ALBERT

Description: Bortezomib is a very useful drug in the treatment of multiple myeloma (MM) patients. Used in combination with other antineoplastic drugs it has a well documented impact in progression free survival (PFS) and overall survival (OS) of any age patients, elegible or not for hematopoietic cell transplant. Standard dose (1,3 mg/m2) is used in almost all patients and low dose (0,7-0,8mg/m2) is reserved to patients with kidney disease and neuropathy. However, bortezomib doses used in phase 1 and 2 initial studies were described between 0,7 and 1,3 mg/m2 and were equally effective. The aim of this study was to evaluate the cytometric response of MM naive patients to two different bortezomib doses. We retrospectively analyzed the flow cytometry of fourty eight patients with naive MM treated with VCD scheme (Bortezomib-Cyclophosphamide-Dexametasone), without kidney failure nor neuropathy, of whom 21 received low doses of bortezomib (0.8mg/m2) and 27 standard doses (1.3 mg/m2). Flow cytometry was analyzed at diagnosis and at the end of treatment according to the expression of several clusters of differentiation (CD), establishing the presence of plasmoblastic myeloma clones (〉95% of plasma cells with immunophenotype CD19 (-) CD56(+) CD45(-) CD38(+) and restriction of intra cytoplasmatic kappa and or lambda light chains) and normal mature plasma cells (CD19(+) CD56(-) CD45 (+) CD38 (++) with a policlonal expression of kappa/lambda light chains). Cytometric complete response was defined as normalization of the immunophenotype of plasma cells and absence of pathological cells. We found no statistical differences between the 2 groups in flow cytometric response (p〉0.1), as shown in figure 1. This retrospective analysis suggests that lower doses of bortezomib could have similar effects in disease control, at least in cytometric response, to standard doses. Further studies should be made to evaluate clinical response and overall survival in patients treated with low doses compared to standard doses of bortezomib. In our country high costs of new generation antineoplastic drugs makes it necessary to find less expensive and equally effective schemes in order to make these well known beneficial treatments available to a greater number of patients. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Autologous hematopoietic transplantation (autoHT) is an effective treatment in myeloma and lymphoma patients. To perform it, an adequate harvest of stem cells is required. Collection of stem cells can be challenging in some patients, because they do not achieve satisfactory CD34 cell counts with GCSF + - chemotherapy. Plerixafor is a potent drug that promotes the release of stem cells from medullar niche to peripheral blood and allows satisfactory harvests but at a high cost. Different criteria of use have been applied in several countries to select patients eligible for treatment with plerixafor, with a high variability of prescription modalities. Even more, there are difficulties in precise the optimal schedule and dosification mainly by differences in the number defined as optimal collection, because some centers use the minimum tolerated collection cellularity of 2.0 x106 CD34/ kg and others use more stringent cells recounts. Development of our own algorithm for stem cell harvest is mandatory. Methodology We performed a retrospective analysis of the harvests performed in patients treated with autoHT in our institution since 1993. In 2013 plerixafor was available in our country and was included in our transplantation program. Satisfactory harvest was defined with total cellularity obtained of 2.5 x106 CD34/ kg. Results During the last 26 years, 273 patients with myeloma and lymphoma were treated with autoHT. Before 2013, all patients (n=112) were mobilized with GCSF +- chemotherapy. In this period, 75% of patients had successful harvests, requiring more than 2 apheresis procedures in 30% of them. Median cellularity obtained was 2.7 x106 CD34/ kg (range 1.2-15). Since 2013, 161 patients were treated with autoHT and we found that 80% of patients obtained satisfactory harvests with 1 apheresis and satisfactory harvests were obtained in 97% using plerixafor in 50% of them (p 〈 0.001). Median cellularity obtained was 4.8 x106 CD34/ kg (range 2-14) (p 〈 0.001). In multivariate analysis, after 2013 the only factor that predicted the need for plerixafor was the presence of less than 30,000 CD34 / ul at the day of the apheresis (OR 0,3 p

Description: Introduction. The use of cryopreservation of hematopoietic precursors for autologous or allogeneic transplantation with DMSO is a procedure commonly used in many countries, but it is expensive and is not exempt of risks, since serious adverse events have been described. Our group recently published a comparative study between two centers and showed that avoiding DMSO cryopreservation favors better transplantation tolerance, significantly shorter hospitalizations, fewer episodes of febrile neutropenia and mucositis. In this report we show the financial analysis of both modalities of CRYO and Non CRYO preserved transplants. Methodology Database of the adult hematopoietic transplant program of our institution was retrospectively analyzed. Since Non CRYO modality was initiated in our institution on 2015, we compared 3 years before and after that date, assigning two groups (CRYO and Non CRYO). Costs data of mobilization, apheresis, hospitalization, freezing and blood banking were analyzed. Results Between 2013 and 2018, 90 autologous hematopoietic transplants were performed, 41 CRYO and 49 Non CRYO. The average cost of mobilization therapy with filgrastim and the use of plerixafor did not differ between groups (p = 0.26). The number of apheresis needed to achieve a satisfactory count was higher in CRYO (median 1.5 vs 1.2 p = 0.001) with 55% higher cost on average. The cost of transplant hospitalization including antibiotics costs, blood banking costs, analgesics requirements and nutritional parenteral support was lower in Non CRYO (minimum cost USD 8000, maximum USD 160000 average value USD 20.000) than in CRYO (minimum cost USD 11.000, maximum USD 200.000, average value USD 32000) (p = 0.001). Conclusions In addition to promoting better patient tolerance, Non CRYO modality in our country has lower cost. This information has important relevance for health systems of developing countries and can promote better access to transplant. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Autologous hematopoietic transplantation (AHT) is an established therapy in multiple myeloma (MM) and lymphoma. Standard mode (CRYO) consists on collection of autologous precursors, freezing with dimethyl sulfoxide (DMSO) and subsequent thawing and reinfusion. However, this process is toxic and increases transplantation costs. Non-Cryopreserved (Non-CRYO) mode is a less expensive mode of AHT that has shown same transplantation outcomes in several single-center experiences. The Pontificia Universidad Católica de Chile transplant program began Non-CRYO AHT in 2015. In this study, we have compared patients who had Non-CRYO AHT in Chile with patients who had standard CRYO AHT in Spain at the same period of time. Aims: Our main objective was to compare short-term complications between both modes of AHT in terms of severe mucositis measured by use of morphine, total parenteral nutrition requirements, febrile neutropenia, engraftment and length of hospitalization. Other objectives were overall response, non-relapse mortality and overall survival. Methods. This is a prospective analysis of all consecutive adult patients treated with AHT in both centers from January 2015 to May 2016. CRYO mode procedure consisted of the stimulation of hematopoietic progenitors with filgrastim +/- plerixafor in both MM and lymphoma patients, CD34-apheresis on day 5, freezing of product with DMSO, subsequent thawing and reinfusion post conditioning. In Non-CRYO mode, once patients achieved the best response, they received the same filgrastim +/- plerixafor treatment followed by CD34-apheresis without DMSO freezing. Apheresis product was kept at 5°C during conditioning and then re-infused. Conditioning regimen for MM patients was high dose melphalan and for lymphoma patients BEC or BEAM protocols. All patients were hospitalized during the period of pancytopenia and received transfusions, antibiotics and symptomatic measures as usual. Patients were discharged when they reached 〉500 neutrophils/uL and 25.000 platelets/uL without the need of transfusions, and did not have active infections. Results. Since 2015, 29 Non-CRYO and 58 CRYO AHT were performed in both centers. General characteristics are detailed in table 1. No significant differences were observed regarding demographic characteristics, basal disease and status, and CD34 cellularity. 7AAD FACS viability at infusion day was greater than 92% in Non-CRYO and all patients engrafted in both groups. As we show in table 2, neutrophil and platelet engraftments were significantly earlier in Non-CRYO group vs CRYO group (p = 0.003). Less gastrointestinal toxicity was seen in Non-CRYO group in terms of morphine use (11% vs 55%, p= 0.001) and total parenteral nutrition requirements (11% vs 14%, p= 0.06). The incidence of febrile neutropenia was lower in Non-CRYO group (28% vs 85% respectively, p=0.0001). Finally, lengh of hospitalization was shorter in Non-CRYO (p=0.008). Overall response obtained after transplant was similar in both groups. Non relapse mortality was low and similar in both groups (0 vs 0.5%). We found no differences in relapse nor overall survival. Conclusions. This analysis demonstrates a clear advantage of Non-CRYO AHT over CRYO AHT in terms of short term complications, in particular, faster engraftment, shorter hospital stay and lower incidence of febrile neutropenia and severe pain manifested by morphine use. These data are especially relevant to transplant centers with high flow of patients or limited resources. The savings in costs of freezing process and shorter hospitalizations should be evaluated in further investigations. Disclosures No relevant conflicts of interest to declare.