14 results on '"Rizzo, J. Douglas"'
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2. Significant Improvement in Survival After Allogeneic Hematopoietic Cell Transplantation During a Period of Significantly Increased Use, Older Recipient Age, and Use of Unrelated Donors.
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Hahn, Theresa, McCarthy Jr., Philip L., Hassebroek, Anna, Bredeson, Christopher, Gajewski, James L., Hale, Gregory A., Isola, Luis M., Lazarus, Hillard M., Lee, Stephanie J., LeMaistre, Charles F., Loberiza, Fausto, Maziarz, Richard T., Rizzo, J. Douglas, Joffe, Steven, Parsons, Susan, and Majhail, Navneet S.
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- 2013
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3. American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin in Adult Patients With Cancer.
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Rizzo, J. Douglas, Brouwers, Melissa, Hurley, Patricia, Seidenfeld, Jerome, Somerfield, Mark R., and Temin, Sarah
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GUIDELINES , *DRUG administration , *ONCOLOGY , *HEMATOLOGY , *CANCER treatment , *MORTALITY , *THROMBOEMBOLISM risk factors , *DRUG efficacy , *ANEMIA treatment , *MEDICAL societies , *SOCIETIES - Abstract
The article offers information on the American Society of Clinical Oncology (ASCO)/American Society of Hematology Clinical Practice Guidelines Update on the Use of Epoetin and Darbepoetin in Adult Patients with Cancer. It says that the 2010 guideline update concerns the issue of using erythropoiesis-stimulating agents (ESA) in treating cancer which reportedly increases mortality and increases the risk of thromboembolism. However, it adds that there are no studies comparing epoetin and darbepoetin, and thus Update Committee still consider its use in cancer-related events as well as in chemotherapy-induced anemia. Moreover, it mentions that several ESAs have been limited to patients who undergo certain types of therapies, while other previous recommendation guidelines have not been changed.
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- 2010
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4. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update.
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Rizzo JD, Somerfield MR, Hagerty KL, Seidenfeld J, Bohlius J, Bennett CL, Cella DF, Djulbegovic B, Goode MJ, Jakubowski AA, Rarick MU, Regan DH, Lichtin AE, American Society of Clinical Oncology, Rizzo, J Douglas, Somerfield, Mark R, Hagerty, Karen L, Seidenfeld, Jerome, Bohlius, Julia, and Bennett, Charles L
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- 2008
5. Long-term survival and late deaths after allogeneic hematopoietic cell transplantation.
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Wingard JR, Majhail NS, Brazauskas R, Wang Z, Sobocinski KA, Jacobsohn D, Sorror ML, Horowitz MM, Bolwell B, Rizzo JD, and Socié G
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- Adolescent, Adult, Age Factors, Aged, Cause of Death, Child, Child, Preschool, Female, Follow-Up Studies, Graft vs Host Disease epidemiology, Hematologic Diseases surgery, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Infant, Male, Middle Aged, Risk Factors, Transplantation, Homologous, Young Adult, Hematopoietic Stem Cell Transplantation mortality
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Purpose: Allogeneic hematopoietic cell transplantation (HCT) is curative but is associated with life-threatening complications. Most deaths occur within the first 2 years after transplantation. In this report, we examine long-term survival in 2-year survivors in the largest cohort ever studied., Patients and Methods: Records of 10,632 patients worldwide reported to the Center for International Blood and Marrow Transplant Research who were alive and disease free 2 years after receiving a myeloablative allogeneic HCT before 2004 for acute myelogenous or lymphoblastic leukemia, myelodysplastic syndrome, lymphoma, or severe aplastic anemia were reviewed., Results: Median follow-up was 9 years, and 3,788 patients had been observed for 10 or more years. The probability of being alive 10 years after HCT was 85%. The chief risk factors for late death included older age and chronic graft-versus-host disease (GVHD). For patients who underwent transplantation for malignancy, relapse was the most common cause of death. The greatest risk factor for late relapse was advanced disease at transplantation. Principal risk factors for nonrelapse deaths were older age and GVHD. When compared with age, sex, and nationality-matched general population, late deaths remained higher than expected for each disease, with the possible exception of lymphoma, although the relative risk generally receded over time., Conclusion: The prospect for long-term survival is excellent for 2-year survivors of allogeneic HCT. However, life expectancy remains lower than expected. Performance of HCT earlier in the course of disease, control of GVHD, enhancement of immune reconstitution, less toxic regimens, and prevention and early treatment of late complications are needed.
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- 2011
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6. Reducing the risk for transplantation-related mortality after allogeneic hematopoietic cell transplantation: how much progress has been made?
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Horan JT, Logan BR, Agovi-Johnson MA, Lazarus HM, Bacigalupo AA, Ballen KK, Bredeson CN, Carabasi MH, Gupta V, Hale GA, Khoury HJ, Juckett MB, Litzow MR, Martino R, McCarthy PL, Smith FO, Rizzo JD, and Pasquini MC
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- Adult, Analysis of Variance, Cohort Studies, Disease-Free Survival, Female, Follow-Up Studies, Forecasting, Graft Rejection, Graft Survival, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Humans, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute surgery, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Reference Values, Retrospective Studies, Risk Assessment, Survival Analysis, Tissue Donors, Transplantation Conditioning methods, Transplantation, Homologous adverse effects, Transplantation, Homologous mortality, Treatment Outcome, Young Adult, Cause of Death, Hematopoietic Stem Cell Transplantation mortality, Leukemia, Myeloid, Acute mortality, Transplantation Conditioning mortality
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Purpose: Transplantation-related mortality (TRM) is a major barrier to the success of allogeneic hematopoietic cell transplantation (HCT)., Patients and Methods: We assessed changes in the incidence of TRM and overall survival from 1985 through 2004 in 5,972 patients younger than age 50 years who received myeloablative conditioning and HCT for acute myeloid leukemia (AML) in first complete remission (CR1) or second complete remission (CR2)., Results: Among HLA-matched sibling donor transplantation recipients, the relative risks (RRs) for TRM were 0.5 and 0.3 for 2000 to 2004 compared with those for 1985 to 1989 in patients in CR1 and CR2, respectively (P < .001). The RRs for all causes of mortality in the latter period were 0.73 (P = .001) and 0.60 (P = .005) for the CR1 and CR2 groups, respectively. Among unrelated donor transplantation recipients, the RRs for TRM were 0.73 (P = .095) and 0.58 (P < .001) for 2000 to 2004 compared with those in 1990 to 1994 in the CR1 and CR2 groups, respectively. Reductions in mortality were observed in the CR2 group (RR, 0.74; P = .03) but not in the CR1 group., Conclusion: Our results suggest that innovations in transplantation care since the 1980s and 1990s have reduced the risk of TRM in patients undergoing allogeneic HCT for AML and that this reduction has been accompanied by improvements in overall survival.
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- 2011
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7. American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer.
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Rizzo JD, Brouwers M, Hurley P, Seidenfeld J, Arcasoy MO, Spivak JL, Bennett CL, Bohlius J, Evanchuk D, Goode MJ, Jakubowski AA, Regan DH, and Somerfield MR
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- Adult, Anemia drug therapy, Anemia etiology, Darbepoetin alfa, Disease Progression, Humans, Neoplasms drug therapy, Neoplasms mortality, Recombinant Proteins, Erythropoietin analogs & derivatives, Erythropoietin therapeutic use, Hematinics therapeutic use, Neoplasms physiopathology
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Purpose: To update American Society of Clinical Oncology/American Society of Hematology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer., Methods: An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched., Results: The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews., Recommendations: For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.
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- 2010
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8. Relapse and late mortality in 5-year survivors of myeloablative allogeneic hematopoietic cell transplantation for chronic myeloid leukemia in first chronic phase.
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Goldman JM, Majhail NS, Klein JP, Wang Z, Sobocinski KA, Arora M, Horowitz MM, and Rizzo JD
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- Adolescent, Adult, Child, Cohort Studies, Female, Graft vs Host Disease mortality, Histocompatibility Testing, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Remission Induction, Retrospective Studies, Survival Rate, Time Factors, Transplantation Conditioning, Transplantation, Homologous, Treatment Outcome, Young Adult, Graft vs Host Disease diagnosis, Hematopoietic Stem Cell Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local therapy, Survivors
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PURPOSE Allogeneic hematopoietic cell transplantation (HCT) is curative therapy for chronic myeloid leukemia (CML), but its long-term outcomes are not well described. We studied the long-term outcomes of CML patients in first chronic phase who receive an allogeneic HCT. PATIENTS AND METHODS Our study included 2,444 patients who received myeloablative HCT for CML in first chronic phase between 1978 and 1998 and survived in continuous complete remission for at least 5 years (median follow-up, 11 years; range, 5 to 25 years). Donor sources were human leukocyte antigen-matched siblings in 1,692 patients, unrelated donors in 639 patients, and other related donors in 113 patients. RESULTS Overall survival rates at 15 years were 88% (95% CI, 86% to 90%) for sibling HCT and 87% (95% CI, 83% to 90%) for unrelated donor HCT. Corresponding cumulative incidences of relapse were 8% (95% CI, 7% to 10%) and 2% (95% CI, 1% to 4%), respectively. The latest relapse was reported 18 years post-HCT. In multivariable analyses, history of chronic graft-versus-host disease increased risks of late overall mortality and nonrelapse mortality but reduced risks of relapse. In comparison with age-, race-, and sex-adjusted normal populations, the mortality of HCT recipients was significantly higher until 14 years post-HCT; thereafter, mortality rates were similar to those of the general population (relative mortality ratio at 15 years, 2.3; 95% CI, 0 to 4.9). CONCLUSION Recipients of allogeneic HCT for CML in first chronic phase who remain in remission for at least 5 years have favorable subsequent long-term survival, and their mortality rates eventually approach those of the general population.
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- 2010
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9. Late effects of cancer and hematopoietic stem-cell transplantation on spouses or partners compared with survivors and survivor-matched controls.
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Bishop MM, Beaumont JL, Hahn EA, Cella D, Andrykowski MA, Brady MJ, Horowitz MM, Sobocinski KA, Rizzo JD, and Wingard JR
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- Adult, Female, Humans, Linear Models, Male, Middle Aged, Social Support, Surveys and Questionnaires, Hematopoietic Stem Cell Transplantation psychology, Neoplasms psychology, Neoplasms therapy, Quality of Life, Sexual Partners psychology, Spouses psychology, Survivors psychology
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Purpose: Little is known about the long-term effects of cancer and hematopoietic stem-cell transplantation (HCT) on spouses or partners. The purpose of this study was to examine the health-related quality of life and post-traumatic growth (PTG) of spouses/partners compared with survivors and controls and to identify factors associated with those outcomes., Patients and Methods: HCT survivor/partner pairs (n = 177), coupled continuously since HCT, were drawn from 40 North American transplantation centers. Married peer-nominated acquaintances (of survivors) served as controls (n = 133). Outcomes were measured a mean of 6.7 years after HCT (range, 1.9 to 19.4 years)., Results: As expected, self-reported partner physical health was similar to controls and better than survivors (P < .001). However, partners reported more fatigue and cognitive dysfunction than controls (P < .001 for both), although less than survivors. Partners and survivors reported more depressive symptoms and sleep and sexual problems than controls (P < .001, P < .01, and P < .01, respectively). Odds of partner depression were nearly 3.5 times that of controls (P < .002). Depressed partners were less likely than depressed survivors to receive mental health treatment (P < .04). Partners reported less social support (P < .001), dyadic satisfaction (P < .05), and spiritual well-being (P < .05) and more loneliness (P < .05) than both survivors and controls. In contrast to survivors, partners reported little PTG (P < .001). Factors associated with partner outcomes included partner health problems, coping, female sex, social constraint, survivor depression, optimism, multiple life changes, and social support., Conclusion: Spouses/partners experience similar emotional and greater social long-term costs of cancer and HCT than survivors without the potential compensatory benefits of PTG. Some of the factors associated with partner outcomes are amenable to intervention.
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- 2007
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10. Long-term health-related quality of life, growth, and spiritual well-being after hematopoietic stem-cell transplantation.
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Andrykowski MA, Bishop MM, Hahn EA, Cella DF, Beaumont JL, Brady MJ, Horowitz MM, Sobocinski KA, Rizzo JD, and Wingard JR
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- Adult, Aged, Case-Control Studies, Female, Humans, Male, Mental Health, Middle Aged, Multivariate Analysis, Neoplasms therapy, Social Support, Hematopoietic Stem Cell Transplantation psychology, Quality of Life, Spirituality, Survivors psychology
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Purpose: To examine health-related quality of life (HRQOL) and growth, and spiritual well-being in adult survivors of hematopoietic stem-cell transplantation (HSCT) for a malignant disease., Methods: HSCT survivors (n = 662) were recruited through the International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry and were drawn from 40 transplantation centers. HSCT survivors completed a telephone interview and a set of questionnaires a mean of 7.0 years post-HSCT (range, 1.8 to 22.6 years). Study measures included a variety of standardized measures of HRQOL and growth and spiritual well-being. An age- and sex-matched healthy comparison (HC) group (n = 158) was recruited using a peer nomination method. The HC group completed a parallel telephone interview and set of questionnaires., Results: Multivariate analysis of variance analyses found the HSCT survivor group reported poorer status relative to the HC group for all HRQOL outcome clusters including physical health, physical functioning, social functioning, psychological adjustment, and dyadic adjustment. In contrast, the HSCT survivor group reported more psychological and interpersonal growth. Mean effect size for the 24 outcome indices examined was 0.36 standard deviations, an effect size often considered clinically meaningful or important. The largest group differences were found for measures of general health, physical function and well-being, depression, cognitive function, and fatigue., Conclusion: The experience of HSCT for a malignant disease has a wide-ranging, longstanding, and profound impact on adult recipients. Relative to healthy controls, HSCT survivors reported poorer physical, psychological, and social functioning but, conversely, more psychological and interpersonal growth, differences that appeared to persist many years after HSCT.
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- 2005
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11. Trends in survival rates after allogeneic hematopoietic stem-cell transplantation for acute and chronic leukemia by ethnicity in the United States and Canada.
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Serna DS, Lee SJ, Zhang MJ, Baker kS, Eapen M, Horowitz MM, Klein JP, Rizzo JD, and Loberiza FR Jr
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- Acute Disease, Adult, Black or African American, Canada, Chronic Disease, Ethnicity, Female, Hispanic or Latino, Humans, Male, Survival Rate, Time Factors, United States, White People, Hematopoietic Stem Cell Transplantation, Leukemia ethnology, Leukemia mortality, Leukemia therapy
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Purpose: Differences in survival among ethnic groups in the United States are reported in numerous diseases and treatment strategies. Whether survival after allogeneic hematopoietic stem-cell transplantation (HSCT) differs by ethnicity is uncertain., Patients and Methods: Patients (n = 6443) receiving HLA-identical sibling HSCT for acute or chronic leukemia in the United States or Canada between 1985 and 1999 and reported to the International Bone Marrow Transplant Registry were included. The survival of recipients reported as white, black, Hispanic, or Asian was compared using Cox proportional hazards regression adjusting for other clinical factors. Three 5-year periods were studied to evaluate changes over time., Results: Hispanics compared with whites had lower 1-year (53% v 65%; P <.001) and 3-year adjusted survival rates (38% v 53%; P <.001) between 1995 and 1999, the most recent period studied. We failed to find significant differences in survival rates comparing whites with blacks or with Asians in any of the time periods. Overall survival for the entire cohort improved over time, from 56% to 63% at 1 year and from 43% to 51% at 3 years, with greater improvements noted among blacks (45% to 61% at 1 year and 34% to 48% at 3 years)., Conclusion: Disparities remain in survival rates between whites and Hispanics despite adjustment for clinical factors. Factors not accounted for in this analysis, such as comorbid disease, socioeconomic status, healthcare access and delivery, and psychosocial and cultural variables, require further prospective study.
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- 2003
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12. Syngeneic hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma: a comparison with allogeneic and autologous transplantation--The Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation.
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Bierman PJ, Sweetenham JW, Loberiza FR Jr, Taghipour G, Lazarus HM, Rizzo JD, Schmitz N, van Besien K, Vose JM, Horowitz M, and Goldstone A
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- Adolescent, Adult, Aged, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Male, Middle Aged, Multivariate Analysis, Neoplasm Recurrence, Local, Transplantation, Autologous, Transplantation, Homologous, Treatment Outcome, Graft vs Tumor Effect, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Non-Hodgkin therapy
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Purpose: To compare results of syngeneic, allogeneic, and autologous hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma (NHL)., Patients and Methods: The databases of the International Bone Marrow Transplant Registry (IBMTR) and the European Group for Blood and Marrow Transplantation were used to identify 89 NHL patients who received syngeneic transplants. These patients were compared with NHL patients identified from the IBMTR and the Autologous Blood and Marrow Transplant Registry who received allogeneic (T-cell depleted and T-cell replete) and autologous (purged and unpurged) transplants., Results: No significant differences in relapse rates were observed when results of allogeneic transplantation were compared with syngeneic transplantation for any histology. T-cell depletion of allografts was not associated with a higher relapse risk, but was associated with improved overall survival for patients with low-grade and intermediate-grade histology. Patients who received unpurged autografts for low-grade NHL had a five-fold (P =.008) greater risk of relapse than recipients of syngeneic transplants, and recipients of unpurged autografts had a two-fold (P =.0009) greater relapse risk than patients who received purged autografts. Among low-grade NHL patients, the use of purging was associated with significantly better disease-free survival (P =.003) and overall survival (P =.04) when compared with patients who received unpurged autografts., Conclusion: These analyses failed to find evidence of a graft-versus-lymphoma effect, but do provide indirect evidence to support the hypothesis that tumor contamination may contribute to lymphoma relapse, and that purging may be beneficial for patients undergoing autologous hematopoietic stem-cell transplantation for low-grade NHL.
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- 2003
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13. Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology.
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Rizzo JD, Lichtin AE, Woolf SH, Seidenfeld J, Bennett CL, Cella D, Djulbegovic B, Goode MJ, Jakubowski AA, Lee SJ, Miller CB, Rarick MU, Regan DH, Browman GP, and Gordon MS
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- Anemia etiology, Humans, Neoplasms drug therapy, Societies, Medical, Anemia drug therapy, Erythropoietin therapeutic use, Evidence-Based Medicine, Neoplasms complications, Practice Guidelines as Topic
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Anemia resulting from cancer, or its treatment, is an important clinical problem increasingly treated with the recombinant hematopoietic growth factor erythropoietin. To address uncertainties regarding indications and efficacy, the American Society of Clinical Oncology and the American Society of Hematology developed an evidence-based clinical practice guideline for the use of epoetin in patients with cancer. The guideline panel found good evidence to recommend use of epoetin as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin level less than 10 g/dL. Use of epoetin for patients with less severe anemia (hemoglobin < 12 g/dL but never below 10 g/dL) should be determined by clinical circumstances. Good evidence from clinical trials supports the use of subcutaneous epoetin thrice weekly (150 U/kg tiw) for a minimum of 4 weeks. Less strong evidence supports an alternative weekly (40,000 U/wk) dosing regimen, based on common clinical practice. With either administration schedule, dose escalation should be considered for those not responding to the initial dose. In the absence of response, continuing epoetin beyond 6 to 8 weeks does not appear to be beneficial. Epoetin should be titrated once the hemoglobin concentration reaches 12 g/dL. Evidence from one randomized controlled trial supports use of epoetin for patients with anemia associated with low-risk myelodysplasia not receiving chemotherapy; however, there are no published high-quality studies to support its use for anemia in other hematologic malignancies in the absence of chemotherapy. Therefore, for anemic patients with hematologic malignancies, it is recommended that physicians initiate conventional therapy and observe hematologic response before considering use of epoetin.
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- 2002
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14. Association of depressive syndrome and early deaths among patients after stem-cell transplantation for malignant diseases.
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Loberiza FR Jr, Rizzo JD, Bredeson CN, Antin JH, Horowitz MM, Weeks JC, and Lee SJ
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- Adaptation, Psychological, Adult, Aged, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Male, Middle Aged, Neoplasms mortality, Neoplasms psychology, Proportional Hazards Models, Prospective Studies, Quality of Life, Survival Analysis, Depression etiology, Hematopoietic Stem Cell Transplantation psychology, Neoplasms therapy
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Purpose: The association of depression and increased mortality in the general population, and also various medical conditions, is well documented. However, depression is not well studied in the setting of hematopoietic stem-cell transplantation (HSCT). We examined the association between depressive syndrome and survival after HSCT., Patients and Methods: A total of 193 patients who received autologous or allogeneic HSCT from Brigham and Women's Hospital or Dana-Farber Cancer Institute were evaluated prospectively. The self-rated Likert-scaled symptom checklist, the SF-36, and the Spitzer Quality of Life Index Scale were administered. Outcomes evaluated included survival and quality of life., Results: Sixty-seven patients (35%) satisfied the criteria for depressive syndrome. The 1-year probability of survival for the depressed and nondepressed patients was 85% (95% confidence interval [CI], 74% to 92%) and 94% (95% CI, 89% to 97%), respectively (P =.04). In multivariable modeling, depressed patients have a three-fold greater risk of dying than nondepressed patients (95% CI, 1.07 to 8.30; P =.04) between 6 and 12 months after HSCT after adjusting for other prognostic factors. Global inferiority in quality of life was observed in the depressed cohort when last measured at 24 months after transplantation., Conclusion: Depressive syndrome after HSCT is associated with decreased survival, at least from 6 to 12 months after transplantation. Persistence of this association after controlling for possible confounding factors suggests that depression may be more than simply a marker for concurrent ill health. This study raises an interesting hypothesis as to whether psychological or pharmacologic intervention for depression after HSCT can improve survival and/or quality of life.
- Published
- 2002
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