),presentaron menor grado de infección. En las muestras inoculadas con concentrado crudo tóxico sereflejaron diferencias estadísticas entre los tratamientos y el control. Se puso en evidencia un menorgrado de infección en muestras tratadas con la combinación de los tres elementos a mayor concentración(T8). Abstract This study had as its objectives to determine the influence of calcium, copper and boron on growthparameters, in vitro of banana plants and their behavior in the development of black Sigatoka. For thestudy, eight treatments were designed with different combinations and concentrations of the threeelements under study. From these treatments, the culture medium were prepared. The propagules wereplanted in the culture medium. Also, a control consists of the medium MS commercial. The agronomicparameters of vitroplántulas during 45 days. Subsequently, leaf discs were inoculated with conidia andconcentrated crude toxic of M. fijiensis, damage were evaluated. In the statistical analysis showedstatistical differences between treatments and control when the agronomic parameters were analyzed.The evaluations performed with conidia were not statistically different despite the treatments (T3, T4, T5,T6, T7 and T8), they presented lower levels of infection. In the samples inoculated with concentrated toxiccrude statistical differences were reflected between treatments and control. It was revealed a lower levelof infection in samples treated with the combination of three elements at a higher concentration (T8).

Constitutive activation of signal transducer and activator of transcription‐3 (STAT3) was detected in blasts from approximately 50% of patients with acute myeloid leukemia (AML) and was correlated with an adverse outcome. In vitro treatment of AML blasts with arsenic trioxide (ATO) down‐regulated STAT3 activity within 6 hours associated with a reduced viability within 48 hours.

Blastic transformation of myeloproliferative neoplasms (MPN) is still poorly understood. We describe a cohort of 23 Roswell Park Cancer Institute (RPCI) patients and 89 additional cases from the English literature for whom biologic features were described. We initially compared our 23 patients to the 89 cases from the literature. Our population had significantly less patients with prior history of polycythemia vera (PV), shorter time from MPN diagnosis to blastic transformation, <3 prior therapies, more frequent use of hydroxyurea and erythropoietin and less frequent use of alkylating agents. Interestingly, the overall survival of the two cohorts from the time of blastic transformation was similar. We therefore looked at the outcome of the entire cohort (n=112). Patients with prior history of essential thrombocythemia survived longer than patients with prior history of myelofibrosis or PV. Further, patients with <3 prior therapies, those who lacked complex karyotype and those <60 year old at MPN diagnosis had significantly longer survival. Among the PRCI population, 20/23 patients underwent induction treatment with cytarabine and an anthracycline containing regimens; 12 achieved remission and their overall survival was significantly longer than those who did not. Three patients underwent an allogeneic transplantation and their survival was significantly longer than those who did not. Patients with <3 prior therapies, those who lack complex karyotype and those <60 at MPN diagnosis have longer survival following blastic transformation. Finally, allogeneic transplantation represents the only chance for long-term survival in these patients.

Abstract Abstract 1041 Several studies suggest that subnormal vitamin D levels may be prognostic in a number of malignancies, including non Hodgkin lymphoma, prostate, breast, colon and lung cancer. However, no studies have evaluated the impact of subnormal vitamin D levels on treatment outcome in AML. Vitamin D levels were evaluated in 97 consecutive newly diagnosed similarly treated patients with AML (excluding AML M3). There were 50 (52%) males and 47 (48%) females with a median age of 60 years (range 19–91). The median white blood cell (WBC) count at diagnosis was 18×109/L (range 0.57–555.23). Karyotype was favorable in 11%, intermediate in 50%, adverse in 23%, of unknown significance in 11% and not available in 5%. A total of 74 patients (76%) had de novo AML. Albumin levels were subnormal (<3.5g/dl) in 33 (34%) patients and normal (≥3.5g/dl) in 64 (66%) patients. Body mass index (BMI) was calculated on all patients, normal weight (BMI 18–24.9) 33 (32%) patients, overweight (BMI 25–29.9) 34 (35%) patients, obese (BMI 30–34.9) 16 (16%) and very obese (BMI ≥35) 15 (15%) patients. Induction consisted of cytarabine (100mg/m2 × 7 days), daunorubicin (90mg/m2 for <60 and 60mg/m2, for ≥60 × 3 days) and etoposide (100mg/m2 × 3 days) (ADE 7+3+3). Consolidation therapy consisted of either high-dose cytarabine (47%), ADE (5+2+2) (15%), allogeneic (8%) transplantation, or other/no further treatment (30%). The median follow-up was 8.1(range, <1-66) months. Serum samples were obtained at diagnosis and studied for 25-(OH)-Vitamin D levels using radioimmunoassay. Thirty-four (35%) patients had normal vitamin D levels (32-100 ng/mL), and 63 (65%) patients had levels <32ng/ml.; 34 (35%) patients had levels considered insufficient (20-31.9ng/ml) and 29 (30%) patients were deficient (<20ng/ml). We have studied vitamin D concentrations in a cohort of 100 healthy volunteers from Western New York and found a similar frequency of vitamin D serum concentrations subnormal. Complete remission rate was similar in those with normal and subnormal vitamin D levels (50% vs. 57%; P=0.53). In univariate analysis, WBC count ≥100×109/L was associated with worse progression-free survival (PFS) and overall survival (OS) [14.3 vs. 2.2 months; 95% confidence interval (CI) 8.9 to 21.9 vs. 0.49 to 5.9 for PFS (P=<0.0001) and 17.3 vs. 2.2 months; 95% CI 13.6 to 24.6 vs. 0.49 to 6.7 for OS (P=<0.0001). Similarly, secondary AML was associated with worse PFS and OS [14.9 vs. 6.3 months; 95% CI 9 to 26.7 vs. 4.1 to 10.1 for PFS (P=0.028) and 18.9 vs. 6.7; 95% CI 13.6 to NA vs. 5.6 to 16.7 for OS (P=0.048)]. In addition, unfavorable karyotype, when compared with intermediate and favorable karyotypes, was associated with worse OS [6.6 vs. 18.9 vs. 21.2 months; 95% CI 4.8 to 16.7 vs. 11.5 to NA vs. 14.2 to NA for OS (P=0.04)]. Interestingly, in this cohort, age affected neither PFS nor OS and karyotype had no effect on PFS. Subnormal vitamin D levels were associated with worse PFS and OS [7.9 vs. 16.5 months; 95% CI 5.0 to 12.8 vs. 14.3 to NA for PFS (P=0.007) and 9.2 vs. 21.2 months; 95% CI 6.6 to 18.9 vs. 16.5 to NA for OS (P=0.01)] (Figure 1A and B). Nutritional status, assessed by albumin and BMI, did not affect PFS and OS. In multivariate analyses, only vitamin D (P=0.03 and P=0.049) and WBC count (P=0.02 and P=0.02) retained their statistical significance for PFS and OS. In summary, AML patients with subnormal vitamin D levels had significantly inferior PFS and OS compared to patients with normal vitamin D levels. Additional investigations to validate this observation and determine the mechanisms by which vitamin D levels are associated with inferior survival in AML are warranted. If confirmed, studies of the role of vitamin D supplementation in AML patients would be valuable. Disclosures: No relevant conflicts of interest to declare.

T-cell large granular lymphocyte (T-LGL) leukemia is a rare indolent lymphoproliferative disorder diagnosed by presence of >2,000/μL peripheral CD3+CD8+CD16+/−CD56 +/−CD57+ LGL and/or evidence of T-LGL clonality by T-cell receptor (TCR) gene rearrangement, accompanied by neutropenia and/or other cytopenias. We reported the efficacy of cyclosporin A (CsA) in the treatment of LGL-associated neutropenia [Blood 1998; 91:3372–8] and we report here long-term follow-up of our larger patient (pt) cohort. Between 1982 and 2006, 18 pts were diagnosed with T-LGL leukemia with the above strict criteria (M:F 11:7; median age, 67; range, 48–84 years). Mean follow-up from diagnosis is 59 (range, 2–303) months. Autoimmune phenomena were present in 6 (33%), including pure red cell aplasia in two, lymphocytic colitis and ascites in one, and erosive osteoarthritis and pulmonary granulomatous vasculitis in one other. Splenomegaly was present in 6 (33%). Median (range) hemoglobin (Hb), absolute neutrophil count (ANC) and platelet count were 10.4 (3.6–15.5) g/dL, 1,100 (0–5,900)/μL and 152,000 (69,000–583,000)/μL. Anemia, neutropenia (ANC<1,000/μL), severe neutropenia (ANC<500/μL) and thrombocytopenia were present in 9 (50%), 13 (72%), 6 (33%), and 5 (28%), respectively. Four (22%) had one cytopenia, ten (56%) bicytopenia and one (6%) pancytopenia. Median (range) absolute number and percentage of peripheral LGL by flow cytometry were 1,147 (59–9,327)/μL and 31 (3.3–66.9) %. TCR gene rearrangement was present in 16 (89%). Fourteen pts (78%) required treatment early; median treatment-free survival was only 1.0 (95% CI, 0–8.4) months. Indications for initiation of treatment included Hb<9 g/dL, ANC<500/μL, ANC<1,000/μL with recurrent infections and platelet count<50,000/μL. CsA was initiated in 11 pts (61%). The median duration of CsA therapy was 47 (range, 4.5–186) months. Four pts were still receiving CsA at last follow-up. Four pts (40%) achieved sustained complete hematologic improvement (HI) by MD Anderson response criteria [Leuk Res 2007;31:939–45], 1 (10%) major HI and 2 minor HI (20%), resulting in an overall HI of 70%. One other (10%) had mixed HI and 2 (20%) had progressive disease. G-CSF was initiated simultaneously with, and added later to, CsA in 1 (10%) and 2 (20%) pts, respectively, and erythropoietin (Epo) in 1 (10%) and 3 (30%), respectively. The addition of growth factor resolved neutropenia and/or anemia in two additional pts, resulting in overall and complete HI of 80% and 50% respectively. Median time (range) to maximum HI with CsA, G-CSF and Epo were 2.5 (0.2–27), 0.7(0.6–1.9) and 1.5 (0.9–1.9) months, respectively. Renal insufficiency, hypertension and/or hypomagnesemia occurred in 7 (70%). CsA tapering and discontinuation were successful in two (40%) of the five pts who achieved complete HI, 91 and 186 months after initiation. Four pts (22.2%) have not required any treatment 8, 8, 33 and 80 months after diagnosis, and two received Epo and one HIV therapy alone. All except one were alive at the mean follow-up time of 59 (range, 2–303) months and median survival has not been reached. Thus T-LGL leukemia usually requires treatment early after diagnosis, but has an excellent prognosis. CsA with or without growth factor support is an effective treatment, leading to overall and complete HI in 80% and 50%, respectively. Successful tapering and discontinuation of therapy may be possible in 40% of pts who achieve long-term complete HI.

This paper reports a 73-year old woman with simultaneous presentation of acute monoblastic leukemia (acute myeloid leukemia (AML), French-American-British (FAB) type M5a) and mantle cell lymphoma. The patient presented with wasting, generalized lymphadenopathy, an extensive infiltrative rash and pancytopenia. Bone marrow and lymph node histopatholology showed extensive infiltration by leukemic monoblasts. Marrow cytogenetics revealed a complex karyotype, including t(8;16)(p11;p13). Flow cytometric immunophenotyping of peripheral blood, lymph node and bone marrow demonstrated two populations, expressing CD5, CD19, CD20 and CD22 and CD45, HLA-DR, CD13, CD33, CD14 and CD38, respectively. A focus of abnormal lymphocytes in the lymph node biopsy demonstrated BCL1 expression and t(11;14)(p11;p13) by fluorescence in situ hybridization and immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction. The patient received infusional cytarabine, daunorubicin and etoposide chemotherapy, with complete remission of both the AML and the mantle cell leukemia. To the authors' knowledge, this is the first report of simultaneous presentations of AML, FAB M5a and mantle cell lymphoma. The case is discussed and the literature is reviewed.

Novel agents have demonstrated enhanced efficacy when combined with other antimyeloma agents especially dexamethasone. The steroid doses employed in myeloma regimens are often poorly tolerated. Therefore, in a phase II clinical trial we investigated the efficacy of a steroid-free combination including bortezomib, pegylated liposomal doxorubicin and thalidomide (VDT regimen). Twenty-three patients with relapsed or refractory myeloma or other plasma cell cancers were treated with the VDT regimen. Patient had a median of five prior therapies and 65.2% were refractory to their last regimen. The overall response rates were 55.5% and 22%, respectively. The median progression free survival was 10.9 months (95% CI: 7.3–15.8) and the median overall survival was 15.7 months (95% CI: 9.1–not reached). Fatigue and sensory neuropathy were the most common side effects noted. We observe that VDT is an effective steroid-free regimen with ability to induce durable remission even in patients with refractory myeloma.

BACKGROUND: Treating the octogenarian and nonagenarian patients who have acute myeloid leukemia (AML) with intensive chemotherapy is controversial. Several models to predict outcome were proposed, including the use of a comorbidity index. However, it is unclear whether the Charlson comorbidity index (CCI) or the hematopoietic cell transplant comorbidity index (HCTCI) is more sensitive. METHODS: The authors analyzed their experience with 92 patients aged >= 80 years who had AML. Patients' pretreatment characteristics and their treatment outcomes were recorded. RESULTS: All patients were offered intensive treatment; 59 patients (64%) were treated intensively with a variety of regimens, whereas 33 patients (36%) elected to receive supportive care. The CCI and the HCTCI had similar predictive ability for outcome in both groups. A multivariate analyses of prognostic factors identified near-normal albumin (48% of patients; 1-year survival rate, >27%) as a favorable factor for the whole cohort, age <83 years (47% of patients; 1-year survival rate, >25%) and nonmonocytic morphology (75% of patients; 1-year survival rate, >26%) as favorable factors for the intensively treated cohort, and bone marrow blasts <46% (50% of patients; 1-year survival rate, >19%) as a favorable factor for patients who received supportive care. CONCLUSIONS: This retrospective analysis was developed to assist in treatment decisions for octogenarian and nonagenarian patients with AML. The findings will need validation in a prospective study. Cancer 2009;115:2472-81. (C) 2009 American Cancer Society.

Smoking is associated with both acute myeloid leukemia (AML) and lung cancer. We therefore searched our database for concomitant presentation of AML and lung cancer. Among 775 AML cases and 5225 lung cancer cases presenting to Roswell Park Cancer Institute between the years January 1992 and May 2008 we found 12 (1.5% of AML cases; 0.23% of lung cancer cases) cases (seven metachronous and five synchronous) with AML and lung cancer. All but one patient were smokers. There were no unique characteristic of either AML or lung cancer in these patients. Nine patients succumbed to AML, one died from an unrelated cause while undergoing treatment for AML, one died of lung cancer and one patient is alive after allogeneic transplantation for AML. In summary, this study supports the need for effective smoking cessation programs.