Publications by authors named "AnneMarie W Block"

28 Publications

  • Page 1 of 1

Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body Irradiation for Allogeneic Hematopoietic Cell Transplantation: The Effect of Increasing Melphalan Dose on Underlying Disease and Toxicity.

Biol Blood Marrow Transplant 2019 04 6;25(4):689-698. Epub 2018 Oct 6.

BMT Program, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Disease relapse and toxicity are the shortcomings of reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (alloHCT). We hypothesized that adding total body irradiation (TBI) to and decreasing melphalan (Mel) from a base RIC regimen of fludarabine (Flu) and Mel would increase cytoreduction and improve disease control while decreasing toxicity. We performed a phase II trial of Flu 160 mg/m, Mel 50 mg/m, and TBI 400 cGy (FluMelTBI-50, n = 61), followed by a second phase II trial of Flu 160 mg/m, Mel 75 mg/m, and TBI 400cGy (FluMelTBI-75, n = 94) as RIC for alloHCT. Outcomes were compared with a contemporaneous cohort of 162 patients who received Flu 125 mg/m and Mel 140 mg/m. Eligibility criteria were equivalent for all 3 regimens. All patients were ineligible for myeloablative/intensive conditioning. The median (range) follow-up for all patients was 51 (15 to 103) months. Day 100 donor lymphoid chimerism and transplant-related mortality, neutrophil and platelet engraftment, acute and chronic graft versus host disease incidence, overall survival (OS), and progression-free survival (PFS) were equivalent between FluMel, FluMelTBI-50, and FluMelTBI-75. Stomatitis wasdecreased for FluMelTBI versus FluMel (P < .01). PFS for patients not in complete remission on alloHCT was improved for FluMelTBI-75 versus FluMel (P = .03). On multivariate analysis, OS (P = .05) and PFS (P = .05) were significantly improved for FluMelTBI-75 versus FluMel. FluMelTBI-75 is better tolerated than FluMel, with improved survival and disease control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2018.09.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451676PMC
April 2019

Genetic association with B-cell acute lymphoblastic leukemia in allogeneic transplant patients differs by age and sex.

Blood Adv 2017 Sep 8;1(20):1717-1728. Epub 2017 Sep 8.

College of Pharmacy, The Ohio State University, Columbus, OH.

The incidence and mortality rates of B-cell acute lymphoblastic leukemia (B-ALL) differ by age and sex. To determine if inherited genetic susceptibility contributes to these differences we performed 2 genome-wide association studies (GWAS) by age, sex, and subtype and subsequent meta-analyses. The GWAS included 446 B-ALL cases, and 3027 healthy unrelated blood and marrow transplant (BMT) donors as controls from the Determining the Influence of Susceptibility Conveying Variants Related to One-Year Mortality after BMT (DISCOVeRY-BMT) study. We identified 1 novel variant, rs189434316, significantly associated with odds of normal cytogenetic B-ALL (odds ratio from meta-analysis [OR] = 3.7; 95% confidence interval [CI], 2.5, 6.2; value from meta-analysis [] = 6.0 × 10). The previously reported pediatric B-ALL GWAS variant, rs11980379 (), replicated in B-ALL pediatric patients (OR = 2.3; 95% CI, 1.5, 3.7; = 1.0 × 10), with evidence of heterogeneity ( = .02) between males and females. Sex differences in single-nucleotide polymorphism effect were seen in those >15 years (OR = 1.7; 95% CI, 1.4, 2.2, = 6.38 × 10/OR = 1.1; 95% CI, 0.8, 1.5; = .6) but not ≤15 years (OR = 2.3; 95% CI, 1.4, 3.8; = .0007/OR = 1.9; 95% CI, 1.2, 3.2; = .007). The latter association replicated in independent pediatric B-ALL cohorts. A previously identified adolescent and young-adult onset ALL-associated variant in is associated with B-ALL risk in those >40 years. Our findings provide more evidence of the influence of genetics on B-ALL age of onset and we have shown the first evidence that associations with B-ALL may be sex and age specific.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2017006023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728332PMC
September 2017

Early versus late preemptive allogeneic hematopoietic cell transplantation for relapsed or refractory acute myeloid leukemia.

Biol Blood Marrow Transplant 2014 Sep 24;20(9):1369-74. Epub 2014 May 24.

Department of Medicine, BMT Program, Roswell Park Cancer Institute, Buffalo, New York. Electronic address:

Many patients with relapsed or refractory acute myeloid leukemia (AML) do not receive allogeneic hematopoietic cell transplantation (alloHCT) because they are unable to achieve a complete remission (CR) after reinduction chemotherapy. Starting in January 2003, we prospectively assigned patients with AML with high-risk clinical features to preemptive alloHCT (p-alloHCT) as soon as possible after reinduction chemotherapy. High-risk clinical features were associated with poor response to chemotherapy: primary induction failure, second or greater relapse, and first CR interval <6 months. We hypothesized that any residual disease would be maximally reduced at the time of transplant, resulting in the best milieu and most lead time for developing a graft-versus-leukemia effect and in improved long-term overall survival (OS) without excess toxicity. This analysis studied the effect of transplant timing on p-alloHCT in 30 patients with high-risk clinical features of 156 consecutive AML patients referred for alloHCT. We compared early p-alloHCT within 4 weeks of reinduction chemotherapy before count recovery with late p-alloHCT 4 weeks after reinduction chemotherapy with count recovery. OS and progression-free survival (PFS) at 2 years were not significantly different for early versus late p-alloHCT (OS 23% versus 33%, respectively, P > .1; PFS 18% versus 22%, respectively, P > .1). Day 100 and 1-year transplant-related mortality were similar (33.3% versus 22.2%, P > .1; 44.4% versus 42.9%, P > .1, respectively). Preemptive alloHCT allowed 30 patients to be transplanted who would normally not receive alloHCT. Clinical outcomes for early p-alloHCT are similar to those for late p-alloHCT without excess toxicity. Early p-alloHCT is a feasible alternative to late p-alloHCT for maximizing therapy of AML that is poorly responsive to induction chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2014.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292802PMC
September 2014

Low 25(OH) vitamin D3 levels are associated with adverse outcome in newly diagnosed, intensively treated adult acute myeloid leukemia.

Cancer 2014 Feb 25;120(4):521-9. Epub 2013 Oct 25.

Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York.

Background: Several studies have suggested that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in patients with acute myeloid leukemia (AML).

Methods: Vitamin D levels were evaluated in 97 consecutive, newly diagnosed, intensively treated patients with AML. MicroRNA expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome.

Results: Thirty-four patients (35%) had normal 25(OH) vitamin D3 levels (32-100 ng/mL), 34 patients (35%) had insufficient levels (20-31.9 ng/mL), and 29 patients (30%) had deficient levels (<20 ng/mL). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared with normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3 , smoking, European Leukemia Network genetic group, and white blood cell count retained their statistical significance for RFS. Several microRNAs and SNPs were associated with 25(OH) vitamin D3 levels, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with a lower complete remission rate (P = .0442) and with shorter RFS (P = .0058) and overall survival (P = .0011).

Conclusions: It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve outcomes for patients with AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.28368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948325PMC
February 2014

Phase II trial of clofarabine and daunorubicin as induction therapy for acute myeloid leukemia patients greater than or equal to 60 years of age.

Leuk Res 2013 Nov 15;37(11):1468-71. Epub 2013 Aug 15.

Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.

We designed a phase II study evaluating the upfront combination of clofarabine and daunorubicin in acute myeloid leukemia (AML) patients≥60 years old. The median age of the 21 patients was 69 (range 60-85) years. Fourteen patients (67%) had unfavorable risk features. The principal toxicities were grade ≥3 infections and prolonged myelosuppression. Three (14%) deaths occurred from infectious complications. Six (28.6%) patients achieved complete remission including three (21.4%) of 14 patients with unfavorable AML. The median disease-free survival was 6.8 months and the median overall survival was 11.2 months.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2013.07.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818466PMC
November 2013

Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia.

J Clin Oncol 2012 Dec 17;30(36):4515-23. Epub 2012 Sep 17.

The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210-1228, USA.

Purpose: To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML).

Patients And Methods: We analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), and overall survival (OS) among patients classified into the four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse) separately for 818 younger (age < 60 years) and 732 older (age ≥ 60 years) patients.

Results: The percentages of younger versus older patients in the favorable (41% v 20%; P < .001), intermediate-II (19% v 30%; P < .001), and adverse (22% v 31%; P < .001) genetic groups differed. The favorable group had the best and the adverse group the worst CR rates, DFS, and OS in both age groups. Both intermediate groups had significantly worse outcomes than the favorable but better than the adverse group. Intermediate-I and intermediate-II groups in older patients had similar outcomes, whereas the intermediate-II group in younger patients had better OS but not better CR rates or DFS than the intermediate-I group. The prognostic significance of ELN classification was confirmed by multivariable analyses. For each ELN group, older patients had worse outcomes than younger patients.

Conclusion: The ELN classification clearly separates the genetic groups by outcome, supporting its use for risk stratification in clinical trials. Because they have different proportions of genetic alterations and outcomes, younger and older patients should be reported separately when using the ELN classification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2012.43.4738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518729PMC
December 2012

Image cytometry-based detection of aneuploidy by fluorescence in situ hybridization in suspension.

Cytometry A 2012 Sep 26;81(9):776-84. Epub 2012 Jul 26.

Flow and Image Cytometry Laboratory, Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

Cytogenetic abnormalities are important diagnostic and prognostic criteria for hematologic malignancies. Karyotyping and fluorescence in situ hybridization (FISH) are the conventional methods by which these abnormalities are detected. The sensitivity of these microscopy-based methods is limited by the abundance of the abnormal cells in the samples and therefore these analyses are commonly not applicable to minimal residual disease (MRD) stages. A flow cytometry-based imaging approach was developed to detect chromosomal abnormalities following FISH in suspension (FISH-IS), which enables the automated analysis of several log-magnitude higher number of cells compared with the microscopy-based approaches. This study demonstrates the applicability of FISH-IS for detecting numerical chromosome aberrations, establishes accuracy, and sensitivity of detection compared with conventional FISH, and feasibility to study procured clinical samples of acute myeloid leukemia (AML). Male and female healthy donor peripheral blood mononuclear cells hybridized with combinations of chromosome enumeration probes (CEP) 8, X, and Y served as models for disomy, monosomy, and trisomy. The sensitivity of detection of monosomies and trisomies amongst 20,000 analyzed cells was determined to be 1% with a high level of precision. A high correlation (R(2) = 0.99) with conventional FISH analysis was found based on the parallel analysis of diagnostic samples procured from 10 AML patients with trisomy 8 (+8). Additionally, FISH-IS analysis of samples procured at the time of clinical remission demonstrated the presence of residual +8 cells indicating that this approach may be used to detect MRD and associated chromosomal defects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cyto.a.22101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384178PMC
September 2012

Monoallelic and biallelic deletions of 13q14.3 in chronic lymphocytic leukemia: FISH vs miRNA RT-qPCR detection.

Am J Clin Pathol 2012 Apr;137(4):641-6

Molecular Diagnostics Laboratory, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Deletion of 13q14.3 (del(13q)) is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL) and implies a favorable prognosis. We explored the feasibility of detecting del(13q) by real-time quantitative polymerase chain reaction (PCR) for miR-15a and miR-16-1, whose loci are located in the deleted region. We analyzed 23 cases of B-CLL with monoallelic (10 cases) or biallelic del(13q) (5 cases) and used trisomy 12-positive CLL samples (n = 8) as control samples. As expected, miR-15a was expressed at significantly lower levels in monoallelic del(13qx1) samples compared with trisomy 12 control samples (P = .001). Biallelic del(13q) (del(13qx2)) samples showed further reduction of miR-15a levels compared with monoallelic del(13q) (del(13qx1)) (P = .009). In contrast, miR-16-1 expression levels were generally much lower and variable, with the highest levels detected in del(13qx1). Analyzed retrospectively, miR-15a levels differ among the del(13q) groups. However, only del(13qx2) miR-15a levels are reduced enough to determine the allelic status of an individual sample prospectively by real-time quantitative PCR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1309/AJCPP31FSSRQTTAQDOI Listing
April 2012

Is obesity a prognostic factor for acute myeloid leukemia outcome?

Ann Hematol 2012 Mar 21;91(3):359-65. Epub 2011 Sep 21.

Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.

Obesity adversely affects outcome in pediatric acute lymphocytic leukemia and acute myeloid leukemia (AML). We asked if obesity, measured by body mass index (BMI), affected outcome in 329 adult AML patients treated with high-dose cytarabine and idarubicin-containing regimens administered according to actual body weight. Age ≥ 60, unfavorable karyotype, secondary AML, and positive smoking status had adverse impact on overall survival in a multivariate analysis, while BMI did not. We conclude that high BMI should not be a barrier to administer high-dose cytarabine-containing regimens for AML induction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-011-1319-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469945PMC
March 2012

The significance of quantifiable residual normal karyotype hematopoietic cells for toxicity and outcome.

Leuk Lymphoma 2011 Jun;52(6):943

Leukemia Section, Department of Medicine, Park Cancer Institute, Buffalo, NY 14263, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10428194.2011.580479DOI Listing
June 2011

Smoking adversely affects survival in acute myeloid leukemia patients.

Int J Cancer 2012 Mar 2;130(6):1451-8. Epub 2011 Aug 2.

Department of Medicine, Leukemia Section, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Smoking adversely affects hematopoietic stem cell transplantation outcome. We asked whether smoking affected outcome of newly diagnosed acute myeloid leukemia (AML) patients treated with chemotherapy. Data were collected on 280 AML patients treated with high-dose cytarabine and idarubicin-containing regimens at Roswell Park Cancer Institute who had smoking status data at diagnosis. Patients' gender, age, AML presentation (de novo vs. secondary), white blood cell (WBC) count at diagnosis, karyotype and smoking status (never vs. ever) were analyzed. Among the 161 males and 119 females with a median follow-up of 12.9 months, 101 (36.1%) had never smoked and 179 (63.9%) were ever smokers. The proportion of patients between never and ever smokers was similar to respect to age, AML presentation, WBC count at diagnosis or karyotype based on univariate analysis of these categorical variables. Never smokers had a significantly longer overall survival (OS) (60.32 months) compared to ever smokers (30.89; p = 0.005). In multivariate analysis incorporating gender, age, AML presentation, WBC count, karyotype and smoking status as covariates, age, karyotype and smoking status retained prognostic value for OS. In summary, cigarette smoking has a deleterious effect on OS in AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.26151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202035PMC
March 2012

Phase 1 study of arsenic trioxide, high-dose cytarabine, and idarubicin to down-regulate constitutive signal transducer and activator of transcription 3 activity in patients aged <60 years with acute myeloid leukemia.

Cancer 2011 Nov 31;117(21):4861-8. Epub 2011 Mar 31.

Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

Background: Constitutive activation of signal transducer and activator of transcription-3 (STAT3) was detected in blasts from approximately 50% of patients with acute myeloid leukemia (AML) and was correlated with an adverse outcome. In vitro treatment of AML blasts with arsenic trioxide (ATO) down-regulated STAT3 activity within 6 hours associated with a reduced viability within 48 hours.

Methods: A phase 1 clinical trial to evaluate the biologically effective dose and/or the maximally tolerated dose (MTD) of ATO in vivo in conjunction with high-dose cytarabine (Hidac) and idarubicin (Ida) in patients with AML aged <60 years was conducted. Data were compared with 117 historic AML patients who had received treatment with Hidac/Ida.

Results: In total, 61 patients were enrolled onto 11 different dose levels (from 0.01 to 0.65 mg/kg ideal body weight). The MTD was 0.5 mg/kg. Compared with historic controls, patients who received ATO/Hidac/Ida, although they had similar pretreatment characteristics, had better overall survival (P = .039).

Conclusions: ATO priming may have improved the outcome of patients aged <60 years with AML who received Hidac/Ida. The current data suggested that ATO may enhance the effect of chemotherapy. The authors concluded that further studies of this novel combination are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.26097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129468PMC
November 2011

Myeloid blastic transformation of myeloproliferative neoplasms--a review of 112 cases.

Leuk Res 2011 May 19;35(5):608-13. Epub 2010 Aug 19.

Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.

Blastic transformation of myeloproliferative neoplasms (MPN) is still poorly understood. We describe a cohort of 23 Roswell Park Cancer Institute (RPCI) patients and 89 additional cases from the English literature for whom biologic features were described. We initially compared our 23 patients to the 89 cases from the literature. Our population had significantly less patients with prior history of polycythemia vera (PV), shorter time from MPN diagnosis to blastic transformation, <3 prior therapies, more frequent use of hydroxyurea and erythropoietin and less frequent use of alkylating agents. Interestingly, the overall survival of the two cohorts from the time of blastic transformation was similar. We therefore looked at the outcome of the entire cohort (n=112). Patients with prior history of essential thrombocythemia survived longer than patients with prior history of myelofibrosis or PV. Further, patients with <3 prior therapies, those who lacked complex karyotype and those <60 year old at MPN diagnosis had significantly longer survival. Among the PRCI population, 20/23 patients underwent induction treatment with cytarabine and an anthracycline containing regimens; 12 achieved remission and their overall survival was significantly longer than those who did not. Three patients underwent an allogeneic transplantation and their survival was significantly longer than those who did not. Patients with <3 prior therapies, those who lack complex karyotype and those <60 at MPN diagnosis have longer survival following blastic transformation. Finally, allogeneic transplantation represents the only chance for long-term survival in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2010.07.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017628PMC
May 2011

A GOG 210 aCGH study of gain at 1q23 in endometrioid endometrial cancer in the context of racial disparity and outcome.

Genes Chromosomes Cancer 2010 Sep;49(9):791-802

Division of Molecular Pathology, Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

The goal of this study was to identify recurrent regions of genomic gain or loss in endometrial cancer of the endometrioid type in the context of racial disparities in mortality for this disease. Array comparative genomic hybridization (aCGH) analysis was performed on 80 frozen primary tumors from the Gynecologic Oncology Group (GOG)-210 bank using the RPCI 19K BAC arrays. The 80 patients included 20 African American (AA) Stage I, 20 White (W) Stage I, 20 African American (AA) Stage IIIC/IV, and 20 White (W) Stage IIIC/IV. A separate subset of 220 endometrial cancers with outcome data was used for validation. A 1.6-Mbp region of gain at 1q23 was identified by aCGH in all AA patients and high grade W patients, but not W low grade patients. In the validation arm of 220 patients copy number gain at this region was validated using FISH and locus specific BACs. The number of AA patients in the validation arm was too small to confirm the aCGH association with racial disparity. Kaplan-Meier curves for survival showed a significant difference for gain at 1q23 versus no gain (log rank P = 0.0014). When subdivided into various groups of risk by stage and grade the survival curves showed a decreased survival for high grade and/or stage tumors, but not for low grade and/or stage endometrioid tumors. Univariate analyses for gain at 1q23 showed a significant association (P = 0.009) with survival. Multivariate analysis for gain at 1q23 did not show a significant association with survival (P = 0.14).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gcc.20782DOI Listing
September 2010

Efficacy of lenalidomide in patients with chronic lymphocytic leukemia with high-risk cytogenetics.

Leuk Lymphoma 2010 Jan;51(1):85-8

Department of Medicine, Roswell Park Cancer Institute, NY 14263, USA.

Patients with chronic lymphocytic lymphoma (CLL) with high-risk cytogenetics [del(11q)(q22.3) or del(17p)(p13.1)] have limited therapeutic options and their prognosis remains poor. This analysis was conducted to determine the clinical activity of lenalidomide in patients with high-risk disease. Relapsed/refractory patients with CLL enrolled in a phase II clinical trial who had del(11q)(q22.3) or del(17p)(p13.1) were included in this analysis. Patients received single agent lenalidomide for 21 days of the 4 week treatment cycle. The overall response rate among patients with high-risk cytogenetics was 38%, with 19% of patients achieving a complete response. Median progression-free survival was 12.1 months, which is higher than demonstrated with other agents in comparable patient populations. In addition, the estimated 2-year survival probability was 58%, demonstrating that the responses achieved with lenalidomide are durable, even in patients with CLL with high-risk disease with poor risk cytogenetics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10428190903406806DOI Listing
January 2010

Treating octogenarian and nonagenarian acute myeloid leukemia patients--predictive prognostic models.

Cancer 2009 Jun;115(11):2472-81

Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

Background: Treating the octogenarian and nonagenarian patients who have acute myeloid leukemia (AML) with intensive chemotherapy is controversial. Several models to predict outcome were proposed, including the use of a comorbidity index. However, it is unclear whether the Charlson comorbidity index (CCI) or the hematopoietic cell transplant comorbidity index (HCTCI) is more sensitive.

Methods: The authors analyzed their experience with 92 patients aged >or=80 years who had AML. Patients' pretreatment characteristics and their treatment outcomes were recorded.

Results: All patients were offered intensive treatment; 59 patients (64%) were treated intensively with a variety of regimens, whereas 33 patients (36%) elected to receive supportive care. The CCI and the HCTCI had similar predictive ability for outcome in both groups. A multivariate analyses of prognostic factors identified near-normal albumin (48% of patients; 1-year survival rate, >27%) as a favorable factor for the whole cohort, age <83 years (47% of patients; 1-year survival rate, >25%) and nonmonocytic morphology (75% of patients; 1-year survival rate, >26%) as favorable factors for the intensively treated cohort, and bone marrow blasts <46% (50% of patients; 1-year survival rate, >19%) as a favorable factor for patients who received supportive care.

Conclusions: This retrospective analysis was developed to assist in treatment decisions for octogenarian and nonagenarian patients with AML. The findings will need validation in a prospective study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.24285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688783PMC
June 2009

Metachronous and synchronous presentation of acute myeloid leukemia and lung cancer.

Leuk Res 2009 Sep 31;33(9):1208-11. Epub 2009 Jan 31.

Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Smoking is associated with both acute myeloid leukemia (AML) and lung cancer. We therefore searched our database for concomitant presentation of AML and lung cancer. Among 775 AML cases and 5225 lung cancer cases presenting to Roswell Park Cancer Institute between the years January 1992 and May 2008 we found 12 (1.5% of AML cases; 0.23% of lung cancer cases) cases (seven metachronous and five synchronous) with AML and lung cancer. All but one patient were smokers. There were no unique characteristic of either AML or lung cancer in these patients. Nine patients succumbed to AML, one died from an unrelated cause while undergoing treatment for AML, one died of lung cancer and one patient is alive after allogeneic transplantation for AML. In summary, this study supports the need for effective smoking cessation programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2008.12.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749654PMC
September 2009

Central review of cytogenetics is necessary for cooperative group correlative and clinical studies of adult acute leukemia: the Cancer and Leukemia Group B experience.

Int J Oncol 2008 Aug;33(2):239-44

Division of Hematology and Oncology and the Comprehensive Cancer Center, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH 43210-1228, USA.

The Cancer and Leukemia Group B has performed central review of karyotypes submitted by institutional cytogenetics laboratories from patients with acute myeloid (AML) and acute lymphoblastic (ALL) leukemia since 1986. We assessed the role of central karyotype review in maintaining accurate, high quality cytogenetic data for clinical and translational studies using two criteria: the proportion of karyotypes rejected (i.e. inadequate), and, among accepted (i.e. adequate) cases, the proportion of karyotypes whose interpretation was changed on central karyotype review. We compared the first four years during which central karyotype review was performed with a recent 4-year period and found that the proportion of rejected samples decreased significantly for both AML and ALL. However, during the latter period, central karyotype reviews still found 8% of AML and 16% of ALL karyotypes inadequate. Among adequate cases, the karyotype was revised in 26% of both AML and ALL samples. Some revisions resulted in changing the patients' assignment to particular World Health Organization diagnostic categories and/or moving patients from one prognostic group to another. Overall, when both data on rejection rates and data on karyotype revisions made in accepted cases were considered together, 32% of AML and 38% of ALL samples submitted were either rejected or revised on central karyotype review during the recent 4-year period. These data underscore the necessity of continued central karyotype review in multi-institutional cooperative group studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607284PMC
August 2008

Therapy-related myelodysplastic syndrome and acute myeloid leukemia following treatment of acute myeloid leukemia: possible role of cytarabine.

Leuk Res 2008 Jul 21;32(7):1043-8. Epub 2008 Feb 21.

Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, United States.

Therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/t-AML) have been reported only rarely following treatment of AML. We report five patients treated for de novo AML who developed t-MDS/t-AML, all with chromosome 7 abnormalities, including -7, del(7)(q22q36) and del(7)(p11.22p22). All had been treated with cytarabine, topoisomerase 2 inhibitors and granulocyte or granulocyte-monocyte colony-stimulating factor and three with alkylating agents as part of autologous transplant regimens. These cases further document t-MDS/t-AML as a complication of therapy for AML. Presence of chromosome 7 abnormalities in patients with and without prior alkylating agent therapy suggests possible association with the antimetabolite cytarabine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2007.11.006DOI Listing
July 2008

Unsuspected Klinefelter syndrome diagnosed during oncologic evaluation: a case series.

J Am Board Fam Pract 2005 Mar-Apr;18(2):132-9

Division of Cancer Prevention & Population Sciences, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Klinefelter syndrome is an underdiagnosed chromosomal disorder that has significant implications for health and for medical management. This report presents 5 adult male patients diagnosed with previously unsuspected Klinefelter syndrome as a result of cytogenetic testing for suspected hematologic malignancies. This case series highlights the importance of maintaining a comprehensive and holistic approach to medical care. The medical, genetic, and psychosocial implications of the Klinefelter diagnosis are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3122/jabfm.18.2.132DOI Listing
August 2005

Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype: a cancer and leukemia group B study.

J Clin Oncol 2005 Jan 8;23(3):482-93. Epub 2004 Nov 8.

Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, A433A Starling-Loving Hall, 320 W Tenth Avenue, Columbus, OH 43210, USA.

Purpose: Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML).

Patients And Methods: In 490 patients, induction included cytarabine and daunorubicin (AD) or cytarabine and escalated doses of daunorubicin and etoposide +/- PSC-833 (ADE/ADEP). Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV).

Results: Of 350 patients receiving AD, 73% achieved complete remission (CR), compared with 82% of 140 receiving ADE/ADEP (P = .04). Splenomegaly was associated with a lower CR rate (P < .001), and ADE/ADEP, with a higher CR rate in younger patients (P = .005). The 5-year disease-free survival (DFS) rate was 28% each for intensification groups I and II, compared with 41% and 45% for groups III and IV, respectively (P = .02). The 5-year cumulative incidence of relapse (CIR) was 62% and 67% for groups I and II, respectively, compared with 54% and 44% for groups III and IV, respectively (P = .049). The type of postremission intensification remained significant for DFS and CIR in multivariable analysis.

Conclusion: In younger adults with normal cytogenetics AML, splenomegaly predicts a lower CR rate, and the postremission strategies of either four cycles of I/HDAC or one cycle of HDAC/etoposide followed by ASCT are associated with improved DFS and reduced relapse compared with therapies that include fewer cycles of cytarabine or no transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2005.06.090DOI Listing
January 2005

Extra copies of chromosome 2 are a recurring aberration in ALK-negative lymphomas with anaplastic morphology.

Mod Pathol 2005 Feb;18(2):235-43

Department of Pathology, Buffalo General Hospital, The State University of New York, Buffalo, NY, USA.

The purpose of this study was to evaluate fluorescence in situ hybridization abnormalities of the 2p23 anaplastic lymphoma kinase (ALK) gene loci in lymphomas with anaplastic morphology. We studied 24 anaplastic large cell lymphomas (ALCL) classified by World Health Organization criteria [17 primary nodal/systemic (10 ALK+, 7 ALK-), seven primary cutaneous], and 17 additional non-Hodgkin's lymphomas [one ALK+ B-lineage lymphoma, 14 ALK- diffuse large B-cell lymphomas (seven anaplastic variants, five nonanaplastic, two secondary CD30+), two follicular lymphomas]. ALK- lymphomas with anaplastic morphology showed extra nonrearranged anaplastic lymphoma kinase gene loci (P=0.004) due to trisomy 2 irrespective of the following factors: B or T/null phenotype (P=0.315), diagnostic categories of systemic or cutaneous ALCL or the above-mentioned B-cell lymphomas (P=0.131), and CD30 positivity by immunohistochemistry (P=1.000). Trisomy 2 was absent in all ALK+ lymphomas (P=0.009), which showed rearranged ALK gene loci (P<0.001). Whether trisomy 2 is a primary or secondary event that leads to ALK- lymphomas cannot be determined from this study. Its presence in secondary B-cell lymphomas suggests that trisomy 2 may be a secondary cytogenetic aberration in lymphomas in general. Further investigation of this finding is necessary to further our understanding of the heterogeneous group of ALK- lymphomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/modpathol.3800299DOI Listing
February 2005

Precursor B lymphoblastic leukemia with surface light chain immunoglobulin restriction: a report of 15 patients.

Am J Clin Pathol 2004 Apr;121(4):512-25

Department of Pathology, Buffalo General Hospital, the State University of New York at Buffalo, USA.

We describe 15 patients (9 children) with precursor B-cell (pB) acute lymphoblastic leukemia (ALL) with surface immunoglobulin (sIg) light chain restriction revealed by flow cytometric immunophenotyping (FCI). The same sIg+ immunophenotype was present at diagnosis and in 3 relapses in 1 patient. In 15 patients, blasts were CD19+ CD10+ (bright coexpression) in 14, CD34+ in 12, surface kappa+ in 12, surface lambda+ in 3; in 8 of 8, terminal deoxyribonucleotidyl transferase (TdT)+; and in 4, surface IgD+ in 2 and surface IgM+ in 1. The 3 CD34- cases included 1 TdT+ case, 1 with t(1;19)(q23;p13), and 1 infant with 70% marrow blasts. One adult had CD10- CD19+ CD20- CD22+ CD34+ TdT+ sIg+ blasts with t(2;11)(p21;q23). Blasts were L1 or L2 in all cases (French-American-British classification). Karyotypic analysis in 12 of 12 analyzable cases was negative for 8q24 (myc) translocation. Karyotypic abnormalities, confirmed by fluorescence in situ hybridization in 6 cases, included hyperdiploidy, t(1;19)(q23;p13), t(12;21)(p13;q22), t(9;22)(q34;q11), t(2;11)(p21;q23), and trisomy 12. The sIg light chain restriction in pB ALL might be present in neoplasms arising from the early, intermediate, and late stages of precursor B-cell maturation; sIg light chain restriction revealed by FCI does not necessarily indicate a mature B-cell phenotype, further emphasizing the importance of a multidisciplinary approach to diagnosing B-lymphoid neoplasms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1309/WTXC-Q5NR-ACVX-TYBYDOI Listing
April 2004

Massive hyperdiploidy and tetraploidy in acute myelocytic leukemia and myelodysplastic syndrome.

Cancer Genet Cytogenet 2004 Jan;148(1):29-34

Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.

Massive hyperdiploidy (>50 chromosomes) and tetraploidy (4n) are rare cytogenetic abnormalities in myelocytic malignancies, and their significance is unknown. We report on 11 patients with acute myelocytic leukemia (AML) and two patients with a myelodysplastic syndrome (MDS) with massive hyperdiploidy (10 patients) or tetraploidy (3 patients) seen at our institution over a 12-year period. Eleven patients were male and two were female. Age range was 44-84 years (median, 70 years). Only one AML patient had a previous MDS, and no patient had therapy-related disease. One or more copies of chromosomes 8 and 19 were gained in eight patients each; other frequently gained chromosomes included 13, 15, and 21. Eight patients had structural abnormalities in addition to chromosome gain; del(5q) was most common (five patients). Eleven patients received induction chemotherapy, but only four achieved complete remission. Survival ranged from 1 to 22 months, with a median of 6 months. We conclude that massive hyperdiploidy and tetraploidy are infrequent abnormalities in AML and MDS, are seen primarily in de novo disease in older male patients and are associated with a low remission rate and short survival. Massive hyperdiploidy and tetraploidy define a prognostically unfavorable cytogenetic group in de novo AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0165-4608(03)00214-0DOI Listing
January 2004

Rare recurring balanced chromosome abnormalities in therapy-related myelodysplastic syndromes and acute leukemia: report from an international workshop.

Genes Chromosomes Cancer 2002 Apr;33(4):401-12

Clinical Cytogenetics Laboratory, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

Seventy-seven patients were identified with Rare recurring (excluding 11q23, 21q22, inv(16), and t(15;17)) chromosome abnormalities among 511 patients with treatment-related myelodysplastic syndromes and acute leukemia accepted from centers in the United States, Europe, and Japan. The abnormality subsets included 3q21q26 (17 patients), 11p15 (17 patients), t(9;22)(q34;q11) (10 patients), 12p13 (9 patients), t(8;16)(p11;p13) (9 patients), and an "other" subset, which included t(6;9)(p23;q34) (3 patients), t(10;11)(p13;q13 approximately q21) (3 patients), t(1;17)(p36;q21) (2 patients), t(8;14)(q24;q32) (2 patients), t(11;19)(q13;q13) (2 patients), t(1;3)(p36;q21) (2 patients), and t(3;5)(q21;q31) (1 patient). Increased karyotypic complexity with additional balanced and unbalanced rearrangements was observed in 70% of cases. Among 54 cases with secondary abnormalities, chromosome 5 and/or 7 abnormalities were observed in 59%. The most frequent primary diseases were breast cancer (24 cases), Hodgkin disease (14 cases), non-Hodgkin lymphoma (10 cases), and de novo ALL (5 cases). Thirty-seven patients received alkylating agents plus topoisomerase II inhibitors with or without radiation therapy. The presenting diagnosis was t-AML in 47 cases, t-MDS in 23 cases (10 progressed to t-AML), and t-ALL in seven cases, five of whom had a t(9;22). The median latency time from initiation of original therapy to therapy-related disease diagnosis was quite long (69 months), and the overall median survival from the date of therapy-related disease diagnosis was very short (7 months). The 1-year survival rate was 34 +/- 7%, with no significant differences among subsets. Comparison with previously reported cases showed increased karyotypic complexity and adult presentation of pediatric-associated chromosome abnormalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gcc.10044DOI Listing
April 2002

Genomic instability measurement in the diagnosis of thyroid neoplasms.

Head Neck 2002 Mar;24(3):290-5

Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, New York, USA.

Background: Clinically palpable thyroid nodules are present in approximately 10% of the population, although only 5% to 7% of these nodules harbor malignancy. Fine-needle aspiration has become one of the central tools in the diagnostic armamentarium of the surgeon/endocrinologist. There is, however, up to a 30% indeterminate diagnostic rate associated with this technique, resulting in unnecessary surgical interventions for patients harboring benign disease. A second issue of clinical importance is the unreliability of predicting outcomes based either on histologic findings alone or in combination with clinical staging. To address these diagnostic and clinical shortcomings, we have used measurement of genomic instability as a diagnostic and prognostic indicator for thyroid neoplasms.

Methods: Genomic instability of thyroid tissue samples was determined by inter-(simple sequence repeat) PCR, microsatellite instability analysis, and fluorescence in situ hybridization (FISH) on thyroid neoplasms from 22 patients.

Results: Inter-(simple sequence repeat) PCR detected genomic instability with an index range 0% to 1.9% (mean, 0.56%) in patients with benign disease, whereas in patients with malignant histologic findings the values ranged from 0% to 6.6% (mean, 2.9%). This difference between benign and malignant values was statistically significant (p =.004). There was no demonstrable microsatellite instability or loss of heterozygosity for six markers examined in this group. Losses of chromosomes 17 and X in benign disease and gains of chromosomes 7, 12, 17, and X in Hurthle cell carcinoma were observed, although not at a significant rate.

Conclusions: Genomic instability as measured by inter-(simple sequence repeat) PCR was significantly higher for malignant diseases compared with benign thyroid tissues, but no such association was seen with aneuploidy or microsatellite instability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.10050DOI Listing
March 2002