ALBERT

Description: Key Points For patients in developing countries with APL, a clinical network of institutions made it possible to reduce significantly the early mortality and improve the OS.

Description: Leukemia relapses occurring in donor cells, so called donor cell leukemias (DCL) after allogeneic hematopoietic stem cell transplantation have been reported in several cases and still are considered as rare diseases. Cytogenetic analysis, flow cytometry and molecular testing have been used to confirm this event in the cases so far reported. The etiology of DCL is unclear, and the reported literature does not suggest a common mechanism. The incidence of this condition is largely unknown, as well as the results of its treatment. We have prospectively searched for DCL in a 12-year period, in a single institution. In a group of 106 consecutive patients allografted because of leukemia; we have identified 7 cases of DCL; six of them were allografted because of relapsed acute lymphoblastic leukemia (ALL) and one because of paroxysmal nocturnal hemoglobinuria / aplastic anemia; these figures suggest that the real incidence of DCL has been underestimated in previous studies. All the patients were allografted from HLA-identical siblings, employing a reduced-intensity conditioning regimen. The cases of DCL appeared one to 40 months (median 10) after the allograft; the number of blast cells when the leukemic activity ensued was above 50% in all cases, whereas the chimerism studies revealed more than 90% cells of donor origin. The origin of the leukemia cells was shown by microsatellites in all cases and in three with a sex mismatch it was confirmed by the enumeration of XX / XY cells in the leukemic cells. The six patients with lymphoblastic DCL were treated prospectively with a pediatric-inspired combined chemotherapy schedule designed for “de novo” ALL patients. A complete response was obtained in 3/6 patients with lymphoblastic DCL these patients being alive in a complete remission at 11, 12 and 98 months after the diagnosis of DCL. The patient with hairy cell DCL has had a benign course, not needing any treatment. In the whole group the median survival (SV) has not been reached, the overall SV being 57% at 98 months. The long-term DCL survivors remain full chimeras and did not need a second transplant. It is concluded that the prevalence of DCL may be higher if it is prospectively looked for, and that acceptable therapeutic results are obtained if patients are treated as “de novo” leukemias employing combined chemotherapy. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4211 Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased platelet destruction and suboptimal platelet production, which results in low platelet counts and mild to severe bleeding. Bleeding events may range from petechiae and purpura to severe intracranial and gastrointestinal haemorrhage. Approximately 5% of adult ITP patients suffer from a fatal bleeding event. However, the risk of severe, fatal bleeding is significantly higher for patients who are unresponsive or intolerant to current therapies, over the age of 60 years, or refractory to splenectomy. The prevalence of diagnosed cases of chronic ITP in the overall population in Canada is reported to be 20.3 per 100,000; thus, it is estimated that there are about 160,000 people in Quebec with chronic ITP. Therapeutic management of ITP include the use of corticosteroids, immunosuppressive agents, and intravenous immunoglobulins (IVIg). IVIg is an expensive and occasionally scarce blood product. Surgical management includes splenectomy. Most recently, thrombopoietin (TPO) mimetic agents such as romiplostim and eltrombopag have been used to treat ITP. Romiplostim is indicated in Canada to increase the platelet levels in adult patients with chronic immune (idiopathic) thrombocytopenic purpura: •Who are non splenectomized and have had an inadequate response or are intolerant to corticosteroids and/or immunoglobulin; •Who are splenectomized and have had an inadequate response to splenectomy. Romiplostim does not have public reimbursement in the province of Quebec. Although the public drug program expert review acknowledged the benefit of romiplostim in substantially reducing the use of IVIg, the reviewers did not recognize the use of IVIg as a maintenance therapy. The objective of this study was to conduct a net cost analysis to determine if using romiplostim instead of IVIg can result in savings to the provincial health care budget in Quebec. Methods: A net cost impact model was developed to provide a detailed analysis of the cost implications of romiplostim utilization compared with IVIg, including the drug treatment costs, costs related to the preparation and administration of medications, monitoring costs, and indirect costs such as patients' time away from usual activities or work. Expert consultation with physicians, pharmacists and nurses in Quebec was used to define treatment algorithms including all health resource utilization required when using romiplostim and IVIg. Costs were assigned to direct (e.g., drugs, medical supplies, laboratory testing, healthcare professionals' time) and indirect (e.g., productivity) healthcare resources. Results: Based on the median weekly dose (3mcg/kg) observed in the pivotal romiplostim clinical trial in splenectomised patients, the annual cost of romiplostim per patient was $47,244. The annual per patient cost of IVIg was $114,548 based on an average dose suggested by a clinical expert (1g/kg every 4 weeks and average administration time of 3.5 hours). Lower costs for drug preparation and administration ($284 vs. $1355) and less time lost from work (valued at $447 vs. $2141) were attributed to romiplostim compared to IVIg. The time attributed to monitoring was the same for both romiplostim and IVIg ($115). The total average annual per patient costs including medication, drug administration, monitoring and lost productivity for romiplostim vs. IVIg were, respectively, $48,090 and $118,159. The use of romiplostim would save, on average, about $70,069 per patient per year. Conclusion: From a societal perspective, treating ITP patients with romiplostim can provide a lower cost alternative to IVIg for the overall provincial healthcare budget. Compared with IVIg, the use of romiplostim results in lower direct costs, reduced health care resource utilization and less indirect costs. As a precious commodity, blood products must be used wisely. As stated by the expert review committee in Quebec, IVIg should remain a last resort option to treat ITP. Romiplostim can allow for improved healthcare resource allocation by reserving IVIg for use in other areas of greater need while also providing cost savings. Romiplostim also potentially improves patients' quality of life by reducing the time required for drug infusion and avoids the risks associated with IV administration. Disclosures: Pettigrew: Amgen Canada Inc.: Consultancy. Deuson:Amgen: Employment, Equity Ownership. Garces:Amgen Canada: Employment, Equity Ownership.