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  • American Society of Hematology  (8)
  • 2010-2014  (8)
  • 1
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    Online Resource
    Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 24 ( 2012-12-06), p. 4873-4881
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 24 ( 2012-12-06), p. 4873-4881
    Abstract: We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P 〈 5 × 10−8) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1 (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 × 10−10); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 × 10−8); and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 × 10−8). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at ARNTL (P 〈 .05). Functional studies identified MUC3 as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated with the expression of MUC3 were robustly associated with circulating levels of PAI-1.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2012-06-436188
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
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  • 2
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    Integrin αIIbβ3-Mediated Outside-in Signaling: Brake or Amplifier of Platelet Activation?
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 4161-4161
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4161-4161
    Abstract: αIIbβ3 is the most prominent integrin in platelets, and binding to its ligands, in addition to supporting platelet aggregation, also results in the transmission of so-called αIIbβ3-mediated outside-in signals into the cell interior. While it is well accepted that integrin-mediated outside-in signaling functions as an amplifier of platelet activation, accumulating evidence suggests that outside-in signaling can, under certain conditions, function as an inhibitor of platelet activation. In this regard, previous studies have shown that ligand binding and platelet aggregation activate the inositol phosphatase SHIP-1, a negative regulator of the PI3K/Akt signaling pathway, to shift activated integrins back to their resting state, leading to dissociation of platelet aggregates. Because the PI3K/Akt signaling pathway is also involved in platelet granule secretion, we examined whether ligand binding to αIIbβ3 might transmit inhibitory signals that suppress platelet granule secretion. Interestingly, we found that antagonists of integrin αIIbβ3 promote both platelet dense- and α-granule secretion stimulated by low dose agonists. In support of this finding, both mouse and human platelets lacking expression of αIIbβ3 exhibited increased granule secretion compared to their wild-type counterparts. Conversely, Mn++-induced fibrinogen binding to αIIbβ3 inhibited low-dose agonist-induced platelet granule secretion. Biochemical analysis revealed that blocking ligand binding to, or absence of, αIIbβ3, enhanced agonist-induced Akt phosphorylation, while at the same time prevented the activation of the inhibitory enzyme, SHIP-1. To further investigate the role of SHIP-1 in inhibitory signaling, we examined the effect on platelet secretion of 3AC, a specific inhibitor of SHIP-1. We found that 3AC not only restores ADP-induced platelet granule secretion, but also increases CRP- or TRAP-induced platelet granule secretion. Taken together, these data demonstrate that integrin αIIbβ3-mediated outside-in signaling act as a brake to restrict unnecessary platelet activation that occurs in the presence of low-dose agonist stimulation. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.4161.4161
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
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    Online Resource
    Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML
    American Society of Hematology ; 2012
    In:  Blood Vol. 119, No. 10 ( 2012-03-08), p. 2314-2324
    Details
    In: Blood, American Society of Hematology, Vol. 119, No. 10 ( 2012-03-08), p. 2314-2324
    Abstract: Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P 〈 .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2011-10-386235
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
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    Identification of key regulatory pathways of myeloid differentiation using an mESC-based karyotypically normal cell model
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 24 ( 2012-12-06), p. 4712-4719
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 24 ( 2012-12-06), p. 4712-4719
    Abstract: Understanding the process of myeloid differentiation offers important insights into both normal and abnormal developmental processes but is limited by the dearth of experimental models. Here we show that myeloid progenitors can be derived from embryonic stem cells, immortalized, and applied to the study of the mechanisms underlying myeloid differentiation. The embryonic stem cell–derived myeloid progenitors, when immortalized with estrogen-regulated Hoxb8 protein, demonstrate normal karyotyping, are genetically tractable, and can be differentiated into functional neutrophils. Using this model, we identified mammalian target of rapamycin complex 1 as a critical regulator of myeloid differentiation. Together, our studies led to a convenient, karyotypically normal, and genetically manipulatable cellular system, which can be used to shed new light on the mechanisms for myeloid differentiation.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2012-03-414979
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
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    A Prospective Multicenter Study Of The Bruton’s Tyrosine Kinase Inhibitor Ibrutinib In Patients With Relapsed Or Refractory Waldenstrom’s Macroglobulinemia
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 251-251
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 251-251
    Abstract: Whole genome sequencing has revealed highly prevalent somatic mutations in WM (Hunter et al, ICML-12, 2013). MYD88 L265P is present in 〉 90% of patients with Waldenstrom’s Macroglobulinemia (WM), and supports malignant growth via signaling involving Bruton’s Tyrosine Kinase (BTK). Ibrutinib inhibits BTK, and in vitro induces apoptosis of WM cells bearing MYD88 L265P (Yang et al, Blood 2013). WHIM-like mutations in CXCR4 are present in 1/3 of patients with WM, and their expression induces BTK activity and confers decreased sensitivity to ibrutinib mediated growth suppression in WM cells (Cao et al, ASH 2013, submitted). We therefore evaluated the efficacy and tolerability of ibrutinib in relapsed or refractory WM, and examined the impact of MYD88 L265P and WHIM-like CXCR4 mutations on ibrutinib response given our laboratory findings. Patients and Methods Symptomatic WM patients who received at least 1 prior treatment were enrolled on this prospective clinical trial. Intended therapy consisted of 420 mg of oral ibrutinib daily for 2 years or until progression, or unacceptable toxicity. Sanger sequencing was used to determine MYD88 and CXCR4 mutations in sorted bone marrow lymphoplasmacytic cells (BM LPC) from 43 and 40 patients, respectively. Forty of 43 (93%) and 10/40 (25%) patients had MYD88 L265P and WHIM-like CXCR4 mutations, respectively. Results 63 patients including 17 with refractory disease were enrolled; all 63 are evaluable for response and toxicity. Median baseline characteristics: Age 63 (range 44-86) ; Prior therapies 2 (range 1-6); Hematocrit 30.8% (range 24.5-41.5); Hemoglobin 10.5 g/dL (8.2-13.8 g/dL); serum IgM 3,610 mg/dL (range 735-8390 mg/dL); serum M-protein 2.14 g/dL (range 0.5-5.4 g/dL); B2M 3.9 mg/L (range 1.3-14.2 mg/L); BM disease involvement 65% (range 3.2-95%). At best response, median serum IgM levels and M-protein declined to 1,340 mg/dL and 0.84 g/dL, respectively (p 〈 0.00001). Median hematocrit and hemoglobin rose to 38.1% and 12.6 g/dL, respectively (p 〈 0.00001). Post-treatment bone marrow assessment at 6 months is available for 34 patients at this time, and showed a reduction from 70% to 45% in WM disease involvement for these patients (p=0.0006). With a median follow-up of 6 (range 2-15 cycles), the best overall response rate i.e. minor response (MR) or better using consensus criteria adapted from the 3rd International Workshop on WM is 81% (4 VGPR; 32 PR, 15 MR), with a major response rate (PR or better) of 57.1% and a median time to response of 4 weeks. 11 patients have stable disease, and 1 patient was a non-responder. Independent disease and response assessments are planned. Grade 〉 2 treatment related toxicities include thrombocytopenia (n=9; 14.3%); neutropenia (n=12; 19.1%); stomatitis (n=1; 1.6%); atrial fibrillation (n=1; 1.6%); diarrhea (n=1; 1.6%); herpes zoster (n=1; 1.6%); hematoma (n=1; 1.6%); hypertension (n=1; 1.6%) and epistaxis (n=1; 1.6%). 59 patients remain on study with 7 on reduced doses of ibrutinib. Reasons for discontinuation include non-response (n=1) in a patient with wild type MYD88; MDS/RAEB (n=1) in a heavily pre-treated patient who attained PR, but who had 5q deletions pre-dating protocol therapy; thrombocytopenia (n=1) in a patient with splenic entrapment; and patient decision (n=1). In patients who underwent tumor sequencing, attainment of major responses was impacted by mutations in CXCR4, but not MYD88 L265P. The major response rate was 77% for patients with wild-type CXCR4 vs. 30% in those with WHIM-like CXCR4 mutations (p=0.018). Decreases in serum IgM (p=0.047) and IgM M-spike (p=0.012), as well as improvements in hemoglobin (p=0.058) were greater in patients with wild-type CXCR4. Patients with wild-type CXCR4 also had increased peripheral lymphocytosis following ibrutinib treatment versus those with WHIM-like CXCR4 mutations (p=0.001). Conclusions Ibrutinib is highly active, and well-tolerated in patients with relapsed or refractory WM. Rapid reductions in serum IgM and improved hematocrit occur in most patients receiving ibrutinib. The presence of WHIM-like CXCR4 mutations impacts responses and peripheral lymphocytosis in WM patients undergoing ibrutinib treatment. Disclosures: Off Label Use: Ibrutinib is a Bruton's Tyrosine Kinase (BTK)inhibitor that, in vitro, induces apoptosis of Waldenstrom's macroglobulinemia cells bearing somatic mutations of MYD88 L265P.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.251.251
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 6
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    Whole Genome Sequencing Identifies Recurring Somatic Mutations in the C-Terminal Domain of CXCR4, Including a Gain of Function Mutation in Waldenstrom's Macroglobinemia.
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 2715-2715
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2715-2715
    Abstract: Abstract 2715 Introduction: Waldenstrom's Macroglobulinemia (WM) is an indolent non-Hodgkin's lymphoma characterized by the accumulation of IgM secreting lymphoplasmacytic cells (LPC) in the bone marrow. Using paired normal/WM lymphoplasmacytic cell paired tissues and whole genome sequencing (WGS), we identified somatic mutations in the CXC chemokine receptor 4 (CXCR4) gene which were present in 16/55 (29%) WM patients. CXCR4 is a G-protein-coupled receptor, together with its ligand, the stromal cell- derived factor-1(CXCL12/SDF-1), play an important role in leukocyte and lymphocyte hematopoiesis and trafficking. Upon SDF-1 stimulation, CXCR4 is phosphorylated and interacts with b-arrestins, which then trigger extracellular signal-regulated kinase (ERK) MAPKs and chemotaxis. CXCR4 signaling is then terminated through receptor internalization which is mediated via phosphorylation of its C-terminal tail. Methods: Sanger sequencing was used to validate WGS results. To clarify the functional significance of one of the most common somatic mutation identified (C1013G), cloning by PCR was undertaken from CD19+ bone marrow cells from a WM patient with the C1013G CXCR4 (C1013G-CXCR4) mutation. Wild type (WT) and C1013G-CXCR4 cDNAs were subcloned into plenti-IRES-GFP vector, and transduced using an optimized lentiviral based strategy for WM cells into BCWM.1 WM cells. Five days after transduction, GFP positive cells were sorted and used for functional studies. Surface expression of CXCR4 was determined by FACS using PE-conjugated anti-CXCR4 monoclonal antibody 12G5. CXCR4 internalization was studied by comparing CXCR4 surface expression before and after SDF-1 stimulation. Chemotaxis studies were performed using a transwell assay. The expression of phosphorylated ERK1/2 and total ERK2 was determined by western blot. Results: Validated somatic mutations in CXCR4 were all present in the C-terminal domain and included premature stop codons (C1013A; C1013G), and frameshift mutations. Importantly, the identified mutations are similar to those reported in the germline of patients with WHIM (Warts, Hypogammaglobulinemia, Infections and Myelokathexis) Syndrome, a dominant autosomal genetic disorder caused by tonic CXCR4 activation by impairment of CXCR4 internalization, and stimulation of G-protein-dependent responses, and chemotaxis. Consistent with such a role, SDF-1a stimulation showed decreased internalization of CXCR4 in C1013G-CXCR4 versus WT CXCR4 transduced BCWM.1 WM cells. SDF-1a stimulated ERK1/2 phosphorylation was also more robust C1013G-CXCR4 versus WT CXCR4 expressing cells. Lastly, C1013G-CXCR4 transduced cells displayed stronger migratory response toward SDF-1a versus WT CXCR4 expressing BCWM.1 cells. Conclusions: C-terminal domain somatic mutations are common in WM and overlap with germline mutation identified in WHIM syndrome. Moreover, the most common of these mutations (C1013G) confers gain of function including decreased CXCR4 internalization, more robust ERK ½ phosphorylation, and chemotaxis. The findings provide new insights into the pathogenesis of WM, and a framework for the study of CXCR4 inhibitors for WM therapy. Disclosures: Treon: Onyx: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.2715.2715
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 7
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    Syngeneic and Allogeneic Hematopoietic Stem Cell Transplantation In Mice With Myelodysplastic Syndrome
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 1515-1515
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1515-1515
    Abstract: The myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies characterized by dysplasia, ineffective hematopoiesis and a propensity for progression to acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative therapy for the majority of patients. However, overall survival (OS) of patients with MDS following allogeneic HSCT is only about 40%, due to both relapse and non-relapse mortality (NRM) including graft versus host disease (GVHD). Available data suggests that long-term survival following HSCT for MDS is due both to myeloablative therapy and a graft versus tumor (GVT) effect. Mice that express a NUP98-HOXD13 (NHD13) transgene develop MDS with virtually 100% penetrance. In order to develop a pre-clinical model for the study of MDS HSCT, we transplanted NHD13 mice, which are bred on a C57 Bl6 background, with bone marrow harvested from syngeneic C57Bl6 donors. Sub lethally irradiated (650 rad) recipient NHD13 mice transplanted with syngeneic donor cells relapsed early, with no therapeutic benefit in terms of hematologic parameters in peripheral blood or survival. However, lethally irradiated (1000 rad) recipient mice that were transplanted with syngeneic donor bone marrow (BM) showed complete normalization of peripheral blood counts significantly enhanced survival (median survival of 15 months) compared with non-transplanted NHD13 mice (median survival 10 months). Although there were no detectable MDS cells for up to 38 weeks post-transplant, all mice eventually relapsed and died. In order to determine if a GVT effect could enhance survival, we performed 3 types of allogeneic HSCT with donor BM that was mismatched at minor histocompatibility antigen loci (C3H.SW x C57Bl6 donors); donor BM only, donor BM with donor splenocytes (6 x 10E06 CD3+ T cells), and donor BM with donor regulatory T cells (Treg). None of these forms of allogeneic HSCT let to enhanced survival compared to that achieved with syngeneic HSCT. The early relapse rate for allogeneic HSCT with donor BM only was decreased compared to the syngeneic HSCT group (8.3% vs 28% at post-transplantation week 6 and 17% vs 43% at post-transplantation week 16); however, the relapse rate at 38 weeks was similar between the two groups (83.3% vs 85.7%). Adding donor splenocytes, containing reactive T-cells, dramatically decreased the relapse rate, such that the relapse rate was only 20% at post-transplantation week 38, suggesting a GVT effect. This GVT effect was accompanied by a severe GVH effect, and OS was not different between the allogeneic BM + splenocyte and the syngeneic HSCT groups. In an attempt to induce a GVT effect without a severe GVHD, we transplanted allogeneic Treg cells along with allogeneic BM, however, survival and relapse rates were similar to those with allogeneic BM only. Taken together, these findings suggest that a lethal dose of ionizing radiation (1000 rads) is insufficient to eradicate the MDS initiating cell, and that transplantation of donor CD3+ splenocytes leads to decreased relapse rates, but at the cost of severe GVHD. We suggest that the NHD13 mice are a feasible pre-clinical model for the study of HSCT for MDS. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.1515.1515
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 8
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    Carfilzomib, Rituximab and Dexamethasone (CaRD) Is Highly Active and Offers a Neuropathy Sparing Approach For Proteasome-Inhibitor Based Therapy In Waldenstrom’s Macroglobulinemia
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 757-757
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 757-757
    Abstract: Bortezomib is active in Waldenstrom’s macroglobulinemia (WM) but associated with considerable peripheral neuropathy (PN). The proteasome inhibitor carfilzomib (CFZ) is approved in the USA for relapsed/refractory myeloma. Herein, we examined the efficacy and safety of carfilzomib, rituximab, and dexamethasone (CaRD) in 31 proteasome inhibitor and rituximab naive WM patients with symptomatic disease. Median baseline characteristics: age 61, prior therapies 0 (range 0-1), hematocrit 32.3%, hemoglobin 10.7 g/dL, serum IgM 3375 mg/dL, serum M-protein 2.185 g/dL, B2M 3.6 mg/L, and bone marrow disease involvement 60%. Therapy consisted of IV CFZ 20 mg/m2 (cycle 1) then 36 mg/m2 (cycles 2 and beyond) with IV dexamethasone (dex) 20 mg given on days 1,2,8,9 and rituximab 375 mg/m2 on days 2,9 of each 21-day cycle. Treatment consisted of six induction cycles, then maintenance beginning 8 weeks after induction (given every 8 weeks for eight cycles; consisted of CFZ 36 mg/m2, and IV dex 20 mg on days 1,2 and rituximab 375 mg/m2 on day 2). Patients with IgM level 〉 4000 mg/dL underwent plasmapheresis and/or had rituximab held until IgM 〈 4000 mg/dL to prevent symptomatic IgM flare. Patients received oral acyclovir (400 mg twice daily) and famotidine (20 mg twice daily) as concomitant medications. For all 31 patients, median serum IgM levels and M-protein declined to 749 mg/dL and 0.7 g/dL, respectively (p 〈 0.00001). Median hematocrit and hemoglobin rose to 40.9% and 13.7 g/dL, respectively (p 〈 0.00001). A total of 30 patients concluded induction therapy with bone marrow tumor involvement reduced to a median of 7.5% (p=0.0003). The best overall response rate using criteria adapted from the 3rd International Workshop on WM was 81% (1 CR, 8 VGPR, 12 PR, 4 Minor Responses). With a median follow-up of 8 cycles, 22 patients remain on study, including 20 currently on maintenance therapy. Median time to response (for minor responders or better) was 2.1 months. Grade 〉 2 treatment related toxicities included asymptomatic elevation in lipase (12.9%), dex-related hyperglycemia (6.45%), reversible neutropenia (9.67%), and cardiomyopathy (3.22%). There were no grade 2 or greater PN events. Treatment discontinuation occurred for non-response (n=8), cardiomyopathy in a patient with multiple cardiac risk factors (n=1), and progressive disease (n=1). CaRD is highly active and offers a neuropathy sparing approach for proteasome-inhibitor based therapy in WM. Disclosures: Off Label Use: Carfilzomib is a novel proteasome inhibitor, which offers a neuropathic sparing approach on waldenstrom macroglobulinemia disease when used in a combination therapy with rituximab and dexamethasome.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.757.757
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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