3453 Individuals undergoing allogeneic transplantation receive multiple red blood cell transfusions both as part of the transplant procedure and as part of the pre-transplant care of the underlying disease. Therefore these patients may be at risk for complications of transfusional iron overload. Several studies have noted that individuals entering the transplant with baseline elevated serum ferritin values have decreased overall survival and higher rates of disease relapse. Whether the iron is a direct contributor to inferior outcomes or is a marker of more advanced disease (thereby requiring greater transfusions) is unclear. Little is known about the incidence and consequences of iron overload among long-term survivors of allogeneic transplantation. Methods: Using Kaplan-Meier and Cox regression analyses, we performed a single center, retrospective cohort study of consecutive allogeneic transplants performed at Hackensack University Medical Center from January 2002 through June 30, 2009 to determine the association between serum ferritin (measured approximately 1 yr post allogeneic transplant) and overall survival. Results: During the study time frame, 637 allogeneic transplants (Donor Lymphocyte Infusion procedures excluded) were performed at our center and 342 (54%) survived ≥ one year. Among 1-year survivors 240 (70%) had post-transplant serum ferritin values available for review, including 132 (55%) allogeneic sibling, 68 (28%) matched unrelated, and 40 (17%) mismatched unrelated donor transplants. The median post-transplant ferritin value among 1-year survivors of allogeneic transplant was 628 ng/ml (95% CI 17, 5010), with 93 (39%) above 1000 ng/ml and 40 (17%) above 2500 ng/ml. The median post-transplant ferritin levels varied by underlying hematologic disease (aplastic anemia = 1147, acute leukemia = 1067, MDS = 944, CLL = 297, CML = 219, lymphoma = 123, multiple myeloma = 90). The Kaplan-Meier projected 5-year survival rate was 76% for the cohort that had survived one year and had available ferritin values. Fifty late deaths have occurred; causes of late death were disease relapse (n=37, 74%), GVHD (n=7, 14%), infection (n=4, 8%), cardiac (n=1, 2%) and second malignancy (n=1, 2%). The 1-year post-transplant serum ferritin value was a significant predictor of long term survival. Using a cut-off ferritin value of 1000 ng/ml, the 5-year projected survivals were 85% (95 CI 75%-91%) and 64% (95% CI 52–73%) for the low and high ferritin cohorts respectively (Figure, log-rank p<0.001), with a hazard ratio of 3.5 (95% CI 2–6.4, p<0.001). Similarly a serum ferritin value >2500 ng/ml was associated with inferior survival (HR 2.97, p<0.001). Underlying hematologic disease also correlated with 5-year projected survival including 70%, 83%, and 89% for acute leukemia/MDS, lymphoma/myeloma/CLL, and aplastic anemia/CML groupings, respectively (log-rank p<0.01 for leukemia/MDS vs other groupings). Patients receiving bone marrow grafts did better than those receiving peripheral blood stem cells (HR = 2.2; p = 0.03). Age, gender, donor type (sibling, matched unrelated, mismatch unrelated) and intensity of regimen (ablative vs. non-myeloablative) were not predictive of inferior survival in univariate analysis. In the multivariate Cox-regression analysis, elevated post-transplant ferritin >1000 ng/ml (HR 3.3, 95%CI 1.6–6.1; p<0.001) and diagnosis of acute leukemia/MDS (HR 4.5, 95%CI 1.1–18.7; p=0.04) remained independent predictors of inferior survival, even when adjusted for age, gender, type of graft, donor type, and intensity of conditioning regimen. Relapse deaths (25% vs. 9%; p<0.001) and GVHD deaths (6% vs 0.6%; p=0.03) were more common in the high ferritin cohort. Conclusions: Among patients who have survived one-year following allogeneic transplantation, a post-transplant serum ferritin value greater than 1000 ng/ml is a predictor of inferior long-term outcomes. To our knowledge this is the first report on the importance of late monitoring of serum ferritin, but it is in agreement with prior studies suggesting a pre-transplant ferritin value is a predictor of outcomes. Prospective studies attempting to modify outcomes by reducing post-transplant iron overload states are needed. Disclosures: No relevant conflicts of interest to declare.
INTRODUCTION: Acute Myelogenous Leukemia (AML) is the most common form of acute leukemia in the adult population, accounting for approximately 80% of acute leukemias in adults. The incidence of AML increases with advancing age. In patients younger than 65 years, the incidence is approximately 1.3 per 100000 people, while patients older than 65 years, the incidence is approximately 12.2 per 100000. Hematologic malignancies, such as acute and chronic leukemias, rarely result in pleural effusion during their clinical course. Pulmonary complications of AML are observed in 19%, infection being the most common. Most cases of leukemic pleural effusion reflect disease severity and have been associated with a poor prognosis.CASE PRESENTATION: This is a case of a 36 year-old male with a past medical history of AML with complex cytogenetics (rearrangements 11q, 17q, 17p); treated with Cytarabine and Daunorubicin who came to the emergency room due to general malaise and epigastric pain. Vitals signs remarkable for tachycardia. Physical examination showed decreased breath sounds on left lower lung and dullness to percussion. Laboratories were remarkable for leukopenia, normocytic anemia and normal platelet count. Renal/hepatic function and electrolyte levels were within normal limits. During hospitalization, patient presented with shortness of breath, tachycardia and decreased peripheral saturation. Chest CT Scan was completed and revealed pulmonary infiltrates with miliary pattern and pleural trabecules associated with a moderate left sided pleural effusion. The patient was initiated on Levofloxacin and consulted to Pneumology services for further work up. Bronchoscopy with BAL was performed and was negative for infection. A thoracentesis was completed and consistent with exudative fluid per lights criteria. Cytology revealed large monomorphic population of atypical blastoid cells showing hypochromcatic irregular nuclei, nucleoli and scant cytoplasm. Immunohistochemistry positive for CD3, CD4, CD15, CD 34, CD68 and Myeloperoxidase with a Ki67. These findings are suggestive of granulocytic sarcoma (chloroma).DISCUSSION: Leukemic involvement of the pleura can manifest with pleural effusion, pleural masses or thickening, or a combination of the two. In leukemic patients, common causes of pleural effusion include bacterial or viral infections, or disseminated solid tumors and complication of chemotherapy. Pleural effusions in these patients are more likely to be benign than malignant.CONCLUSIONS: Pleural effusions may be the first presentation of a hematologic malignancy or may develop during the course of the disease. These are a rare occurrence in patients with AML also known as granulocytic sarcoma or pleural chloroma. This demonstrates the importance of the cytopathology specimens obtained in pleural fluid since an early detection of any determined disease could guide effective therapy.
1040 Poster Board I-62 Treatment of the elderly patient with acute myelogenous leukemia remains problematic as many have poor performance status precluding aggressive therapy and others have high risk features including abnormal cytogenetics. The success of 5-azacitidine among patients with advanced myelodysplastic syndromes in controlling blast cells and prolonging survival has led to its use in AML. However choosing between potentially curative hospital-based induction chemotherapy and palliative outpatient hypomethylating treatments is difficult. The availability of predictive comorbidity scores may aid in guiding patients in this decision. Methods: Patients with a new diagnosis of AML, ages 60 and older, were offered traditional in-patient induction therapy (7 days cytarabine 100 mg/m2 CI with 3 days idarubicin 12mg/m2) or out-patient therapy (5-azacitidine 75 mg/m2 IV 5 days per month). We report a retrospective review of clinical outcomes among patients treated between June 2003 and August 1, 2009. A review of presenting clinical features, placing patients into prognostic groupings by the Charlson Comorbidity Index (J Chronic Dis 1987; 40:373), Hematopoietic Cell Transplantation – Specific Comorbidity Index (Blood 2007; 110:4606), and the Myelodysplastic Syndrome – Specific Comorbidity Index (Blood 2008; 112: abstr 2677) was performed. Points for a diagnosis of leukemia were excluded from the indices. Results: 99 patients with AML were treated at our center, all with leukemic blasts >20% (median 48%). 75 chose traditional 7+3 and 24 chose 5-aza. The median age was younger for those choosing 7+3 (67 vs 77 years, p<0.001). The median survival for all patients was 340 days (95% CI 258, 422). The median survival was longer with 7+3 at 367 days (95% CI 306,428) compared to a median survival with 5-aza of 186 days (95% CI 122, 250) (p=0.07). Only one patient age <65 chose 5-aza. The median survival for pts with 7+3 was similar by age groups: <65 yrs (n=34) 367 days, 65-69 yrs (n=19) 340 days, and ≥70 yrs (n=22) 467 days (log-rank p=0.31). Cytogenetic features (SWOG criteria) at baseline correlated with survival: good risk (n=3) 186 days, intermediate risk (n=54) 604 days, and poor risk (n=28) 241 days. (p=0.03). Similarly, cytogenetic risk continued to remain significant regardless of treatment choice: 7+3: intermediate/poor risk karyotype 664 days vs 340 days, and 5-aza: intermediate/poor risk 604 days vs 67 days (p=0.03). All 3 examined comorbidity indices were able to predict overall survival for the entire cohort (n=99). Using the CCI, better scores led to improved outcome (log-rank p=0.007): Score 0 (n=41): 475 days; score 1 (n=23): 213 days; score 2 (n=25): 196 days; score 3 (n=8): 186 days; score 4 (n=2) 1404 days. Similar results were obtained using the HCTS-CI (log-rank p=0.01): Score 0 (n=33): 475 days; score 1 (n=24): 353 days; score 2 (n=13): 146 days; score 3 (n=17): 196 days; score 4 (n=5) 1113 days; score 5 (n=5) 337 days; score 8 (n=1) 1404 days. And using the MDS-CI (log-rank p=0.02) better scores predicted improved survival: Score 0 (n=64): 375 days; score 1 (n=18): 241 days; score 2 (n=13): 186 days; score 3 (n=3): 69 days; score 4 (n=1) 1404 days. In addition, patients who scored well on the CCI did better (p=0.005) than patients with poor scores by type of treatment (ie, a low score patient treated with 7+3 did better than a high score patient treated with 7+3, and a low score patient treated with 5-aza did better than a high score patient treated with 5-aza). Similar relationships were noted between scores on the HCTS-CI and MDS-CI and treatment choice. However, in all CCI score categories, 7+3 treatment was superior to 5-aza (score 0: 839 vs 298 days; score 1: 276 vs 69 days; score 2: 279 vs 106 days; score 3: 435 vs 90 days) (p=0.08). Similarly 7+3 treatment appeared superior to 5-aza by HCTS-CI score (p=0.02) and MDS-CI (p=0.05). Conclusions: Elderly patients with AML can achieve survivals approaching one year with current treatment options. 5-azacytidine is a reasonable option for patients declining aggressive hospital based treatments especially if cytogenetic features are favorable, however overall survival may be inferior to standard induction chemotherapy. Although comorbidity indices are able to stratify potential outcomes among elderly patients with AML choosing a particular treatment, in our series we could not identify a comorbidity score that would dissuade aggressive treatment in favor of less intensive therapy. Disclosures: Goldberg: Celgene: Speakers Bureau. Off Label Use: 5-azacytidine use in AML. Masood:Celegene: Speakers Bureau.
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