ALBERT

Description: Background Splenectomy (SE) at the Myelofibrosis (MF) is one of the difficult operations on the techniques and perioperative complications. There are a lot of complications such as inflammatory and adhesive processes, a massive bleeding associated with disorders of hemostasis in thrombocytopenia or thrombocytosis, enlargement of varicose veins, concomitant pathology. A SE doesn’t cure myelofibrosis but may be performed in some cases. Success is unpredictable, and the operative mortality of SE is on the order of 10%. Objectives Evaluate the clinical and hematologic SE efficiency in patients with MF, resistant to traditional treatment. Patients and methods We analyzed the medical case history of 52 patients with MF, which were observed in the National Research Center for Hematology from 2004 to 2013. All patients were performed SE. 47 patients diagnosed with primary MF, and 4 – post-polycitaemic MF and 1 patient post-trombocitaemic MF. PMF was diagnosed according to the criteria established by WHO (2008), which include bone marrow fibrosis, and splenomegaly leyko-eritroblastosis in peripheral blood. The average age at diagnosis was 47 years (24 – 78 years), and before the SE – 53 (25 – 79 years). Women and men ratio was 1.3:1. According to the predictive model of the Dynamic International Prognostic Score System - (DIPSS) 38 (73%) patients before the SE attributed to intermediate risk 2, 14 (27%) patients – high risk. BCR-ABL gene not found a single patient, and the gene mutation JAK2V617F at different stages of the disease is detected in 53% of cases. Genetic adverse factors are not taken into account because of the small number of studies. Massive and huge splenomegaly was present in 37 (71%) patients. Spleen weight 0.9 to 2.9 kg is removed in 15 (29%) patients, from 3 to 7 kg is removed in 35 (67%) patients. In two cases, removal of the spleen weight of 10 and 11 kg. Statistical analysis were done using SAS 9.3 and JMP 10.0 (SAS Institute Inc., Cary, NC). Results Disease duration was about 76 months and ranged from 1 to 240 months. Surgical complications occurred in 21 patients, including bleeding 3, thrombosis 1, infection 2. Surgical complications from SE in intra-and early postoperative period was 8% from 1978 to 2003. Surgical complications from SE in intra-and early postoperative period was not fixed from 2004 to 2013. After SE complications were hepatomegaly, resistant thrombocytosis (platelet count ≥ 600 × 109/L), leukocytosis (white blood cell count greater than 10 x 109/l) and blast transformation of the disease. More than 80% of patients after SE had no symptoms of intoxication. 22 patients with MF had transfusion dependent anemia, 11 (50%) had disappeared transfusion requirements after SE in and the effect lasted for about a year. Only 4 of the 15 patients with thrombocytopenia who underwent SE due to refractory thrombocytopenia were observed a significant increase in platelet count above 100h109 / L, for an average of 6 months. The possibility of the resumption of long-term cytoreductive therapy appeared in 30 (58%) patients. Currently alive 19 (37%) patients, mean follow-up was 37 months (4 to 72 months) after the SE and of 105 (12-264) months after diagnosis. 33 (63%) patients died during the observation period after SE (1 – 84 months, mean – 27 months). Among these, 27 (82%) patients died of transformation disease and 6 (18%) died of comorbidity. 19 (37%) patients, with a mean follow-up of 37 months after SE (from 4 to 72 months) continue treatment with hydroxyurea. Median survival after SE is 3 years (Figure 1), with a median overall survival - 11 years (Figure 2). Conclusion Despite the potential complications SE is an effective palliative method for patients with MF in the absence of leukemic progression. SE indicated in patients with drug refractory MF, acute constitutional symptoms, anemia, transfusion-dependent, and portal hypertension. Modern methods of surgery, as well as supporting therapy in the perioperative period can safely perform the SE. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1879 Splenectomy in patients with MDS is a treatment option that is beeing applied very rare [Steensma D., et al, Leuk Res.,2003; Bourgeosis E., et al, Leukemia, 2001]. There are anecdotal reports with very few patients demonstrating its efficacy. In most cases splenectomy was indicated for MDS patients with immune related thrombocytopenia. Here we would like to report the results of 33 splenectomies in patients with MDS who have been treated in our Center during 1994–2010. Within this period of follow-up totally 155 patients were diagnosed with different forms of MDS, 35% of them presenting with hypoplasia. The MDS treatment algorithm in our Center incorporates splenectomy as one of the options for pts with hypoplastic forms of MDS with bone marrow blast count less than 10%, refractory to initial cyclosporin A treatment or refractory to transfusions. Among patients who were splenectomised there were 20 females, 13 males with a median age of 40 years (range 18–74). Median time from diagnosis to splenectomy was 12 months (range 4–107). By WHO-classification there were 2 patients with RA, 22 – with RCMD, 2 – with MDS and del (5q), 6 - with RAEB, 1 - with AML after MDS. Cytogenetic analysis was available in 32 cases, and karyotype was normal in 15 patients (47%).The most common abnormalities were: del (5q) - 3, del (20q) - 2, trisomy 8 - 2, tetrasomy 8 - 1, monosomy 7 - 2, complex karyotype - 4. Bone marrow biopsy revealed hypoplasia in 25 patients (75%), myelofibrosis – in 7 (21%). The median WBC count was 2,6*109/L (range 0,6-8,7), hemoglobin 6,9 g/dL (47-119) and platelets 26*109/L (6-170). 27 pts (82%) were RBC transfusion dependent, 22 (67%) - platelets transfusion dependent. 13 pts had received immunosuppression therapy (ATG, cyclosporine A) before splenectomy, 2 - cytotoxic chemotherapy, 3 - decitabine. The majority of splenectomies were done by laparoscopic method - 26 (79%), in one case the convertion was done. In all cases we performed liver biopsy. Postoperative complications (hemorrhage) occurred in 1 patient but there were no deaths due to operation. One death occurred in 7 days after splenectomy due to fulminant progression to AML. Median spleen weight was 180 gms (range 70–930). Median intraoperative blood loss was 250 ml (range 50–9350). Histology was available in 30 patients. Extramedullary hematopoesis was revealed in 3 cases (10%), blast infiltration - in 2 (7%), massive lymphoid infiltration was detected in 5 cases and in one patient in was proved to be clonal (marginal zone lymphoma, MZL). Hemosiderin depositions in the macrophages were seen in half of the cases -16 (53%). One case was characterized by granulomatosis in spleen and liver with negative immunohistohemical staining to Mycobacteria tuberculosis. Splenectomy lead to sustained improvement of cytopenias in 16 cases (48%): decreased transfusion dependence in 14 (42%) and transfusion independence in 2 (6%). After splenectomy 5 patients were followed by “wait and see” approach, 17 continued with immunosuppressive therapy (ATG,CyA), 3 patients were treated with cytotoxic chemotherapy, 1 – with decytabine, 2 received EPO, 1- danazol, 2 - iron chelation therapy, 2 – only transfusions therapy. We did not noticed the infections rate augmentation after splenectomy. Transformation to AML was registered 6 (18%) at median 6 months (0,3 -9). 13 splenectomized patients (39%) died at a median 12 months (range 0,3-84) and the main death reasons were: AML progression, aplasia deterioration followed by infections and hemorrhage. 20 patients are alive with a median follow-up after splenectomy 33 months (2-108). Analysis of our 15-years study data give us a confidence to conclude that splenectomy still may be an adequate option for distinct forms of MDS (hypoplastic forms with bone marrow blast count less than 10%, refractory to initial immunosupressive treatment or refractory to transfusions), producing cytopenia improvement in half of the patients with decreasing transfusion dependance also in half of the patients, sometimes bringing a clear diagnosis (MZL). The mechanism of action is not very clear but we can speculate that splenectomy removes the “cell-destroying” organ, deminishes immune pathways of cytopenias due to large lymphoid compartment deletion, provides the resustainment of sensitivity to immunosupressive agents. Disclosures: No relevant conflicts of interest to declare.