Gordon W Dewald

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (266)1569.62 Total impact

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    ABSTRACT: ABSTRACT Fludarabine (F) and cyclophosphamide (C) remain backbones of up-front chemotherapy regimens for chronic lymphocytic leukemia (CLL). We report long-term follow-up of a randomized F versus FC trial in untreated, symptomatic CLL (NCT00003764, clinicaltrials.gov). With median follow-up of 88 months, estimated median progression-free survival (PFS) was 19.3 versus 48.1 months for F (N=109) and FC (N=118) respectively (p<0.0001), while median overall survival (OS) was 88.0 versus 79.1 months respectively (p=0.96). In multivariable analyses, variables associated with inferior PFS and OS respectively were older age (p=0.002, p<0.001), Rai stage ≥II (p=0.006, p=0.02) and sex (p=0.03, PFS only). Occurrence of del(17)(p13.1) predicted shorter PFS and OS (p<0.0001 for each), as did del(11q)(22.3) (p<0.0001 and p=0.005, respectively), trisomy 12 with mutated Notch1 (p=0.003 and p=0.03, respectively) and unmutated IGHV (p=0.009 and p=0.002, respectively), all relative to patients without these features. These data confirm results from shorter follow-up and further justify targeted therapies for CLL.
    Leukemia and Lymphoma 02/2015; 56(11):1-24. DOI:10.3109/10428194.2015.1023800 · 2.89 Impact Factor
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    ABSTRACT: This retrospective study performed by the Eastern Cooperative Oncology Group and the Southwest Oncology Group enrolled 140 acute promyelocytic leukemia (APL) patients with t(15;17) to determine the influence of additional karyotypic abnormalities on treatment outcome. Karyotypes were centrally reviewed by both study groups. The complete response rate after induction for patients with t(15;17) treated with chemotherapy, or all-trans retinoic acid (ATRA) as induction therapy was not affected by additional cytogenetic aberrations. Disease-free (DFS) and overall survival (OS) were unaffected by additional cytogenetic abnormalities if treatment was chemotherapy without ATRA. Patients with t(15;17) only, treated with ATRA with or without chemotherapy, had an improved DFS (P = 0.06) and a better OS (P = 0.01) compared with ATRA-treated patients with additional cytogenetic abnormalities. Patients with APL and t(15;17) alone are significantly more sensitive to treatment with ATRA than are patients with t(15;17) and additional cytogenetic abnormalities.
    Medical Oncology 05/2012; 29(3):2095-101. DOI:10.1007/s12032-012-0251-7 · 2.63 Impact Factor
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    ABSTRACT: In patients with myelodysplastic syndromes (MDS), chromosome anomalies are detected by conventional cytogenetic studies (CCS) and/or interphase fluorescence in situ hybridization (FISH) of bone marrow (BM) samples and provide prognostic and diagnostic information, which can direct therapy. Whether peripheral blood (PB) can be substituted for bone marrow in these cases and can provide the same information remains unknown. Concurrent BM and PB specimens collected from 100 patients with recently diagnosed MDS were studied using both CCS and FISH. While 68% of BM samples showed an abnormal karyotype by CCS, only 31% of PB samples were abnormal by CCS. In 12% of patients, FISH and CCS were discordant due to the inability of the FISH panel to detect all possible abnormalities. However, only one case (1%) had a cryptic abnormality detected by FISH. BM and PB FISH were discordant in 3% of cases, most likely due to the smaller clone size in PB vs. BM. While PB should not be substituted for BM at diagnosis, it is a viable alternative for monitoring patients using the appropriate FISH probe(s).
    Leukemia research 04/2012; 36(7):832-40. DOI:10.1016/j.leukres.2012.03.013 · 2.35 Impact Factor
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    ABSTRACT: Chemotherapy-related myeloid neoplasia (t-MN) is a significant late toxicity concern after cancer therapy. In the randomized intergroup phase 3 E2997 trial, initial therapy of chronic lymphocytic leukemia with fludarabine plus cyclophosphamide (FC) compared with fludarabine alone yielded higher complete and overall response rates and longer progression-free, but not overall, survival. Here, we report t-MN incidence in 278 patients enrolled in E2997 with a median 6.4-year follow-up. Thirteen cases (4.7%) of t-MN occurred at a median of 5 years from initial therapy for chronic lymphocytic leukemia, 9 after FC and 4 after fludarabine alone. By cumulative incidence methodology, rates of t-MN at 7 years were 8.2% after FC and 4.6% after fludarabine alone (P = .09). Seven of the 9 cases of t-MN after FC occurred without additional therapy. Abnormalities involving chromosomes 5 or 7 were found in 10 cases, which suggests alkylator involvement. These data suggest that FC may induce more t-MN than fludarabine alone.
    Blood 07/2011; 118(13):3525-7. DOI:10.1182/blood-2011-03-342485 · 10.45 Impact Factor
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    ABSTRACT: We report the results of a prospective, randomized phase 3 trial evaluating the use of gemtuzumab ozogamicin (GO) in an intensive consolidation approach in 657 patients 17-60 years of age. Patients in first complete remission (CR1) after cytarabine and standard- or high-dose daunorubicin induction received 2 cycles of consolidation with high-dose cytarabine followed by peripheral blood progenitor cell collection. The 352 patients who entered consolidation were randomized to receive GO (n = 132) or not (n = 138) and then proceeded to autologous hematopoietic cell transplantation (HCT). GO was given to 67 patients. Median follow-up was 50.9 months. Results of the intention-to-treat analysis demonstrated a 4-year disease-free survival (DFS) of 33.6% versus 35.9% (P = .54) and an overall survival (OS) of 41.3% versus 41.9% (P = .52) for those randomized to receive GO versus no GO, respectively. Patients with favorable- and intermediate-risk acute myeloid leukemia (AML) treated with high-dose daunorubicin and autologous HCT had 4-year DFS rates of 60% and 40% and OS rates of 80% and 49.3%, respectively. For younger AML patients in CR1, autologous HCT should be considered in favorable- and intermediate-cytogenetic risk patients who do not have an allogeneic donor. The addition of a single dose of GO in this setting did not improve outcomes.
    Blood 03/2011; 117(20):5306-13. DOI:10.1182/blood-2010-09-309229 · 10.45 Impact Factor
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    ABSTRACT: Five laboratories in the Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) investigated standardizing and pooling of fluorescence in situ hybridization (FISH) results as a collaborative research project. This investigation used fixed bone marrow and blood cells available from previous conventional cytogenetic or FISH studies in two pilot studies, a one-day workshop, and proficiency test. Multiple FISH probe strategies were used to detect 6q-, 11q-, +12, 13q-, 17p-, and IGH rearrangements. Ten specimens were studied by participants who used their own probes (pilot study 1). Of 312 FISH interpretations, 224 (72%) were true-negative, 74 (24%) true-positive, 6 (2%) false-negative, and 8 (3%) false-positive. In pilot study no. 2, each participant studied two specimens using identical FISH probe sets to control for variation due to probe sets and probe strategies. Of 80 FISH interpretations, no false interpretations were identified. At a subsequent workshop, discussions produced agreement on scoring criteria. The proficiency test that followed produced no false-negative results and 4% (3/68) false-positive interpretations. Interpretation disagreements among laboratories were primarily attributable to inadequate normal cutoffs, inconsistent scoring criteria, and the use of different FISH probe strategies. Collaborative organizations that use pooled FISH results may wish to impose more conservative empiric normal cutoff values or use an equivocal range between the normal cutoff and the abnormal reference range to eliminate false-positive interpretations. False-negative results will still occur, and would be expected in low-percentage positive cases; these would likely have less clinical significance than false positive results. Individual laboratories can help by closely following rigorous quality assurance guidelines to ensure accurate and consistent FISH studies in their clinical practice and research.
    Cancer genetics and cytogenetics 12/2010; 203(2):141-8. DOI:10.1016/j.cancergencyto.2010.08.009 · 1.93 Impact Factor
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    ABSTRACT: To use fluorescence in situ hybridization (FISH) to visualize genetic abnormalities in interphase cell nuclei (interphase FISH) of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas. Between April 4, 2007, and December 4, 2008, interphase FISH was used to study paraffin-embedded preparations of tissue obtained from 18 patients listed in the Mayo Clinic Biospecimen Resource for Pancreas Research with a confirmed diagnosis of acinar cell carcinoma, ductal adenocarcinoma, islet cell carcinoma, or pancreas without evidence of neoplasia. FISH probes were used for chromosome loci of APC (see glossary at end of article for expansion of all gene symbols), BRCA2, CTNNB1, EGFR, ERBB2, CDKN2A, TP53, TYMP, and TYMS. These FISH probes were used with control probes to distinguish among various kinds of chromosome abnormalities of number and structure. FISH abnormalities were observed in 12 (80%) of 15 patients with pancreatic cancer: 5 of 5 patients with acinar cell carcinoma, 5 of 5 patients with ductal adenocarcinoma, and 2 (40%) of 5 patients with islet cell carcinoma. All 3 specimens of pancreatic tissue without neoplasia had normal FISH results. Gains of CTNNB1 due to trisomy 3 occurred in each tumor with acinar cell carcinoma but in none of the other tumors in this study. FISH abnormalities of all other cancer genes studied were observed in all forms of pancreatic tumors in this investigation. FISH abnormalities of CTNNB1 due to trisomy 3 were observed only in acinar cell carcinoma. FISH abnormalities of genes implicated in familial cancer, tumor progression, and the 5-fluorouracil pathway were common but were not associated with specific types of pancreatic cancer.
    Mayo Clinic Proceedings 10/2009; 84(9):801-10. DOI:10.1016/S0025-6196(11)60490-4 · 6.26 Impact Factor
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    ABSTRACT: The treatment of relapsed acute myeloid leukaemia (AML) remains unsatisfactory. We conducted a phase II randomized trial where patients received intermediate-dose cytarabine for 4 d followed by gemtuzumab ozogamicin on day 5 (Arm A), or combined with liposomal daunorubicin for 3 d (Arm B), or cytarabine given for 5 d combined with cyclophosphamide for 3 d and topotecan by continuous infusion for 5 d (Arm C). Eligible patients had primary refractory AML, a first relapse after a remission of <1 year, or a second or greater relapse. The primary objective of this trial was attainment of a conventional complete remission (CR) or a CR without platelet recovery (CRp) in at least 40% of patients. The CR/CRp rates for the 82 eligible patients were 3/26 (12%) in Arm A, 2/29 (7%) in Arm B, and 1/27 (4%) in Arm C. No patients who had relapsed within 6 months of initial CR or who had suffered multiple relapses responded. More than 95% of patients subsequently died of AML. No unexpected toxicities were encountered. We conclude that none of these three regimens were effective enough in the treatment of high-risk relapsed or refractory AML to warrant further study. This trial was registered at http://www.clinicaltrials.gov as #NCT00005962.
    British Journal of Haematology 10/2009; 148(2):217-25. DOI:10.1111/j.1365-2141.2009.07917.x · 4.71 Impact Factor
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    ABSTRACT: The biology and outcome of adult T-cell acute lymphoblastic leukemia are poorly understood. We present here the clinical and biologic features of 356 patients treated uniformly on the prospective trial (UKALL XII/ECOG 2993) with the aim of describing the outcome and identifying prognostic factors. Complete remission was obtained in 94% of patients, and 48% survived 5 years. Positivity of blasts for CD1a and lack of expression of CD13 were associated with better survival (P = .01 and < .001, respectively). NOTCH1 and CDKN2A mutations were seen in 61% and 42% of those tested. Complex cytogenetic abnormalities were associated with poorer survival (19% vs 51% at 5 years, P = .006). Central nervous system involvement at diagnosis did not affect survival (47% vs 48%, P = not significant). For 99 patients randomized between autograft and chemotherapy, 5-year survival was 51% in each arm. Patients with a matched sibling donor had superior 5-year survival to those without donors (61% vs 46%, chi(2), P = .02); this was the result of less relapse (25% vs 51% at 5 years, P < .001). Only 8 of 123 relapsed patients survive. This study provides a baseline for trials of new drugs, such as nelarabine, and may allow risk-adapted therapy in patients with poor-prognosis T-cell ALL.
    Blood 10/2009; 114(25):5136-45. DOI:10.1182/blood-2009-08-231217 · 10.45 Impact Factor
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    ABSTRACT: In young adults with acute myeloid leukemia (AML), intensification of the anthracycline dose during induction therapy has improved the rate of complete remission but not of overall survival. We evaluated the use of cytarabine plus either standard-dose or high-dose daunorubicin as induction therapy, followed by intensive consolidation therapy, in inducing complete remission to improve overall survival. In this phase 3 randomized trial, we assigned 657 patients between the ages of 17 and 60 years who had untreated AML to receive three once-daily doses of daunorubicin at either the standard dose (45 mg per square meter of body-surface area) or a high dose (90 mg per square meter), combined with seven daily doses of cytarabine (100 mg per square meter) by continuous intravenous infusion. Patients who had a complete remission were offered either allogeneic hematopoietic stem-cell transplantation or high-dose cytarabine, with or without a single dose of the monoclonal antibody gemtuzumab ozogamicin, followed by autologous stem-cell transplantation. The primary end point was overall survival. In the intention-to-treat analysis, high-dose daunorubicin, as compared with a standard dose of the drug, resulted in a higher rate of complete remission (70.6% vs. 57.3%, P<0.001) and improved overall survival (median, 23.7 vs. 15.7 months; P=0.003). The rates of serious adverse events were similar in the two groups. Median follow-up was 25.2 months. In young adults with AML, intensifying induction therapy with a high daily dose of daunorubicin improved the rate of complete remission and the duration of overall survival, as compared with the standard dose. (ClinicalTrials.gov number, NCT00049517.)
    New England Journal of Medicine 09/2009; 361(13):1249-59. DOI:10.1056/NEJMoa0904544 · 55.87 Impact Factor
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    ABSTRACT: This phase 3 prospective randomized trial evaluated the efficacy and long-term safety of erythropoietin (EPO) with or without granulocyte colony-stimulating factor plus supportive care (SC; n = 53) versus SC alone (n = 57) for the treatment of anemic patients with lower-risk myelodysplastic syndromes. The response rates in the EPO versus SC alone arms were 36% versus 9.6%, respectively, at the initial treatment step, 47% in the EPO arm, including subsequent steps. Responding patients had significantly lower serum EPO levels (45% vs 5% responses for levels < 200 mU/mL vs > or = 200 mU/mL) and improvement in multiple quality-of-life domains. With prolonged follow-up (median, 5.8 years), no differences were found in overall survival of patients in the EPO versus SC arms (median, 3.1 vs 2.6 years) or in the incidence of transformation to acute myeloid leukemia (7.5% and 10.5% patients, respectively). Increased survival was demonstrated for erythroid responders versus nonresponders (median, 5.5 vs 2.3 years). Flow cytometric analysis showed that the percentage of P-glycoprotein(+) CD34(+) marrow blasts was positively correlated with longer overall survival. In comparison with SC alone, patients receiving EPO with or without granulocyte colony-stimulating factor plus SC had improved erythroid responses, similar survival, and incidence of acute myeloid leukemia transformation.
    Blood 07/2009; 114(12):2393-400. DOI:10.1182/blood-2009-03-211797 · 10.45 Impact Factor
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    ABSTRACT: Lenalidomide is the first karyotype-selective therapeutic approved for the treatment of myelodysplastic syndromes (MDS) owing to high rates of erythroid and cytogenetic response in patients with chromosome 5q deletion [del(5q)]. Although haploinsufficiency for the RPS14 gene and others encoded within the common deleted region (CDR) have been implicated in the pathogenesis of the del(5q) phenotype, the molecular basis of the karyotype specificity of lenalidomide remains unexplained. We focused our analysis on possible haplodeficient enzymatic targets encoded within the CDR that play key roles in cell-cycle regulation. We show that the dual specificity phosphatases, Cdc25C and PP2Acalpha, which are coregulators of the G(2)-M checkpoint, are inhibited by lenalidomide. Gene expression was lower in MDS and acute myeloid leukemia (AML) specimens with del(5q) compared with those with alternate karyotypes. Lenalidomide inhibited phosphatase activity either directly (Cdc25C) or indirectly (PP2A) with corresponding retention of inhibitory phospho-tyrosine residues. Treatment of del(5q) AML cells with lenalidomide induced G(2) arrest and apoptosis, whereas there was no effect in nondel(5q) AML cells. Small interfering RNA (shRNA) suppression of Cdc25C and PP2Acalpha gene expression recapitulated del(5q) susceptibility to lenalidomide with induction of G(2) arrest and apoptosis in both U937 and primary nondel(5q) MDS cells. These data establish a role for allelic haplodeficiency of the lenalidomide inhibitable Cdc25C and PP2Acalpha phosphatases in the selective drug sensitivity of del(5q) MDS.
    Proceedings of the National Academy of Sciences 06/2009; 106(31):12974-9. DOI:10.1073/pnas.0811267106 · 9.67 Impact Factor
  • M. L. Slovak · G. Dewald ·

    Leukemia Research 05/2009; 33. DOI:10.1016/S0145-2126(09)70013-X · 2.35 Impact Factor
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    ABSTRACT: Smudge cells are ruptured chronic lymphocytic leukemia (CLL) cells appearing on the blood smears of CLL patients. Our recent findings suggest that the number of smudge cells may have important biologic correlations rather than being only an artifact of slide preparation. In this study, we evaluated whether the smudge cell percentage on a blood smear predicted survival of CLL patients. We calculated smudge cell percentages (ratio of smudged to intact cells plus smudged lymphocytes) on archived blood smears from a cohort of previously untreated patients with predominantly early-stage CLL enrolled onto a prospective observational study. The relationship between percentage of smudge cells, patient survival, and other prognostic factors was explored. Between 1994 and 2002, 108 patients were enrolled onto the study and had archived blood smears available for review; 80% of patients had Rai stage 0 or I disease. The median smudge cell percentage was 28% (range, 1% to 75%). The percentage of smudge cells was lower in CD38(+) versus CD38(-) patients (P = .019) and in Zap70-positive versus Zap70-negative patients (P = .028). Smudge cell percentage as a continuous variable was associated with prolonged survival (P = .042). The 10-year survival rate was 50% for patients with 30% or less smudge cells compared with 80% for patients with more than 30% of smudge cells (P = .015). In multivariate analysis, the percentage of smudge cells was an independent predictor of overall survival. Percentage of smudge cells on blood smear is readily available and an independent factor predicting overall survival in CLL.
    Journal of Clinical Oncology 04/2009; 27(11):1844-9. DOI:10.1200/JCO.2008.17.0795 · 18.43 Impact Factor
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    ABSTRACT: Prospective data on the value of allogeneic hematopoietic stem cell transplantation (alloHSCT) in Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) are limited. The UKALLXII/ECOG 2993 study evaluated the outcome of assigning alloHSCT with a sibling (sib) or matched unrelated donor (MUD) to patients younger than 55 years of age achieving complete remission (CR). The CR rate of 267 patients, median age 40, was 82%. Twenty-eight percent of patients proceeded to alloHSCT in first CR. Age older than 55 years or a pre-HSCT event were the most common reasons for failure to progress to alloHSCT. At 5 years, overall survival (OS) was 44% after sib alloHSCT, 36% after MUD alloHSCT, and 19% after chemotherapy. After adjustment for sex, age, and white blood count and excluding chemotherapy-treated patients who relapsed or died before the median time to alloHSCT, only relapse-free survival remained significantly superior in the alloHSCT group (odds ratio 0.31, 95% confidence interval 0.16-0.61). An intention-to-treat analysis, using the availability or not of a matched sibling donor, showed 5-year OS to be nonsignificantly better at 34% with a donor versus 25% with no donor. This prospective trial in adult Ph(+) ALL indicates a modest but significant benefit to alloHSCT. This trial has been registered with clinicaltrials.gov under identifier NCT00002514 and as ISRCTN77346223.
    Blood 02/2009; 113(19):4489-96. DOI:10.1182/blood-2009-01-199380 · 10.45 Impact Factor
  • Gordon W. Dewald ·
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    ABSTRACT: Various aneuploidies of the sex chromosomes are the most common chromosome abnormalities encountered in autopsies of adults. The Turner (usually 45,X but mosaicism is common) and Klinefelter (47,XXY) syndromes are two examples (1). Deletions or unbalanced translocations and inversions are rarely seen in autopsies of adults because patients with these abnormalities seldom survive into adulthood. Approximately 1/500 adults carries a genetically balanced abnormality of chromosome structure. These balanced chromosome anomalies may affect the reproductive history of an individual, but rarely affect the phenotype (2). Some adults have sporadic chromo some changes as part of a chromosome breakage syndrome such as Fanconi anemia (3), ataxia-telangiectasia (4), Bloom syndromes (5), and others.
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    ABSTRACT: Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 11/2008; 23(4):796-800. DOI:10.1038/leu.2008.279 · 10.43 Impact Factor
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    ABSTRACT: Among 59 consecutive patients with myelofibrosis (MF) in whom peripheral blood (PB) cytogenetic studies were performed, at least two analyzable metaphases (median 20, range 2-31) were obtained in 49 (81%) patients and in all 37 (100%) cases with PB myeloid progenitor cell count of 0.1 x 10(9)L(-1) or above (p=0.02). Twenty-two patients had concomitant PB and bone marrow (BM) cytogenetic studies; 6 showed similarly abnormal findings in both BM and PB. In another 2 cases, results were abnormal in BM but normal in PB; the opposite was seen in 1 case. These results suggest that PB can be considered as an alternative to BM for cytogenetic studies as currently used in MF but additional prospective studies are needed to support change in practice.
    Leukemia Research 11/2008; 32(10):1597-600. DOI:10.1016/j.leukres.2007.12.005 · 2.35 Impact Factor
  • Marilyn L Slovak · Gordon W Dewald ·
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    ABSTRACT: The inaugural meeting of the International Working Group on MDS cytogenetics convened 22-23 October 2007 in Chicago, IL. Under the sponsorship of the Myelodysplastic Syndromes Foundation, the group was organized to address the substantial need for worldwide standardized cytogenetic testing for MDS in clinical practice and research. Eighteen cytogeneticists from 10 countries attended the first working group meeting. Representatives from France and Austria were unable to attend the Chicago meeting. Marilyn L. Slovak, PhD (City of Hope, USA) served as Working Group Chair and Gordon Dewald, PhD (Mayo Clinic, USA), served as Working Group Advisor and Co-Chair. Other members in attendance included: Mette Andersen, Rigshospitalet, Denmark; Lynda Campbell, St. Vincent's Hospital Melbourne, Australia; Athena Cherry, Stanford University, USA; Kathy Chun, North York General Hospital, Canada; Mike Griffiths, West Midlands Regional Genetics Lab, UK; Detlef Haase, Georg-August-Universität, Germany; Claudia Haferlach, MLL Münchner Leukämielabor GmbH, Germany; Anne Hagemeijer, University of Leuven, Belgium; Barbara Hildebrandt, Institut für Humangenetik & Anthropologie Dupsilonsseldorf, Germany; Douglas Horsman, BC Cancer Agency, Canada; M. Anwar Iqbal, University of Rochester, USA; Suresh Jhanwar, Memorial Sloan-Kettering Cancer Center, USA; Bertil Johansson, University Hospital, Sweden; Michelle LeBeau, University of Chicago, USA; Kazuma Ohyashiki, Tokyo Medical University, Japan; Francesc Solé, Hospital del Mar, Spain. The focus of the working group was to establish the natural history and clinical significance of cytogenetic anomalies associated with the myelodysplastic syndromes (MDS), and to incorporate cytogenetic testing into the development of new treatments to cure MDS. Three specific goals were discussed in an effort to rapidly improve the care of patients with MDS. The first goal was how to educate physicians on the appropriate use of cost effective cytogenetic testing for their patients with MDS. The second goal discussed was how best this working group could assist pharmaceutical companies with the use of appropriate cytogenetic testing in their evaluation of new drugs. The final goal discussed was how to advance cytogenetic research into the origin, progression and clinical significance of genetic anomalies associated with MDS.
    Leukemia Research 09/2008; 32(9):1329-32. DOI:10.1016/j.leukres.2008.03.009 · 2.35 Impact Factor
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    ABSTRACT: To better estimate prognosis for patients with myelodysplastic syndromes (MDS) associated with clonal interstitial deletions of the long arm of chromosome 5 (del(5q)), we reviewed the medical records of 130 adults with del(5q) MDS seen at our institution over a 15-year period. Overall median survival of this cohort was 9.5 months, shorter than reported in earlier series. The least favorable outcomes are associated with complex cytogenetics, lack of any normal metaphases, normocytic rather than macrocytic erythrocyte indices, and low baseline lymphocyte counts. Lymphopenia but not neutropenia at the time of diagnosis appears to be a new adverse prognostic indicator. Cytogenetic breakpoints defined by G-banded karyotyping correlate poorly with particular disease features. Surprisingly, survival of patients with treatment-related MDS was equivalent to that of de novo MDS with del(5q) in this series. Morphologic features associated with del(5q) are diverse. Most patients with del(5q) MDS do not meet criteria for WHO-defined 5q-syndrome, and the presence of del(5q) does not appear to modify the clinical phenotype otherwise risk-stratified by the International Prognostic Scoring System (IPSS). Additional important prognostic factors not taken into account by the IPSS include the baseline erythrocyte indices, lymphocyte count, and clonal burden.
    American Journal of Hematology 09/2008; 83(9):708-13. DOI:10.1002/ajh.21245 · 3.80 Impact Factor

Publication Stats

14k Citations
1,569.62 Total Impact Points


  • 1974-2012
    • Mayo Clinic - Rochester
      • • Department of Hematology
      • • Department of Laboratory Medicine & Pathology
      Рочестер, Minnesota, United States
  • 2008
    • Columbus State University
      Columbus, Georgia, United States
  • 2007
    • The Ohio State University
      Columbus, Ohio, United States
    • Northwestern University
      • Department of Pathology
      Evanston, IL, United States
    • University of Southampton
      Southampton, England, United Kingdom
  • 2006
    • University of Utah
      • Division of Pediatric Genetics
      Salt Lake City, UT, United States
  • 2003-2005
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2004
    • University of Rochester
      Rochester, New York, United States
  • 2001
    • Mayo Foundation for Medical Education and Research
      • Division of Hematology
      Scottsdale, AZ, United States
  • 1996
    • Stony Brook University
      스토니브룩, New York, United States
  • 1990
    • University of New Mexico Hospitals
      Albuquerque, New Mexico, United States
  • 1986
    • University of Minnesota Duluth
      • Medical School
      Duluth, Minnesota, United States