ALBERT

Description: Abstract 4272 Background: Globally, a number of management guidelines provide recommendations for transfusion and iron chelation therapy across various transfusion-dependent anemias. Most treatment guidelines aim to control body iron burden by maintaining serum ferritin 2500 ng/mL across all anemias. Serum ferritin levels were ≥2500 ng/mL in 61.3% of patients across regions (50.6% [Europe], 59.3% [Middle East/Africa] and 74.3% [Asia-Pacific]). For patients with TM, TI, AA and SCD, serum ferritin levels were substantially higher in the Asia-Pacific region compared with other regions (Figure). In the Asia-Pacific region, the proportion of patients with serum ferritin levels ≥4000 ng/mL varied between 31.1% and 53.6% across anemias, compared with 14.3–37.5% in Europe. Conclusions: There are many differences in transfusion and iron chelation practices across regions, with most prominent differences in the Asia-Pacific region. Factors contributing to these differences might include regional variations in specific disease characteristics (severity, transfusion requirement), treatment practices (eg, hemoglobin level at which transfusion is initiated), the availability and accessibility of transfusion and iron chelation therapy including patients' compliance and physician attitude and adherence to treatment guidelines. The high proportion of patients with baseline serum ferritin 〉2500 ng/mL suggests that previous iron chelation regimens with DFO and/or deferiprone prior to the EPIC study were suboptimal with limitations for adequate control of iron burden across geographical regions. A greater improvement in iron chelation practices is warranted across the globe with an immediate focus on the Asia-Pacific region. Disclosures: Viprakasit: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gattermann:Novartis: Honoraria, Research Funding. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Taher:Novartis: Honoraria, Research Funding. Habr:Novartis: Employment. Roubert:Novartis: Employment. Domokos:Novartis: Employment. Cappellini:Novartis: Speakers Bureau.

Description: Abstract 5158 Objectives. Classic clinical and animal studies with deferoxamine (DFO) showed that two major chelatable pools exist in thalassemia major (TM), the first derived from hepatocytes and the second from red cell catabolism. Knowledge about the origin of chelatable iron with deferiprone (DFP) treatment, alone or when combined with DFO, is relatively limited. We hypothesized that changes in plasma iron species during chelation therapy may be proportional to the magnitude of chelatable iron pools. In this study, we have examined the relationship between urinary iron excretion (UIE), transfusional iron loading rates (ILR), liver iron concentration (LIC) and plasma concentrations of non-transferrin bound iron (NTBI) and labile plasma iron (LPI) before and after DFP therapies. Patients and methods. 12 TM patients were randomized to one year of DFP monotherapy (25mg/kg tds) or 9 to DFP at the same dose with the addition of subcutaneous DFO (40-50mg/kg), 2 nights a week (COMB). Plasma samples were taken for NTBI and LPI measurements, at baseline, at 1 week and at 52 weeks. These were obtained at 9am, which was 10hrs following the previous DFP dose, and 24h after the second of two weekly DFO doses for COMB patients. A 24h urine iron was collected at baseline, 1 week and 52 weeks of treatment. The ILR, expressed in mg/kg/day, was calculated from the blood volume transfused during the 1 year study. Results. After 1 week of treatment, there was a significant increase in NTBI from baseline in DFP and in COMB patients. A significant increase in LPI was also seen in DFP patients at this time (p=0.039). In all patients, absolute LPI levels at 1 week correlated with those of NTBI and increments in LPI also correlated with increments in NTBI from baseline to 1 week (r=0.52, p=0.002). Plasma NTBI levels at 1 week were proportional to UIE mg/kg/day)(r=0.51, p= 0.02), to LIC mg/g dry wt (r=0.54, p=0.01) and inversely proportional to the ILR (r=0.74, p=0.0001). By weighting the LIC and ILR pools equally, a combined chelatable pool index was derived: this was significantly proportional to both absolute NTBI at 1 week (r=0.72, p=0.003) and increments in NTBI from baseline. This index was also significantly correlated with UIE (p=0.66, p=0.0017) and with LPI at 1 week. Interpretation and conclusions. Urinary iron excretion with DFP (the predominant route of iron excretion with DFP) and COMB therapy is directly proportional to the LIC, as well as to plasma NTBI and LPI and is inversely proportional to the ILR. This is consistent with the existence of two major chelatable iron pools; the first being liver derived and the second derived from red cell catabolism. This latter pool appears to be larger for those patients who require less blood transfusion and who presumably have greater rates of ineffective eryrthropoiesis. The origin of chelatable iron with this form of COMB therapy, with DFO only two days a week, appears is similar to that of DFP monotherapy. Disclosures: Aydinok: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: Deferiprone and desferrioxamine are indicated and approved for the chelation therapy of iron-overloaded patients with beta thalassemia. The combination of both agents as treatment regimen for patients with beta thalassemia is part of the investigation described in the abstract and is not approved for use. Manz:Lipomed AG: Employment. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Description: Cardiac iron overload causes most deaths in β-thalassemia major. The efficacy of deferasirox in reducing or preventing cardiac iron overload was assessed in 192 patients with β-thalassemia in a 1-year prospective, multicenter study. The cardiac iron reduction arm (n = 114) included patients with magnetic resonance myocardial T2* from 5 to 20 ms (indicating cardiac siderosis), left ventricular ejection fraction (LVEF) of 56% or more, serum ferritin more than 2500 ng/mL, liver iron concentration more than 10 mg Fe/g dry weight, and more than 50 transfused blood units. The prevention arm (n = 78) included otherwise eligible patients whose myocardial T2* was 20 ms or more. The primary end point was the change in myocardial T2* at 1 year. In the cardiac iron reduction arm, the mean deferasirox dose was 32.6 mg/kg per day. Myocardial T2* (geometric mean ± coefficient of variation) improved from a baseline of 11.2 ms (± 40.5%) to 12.9 ms (± 49.5%) (+16%; P 〈 .001). LVEF (mean ± SD) was unchanged: 67.4 (± 5.7%) to 67.0 (± 6.0%) (−0.3%; P = .53). In the prevention arm, baseline myocardial T2* was unchanged from baseline of 32.0 ms (± 25.6%) to 32.5 ms (± 25.1%) (+2%; P = .57) and LVEF increased from baseline 67.7 (± 4.7%) to 69.6 (± 4.5%) (+1.8%; P 〈 .001). This prospective study shows that deferasirox is effective in removing and preventing myocardial iron accumulation. This study is registered at http://clinicaltrials.gov as NCT00171821.

Description: Abstract 3570 Mantle cell lymphoma (MCL) is a small B cell lymphoma, incurable with standard chemo-immunotherapy. The best initial treatment regimen remains unclear. Although it is generally acknowledged that aggressive approaches using combination chemotherapy and/or high dose chemotherapy can prolong survival, consensus on upfront treatment strategies for advanced MCL is currently lacking without randomized controlled data to guide treatment decisions. We conducted a retrospective cohort analysis to describe and compare the survival experiences of MCL patients at the University of Pennsylvania treated in the first-line setting with R-HCVAD (N=43) with or without autologous stem cell transplant (ASCT) or Rituximab maintenance. The primary study endpoints were PFS and OS as assessed by chart review and confirmed by SSDI database. Median follow up for all pts was 3 years. The median age was 53.7, and 76.7 % (n=33) were stage IV at diagnosis. 15 patients underwent consolidative ASCT. 11 pts received Rituximab maintenance. Comparing patients treated with R-HCVAD vs R-HCVAD + R maintenance vs. R-HCVAD + ASCT, there were no statistical differences in terms of age, ECOG PS, LDH, WBC, beta-2microglobulin, BM or GI involvement, bulky disease or blastoid variant at baseline. Median PFS for all patients was 3.9 years: R-HCVAD alone 2.1 years vs. R-HCVAD+R 3.9 years (P=0.02, HR 3.51, 95%CI: 1.2–10.2) vs R-HCVAD + SCT not reached (p=0.017, HR 3.7, 95%CI: 1.26–10.63). PFS survival rates at 2 years were 50%, 88% and 70%; 33%, 71/% and 63% respectively at 3 years, and 0%, 33% and 33 % at 5 years. 3 year OS for all patients was 84% (95% CI: 65–94) with no significant differences among the three approaches. Notably, only 1/8 patients treated with R-HCVAD + SCT relapsed after 2 years, with a median follow up of 4.8 years for these patients. Our data suggest a further improved PFS when R-HCVAD is consolidated with either Rituximab maintenance or ASCT. While neither of the two consolidative approaches appears superior in our limited data set, both show significant PFS prolongation when compared to R-HCVAD alone. Further prospective investigation of consolidative approaches after RHCVAD in a randomized fashion is warranted. Figure 1: Figure 1:. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 600 Although therapy for Bcr-Abl+ leukemia has been revolutionized by the development of the tyrosine kinase inhibitors (TKI), some patients, particularly those with advanced phase chronic myeloid leukemia or acute lymphoblastic leukemia (ALL) have unsatisfactory responses. We have demonstrated that inhibition of calcineurin with cyclosporine (CsA) increases the sensitivity of Bcr-Abl cells to TKI; furthermore, combination therapy with CsA plus dasatinib cured all mice with Bcr-Abl+ ALL, whereas all of the mice treated with dasatinib alone died with leukemia (Gregory et al, Cancer Cell, 2010). While the synergistic effect is independent of MDR1 inhibition by CsA in vitro, the possibility remains that the demonstrated survival advantage of combination therapy is due to altered pharmacokinetics (PK)and increased dasatinib exposure. We sought to determine if co-administration of CsA with dasatinib alters dasatinib PK, if differences in PK are sufficient to explain differences in response to therapy in vivo, and if combination therapy appears to adversely affect T-cell numbers. Bl6 mice were treated with dasatinib (20mg/kg/d), cyclosporine (25mg/kg/d), or both by oral gavage. Serum from peripheral blood was obtained at 0, 1, 2, 4, 8, 12, 24, and 48 hours after single doses and after one week of therapy (trough, 1, 2, 4, 8, and 12 hours). Dasatinib levels were determined by LC/LC-MS/MS. Pharmacokinetic (PK) analyses indicate that after 1 week of therapy, co-administration of CsA with dasatinib increases the Cmax and AUCinf of dasatinib as compared to dasatinib alone (277.4 v. 107.7 ng/ml and 916.8 v 487.4 ng/ml*hr, respectively; Figure A). The PK profiles suggest that co-administration of CsA with dasatinib enhances enteric absorption of dasatinib, but has little effect on its systemic elimination. Next, Arf-/-Bcr-Abl+GFP+ leukemia cells (Williams et al, Genes Dev, 2007) were transferred into unirradiated recipients which were treated with dasatinib (10 or 20 mg/kg/d) or with combination therapy (CsA 25mg/kg/d with dasatinib 5 or 10 mg/kg/d) for 7 days. Leukemia bearing mice were euthanized and the bone marrow (BM), peripheral blood (PBL) and spleens (SPL) were assessed for leukemia burden by flow cytometry. Combined CsA and dasatinib results in better disease control, even at doses predicted to result in similar exposure to dasatinib alone (i.e. half). For example, the mean percentage of GFP+B220+ BM cells was 6.7% in mice treated with dasatinib 10mg/kg/d as compared to 0.1% in mice treated with dasatinib 5mg/kg/d plus CsA (p

Description: Abstract 4574 Background CTCLs are generally incurable with conventional therapies. In particular, advanced mycosis fungoides (MF), Sézary syndrome (SS) and gamma delta varieties of CTCL have poor survival rates and are often refractory to traditional chemotherapy. Allogeneic SCT may provide a GVL effect and improve outcomes for these patients. Methods A retrospective analysis was performed at the University of Pennsylvania to identify all patients with CTCL who underwent allogeneic transplantation. 12 patients were identified who were transplanted between 2004 to 2010. A chart review was performed to obtain data about demographics, diagnosis, staging, treatment, transplantation and outcomes. Results Median age at diagnosis was 49 yrs and M:F ratio was 5:7. Prior to transplantation, 4 had MF (stages IIB, IIIB, IVA1, IVB; 2 with nodal transformation), 4 had SS (one stage IVA1, three IVA2; 1 with nodal transformation), and 3 had gamma delta T-cell lymphoma (all T3b). Median time from diagnosis to transplantation was 3.3 yrs (range 0.5@02b97 yrs). Patients had received a median of 8 non-chemotherapy, and 2 chemotherapy-based treatment modalities before being transplanted. Only 3 patients were in complete remission (CR) at the time of conditioning and 9 had evidence of active disease. Reduced intensity conditioning (RIC) was used in 10 cases (Flu/Bu, Flu/Cy or Flu/Mel), and conventional myeloablative conditioning (Cy/TBI) was used in 2. GVHD prophylaxis consisted of calcineurin inhibitor and methotrexate in all patients. The median follow up for all pts is 6.6 months (range 1.4 to 37.1 months) and 11.2 months for surviving patients. All patients engrafted with an ANC 〉500 a median 13 days after SCT. Median donor chimerism at day 100 after SCT in 10 evaluable pts was 97%. 7 of 12 patients developed acute GVHD, 4 of whom had grade 3 GVHD. Two patients died within the first 100 days, from sepsis with active disease. At day 100, 7 of 10 evaluable patients were in CR, with an additional patient achieving CR shortly after; therefore transplant induced and maintained CR in 6 pts with active disease. 3 patients relapsed after achieving CR a median of 11.4 months (range 5.3–13.0 months) after SCT. 2 patients never achieved CR, and progressed within a month of transplantation. The median PFS for all pts was 31 wks, and 1 yr and 2 yr PFS were 48% and 32% without an obvious plateau. 2 year OS was 53% (Figure 1). Median OS is not reached. 6 patients have died from progression (5) and GVHD (1), 5 remain in CR and 1 is alive with active disease. Conclusion RIC SCT can provide long-term disease control in patients with advanced CTCL otherwise refractory to immunotherapy and chemotherapy. Given the limited TRM, consideration for earlier transplant should be given. Larger retrospective and ideally prospective studies will further define the role of allogeneic SCT in this disease. Disclosures: Rook: Therakos: Speakers Bureau; HY Biopharma: Consultancy. Kim:TenX: Research Funding; Biocryst: Research Funding; Genmab: Research Funding; Glouchester: Research Funding; Celgene: Research Funding; Eisai: Consultancy.

Description: Abstract 3772 Genetic modification of autologous hematopoietic stem cells (HSC) has the potential for effective treatment of a wide variety of inherited blood disorders. However, HSC gene therapy has shown limited clinical efficacy (with notable exceptions), in part because of the small proportion of engrafted genetically corrected HSCs. The use of drug-resistance genes to enable selection for transduced HSCs has been explored, but with limited success. Previous studies from our laboratory have indicated that murine HSC can be selected with 6-Thioguanine (6TG), a relatively non-toxic drug used in the treatment of leukemias, after knocking down the expression of hypoxanthine-guanine phosphoribosyltransferase (HPRT), an enzyme that metabolizes 6TG to its active state. We sought to determine if these findings can be translated to human hematopoietic cells. In the present study, we transduced human myeloid (Molm13, MV4-11) and lymphoid cell lines (Reh) with lentiviral vectors expressing shRNA constructs targeting HPRT or a non-targeted control sequence (Ctrl). Two of the most promising constructs directed against HPRT (491 and 50) were studied in more detail to determine which is most effective. Cells were selected in puromycin and cell lysates analyzed for HPRT gene expression. Reverse-transcription, real-time PCR (RT qPCR) and western blotting demonstrated that construct 491 was most efficient in knocking down HPRT in human hematopoietic cell lines compared to construct 50 (and Ctrl). To determine whether knockdown of HPRT provided resistance to 6TG, cells were cultured in the absence or presence of different doses of 6TG and live cell concentrations were determined. While Ctrl transduced cells decreased in a dose dependent manner after 72h of 6TG treatment, cells transduced with constructs 491 and 50 were relatively resistant to 6TG. IC50 values for construct 491 were significantly higher (114μM for Molm13 and 46μM for Reh cell lines) than construct 50 (1μM for Molm13 and 10μM for Reh) in comparison to control transduced cells (0.4μM for Molm13 and 3.5μM for Reh). We assessed cell death in human hematopoietic cell lines by annexin V staining after exposure to 6TG at 48 and 72h. As expected, control transduced cells died of apoptosis upon 6TG treatment, while 491 and 50 transduced cells were resistant. Furthermore, 491 transduced cells were more resistant to apoptosis than 50 transduced cells. Based on these results, construct 491 was used to transduce human CD34+ progenitor cells isolated from umbilical cord blood along with control shRNA. Transduction efficiency varied from 25–35% as determined by %GFP expression by flow cytometry. Sorted GFP+ cells showed reduced expression of HPRT in 491 transduced cells compared to controls, as measured by RT qPCR. Similar to the effects in cell lines, in vitro proliferation of control transduced CD34+ cells diminished in response to increasing 6TG concentrations. There was an increase in the percentage of GFP+ cells in 6TG treated 491 transduced cells compared to untreated controls in a dose dependent fashion, indicating a selective advantage conferred to 491 transduced cells in the presence of 6TG. Importantly, 491 transduced cells continued to proliferate despite treatment with 6TG. Like 6TG, cisplatin requires mismatch repair (MMR) for cytotoxicity. To determine if HPRT knockdown had off-target effects impairing MMR, transduced cells were also treated with cisplatin. Both control and 491 transduced cells stopped proliferating in the presence of cisplatin indicating that MMR remained intact. These data indicate that human hematopoietic progenitor cells can be selected in vitro by knock-down of HPRT and treatment with 6TG. Xenografts of Ctrl and 491 transduced human CD34+ cord blood cells have been generated and are being treated with 6TG to determine if human cells can be selected with 6TG in vivo. Disclosures: Off Label Use: Off label use of 6-thioguanine will be suggested.

Description: Abstract 1970 Background: An effective and convenient regimen is appealing for Multiple Myeloma (MM) therapy. Lenalidomide and dexamethasone combination is highly effective in MM. However, at the FDA approved dose, dexamethasone related toxicity remains challenging. We report the efficacy and side effect profile of an all oral, dexamethasone-sparing combination of lenalidomide, cyclophosphamide and prednisone in newly diagnosed MM. Methods: The treatment protocol consisted of lenalidomide (Revlimid®) given orally at a dose of 25 mg daily on days 1–21 of a 28-day cycle, cyclophosphamide at a dose of 50 mg b.i.d. days 1–21 of a 28-day cycle, and prednisone 50 mg q.o.d (RCP). Responses were assessed on intent-to-treat basis based on the International Uniform Response Criteria. Treatment was planned for 6 cycles. Responding patients proceeded to observation, or transplantation, based on patient's preferred choices. All patients received, unless contraindicated, aspirin prophylaxis (81 or 325 mg daily) for prevention of deep-vein thrombosis, acyclovir for herpes zoster prevention, and bisphosphonates. Results: Forty six patients were enrolled from October 2007 to August 2010. Median follow up duration was 5.6 months. At this time, 38 of 46 patients are evaluable for confirmed responses (i.e., off-study or completed at least 4 cycles of therapy). The median age was 63 years (range, 41–76). 16 patients had ISS stage II (42%) and 8 (21%) had stage III disease. The median number of cycles was 6 (range: 1 – 6). Among the 38 evaluable patients, the overall response rate was 95%, consisting of CR: 1 (3%), VGPR: 9 (24%) and PR: 26 (68%). One patient had stable disease (1%) after the first cycle and treatment is ongoing. One patient had progression (3%). Thirty twoof 38 patients have discontinued study treatment. Reasons for treatment discontinuation are: completed study per protocol (24), disease progression (3), adverse event (2), non compliance (1), alternate treatment (1) and withdrawal of consent unrelated to toxicity (1). The most common toxicity was sensory neuropathy (24%): 8 (21%) grade I and 1 (3%) grade II. Other common toxicity included constipation (21%), pruritus (21%) and edema of limbs (18%). The most common hematologic toxicity was neutropenia (18%); 4 grade III and 2 grade IV. Infections were seen in 4 patients (2 febrile neutropenia and 2 with normal ANC). Five patients had grade 4 metabolic abnormalities (2 renal failure attributed to dehydration and tumor lysis, 2 hyperglycemia. and 1 hypokalemia). Thirteen patients had dose adjustments or interruption, most commonly due to hematological toxicity attributed to lenalidomide or cyclophosphamide. Twenty-five patients had stem cell collection. In all, sufficient numbers of stem cells (CD34+ cells ≥ 4.0 × 106 cells/kg) were collected for the transplantation use. To date, fifteen have undergone high dose chemotherapy and stem cell transplantation. Of eight patients with PR on RCP, seven achieved VGPR and one achieved CR post transplant. Of four patients with VGPR on RCP, 2 achieved CR and 2 remained in VGPR post transplant. Post-transplant response is not yet evaluable in the 3 remaining patients. Conclusions: The combination of lenalidomide, cyclophosphamide, and prednisone (RCP) has excellent activity in the setting of newly diagnosed myeloma. Overall toxicities were manageable. The study is still ongoing with the total accrual goal of up to 48 patients. The updated data for response and toxicities will be presented at the ASH Annual Meeting. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 407 Since the hematopoietic system is exquisitely sensitive to environmental and iatrogenic injury, the bone marrow microenvironment likely provides protective mechanisms during times of injury or stress. We have previously demonstrated that prostaglandin E2 (PGE2), which can be produced by many cell types in the bone marrow, targets both the bone marrow microarchitecture and primitive hematopoietic cells when administered systemically to mice (Porter, Frisch et. al., Blood, 2009). Since PGE2 is a local mediator of injury and is known to play a protective role in other cell types, we hypothesized that it could be an important microenvironmental regulator of HSPCs during times of injury. To test this hypothesis, we injured mice with a sub-lethal dose of gamma radiation, 6.5 Gy TBI, and sacrificed mice at varying time points from 1 hour to 6 days post-radiation. Bone marrow supernatant was collected and used for quantification of local PGE2 levels by ELISA. We found that, compared to non-irradiated mice, the PGE2 levels were increased greater than two-fold by 4 hours after irradiation (p=0.0030; n=3–6 mice/group), and these levels remain elevated until at least 6 days after injury (p

Description: Abstract 1533 Background: Advances in treatment of thalassemia have led to increased life expectancy for patients, making outcomes such as health related quality of life (HRQOL) an important consideration of therapy. However little has been published about the HRQOL of patients living with thalassemia, especially as it may change over time. Our study reports changes in patient-reported HRQOL from baseline to year 1 in the Thalassemia Clinical Research Networks (TCRN) Thalassemia Longitudinal Cohort (TLC) study. Methods: The TCRN is an NIH sponsored network of 16 major thalassemia centers in the US, Canada and London. We report here on the results from 220 patients (approximately 80% of the total cohort) over the age of 14 who completed baseline and year 1 assessments. HRQOL was measured by self-report with the Medical Outcomes Study 36-Item Short Form Health Survey version 2 (SF36v2). We defined a clinically significant change as a difference of at least 2 points on any SF-36 subscale. Results: Overall the patients were 46% male with a mean age of 29 years at baseline (range 14–58). Across the TLC population, mean self-reported HRQOL showed little change over the 1 year study period, with only social functioning showing a significant increase (p=0.04). However in each SF-36 domain over 50% of patients reported a signficant change in scores (an increase or decrease of more than 2 points) (Figure 1). All patients had a significant change on at least one domain, with a mean of 7 domains affected. Overall a small majority of patients (56%) reported that their health in general was “about the same” at year 1 as at baseline; 14% reported it was somewhat worse, 19% somewhat better, and 11% much better. Forty-nine % of patients reported requiring fewer transfusions in year 1, while 34% needed more, and 17% had no change. Most patients (82%) made no change in their chelator, although 8% changed from deferoxamine (DFO) to an oral chelator, fewer than 1% changed from oral to DFO, and 3% each stopped and started chelation. Most patients (61%) reported the same general adherence rate, although taken together there was slightly better reported adherence in year 1. Almost half of patients (47%) reported no change in chelator side effects, although again there was a slight overall decrease in reported side effects across the group. Most patients (92%) reported no new secondary complications in year 1. As expected, increasing age was associated with decreased HRQOL in the following domains: physical function, bodily pain, vitality, social function, mental health, and physical summary scales, although only bodily pain showed a clinically significant change (+2.1 points). Gender, race, change in number of transfusions, and change in chelator were not associated with change in HRQOL, although there was a trend towards improved general health in patients who made any change in chelation. A decrease in reported side effects from chelation was associated with an improvement in physical functioning (+2.8) and the mental summary score (+3.48), while development of a new complication during the one year study period was associated with a decrease in role-emotional (-8.2). Surprisingly an increase in reported adherence was associated with a decrease in social functioning (-5.1), role emotional (-7.7) and the mental summary score (-5.4). Conclusions: As a population, the TLC showed overall stability in clinical status and SF-36 scores over the 1 year study period. However individual patients reported significant changes, both positive and negative, in an average of 7 SF-36 domains. HRQOL appears to be most affected by age, with some association with changes in chelator, secondary complications, side effects and adherance. Further analysis is needed in order to fully understand these associations. Disclosures: Neufeld: Novartis, Inc: Research Funding; Ferrokin, Inc: Research Funding.