Search

Granulocyte colony-stimulating factor (G-CSF) is often administered after hematopoietic-cell transplantation (HCT) to accelerate neutrophil recovery, but it is unclear what impact G-CSF has on long-term transplantation outcomes. We analyzed within the database of the Center for International Blood and Marrow Transplant Research the impact of giving posttransplantation G-CSF on the outcomes of allogeneic HCT for acute myelogenous leukemia and chronic myelogenous leukemia in 2719 patients who underwent transplantation between 1995 and 2000. These included 1435 recipients of HLA-identical sibling bone marrow (BM), 609 recipients of HLA-identical peripheral-blood stem cells (PBSCs), and 675 recipients of unrelated donor BM transplants. Outcomes were compared between patients receiving or not receiving G-CSF within 7 days of HCT according to graft type. Median follow-up was more than 30 months (range, 2-87 months). G-CSF shortened the posttransplantation neutropenic period, but did not affect days +30 and +100 treatment-related mortality (TRM). Probabilities of acute and chronic graft-versus-host disease (GVHD), leukemia-free survival (LFS), and overall survival were similar whether or not G-CSF was given. Multivariate analyses confirmed that giving G-CSF did not affect the risk of GVHD, TRM, LFS, or survival. In conclusion, results of this study found no long-term benefit or disadvantage of giving G-CSF after transplantation to promote hematopoietic recovery.

Granulocyte colony-stimulating factor (G-CSF) is often administered after hematopoietic-cell transplantation (HCT) to accelerate neutrophil recovery, but it is unclear what impact G-CSF has on long-term transplantation outcomes. We analyzed within the database of the Center for International Blood and Marrow Transplant Research the impact of giving posttransplantation G-CSF on the outcomes of allogeneic HCT for acute myelogenous leukemia and chronic myelogenous leukemia in 2719 patients who underwent transplantation between 1995 and 2000. These included 1435 recipients of HLA-identical sibling bone marrow (BM), 609 recipients of HLA-identical peripheral-blood stem cells (PBSCs), and 675 recipients of unrelated donor BM transplants. Outcomes were compared between patients receiving or not receiving G-CSF within 7 days of HCT according to graft type. Median follow-up was more than 30 months (range, 2-87 months). G-CSF shortened the posttransplantation neutropenic period, but did not affect days +30 and +100 treatment-related mortality (TRM). Probabilities of acute and chronic graft-versus-host disease (GVHD), leukemia-free survival (LFS), and overall survival were similar whether or not G-CSF was given. Multivariate analyses confirmed that giving G-CSF did not affect the risk of GVHD, TRM, LFS, or survival. In conclusion, results of this study found no long-term benefit or disadvantage of giving G-CSF after transplantation to promote hematopoietic recovery.

Reported risk factors for bronchiolitis obliterans (BO) in allogeneic hematopoietic stem-cell transplant recipients come from modest-sized studies and are limited to experiences of single institutions. We sought to identify risk factors for BO using data from the International Bone Marrow Transplant Registry.

The effect of the organization and delivery of health care at medical centers, referred to as “center effects,” with clinical outcomes after hematopoietic stem cell transplantation (HSCT) is not clear. We examined the association between center and treatment provider factors and mortality after HSCT. We surveyed 163 (87% response rate) United States transplantation centers that performed HLA-identical sibling HSCT for leukemia or autologous HSCT for lymphoma between 1998 and 2000 among patients at least 18 years old. One hundred thirteen (69%) centers performed HLA-identical sibling transplantations, whereas 162 (99%) performed autologous transplantations. Factors associated with decreased 100-day mortality in the allogeneic setting include a higher patient-per-physician ratio (P= .003) and centers where physicians answer calls after office hours (P= .03). Medical school affiliation was not associated with increased 100-day mortality except in centers where students/residents are present without fellows (P= .02). Center effects were weaker in autologous HSCT at 1 year. Differences in 100-day mortality in patients receiving transplants in centers with favorable versus unfavorable factors were greater in allogeneic than autologous HSCT. Greater physician involvement in patient care is important in producing favorable outcomes after HSCT. To more clearly establish the role of the factors we identified, further studies are recommended.

The effect of the organization and delivery of health care at medical centers, referred to as “center effects,” with clinical outcomes after hematopoietic stem cell transplantation (HSCT) is not clear. We examined the association between center and treatment provider factors and mortality after HSCT. We surveyed 163 (87% response rate) United States transplantation centers that performed HLA-identical sibling HSCT for leukemia or autologous HSCT for lymphoma between 1998 and 2000 among patients at least 18 years old. One hundred thirteen (69%) centers performed HLA-identical sibling transplantations, whereas 162 (99%) performed autologous transplantations. Factors associated with decreased 100-day mortality in the allogeneic setting include a higher patient-per-physician ratio (P = .003) and centers where physicians answer calls after office hours (P = .03). Medical school affiliation was not associated with increased 100-day mortality except in centers where students/residents are present without fellows (P = .02). Center effects were weaker in autologous HSCT at 1 year. Differences in 100-day mortality in patients receiving transplants in centers with favorable versus unfavorable factors were greater in allogeneic than autologous HSCT. Greater physician involvement in patient care is important in producing favorable outcomes after HSCT. To more clearly establish the role of the factors we identified, further studies are recommended.

The association of ethnicity with the incidence of graft-versus-host disease (GVHD) and other clinical outcomes after transplantation is controversial. We compared the results of HLA-identical sibling bone marrow transplantations for leukemia, performed between 1990 and 1999, among different ethnic populations, including 562 Japanese, 829 white Americans, 71 African Americans, 195 Scandinavians, and 95 Irish. Results for adults and children were analyzed separately. Multivariate analyses of adult patients showed that white Americans, African Americans, and Irish cohorts were at significantly higher risk for acute GVHD than Japanese or Scandinavian cohorts (relative risk [RR] = 1.77, P< .001; RR = 1.84, P< .006; RR = 2.22, P< .001, respectively). White Americans, African Americans, and Irish, but not Scandinavians, were at significantly higher risk for early (within 3 months of transplantation) transplant-related mortality (TRM) compared with Japanese (RR = 2.99, P< .001; RR = 5.88, P< .001; RR = 2.66, P< .009, respectively). No differences in the risk for chronic GVHD, relapse, and overall survival were noted. In the pediatric cohort (limited to Japanese and white Americans), white Americans were at significantly higher risk for acute (RR = 1.93; P= .04) and chronic (RR = 3.16; P= .002) GVHD. No differences in other clinical outcomes were noted. Our findings suggest that ethnicity may influence the risk for GVHD, though overall survival rates after transplantation remain similar.

The association of ethnicity with the incidence of graft-versus-host disease (GVHD) and other clinical outcomes after transplantation is controversial. We compared the results of HLA-identical sibling bone marrow transplantations for leukemia, performed between 1990 and 1999, among different ethnic populations, including 562 Japanese, 829 white Americans, 71 African Americans, 195 Scandinavians, and 95 Irish. Results for adults and children were analyzed separately. Multivariate analyses of adult patients showed that white Americans, African Americans, and Irish cohorts were at significantly higher risk for acute GVHD than Japanese or Scandinavian cohorts (relative risk [RR] = 1.77, P < .001; RR = 1.84, P < .006; RR = 2.22, P < .001, respectively). White Americans, African Americans, and Irish, but not Scandinavians, were at significantly higher risk for early (within 3 months of transplantation) transplant-related mortality (TRM) compared with Japanese (RR = 2.99, P < .001; RR = 5.88, P < .001; RR = 2.66, P < .009, respectively). No differences in the risk for chronic GVHD, relapse, and overall survival were noted. In the pediatric cohort (limited to Japanese and white Americans), white Americans were at significantly higher risk for acute (RR = 1.93; P = .04) and chronic (RR = 3.16; P = .002) GVHD. No differences in other clinical outcomes were noted. Our findings suggest that ethnicity may influence the risk for GVHD, though overall survival rates after transplantation remain similar.

Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used in patients with lymphoma who experience disease relapse after autologous hematopoietic stem cell transplantation (auto-HSCT) because the allograft is tumor free and may induce a graft-versus-tumor effect. We analyzed 114 patients treated with this approach from 1990 to 1999 to assess disease progression, progression-free survival (PFS), and overall survival (OS). Cumulative incidence of disease progression at 3 years was 52%, whereas treatment-related mortality was 22%, lower than previously reported. Three-year probabilities of OS and PFS were 33% and 25%, respectively. With prolonged follow-up, however, nearly all patients experienced disease progression, and 5-year probabilities were 24% and 5%, respectively. Complete remission at the time of allo-HSCT and use of total body irradiation (TBI) in patients with non-Hodgkin lymphoma (NHL) were associated with lower rates of disease progression and higher rates of OS. In summary, allo-HSCT is feasible for patients with lymphoma who have relapses after auto-HSCT and can result in prolonged survival for some, but it is usually not curative. Most likely to benefit are patients who have HLA-matched sibling donors, are in remission, and have good performance status.

Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used in patients with lymphoma who experience disease relapse after autologous hematopoietic stem cell transplantation (auto-HSCT) because the allograft is tumor free and may induce a graft-versus-tumor effect. We analyzed 114 patients treated with this approach from 1990 to 1999 to assess disease progression, progression-free survival (PFS), and overall survival (OS). Cumulative incidence of disease progression at 3 years was 52%, whereas treatment-related mortality was 22%, lower than previously reported. Three-year probabilities of OS and PFS were 33% and 25%, respectively. With prolonged follow-up, however, nearly all patients experienced disease progression, and 5-year probabilities were 24% and 5%, respectively. Complete remission at the time of allo-HSCT and use of total body irradiation (TBI) in patients with non-Hodgkin lymphoma (NHL) were associated with lower rates of disease progression and higher rates of OS. In summary, allo-HSCT is feasible for patients with lymphoma who have relapses after auto-HSCT and can result in prolonged survival for some, but it is usually not curative. Most likely to benefit are patients who have HLA-matched sibling donors, are in remission, and have good performance status.

In this article, we report on 904 patients undergoing transplantation for follicular lymphoma. A total of 176 (19%) received allogeneic, 131 (14%) received purged autologous, and 597 (67%) received unpurged autologous transplants. Five-year treatment-related mortality (TRM) rates were 30%, 14%, and 8% and 5-year recurrence rates were 21%, 43%, and 58% after allotransplantation, purged autotransplantation, and unpurged autotransplantation, respectively. In multivariate analyses, allotransplantation had higher TRM and lower disease recurrence. Purged autotransplantation had a 26% lower recurrence risk than unpurged autotransplantation. Five-year probabilities of survival were 51%, 62%, and 55% after allogeneic, purged autotransplantation, and unpurged autotransplantation, respectively. Advanced age, prolonged interval from diagnosis to transplantation, high lactate dehydrogenase (LDH), refractory disease, bone marrow involvement, low performance scores, and transplantation between 1990 and 1993 were associated with adverse outcomes. Total body irradiation was associated with higher TRM but lower recurrence. There was no association between acute or chronic graft-versus-host disease and recurrence after allotransplantation. We conclude that both allogeneic and autologous transplantation can induce durable remissions. There may be a benefit to graft purging in autologous transplantation. The decreased recurrence after allotransplantation is offset by increased TRM. We did not detect a correlation between graft-versus-host disease (GVHD) and recurrence. Finally, outcomes of transplantation for follicular lymphoma show improvement over the past decade. (Blood. 2003;102:3521-3529)

In this article, we report on 904 patients undergoing transplantation for follicular lymphoma. A total of 176 (19%) received allogeneic, 131 (14%) received purged autologous, and 597 (67%) received unpurged autologous transplants. Five-year treatment-related mortality (TRM) rates were 30%, 14%, and 8% and 5-year recurrence rates were 21%, 43%, and 58% after allotransplantation, purged autotransplantation, and unpurged autotransplantation, respectively. In multivariate analyses, allotransplantation had higher TRM and lower disease recurrence. Purged autotransplantation had a 26% lower recurrence risk than unpurged autotransplantation. Five-year probabilities of survival were 51%, 62%, and 55% after allogeneic, purged autotransplantation, and unpurged autotransplantation, respectively. Advanced age, prolonged interval from diagnosis to transplantation, high lactate dehydrogenase (LDH), refractory disease, bone marrow involvement, low performance scores, and transplantation between 1990 and 1993 were associated with adverse outcomes. Total body irradiation was associated with higher TRM but lower recurrence. There was no association between acute or chronic graft-versus-host disease and recurrence after allotransplantation. We conclude that both allogeneic and autologous transplantation can induce durable remissions. There may be a benefit to graft purging in autologous transplantation. The decreased recurrence after allotransplantation is offset by increased TRM. We did not detect a correlation between graft-versus-host disease (GVHD) and recurrence. Finally, outcomes of transplantation for follicular lymphoma show improvement over the past decade. (Blood. 2003;102:3521-3529)

Lymphoblastic lymphoma (LBL) is a rare, clinically aggressive neoplasm of the young that frequently involves the bone marrow (BM) and/or central nervous system. Because LBL is similar to acute lymphoblastic leukemia, some centers prefer allogeneic hematopoietic stem cell (SC) transplantation to autologous SC transplantation. We retrospectively analyzed outcomes for patients who underwent autologous (auto, n = 128) or HLA-identical sibling (allo, n = 76) SC transplantations from 1989 to 1998 and were reported to International Bone Marrow Transplant Registry (IBMTR) or Autologous Blood and Marrow Transplant Registry (ABMTR). Allo stem cell transplant (SCT) recipients had higher treatment-related mortality (TRM) at 6 months (18% versus 3%,P= .002), and this disadvantage persisted at 1 and 5 years. Early relapse rates after alloSC transplantation and autoSC transplantation were similar, but significantly lower relapse rates were observed in alloSCT recipients at 1 and 5 years (32% versus 46%,P= .05; and 34% versus 56%,P= .004, respectively). No differences were noted in lymphoma-free survival rates between alloSC transplantations and autoSC transplantations (5-year rates 36% versus 39%,P= .82). AutoSCT recipients had higher overall survival at 6 months (75% versus 59%,P= .01), but survival did not significantly differ between the 2 groups at 1 and 5 years (60% versus 49%,P= .09; 44% versus 39%,P= .47, respectively). Multivariate analyses to account for confounding factors confirmed these results. Independent of SCT type, BM involvement at the time of transplantation and disease status more advanced than first complete remission were associated with inferior outcomes. In summary, alloSC transplantation for LBL is associated with fewer relapses than with autoSC transplantation, but higher TRM offsets any potential survival benefit.

Lymphoblastic lymphoma (LBL) is a rare, clinically aggressive neoplasm of the young that frequently involves the bone marrow (BM) and/or central nervous system. Because LBL is similar to acute lymphoblastic leukemia, some centers prefer allogeneic hematopoietic stem cell (SC) transplantation to autologous SC transplantation. We retrospectively analyzed outcomes for patients who underwent autologous (auto, n = 128) or HLA-identical sibling (allo, n = 76) SC transplantations from 1989 to 1998 and were reported to International Bone Marrow Transplant Registry (IBMTR) or Autologous Blood and Marrow Transplant Registry (ABMTR). Allo stem cell transplant (SCT) recipients had higher treatment-related mortality (TRM) at 6 months (18% versus 3%, P = .002), and this disadvantage persisted at 1 and 5 years. Early relapse rates after alloSC transplantation and autoSC transplantation were similar, but significantly lower relapse rates were observed in alloSCT recipients at 1 and 5 years (32% versus 46%, P = .05; and 34% versus 56%,P = .004, respectively). No differences were noted in lymphoma-free survival rates between alloSC transplantations and autoSC transplantations (5-year rates 36% versus 39%,P = .82). AutoSCT recipients had higher overall survival at 6 months (75% versus 59%, P = .01), but survival did not significantly differ between the 2 groups at 1 and 5 years (60% versus 49%, P = .09; 44% versus 39%,P = .47, respectively). Multivariate analyses to account for confounding factors confirmed these results. Independent of SCT type, BM involvement at the time of transplantation and disease status more advanced than first complete remission were associated with inferior outcomes. In summary, alloSC transplantation for LBL is associated with fewer relapses than with autoSC transplantation, but higher TRM offsets any potential survival benefit.

Objectives/HypothesisHealth‐related quality of life (QOL) assessment of patients with nonmelanoma skin cancer is poorly understood. The objectives of the study were to determine the general QOL of patients with cervicofacial skin cancer and to identify patient, clinical, and preventive behavior variables associated with patients' QOL.

In haploidentical transplantation, the mismatched haplotype of the donor can originate from either of the parents. We refer to such mismatched haplotypes as noninherited maternal antigens (NIMA haplotype) or noninherited paternal antigens (NIPA haplotype). To determine whether exposure to maternal HLA antigens benefits patients undergoing bone marrow transplantation, we analyzed graft failure and graft-versus-host disease (GVHD) after transplantations from parental or haploidentical sibling donors. We studied 269 patients receiving 1 or 2 HLA-A, -B, -DR antigen-mismatched sibling or parental non–T-cell–depleted bone marrow transplants for acute myelogenous leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia between 1985 and 1997 that were reported to the International Bone Marrow Transplant Registry. Included were 121 (45%) NIMA-mismatched and 148 (55%) NIPA-mismatched transplantations. Sixty-three (52%) of the NIMA-mismatched transplants and 69 (47%) of the NIPA-mismatched transplants were from haploidentical sibling donors. Sibling transplantations mismatched for NIMA had similar rates of graft failure but lower rates of acute GVHD (P < .02) than NIPA-mismatched sibling transplantations. In the first 4 months after transplantation, mother-to-child transplantations involved significantly less chronic GVHD than father-to-child transplantations (P < .02). Treatment-related mortality (TRM) was significantly higher after parental transplantations (P = .009 for mother; P = .03 for father) than after haploidentical sibling transplantations mismatched for the NIMA. Non–T-cell–depleted bone marrow transplants donated by haploidentical siblings to recipients mismatched for NIPA and transplants donated by parents caused more acute and chronic GVHD and TRM than transplants donated by haploidentical siblings mismatched for NIMA.

In haploidentical transplantation, the mismatched haplotype of the donor can originate from either of the parents. We refer to such mismatched haplotypes as noninherited maternal antigens (NIMA haplotype) or noninherited paternal antigens (NIPA haplotype). To determine whether exposure to maternal HLA antigens benefits patients undergoing bone marrow transplantation, we analyzed graft failure and graft-versus-host disease (GVHD) after transplantations from parental or haploidentical sibling donors. We studied 269 patients receiving 1 or 2 HLA-A, -B, -DR antigen-mismatched sibling or parental non–T-cell–depleted bone marrow transplants for acute myelogenous leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia between 1985 and 1997 that were reported to the International Bone Marrow Transplant Registry. Included were 121 (45%) NIMA-mismatched and 148 (55%) NIPA-mismatched transplantations. Sixty-three (52%) of the NIMA-mismatched transplants and 69 (47%) of the NIPA-mismatched transplants were from haploidentical sibling donors. Sibling transplantations mismatched for NIMA had similar rates of graft failure but lower rates of acute GVHD (P< .02) than NIPA-mismatched sibling transplantations. In the first 4 months after transplantation, mother-to-child transplantations involved significantly less chronic GVHD than father-to-child transplantations (P< .02). Treatment-related mortality (TRM) was significantly higher after parental transplantations (P= .009 for mother; P= .03 for father) than after haploidentical sibling transplantations mismatched for the NIMA. Non–T-cell–depleted bone marrow transplants donated by haploidentical siblings to recipients mismatched for NIPA and transplants donated by parents caused more acute and chronic GVHD and TRM than transplants donated by haploidentical siblings mismatched for NIMA.

Various therapeutic options are available for patients with chronic myelogenous leukemia. Allogeneic stem cell transplantation, though often curative, is associated with high nonrelapse mortality and long-term morbidity, particularly when cells from unrelated donors are used. Many physicians and patients opt for a trial of interferon-α (IFN)–based therapy first, reserving transplantation for patients with inadequate response or intolerance to IFN. Data were analyzed on 740 patients receiving unrelated donor transplants for chronic myelogenous leukemia in first chronic phase provided by the International Bone Marrow Transplant Registry and the National Marrow Donor Program to see whether IFN pretreatment compromised transplantation outcome. A total of 489 (66%) had received IFN prior to transplantation; 251 (34%) had not. Disease characteristics in the 2 groups were similar at diagnosis but at the time of transplantation, hematologic parameters and weight were lower in IFN patients and the interval between diagnosis and transplantation was longer. After adjustment for baseline covariates, no effect of IFN exposure was found on overall survival, leukemia-free survival, nonrelapse mortality, engraftment, relapse, or acute or chronic graft-versus-host disease. Evaluation of effects based on duration of therapy and time off IFN prior to transplantation was limited by missing data and confounding with IFN intolerance and disease responsiveness. In conclusion, no evidence was found for an independent adverse effect of IFN pretreatment on the outcome of subsequent unrelated donor transplantation.

Various therapeutic options are available for patients with chronic myelogenous leukemia. Allogeneic stem cell transplantation, though often curative, is associated with high nonrelapse mortality and long-term morbidity, particularly when cells from unrelated donors are used. Many physicians and patients opt for a trial of interferon-α (IFN)–based therapy first, reserving transplantation for patients with inadequate response or intolerance to IFN. Data were analyzed on 740 patients receiving unrelated donor transplants for chronic myelogenous leukemia in first chronic phase provided by the International Bone Marrow Transplant Registry and the National Marrow Donor Program to see whether IFN pretreatment compromised transplantation outcome. A total of 489 (66%) had received IFN prior to transplantation; 251 (34%) had not. Disease characteristics in the 2 groups were similar at diagnosis but at the time of transplantation, hematologic parameters and weight were lower in IFN patients and the interval between diagnosis and transplantation was longer. After adjustment for baseline covariates, no effect of IFN exposure was found on overall survival, leukemia-free survival, nonrelapse mortality, engraftment, relapse, or acute or chronic graft-versus-host disease. Evaluation of effects based on duration of therapy and time off IFN prior to transplantation was limited by missing data and confounding with IFN intolerance and disease responsiveness. In conclusion, no evidence was found for an independent adverse effect of IFN pretreatment on the outcome of subsequent unrelated donor transplantation.

Peripheral blood cells are increasingly used in place of bone marrow as a source of hematopoietic stem cells for allogeneic transplantation. The relative efficacy of these 2 approaches is unknown. This retrospective multivariate analysis compared results of 288 HLA-identical sibling blood stem cell transplantations with results of 536 HLA-identical sibling bone marrow transplantations. No transplants were T-cell depleted. Median follow-up was 12 months, and analyses focused on 1-year outcomes. Recipients of blood stem cell transplants had more rapid recovery of neutrophils to at least 0.5?×?109/L (median time to recovery, 14 days, compared with 19 days for marrow transplants;P?

This report presents the initial results of a mental health survey of 351 tribal and non-tribal Mount Pinatubo disaster victims 6 years after they were displaced following the volcanic eruption in the Philippines on June 12, 1991. Mental illness prevalence rates in both Filipino ethnic groups were comparable to those found in a U.S. study using the same assessment instrument. Post-traumatic stress disorder (PTSD; 27.6%) and major depression (14.0%) were the two most frequent diagnoses. Diagnostic test-retest interviewer agreement was good for probable alcohol abuse (κ = .65, agreement = 97%) and any mood disorder (κ = .53, agreement = 91%) but was reduced for any anxiety disorder (κ = .15, agreement = 81%) and separately evaluated PTSD (κ = .18, agreement = 69%). Diagnostic test-retest agreement was good among typical Filipinos (mean κ = .66, mean agreement = 93%) but was reduced among tribal aborigines (mean = .30, mean agreement = 86%). Internal consistency of the PTSD rating scale was high within and across both ethnic groups, including total scale (α = .91) and DSM-IV Criteria B, C, and D sub-scales (α = .80, 81, and .78, respectively). With the exception of probable alcohol abuse, construct and criterion validity was demonstrated among both tribal and non-tribal Filipinos for all classes of psychiatric disorders by comparing diagnostic results with respondents' views of their physical and mental health and level of functional impairment. Overall, DSM-IV mood, anxiety, alcohol use, and PTSDs with adequate reliability and construct and criterion validity were made in this culturally diverse, non-Western, disaster victim population. However, test-retest diagnostic agreement was reduced for anxiety disorders and among aboriginal respondents, and validity was not demonstrated for probable alcohol abuse.

PurposeEarly diagnosis of prostate carcinoma has undergone significant evolution mainly due to the widespread use of serum prostate specific antigen, transrectal ultrasonography and spring loaded biopsy devices. A common dilemma faced by clinicians arises when a negative biopsy is obtained in a patient and there is a high suspicion for prostate carcinoma. The literature reveals a 20 to 40% positive repeat biopsy rate in men with elevated prostate specific antigen who had an initial negative biopsy. We determined the yield of 6 systematic sector biopsies as a function of total gland and peripheral zone volumes.Materials and MethodsThe database of transrectal ultrasound guided prostate needle biopsies performed at the Department of Urology, University of Washington Medical Center and Veterans Affairs Puget Sound Health Care System was reviewed. The yield of the 6 biopsies was determined as a function of the total gland and peripheral zone volumes.ResultsA total of 1,057 men who underwent transrectal ultrasound guided prostate needle biopsies were investigated in our study. Of the men 326 were diagnosed with prostate cancer for a positive biopsy rate of 30.8%. No relationship between gland size and cancer yield was seen using total gland volume compared to the first quartile until the largest quartile when a significantly lower cancer detection rate was noted (odds ratio 1.5).ConclusionsThe positive yield of the systematic 6-sector biopsy decreases significantly when the total gland volume is greater than 55.6 cc or peripheral zone volume is greater than 33.61 cc. In men with smaller prostates 6 systematic sector biopsies should be adequate.

PurposeDespite being the most useful tumor marker for the diagnosis of patients with prostate cancer, serum prostate specific antigen (PSA) is still hampered by lack of specificity. A negative prostate biopsy is associated with a 20 to 40% incidence of positive repeat biopsy in men with persistently elevated serum PSA levels. We determine whether the free-to-total PSA ratio could be predictive of prostate cancer in men undergoing repeat biopsy.Materials and MethodsArchival sera, drawn before the first biopsy, were gathered from 51 men with a total serum PSA of 2 to 15 ng./ml. who underwent repeat prostate needle biopsy for various indications. The percent free PSA was calculated using the Hybritech Tandem-R [dagger] free and total PSA as well as Dianon Systems free [double dagger] and Hybritech total PSA assays. The free-to-total PSA ratio results between the cancer and noncancer groups were compared using Student's t test.ResultsThe median Hybritech free-to-total PSA ratio was significantly lower in patients with positive repeat prostate needle biopsy compared to those with negative biopsy (14.9 versus 19.4%, p = 0.05). Total PSA as well as the percent Dianon free-to-Hybritech total PSA ratio were not significantly different between the 2 groups of men.ConclusionsFor total PSA in the range of 2 to 15 ng./ml. Hybritech free-to-total PSA ratio appeared to aid in the prediction of cancer on repeat biopsy.

We previously compared outcomes after allogeneic peripheral-blood stem cell (PBSC) and bone marrow (BM) transplantation in 706 patients with leukemia. We obtained long-term follow up on 413 of 491 patients who were alive at the time of the initial report: 141 PBSC and 272 BM recipients. Chronic graft-versus-host disease (GVHD) was more frequent after PBSC compared to BM transplantation (RR 1.65, P< .001) yet relapse rates were similar in both groups. Leukemia-free survival rates were higher after PBSC than BM transplantation for patients with advanced chronic myeloid leukemia (33% versus 25%) but lower for those in first chronic phase (41% versus 61%) due to higher rates of late transplant-related mortality. Leukemia-free survival was similar after PBSC and BM transplantation for acute leukemia. These data represent the early experience with PBSC grafts. Long-term outcomes in recipients of more recent transplants are required to better evaluate the role of PBSC grafts relative to BM transplantation.

We previously compared outcomes after allogeneic peripheral-blood stem cell (PBSC) and bone marrow (BM) transplantation in 706 patients with leukemia. We obtained long-term follow up on 413 of 491 patients who were alive at the time of the initial report: 141 PBSC and 272 BM recipients. Chronic graft-versus-host disease (GVHD) was more frequent after PBSC compared to BM transplantation (RR 1.65, P < .001) yet relapse rates were similar in both groups. Leukemia-free survival rates were higher after PBSC than BM transplantation for patients with advanced chronic myeloid leukemia (33% versus 25%) but lower for those in first chronic phase (41% versus 61%) due to higher rates of late transplant-related mortality. Leukemia-free survival was similar after PBSC and BM transplantation for acute leukemia. These data represent the early experience with PBSC grafts. Long-term outcomes in recipients of more recent transplants are required to better evaluate the role of PBSC grafts relative to BM transplantation.

No relevant conflicts of interest to declare.

Background:Prior studies have demonstrated unique clinicopathologic features of the BV of MCL including an inferior response to chemotherapy and poor long-term outcomes as compared to other MCL variants in the pre-rituximab era. A paucity of data precludes whether the use of rituximab or intensified therapy can overcome the inferior outcome associated with the BV.

No relevant conflicts of interest to declare.

Armitage: Ziopharm Oncology: Consultancy; GlaxoSmithKline: Consultancy; Spectrum Pharmaceuticals: Consultancy; Roche: Consultancy; Tesaro bio Inc: Membership on an entity's Board of Directors or advisory committees.

Background: The association of clinical trial participation with outcomes in cancer patients is controversial, with some studies reporting better outcomes for trial participants while others do not. It is possible that the difference in outcomes is due to differences in baseline characteristics of participants and non-participants. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 trial was a large randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) for hematopoietic cell transplantation (HCT) from HLA-matched or 1 allele mismatched unrelated donors (URD) in patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndromes. The trial reported no significant survival differences between PB and BM; there was decreased risk of graft failure but increased risk of chronic graft-versus-host disease (GVHD) with PB grafts (Anasetti et al NEJM 2012).

BACKGROUND: With improvements in the treatment of Hodgkin lymphoma (HL) over time, we hypothesized a reduction in disease progression, and an increase in progression-free (PFS) and overall survival (OS) over the past 3 decades.

The use of routine surveillance imaging (RSI) for patients in first complete remission (CR1) following front-line rituximab (R) based anthracycline therapy remains controversial. We compared patients with diffuse large B-cell lymphoma (DLBCL) who received an R-CHOP or a similar regimen, obtained a CR and then were followed by either RSI or clinical surveillance (CS) in which scans were only performed for signs or symptoms.

Our previous studies have shown little or no difference in the overall survival (OS) of urban over rural cohorts with lymphoma. Autologous hematopoietic stem cell transplantation (Auto-HSCT) is a frequently used treatment for non-Hodgkin lymphoma (NHL), but the elderly tend to tolerate transplant less well than their young counterparts. Increased prevalence of chronic conditions, comorbidity and frailty, serve to further complicate treatment in the elderly. We hypothesize that the same factors that contribute to the complexity of Auto-HSCT in the elderly may also contribute to outcome disparity according to area of residence.To determine if area of residence is an independent risk factor for the following clinical outcomes: relapse, non-relapse mortality (NRM), disease-free survival (DFS) and OS following Auto-HSCT in the elderly with NHL.This is a retrospective cohort study of patients (pts) age ≥60y who underwent first Auto-HSCT for NHL between 1985 and 2012. Using pts' residential ZIP codes at the time of transplant, the primary area of residence was categorized as urban or rural according to the Rural-Urban Commuting Area Codes classification system. Multivariate analyses (MVA) were performed using Cox proportional hazards regression analysis to evaluate the association between area of residence and all outcomes while adjusting for significant patient-, disease-, and treatment-related variables.During the study period, 1616 pts underwent Auto-HSCT for NHL; 321 (20%) of whom were elderly. A total of 286 (89%) had classifiable U.S. ZIP codes: urban (n=182, 64%) and rural (n=104, 36%). The median age was 65y (range 60-77), 64% males, and 93% of the NHL types are high-grade. We failed to detect significant differences in all patient-, disease-, and treatment-related factors between the two cohorts except for disease stage at the time of transplant (p=0.03); urban pts tend to be in relapse at the time of transplant (35% vs 25%), while rural pts tend to be in second or more complete remission ( 34% vs 18%). MVA results are summarized in the table below. We failed to detect differences in the risk of relapse and NRM between urban and rural cohorts. Both risk for treatment-failure (inverse of DFS) and mortality were time-dependent such that the association between area of residence and outcome varied before and after 6 months post-transplant. The risk of treatment-failure and mortality was significantly lower in the rural cohort compared to the urban cohort after 6 months; while similar in the first 6 months. Age and year of transplant were significantly associated with DFS and OS; disease stage at the time of transplant was not significant. The probability of OS (see figure) at 5 and 10 years post-transplant in urban and rural cohorts were 44% vs 54% and 26% vs 38%, respectively. The causes of death were not statistically different between the two groups with most dying from relapse, multi-organ failure and second malignancies.The absence of clear differences in characteristics of elderly NHL pts who underwent Auto-HSCT according to area of residence suggests a similar selection process. The better DFS and OS after 6 months that persist over time and is not explainable by marked differences in relapse, NRM or treatment received suggests interplay of other non-biological factors including: attitudes, health seeking behaviors, environment-related factors, or health care follow-up. Further research is needed to determine the underlying cause of the observed outcome disparity among elderly NHL transplant pts.Armitage: Ziopharm: Consultancy; Roche: Consultancy; Genetech : Consultancy; Seattle Genetics: Consultancy; GlaxoSmith Kline : Consultancy; Tesaro bio, Inc. : Membership on an entity’s Board of Directors or advisory committees. Vose:Sanofi-Aventis US, Inc.: Research Funding; Pharmacyclics: Research Funding; Onyx Pharmaceuticals: Research Funding; Millennium: Research Funding; Janssen Biotech : Research Funding; Incyte Corp.: Research Funding; GlaxoSmithKLINE: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Allos Therapeutics/Spectrum: Research Funding; US Biotest, Inc. : Research Funding.

No relevant conflicts of interest to declare.

Timeliness of care is one of 4 main indicators of quality of care cited by the Institute of Medicine. In the US, an individual’s type of insurance or lack thereof has been implicated as a barrier to obtaining timely treatment, including HSCT. We compared the time to insurance approval between private and public payers among those who were undergoing evaluation for HSCT. Additionally, we evaluated if time to insurance approval is associated with survival after HSCT in patients (pts) with hematologic malignancies.This is a retrospective cohort study that used the Insurance Transplant Database of an academic medical center. All pts evaluated for possible HSCT between 2007 and 2011 were included. Time to insurance approval (index of timeliness) was operationally defined in 3 ways: 1) payer approval – from request for approval to actual payer approval, 2) transplant speed – from payer approval to time of actual transplant, and 3) total time – from request for approval to transplant. Multivariate regression analysis was used to evaluate differences in time to approval between public and private payers. The pts who underwent HSCT were compared for pt-, disease- and transplant-related factors according to type of payer and speed of payer approval. The 3 indices of timeliness were dichotomized (using median) to evaluate if shorter (lower half) or longer (upper half) times were associated with 1 year overall survival (OS) using multivariate Cox proportional hazards regression.Of the 1389 pts evaluated for possible HSCT during the study period, 830 (60%) did not proceed to transplant: of these, 454 (55%) were not recommended for HSCT because transplant MD felt transplant was not beneficial, 119 (14%) were referred to other centers, 113 (14%) expired during the evaluation process, 89 (11%) did not want HSCT, 48 (6%) became ineligible because of significant risks due to mix of age, disease stage and comorbidities, and only 7 (1%) were denied by insurance. Of the 559 (40%) who underwent HSCT, 521 underwent first transplant: of these, 421 (80%) had private insurance, 97 (19%) had public payers (Medicare n=74, Medicaid n=23), and 3 (1%) self-pay. Pts with private insurance are likely to: be younger (53y vs 58y), whites, have higher income, reside in urban area, and have no comorbidities. Cohorts were similar in distributions of disease type, disease stage and type of transplant. Time to payer approval was longer in pts with private insurance than public payers [4 d (range 0-90) vs 0 d (0-28), p<0.0001], but time from approval to actual transplant was longer in pts with public payers than private insurance [65 d (14-277) vs 39 d (1-402), p<0.0001]. Total time to transplant was longer for public payers than private insurance [66 d (14-277) vs 48 d (1-407), p<0.001]. These differences persisted in multivariate analyses adjusting for significant covariates. In a subset analysis of the 509 HSCT pts (public or private payers) with hematologic malignancies, we tested if shorter vs longer approval times in the 3 indices of timeliness were associated with pt characteristics and 1 year OS. Pt characteristics did not differ between the groups with fast vs. slow approval times. Multivariate Cox regression adjusting for age, type of payer, and disease stage showed no significant differences in risk of death between slow and fast approval in the 3 indices of timeliness in the models that used: a) all pts, b) autologous HSCT in lymphoma (n=278), c) autologous HSCT in multiple myeloma (n=121); and d) allogeneic HSCT (n=110).Insurance approval is generally fast, although the speed varies between public and private payers in HSCT. Among the cohort who successfully proceeded to HSCT, within the range of approval times observed, we did not see a difference in 1 year overall survival between shorter vs. longer approval times. While insurance approval may cause delays in timeliness of transplant, this study failed to show a significant association with survival.No relevant conflicts of interest to declare.

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas (NHL) characterized by poor treatment outcomes with conventional chemotherapy, including CHOP [complete remission (CR) ∼40%]. Retrospective studies suggest that the incorporation of etoposide into chemotherapy regimens may improve outcomes compared to CHOP. In contrast, anthracyclines appear to have a limited role in PTCL, largely attributed to p-glycoprotein related resistance. Pralatrexate was the first drug approved for patients (pts) with relapsed PTCL, providing a rationale to evaluate it in the front-line setting. Herein, we evaluated the efficacy of a novel combination for the primary therapy of pts with PTCL whereby the anthracycline in CHOP backbone was replaced with etoposide (CEOP) alternating with pralatrexate (P).Pts > 18 years (yrs) with PTCL stages II-IV with no prior therapy and adequate end organ function were eligible. Eligible histologies included, PTCL-NOS, AILT, ALCL (ALK positive pts only allowed if IPI >3). CEOP (Cycle A) was administered as: cyclophosphamide 750 mg/m2 IV d1, etoposide 100 mg/m2 IV d1-3 (or 100 mg/m2 IV d1 and 200 mg/m2 PO days 2-3), vincristine 2 mg IV day 1 and prednisone 100 mg/day X 5 alternating with P (cycle B) 30 mg/m2 IV d 15, 22 and 29 (with vitamin B12 and folate supplementation). Growth factors were used to support both cycles of therapy. Imaging to assess response was done after cycle 2B, 4B and 6B. Pts achieving a remission were eligible for consolidative autologous stem cell transplant (ASCT) after cycle 4B at physician discretion. The primary statistical aim was to improve the CR rate from 40 to 63% with CEOP-P and optional transplant. Secondary objectives included assessment of event free survival (EFS), overall survival (OS) and toxicity of the regimen. A two-stage Simon design (alpha=0.10, 90% power) tested the null hypothesis that the CR rate would be

Our previous studies have shown little or no difference in the overall survival (OS) of urban over rural cohorts with lymphoma. Autologous hematopoietic stem cell transplantation (Auto-HSCT) is a frequently used treatment for non-Hodgkin lymphoma (NHL), but the elderly tend to tolerate transplant less well than their young counterparts. Increased prevalence of chronic conditions, comorbidity and frailty, serve to further complicate treatment in the elderly. We hypothesize that the same factors that contribute to the complexity of Auto-HSCT in the elderly may also contribute to outcome disparity according to area of residence.

The association of transplant provider and center factors with outcomes of allogeneic HCT has not been well described. Potentially modifiable center factors that are found to be associated with better survival could be adopted by centers to improve their quality of transplant care. To study the association of center factors with survival, we (1) conducted a survey of US transplant centers in 2012 to understand their provider and center characteristics, and (2) used patient clinical data submitted by the centers to the CIBMTR for their allogeneic HCTs performed between 2008-2010. The 42 item web based survey was administered to center medical directors and queried about four broad domains: HCT provider characteristics, HCT center resources, institution characteristics and models of care delivery for HCT recipients. Response rate was 79% (85/108 eligible centers). Collectively, the 85 centers represented 1,640 inpatient beds for HCT, 633 HCT physicians and 548 HCT midlevel providers; CIBMTR data for these centers included 11,639 allogeneic HCT recipients over the 3-year time period. We grouped centers into five size categories based on their total allogeneic HCT volume in 2010: ≤ 20 HCT, 21-40 HCT, 41-80 HCT, 81-150 HCT and >150 HCT. Table 1 shows selected provider and center characteristics for our cohort. We also found considerable variation in patient care models among responding centers. For example, the clinical effort of physicians was exclusively dedicated towards care of HCT recipients in 18% of smaller (≤ 20 HCT) centers compared to 80% in larger (>150 HCT) centers. Larger centers were more likely to have a service model with different physicians participating in the inpatient and outpatient care of HCT recipients versus one physician in charge of both inpatient and outpatient care. A greater proportion of larger centers used midlevel providers in the inpatient and outpatient settings and larger centers were more likely to follow patients long-term post-transplant than smaller centers. A variety of care models were identified based on the use of trainees and midlevel providers in the inpatient and outpatient settings, after-hour and emergency care, and care of patients needing ventilator support. The unadjusted 1-year overall survival probabilites for the five center categories were 56% (95% CI, 51-61%), 58% (55-60%), 63% (61-63%), 62% (60-64%) and 66% (64-67%), respectively (log-rank P<0.001). Our study highlights substantial variation in transplant provider and center characteristics and patient care delivery models among US transplant centers. Multivariate analyses will adjust for patient, disease and transplant characteristics to determine whether any center factors, especially those that are potentially modifiable, are independently associated with survival.

The use of routine surveillance imaging (RSI) for patients in first complete remission (CR1) following front-line rituximab (R) based anthracycline therapy remains controversial. We compared patients with diffuse large B-cell lymphoma (DLBCL) who received an R-CHOP or a similar regimen, obtained a CR and then were followed by either RSI or clinical surveillance (CS) in which scans were only performed for signs or symptoms.Patients from three tertiary care center from 2001-2011, who achieved a CR1 with frontline R-CHOP or similar therapy for DLBCL, and had a minimum follow up of 1 year were analyzed. Patients with HIV-related lymphoma, transformed lymphoma, and post-transplant lymphoproliferative disorders were excluded. Patients with composite lymphoma were included only if the DLBCL component was >50%. Patients were stratified into two groups based on the surveillance strategy employed. Baseline patient characteristics, prognostic features, treatment type, and outcomes were compared.391 patients with DLBCL treated with R-CHOP or similar regimens who obtained CR1 were analyzed. There were 129 patients in the CS group and 262 in the RSI group. Patient characteristics (age, gender, stage, and IPI) were similar in the two groups. The median follow up is 5 years (range 1 – 12). Relapse after CR1 was detected in 26 (20%) of patients in the CS group and 46 (18%) of the RSI group. The median number of images in the CS group was 0 (range 0-14) and 4 (range 1-27) in the RSI group, p<0.0001. The median average number of images per year of follow up in the CS group was 0 (range 0-6) and 1 (range 1-13) in the RSI group, p<0.0001. Relapses were detected through clinical manifestations in 100 % of CS cases versus 43% in RSI cases, p=0.01. The 5 year progression-free survival (PFS) was 76% in the CS group and 82 % in the RSI group (p = 0.31). The 5 year overall survival (OS) was 87% in the CS group and 92 % in the RSI group (p=0.15). The table shows an analysis of OS by IPI and type of surveillance.The majority of relapses in patients with DLBCL after achieving CR1 to an R-CHOP or similar regimen occur when signs or symptoms of the disease lead to evaluation and are not detected by RSI. Although asymptomatic relapses are occasionally detected by RSI, in this large cohort of patients neither a PFS nor OS benefit could be demonstrated in favor of RSI. Given the additional cost, radiation exposure and risk of additional procedures, we conclude that the use of RSI in patients with DLBCL in CR1 has limited clinical utility.No relevant conflicts of interest to declare.

Timeliness of care is one of 4 main indicators of quality of care cited by the Institute of Medicine. In the US, an individual's type of insurance or lack thereof has been implicated as a barrier to obtaining timely treatment, including HSCT. We compared the time to insurance approval between private and public payers among those who were undergoing evaluation for HSCT. Additionally, we evaluated if time to insurance approval is associated with survival after HSCT in patients (pts) with hematologic malignancies.

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin's lymphomas (NHL) characterized by poor treatment outcomes with conventional chemotherapy, including CHOP [complete remission (CR) ∼40%]. Retrospective studies suggest that the incorporation of etoposide into chemotherapy regimens may improve outcomes compared to CHOP. In contrast, anthracyclines appear to have a limited role in PTCL, largely attributed to p-glycoprotein related resistance. Pralatrexate was the first drug approved for patients (pts) with relapsed PTCL, providing a rationale to evaluate it in the front-line setting. Herein, we evaluated the efficacy of a novel combination for the primary therapy of pts with PTCL whereby the anthracycline in CHOP backbone was replaced with etoposide (CEOP) alternating with pralatrexate (P).

Lenalidomide and ofatumumab have demonstrated clinical activity as single agents in a variety of types of non-Hodgkin lymphoma (NHL). This trial is a phase I/II trial combining these two agents for treatment of patients with relapsed and refractory B-cell NHL.Patients with relapsed and refractory B-cell NHL of any histology were enrolled on a phase I/II trial combining lenalidomide and ofatumumab. Nine patients were on the phase I part of the trial and received a fixed dose of ofatumumab 1000 mg weekly × 8 doses along with lenalidomide 15 mg (N=3), or10 mg (N=6) for 21/28 days until the time of progression. The phase II portion of the study has 28 patients on the study with adequate follow-up at the time of analysis. The phase II doses were ofatumumab 1000 mg weekly × 8 along with lenalidomide 10 mg on 21/28 days. The lenalidomide was dose adjusted according to standard dose reduction criteria. All patients were on either a daily aspirin or other anticoagulation for thrombosis (DVT) prophylaxis.Thirty seven evaluable patients had adequate follow-up at the time of the analysis. The patients had a median age of 65 years (range 36–81), 76% were male, and 89% have an ECOG performance status of 0–1. The majority of patients had a relapsed indolent lymphoma with 12/37 (32%) follicular lymphoma (FL), 6/37 (16%) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), 7/37 (19%) mantle cell lymphoma (MCL), one unclassifiable indolent lymphoma (3%), and 11/37 (30%) diffuse large B-cell lymphoma (DLBLC). The median duration of follow-up of surviving patients was 13 months (range 4–24). The complete response (CR) rate was 2/37 (5%) (one each FL and DLBCL) and the partial response (PR) rate was 13/37 (35%) for an overall response rate (ORR) of 15/37 (40%). The 1 year progression-free survival (PFS) was 41% (95% CI; 23–58) and the 1-year overall survival (OS) was 68% (95% CI; 49–82). In an analysis of response by patient variables, those significant included the patients with an FL histology (ORR 83%) vs. DLBCL (ORR 18%) or other(SLL, MCL, unclassifiable) (ORR 21%) (p= 0.001) and lactic dehydrogenase (LDH) normal (ORR 56%) vs. elevated (ORR 14%) (p= 0.01). In an analysis of variables for PFS, the variables with significance include diagnosis of FL (1-year PFS 67%) vs. DLBCL (9%) and SLL, MCL, unclassifiable (45%) (p=0.002), LDH normal (1-year PFS 55%) vs. elevated LDH (1-year PFS 19%), and number of prior chemotherapies 1–2 (1-year PFS 58%) vs. > 3 (1-year PFS 19%). Higher grade toxicities included grade 4 neutropenia in 9/37 (24%), one each of grade 4 bacteremia, one grade 4 DVT, stroke, and acute renal failure.The combination of lenalidomide and ofatumumab was well tolerated by most patients. The patients with indolent NHL had a high response rate of 83% and a 1-year PFS of 67%.Vose: Glaxo Smith Kline: Research Funding; Celgene: Research Funding. Off Label Use: Lenalidamide and Ofatumumab will be discussed for use in indolent and aggressive non-Hodgkin lymphoma.

Abstract 3692

Autologous stem cell transplantation (ASCT) is a common treatment modality for patients (pts) with lymphoma and myeloma and in certain settings appears to be associated with improved survival. We evaluated the risk of death and its attributable causes in three sequential cohorts of patients undergoing ASCT between 1983 and 2010 to look for possible changes in outcome over time.Adults ≥ 18 years of age with lymphoma or multiple myeloma who received ASCT between 1983 and 2010 at a university medical center were identified and divided into three cohorts based on time of transplantation: 1983–1990 (I), 1991–2000 (II) and 2001–2010 (III). The primary cause of death (COD) was determined and verified by the attending physician. The risk of dying from a particular cause (relapse, infection, secondary malignancy, organ failure) was compared across time periods using Cox proportional hazards regression while adjusting for age, gender, disease type, stage at transplant, and time from diagnosis to transplant.A total of 2284 pts with lymphoma and myeloma were analyzed, and there were 1215 deaths (with 972 occurring within 5 years of ASCT). Pts transplanted in the more recent time period were older and more likely to be transplanted < 1 year from diagnosis. There was a significant improvement in the 5-year probability of overall survival (OS) over time: 36% vs. 55% vs. 60% (p <0.001) in cohort I, II and III respectively. The most frequent COD was: relapse, organ failure, infection, secondary malignancy and interstitial pneumonitis. The adjusted risk of death from relapse vs. all other causes did not significantly change over time: II vs. I [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.69–1.04], III vs. I [HR 0.86, 95% CI 0.67–1.10]. The risk of death from infection vs. all other causes significantly improved over time: II vs. I [HR 0.20, 95% CI 0.09–0.44, p<0.0001], III vs. I [HR 0.24, 95% CI 0.06–0.09, p 0.003]. The risk of death from organ failure vs. all other causes was not significantly improved: II vs. I [HR 0.78, 95% CI 0.42–1.48)], III vs. I [HR 0.73, 95% CI 0.34–1.54]. The risk of death from second malignancy vs. all other causes was not significantly different across time periods: II vs. I [HR 0.59, 95% CI 0.21–1.66], III vs. I [HR 1.29, 95% CI 0.41–4.04].The OS of patients undergoing ASCT in our institution has improved significantly over the past three decades as assessed in three sequential cohorts. This improvement is related to a measurable decrease in infectious mortality. The reasons for this are likely multifactorial and could include improved supportive care, use of growth factors, cumulative transplant center experience, introduction of peripheral stem cell transplantation vs. bone marrow transplantation, selection of regimens with less toxicity, improved salvage therapies, and patient selection factors. Relapse continues to be the most common cause of death in this patient population with no appreciable change over time. These results suggest that better strategies to improve outcomes are needed which could include better preparative regimens and/or post transplant therapies.Vose: GSK: Research Funding; Millenium: Research Funding; Celgene: Research Funding; BMS: Research Funding; Exelixis: Research Funding; SBio: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding.

No relevant conflicts of interest to declare.

Consolidative high dose chemotherapy [HDT] and autologous peripheral blood hematopoietic stem cell transplant [auto-HSCT] is an effective treatment modality for multiple myeloma [MM]. Many advances during the last two decades have lead to significantly improved progression free survival [PFS] and overall survival [OS]. Novel agents [thalidomide, lenalidomide and bortezomib] have replaced conventional chemotherapy during induction due to superior response rates. Randomized trials have defined melphalan as the optimal preparative regimen prior to auto-HSCT. Further recent attempts to improve the preparative regimen have included the addition of oral busulfan or bortezomib to melphalan. We performed a single institution, retrospective analysis in order to compare the outcomes of patients with newly diagnosed MM, treated with either conventional chemotherapy or novel agents, who received melphalan versus BEAM [carmustine, etoposide, cytarabine, melphalan] regimens during their first auto-HSCT.179 MM patients were treated or referred to the University of Nebraska Medical Center for auto-HSCT between 1999 and 2010. All patients in the analysis were treated with induction regimens that included either VAD [vincristine, doxorubicin, dexamethasone], thalidomide, lenalidomide, or bortezomib. We compared PFS and OS in patients receiving melphalan [140 or 200 mg/m2 (N=103)] versus BEAM [carmustine 300 mg/m2, etoposide 100 mg/m2, cytarabine 100 mg/m2, and melphalan 140 mg/m2 (N=76)]. Characteristics of patients were compared using univariate statistics. The probabilities of PFS and OS were estimated using the Kaplan-Meier method, while the Cox proportional hazard regression analysis was used to evaluate the association between conditioning regimen and PFS or OS while adjusting for significant covariates.No statistical significant differences in age, sex, race, median time from diagnosis to transplant, and disease stage at diagnosis were seen between the two groups. Disease stage at transplant differed between melphalan {CR (complete response) = 5, PR (partial response) = 89, other = 9} versus BEAM {CR = 22, PR = 51, other = 3} [p<0.001]. Median duration of follow-up of survivors for melphalan {60 months} was less than BEAM {100 months} [p<0.0001]. PFS {70 vs 82 at one year [p=0.08], 20 vs 36 at 5 years [p=0.01] – Table 1} and OS {89 vs 88 at one year [p=0.83], 46 vs 59 at 5 years [p=0.05] – Table 2} were improved with BEAM. When compared to melphalan, BEAM was associated with a 30% reduction [HR 0.70, p=0.07] in disease progression and a 37% reduction in treatment failure [HR 0.63, p=0.01]. In addition, BEAM was associated with a 31% reduction [HR 0.69, p=0.009] in death compared to melphalan. With regard to disease progression, treatment failure and death in patients treated with BEAM, patients less than or equal to 60 years old experienced an advantage over patients greater than 60 years old, as demonstrated by increased reductions in disease progression [68% reduction, p=0.005], treatment failure [53% reduction, p=0.005], and death [76% reduction, p=0.006].The use of BEAM as a regimen for newly diagnosed MM patients during their first auto-HSCT was associated with improved PFS and OS when compared to melphalan. BEAM was associated with a reduced risk of disease progression, treatment failure and death. No significant differences were observed based on treatment-related toxicity or treatment related mortality. The improved PFS and OS were independent of the remaining confounding variables in the multivariate analyses with the exception of CR prior to first auto-HSCT and followup time. Therefore, these are potential contributors to the differences in PFS and OS. Further analyses stratified by cytogenetics, induction therapy, therapy after progression of first auto-HSCT and maintenance therapy are required to further characterize the PFS and OS advantage, as well as to potentially identify a specific patient population that may benefit more from BEAM than melphalan. Nevertheless, BEAM appears to be an efficacious, well tolerated preparatory regimen to be considered in future prospective clinical trials.Vose: GSK: Research Funding; Millenium: Research Funding; Celgene: Research Funding; BMS: Research Funding; Exelixis: Research Funding; SBio: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding.

Abstract 1021

Abstract 2040

Studies suggest that many patients with cancer are more optimistic about their life expectancies or chances of cure compared to concurrent estimates from their physicians. In this study, we tested the hypothesis that consultations in which physicians used unambiguous quantitative prognostic communication would be associated with more accurate (concordant) prognostic understanding between patients and their physicians. We also explored the extent to which key patient, physician, and consultation characteristics predicted prognostic agreement. Methods and Subjects: We studied 232 patients having first consultations with 40 physicians from two academic institutions in the HEMA-COMM study. The HEMA-COMM study is an observational study that evaluates doctor-patient communication from patient and physician surveys, patient interviews, and audiotaping and coding of the consultations. The primary outcome for this analysis was prognostic agreement, calculated by subtracting patients' post consultation prognostic estimates from their physicians' post consultation estimates for life expectancy and likelihood of cure. Potential explanatory variables include patient, physician and consultation characteristics, and the occurrence and clarity of prognostic discussions as coded from the consultation audiotapes. Multilevel models tested whether specific physician communication behaviors (provision of quantitative prognostic estimates, inviting questions, or suggesting that prognostic estimates may not apply to the individual, so called “hedging”) predicted patient-physician agreement on prognostic estimates. Results: Median duration of the consultations was 80 minutes. Most patients (over 90%) desired prognostic information, 92% wanted this information in quantitative terms, and 77% of patients said that chance of cure would influence their treatment choice. After the consultation, 85% of patients said their physicians discussed prognosis. Coding of the audiotapes showed that in 77% of consultations, oncologists discussed life expectancy (or survival) in quantitative terms, and in 51% of consultations they discussed chance of cure. One third of patients, however, overestimated their life expectancy by two or more categories, and 34% overestimated chance of cure by 20 percentage points or more. Patients who were younger, less optimistic about their prognoses prior to the consultation, did not have a treatment plan prior to their visits, or were judged by their physicians as “actively seeking prognostic information” were more likely to agree with their physicians about prognosis. Physician communication behaviors such as provision of quantitative prognostic information without hedging and inviting questions were not predictive of patient-physician agreement about prognosis. Conclusion: Providing patients with a clear numerical prognosis does not correlate with improved concordance between physicians and patients about predicted life expectancy and chance of cure, and appears to be insufficient to achieve understanding on its own. Additional approaches to assess and achieve understanding are needed.No relevant conflicts of interest to declare.