scholarly journals Impact of Amotosalen/UVA Pathogen Inactivated Platelet Components on Outcomes after Allogeneic Hematopoetic Stem Cell Transplantation: A Single Center Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1167-1167
Author(s):  
Andreas S. Buser ◽  
Laura Infanti ◽  
Andreas Holbro ◽  
Joerg Halter ◽  
Sabine Gerull ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Risk Scores ◽  
Employment Equity ◽  
Stem Cell Source ◽  
Equity Ownership ◽  
The Impact

Background: Platelet component (PC) transfusion is required for allogeneic hematopoietic stem cell transplantation (HCT) recipients. Contamination with infectious pathogens (bacteria, viruses, or protozoa) and T-cells is a risk factor for transfusion-transmitted infection (TTI) and transfusion associated graft-versus-host disease (TA-GVHD). Pathogen inactivation (PI) treatment of PC with amotosalen-UVA (PI-PC, INTERCEPT Blood System, Cerus Corp) in platelet additive solution (PAS) without bacterial screening, gamma irradiation, CMV serology, and with 7-day storage has been the standard of care in Switzerland since 2011 to manage risk of TTI and TA-GVHD. PI-PC have replaced conventional PC (C-PC) prepared in PAS with gamma irradiation and 5 day storage. We previously reported platelet usage in two consecutive five year periods at the University Hospital of Basel. Mean PI-PC dose was higher (3.0 vs. 2.8 x 1011, p=0.001) and mean storage duration longer (4.2 vs. 3.4 days: p=0.001) than with C-PC. PC expiration wastage was reduced with 7-day PI-PC storage vs. 5-day storage (1.5% vs. 8.7%). For HCT recipients, days of PC support; PC use per patient; and RBC use per patient were similar, despite 24.3% lower corrected count increments (CCI) with PI-PC. Now, we report the impact of these observations on treatment related mortality (TRM) and overall survival (OS) 100 days after HCT. Patients and Methods: A two-period retrospective cohort study was conducted to evaluate PI-PC impact on outcomes of consecutive first allogeneic HCT recipients from January 2006 to December 2010 (Period 1, P1), when gamma-irradiated apheresis C-PC were used, and Period 2 (P2) from January 2011 to December 2017, when apheresis and whole blood-derived PI-PC were used. The review utilized 100-day OS and 100-day TRM to determine the impact of PI-PC on HCT outcomes. Descriptive statistics were used for continuous variables and log-rank analysis for survival outcomes. Univariate analysis was performed using Pearson χ2 statistics. Multivariate Cox regression modelling analyses included: PC period (P1, P2), donor match (HLA identical/twin, matched related, matched unrelated), disease state (early, intermediate, late), and conditioning regimen (reduced intensity, myeloablative) with TRM as the outcome. This was an IRB approved single-center analysis. Results: In P1 and P2, 256 and 557 consecutive first-time allogeneic HCT recipients were included, respectively. By univariate analysis, the distribution of European Group for Bone Marrow Transplantation (EBMT) risk scores (grouped 0-2, 3-4, 5-7) and mean patient age were higher during P2 (p = 0.001 and p <0.001, respectively). Primary disease status (p = 0.039); stem cell source (p <0.001); GVHD prophylaxis with ATG (p <0.001); total body irradiation (p <0.001); and conditioning regimen (p <0.001) were different between P1 and P2. Donor match (p=0.084) and disease status (p = 0.628) were similar in P1 and P2. TRM at day 100 post HCT was significantly less (31/557, 5.5%) for PI-PC recipients in P2 vs. C-PC recipients in P1 (37/256, 14.5%, p<0.001). Overall proportion of survivors at day 100 post HCT was significantly greater for PI-PC recipients (507/557, 91.0 %) compared to C-PC recipients (209/256, 81.6%, p <0.001). By multivariate Cox regression analysis, P2 with PI-PC component support was associated with improved TRM (p = 0.001; adjusted hazard ratio 0.433; 95% confidence interval: 0.262, 0.716). Donor match (p = 0.019), disease state (p = 0.022), and myeloablative conditioning (p = 0.034) were associated with significantly poorer TRM (Table). Stem cell source was not significant (p=0.157) in the model. Hemorrhage was reported as cause of death in 1/50 (2.0%) patients during P2 with PI-PC and 4/47 (8.5%) patients during P1 with C-PCs. Conclusions: Universal implementation of PI-PC in routine with extended storage to 7 days in P2 was associated with reduced TRM and better overall survival 100 days post HCT, despite transplantation of older patients with higher EBMT risk scores. Multivariate analysis revealed an adjusted hazard ratio of 0.433 (95% C.I. 0.262, 0.716) for TRM by 100 days, suggesting better outcomes in P2. This retrospective analysis at a single site indicated that PI-PC treated with amotosalen /UVA stored up to 7 days did not have a negative impact on TRM and OS in HCT recipients, and was an integral part of improving clinical outcomes at our institution. . Table. Disclosures Heim: Novartis: Research Funding. Irsch:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

Allogeneic Stem Cell Transplantation from Unrelated Donors after Reduced Intensity Conditioning in Patients with MDS/sAML. A Report from the Chronic Leukemia Working Party (CLWP) of the EBMT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5176-5176 ◽  
Author(s):  
Nicolaus Kroeger ◽  
Ronald Brand ◽  
Rodrigo Martino ◽  
Philippe Guardiola ◽  
Anja van Biezen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Working Party ◽  
Stem Cell Source ◽  
Unrelated Donors

Abstract We analysed the results of 67 patients with MDS/sAML who were transplanted with allogeneic stem cell transplantation from unrelated donors after a reduced intenisity conditioning and reported to the EBMT. The median age was 52 years (range 17–70 years) and stem cell source was bone marrow (n = 30) or peripheral blood progenitor cells (n = 33).. The graft was HLA matched in 57 patients while 8 patients received SCT from HLA-mismatched donor. The MDS classification was as follows: RA/RARS: n=8, RAEB/CMML: n = 14, RAEB-t/sAML: n = 22. The conditioning regimen consisted of fludarabine/busulfan (n=15), fludarabine/melphalan (n=6), fludarabine and TBI (n=8) or fludarabine and others (n=36)At time of transplantation only 12 (18%) were in first complete remission. The Kaplan-Meier estimates of the probability of 2 years overall and disease free survival were 33 % (95% CI: 21–45 %) and 24 % (95% CI: 12–36 %), respectively. The probability of relapse at two years was 58 % (95% CI: 40–76 %) and of one year treatment-related mortality 37 % (95% CI %: 23–51 %). In an univariate analysis assessing source of stem cells, age, disease type, T-cell depletion, and HLA-matching no factor was significant for OS, EFS, TRM and Relapse. Allogeneic stem cell transplantation after a reduced intensified conditioning followed by unrelated SCT seems to be a feasible approach in those patients who were no candidates for a standard conditioning but is associated with a considerable number of relapses.

Early Mixed T-Lymphocyte and Myeloid Chimerism Is Predictive of Disease Recurrence Following Allogeneic Stem Cell Transplantation for AML/MDS.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3075-3075 ◽  
Author(s):  
Hans C. Lee ◽  
Rima M. Saliba ◽  
Gabriela Rondon ◽  
Julianne Chen ◽  
Yasmeen Charafeddine ◽  
...  
Keyword(s):  
Stem Cell ◽  
Disease Progression ◽  
T Lymphocyte ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Disease Status ◽  
Disease Recurrence ◽  
Free Survival ◽  
Study Population ◽  
The Impact

Abstract Abstract 3075 Background: Allogeneic stem cell transplantation (allo-SCT) is a potential curative therapy for patients with relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the risk for disease recurrence following transplant remains high. The ability to identify patients likely to relapse may allow for preemptive interventions in high-risk patients. The goal of hematopoietic transplantation is to eradicate the recipient myeloid leukemia cells and restore hematopoiesis and immunity with donor cells. Donor lymphoid cells mediate an important graft-vs.-leukemia effect. Post transplant peripheral blood (PB) chimerism analysis represents one potential tool for predicting disease recurrence, although the relationship between mixed chimerism and disease relapse is not well defined. Methods: We conducted a retrospective review of patients with AML/MDS who underwent allo-SCT with fludarabine/busulfan based conditioning regimens at The University of Texas MD Anderson Cancer Center between 2001 and 2011. PB chimerism was assessed between post-transplant days +90–120 using a multiplex PCR-based microsatellite polymorphism assay. Cox's proportional hazards regression was used on univariate and multivariate (MV) analysis to evaluate the impact of chimerism of T-lymphocytes and myeloid cells in PB, as well as patient-, disease-, and transplant-related variables on the rate of disease progression and progression-free survival (PFS). Survival and PFS were assessed in landmark analysis starting on day +120. The cut off levels for assessment of chimerism were based on the respective quartiles of distribution of T-lymphocytes and myeloid cells in the study population. Results: 483 patients who underwent allo-SCT for AML/MDS with fludarabine/busulfan based conditioning regimens between 2001–2011 were analyzed. Within this cohort, 378 patients were alive and without evidence of disease progression on day +120 and were eligible for study evaluation. Patients with disease progression or death within 3 weeks of chimerism assessment were excluded from analyses assessing the impact of chimerism on outcomes. 158 patients were in CR1, 66 in CR2, and 154 had active disease at the time of transplantation. PB T-lymphocyte and myeloid donor cell chimerism data between days +90–120 were available for 265 (70%) and 286 (76%) patients, respectively. The median follow-up time among surviving patients was 54 months (range, 5–126). Progression-free survival from day +120 was 56% (95% CI 39–52) at 3 years, and 46% (95% CI 39–52) overall. On univariate analysis, mixed T-lymphocyte chimerism of ≤87% (HR=1.8, P 0.03, Figure 1) and myeloid chimerism ≤98% (HR=2.4, P 0.005, Figure 2) were significantly associated with a higher rate of 3-year disease progression. These cut-off points were based on the 25th percentile of the respective distributions of T-lymphocyte and myeloid chimerism in the study population. Additional adverse factors included poor-risk cytogenetics (HR=1.5, P 0.04) and disease status other than first or second remission at the time of transplant (HR=2, P 0.002). All factors remained significant on MV analysis, with the exception of myeloid chimerism, which became only marginally significant (HR=1.96, P 0.06). Mixed T-lymphocyte (HR=1.5, P 0.05) and myeloid (HR=1.9, P 0.02) chimerism were also associated with significantly lower 3-year PFS on univariate analysis, but were no longer significant (HR=1.5, 95% CI 0.95–2.3 and HR=1.6, 95%, CI 0.9–2.8, respectively) after adjustment for disease status at transplant. Disease status other than first or second remission at transplant was the only significant predictor of 3-year PFS on MV analysis (HR=1.6, P=0.03). Stem cell source (PB vs. BM), donor type (match-related donor vs. other), age (>50 vs. ≤50 years), and diagnosis (AML vs. MDS) did not impact the rate of disease progression or disease free survival. Conclusion: Mixed T-lymphocyte and myeloid chimerism assessed on day +120 post SCT are associated with the rate of disease progression independently of disease status at transplant. The use of chimerism assessments may be useful in selecting patients at high-risk for relapse for preemptive therapeutic approaches. Disclosures: Champlin: Otsuka: Research Funding.

scholarly journals Risk Factors for Relapse Following Allogeneic Transplant for Acute Myeloid Leukemia in the UCLA Patient Population

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5855-5855
Author(s):  
Harsh Patel ◽  
Alfonso Molina ◽  
Mina Nikanjam ◽  
Gary J. Schiller
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Stem Cell Source ◽  
Donor Type ◽  
Time To Relapse ◽  
Risk Categorization

Abstract Introduction: Allogeneic stem cell transplant for acute myeloid leukemia (AML) is curative for a subset of patients, however carries a substantial risk of adverse outcomes. Additional information identifying factors relating to relapse, in particular early relapse within one year, can be useful in counseling patients on the risks and benefits of this procedure. The current study represents a retrospective analysis on the UCLA patient population with the goal of identifying the subset of patients at higher risk for relapse. Methods: Data were obtained from the UCLA allogeneic stem cell transplant registry and electronic medical record on patients receiving allogeneic stem cell transplants for acute myeloid leukemia between January 2008 and September 2015. Fischer's exact (categorical variables) or t-tests (continuous variables) were used to determine differences between relapsed and non-relapsed patients, while Cox proportional-hazards regression was used to determine how time-to-relapse varied with age, gender, American Society for Blood and Marrow Transplant (ASBMT), risk categorization (low vs. intermediate or high), donor type (matched related vs. matched unrelated or cord blood), stem cell source (peripheral blood vs. bone marrow or cord blood), conditioning regimen (myeloablative vs. reduced intensity), disease status at transplant (first complete remission vs. later remission), and the presence of chronic graft vs. host disease (GVHD) with statistical software (SAS v. 9.4). For the time-to-relapse analyses, patients not relapsing by the last UCLA clinic visit were included as censored patients, while patients who died prior to relapse were treated as a competing risk. Patients who relapsed or died within 100 days of transplant were not included in the chronic GVHD analyses. Results: 164 patients receiving allogeneic stem cell transplant for AML were included in the analysis of which 49 patients had relapsed by June 2016. Median time to relapse was 158 days (range: 41-2449) and for non-relapsed patients median follow-up was 547 days (range: 31 - 2893). Median age for relapsed patients was 54 years (range: 21-71) and for non-relapsed patients was 55 years (range: 18- 75). Chronic GVHD occurred more often in non-relapsed patients (p=0.008), however no significant differences were found between relapsed and non-relapsed patients for age (p=0.99), gender (p=0.24), conditioning regimen (p=0.29), stem cell source (p=0.82), donor type (p=0.86), ASBMT risk categorization (p=0.31), and disease status at transplant (p=0.59). For patients who relapsed within 1 year compared to those who remained in remission at 1 year, chronic GHVD occurred more frequently in patients who remained in remission (p=0.0004), but no significant differences were found for age (p=0.32), gender (p=0.36), conditioning regimen (p=0.34), stem cell source (p=1.00), donor type (p=1.00), ASBMT risk categorization (p=0.27), and disease status at transplant (p=0.70). Time-to-relapse [hazard ratio (95% confidence interval); p-value] was significantly increased by the presence of chronic GVHD [2.88 (1.45-5.70); p=0.0024], while no significant differences were seen with age (1.00 (0.98-1.02); p=0.82), gender [0.75 (0.43-1.31); p=0.31], ASBMT risk categorization [1.49 (0.85-2.58); p=0.16], conditioning regimen [0.70 (0.40-1.24); p=0.22], stem cell source: peripheral blood stem cell vs. bone marrow [1.21 (0.58-2.54);p=0.61] or cord blood [0.91 (0.46-1.82);p=0.80], donor type [1.16 (0.67-2.03); p=0.59], and disease status at transplant [1.28 (0.72-2.27); p=0.41]. Conclusions: The presence of chronic GHVD was found to significantly decrease the risk of relapse after allogeneic stem cell transplant, however no significant differences in factors that can be assessed prior to transplant were found between the relapsed and non-relapsed patient population. It is important to note that the ASBMT criteria may insufficiently assess the risk of relapse since molecular analysis is not routinely captured. Further studies will be needed to determine predictive factors leading to a higher risk of relapse and the patient population that may benefit from clinical trials rather than allogeneic stem cell transplant. Disclosures Schiller: Incyte Corporation: Research Funding.

scholarly journals Characterization of Del(14)(q24q32) in Mature B-Cell Neoplasms By Array-CGH, Cytogenetics and Molecular Mutations

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3901-3901
Author(s):  
Sabine Jeromin ◽  
Wolfgang Kern ◽  
Torsten Haferlach ◽  
Susanne Schnittger ◽  
Claudia Haferlach
Keyword(s):  
B Cell ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Comparative Genomic ◽  
Molecular Characteristics ◽  
Splenic Marginal Zone Lymphoma ◽  
Employment Equity ◽  
Cytogenetic Aberrations ◽  
Mutational Status ◽  
Equity Ownership

Abstract Background: Deletions of 14q occur recurrently in mature B-cell neoplasms at a low frequency of 1.5% (Reindl et al., BJH 2010). In about one-third of these cases breakpoints show a clustering at 14q24.1 (centromeric) and at 14q32.3 (telomeric). Limited genetic data is available on this rare subgroup. Aim: To characterize del(14)(q24q32) using array based comparative genomic hybridization (aCGH) and to analyze cytogenetical and molecular characteristics. Patients and Methods: 34 patients with mature B-cell neoplasms and del(14)(q24q32) by chromosome banding analysis were analyzed. Median age was 72 years (range: 45-94 years). Male:female ratio was 1.4:1. All cases were analyzed by aCGH (Agilent, Waldbronn, Germany) and for mutations in MYD88, NOTCH1, TP53, and SF3B1 as well as for IGHV mutational status by direct Sanger sequencing. IGHV mutated (mut) cases without stereotypic VH3-21 were classified as IGHV favourable (IGHV fav). For statistical analysis of CLL patients data were compared with a cohort of 1,136 untreated CLL patients without del(14q). Results: Patients with del(14)(q24q32) were immunophenotypically classified as follows: 26 (59%) had CLL (n=20) or CLL/PL (n=6), 6 (18%) had splenic marginal zone lymphoma (SMZL), one patient had two B-cell neoplasms (SMZL and CLL/PL: 66% and 10% infiltration, respectively) and one patient had monoclonal B-cell lymphocytosis that progressed to CLL within two years. Analysis with aCGH showed that centromeric breakpoints were detected within a region of 970 kb (69,135,775 - 70,106,558) and telomeric breakpoints localized within a region of 712 kb (105,618,017 - 106,329,974). The median length of the deletions was 36.9 Mb (range: 35.5-37.1). Interestingly, the same breakpoints were present in 4 patients, each: 69,248,772 - 106,329,974 (cluster 1) and 69,271,436 - 106,329,974 (cluster 2). Genes located at the centromeric breakpoint that may be activated by juxtaposition to the IGH locus include FUT8. Its expression contributes to cancer malignancy. Interesting candidate genes located within the deleted region are PPP1R13B (p53 interaction) and NUMB (NOTCH1 interaction). In addition to del(14)(q24q32) 39 cytogenetic aberrations were detected in 23 patients. Two changes were recurrent: trisomy 12 (+12; n = 14) and del(13q) (n = 3). All patients of cluster 1 had +12 (cluster 1 vs. non-cluster 1: 100% vs. 33%, p=0.022). Mutations were detected in TP53 (n = 5, 15%) and NOTCH1 (n = 12, 35%). In SF3B1 a variant and in MYD88 no mutation were found. All mutated cases were CLL or CLL/PL cases only (n.s.). No molecular or cytogenetic differences were detected between CLL or CLL/PL and SMZL. Additionally, the IGHV mutational status was determined in CLL and CLL/PL cases (unmutated in 18 (69%), mutated in 8 (31%)). Further statistical analyses were performed in cases with CLL or CLL/PL with vs. without del(14)(q24q32). NOTCH1 mut (42% vs. 12%, p<0,001) and +12 (46% vs. 14%, p<0.001) were more frequent in patients with del(14q) vs. without. Of note, NOTCH1 mut were not associated with +12 in patients with del(14q) (with vs. without +12: 21% vs. 45%, n.s.), whereas patients without del(14q) showed a significant association (31% vs. 9%, p<0.001). Furthermore, del(13q) was rare in patients with del(14q) (4% vs. 61%, p<0.001) and IGHV fav was detected in less cases (35% vs. 60%, p=0.014). In 978 cases (events = 373; del(14q): n=13, events = 11) data on time to treatment (TTT) was available. TTT was shorter in patients with vs. without del(14q) (4 vs. 95 months, p<0.001). This was also the case when TP53 disrupted (del(17p) and TP53 mut) and +12 cases were excluded from the del(14q) cohort (17 vs. 95, p<0.001). For Cox regression analyses cytogenetic aberrations were hierarchically classified as follows: del(14q), del(17p), del(11q), +12, del(13q) sole. Univariate analysis of cytogenetic subgroups and molecular mutations identified that del(14q), TP53 disrupted, del(11q), +12, NOTCH1 mut, and SF3B1 mut have significant negative impact on TTT and del(13q) sole and IGHV fav are positive prognosticators. Multivariate analysis showed independent impact of del(14q) (HR: 5.2, p<0.001), del(11q) (HR:1.5, p=0.037), SF3B1 mut (HR: 1.5, p=0.008), and IGHV fav (HR: 0.3, p<0.001). Conclusions: del(14)(q24q32) are deletions with a very low variability in breakpoints in mature B-cell neoplasms. In CLL patients they are associated with +12, NOTCH1 mut and independently with a very short TTT. Disclosures Jeromin: MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

Similar Survival after Bone Marrow Versus Peripheral Blood Stem Cell Transplantation from Matched Unrelated Donors in Children with Hematologic Malignancies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2066-2066
Author(s):  
Roland Meisel ◽  
Hans-Juergen Laws ◽  
Stephan Balzer ◽  
Benedikt Bernbeck ◽  
Christof Kramm ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Event Free Survival ◽  
Free Survival ◽  
Stem Cell Source ◽  
Detectable Difference ◽  
Unrelated Donors ◽  
Recipient Age

Abstract Peripheral blood stem cells (PBSC) are increasingly used instead of bone marrow (BM) for allogeneic haematopoietic stem cell transplantation (alloHSCT) in children. Prior studies in adults have suggested a comparable outcome with both stem cell sources in matched unrelated donor (MUD) transplantation. However, relative benefits of PBSC versus BM transplantation may substantially differ in children and adults due to a greater propensity to GvHD in older patients and a higher proliferation rate of blasts in childhood leukemia. Here we present the first comparison of the outcome following PBSC vs. BM transplantation from HLA-matched unrelated donors in an entirely pediatric cohort. Between 1992 and 2004, a total of 61 pediatric patients (pts) with haematologic malignancies underwent PBSC (n=38) or BM (n=23) transplantation from ≥ 5/6 HLA antigen-matched unrelated donors following myeloablative conditioning at our institution. PBSC and BM groups were comparable with regard to GvHD prophylaxis, disease category, disease status at transplant and recipient age, while differences were detected in recipients sex (more male pts in PBSC group, p=0.06), conditioning regimen (more busulfan-based conditioning in PBSC group, p=0.01) and median year of transplant (PBSC transplantations were more recent, p=0.001). Engraftment was achieved significantly faster after PBSC compared to BM transplantation (p=0.001). Median time to neutrophil engraftment was 18 (range: 9–28) and 24 (14–43) days for the PBSC and BM cohort, respectively. The rate of acute GvHD grade III/IV (PBSC vs. BM: 28.9% vs. 19.0%, p=0.54) and chronic GvHD (63.0% vs. 56.3%, p=0.75) was comparable between both groups. While there was a statistically non-significant trend towards increased risk of clinically extensive chronic GvHD following PBSC transplantation (48.1% vs. 25.0%, p=0.2), this did not translate into any detectable difference in treatment-related mortality (PBSC vs. BM: 28.9% vs. 26.1 %) or death of disease (21.7% vs. 21.1%) (p=1.0). With a median follow up of 3.4 years (PBSC) and 10.0 years (BM) overall survival (PBSC vs. BM: 47.5 ± 8.6 % vs. 51.8 ± 10.5 %; p = 0.88) and event-free survival (43.3 ± 8.3 % vs. 51.8 ± 10.5 %; p = 0.60) is without detectable difference between both groups. This result was confirmed in a multivariate analysis including stem cell source, recipient age, recipient sex, conditioning regimen, disease status at transplant and year of transplant as covariates, showing that advanced disease status at transplant is the only significant, independent risk factor for overall mortality (RR 2.4, 95%-CI 1.1–5.2, p=0.02). In conclusion, our data provide evidence that in pediatric recipients of MUD transplantation the use of PBSC instead of BM leads to a faster neutrophil engraftment and a trend towards higher incidence of extensive chronic GvHD. As overall survival and event-free survival is comparable when using PBSC and BM, PBSC is a valid alternate stem cell source for pediatric alloHSCT from MUDs. Supported by the Elterninitiative Kinderkrebsklinik e.V., Duesseldorf

The Influence of PET/Gallium (PET/Gal) Status and High-Dose Rituximab (HDR) in Patients with Aggressive, Large, B-Cell Lymphoma (LBCL) Receiving Autologous Stem Cell Transplants (ASCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3058-3058 ◽  
Author(s):  
Amin M. Alousi ◽  
Rima M. Saliba ◽  
Grace-Julia Okoroji ◽  
Chitra Hosing ◽  
Barry I. Samuels ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
De Novo ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Disease Status ◽  
High Dose ◽  
Free Survival ◽  
The Impact

Abstract Background: PET/Gal status has been reported to be an important predictor of outcome in patients with LBCL who receive an ASCT. Newer conditioning regimens which include high-dose rituximab (HDR) have been shown to improve results (Khouri, JCO, 2005). The impact of HDR on the outcome of patients based on PET/Gal status has not been determined. Methods: A retrospective review of patients with chemo-sensitive, LBCL who received an ASCT on a research protocol at MD Anderson between 1995 and 2005 was performed. Factors that were considered for outcome included: Age, IPI, # of prior chemotherapies, B2-microglobulin, disease status at transplant, HDR and PET/Gal status. In patients who received HDR, it was given with stem cell mobilization and then again on days +1 and +8 following transplant. Results: A total of 188 patients were identified. Median age was 49 years with 108 (57%) male patients. 147 patients (78%) had de novo LBCL and 41 (22%) had a LBCL of follicular origin (LBCL-F). 83 (39%) patients received HDR. At transplantation, 95 patients (50%) were in PR, 71 (38%) in CRU and 22 (12%) in CR. 142 (76%) patients were PET/Gal negative, 37 (20%) PET/Gal positive and 9 (4%) were unknown. Median follow-up was 47 months. On multivariate analysis, for patients with de novo LBCL, PET/Gal status and HDR were the only predictors for progression and progression free survival (PFS). Patients who were PET/Gal negative and those that received HDR had a hazard ratio (HR) of 0.3 (p<0.001) and 0.5 (p=0.02) for progression, respectively (see the table below for the cumulative incidence (CI) for progression and PFS at 54 months according to HDR and PET/Gal status for de novo LBCL undergoing ASCT). PET/Gal Status and HDR were also found to be predictive for patients with LBCL- F on univariate analysis, however due to the small numbers in this subset; multivariate analysis could not be performed. PFS at 54 months for patients with LBCL-F who were PET/Gal negative was 40% versus 17% in the PET/Gal positive group, (p=0.006). PFS for those LBCL-F patients who received HDR was 81% as compared to 23% for those who did not receive HDR, (p=0.007). Conclusions: The two most important predictors of outcome following ASCT are PET/Gal status and whether HDR was given with the transplant regimen. The addition of HDR to the transplant regimen decreases the risk for progression irrespective of PET/Gal status; however the improvement is more significant in patients with a negative PET/Gal scan. C.I. for progression and PFS at 54 months for de novo DLBCL PET/Gal Status HDR CI of Progression (%) Progression Free Survival Positive No 83 17 Positive Yes 54 45 Negative No 35 55 Negative Yes 22 75

Busulfan and Fludarabine Conditioning Regimen Negates the Impact of Comorbidity Score on Nonrelapse Mortality in Patients with AML/MDS

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 799-799
Author(s):  
Uday Popat ◽  
Rima Saliba ◽  
Leandro de Padua Silva ◽  
Borje S Andersson ◽  
Amin M Alousi ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Unrelated Donor ◽  
Comorbidity Score ◽  
Cart Analysis ◽  
Reduced Toxicity ◽  
The Impact ◽  
Primary Predictor

Abstract BACKGROUND: Comorbidities as measured by newly developed Hematopoietic cell transplantation specific comorbidity index (HCT-CI) increases non relapse mortality in patients with hematological malignancies undergoing allogeneic transplantation. Whether this applies to recently treated patients with newer reduced toxicity regimens is not known. To evaluate this, we studied the factors influencing non relapse mortality in patients with AML/MDS. METHODS: 840 consecutive patients with AML/MDS undergoing allogeneic transplantation between January 1996 and April 2008 from a matched related or unrelated donor at our institution were studied. Information about disease characteristics, treatment, and outcomes was prospectively recorded in the departmental database. Comorbidities were retrospectively scored as previously described (Sorror et al Blood106: 2912–2919, 2005). Predictors of non-relapse mortality(NRM) at 2 years post SCT were evaluated on univariate analysis using Cox’s proportional hazards model and included age, sex, disease status at transplant, donor type, graft type, conditioning regimen (reduced intensity, ablative IV Busulfan(Bu) and Fludarabine(Flu), all other ablative regimens), and HCT-CI comorbidity score. Factors significant at the 0.1 level on univariate analysis were considered for classification and regression tree analysis (CART) to adjust for confounding and interaction effects. Statistical significance was defined at the 0.05 level, and cells including less than 10 patients were considered terminal in the CART analysis. RESULTS: There were 470(56%) males and 370(44%) females with a median age of 50 (range 18–77) years. 21% of patients were older than 60 years. HCT-CI comorbidity scores were as follows: 0 in 16% of patients, 1 in 13%, 2 in 13%, 3 or more in 58%. Donors were matched related for 58% of patients and unrelated for 42%. At the time of transplant, 22% of patients were in first complete remission (CR), 15% in second or third CR, and 63% had active disease. 36% of patients had reduced intensity conditioning regimen; 39% had myeloablative regimen consisting of Flu and Bu, and the remaining 25% had other myeloablative regimens. Cumulative incidence of NRM at 2 years was 26% (23–30). Univariate analysis showed that age > 60 (HR 1.6; p 0.002), disease status beyond first complete remission (HR 2.7; p <0.001), matched unrelated donor (HR 1.6; p 0.001), regimen other than Flu/Bu (HR 2.6; p<0.001), and a comorbidity score greater than 2 (HR 1.4; p 0.03) were associated with higher NRM. CART analysis (fig) showed that the use of Flu/Bu conditioning was the primary predictor of lower NRM. Age older than 60 years was the only additional significant predictor of NRM in patients who received Flu/Bu (HR 3.1; p 0.01). In patients who did not receive Flu/Bu, disease status at transplantation was the primary predictor of NRM with CR1 patients having a significantly lower incidence of NRM (CI =16%). The impact of donor type was only significant in patients who were not in CR1 with recipients of a matched related graft having a significantly lower NRM (CI=29%) than recipients of a matched unrelated graft (CI=46%). Comorbidity score did not significantly predict outcome in this analysis. CONCLUSION: Flu/Bu, a fully ablative reduced toxicity conditioning regimen, results in very low NRM, nullifying the impact of comorbidities. Figure Figure

Prognostic Value of “Monosomal Karyotype” in Comparison to “Complex Aberrant Karyotype” in AML: A Study on 824 Cases with Aberrant Karyotype

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 418-418
Author(s):  
Claudia Haferlach ◽  
Tamara Alpermann ◽  
Susanne Schnittger ◽  
Wolfgang Kern ◽  
Torsten Haferlach
Keyword(s):  
Cox Regression ◽  
Complex Karyotype ◽  
Employment Equity ◽  
Cytogenetic Abnormalities ◽  
Cox Regression Analysis ◽  
Poor Risk ◽  
Risk Patients ◽  
Equity Ownership ◽  
The Impact ◽  
Monosomal Karyotype

Abstract Abstract 418 Background: Several classifications based on cytogenetics have been proposed in AML. Typically 3 major categories for prognostication are defined: favorable, intermediate and unfavorable. The assignment to the unfavorable group shows minor differences between the different cytogenetic classifications currently used, however certain cytogenetic subgroups are assigned to the unfavorable subgroup concordantly: −5/5q−, 7q−/−7, −17/abn17p, inv(3)(q21q26)/t(3;3)(q21;q26) and complex karyotype (CK). With respect to CK 3 definitions are used: ≥3, ≥4 or ≥5 unrelated abnormalities. Recently, a so-called “monosomal karyotype” (MSK) defined as a karyotype showing “two or more distinct autosomal chromosome monosomies or one single autosomal monosomy in the presence of structural abnormalities” was introduced (Breems et al. JCO 2008). It was suggested that patients with MSK have a poor outcome being even inferior to CK. Aim: We here evaluated the prognostic power of differently defined cytogenetic subsets in order to identify the best definition for the prognostically most unfavorable subgroup. Patients: From our initial cohort of newly diagnosed AML (n=1,959) patients with t(15;17), t(8;21) or inv(16) (n=170) and AML with normal karyotype (n=965) were excluded. Thus, 824 patients with cytogenetic abnormalities remained for further investigation. Results: 428/824 (51.9%) patients showed an intermediate risk karyotype according to revised MRC criteria (MRC-I) (Grimwade et al. Blood 2010), while the remaining 396/824 (48.1%) cases belonged to the unfavorable MRC group (MRC-U). 162/824 cases (19.7%) fulfilled the criteria of MSK. According to MRC, 4 of these 162 cases with MSK were classified MRC-I while 158 were classified MRC-U. The overlap in classification between CK and MRC-U differed depending on the number of aberrations used to define CK. As such, the number of cases with CK was 272 (33.0%; MRC-I: 17, MRC-U: 255) using ≥3 clonal aberrations, and decreased to 222 (26.9%; all MRC-U) patients using ≥4 clonal aberrations or 196 (23.8%; all MRC-U) cases when applying the criterion of ≥5 clonal aberrations, respectively. Univariate Cox regression analysis revealed that unfavorable cytogenetics as defined by MRC-U, MSK, CK defined as ≥3, ≥4 or ≥5 unrelated abnormalities were all significantly associated with inferior OS as compared to the respective remaining intermediate group (for all p<0.001). Hazard ratios were 1.61, 1.93, 1.68, 1.94, and 1.92, respectively. Median OS in the respective categories was 8.5, 5.7, 6.3, 5.7, and 5.7 months, respectively. We then performed further analyses within the unfavorable risk group defined according to MRC and tested the impact of the 4 definitions for unfavorable subsets. In each comparison the median OS was significantly shorter for the subset with MSK, or CK defined as ≥3, '4 or ≥5 unrelated abnormalities as compared to the remaining MRC-U cases (5.7 vs 11.7 mo p=0.005; 6.3 vs 10.6 mo, p=0.031; 5.7 vs 11.0 mo, p=0.003; 5.7 vs 10.9 mo, p=0.006). Furthermore OS of patients within MRC-U excluding cases with MSK, or CK with ≥3, ≥4 or ≥5 unrelated abnormalities did not differ from patients with cytogenetic abnormalities assigned to MRC-I (median OS 11.7, 10.6, 11.0 and 10.9 mo, respectively vs 21.1 mo, p=0.072, p=0.16, p=0.28, and p=0.11, respectively). Within the MRC-U cohort only 124 cases fulfilled both criteria: MSK and CK≥4 (median OS 5.3 mo), 97 were CK≥4 only (median OS 6.3 mo) and 35 MSK only (median OS 6.7 mo). OS did not differ between these 3 subgroups but was significantly shorter for all comparisons to patients included in none of these subgroups (p<0.001, p=0.009, p=0.012, respectively). On the other hand OS of the 33 cases with 3 unrelated abnormalities did not differ from MRC-U cases with 1 or 2 abnormalities (18.9 vs 10.6, p=0.48). Conclusions: All definitions of very poor risk AML patients allow to identify a subset within MRC-U that shows significantly shorter OS than the remaining MRC-U cases. However, “complex karyotype defined as ≥4 unrelated abnormalities” is the best parameter as it identifies the largest proportion of very poor risk patients. Even more important, the application of the monosomal karyotype for prognostication and clinical guidance in AML misses 24.5% of the very poor risk patients identified based on CK ≥4. This may lead to suboptimal treatment decisions in this clinically proven very high risk patients. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Alpermann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

WT1 Mutations Are Secondary Events In AML and Show Varying Frequencies Within Genetic Subgroups and Different Impact On Prognosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2542-2542
Author(s):  
Susanne Schnittger ◽  
Christiane Eder ◽  
Tamara Alpermann ◽  
Frank Dicker ◽  
Madlen Ulke ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Median Time ◽  
Univariate Analysis ◽  
Normal Karyotype ◽  
Adverse Impact ◽  
Prognostic Impact ◽  
Employment Equity ◽  
Genetic Aberrations ◽  
Equity Ownership ◽  
The Impact

Abstract Background Mutations (mut) in the WT1 gene belong to the first genetic aberrations described in AML. In contrast to recurrent fusion genes or NPM1mut WT1mut do not seem to be disease defining. Also in contrast to other mutations in AML, for most of which a certain prognostic value has been established, the impact of WT1mut still is discussed controversially. Aim Analyze the frequency and prognostic impact of WT1 mutations in comparison to other genetic aberrations. Patients and Methods 3,157 unselected AML patients (pts) were analyzed (de novo: n=2,699, s-AML: n=234, t-AML: n=224). 1,708 pts were male and 1,449 female. Median age was 67.1 years (y) (range: 17.8-100.4 y) with 1,108 pts <60 y and 2,049 ≥60 y. The mutational hot spot regions of WT1 (exons 7 and 9) were analyzed by direct Sanger sequencing with a sensitivity of ∼10%. Karyotype and WT1 mutation status was available in all cases. Other mutations were assessed in subsets: ASXL1 (n=1,951), CEBPA (n=2,670), DNMT3A (n=1,293), FLT3-ITD (n=3,149), FLT3-TKD (n=3,004), IDH1R132 (n=2,431), IDH2R140 (n=2,380), IDH2R172 (n=2,412), KRAS (n=1,409), NRAS (n=1,780), NPM1 (n=3,003), MLL-PTD (n=2,961), RUNX1 (n=2,390), TET2 (n=1,016) and TP53 (n=1,215). Results A total of 189 WT1 mutations were detected (exon 7: n=151, exon 9: n=38). The total frequency of WT1mut pts was 175/3,157 (5.5%). 11 pts were double to quadruple mutated. The frequency was heterogeneous with respect to AML subtypes. Compared to all others, significantly higher frequencies were detected in biallelic CEBPAmut (15/110; 13.6%; p=0.001), followed by t(15;17)/PML-RARA (18/164; 11.0%, p=0.004), and FLT3-ITD (58/682; 8.5%, p<0.001). Lower frequencies were observed in DNMT3Amut (18/412; 4.3%, p=0.014, ASXL1mut (6/355; 1.7%, p<0.001), IDH2R140 (5/286; 1.7%, p=0.001), and IDH1R132 (2/222; 0.9%, p<0.001). WT1mut were never detected in pts with complex karyotypes (0/175; p=0.047) or those with IDH2R172 (0/68; p=0.020). Further, WT1mut were more frequent in females (95/1,449, 6.6%) than in males (80/1,708, 4.7%) (p=0.014) and in younger pts (<60 y: 102/1,108, 9.2% vs ≥ 60 y: 73/2,049, 3.6%; p<0.001). Median age of pts with WT1mut was 55.5 y compared to 63.6 in WT1wt (p<0.001). Further, WT1mut were associated with lower platelet count (58.4 vs 84.7 x109/L; p<0.001) and lower hemoglobin level (8.8 vs 9.3 g/dL, p=0.001). There was no association to the history of the disease or white blood cell count. Stability of WT1mut was analyzed in 35 paired diagnostic and relapse samples (median time of relapse after diagnoses: 11.1 months (m); range: 2.6-60.6 m). In 23 cases (65.7%) the WT1mut was retained at relapse and in 12 cases (34.3%) it was lost. In 5 cases a sample at 2nd relapse was available (median time from 1st relapse: 8.5 m, range: 6.0-18.0 m). 3 of these cases retained and 2 lost the WT1mut. Analysis of prognostic impact was restricted to intensively treated pts (n=1,936, WT1mut: n=132, 6.8%). In the total cohort, there was no impact of WT1mut on prognosis. In pts ≥60 y there was a trend to shorter event free survival (EFS) for WT1mut (9.3 vs 12.3 m, p=0.052). In the two prognostically favorable groups with high WT1mut incidences (biallelic CEBPAmut and PML-RARA) no effect on outcome was seen. When restricting the analysis to normal karyotype AML (WT1mut: n=85, WT1wt: n=1,093) WT1mut pts had shorter EFS (10.8 vs 17.9 m, p=0.008). This was true for the younger (12.2 vs 29.0 m, p=0.007) as well as for the older pts (9.3 vs 13.9 m, p=0.016). In a multivariate analysis all parameters with significant impact on EFS in univariate analysis were included: age (p<0.001, HR: 1.24), ASXL1mut (p<0.001, HR: 1.36), FLT3-ITD (p<0.001, HR: 1.55), NPM1mut/FLT3-ITD wild-type (p<0.001, HR:1.55), RUNX1 (p=0.019, HR: 1.23, and WT1mut (p=0.009, HR: 1.64). In multivariate analysis WT1mut was found to have independent adverse impact on EFS (p=0.002, HR: 1.64) besides FLT3-ITD status (p<0.001, HR: 1.71) and age (p<0.001, HR: 1.28). Conclusions WT1 mutations are 1) more frequent in females and younger AML, 2) more frequent in t(15;17)/PML-RARA, biallelic CEBPAmut, FLT3-ITD mutated AML, and nearly mutually exclusive of ASXL1, IDH1, IDH2 and complex karyotype. 3) The distribution pattern in different genetic subtypes and the instability during follow-up as shown by paired sample analyses clearly emphasize a secondary character of this mutation. 4) For AML with normal karyotype an independent adverse impact of WT1mut on EFS was shown. Disclosures: Schnittger: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Eder:MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Dicker:MLL Munich Leukemia Laboratory: Employment. Ulke:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Kuznia:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

scholarly journals Landscape Of Genetic Lesions In 944 Patients With Myelodysplastic Syndromes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 521-521 ◽  
Author(s):  
Yasunobu Nagata ◽  
Vera Grossmann ◽  
Yusuke Okuno ◽  
Ulrike Bacher ◽  
Genta Nagae ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Cox Regression ◽  
Molecular Model ◽  
Clonal Evolution ◽  
Univariate Analysis ◽  
Gene Mutations ◽  
Risk Groups ◽  
Employment Equity ◽  
Linear Predictor ◽  
Equity Ownership

Abstract Background Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by varying degrees of cytopenias and a predisposition to acute myeloid leukemia (AML). With conspicuous clinical and biological heterogeneity in MDS, an optimized choice of treatment based on accurate diagnosis and risk stratification in individual patients is central to the current therapeutic strategy. Diagnosis and prognostication in patients with myelodysplastic syndromes (MDS) may be improved by high-throughput mutation/copy number profiling. Methods A total of 944 patients with various MDS subtypes were screened for gene mutations and deletions in 104 known/putative genes relevant to MDS using targeted deep-sequencing and/or array-based genomic hybridization. Impact of genetic lesions on overall survival (OS) was investigated by univariate analysis and a conventional Cox regression, in which the Least Absolute Shrinkage and Selection Operator (lasso) was used for selecting variables. The linear predictor from the Cox regression was then used to assign the patients into discrete risk groups. Prognostic models were constructed in a training set (n=611) and confirmed using an independent validation cohort (n=175). Results After excluding sequencing/mapping errors and known or possible polymorphisms, a total of 2,764 single nucleotide variants (SNVs) and insertions/deletions (indels) were called in 96 genes as high-probability somatic changes. A total of 47 genes were considered as statistically significantly mutated (p<0.01). Only 6 genes (TET2, SF3B1, ASXL1, SRSF2, DNMT3A, and RUNX1) were mutated in >10% of the cases. Less common mutations (2−10%) involved U2AF1, ZRSR2, STAG2, TP53, EZH2, CBL, JAK2, BCOR, IDH2, NRAS, MPL, NF1, ATM, IDH1, KRAS, PHF6, BRCC3, ETV6, and LAMB4. Intratumoral heterogeneity was evident in as many as 456 cases (48.3%), even though the small number of gene mutations available for evaluation was thought substantially to underestimate the real frequency. The number of observed intratumoral subpopulations tended to correlate with the number of detected mutations and therefore, advanced WHO subtypes and risk groups with poorer prognosis. Mean variant allele frequencies (VAFs) showed significant variations among major gene targets, suggesting the presence of clonogenic hierarchy among these common mutations during clonal evolution in MDS. The impact of these genetic lesions on clinical outcomes was initially investigated in 875 patients. In univariate analysis, 25 out of 48 genes tested significantly affected overall survival negatively (P<0.05), and only SF3B1mutations were associated with a significantly better clinical outcome. Next, to evaluate the combined effect of these multiple gene mutations/deletions, together with common clinical/cytogenetic variables used for IPSS-R, OS was modeled by a conventional Cox regression. A total of 14 genes, together with age, gender, white blood cell counts, hemoglobin, platelet counts, cytogenetic score in IPSS-R, were finally selected for the Cox regression in a proportional hazard model and based on the linear predictor of the regression model, we constructed a prognostic model (novel molecular model), in which patients were classified into 4 risk groups showing significantly different OS (“low”, “intermediate”, “high”, and “very high risk”) with 3-year survival of 95.2%, 69.3%, 32.8%, and 5.3%, respectively (P<0.001). These results demonstrated that the mutation/deletion status of a set of genes could be used as variables independent of clinical parameters to build a clinically relevant prognostic score. When applied to the validation cohort, the novel molecular model was even shown to outperform the IPSS-R. Conclusions Large-scale genetic and molecular profiling by cytogenetics, NGS and array-CGH not only provided novel insights into the pathogenesis and clonal evolution of MDS, but also helped to develop a powerful prognostic model based on gene mutations and other clinical variables that could be used for risk prediction. Molecular profiling of multiple target genes in MDS is feasible and provides an invaluable tool for improved diagnosis, biologic subclassification and especially prognostication for patients with MDS. Disclosures: Grossmann: MLL Munich Leukemia Laboratory: Employment. Bacher:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Alpermann:MLL Munich Leukemia Laboratory: Employment. Roller:MLL Munich Leukemia Laboratory: Employment. Nadarajah:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

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