Transfusion-dependent Myelodysplastic Syndromes Patients Research Articles

Myocardial iron loading by magnetic resonance imaging T2* in good prognostic myelodysplastic syndrome patients on long‐term blood transfusions

Magnetic resonance imaging (MRI) was used to quantify myocardial iron loading by T2* in 11 transfusion-dependent good prognostic myelodysplastic syndrome (MDS) patients. Myocardial T2*, left ventricular function and hepatic T2* were measured simultaneously. Patients had been on transfusion therapy for 13-123 months and had serum ferritin levels of 1109-6148 microg/l at the time of study. Five patients had not commenced iron chelation and had been transfused with a median of 63 red cell units and had a median serum ferritin level of 1490 microg/l. Six patients were on iron chelation and had been transfused with a median of 112 red cell units and had a median serum ferritin level of 4809 mug/l. Hepatic iron overload was mild in two, moderate in seven and severe in two patients. The median liver iron concentration was 5.9 mg/g dry weight in chelated patients and 9.5 mg/g in non-chelated patients (P = 0.17; not significant). Myocardial T2* indicated absent iron loading in 10/11 patients (91%; 95% confidence interval 62-98%) and borderline-normal in one patient. Left ventricular function was normal in all patients. No correlation was observed between increasing serum ferritin levels, hepatic iron overload and myocardial T2*. A long latent period relative to hepatic iron loading appears to predate the development of myocardial iron loading in transfusion-dependent MDS patients.

Thalidomide therapy in adult patients with myelodysplastic syndrome

The results recently published in Cancer by Moreno-Aspitia et al.1 concerning the unsatisfactory therapeutic effects of thalidomide in myelodysplastic syndromes (MDS) warrants some comments. This study was designed in 1998, the enrollment of patients closed in 2002, and the full paper published in 2006. During this very long time, at least 4, noncited, additional articles dealing with the same topic were published,2-5 reporting an overall response rate ranging from 16 to 56% in the intention-to-treat setting and from 31% up to 88% when considering only patients able to receive the drug for an adequate time (12–16 weeks). The high drop-out rate due to severe side-effects that occurred, likely correlated with the very high thalidomide doses employed in their study, certainly contributed to the quite different and disappointing results obtained by Moreno-Aspitia and coworkers. However, there are other possible reasons to explain such differences, first of all, the selection of patients. Moreno-Aspitia et al. enrolled not only anemic subjects but also patients with transfusion-dependent thrombocytopenia or marked neutropenia. It is now clear by other studies that the large majority of responses in MDS patients who are receiving thalidomide are erythroid in nature and that patients with “advanced disease” (criterion for inclusion in that trial) are significantly less prone to respond. This is particularly true if these patients have a long history of disease, as suggested by the very short median survival (only 17 months!) observed even in the “favourable group”, which included patients with an International Prognostic Scoring System (IPSS) score of 0–1, who usually have an expected survival of 3–5 years. In addition, the elevated mean age of patients and the high proportion of MDS with blast excess reported also represent potential predictive factors of poor response to thalidomide. Indeed, in our updated, still unpublished experience, which currently includes 67 anemic, transfusion-dependent MDS patients treated with thalidomide, patients aged younger than 70 years, with anemia as single cytopenia, no blast excess, and a short history of disease had the highest chance (62.5%) to obtain an interruption of their red cell transfusional support after a treatment with individualized (but no more than 200 mg/day) doses of thalidomide. In particular, we observed significant (and sometimes long-lasting) erythroid responses even in patients who did not tolerate “conventional” (100–200 mg/day) doses of thalidomide, but who were able to assume 50 mg/day or even on alternate days for at least 3 months. Thus, in my opinion, thalidomide remains a possible therapeutic option for selected MDS patients, if appropriately used and managed. Pellegrino Musto MD*, * Unit of Hematology and Stem Cell Transplantation Centro di Riferimento Oncologico della Basilicata (C.R.O.B.) Rionero in Vulture (PZ) Italy.

Evolving Applications of Lenalidomide in the Management of Anemia in Myelodysplastic Syndromes

Lenalidomide has emerged as an effective therapeutic alternative for the management of anemia in lower-risk myelodysplastic syndromes (MDS). Compelling results from phase I and phase II clinical studies prompted the US Food and Drug Administration to approve lenalidomide for the treatment of transfusion-dependent MDS patients with interstitial deletion of chromosome 5q [del(5q)]. Subsequently, the National Comprehensive Cancer Network (NCCN) has incorporated lenalidomide into their current treatment algorithm for the treatment of lower-risk del(5q) patients. This discussion examines the current NCCN guidelines for the treatment of these patients, including the management of anemia in lower-risk MDS, and discusses the potential future therapeutic applications of lenalidomide in this disease.

Disparities in Criteria for Initiating Chelation Therapy for Iron Overload in Patients with Myelodysplastic Syndromes (MDS).

In the majority of MDS cases, isolated anemia is the only clinical evidence of impaired hematopoiesis at the time of MDS diagnosis. It is estimated that >40% of MDS patients require regular red blood cell transfusions during some stage of their disease. Findings from The MDS Foundation's 2004–2005 Practices & Treatment Survey indicate that a substantial proportion of MDS patients in all International Prognostic Scoring System (IPSS) risk groups are transfusion-dependent: Low, 30%; Intermediate-1, 50%; Intermediate-2, 70%; High, 90% (median values). Seventy (38 US and 22 international) of the MDS Foundation's102 Centers of Excellence responded to the survey as of July 1, 2005. Survey responses revealed that an average of 30% of transfusion-dependent patients receive parenteral iron chelation therapy (median, 20%; range: 3–100%) and that the criteria for initiating chelation therapy are not uniform. The number of transfusions was reported as a determining criterion by 46% of respondents, with a mean number of 35 transfusions (median, 30; range: 4–100). 15% of respondents indicated at the number of transfusions was the sole criterion used. Serum ferritin levels were reported as a determining criterion by 57% of respondents, with the following cutoff values:Ferritin concentrations for initiating chelation therapy>1000 ng/mL41%*>1500 ng/mL11%>2000 ng/mL37%Other (>3000, unspecified)9%*% respondents using this cutoff as criterion32% of respondents indicated that serum ferritin was the sole criterion used. (Irrespective of chelation therapy, 92% indicated that they monitored ferritin levels in transfusion-dependent patients.) Other criteria used to determine start of chelation therapy included age/life expectancy, MDS subtype, clinical signs of hemochromatosis, quantitative CT liver iron estimation, liver function, transferrin saturation >50%, BMT, anticipated chronic transfusion need, and logistical issues and insurance coverage. A combination of criteria was reported to be used by 38% of respondents. The majority of respondents (90%) reported that they would increase the number of patients on chelation therapy if an oral agent were available. Although the decision for initiating chelation therapy in transfusion-dependent anemic MDS patients is individualized because of the heterogeneous patient population, this data analysis suggests a need for the standardization of select criteria (e.g., number of transfusions, serum ferritin).

Economic burden of transfusion dependence in patients with myelodysplastic syndromes

6064 Background: Few studies have examined health economic burden in transfusion-dependent patients with myelodysplastic syndromes (MDS). Two-thirds of MDS patients are estimated to have anemia and require red blood cell transfusions, costing approximately $550/unit transfused. This study explored health care costs and utilization in this population. Methods: Administrative claims data from a large US health plan with commercial, Medicare, and Medicaid members were used to identify transfusion-dependent patients from 5/1/00 through 3/31/03 that were ≥ 55 years of age. Transfusion dependence (TD) was defined as ≥ 2 transfusion events in an 8-week period as indicated by procedure and/or revenue codes and service dates for whole or red blood cell transfusions, and a minimum of a third transfusion occurring 3–6 months from the initial transfusion. MDS was identified from medical claims data with an ICD-9-CM diagnosis code (238.7, 284.9, 285.0, 205.20, 208.20) in the 6 months prior to and up to 12 months following the index transfusion date. Patients with evidence of chemotherapy-induced anemia were excluded. Deferoxamine use was identified in all TD patients, regardless of MDS status, and one year of claims data following first administration was captured. Medical costs were defined as transfusion-related if costs occurred on the same day as a transfusion event. Results: A total of 338 transfusion-dependent MDS patients were identified. Average age was 73.6 years. Annualized average total medical and pharmacy costs were $58,457. 82.7% of transfusions occurred in an outpatient setting with an average of 11.03 outpatient transfusions per patient per year. Annualized transfusion-related medical costs in the outpatient setting were $9,270. 49.41% of patients had erythropoietin use and average costs per treated patient were $12,589. For 20 TD patients with deferoxamine use and one year of continuous follow-up, the average duration of therapy was 276.35 days; and average costs per year were $7,437. Conclusions: The economic burden in TD MDS patients is high. Significant opportunity exists to decrease economic burden if transfusion independence can be achieved in this population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene

Quality of Life and Economic Impact of Red Blood Cell (RBC) Transfusions on Patients with Myelodysplastic Syndromes (MDS).

Background: Supportive care with blood product transfusions is the primary management strategy for the majority of patients with MDS. Approximately 80% of MDS patients are anemic at the time of presentation and more than 40% require regular RBC transfusions at some stage of disease, while platelet transfusions are less often required.Methods: In an effort to systematically study quality of life and economic cost associated with transfusion dependency (especially RBC transfusions), The MDS Foundation has disseminated a practices and treatment survey to its Centers of Excellence and is also accumulating transfusion data. Retrospective and prospective data collected include hematologic parameters defining transfusion need; percentage (%) of MDS patients requiring transfusion; % of transfusion-dependent MDS patients by subtype and International Prognostic Scoring System (IPSS) risk group; per patient frequency of transfusions; % of patients requiring iron chelation therapy.Results: A total of 30 Centers have replied to the survey to date, and responses reveal that a substantial proportion of MDS patients receive multiple RBC transfusions with most of these patients needing chelation therapy with desferoxamine (generally subcutaneous administration, 4-times weekly): Table 1.In addition, detailed data are available from 4 European Centers that have provided transfusion records from randomly selected multiply-transfused MDS patients: 38 patients (median age: 73) received a median of 42 transfusions over the last 24 months (range: 11–207). The average per transfusion costs calculated from estimates provided by the 4 European centers is 436 euros or $ 526 ($1 US dollar = 0.83 euros), where the per transfusion cost includes 2 filtered red blood cell units, blood collection, administrative costs, and staff time, resulting in a median per patient cost over the last 24 months of 11,118 euros (range: 5668–21,800 euros). This does not include the cost of chelation therapy (300 euros/month for desferioxamine SC) and indirect costs (e.g., time spent at transfusion facility, travel time for patient to facility, travel and wait time for private caretaker or family member).Conclusion: Preliminary data analysis from the ongoing retrospective study suggests that the transfusion burden to MDS patients and to society, in terms of quality of life and cost, is much greater than generally appreciated. Updated data of this study will be presented.Table 1: RBC Transfusion-dependent MDS patientsMean %IPSS low risk39IPSS intermediate-1 risk50IPSS intermediate-2 risk63IPSS high risk79Iron chelation therapy28