ALBERT

Description: Background: The trombopoietin receptor agonists (TRAs) romiplostim and eltrombopag are effective and safe in the treatment of chronic immune thrombocytopenia (ITP). However, when no response is achieved or when adverse events occur with one TRA the value of the sequential use of romiplostim and eltrombopag has not been clearly established. Here we have evaluated the efficacy and tolerance of using eltrombopag after romiplostim in ITP. Methods: Fifty-one primary ITP patients (aged 18 years or more) who had been sequentially treated first with romiplostim and then with eltrombopag in the Spanish Eltrombopag Registry were retrospectively evaluated. In accordance with the usual standards, complete response was defined as a platelet count of 100x109/L and a response as a platelet count of 30x109/L or a count of at least twice the initial (pre-treatment) value. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age of our cohort was 49 [range, 18–83] years. There were 32 women and 19 men. According to the standard definition, patients were allocated to newly diagnosed (n=2), persistent (n=5) and chronic (n=44) ITP groups. The median number of therapies prior to administration of eltrombopag was 4 [range, 2–9], including splenectomy (39%), rituximab (33%) and romiplostim (100%). The median duration of romiplostim use before switching to eltrombopag was 12 (IQR 5–21) months. The reasons for switching from the romiplostim to eltrombopag were: lack of efficacy of romiplostim (n=25), patient's preference (n=16), platelet-count fluctuation (n=6), and side-effects (n=4). The initial response rate to eltrombopag was 41/51 (80.5%), including 67% (n=34) of cases with complete remission. After a median follow-up of 13 months with eltrombopag, 39 patients maintained their response. When eltrombopag was used for patients who were refractory to the maximum romiplostim dose the initial response rate of eltrombopag was 25%. However, 83% of patients who relapsed after their initial response to romiplostim responded to eltrombopag. Sixteen romiplostim responders requested their physicians to switch them to eltrombopag because they preferred an oral drug. The efficacy was maintained after switching in all 16 patients. In the platelet-count fluctuation group, the initial response rate was also 100%. All 4 patients who were switched to eltrombopag because they experienced side-effects of romiplostim achieved complete remission with eltrombopag and their adverse events were resolved. 16 / 51 (33%) patients experienced one or more adverse event during treatment with eltrombopag. The frequency of grade 3–4 adverse events during treatment with eltrombopag was 9.8%. Conclusion: The use of eltrombopag after romiplostim for treating ITP is effective and safe. The reason for discontinuing romiplostim was associated with the response to eltrombopag. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Temsirolimus (TEM) is an mTOR inhibitor EMA approved for the treatment of patients (pts) with relapsed or refractory (R/R) mantle cell lymphoma (MCL). In a phase III trial TEM 175mg weekly for 3 weeks followed by 75mg weekly significantly improved PFS (4.8 months)  and objective response rate (22%) compared with investigator’s choice (1.8 months, 2% respectively). TEM has also been tested in combination with rituximab (RTX) in a phase II trial with encouraging efficacy results (ORR 59%, median time to progression 9.7 months) even in rituximab-refractory pts. However, few data have been reported on the use of TEM in everyday clinical practice. Methods Sixteen Spanish centres participated in this retrospective, observational and multicenter study: Inclusion criteria were as follows: pts ≥18 at the time of treatment, confirmed diagnosis of R/R MCL treated with TEM between January 1st 2010 and  December 31st 2012. Endpoints were overall response (ORR), partial response (PR) and complete response (CR) rate, toxicity as CTCAE v3.0 of NCI scale and overall survival (OS) and progression free survival (PFS).This study was approved by the Ethic Committee of all participant sites (PFI-TEM-2010-01). Results A total of 24 patients were included, 15 pts treated with TEM in monotherapy (TEM 175mg weekly for 3 weeks followed by 75mg weekly) and 9 in combination with RTX (TEM 25mg/week plus RTX 375mg/m2 per week during the first cycle and a single dose of RTX every other 28-day cycle). 22 were male and the median age was 71 (range 53 to 84). Regarding histology grade, 17 (74%) pts had classic, 1 (4.3%) blastoid and 5 (21.7%) unknown. According to simplified MIPI prognostic score, 6 (26.1%) pts had low risk, 10 (43.5%) intermediate risk and 7 (30.4%) high risk. Five pts had 10-40% of Ki 67 index, 3 had 〉40% and 14 pts unknown. Median number of prior therapies in TEM monotherapy cohort was 2 (range 1 to 7) and 4 (range 2 to 8) in the combination cohort. Median duration of therapy was 3.07 months in the TEM monotherapy cohort and 2.03 months in the combination cohort. The overall response rate (ORR) with TEM in monotherapy was 60% (40% CR and 20% PR) and 6.7% of disease stabilization. For those patients treated with TEM plus RTX, the ORR was 78% (56% CR and 22% PR) and 20% of disease stabilization. Median PFS for patients who reached CR in TEM monotherapy cohort was 12.73 months (95%CI, 1.28 to 24.19) and 10.93 months (95%CI, 1.40 to 20.46) in the combination cohort. Overall the median PFS for all patients was 7.30 months (95%CI, 2.36 to 12.24). Two pts underwent allogeneic stem cell transplantation after successful TEM monotherapy treatment. In terms of tolerability, 13 pts of 15 developed at least one adverse event (AE) in the TEM monotherapy cohort and 5 pts of 9 in the combination cohort. Most common AE (all grades) were thrombocitopenia (75%) in both cohorts, rash (37%), diarrhea (12%), hyperglucemia  (12%), hyperlipemia (8%), mucositis (8%) and neumonitis (8%). Most common G3/4 adverse event was thrombocytopenia (33%). Conclusions Although this is a small sample size, TEM efficacy in this study seems to be higher compared to previous Phase II and III trials with an acceptable toxicity profile in pts with MCL. The median PFS in the combination therapy cohort was surprisingly lower than in the monotherapy cohort which may be explained by differences in clinical features between both groups. Disclosures: Off Label Use: Use of temsirolimus in combination with rituximab. Morán:Pfizer: Employment. Viqueira:Pfizer: Employment.

Description: Background: Eltrombopag is an oral thrombopoietin receptor agonist (TPO-RA) drug approved in primary chronic ITP. Lack of clinical trials in secondary ITP avoids a clear demonstration of its potential in terms of safety and efficacy on secondary ITP. Aims: To evaluate the efficacy and safety of eltrombopag in secondary ITP patients in daily clinical practice in Spain. Methods: Ninety-eight secondary ITP patients (aged 18 years or more) from 30 Spanish centers, treated with eltrombopag and included in the Spanish Eltrombopag Registry were retrospectively evaluated. Our study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: Our case series included 98 patients we allocated to four categories: immune disorders (n=47), infections (n=23), lymphoproliferative disorders (n=20), and neoplasms (n=8). The median age of the cohort was 62 (IQR, 40-71) years with 38 men and 60 women. At diagnosis, 34 patients had a Charlson Comorbidity Index score of 2 or more. Median time from ITP diagnosis to eltrombopag initiation was 13 (IQR, 2-66) months. Median number of therapies against thrombocytopenia before eltrombopag was 2 (IQR, 1-3), including rituximab (24), splenectomy (18) and romiplostim (13). Median platelet count when treatment started was 15 x 109/L (IQR, 5-43 x 109/L). Meanwhile, 44 patients had bleeding symptoms. Concomitant therapy was administered to 55 ITP (corticoids in 33) (Table I). Whole cohort eltrombopag response rate was 59% of responses (R; platelet count ≥30 x109/L and at least 2-fold increase the baseline count and absence of bleeding) with 52% of complete responses (CR; platelet count 〉100 x 109/L). Regarding the disease associated to ITP we observed high response rates in immune disorders and infection groups (67% of R, 76 % of R, respectively). Nevertheless, in lymphoproliferative disorders and neoplastic groups efficacy rates were much lower (36 % of R, 37 % of R respectively). The proportion of patients achieving platelet response was quite similar regardless the other studied parameters: age, sex, concomitant treatment, bleeding and platelet count at start of eltrombopag treatment. 30 adverse events were reported with eltrombopag, being 18 of them grade 3-4. 14 deaths were observed but only two were caused by bleeding. The remaining causes of death were: 4 because of bacterial sepsis and another 4 due to progression of basal disease. 2 secondary neoplasms, 1 aspergillosis and one death due to a non-treated severe anemia were also reported (Table II). Conclusion: The use of eltrombopag for treating secondary ITP is effective and safe. To point out, its efficacy in lymphoproliferative disorders and in neoplasm-associated ITP is lower than in benign diseases. Certainly, more studies are needed to confirm usefulness of TPO-RAs in secondary ITP cases. Table 1. Patient characteristics Variable Total(n = 98) Type of disease, n Immune disorders  SLE 13  Evans Syndrome 8  Antiphospholipid Syndrome 6  Sjögren Syndrome 5  Rheumatoid Arthritis 3  Immunodeficiencies 3  Autoimmune Hepatitis 2  Primary Biliary Cirrhosis 2  Psoriatic arthritis 1  Evans Syndrome-Immunodeficiencies 1  Evans Syndrome-HCV 1  Graves-Basedow disease 1  Inflammatory Bowel disease 1 Lymphoproliferative disorders  Lymphoproliferative diseases 16  HCV-Lymphoma 3  HIV-Lymphoma 1 Infections  Hepatitis C Virus 16  HIV 5  HCV-HIV 2 Neoplasms  Myeloid Neoplasms 8 Age, years, median [Q1;Q3] 62[40;71] Men/Women n 38/60 Bleeding at start of eltrombopag treatment, n 44 Concomitant treatment, n 55  Corticoids 33  Immunoglobulins 6  Corticoids and Immunoglobulins 7 Table 2. Adverse events with Eltrombopag Variable n Total, n 30 Serious Adverse Events (Grade 3-4), n 18  Progression of basal disease 4  Severe Bacterial Infections 3  Deep venous thrombosis 3  Stroke 2  Medullary fibrosis 2  Severe Bleeding 1  Aspergillosis 1  Pulmonary Embolism 1  Secondary neoplasms 1  Acute Pancreatitis 1  Acute Myocardial Infarction 1 Deaths, n 14  Bacterial Infections 4  Progression of basal disease 4  Secondary neoplasms 2  Severe Bleeding 2  Aspergillosis 1   Severe Anemia due to negative of patient to transfusion 1 Disclosures Off Label Use: We describe the possibility of using eltrombopag, an oral thrombopoietin receptor analog, for secondary ITP patients..

Description: Background: Eltrombopag is a thrombopoietin receptor agonist approved for primary chronic ITP patients. Due to the non-existence of clinical trials using eltrombopag in persistent and newly diagnosed ITP, there are no clear data about its usefulness in this setting. Aims: To evaluate efficacy and safety of eltrombopag in persistent, newly diagnosed and chronic ITP in routine clinical practice in Spain. Methods: Two hundred and twenty adult ITP patients from thirty Spanish centers who had been treated with eltrombopag and included in the Spanish Eltrombopag Registry were retrospectively evaluated. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: Here we report efficacy and safety results of primary ITP Spanish Eltrombopag Registry cohort. According to the standard definition, patients were allocated to newly diagnosed (n=30), persistent (n=30) and chronic (n=160) ITP groups. Each group is described separately in Table I. There are no statistical significant differences regarding response and duration of response among ITP groups. There is a trend towards a greater efficacy in newly diagnosed ITP with 93.3% of responses (platelet count ≥30 x109/L and at least two-fold increase the baseline count and absence of bleeding) and 86.7% of complete responses (CR; platelet count 〉100 x 109/L). Persistent ITP achieved 83.3% of responses and 80.0% of CR. Similarly 79.4% of responses with 73.1 of CR were observed in chronic ITP. Response rates were similar in all groups regardless all other studied parameters. Another trend towards a longer response duration in persistent ITP was found, with a median of 424 (IQR, 288-664) days. Response durations were similar in chronic ITP (median, 370 days; IQR, 174-624) and in newly diagnosed ITP (median, 378 days; IQR, 154-485). In newly diagnosed ITP, eight adverse events (AEs) with only three grade 3-4 AEs were observed. We reported three deaths; Two of them were due to upper respiratory tract infections in previously diagnosed pulmonary patients. A cerebral hemorrhage was the only death directly related to thrombocytopenia. In persistent ITP, four grade 1-2 AEs and two grade 3-4 AEs (one stroke, one cerebral bleeding) were reported. The only observed death was secondary to the mentioned cerebral hemorrhage. Twenty-one grade 1-2 AEs, ten grade 3-4 AEs and eight deaths (only two caused by bleeding) occurred in chronic ITP. Conclusion: Use of eltrombopag for treating persistent and newly diagnosed ITP is effective and safe. However, more studies are needed to confirm usefulness of TPO-RAs in this setting. Table 1. Patient characteristics Variable Newly-Diagnosed ITP (n = 30) Persistent ITP(n=30) Chronic ITP (n=160) Age, years, median [Q1;Q3] 66[46;79] 66[47;76] 61[47;75] Men/Women n 12/18 15/15 47/113 Charlson comorbidity Index 〉 1, n (%) 7(25.9) 5(17.2) 25(16.7) Months with ITP, median [Q1;Q3] 1[1;2] 6[4;10] 79[30;193] Past ITP treatments, median [Q1;Q3] Rituximab, n (%) Splenectomy, n (%) Romiplostim, n (%) 2[1;3] 3(10.7) 2(7.1) 3(10.7) 2[1;3] 5(17.2) 4(13.8) 4(13.8) 3[2;4] 43(28.3) 47(30.7) 37(24.3) Platelet count at start of eltrombopag treatment, (x109/L), median [Q1;Q3]Bleeding at start of eltrombopag treatment , n (%)Concomitant treatment, n (%) Corticoids Immunoglobulins Corticoids and Immunoglobulins 15[7;29] 13(43.3) 10(33.3) 6(60) 0 2(20) 14[6;26] 10(33.3) 9(30) 7(77.8) 0 2(22.2) 22 [9;38] 50 (31.3) 46 (28.8) 27 (57.4) 10 (21.3) 8 (17) Disclosures Off Label Use: We describe the possibility of using eltrombopag, an oral thrombopoietin receptor analog, for persistent and newly diagnosed ITP patients..

Description: Background: Eltrombopag is effective and safe for treating chronic immune thrombocytopenia (ITP) patients who have not responded to previous therapy. Interestingly, some patients in whom hemostatic platelet counts are achieved with eltrombopag may sustain the platelet response when eltrombopag ceases to be administered. However, the frequency of sustained responses after discontinuing eltrombopag without additional therapy for ITP is largely unknown. Methods: A total of 260 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry were retrospectively evaluated. The study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age was 62 [range, 18–93] years. There were 165 women and 95 men. According to the standard definition, patients were allocated to newly diagnosed (n=29), persistent (n=36) and chronic (n=195) ITP groups. The median time from diagnosis to eltrombopag initiation was 24 [range, 1–480] months. The median number of previous therapies was 3 [range, 0–10], including splenectomy (22%), rituximab (23%) and romiplostim (19%). The initial response rate to eltrombopag was 231/260 (89%), including 77% (n=201) cases of complete remission (platelet count ≥100 x 109/L). The median duration of eltrombopag treatment was 6 [range, 1–54] months. Eltrombopag was discontinued in 80 out of 201 (39.8%) patients who achieved CR. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=33), platelet count 〉400x109/L (n=29), patient’s request (n=5), aspartate aminotransferase elevation (n=3), diarrhea (n=3), thrombosis (n=3) and other reasons (n=4). For analysis of discontinuation, patients with follow-up 〈 6 months (n=15), newly diagnosed ITP (n=11) or patients who received concomitant or previous (6 months before) treatments at the start of eltrombopag use (n=5) were excluded. Of the 49 evaluable patients, 22 (45%) had an immediate relapse after stopping eltrombopag. One patient with sustained response after stopping treatment relapsed at 10 months. A total of 26 patients (53%) showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 [range, 6–25] months. These patients were characterized by a median time since ITP diagnosis of 46.5±114.1 months, with 4/26 having ITP

Description: Type 1 Gaucher disease (GD1) is caused by the deficiency in the lysosomal enzyme glucocerebrosidase and causes the accumulation of glucocerebroside mainly in macrophages, inducing deterioration of the organs in which it is deposited.The new substrate inhibitor Eliglustat (ELI), approved by EMA in 2015 and available in Spain since January 2017, has proved to be an effective therapy that selectively inhibits the enzyme glucosylceramide synthase, decreasing the accumulation of substrate. It is indicated in GD1 extensive, intermediate or poor metabolizers of the cytochrome CYP2D6. The phase 2 and 3 clinical trials have demonstrated improvement and stabilization of the parameters in the naïve patients and in switched from enzyme replacement therapy. In this work we present the design of a prospective follow-up post-authorization study (GEE-ELI-2017-01) to asure the traceability of eliglustat therapy in Spanish GD1patients (TRAZELGA) is exposed. MethodsThe national multi-center study TRAZELGA, designed as a tool to uniformly evaluate the response to ELI therapy during one year, analyzing clinical parameters, biomarkers, changes in medullary infiltration quantified by MRI and DEXA, compliance and side effects. In addition, a quality of life sub-study is included as well as an exploratory study to analyze immune system activation markers (cytokine profile, ferritin, lipocalin, gamma globulins, oxidative stress markers). All the current recommendations previous ELI therapy have been reinforced, including cardiac, hepatic and renal function assessment and suitability according concomitant medications. An electronic tool has been designed to help physicians to easily registry and update the patient information. All the current rules for data protection were taken in account. Results: 40 GD1 patients have started oral treatment with Eliglustat. In this presentation we provide preliminary results of 32 patients whom fulfilled 6 months of follow-up (median age: 43.8 years (23-75), 47% males), genotype c.1226A〉G in homozygosity (29.4%), c.1226A〉G/c.1448T〉C (41.2% ), other double heterozygotes with c.1226A〉G (29.4%); metabolism of CYP2D6 (12% poor metabolizers, 64.5% intermediate and 33.5% extensive), no patient received the treatment in first line and its baseline characteristics (table1), are from patients stabilized with ERT (23 cases) or miglustat (9).Two splenectomized patients, 3 patients with palpable splenomegaly at the time of inclusion, 6 patients with multimorbidities and polymedications and 6 patients complained of fatigue as the main symptom before inclusion in the study. The median follow-up is 6 (6-14) months. Conclusions: The acceptance of the project in the medical community has been excellent with a good inclusion page. At the end of the one year follow-up period we will be available to analyze the influence of Eliglustat on biomarkers, markers of inflammation, bone mineral density also to provide information about adherence and adverse events in every day clinical practice. This work has been partially granted by FEETEG Disclosures No relevant conflicts of interest to declare.

Description: Introduction The inherited platelet disorders (IPD) are a heterogeneous group of rare diseases including quantitative and/or qualitative platelet defects. Classically, patients with IPD are first functionally tested to know the possible defect before sequencing a single or a few genes. Phenotipyc diagnostic of IPD often requires light transmission aggregometry, quantitative analysis of receptors by flow cytometry and fluorescence and electron microscopy. This diagnostic strategy is complex, poorly standardised and time consuming. In addition, the phenotype can seldom guide the singles candidates genes for conventional Sanger squencing. Therefore, many patients remain without a accurate diagnosis of their IPD. Next generation sequencing (NGS) enables the simultaneous analysis of large groups of candidate genes in IPD and may be useful for rapid genetic diagnosis. The aim of this study was to design and validate a NGS panel for IPD. Patients & Methods We describe a strategy for rapid genetic diagnosis of IPD with Illumina sequencing of 60 candidates genes previously associated with IPD (table1). The baits were designed to tile 400 kb of gDNA sequence corresponding to the exons and splice sites in all known transcripts of the candidate genes identified. The bait library was tested by enriching the candidate IPD genes from 50 ng DNA obtained and sequencing by Nextera Rapid Custom Enrichment system. Results were analysed by Variant Studio system and Sequencing Analysis Viewer. A total of 21 patients were studied. For the validation process, DNA samples of 9 unrelated patients with IPD and their mutation known were used: two patients with Glanzmann Thrombasthenia (ITGA2B, p.Ala989Thr, p.Val982Met and p.Glu538Stop; ITGB3, p.Leu222Pro and p.Tyr216Cys), one Hermansky-Pudlak Sd. (HPS1, p.Glu204 Stop), another with Bernard-Soulier Sd. (GPIX, p.Phe71Stop), a case of Congenital Amegakaryocytic Thrombocytopenia (MPL, p.Arg102Cys), and 2 patients with Chediak Higashi Sd. (LYST, p.Gly3725Arg and p.Cys258Arg). Once validated, the NGS panel was used for genetic diagnostic of 8 patients with suspected IPD. Results Eleven mutations, previously identified in another center by conventional sequencing, were detected by our panel NGS (100% success in the validation process). We then tested this strategy for patients with suspected of IPD without diagnosis: I. a 13 years old girl with agenesis of the corpus callosum, facial dysmorphia, renal agenesis and thrombocytopenia was diagnosed of Thrombocytopenia FLNA-related and Periventricular Nodular Heterotopia (PNHV)[mutation in the FLNA was detected (p.Thr1232Ile)]. II. A two years old patient with severe thrombocytopenia and recurrent infections was diagnosed of Wiskott-Aldrich Sd (WAS, p.Arg268Gly fs Stop40). III. A patient with deafness, macrothrombocytopenia, and Döhle bodies was diagnosed by MYH9 deletion (MYH9; p.Asp1925Thr fs Stop23). IV. Six members of a family (2 of them with symptoms of mucocutaneous bleeding, and macrothrombocytopenia), in which an insertion in NBAL2 (p.Gly1142Arg fs Stop49) gene was found. Therefore, Gray Platelet Sd was diagnosed. Moreover, one patient with aspirin-like syndrome showed a P2RY12 mutation (p.Val279Met). Finally, mother and son with mild Hemophilia A (F8; p.Gln2208Arg) were detected. Conclusions This NGS panel enables a rapid genetic diagnostic of IPD. The use of NGS-based strategy is a feasible tool for the diagnosis of IPD that could be added to the screening of these disorders. Five mutations have not previously been described in the literature. Table 1: Sixty candidates' genes previously associated with IPD: Inherited Platelet Disorders Genes = 60 Cytoskeletal Assembly and Structural Proteins GP1BA, GP1BB, GP5, A2M, GP9, VWF, ITGA2, ITGA2B, ITGB3, ABCA1, ANO6,FERMT3, ACTN1, MASTL Disorders of agonist platelet receptors P2RX1, P2RY1, P2RY12, TBXA2R, TBXAS1, ADRA2A, GP6, CD36 o GP4, DTNBP1 Disorders signal transduction GNAI3, GNAQ, GNAS, PLA2G7, PLCB2PTS, GGCX, DPAGT1, DHCR24 Disorders of platelet granules NBEAL2, GFI1B, PLAU, HPS1, HPS3, HPS4, HPS5, HPS6, LYST, MLPH, BLOC1S3, BLOC1S6, AP3B1, VIPAS39, VPS33B, RAB27A, MYO5A, USF1 Thrombocytopenias and syndromes WAS, MYH9, FLNA, FLI1, STIM1, HOXA11, ANKRD26, MPL, RBM8A RUNX1, GATA1 Disclosures No relevant conflicts of interest to declare.

Description: To achieve CR is an important goal in the treatment of most Hematological malignancies. In Multiple Myeloma (MM) although there is evidence demonstrating an association between CR and long-terms outcomes, some trials have failed to find such a correlation. In addition, it is not clear whether different responses categories, such as CR, near-CR (nCR) o Very Good Partial Response represent different prognostic subgroups or include an homogeneous group of patients with similar outcomes. Therefore, the confirmation of a possible association between different responses categories and long-term outcomes is required. We evaluated the prognostic influence on EFS and OS of pre- and post-transplant responses in newly diagnosed MM patients. Patients and Methods: We analyzed 632 patients who had been included in the prospective GEM2000 trial. All were uniformly treated with VBCMP/VBAD induction followed by high-dose therapy and autologous stem cell transplant and maintenance therapy with interpheron plus prednisone. Disease response was assessed post-induction and post-transplant using EBMT criteria, modified to include nCR. CR required at least 6 weeks of negative immunofixation (IFx) in serum and urine plus less than 5% plasma cells in BM. nCR was defined as electrophoresis-negative but IFx-positive. Partial response (PR) required greater than 50% reduction in M-protein and Stable disease (SD) included patients with minimal response and no change by EBMT criteria. Results: Probability of achieving CR post-transplant was significantly higher among patients achieving nCR versus PR (p= 0.004) versus SD or PD (p= 0.0003) pre-transplant. Patients achieving nCR or PR post-induction had similar outcomes, and both response categories showed a trend to have inferior EFS and OS as compared to patients in CR. After transplant, only borderline differences in EFS were detected upon comparing nCR with PR (nCR: median 40 months; PR median 34 months, p=0.07), by contrast the EFS of CR patients (median 61 months) was significantly longer than that of nCR or PR categories (both comparisons p

Description: One hundred ten patients with multiple myeloma (MM) failing to achieve at least near-complete remission (nCR) after a first autologous stem cell transplantation (ASCT) were scheduled to receive a second ASCT (85 patients) or a reduced-intensity-conditioning allograft (allo-RIC; 25 patients), depending on the human leukocyte antigen (HLA)–identical sibling donor availability. There was a higher increase in complete remission (CR) rate (40% vs 11%, P = .001) and a trend toward a longer progression-free survival (PFS; median, 31 months vs not reached, P = .08) in favor of allo-RIC. In contrast, it was associated with a trend toward a higher transplantation-related mortality (16% vs 5%, P = .07), a 66% chance of chronic graft-versus-host disease and no statistical difference in event-free survival and overall survival. Although the PFS plateau observed with allo-RIC is very encouraging, this procedure is associated with high morbidity and mortality, and therefore it should still be considered investigational and restricted to well-designed prospective clinical trials. This trial is registered at ClinicalTrials.gov ID number NCT00560053

Description: Waldenström’s Macroglobulinemia (WM) patients are classified in two main subtypes: symptomatic and asymptomatic. In this study we have analyzed the clinical, biological, immunophenotypical and cytogenetic characteristics of 85 WM, including 59 symptomatic WM (SWM) and 26 indolent WM (IWM). Clinical behaviour of SWM, as expected, was clearly different from that of IWM. Characteristics of the first group included: poor performance status (30%), hyperviscosity syndrome (19%), B symptoms (29%) and neurological symptoms (25%). None of these features were present in IWM. Regarding biology, most SWM patients (75%) had hemoglobin levels below 12 g/dl while only 8% of IWM showed this feature (p