Good Hematologic Response Research Articles

PB2138 LIGHT CHAIN (AL) AMYLOIDOSIS: A SINGLE CENTRE EXPERIENCE AND THE EFFECTIVENESS OF BORTEZOMIB BASED THERAPY AS FIRST LINE THERAPY

Background:Amyloidosis is a heterogenous disease characterised by deposition of amyloid fibrils in soft tissue. Light chain (AL) amyloidosis is the most common form of systemic amyloidosis and is a complication of plasma cell dyscrasia. It can affect a wide range of organs including kidneys, heart, nervous system, liver, gastrointestinal tract and spleen which make the diagnosis difficult. Kidneys are the most commonly affected organ in AL amyloidosis and most patients present with nephrotic range proteinuria.In light chain amyloidosis, clonal plasma cells use proteasome to cope with misfolded light chain induced proteotoxicity, and the proteasome inhibitor bortezomib is a potential targeted therapy. Studies have demonstrated that Cyclophosphamide, Bortezomib, Dexamethasone (CyBorD) is a useful, highly effective upfront option.Aims:A retrospective study to evaluate the experience of a single centre, Waitemata District Health Board on the source of referral, biopsy source and the effectiveness of Bortezomib‐based therapy with long term follow up.MethodsDatabase at Waitemata District Health Board was searched for newly diagnosed patients with amyloidosis between 2001 and 2018. 55 out of 70 cases reported to New Zealand Cancer Registry were included. The source of referral, light chain subtype, disease association and biopsy source were analysed.43 patients who received Bortezomib based therapy as first line had been identified. The haematological response was assessed according to the International Society of Amyloidosis criteria. The duration to complete remission and relapse rates were also analysed.Results:55 patients were diagnosed with AL amyloidosis between 2001 and 2018. Half of the patients were referred by renal service (49%) and 11/55 (20%) were from cardiology service. Two third (38/55) of the patients had lambda light chains. Vast majority (87%) had either MGUS or smouldering myeloma.Half of the patients were diagnosed from renal biopsy. Other sites of diagnostic biopsy sample include bone marrow, lymph node, cardiac, GI tract, liver and tongue. Congo red stain was done on 39/50 bone marrow trephine samples and 16 of them (41%) were positive (8 muscular layer, 1 cortical bone, 7 marrow interstitium). Rectal biopsies were done on 10 patients with 7 positive result (70%).Of the 43 patients who received Bortezomib based therapy as first line treatment, 14 (32.6%) achieved complete response within 30 days of commencing treatment. Three patients (21.4%) relapsed with median time to relapse of 3.6 years. 15 patients (34.9%) achieved complete response after 30 days of commencing therapy and 5 patients (33.3%) relapsed with median time of 2 years. Five patients achieved very good partial response (VGPR), six patients with limited or no response.Summary/Conclusion:Renal disease is the most common presentation of AL amyloidosis followed by cardiac involvement. 2/3 of patients have elevated serum free lambda light chain and most of them have either MGUS or smouldering myeloma on bone marrow biopsy. Diagnoses are mostly made on renal biopsy but rectal biopsy seems to be sensitive for diagnosis of amyloidosis infiltration as well. Bortezomib based therapy appeared to be effective treatment as first line therapy with 79% achieving good haematological response with sustainable remission status. Ongoing follow up and larger cohort will be required for more conclusive results.

PS1297 EFFICACY AND SAFETY OF INTRAVENOUS IRON THERAPY IN CHILDREN: A KOREAN SINGLE CENTER STUDY

Background:Although Intravenous (IV) iron is widely and safely administrated to adults for various indications including severe anemia, chronic blood loss and postoperative anemia, Administration of IV iron is rarely used in children due to lack of pediatric data.Aims:The aim of this study was to determine the indications for IV iron and to evaluate the efficacy and safety of IV iron infusions to children who were visited a single Korean center.Methods:This retrospective study collected data from ≤18 year‐old children who were received IV iron at the Keimyung University Dongsan Medical Center between July 2003 to December 2018. Exclusion criteria included: (1) receiving a packed red blood cell transfusion or erythropoietin, (2) surgery or massive bleeding before obtaining the laboratory results of post IV iron infusion. We compared laboratory results including hemoglobin (Hb) concentrate, mean corpuscular volume (MCV), serum ferritin level between pre and post‐IV iron infusion. Also, the medical records were reviewed for adverse effects. All statistical analyses were performed using IBM SPSS software (version 23.0; IBM Corp., Armonk, NY), and P‐values of <0.05 were considered statistically significant.Results:Total 31 children (male:female = 18:13; median age 4.5 years, range 0.3–17.9) received total 80 infusions of IV iron therapy. The most common etiology of anemia was gastrointestinal cause. Oral iron intolerance (32%) and refractoriness (26%) were common indications for IV iron infusion. Seventeen patients received a total 43 infusions of iron sucrose (median dose, 3.9 mg/kg, range 1.0 to 20.4), fifteen patients received a total 37 infusions of ferric carboxymaltose (median dose, 5 mg/kg, range 3.3 to 18.8). All Patients had follow up laboratory test at 1–120 days (median 15 days) after their infusions. Except 2 patients, all patients showed good hematologic response. The median pre‐infusion Hb, MCV and ferritin values were 9.0 g/dL (range 6.1–13.6), 75.9 fL (55.9–94.3) and 12.2 ng/mL (1.7–284.9), respectively. The median post‐infusion Hb, MCV and ferritin values were 10.7 g/dL (6.3–14.7), 79.6 fL (64.9–103.5) and 54.0 ng/mL (3.9–842.8), respectively. There were statistically significant improvements in these values (p‐value <0.001). No patients experienced severe adverse effects such as anaphylaxis.Summary/Conclusion:The most common indication for IV iron among Korean children was oral iron intolerance. The use of IV iron is effective and safe treatment in children.image

Helicobacter pylori and hematological disorders.

Helicobacter pylori (H. pylori) is one of the most common worldwide infections, which can affect both adults and children. The prevalence of this bacterium is variable in different countries, depending on various hygienic and socioeconomic conditions and living customs. The major damaged tissues of the infection are in the upper gastrointestinal tract, causing gastritis, gastric and duodenal ulcer and gastrointestinal malignancy. Nevertheless, other disorders are associated with this pathogen, including several hematological diseases, such as iron deficiency anemia, immune thrombocytopenia and vitamin B12 deficiency. A huge of data in literature support these associations, enough to recognize them in the last Maastricht V/Florence Consensus Report by European Study Group. The pathogenic mechanisms underlying the linkage between H. pylori and these hematological disorders are not clearly identified, but certainly the good hematological response reaches after eradication therapy confirm a central role of the bacterium in this scenario. Instead, the pathogenic mechanisms of H. pylori infection, which lead to the occurrence of mucosa-associated lymphoid tissue (MALT) lymphoma are clearer and more consolidated; so much that nowadays eradication therapy alone represents the only treatment in this disorder, when localized and with a concomitant H. pylori infection. This review focuses on the hematologic diseases related to H. pylori, particularly on iron deficiency anemia, vitamin B12 deficiency, immune thrombocytopenia and gastric MALT lymphoma.

Pomalidomide and Dexamethasone Grant Rapid Hematologic Responses in Patients with Relapsed and Refractory AL Amyloidois: A European Retrospective Series of 150 Patients

Background: The immunomodulatory agent pomalidomide is active in patients with relapsed/refractory multiple myeloma, including those who failed prior lenalidomide and bortezomib. Phase II clinical trials showed that pomalidomide is also effective in previously treated AL amyloidosis. The combination of pomalidomide and dexamethasone (PDex) showed a good hematologic response rate (more than partial response from 48 to 68%). Aim of this study is to report the efficacy of PDex in a retrospective real-world series of patients with AL amyloidosis from three European referral centers.Methods: The databases of the Pavia Amyloid Research and Treatment Center (Italy), the Heidelberg Amyloidosis Center (Germany) and the National Amyloidosis Center of London (United Kingdom) were searched for patients with a diagnosis of AL amyloidosis treated with pomalidomide and dexamethasone (PDex). The patients received 28-day cycles of pomalidomide (from day 1 to 21) and dexamethasone (once weekly). All patients gave written informed consent for their clinical data to be used for research purposes. Hematologic and organ responses were assessed according to the International Society of Amyloidosis criteria.Results: One hundred and fifty patients were included, 91 treated in Pavia, 30 in Heidelberg and 29 in London. Median age at the time of PDex initiation was 65 years (range: 34-85 years) and 92 (61%) patients were males. The heart was involved in 92 (61%) patients, the kidney in 87 (58%) and 91 (60%) of patients had two or more organs involved. The median NT-proBNP concentration at the time of PDex initiation was 1.670 ng/L (interquartile range, IQR: 527-4.963 ng/L) and 23 (15%) had NT-proBNP >8.500 ng/L. The estimated glomerular filtration rate was <30 mL/min per 1.73 m2 in 13 (9%) of patients and 16 (11%) were on dialysis at the time of PDex initiation. Median bone marrow plasma cells infiltrate at diagnosis was 18% (IQR: 10-30%) and this was ≥10% in 114 (76%) subjects. The median difference between involved and uninvolved concentration of free light chains (dFLC) was 150 mg/L (IQR: 76-397 mg/L). Median time from AL amyloidosis diagnosis to PDex treatment initiation was 11 months (IQR: 5-24 months). The median number of previous lines of therapy was 3 (range: 2-7) with 98 (65%) patients refractory to previous lines. One hundred and thirty-eight (92%) patients had previously received bortezomib, 120 (80%) lenalidomide and 114 (76%) melphalan and 39 (26%) underwent autologous stem cell transplant. The median number of PDex cycles performed was 3 (range: 1-30). Pomalidomide dosage was 4 mg in 56% of patients, 2 mg in 27%, 3 mg in 14% and 1 mg in 3% of subjects. Adverse events observed in 42 (28%) of subjects. With the limit of the retrospective setting, the more frequently reported were infections in 13 (31%), cardiac heart failure in 11 (26%), creatinine increase in 7 (16%) and cytopenia 4 (9%). The hematologic response rate at the end of cycle 3 was 36%, with 14 (16%) very good partial responses (VGPR) and 20 (20%) partial responses (PR). After cycle 6, the overall hematologic response rate was 56%, with 15 (26%) VGPR and 17 (30%) PR. A hematologic response to therapy was noted in 16 out of 39 subjects who were previously refractory to bortezomib, lenalidomide and melphalan. Median follow-up of living patients was 12 months (IQR: 7-27 months) and 64 (42%) patients died. Obtaining at least partial response at the end of cycle 3 was associated with a significant survival advantage (median survival not reached vs. 25 months, P=0.007, Figure). Cardiac responses were observed in 7 of 74 patients with measurable NT-proBNP (10%), but this can be underestimated due to the pomalidomide-related increase of NT-proBNP, and renal response in 13 of the 56 evaluable patients (23%).Conclusions: The combination of pomalidomide and dexamethasone is active, with a 56% of response rate at cycle 6, in heavily pretreated patients with AL amyloidosis. The hematologic response rate of this real word retrospective study compares with those reported in phase 2 clinical trials, improved over time and patients who obtained a quick reduction of the burden of free light chains, had a significant survival benefit. Pomalidomide is an effective rescue agent for relapsed refractory AL amyloidosis. [Display omitted] DisclosuresMerlini:Akcea: Consultancy; Janssen: Consultancy; Ionis: Consultancy; Millenium: Consultancy; Prothena: Consultancy; Pfizer: Consultancy. Wechalekar:Janssen: Honoraria. Palladini:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel support; Prothena: Honoraria.

Comparison of efficacy of antithymocyte globulin/antilymphocyte globulin combined with cyclosporin A and allogeneic hematopoietic stem cell transplantation in treatment of patients with aplastic anemia

Objective To analyze efficacy and safety of antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) combined with cyclosporine A and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of patients with aplastic anemia (AA). Methods From February 2014 to February 2017, a total of 68 AA patients who were admitted to Department of Hematology, Tangdu Hospital, Fourth Military Medical University were included in this study. According to different treatment strategies, they were divided into ATG/ALG combined with cyclosporin A group (n=27) and allo-HSCT group (n=41). Clinical data of patients in two groups were analyzed retrospectively, and efficacy and treatment-related adverse reactions of patients in two groups were compared. Age, neutrophil count (ANC), platelet count, reticulocytes absolute count, hemoglobin (Hb) value, and follow-up period of patients in two groups were analyzed by two-sample t test or Mann-Whitney U test. Ratio of patients with severe aplastic anemia (SAA), good hematologic response rate, hematologic response rate, treatment-related adverse reaction rate, early case fatality ratio, total case fatality ratio, ratio of patuients with recurrence or progression were analyzed by χ2 test or corrected χ2 test. Overall survival (OS) rates and progression free survival (PFS) rates of patients in two groups were analyzed by Kaplan-Meier method and Log-rank test. The procedure of this study is accordance with the requirement of the revised World Medical Association Declaration of Helsinki in 2013. Informed consent was obtained from all participants. Results ① Gender of male and female composition ratio was 0.7∶1 in ATG/ALG combined with cyclosporine A group, and was lower than that of 2.2∶1 in allo-HSCT group, and the difference was statistically significant (χ2=5.052, P=0.025). There were no significant differences in average age, average ANC, median platelet count, median reticulocytes absolute count, median Hb value, and ratio of patients with SAA between 2 groups (P>0.05). ② Good hematological response rate (58.5%, 24/41) and hematologic response rate (82.9%, 34/41) of patients in allo-HSCT group were higher than those in ATG/ALG combined with cyclosporine A group, which were 14.8% (4/27) and 51.9% (14/27), and the differences were statistically significant (χ2=12.850, P 0.05). ⑤ Median follow-up period was 9.0 months (5.0-19.0 months) in ATG/ALG combined with cyclosporin A group, and 12.0 months (7.0-22.5 months) in allo-HSCT group, and the differences were not statistically significant (P>0.05). Results of survival analysis showed that OS rates of patients in two groups were 96.3% and 86.3%, and PFS rates were 92.4% and 84.0%, and both differences were not statistically significant (P>0.05), respectively. Conclusions Clinical efficacy of ATG/ALG combined with cyclosporin A in the treatment of AA patients was not as good as allo-HSCT, but its safety was higher than that of allo-HSCT treatment strategy. Applying allo-HSCT for AA treatment, prevention and treatment of transplant-related adverse reactions should be highly addressed. Key words: Anemia, aplastic; Immunosuppression; Hematopoietic stem cell transplantation; Comparative effectiveness research; Retrospective studies

Evaluation of efficacy of immunosuppressive therapy plus recombinant human thrombopoietin for children with severe aplastic anemia

Objective: To evaluate the therapeutic efficacy and safety of immunosuppressive therapy (IST) combined with recombinant human thrombopoietin (rhTPO) for severe aplastic anemia (SAA) in pediatric patients. Method: A retrospective case-control study was conducted and the clinical data of 45 pediatric patients with de novo SAA admitted to the Anemia Diagnosis and Treatment Center of Chinese Academy of Medical Sciences & Blood Disease Hospital during the period from December 2009 to December 2014 were analyzed. Among them, 15 patients were treated with the regimen of IST together with rhTPO and 30 patients were given IST treatment only. The variation characteristics of the peripheral blood routine as well as the transfusion of blood products was dynamically observed, and the therapeutic efficacy was assessed respectively after 3, 6 and 12 months after the treatment. In the meantime, adverse effects related to rhTPO application were recorded. Thereafter, the statistics of the two groups were compared by non-parametric rank sum test. Result: Among 45 pediatric patients, there were 26 male and 19 female, and the median age was 11 years (6-14). The number of patients received good hematological response(complete remission (CR) plus good partial response (GPR)) in the combinatory group versus vs. the IST group was 6 vs. 3 patients (χ(2)=3.906, P=0.048) at the 3rd month, 7 vs. 7 patients (χ(2)=1.568, P=0.210) at the 6th month, and 13 vs. 14 patients (χ(2)=6.667, P=0.01) at the 12th month respectively. For those achieved good hematological response at the 3rd month, the amount of platelets transfusion and red blood cells transfusion of the combined group were both less than that of the IST group during the period from the 10th to the 12th weeks (platelets transfusion: 1.4 U vs. 2.9 U, t=-3.523, P=0.002; red blood cells transfusion: 0.8 U vs. 2.6 U, t=-2.392, P=0.026). No serious adverse effect related to rhTPO application was observed in the IST combined with rhTPO group. Conclusion: Application of rhTPO can improve the short-term therapeutic efficacy of IST for pediatric SAA, alleviate transfusion dependence, and has a good safety profile.

Long Term Outcomes in Monoclonal Gammopathy of Renal Significance (MGRS)

Abstract Background: MGRS is a heterogeneous group of pathologic renal conditions attributed to a clonal plasma cell disorder, without classical features of myeloma. However, there is a need to distinguish MGRS from MGUS and unrelated renal abnormality as the clonal protein in MGRS plays a direct role in kidney damage and requires treatment of the underlying clone. Outcomes in patients with diagnosis of cast nephropathy and renal amyloidosis have been previously reported. But long-term outcomes of MGRS patients with other renal histologies remain unclear. Also data on whether the level of tumour burden in the marrow and type of treatment for MGRS influence long-term outcomes is lacking. This analysis was conducted to study long term outcomes in renal biopsy proven (non cast nephropathy & AL Amyloid) MGRS patients. Aims: This multi-centre retrospective study was set up to analyse clinical outcomes in renal biopsy proven MGRS patients. Long-term haematological and renal outcomes were analysed. Correlation between tumour burden, type of treatment applied and level of response obtained was also analysed. Methods: Thirty-seven MGRS patients were retrospectively audited across 3 centres in the United Kingdom and 1 centre in the Republic of Ireland between 2004 and 2016. Patients were eligible for inclusion if they had a confirmed diagnosis of MGRS by renal biopsy. Patients with cast nephropathy and renal AL Amyloidosis were excluded. Renal survival was defined as the time until renal replacement therapy was required or failure to come off the renal replacement therapy commenced at diagnosis. Overall survival (OS) was calculated from the time of MGRS diagnosis until death from any cause. Results: Median age at diagnosis was 68 years and median follow-up was 33.5 months (range, 0.7-141.7 months). There were 29 male patients and 8 female patients. 20/25 patients had hypertension at the time of diagnosis (records unavailable for 12 patients). Majority of patients were kappa light chain restricted 85% vs 15% lambda LC restricted. Renal histology showed: 65% Light Chain Deposition Disease, 8% Mixed Heavy and Light Chain Deposition Disease, 1 % Proliferative Glomerulonephritis with monoclonal IgG, 11% Light Chain Tubulopathy, 6% Cryoglobulunemia, 3% Immunotactoid Glomerulonephritis. Renal survival for the whole cohort was 74% and overall survival was 84%. At the time of renal biopsy, 43% of patients had >10% plasma cells versus 46% of patients with 10% plasma cells versus 70 % in 10% plasma cells, not statistically significant (P = 0.14). Chemotherapy treatment was administered in 24 patients (65%) for their MGRS versus 13 patients (35%) who had no treatment for their PC clone. Of the 24 patients who had treatment: 20 had Bortezomib-based therapy (VEL), 6 had Thalidomide-based therapy, 4 had Lenalidomide and 4 had stem cell transplant. Patients who received VEL treatment for PC clone had a renal survival of 84 % versus 63% in patients who did not have VEL treatment (P = 0.45). OS in patients who received VEL was 95 % versus 72 % in patients who did not receive VEL treatment (P= 0.1). Good haematological response (≥VGPR) in 11/37 patients achieved and renal survival in these patients was significantly better at 90 % versus 61 % in patients who had Conclusion: We report long-term outcomes in a large cohort of MGRS patients: 74% renal survival and 84% overall survival at a median of 33 months follow up. For the first time, we show treatment for the PC clone shows better outcomes; with patients treated with VEL therapy significantly improved renal survival. Patients with higher tumour burden have a non-significant reduction in overall survival. Overall, the results of this study show better OS in MGRS patients when compared with outcomes previously reported in cast nephropathy and renal AL amyloid. Download : Download high-res image (110KB) Download : Download full-size image Disclosures Ramasamy: Celgene: Honoraria, Research Funding.

Long Term Outcomes in Monoclonal Gammopathy of Renal Significance (MGRS)

Background: MGRS is a heterogeneous group of pathologic renal conditions attributed to a clonal plasma cell disorder, without classical features of myeloma. However, there is a need to distinguish MGRS from MGUS and unrelated renal abnormality as the clonal protein in MGRS plays a direct role in kidney damage and requires treatment of the underlying clone. Outcomes in patients with diagnosis of cast nephropathy and renal amyloidosis have been previously reported. But long-term outcomes of MGRS patients with other renal histologies remain unclear. Also data on whether the level of tumour burden in the marrow and type of treatment for MGRS influence long-term outcomes is lacking. This analysis was conducted to study long term outcomes in renal biopsy proven (non cast nephropathy & AL Amyloid) MGRS patients.Aims: This multi-centre retrospective study was set up to analyse clinical outcomes in renal biopsy proven MGRS patients. Long-term haematological and renal outcomes were analysed. Correlation between tumour burden, type of treatment applied and level of response obtained was also analysed.Methods: Thirty-seven MGRS patients were retrospectively audited across 3 centres in the United Kingdom and 1 centre in the Republic of Ireland between 2004 and 2016. Patients were eligible for inclusion if they had a confirmed diagnosis of MGRS by renal biopsy. Patients with cast nephropathy and renal AL Amyloidosis were excluded. Renal survival was defined as the time until renal replacement therapy was required or failure to come off the renal replacement therapy commenced at diagnosis. Overall survival (OS) was calculated from the time of MGRS diagnosis until death from any cause.Results: Median age at diagnosis was 68 years and median follow-up was 33.5 months (range, 0.7-141.7 months). There were 29 male patients and 8 female patients. 20/25 patients had hypertension at the time of diagnosis (records unavailable for 12 patients). Majority of patients were kappa light chain restricted 85% vs 15% lambda LC restricted. Renal histology showed: 65% Light Chain Deposition Disease, 8% Mixed Heavy and Light Chain Deposition Disease, 1 % Proliferative Glomerulonephritis with monoclonal IgG, 11% Light Chain Tubulopathy, 6% Cryoglobulunemia, 3% Immunotactoid Glomerulonephritis. Renal survival for the whole cohort was 74% and overall survival was 84%. At the time of renal biopsy, 43% of patients had >10% plasma cells versus 46% of patients with <10% plasma cells. Renal survival was comparable between these cohorts with 74% renal survival in patients with >10% plasma cells versus 70 % in <10% plasma cells (P = 0.87). OS was better in patients with <10% plasma cells 94 % versus 75% in patients with >10% plasma cells, not statistically significant (P = 0.14).Chemotherapy treatment was administered in 24 patients (65%) for their MGRS versus 13 patients (35%) who had no treatment for their PC clone. Of the 24 patients who had treatment: 20 had Bortezomib-based therapy (VEL), 6 had Thalidomide-based therapy, 4 had Lenalidomide and 4 had stem cell transplant. Patients who received VEL treatment for PC clone had a renal survival of 84 % versus 63% in patients who did not have VEL treatment (P = 0.45). OS in patients who received VEL was 95 % versus 72 % in patients who did not receive VEL treatment (P= 0.1). Good haematological response (≥VGPR) in 11/37 patients achieved and renal survival in these patients was significantly better at 90 % versus 61 % in patients who had <VGPR (P = 0.05) Figure 1. ). OS was also improved at 91 % versus 82 % in patients who had <VGPR (P = 0.53). Two out of four patients were able to come off renal replacement therapy after being treated with Bortezomib and achieving a complete haematological response.Conclusion: We report long-term outcomes in a large cohort of MGRS patients: 74% renal survival and 84% overall survival at a median of 33 months follow up. For the first time, we show treatment for the PC clone shows better outcomes; with patients treated with VEL therapy significantly improved renal survival. Patients with higher tumour burden have a non-significant reduction in overall survival. Overall, the results of this study show better OS in MGRS patients when compared with outcomes previously reported in cast nephropathy and renal AL amyloid. [Display omitted] DisclosuresRamasamy:Celgene: Honoraria, Research Funding.

Nationwide Survey on the Use of Eltrombopag in Patients with Severe Aplastic Anemia: Report on Behalf of the French Reference Center for Aplastic Anemia

▪ BACKGROUNDFew therapeutic options are currently available for patients (pts) with severe aplastic anemia (SAA) refractory to antithymocyte globulin (ATG) plus ciclosporine (CsA) and not eligible for allogeneic stem cell transplantation. It has recently been reported that eltrombopag (ELT), a TPO receptor agonist, is efficient to improve tri-lineage blood counts in this setting. However, real-life use of this drug is still largely unknown. In pts with SAA refractory to ATG, physicians can accede to ELT in France through a compassionate use program. We took advantage of this program to assess the efficacy and safety of ELT in SAA pts. PATIENTS AND METHODSThe French National Reference Center for Aplastic Anemia conducted this study in pts who received ELT for the treatment of SAA. Latest guidelines were used to define disease severity, treatment indication, and response rates (Marsh et al, BJH 2014). The diagnosis of SAA was confirmed by marrow biopsy and Camita criteria for all pts. Pts were eligible if they received at least 2 months of ELT alone or in combination with other treatment in case of relapsed/refractory disease or front-line therapy for pts not eligible to the association of ATG and CsA. Pts were identified through a national e-mailing on behalf of the French reference center for SAA and the French Society of Hematology. All data presented here were collected at the reference date of June 26th, 2016. The study was conducted according to Helsinki's Declaration. RESULTSForty-six pts (male, 54%) who received ELT between July 2012 and February 2016 were identified in 17 French centers. Indications for ELT were relapsed/refractory SAA in 35 pts (76%) after 1 (49%), 2 (29%) or 3 (9%) courses of CsA+ATG. Eleven pts considered unfit for ATG also received the drug as first line therapy. The characteristics of the pts according to ELT indications are shown in Table 1. Median age at time of ELT initiation was 61 years [IQR 40 to 70]. 44 pts had idiopathic SAA including 17 (37%) with a detectable PNH clone (median size 7%). Two pts (4%) with dyskeratosis congenita also received ELT. ELT was introduced 17 months [8-50] after the initial diagnosis of SAA and with a median of 6 months [3-14] after the last course of immunosuppressive therapy. The maximal dose was 150 mg/day [100-150] for a median duration time of 6 months [4-12]. At last follow-up 22(48%) pts were still on treatment, 4(9%) pts stopped because of good hematological response, 1(2%) and 15(33%) after limited toxicity and failure to improve hematological status. Before treatment, median neutrophils count was 790/mm3 [500-1215] and pts received a median number of 4 red blood cells packs [2-4] and 3 platelets apheresis units [2-4] every month. Neutrophils counts were 765 [515-1475], 1100 [600-1800], 1200 [670-1915] and 1200/mm3 [757-2300] at 1, 3, 6 months and at last follow-up respectively. The rates of transfusion independence for both red cells and platelets were 7%, 33%, 46% and 46% at 1, 3, 6 months and at last follow-up. In pts achieving transfusion independence, hemoglobin and platelets level improved of 3 gr/dL [1.4, 4.5] and 42 G/L [11, 100], respectively. The rate of transfusion independence was not different among first line and refractory pts (p=0,5). We did not observe any response in the 2 patients with dyskeratosis congenita. No factor associated with hematological response to ELT was identified.Liver toxicity (cytolysis) occurred in 11 pts (1 grade 3 that required withdrawal of the treatment and 10 grade 1 who responded to dose reduction). 2 pts had a grade 2 intestinal toxicity which improved after dose reduction. Other side effects where related to SAA (28% infections, 13% hemorrhages). Bone marrow karyotype analysis after ELT was done in twelve pts (26%) (median time 14 months [5-22] after ELT start). In 10 pts the karyotype was normal, in one, trisomy 8 was identified (already seen at SAA diagnosis), and karyotype was a failure in 1 pt. CONCLUSIONWe report here the first real-life multicenter study about the use of ELT in SAA. In a particular severe pts population with no other treatment possibility, we confirm a 40% rate of hematological improvement with transfusion independence. Some of the pts who were not eligible to ATG plus CsA (comorbidities) also received ELT first line with similar response rates. Elderly pts unfit for ATG may thus benefit from this treatment which at the best should be given through prospective clinical trials. [Display omitted] DisclosuresAdes:Celgene, Takeda, Novartis, Astex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Terriou:Novartis: Consultancy; amgen: Consultancy. Peffault de Latour:Alexion: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Research Funding.

Low Dose Once Daily Oral Iron Treatment of Young Children with Nutritional Iron Deficiency Anemia

▪BackgroundIron deficiency anemia (IDA) is prevalent in young children whose diet includes prolonged breast feeding without iron supplementation and/or excessive cow milk consumption. Oral iron therapy is recommended to correct the anemia and reconstitute iron stores, but few data exist to guide clinical decision-making. The recommended dosing of elemental iron has been inconsistent in the literature, ranging from 2 to 6 mg/kg/day, given one to three times daily. To address the paucity of treatment data, the BESTIRON study (Clinicaltrials.gov NCT01904864) was initiated to compare two liquid oral iron agents (ferrous sulfate and NovaFerrum, an iron polysaccharide) using a once daily, low-dose regimen.MethodsThis study is a single center, double-blinded, randomized controlled superiority trial. Inclusion criteria include: age 9 months to 4 years with nutritional IDA by history and laboratory indices (Hgb <10 g/dL, MCV <70 fl, reticulocyte hemoglobin equivalent (Ret He) <25 pg, serum ferritin <15 ng/mL and/or TIBC >425 mg/dL). Exclusion criteria include: evidence of blood loss, malabsorption, other cause of anemia, prematurity (gestational age <30 weeks), major co-morbidity, adequate response to prior iron therapy, or previous receipt of intravenous iron.Upon enrollment, subjects are randomized 1:1 to either ferrous sulfate (15 mg/mL) or NovaFerrum (15 mg/mL) dosed at 3 mg/kg elemental iron once daily at bedtime. Follow-up visits occur at 4, 8, and 12 weeks following study initiation. Definition of complete response at study exit is: Hgb >11 g/dL, MCV >70 fl, Ret He >25 pg, serum ferritin >15 ng/mL, and TIBC <425 mg/dL. The primary outcome, rate of change in hemoglobin concentration over 12 weeks, cannot yet be determined as enrollment is ongoing. Here we present the overall combined hematologic response to this "minimalist" treatment regimen for subjects who have completed the study to date.ResultsFrom 9/1/2013 to 8/1/2015, 72 patients (target accrual 80) enrolled in the study. Sixty-two subjects (56% male) completed it and are included in the analysis. Median age was 19 months (range 11 - 41 months). Subjects were predominantly Caucasian/White (Latino) (61%). Median baseline and week 12 laboratory values are shown in the Table. Thirteen patients received a transfusion for severe symptomatic anemia (median Hgb 3.6 g/dL, range 2.2 - 5.3 g/dL) prior to study entry. Forty-six of the 62 subjects (74%) completed all 3 study follow-up visits. Eleven subjects were lost to follow-up or discontinued study participation. Five others were considered treatment failures at 8 weeks (hemoglobin increment <0.5 g/dL above baseline) and removed from the study. Of the 46 subjects who completed all study visits, 20 (43%) met the definition of complete resolution (38% of subjects with baseline hemoglobin <8 g/dL compared to 50% among those with baseline hemoglobin >8 g/dL) and received no further iron therapy.ConclusionThis analysis of children with nutritional IDA receiving a "patient-friendly" regimen of a single daily dose of 3 mg/kg elemental iron for 12 weeks demonstrates a good hematologic response and suggests that higher doses of iron therapy are not necessary to achieve resolution of anemia. While most subjects achieved a normal hemoglobin concentration, some required continued iron therapy to assure repletion of iron stores. Adverse effects ascribed to oral iron treatment may result in part from prescribing higher or more frequent iron doses, which may contribute to poor adherence and treatment failure.We acknowledge Gensavis Pharmaceuticals, LLC for their support of this investigator-initiated study.Table 1Median Laboratory Values at Baseline and Week 12Baseline (N=62) Median (Range)Week 12 (N=46) Median (Range)Hemoglobin concentration (g/dL)8.0 (4.4 - 10.6)11.9 (9.0 - 13.6)Mean cell volume (fl)59.9 (47.3 - 69.8)72.0 (54.7 - 81.9)Red cell distribution width (%) Baseline (n=56), Week 12 (n=46)21.1 (15.5 - 36.5)18.7 (12.5 - 26.4)Reticulocyte count (%) Baseline (n=60), Week 12 (n=45)1.4 (0.3 - 3.9)0.9 (0.4 - 1.8)Reticulocyte hemoglobin equivalent (pg) Baseline (n=41), Week 12 (n=40)17.2 (10.6 - 28.4)29.5 (15.9 - 34.3)Serum iron (mcg/dL)20 (9 - 349)51 (15 - 394)Serum ferritin (ng/mL)2.5 (0.5 - 49.2)11 (2.4 - 46)Total iron binding capacity (mg/dL)513 (236 - 636)394 (287 - 560) DisclosuresPowers:Gensavis Pharmaceuticals, LLC: Research Funding. Mccavit:Gensavis Pharmaceuticals, LLC: Research Funding; Pfizer: Speakers Bureau; Novartis: Speakers Bureau. Adix:Gensavis Pharmaceuticals, LLC: Research Funding. Buchanan:Gensavis Pharmaceuticals, LLC: Research Funding.

Clinical presentation and treatment responses in IgM-related AL amyloidosis

Amyloid light-chain (AL) amyloidosis is a multi-organ disease due to deposition of misfolded monoclonal immunoglobulin light chains. IgM AL amyloidosis is a rare variant, about 6% of AL amyloidosis cases, and more data are needed for treatment guidance. In IgM AL amyloidosis, the clonal cell of origin may be a plasma or lymphoplasmacytic cell, and treatments targeting each are employed. We describe presenting clinical and laboratory features of 95 patients with IgM AL amyloidosis treated at Boston University Amyloidosis Center from 1996 to 2012. The median diagnosis age was 66 years (range: 38–89) with 56% males. Organ involvement rates were: kidney (51%); heart (40%); lymph nodes (25%) and gastrointestinal tract (17%). Treatment responses were analyzed for 46 patients seen after 2003. Five treatment regimens were assigned by bone marrow pathology and patient-specific factors. Overall hematologic response rates and very good partial or complete hematologic response rates, respectively, were: high-dose melphalan/stem cell transplant (HDM/SCT) 100%;80%, Bortezomib 82%;27%, Rituximab 80%;27%, immunomodulatory agents (IMids) 75%;0%, and standard dose alkylating agents (Melphalan or cyclophosphamide) 63%;19%. Overall, 5-year survival rates were significantly higher in patients with a hematological response: 79.2 ± 8.5% versus 41 ± 14.9% in non-responders, which is more favorable than typically expected in AL amyloidosis.

The Evaluation and Comparison of the Efficacy and Safety of Ferrous Fumarate and Carbonyl Iron in Pregnancy Induced Iron Deficiency

Iron deficiency anemia is the commonest medical disorder to occur in pregnant women affecting around 80% of the pregnant females. The objective of the study was to compare the efficacy and tolerability of a marketed formulation containing ferrous fumarate and carbonyl iron in the treatment of pregnancy induced ID. This is a prospective study with a total of 300 pregnant females. And they were randomly assigned into two groups of 150 each and were allocated to receive formulation A, LIVOGEN- Z or formulation B, CARBOFER-Z. The enrolled patients were followed up after every 4 weeks during which their Efficacy evaluation was noted using hemoglobin value and Clinical safety was evaluated based upon the nature and severity of adverse effects. The response and tolerability to therapy was recorded on a 5-point rating scale using PGART and PGATT. The patients were also given counselling, interventional programs leaflets and thank you form during the study period. The rise in hemoglobin in the patients receiving a ferrous fumarate preparation was significantly better than that seen in the patients receiving a carbonyl iron preparation. The adverse reaction was also noted and the ferrous fumarate group showed a significantly better outcome with respect to response to therapy (p<0.0001) as well as tolerability (p=0.002). Ferrous fumarate is not only significantly superior in efficacy but is better tolerated than carbonyl iron. Ferrous fumarate is safe in pregnancy and gives a good hematological response with minimal adverse effects and can be used for the treatment of iron deficiency during pregnancy.

Long Term Follow-up of 107 Patients with Essential Thrombocythemia: Role of Cardiovascular Events

BACKGROUND Essential Thrombocythemia (ET) is a Philadelphia-negative chronic myeloproliferative neoplasm characterized by haemorrhagic and thrombotic complications. Haemorrhagic events and arterial and venous thrombosis, including microcirculation transient occlusions, are the major causes of morbidity in ET patients. The control of these events represents the goal of standard therapeutic approaches.MATERIALS AND METHODS We retrospectively analysed data about 107 ET patients who received diagnosis between January 1980 and June 2014. Median follow-up was 80 months,16 patients were lost during follow-up. The medium age at diagnosis was 60 years, with a prevalence of female (66 patients).We recorded adverse cardiovascular events at diagnosis and during follow-up, assessing whether cytoreductive ad antiplatelet therapy could reduce such events and improve quality of life. Finally, we evaluated the impact of additional cardiovascular risk factors.OBJECTIVES to observe incidence and kind of thrombotic events in patients affected by ET at diagnosis and during follow-up.RESULTS 30 patients (27.7%) had a history of thrombosis at diagnosis (8 transient cerebral ischemia, 7 myocardial infarction/unstable angina, among them 7 patients experienced a rethrombosis during follow-up. 16 patients (15%) developed a first thrombotic event, all patients were under cytoreductive treatment. 21 patients with a history of thrombosis had more than 60 years at diagnosis, 19 patients (63%) had at least one additional cardiovascular risk factor among arterial hypertension, dyslipidemia, diabetes, obesity, hyperuricemia and smoking. Median platelet count was 813000/mm3, leukocyte count greater was more than 10000/mm3 in half of patients. Evolution to acute leukemia/myelofibrosis occurred in 3 (2,7%) and 7 (6,5%) patients of total.CONCLUSIONS The occurrence of thrombotic events even in patients with good hematologic response of disease and during antiplatelet and cytoreductive therapy, indicates the presence of a residual risk of thrombosis. This risk is not yet fully clarified by retrospective studies published until now. Prospective studies will be useful to evaluate the role and the importance of comorbidity in these patients with long-prognosis, in order to optimize therapy, reduce cardiovascular events and improve quality of life DisclosuresNo relevant conflicts of interest to declare.

Clonal Evolution In Aplastic Anemia Is Driven By Chromosomal Instability Rather Than Mutations In Myeloid Malignancy Candidate Gene

▪The pathophysiology of human aplastic anemia (AA) is immune-mediated destruction of bone marrow stem and progenitor cells. Most patients respond to immunosuppressive therapies (IST), which markedly improved survival in this disease. However, a minority of patients undergoes transformation to malignant hematologic disease, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), usually accompanied by the cytogenetic abnormality monosomy 7. Clonal evolution in AA confers a poor prognosis in the clinic but is an opportunity to assess early events in oncogenesis in the setting of inflammation and tissue regeneration. We previously reported that low mean telomere length of leukocytes at the time of diagnosis of AA (Scheinberg et al., JAMA 2010) was associated with increased risk of progression to MDS. In the current study, we directly compared acquired mutations in candidate genes and chromosomal instability, as measured by telomere length, in a cohort of AA patients that had progressed to MDS.Thirteen AA patients who developed monosomy 7 were compared with 30 AA patients who had received similar treatments but did not progress to MDS. Leukocytes telomere content was measured by qPCR in samples obtained at different time points from the diagnosis of AA and chromosome-specific telomere length was assessed by single telomere length assay (STELA) for Xp, Yp, 12q, and 17p. In the AA patients who had evolved to MDS and AML, analysis of acquired mutations in myeloid-specific genes was performed by comparison with control “germline” DNA from purified CD3 lymphocytes by exome sequencing.Cells from AA patients with clonal evolution showed marked progressive telomere attrition, 419 bp/year during the period preceding development of monosomy 7. Telomere attrition was progressive from the time of diagnosis of AA. By STELA, accumulation of very short telomere fragments was apparent at 6 months after IST. In contrast, for the AA control group, patients whose disease was stable, telomere attrition was not accelerated in serial qPCR determinations, nor was there increased accumulation of short telomere fragments by STELA. A similar pattern of increased telomere attrition was reproduced in vitro by cultivation of bone marrow cells obtained six months after IST in all AA patients who developed MDS, while none of the AA control bone marrow cultured cells developed shorter telomeres.We examined bone marrow myeloid cells at the time of monosomy 7 for acquired mutations in 125 candidate genes reported to be recurrently mutated in AML and MDS. Exome sequencing was performed using Agilent SureSelect Target Enrichment System. The raw reads were mapped to UCSC Human Genome hg19 by BWA software with default setting. With an average of 111-fold coverage on selected exon regions, somatic mutations were identified between paired samples using SAMtools and Shimmer software for SNP detection. Acquired mutations in myeloid cells were found in two cases. One patient had a heterozygous mutation in DNMT3A (K829T) present since diagnosis of AA. The other patient also had a heterozygous mutation in DNMT3A (P904S) as well as mutations in DOTL1, ASXL1, SETBP1, and STAT3. All these mutations were identifiable after IST as neutrophils recovered. Despite the presence of multiple mutations, this patient had shown a good hematologic response to IST; evolution was manifest as recurrent pancytopenia and stable marrow myeloblasts at about 5% for over 2 years after first detection of monosomy 7. The remaining 11 patients, all of whom lacked candidate gene mutations, had progressive increase in bone marrow myeloblast numbers; the only other three survivors in this cohort had received hematopoietic stem cell transplant.In conclusion, telomere shortening rather than accumulation of point mutations in hematopoietic cells preceded aneuploidy and malignant transformation at an early stage of oncogenesis in this group of patients. These results from AA may be generalizable to other cancers arising in the setting of inflammation and tissue regeneration in other organs. Identification of critically short telomeres before the development of cytogenetic abnormalities may allow for improved management of patients at risk of clonal evolution, and pharmacologic strategies to increase telomerase activity might mitigate the risk of cancer in these settings Disclosures:No relevant conflicts of interest to declare.

A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis

AbstractTreatment outcomes of patients with cardiac stage III light chain (AL) amyloidosis remain poorly studied. Such cases have been excluded from most clinical studies due to perceived dismal prognosis. We report treatment outcomes of 346 patients with stage III AL amyloidosis from the United Kingdom, Italy, Germany, and Greece. Median overall survival (OS) was 7 months with OS at 3, 6, 12, and 24 months of 73%, 55%, 46%, and 29%, respectively; 42% died before first response evaluation. On an intention-to-treat basis, the overall hematologic response rate was 33%, including a complete response rate of 12%. OS rates at 12 and 24 months, respectively, for 201 response evaluable patients were 88% and 85% for complete responders, 74% and 53% for partial responders, and 39% and 22% for nonresponders. Forty-five percent of responders achieved an organ response. Amino-terminal fragment of brain-type natriuretic peptide (NT-proBNP) >8500 ng/L and systolic blood pressure (SBP) <100 mm Hg were the only factors that independently impacted OS and identified an especially poor prognosis subgroup of patients with a median OS of only 3 months. Outcome and organ function of stage III AL amyloidosis without very elevated NT-proBNP and low SBP is improved by a very good hematologic response to chemotherapy.

Pegylated Interferon-Alfa-2a Induces Complete Hematologic and Molecular Responses with Low Toxicity in Essential Thrombocythemia

AbstractAbstract 1743Essential thrombocythemia (ET) is a myeloproliferative Neoplasm (MPNs) marked by a risk of thrombotic and hemorrhagic complications, and by a long-term risk of evolution to myelofibrosis (MF), myelodys-plastic syndrome (MDS), and acute leukemia (AL). In addition to its role in pathophysiology and diagnosis, the constitutively active JAK2V617F mutation may be a prognostic marker because the percentage of circulating mutated alleles (%V617F) appears to be significantly higher in patients who develop vascular complications.Interferon alfa2a (pegasis) is a nonleukemogenic drug that can induce cytogenetic remissions or reversion from monoclonal to polyclonal patterns of hematopoiesis in some cases, this is the first study addressing the effects of pegasis in ET. Methods.Inclusion criteria were: Patients with ET diagnosed as per WHO classification 2008, age 18 to 45 years, and either no previous treatment or Hydroxyurea or anagralide for less than 1 years. ET diagnosis workup included ferritin, exclusion of secondary causes like infections and not meeting WHO criteria for PV, MDS and CML Pretreatment evaluation also included patient history, physical examination, complete blood count (CBC) and serum chemistries (UE), including liver and renal function studies, thyroid function tests (TFT), and molecular study for JAK2V617F mutation.Exclusion criteria included (significant hepatic and renal dysfunction, history of psychiatric disorder, in particular depression, autoimmune hepatitis, severe cardiac dysfunction, known hypersensitivity to IFN. The primary end point was hematologic response to pegasis at 12 months. Complete hematologic response (CR) as per ELN guidelines’ and Molecular response (MR) was defined as “complete” when JAK2V617F became undetectable with the technique used (ie, %V617F < 1%), “partial” when > 50% decrease of baseline %V617F was obtained, and “minor” when %V617F decrease was between 20% and 49%. Follow-up evaluations included adverse event (AE) assessment monthly for 3 months, then every third month until the 12th month with CBC, UE weekly during the first month and monthly thereafter. TFT, CBC, JAK2 mutation studies were taken every 6 months. After inclusion, HU was stopped 2 weeks before Pegasis initiation. Pegasis was started subcutaneously at 50 microgram weekly for 4 weeks then 135 microgramg/wk from week 5.Baseline characteristics of the patients are. Median age was 31.5 years (19–44) years), and 16 patients were males 24 were femals Five patients had a history of major thrombotic events. Treatment before inclusion included HU in 15 patients, and no treatment in the remaining 25 patients, all recently diagnosed.JAK2 mutation was found in all patientsAll the patients responded to Pegasis at the 12-month evaluation including 35 hematologic CRs (94.6%), and 5 PRs (5.4%). Cumulative incidences of hematologic CRs and PRs showing that 100% of responses were achieved within 12 months.No patient experienced signs or symptoms of thrombosis or hemorrhage during the whole study period. Median relative decrease of %V617F during the first year was 50% (33%-60%). %V617F decreased in all patients,After the first year, %V617F continued to decrease without evidence for a plateau, the proportion of mutant JAK2 being always similar or lower in the last sample compared with the previous one and none of the responding patient experienced an increase of %V617F during follow-up. Median %V617F was, 58% at 12 months, (P<.001). Complete or partial MR was observed in all patients.Hematologic response was achieved in all of the patients within 2 months and were sustained beyond the first year. Most common toxicities during the first month included musculoskeletal pain in 6 patients, skin toxicity in 4, and GI symptoms in 2, none of the toxicity exceeds WHO Grade 2. Conclusion.Pegylated Interferon alfa2a is effective and promising treatment for ET Reducing the vascular risk and preventing evolution to MF, MDS, and AL.with low toxicity profiles and good Hematological and Molecular response, Percentage of V617F appears to be a good tool to monitor minimal residual disease and to evaluate treatment efficacy however further studies are needed to confirm these results. Disclosures:Yassin:Qatar National Research Fund: Patents & Royalties, Research Funding. Off Label Use: use of pegelated interferon alfa 2a in treatment of patients with ET. Al-Dewik:Qatar National Research Fund: Patents & Royalties, Research Funding. Rafii El-Ayoubi:Qatar National Research Fund: Patents & Royalties, Research Funding.

Novel Strategy for MDS with Thalidomide, 5-Azacitidine and Stem Cell Transplantaion

Abstract 4960 Background:MDS ‘s clinical pathology is heterogeneous such as the intensity of cytopenia and the rate and the timing of AML evolution. The definite algorithm is difficult to be settled. We have several approved agents as the MDS therapy in Japan, Thalidomide, Lenalidomide and 5-Azacytidine (AZA) in addition to the conventional agents such as immunosuppressive agents (predonisolone and cyclospoline-A) and hematopoietic cytokines (G-CSF, Erythropoietin). We retrospectively analyze 36 MDS patients who were treated since 2004 in our hospital. The first current treatment was the conventional agents and transfusion that we call best supportive care (BSC). Since 2006 we could treat by thalidomide in addition to the conventional ones. Lenalidomide is limited to use only for 5q- MDS that is not included in 36 MDS. It was 2011 that we applied stem cell transplantation (SCT) for AML/MDS (AML evoluted from MDS). This conditioning regimen is low dose or non-myeloablative that is feasible to older individuals. The stem cell source of haploidentical donor or cord blood is immediately available at the time of urgent transplantation. The rate of GVHD of these HLA-mismatch transplantations is not so high as generally thought. The optimal SCT timing is very difficult and important. Patients and methods:In the baseline characteristics of consecutive 36 MDS patients, the median age was 70 (range 39 ∼ 90), F/M was 24/12. The 26 of them were treated by thalidomide daily 50mg∼100mg as the first line therapy, whose diagnosis was RCUD n=6, RARS n=2, RCMD n=9, RAEB-1 n=2 RAEB-2 n=4 and AML/MDS n=3. Using IPSS score, there were 9 patients with low, 6 int-1, 7 int-2 and 4 high (including 3 AML/MDS). 8 int-2 and 1 high had complex karyotype that is cytogenetically high risk. The other 8 patients received the best supportive care (BSC) by immunosuppressive agents, cytokines and transfusion. Two another patients were treated by AZA as the first line. Two of three AML/MDS had received stem cell transplantation (62 years male received haplo-mini SCT and 75 years female received cord blood SCT). Results:Thalidomide produced hematological improvement in 70% of lower IPSS (low and int-1) simultaneously with transfusion independency. On the contrary, int-2 improved only in 14%, high and AML/MDS in 0% (Fig 1). The improvement by thalidomide of RARS was 100% and RCMD was 67%. The p value about the improvement about WHO classification was 0. 182 because of the insufficiency of the number of patients. When the over all survival of thalidomide treated patients is compared with BSC patients, there was no statistically difference between them in lower risk MDS. In higher risk MDS, two int-2 patients who had failed with the single use of thalidomide achieved the hematological improvement by the combination of thalidomide and AZA. One of them was cytogenetically high risk. Their AZA cycles were 14 and 12. They were still receiving AZA. After the long-term follow-up, it will be clear that this combination makes statistical predominant in OS. This combination was completely ineffective against AML/MDS who received stem cell transplantation as second-line therapy. After the transplantation they received AZA maintenance that is expected to suppress minimal residual disease while monitoring WT1 expression. They are alive now for 1. 41 and 1. 01 years since they were diagnosed as AML/MDS. Conclusion:Thalidomide makes good hematological response of lower risk MDS and bring the free of transfusion that elevates and maintains the QOL of the patients. About the higher risk of MDS, thalidomide single therapy has no works but its' combination with AZA is very effective and bring not only the hematological improvement but also the possibility of longer overall survival. For AML/MDS, stem cell transplantation is the only potential curative treatment. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Leptomeningeal myelomatosis in previously treated high-risk kappa light chain multiple myeloma: case report and literature review

Leptomeningeal myelomatosis in previously treated high-risk kappa light chain multiple myeloma: case report and literature review Maro Ohanian1, James Alaly2, Stephen Samuel3, Christian Cable1, Kathleen Halka11Department of Hematology/Oncology, 2Department of Radiology, 3Department of Hematopathology, Scott and White Healthcare, The Texas A&amp;M Health Science Center College of Medicine, Temple, Texas, USAObjective: To describe leptomeningeal myelomatosis (LM) in previously treated high-risk kappa light chain multiple myeloma (MM) and to review the literature.Case report: A 71-year-old female with previously treated kappa light chain myeloma presented with right lumbosacral discomfort. Magnetic resonance imaging (MRI) of spine revealed multiple intradural masses involving the cauda equina, with mass effect on adjacent nerve roots. Brain MRI was unremarkable. Cerebrospinal fluid flow cytometry confirmed an abnormal population of plasma cells with kappa restriction; CD38, CD138, and CD56 were positive. She was originally diagnosed with kappa light chain myeloma 10 months earlier while hospitalized for anemia, thrombocytopenia, renal failure, and hypercalcemia. Bone marrow revealed plasma cell myeloma approaching 100% cellularity, with 92% plasma cells, atypical plasmacytoid cells with prominent nucleoli, and significant cytogenetic abnormalities: deleted 13, c-myc rearrangements, -X, +1. Treatments consisted of seven cycles of bortezomib with weekly dexamethasone. Her last dose had been 4 months earlier. After treatment, bone marrow demonstrated a complete remission with normal cytogenetics. Her clinical course had otherwise been indolent with a good hematologic response. After diagnosis of LM, therapy included focal external beam radiation to the cauda equina, weekly bortezomib and dexamethasone, intrathecal (IT) cytarabine liposomal every 2 weeks for five doses, and monthly IT cytarabine liposomal thereafter. The cerebrospinal fluid gradually cleared on serial lumbar punctures and follow-up MRI demonstrated near complete resolution of the intradural masses. Five months after diagnosis the patient is essentially asymptomatic.Conclusion: The incidence of central nervous system (CNS) involvement in MM patients is 1%. LM is associated with cytogenetic abnormalities and plasmablastic morphology. It can occur with a seemingly low tumor burden. Novel agents such as bortezomib allow for prolonged survival in high-risk patients; however, with inadequate CNS penetration, complications such as LM may be inevitable.Keywords: leptomeningeal myelomatosis, intrathecal, complete remission

Partial Splenectomy for Hereditary Spherocytosis

Partial Splenectomy for Hereditary Spherocytosis

A case of non-regenerative immune-mediated anemia treated by combination therapy of human immune globulin and mycophenolate mofetil in a dog

A 12-year-old female Shih Tzu dog was referred with diarrhea. Hematological examination indicated severe non-regenerative anemia. Bone marrow aspiration smears and core biopsy specimens revealed normal bone marrow. Based on those results, non-regenerative immune-mediated anemia was diagnosed. The dog was initially treated using prednisolone and cyclosporine. However, this treatment regimen did not prove effective. Nevertheless, the patient achieved a good hematological response after the administration of a combination therapy of human immune globulin and mycophenolate mofetil. Such a combination therapy may prove effective against non-regenerative immune-mediated anemia.