15 research outputs found
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Cytogenetic Classification Systems and Overall Survival Following Bone Marrow Transplant (BMT) for Acute Myelogenous Leukemia (AML)
Abstract
Risk-adapted therapy for AML in first complete remission generally calls for allogeneic BMT for patients with poor risk cytogenetics. However, poor risk cytogenetics is defined differently in commonly-applied classification schemes. We hypothesized that differences in cytogenetic classification might result in differences in survival after BMT. From September 1991 to December 2003, we treated 47 patients with AML in first complete remission with high-dose busulfan-containing preparative regimens and an HLA-matched sibling BMT. The median age was 42 years (range 18 to 60). At the time of diagnosis, 35 patients had either a normal karyotype or at least one clonal abnormality. Cytogenetic analysis was unavailable for the other 12 patients. The 47 patients were then classified according to the SWOG/ECOG (Blood96:4075, 2000), MRC (Blood92:2322, 1998), or CALGB (Blood100:4325, 2002) cytogenetic classification systems and analyzed for overall survival. With a median follow-up of 4.9 years, 3 year overall survival for various cytogenetic risk groups are displayed in the table:
SWOG/ECOG CALGB MRC Intermediate risk 69% 63% 74% Poor risk 43% 42% 18% Unknown risk 45% 52% 45%
Concordance indices were 0.58 for CALGB, 0.60 for SWOG, and 0.66 for MRC, demonstrating a slight superiority of the MRC system. Consistent with reports of large, prospective randomized trials of BMT for AML in first remission, patients with poor risk cytogenetics have worse overall survival compared to patients with intermediate risk cytogenetics. Overall survival appears to be different for patients classified as poor risk by MRC criteria. Larger, prospective studies are needed to confirm this observation, but our results suggest that standardized, international cytogenetic risk criteria are needed to develop risk-adapted strategies for the treatment of AML
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FISH and SNP-Array Karyotyping Improve the Detection of Recurrent Chromosomal Defects Including Del(5q), Monosomy 7, Del(7q), Trisomy 8, and Del(20q) in Myelodysplastic Syndromes
Abstract
Cytogenetic aberrations identified by conventional metaphase cytogenetics (MC) have an important diagnostic and prognostic role in evaluating patients with myelodysplastic syndromes (MDS), and results can affect the choice of therapy. Fluorescence in situ hybridization (FISH) can complement MC by providing information derived from both interphase and metaphase nuclei. However, clinically practical FISH strategies are limited to detection of the most common lesions in MDS, including −5/del(5q), −7/del(7q), del(20q), and trisomy 8. The ability to obtain informative results from interphase nuclei and the relative ease of scoring greater numbers of cells are advantages of FISH as compared to MC. Still, the clinical relevance of small numbers of abnormal cells, apart from detection of residual disease, remains unclear. Single nucleotide polymorphism array (SNP-A)-based karyotyping can reveal genetically unbalanced defects with superior resolution compared to MC and FISH, as well as identify segmental uniparental disomy (UPD) that cannot be detected by either method. We sought to determine whether the overall diagnostic yield for detecting common recurring genetic defects associated with MDS could be improved using a strategy incorporating MC, FISH and SNP-A. Using a standardized approach, we focused our investigation on detection of −5/del(5q), −7/del(7q), trisomy 8, and del(20q). We studied 62 patients, including 42 MDS, 5 MDS/MPD, and 15 secondary AML, with standard MC, FISH probes for chromosomes 5, 7, 8, and 20, and SNP-A karyotyping using Affymetrix 250K and/or 6.0 SNP array platform. The detection rate for del(5q) was 35%, 35%, and 37% by MC, FISH, and SNP-A, respectively. No single method detected all of the defects, and detection rates improved when results of all methods were combined. For example, the rate for detection of del(5q) increased incrementally to 39% (MC+FISH), 44% (MC+SNP-A), 42% (FISH+SNP-A), and 44% when all 3 methods were applied. Similar findings were observed for −7/del(7q), trisomy 8, and −20/del(20q): after combining all methods the detection rates improved from 8% to 17%, from 10% to 17%, and from 8% to 10%, respectively, as compared with MC alone. Discrepant results among these methods were related to poor growth (N=2) and low percentage of positive metaphases (small clonal size; N=2). In addition, small somatic deletions (N=6) and UPD (N=2) were not detected by MC or FISH. Larger defects that were detected by SNP-A (e.g., from 5q14.2 to 5q23.1) did not overlap with either loci 5p15.2 (D5S630) or 5q31 (EGR1) used in the FISH probes. We conclude that metaphase cytogenetics, interphase FISH, and SNP-A are complementary techniques that, when applied and interpreted together, can improve the diagnostic yield for identifying genetic lesions in MDS. SNP-A allows for identification of topographically smaller defects and copy-neutral loss of heterozygosity without a requirement for successful cytogenetic analysis. While FISH affords the ability to quantitate the number of affected cells, it is only useful to screen for specific, known defects of a certain size. Whether novel defects as identified by FISH or SNP-A karyotyping will have prognostic impact or affect the results of therapy is the subject of ongoing investigation
FISH and SNP-A karyotyping in myelodysplastic syndromes: Improving cytogenetic detection of del(5q), monosomy 7, del(7q), trisomy 8 and del(20q)
Cytogenetic aberrations identified by metaphase cytogenetics ( MC) have important diagnostic, prognostic and therapeutic roles in myelodysplastic syndromes (MDS). Fluorescence in situ hybridization ( FISH) complements MC by the ability to evaluate large numbers of both interphase and metaphase nuclei. However, clinically practical FISH strategies are limited to detection of known lesions. Single nucleotide polymorphism array (SNP-A)-based karyotyping can reveal unbalanced defects with superior resolution over MC and FISH and identify segmental uniparental disomy (UPD) undetectable by either method. Using a standardized approach, we focused our investigation on detection of -5/del(5q), -7/del(7q), trisomy 8 and del(20q) in patients with MDS (N=52), MDS/myeloproliferative overlap syndromes (N=7) and acute myeloid leukemia (N=15) using MC, FISH and SNP-A karyotyping. The detection rate for del(5q) was 30, 32 and 32% by MC, FISH, and SNP-A, respectively. No single method detected all defects, and detection rates improved when all methods were used. The rate for detection of del(5q) increased incrementally to 35% (MC+FISH), 38% (MC+SNP-A), 38% (FISH+SNP-A) and 39% (all three methods). Similar findings were observed for-7/del(7q), trisomy 8 and-20/del(20q). We conclude that MC, FISH and SNP-A are complementary techniques that, when applied and interpreted together, can improve the diagnostic yield for identifying genetic lesions in MDS and contribute to the better description of abnormal karyotypes. (C) 2009 Elsevier Ltd. All rights reserved
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A Psychosocial Assessment of Patients before and after Autologous Stem Cell Transplantation
Abstract
There are relatively few reports in the medical literature describing psychosocial assessment of bone marrow transplant patients; what data exists primarily focuses on allogeneic transplant recipients. We have begun to prospectively assess psychosocial parameters of patients undergoing autologous transplantation using the Functional Assessment of Cancer Therapy-BMT (FACT-BMT) tool. The general questions consist of four subscales developed and normed in cancer patients that measure; physical well-being; social/family well-being; emotional well-being; functional well-being; and a specific module to address BMT-specific concerns. Each subscale is positively scored, with higher scores indicating better functioning. A baseline survey is collected by the social worker pre-transplant and a follow-up survey is administered and collected approximately 6 weeks post-transplant by the Transplant Coordinator. 56 consecutive patients undergoing autologous stem cell transplant have FACT-BMT data both pre-transplant and approximately one month post-discharge. Median age was 50. 52% are male; underlying diagnoses include NHL (45%), Hodgkin’s disease (32%), myeloma (16%), AML (5%), testicular cancer (2%). 93% had chemosensitive disease at the time of transplant. All patients received peripheral blood progenitor cells (PBPCs), and all received a chemotherapy-only preparative regimen. All patients were hospitalized for approximately three weeks for the transplant. For most of the variables measured by the FACT-BMT tool, there was no significant difference in pre-transplant and post-transplant scores. The one variable that did change was emotional well-being: patients scored statistically significantly higher post-transplant as compared to the pre-transplant score (p<0.001). We also have collected baseline FACT-BMT data on 42 consecutive allogeneic BMT recipients, as well as 12 recipients of non-myeloablative allogeneic BMT transplants. There is no significant difference in any pre-transplant variables measured by the FACT-BMT score between autologous recipients, ablative allogeneic recipients, and non-myeloablative allogeneic recipients. We conclude that patients undergoing an autologous stem cell transplant have a higher sense of emotional well-being after engraftment and hospital discharge. Presumably this reflects positive feelings about accomplishing this intensive treatment for their underlying malignancy, and suggests that emotional and physical recovery after auto-BMT is reasonably rapid. A larger dataset will hopefully allow a more detailed comparison of allo and auto BMT recipients
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Psychosocial Factors in Decision-Making of Patient Eligibility for Allogeneic Bone Marrow Transplantation
Abstract
Oncologists specializing in bone marrow transplants (BMT) make daily decisions about appropriate medical candidates for allogeneic BMT based on clinical criteria. It is not clear how, and if, patient eligibility decisions are made based on psychosocial criteria. Although setting limits of patient eligibility based on psychosocial criteria has been researched in solid organ transplantation, data is sparse in BMT. This report focuses on physician responses to a psychosocial survey. An IRB approved survey was mailed to members of the ASBMT (North America) mailing list. Of 704 members, 663 were deemed viable respondents: excluded were non-physician members and physicians specializing in research or not working with allogeneic BMT patients. These surveys were mailed in April 2004. As of 7/6/04, 253 surveys were returned, representing a 38% response rate. Average age of responders was 47 years. Average number of years experience in BMT was 14, with a range of 2–39 years. 17 case vignettes were presented. These vignettes asked whether or not it was appropriate to proceed with allo BMT (assuming an appropriate donor was available) based on a specific psychosocial problem. In virtually every case vignette, at least 10% of respondents stated they would not proceed with allogeneic BMT based on the issues raised in the vignette. In seven case vignettes, the majority of respondents stated that they would recommend not proceeding with BMT. The general theme/construct of these 7 vignettes appears to be ability to comply with treatment plans. Specifically, the following were case vignettes in which the majority of respondents recommended not to proceed with transplant: no caregiver available to assist with the patient post-transplant (do not proceed = 70%); the patient is actively alcoholic (do not proceed = 62%); the patient is non-compliant (do not proceed = 75%); the patient is currently suicidal (do not proceed = 84%); the patient is currently using addictive illicit drugs (do not proceed = 73%); the patient has mild dementia (do not proceed = 55%); the patient cannot pay for the transplant (do not proceed = 52%). Conversely, the following case vignettes were less worrisome to the survey respondents, and in general represented surmountable psychosocial and/or clinical issues. These vignettes included; a history of prior suicidal attempts although not currently suicidal (proceed with transplant = 86%); controlled schizophrenia (proceed with transplant = 83%); daily marijuana use (proceed with transplant = 82%); smokes tobacco (proceed with transplant = 79%); morbid obesity (proceed with transplant = 71%); major depression (proceed with transplant = 84%). These findings underline the importance of post-transplant longitudinal care in determining the ultimate success of an allogeneic BMT, and underscore their importance in patient eligibility decision-making. These findings also illustrate that psychosocial variables play a significant role in determining patient eligibility for allogeneic BMT and that there is no clear-cut consensus on this topic, highlighting the need for ongoing clinical research