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  • American Society of Hematology  (116)
  • 1
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    Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia
    American Society of Hematology ; 2013
    In:  Blood Vol. 121, No. 15 ( 2013-04-11), p. 3005-3015
    Details
    In: Blood, American Society of Hematology, Vol. 121, No. 15 ( 2013-04-11), p. 3005-3015
    Abstract: CMML is a heterogeneous disorder with a highly variable prognosis that clearly requires a specific and widely accepted prognostic scoring system. CPSS is a powerful prognostic score that defines 4 risk groups for survival and AML evolution, developed and validated in the largest CMML series to date.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2012-08-452938
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
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  • 2
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    A Characteristic Cytokine/Chemokine Milieu Is Present in the Bone Marrow Environment of Multiple Myeloma Patients Before and After Allogeneic Stem Cell Transplantation.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 2795-2795
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2795-2795
    Abstract: Abstract 2795 Poster Board II-771 Background: The interaction of Multiple Myeloma (MM) with its bone marrow (BM) microenvironment is important for the homing, survival, and proliferation of the malignant plasma cells. In this study, we aimed at answering the question which cytokines, chemokines, and growth factors are typically found in the BM of untreated MM patients as well as in MM patients after allogeneic stem cell transplantation (alloSCT) and might be involved in the pathogenesis of MM and/or Graft-versus-Host Disease (GvHD). Design and Methods: Applying Multiplex Bead-based Luminex technology and Quantikine ELISAs, we determined the concentrations of 34 cytokines/chemokines in the supernatants of 10 myeloma cell lines as well as in the plasma derived from BM and peripheral blood (PB) samples of 10 newly diagnosed MM patients, 20 MM patients post alloSCT, and 20 healthy donors. Results: Besides factors known to be secreted by myeloma cell lines (IL-1RA, IL-8, MCP-1, MIP-1α, MIP1β, MIP-3α) we observed secretion of other cytokines/chemokines such as EGF, HGF, IL2R, IL-12p40/p70, IL-22, IP-10, MIG, and RANTES. In the BM plasma samples of MM patients, we detected elevated levels of HGF, IL-2R, IL-16, EGF, IL-1RA, IP-10, MCP-1, and MIG (p 〈 0.01 or p 〈 0.05). Most of these factors were significantly increased in the BM compared to PB. In addition to increased levels of the factors mentioned above, the BM plasma of MM patients post alloSCT showed selectively elevated concentrations of IL-4, IL-6, IL-8, IL-12p40/p70, and eotaxin (p 〈 0.01 or p 〈 0.05). Eotaxin levels were particularly high in patients with chronic GvHD. Correlating the BM cytokine/chemokine levels with the clinical characteristics of MM patients, we observed that BM levels of IL-16 (r=0.829, p=0.003) and HGF (r=0.805, p=0.005) correlated positively with myeloma cell infiltration within the BM. In addition, IP-10 (r=0.770, p=0.009), HGF (r=0.645, p=0.044), and IL-6 (r=0.664, p=0.036) correlated significantly with the initial stage of disease. Conclusions: Our study demonstrates that myeloma cells themselves generate a significantly higher number of cytokines/chemokines than previously described. We show that characteristic cytokine/chemokine patterns exact in the BM environment of MM patients before and after alloSCT. Certain factors, such as MIP-1α, MCP-1, HGF, IL-16, IP-10, and eotaxin might not only be developed into diagnostic instruments and/or predictive biomarkers, but might also represent potential targets for future myeloma- or GvHD-specific therapies. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.2795.2795
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
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  • 3
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    Longitudinal Analysis of Cancer-Testis Antigen Expression in Multiple Myeloma.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 4826-4826
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4826-4826
    Abstract: BACKGROUND: Based on their immunogenicity and restricted tissue expression, cancer-testis (CT) antigens seem ideal targets for active immunotherapies. We have recently reported a frequent expression of CT antigens in multiple myeloma (Blood2007;109:1103–12). However, CT antigen expression has not been examined over time in patients with multiple myeloma (MM) or other malignancies. This seems surprising, since data on the persistence of CT antigen expression are needed in order to evaluate their usefulness as diagnostic markers and targets of immunotherapeutic approaches, especially in the case of minimal residual disease (MRD). METHODS: We analyzed 336 bone marrow (BM) samples obtained from 130 myeloma patients for expression of CT antigens. Samples of 41 healthy BM donors were used as controls. Expression of MAGEC1/CT7, MAGEC2/CT10, MAGEA3, and SSX2 was examined using qualitative RT-PCR. Real-time PCR was applied to quantify MAGEC1/CT7 expression over time. RESULTS: In MM patients with significant tumor load ( 〉 = 10% BM plasma cells), MAGEC1/CT7 was expressed in 69%, MAGEA3 in 55%, MAGEC2/CT10 in 44%, and SSX2 in 14% of samples. CT antigens were not expressed in healthy BM. Since expression of the remaining CT antigens was rarely observed without expression of MAGEC1/CT7, this CT antigen seemed to fulfill a ‘gatekeeper’ function. Expression of CT antigens correlated positively with clinical stage and was increased in recurrent disease compared to newly diagnosed MM. Noticeably, 76% of samples from patients who had not responded to therapy, 28% of samples from patients in partial remission, and only 8% of patients in complete remission expressed at least one CT antigen. Samples of patients who had received chemotherapy alone more frequently expressed CT antigens than samples of patients post autologous stem cell transplantation. The lowest frequency of CT antigen expression was observed in patients post allogeneic stem cell transplantation. Remarkably, in case a patient with significant tumor load had expressed a CT antigen once, 97% (MAGEC1/CT7), 88% (SSX2), 81% (MAGEA3), 67% (MAGEC2/CT10) of the subsequent BM samples of the same patient were positive for the respective antigen. When we analyzed 22 MM patients with at least three consecutive BM samples (median follow-up 21 months [range 4–35 months]) longitudinally and quantitatively for CT antigen expression, we observed a correlation between the BM expression of CT7/MAGEC1 mRNA and the clinical course of the disease as indicated by BM plasma cell infiltration (r=0.51, p 〈 0.01) and, even more significantly, serum paraprotein levels (r=0.73, p 〈 0.01). CONCLUSIONS: Performing the first longitudinal analysis of CT antigen expression in a human cancer, we demonstrate that in myeloma patients expression of MAGEC1/CT7, SSX2, MAGEA3, and MAGEC2/CT10 persists over time and represents an independent tumor marker. These findings suggest that downregulation of CT antigen expression is not a common tumor escape mechanism in myeloma and that CT antigens might, therefore, serve as diagnostic markers and targets for active immunotherapy, i.e. in the clinical setting of MRD.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.4826.4826
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 4
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    Valproic Acid (VPA) Achieves High Response Rates in Patients with Low-Risk Myelodysplastic Syndromes.
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 789-789
    Details
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 789-789
    Abstract: Valproic acid shows in-vitro activity against AML blasts and synergizes with ATRA in differentiation induction. We reported in-vivo activity of VPA and VPA+ATRA in patients with MDS and AML. Here we present follow-up data on 119 patients treated between February, 2002, and July, 2005. 87 patients were started on VPA monotherapy. Addition of ATRA was planned for patients who did not respond or relapsed after an initial response. 32 patients were treated with VPA +ATRA from the start. VPA was targeted to reach serum concentrations of 50–110 μg/ml. Median treatment duration was 4 months ( & lt;1–42) for VPA and 3 months ( & lt;1–35) for ATRA. 25 patients (21%) achieved responses according to International Working Group (IWG) criteria for MDS. The response rate was 28% in MDS (n=58) and 15% in AML (n=61). One patient achieved CR, and another patient achieved PR. 23 patients showed hematologic improvement. The median response duration was 4 months (2–33). 45 patients (38%) had stable disease, and 49 (41%) showed progressive disease. Among the 25 responders, 17 relapsed. 10 of these subsequently received ATRA, which resulted in a second remission in 4. Median response duration of the second responses (20 months, n=4) was significantly longer than the first response (4 months, n= 25, p=0,008). Of 94 nonresponders, 25 received additional ATRA without response. The response rate among the 87 patients on VPA monotherapy was higher than among the 32 patients receiving VPA+ATRA from the start (24% vs. 13%). We found a response rate of 42% in MDS with a normal blast count (PSA, RSA, RCMD, RSCMD; n=36), 6% in RAEB (RAEB I+II; n=18), 15% in AML (n=61), and 0% in CMML (n=4). The difference in response rate was significant when RSA, RCMD, and RSCMD were taken together and compared with all other disease types (p = 0.001). Treatment responses were correlated with risk assessment according to the International Prognostic Scoring System. Patients with low-risk MDS (IPSS low + int-1) had a significantly higher response rate than all other risk groups (p = 0.049). The response rate was 44% in low-risk (n=16), 29% in intermediate-1 (n=28), 10% in intermediate-2 (n=10), and 0% in high-risk MDS (n=4). We compared response duration in patients with PSA, RSA, RCMD, and RSCMD, and patients with RAEB I+II and AML, using the Kaplan-Meyer method. We found a significantly longer response duration in good-risk patients (3 months (2–26) vs. median not reached (2–33); p=0,043). Bone marrow blast count was predictive of response (p = 0.004). For cytogenetic risk groups, there was a trend of lower responses in patients with a high-risk karyotype (11%), compared to an intermediate (17%) or low-risk karyotype (28%). 72 patients had a bone marrow blast count & gt;5%. In 3 of these patients, the blast count normalized, 4 achieved a reduction by more than 50%, and 3 had a complete peripheral blast clearance. We conclude that VPA has a high response rate in low-risk MDS. In patients responding to VPA monotherapy, subsequent combination with ATRA may lead to prolonged responses. For patients with high-risk MDS, combination regimens including inhibitors of signal transduction, or demethylating agents should be investigated.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V106.11.789.789
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 5
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    Critical Role for CCR1:CCL5 (RANTES) Receptor Ligand Interactions in Modulating Allogeneic T Cell Responses Following Bone Marrow Transplantation.
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 3107-3107
    Details
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 3107-3107
    Abstract: Acute graft versus host disease (GVHD) and leukemic relapse are the most serious complications of allogeneic (allo) stem cell transplantation (SCT), and separating desirable graft-versus-leukemia (GVL) effects from GVHD remains the ultimate challenge to successful outcomes. The recruitment of activated T cells to host target tissues (GVHD) or sites of leukemic infiltration (GVL) is likely mediated by chemokine receptor:ligand interactions. CCR1 is a chemokine receptor that binds to CC chemokines including RANTES (CCL5), and is expressed on a variety of cells including activated T cells, monocytes, and macrophages. We have previously shown that mRNA expression of both CCR1 and RANTES is increased in GVHD target tissues following allo-SCT. Using a well established murine SCT model (B6- & gt;B6D2F1) and mice deficient in CCR1, we examined the contribution of CCR1 expression to allo T cell responses in vitro and to GVH and GVL effects in vivo. Lethally (1100cGy) irradiated B6D2F1 mice received SCT either from syngeneic (B6D2F1) or allogeneic (B6) CCR1+/+ or CCR1−/− donors. The severity of GVHD was assessed by survival and a well described clinical scoring system. Syngeneic SCT recipients all survived and were indistinguishable from naïve, untransplanted controls, whereas animals receiving allo-SCT from CCR1+/+ donors developed significant GVHD. By contrast, allo-SCT with CCR1−/− donor cells resulted in significantly improved survival (92% vs. 50%) and less severe clinical GVHD (p & lt;0.01) by day 35 compared to allo-CCR1+/+ controls. GVL effects were next assessed by adding 500 P815 tumor cells (H-2d and syngeneic to host) to the bone marrow inoculum on day 0. F1 recipients of syngeneic BMT all died from tumor infiltration by day +15. Although all allo-SCT recipients effectively rejected their tumor, mice receiving CCR1-/− SCT had significantly improved leukemia free survival (45% vs. 5%) by day 60 compared to allo controls. At higher tumor doses, significant GVL activity remained in CCR1−/− SCT recipients, but the survival advantage was lost. Further examination of allo T cell responses in vivo revealed that day 7 splenic T cell expansion and serum IFNγ levels were significantly lower following CCR1−/− SCT (p & lt; 0.01). Surprisingly, proliferation and IFNγ secretion were also reduced by ~70% when CCR1−/− T cells were stimulated with host antigens in vitro, whereas CTL activity remained equivalent to CCR1+/+ controls. The reduction in proliferation was not secondary to a migration defect, but was dependent on interactions between CCR1 and RANTES; neutralization of RANTES with a monoclonal antibody significantly reduced proliferation of CCR1+/+ T cells in a dose dependent manner. Finally, we found that GVHD mortality was also less when RANTES−/− mice were used as recipients in a second, MHC-disparate, SCT model (p = 0.03). Collectively these data demonstrate a critical role for CCR1 in donor T cell alloreactivity following SCT. These responses contribute to both GVHD and GVL effects in vivo and are likely dependent upon interactions between CCR1 and the chemokine ligand RANTES.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V106.11.3107.3107
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 6
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    The Influence of Age and Gender on the Prognostic Impact of Karytoypic Subgroups in Myelodysplastic Syndromes - a Multicenter Analysis.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 1448-1448
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 1448-1448
    Abstract: In myelodysplastic syndromes (MDS) cytogenetic analysis has a major role to assess the individual risk of patients. According to the International Prognostic Scoring System (IPSS) three cytogenetic subgroups can be distinguished: favorable [-y,del(5)(q),del(20)(q)], poor [chr. 7 abnormalities, complex] and intermediate [other abnormalities]. In a multicenter analysis the prognostic impact of karyotypic patterns in a series of 1159 primary MDS patients with cytogenetic data was investigated. Aim of the presented analysis was to study the influence of age and gender on this prognostic model. Median age was 66 years, median survival 37 months, 654 patients (56,4%) were male and 505 (43,6%) female. According to the three cytogenetic riskgroups defined by the IPSS the distribution and the median survival duration were as follows: favorable 739 pts. (63,8%), 53 months; intermediate 206 pts. (17,8%), 31 months; poor 214 pts. (18,4%), 11 months. These results are concordant with other published data, especially the original publication of the IPSS. Focussing on age and gender we divided the whole patient cohort in 4 subgroups:male, female, age at time of diagnosis 〈 66 years (579 pts.) and ≥ 66 years (580 pts.) The distribution and survival data are shown in table 1. Risk distribution was comparable among all different subgroups. Analysis of the influence of gender showed significant shorter survival for men in the low risk group, in the other two subgroups median survival duration was not significantly different in favor of the male cohort (interaction p=0.0057). In the two different age groups the younger subgroup with favorable or intermediate cytogenetics lived significantly longer, in the high risk group survival difference was not significant, but substantially the same as in the other risk groups. The observed difference in the low risk subgroup between men and women could be due to a considerable higher frequency of del(5)(q) in female patients (60 females of 83 cases). The shorter survival of the older patient cohorts with favorable or intermediate cytogenetics could be due to non-hematological comorbidity, which has more impact on survival in the lower risk subgroups, while the disease itself is the predominant factor limiting lifetime in the elderly high risk group as defined by cytogenetics. Table 1 Female Male P (sex) 〈 66 years ≥66 years P(age) Favorab. n(%), survival 314(62,2%) 70mo 425(65%) 40mo 〈 0.00001 348(60,1%) 58mo 391(67,4%) 48mo 0.001 Intermed. n(%), survival 86(17%) 30mo 120(18,3%) 33mo 0.70 117(20,2%), 40mo 89(15,3%) 27mo 0.008 Poor n(%), survival 105(20,8%) 10mo 109(16,7%) 13mo 0.81 114(19,7%) 15mo 100(17,3%) 8mo 0.11 P (risk groups) 〈 0.00001 〈 0.00001 〈 0.00001 〈 0.00001
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.1448.1448
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 7
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    DNA Methylation Independent Silencing of the RARα Gene Expression in Acute Myeloid Leukemia.
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-01), p. 2225-2225
    Details
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-01), p. 2225-2225
    Abstract: All-trans-retinoic acid (ATRA) and the gene encoding retinoic acid receptor-α (RARα) have been implicated in the pathogenesis and treatment of acute promyelocytic leukemia (APL). Nevertheless, the role of these molecules in the pathogenesis and therapy of non-APL acute myeloid leukemias (AMLs) remains unclear. Previously we have shown that expression of the ATRA-inducible RARα2 isoform is downregulated in a variety of AML cell lines and increases with hematopoietic differentiation along the myelomonocytic lineage. Using quantitative real-time PCR we have now investigated expression of the RARα gene in primary AML cells (n=23) and report that as in AML cell lines the levels of RARα2 mRNAs are markedly reduced (by 48 fold in APL, p≤0.05, and by 52 fold in non-APL AML, p≤0.01) relative to cord blood (CB) derived CD33 (or CD34) positive cell population (n=4). However, in contrast to the AML cell lines and normal hematopoietic progenitors, the expression of the RARα1 isoform was also significantly reduced in primary AML samples (up to 26 fold, p≤0.05). Examination of potential mechanisms underlying the silencing of the RARα gene expression in AML revealed that the RARα2 promoter possesses two small CpG islands that are fully methylated in all AML cell lines examined. Consistent with the expression pattern of RARα1 a single CpG island in the RARα1 promoter region was unmethylated in all these samples. As expected from such results expression of RARα2, but not RARα1, could be stimulated with a DNA demethylating agent 5-aza-2′deoxycytidine and synergistic effects between 5-aza-2′deoxycytidine and ATRA were observed on both RARα2 expression and cellular differentiation of APL and non-APL AML cell lines. Extending this analysis to clinical material we have surprisingly discovered that RARα1 and RARα2 CpG islands are unmethylated in all AML patient samples, including 3 APL cases, suggesting that DNA methylation may not play a significant role in silencing of the RARα gene expression in primary AML cells. Chromatin immunoprecipitation of the RARα2 regulatory region with antibodies to specific histone modifications revealed presence of other negatively acting chromatin states in primary AML samples (relative to normal CD33 positive CB cells), including decreased histone H3 acetylation as well as decreased di- and tri-methylation of histone H3 lysine 4. A possibility that microRNAs targeting sequences in the common 3′-UTR regions of the RARα1 and α2 isoforms may also contribute to silencing of both RARα1 and α2 expression in AML cannot be excluded. These results underscore the complexities of mechanisms that are responsible for silencing of gene expression in AML and support the notion that diminished RARα expression contributes to leukemogenesis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V108.11.2225.2225
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 8
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    Coinherited genetics of multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance
    American Society of Hematology ; 2020
    In:  Blood Advances Vol. 4, No. 12 ( 2020-06-23), p. 2789-2797
    Details
    In: Blood Advances, American Society of Hematology, Vol. 4, No. 12 ( 2020-06-23), p. 2789-2797
    Abstract: So far, 23 germline susceptibility loci have been associated with multiple myeloma (MM) risk. It is unclear whether the genetic variation associated with MM susceptibility also predisposes to its precursor, monoclonal gammopathy of undetermined significance (MGUS). Leveraging 2434 MM cases, 754 MGUS cases, and 2 independent sets of controls (2567/879), we investigated potential shared genetic susceptibility of MM and MGUS by (1) performing MM and MGUS genome-wide association studies (GWAS); (2) validating the association of a polygenic risk score (PRS) based on 23 established MM loci (MM-PRS) with risk of MM, and for the first time with MGUS; and (3) examining genetic correlation of MM and MGUS. Heritability and genetic estimates yielded 17% (standard error [SE] ±0.04) and 15% (SE ±0.11) for MM and MGUS risk, respectively, and a 55% (SE ±0.30) genetic correlation. The MM-PRS was associated with risk of MM when assessed continuously (odds ratio [OR] , 1.17 per SD; 95% confidence interval [CI], 1.13-1.21) or categorically (OR, 1.70; 95% CI, 1.38-2.09 for highest; OR, 0.71; 95% CI, 0.55-0.90 for lowest compared with middle quintile). The MM-PRS was similarly associated with MGUS (OR, 1.19 per SD; 95% CI, 1.14-1.26 as a continuous measure, OR, 1.77, 95%CI: 1.29-2.43 for highest and OR, 0.70, 95%CI: 0.50-0.98 for lowest compared with middle quintile). MM and MGUS associations did not differ by age, sex, or MM immunoglobulin isotype. We validated a 23-SNP MM-PRS in an independent series of MM cases and provide evidence for its association with MGUS. Our results suggest shared common genetic susceptibility to MM and MGUS.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    URL: Article
    DOI: 10.1182/bloodadvances.2020001435
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 9
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    Comparison of outcomes of HCT in blast phase of BCR-ABL1 − MPN with de novo AML and with AML following MDS
    American Society of Hematology ; 2020
    In:  Blood Advances Vol. 4, No. 19 ( 2020-10-13), p. 4748-4757
    Details
    In: Blood Advances, American Society of Hematology, Vol. 4, No. 19 ( 2020-10-13), p. 4748-4757
    Abstract: Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1− myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI] , 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80] ). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96] ) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation–based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    URL: Article
    DOI: 10.1182/bloodadvances.2020002621
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 10
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    Impact of second primary malignancy post–autologous transplantation on outcomes of multiple myeloma: a CIBMTR analysis
    American Society of Hematology ; 2023
    In:  Blood Advances Vol. 7, No. 12 ( 2023-06-27), p. 2746-2757
    Details
    In: Blood Advances, American Society of Hematology, Vol. 7, No. 12 ( 2023-06-27), p. 2746-2757
    Abstract: The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with the use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials using auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in patients with MM after auto-HSCT using CIBMTR registry data. Adult patients with MM who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n = 3948). At a median follow-up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (hazard ratio [HR] 2.62, P  & lt; .001 and HR 5.01, P  & lt; .001, respectively) and OS (HR 3.85, P  & lt; .001 and HR 8.13, P  & lt; .001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% vs 30% and 53% vs 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in patients with MM and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post–auto-HSCT.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    URL: Article
    DOI: 10.1182/bloodadvances.2022009138
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2023
    detail.hit.zdb_id: 2876449-3
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