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Study objectives: 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 [...]

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 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.

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.

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.

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.

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.

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

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.

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

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Vose: Millennium Pharmaceuticals, Inc.: Research Funding.

Previous studies in patients with hematologic malignancies who underwent hematopoietic cell transplantation show only 50% have participated in advance care planning (ACP) at the time of transplant. Moreover, the group that lacked ACP had a higher mortality rate, suggesting that the group least likely to have ACP is the group most likely to need it. Having ACP is thought to be an indicator of quality of care, thus efforts to increase in engagement of ACP are becoming part of clinical practice. However, many argue that discussions about possible death can potentially add to the stress cancer patients already face. We therefore studied the psychological correlates of having ACP to help understand how best to design intervention(s) that may increase engagement in ACP.Data are derived from the HEMA-COMM study cohort – an observational study of patients with hematologic malignancies evaluating doctor-patient communication; 293 patients had self-reported information about ACP and were categorized as to presence or absence of ACP. ACP+ was defined as both having a designated health care proxy and completion of a living will. ACP- lacked one or both. Variables compared include: socio-demographic characteristics, diagnosis, previous treatments, patient and physicians estimate of cure and life expectancy, discussions of wishes for life support, and various measures for coping (BRIEF-COPE), depression/anxiety (HADS), denial, social support (MOS) and quality of life (SF-36). Multivariate logistic regression was used to evaluate the association between the different psychosocial measures and having ACP while adjusting for patient characteristics.Of the 293 patients included, 149 (51%) had ACP. Patients with ACP were more likely to be older (56y v 52y), have higher income, have leukemia or MDS, and have received prior cancer treatment. Of the patients with ACP, only 30% had discussed them with physicians with or without family, 62% had discussed with family only, while 8% had not discussed wishes for life support at all. Patients with ACP had worse estimated prognosis as measured by lower cure rate and life expectancy estimates provided by their physicians. In the multivariate analysis after adjustment for age, diagnosis, income, prior treatment, and patients' perceived life expectancy, patients who use the following coping styles were more likely to have ACP: 1) use of instrumental support (advice, assistance or information), p<0.001; 2) active coping (doing something), p=0.006; 3) use of emotional support (seek moral support, discuss feelings), p=0.009; 4) planning (strategize a plan of action), p=0.04; and 5) positive reframing (positive outlook), p=0.04. These coping styles are all consistent with problem-focused coping as opposed to emotion-focused coping. Discussing ACP wishes with physicians was associated with general health (p=0.007) and overall physical composite SF-36 score (p=0.03). Measures of depression, anxiety, social support, and level of denial were not associated with having or discussing ACP.Our results suggest that patients who engage in ACP have problem-focused coping patterns and may perceive a need based on worse prognosis. Our findings could also suggest that engagement in ACP may be reflective of a patient's realistic or pragmatic view of clinical outcomes. Therefore, efforts to increase engagement in ACP should emphasize the practical benefits of ACP regardless of prognosis and de-emphasize the emotional content of ACP. These approaches may be more appealing to patients regardless of coping style and help increase ACP participation.No relevant conflicts of interest to declare.

Communications literature suggests that optimal doctor-patient communication in medical encounters should include several specific behaviors to enhance successful communication. Very little is known about how often hematologic malignancy subspecialists engage in these behaviors, but several studies have documented that patients are more optimistic about their prognoses than their physicians. We anticipated that a first consultation with a hematology-oncology subspecialist would provide an opportunity to study doctor-patient communication in a particularly intense situation, since the patient and physician are meeting for the first time, discussing a life-threatening disease, and usually confirming or deciding on a treatment plan. Methods and Subjects: We studied 236 patients having first consultations with 40 physicians at two academic institutions in the HEMA-COMM study. The HEMA-COMM study is an observational study designed to evaluate doctor-patient communication with data collected through patient and physician surveys, patient interviews, and audiotaping and coding of the consultations. Results: Median patient age was 55 years and 53% were men, 89% White, 78% married and 60% had at least a college education. Diagnoses included lymphoma (31%), acute leukemia (19%), myelodysplastic syndrome (17%), multiple myeloma (16%) and chronic leukemia (16%). Median age of physicians was 47 years and 85% were men. The median year of fellowship completion was 1992. Physicians estimated they saw a median of 8 new patients a month, 80% of whom were direct referrals. Results: Median duration of the consultations was 80 minutes. Coding of recorded consultations showed the frequency at which recommended communication behaviors occurred: discussion about purpose of the visit (78%), patient prior knowledge about disease (89%), patient preference for decision-making role (37%), patient understanding of presented information (31%), and patient preference for information (5%). Consultations addressed treatment recommendations (97%) and treatment impact on quality of life (52%), but rarely patient participation in recovery (1%). Qualitative prognostic information was provided in 97% of consultations and quantitative information in 90%, but “hedging” (suggestions that prognostic estimates do not apply to the individual) occurred in 23%. Overall, 64% of consultations included clear discussion of mortality risk without hedging and 49% included clear discussions of cure risk without hedging. The median number of patient questions was 23 (range 0-122). The percentage of patients with a treatment plan increased from 31% before the consultation to 79% after the consultation and 98% of patients were happy with their level of involvement in decision-making. Patients were satisfied with their consultations and 80% were very likely to recommend the consulting physician to other patients. Conclusion: Physicians could improve their verbal communication by assessing patients' preferences for information and decision-making roles, and checking for patient understanding during consultations. Approximately half of consultations in our study clearly addressed prognostic topics such as mortality and cure. These data form the basis for investigating factors which contribute to optimal doctor-patient communication about life-threatening disorders.No relevant conflicts of interest to declare.

There is a critical need to have a better understanding of the role health providers play and the need to develop clinical tools to help clinicians identify patients who after completion of treatment for hematologic malignancies may benefit from a more intense follow-up care. The primary purpose of this study was to examine if number of follow-up providers (FUPs) - single versus multiple, influence healthcare utilization (HCU), quality of life and patient satisfaction at 6 months in a cohort of patients who completed treatment for hematologic malignancies. A secondary purpose was to evaluate characteristics of follow-up care that may identify patients at risk for urgent care or hospitalization within 6 months.We utilized data from CANCER-CARES, a longitudinal prospective study of 928 patients with various cancers evaluating follow-up care after completing cancer treatment from a university-based hospital. This study was confined to 314 (52%) patients who had leukemia, lymphoma or multiple myeloma with available 6 month follow-up information. The cohort was divided according to the number of FUPs - single versus multiple. FUP is defined as a physician(s) responsible for managing any aspect of patient's health after cancer treatment. Single FUP may consist solely of a university or community oncologist or other physicians, while multiple FUP may be any combination of the above. Outcomes evaluated included healthcare utilization (HCU) - defined as an emergency room visit or hospitalization within 6 mos, quality of life (SF-12) and patient satisfaction (PSQ-18). Characteristics of follow-up care assocatied with HCU were determined using multivariate logistic regression. Factors determined to be predictive of HCU were assigned one point each. The summated score was used to represent the Follow-up Index Score (FUIS). We used the median FUIS of ≤ 2 to dichotomize the cohort to low vs high scores. The association of the FUIS according to single or multiple FUP with HCU was evaluated using multivariate logistic regression to adjust for patient characteristics.Of the 314 patients, 214 (68%) sought follow-up care with a single FUP (80% remained with university providers, 20% moved back to community providers), while 100 (32%) sought follow-up care with multiple FUPs. Patients seen by single FUP were more likely to be older (median 59y vs 55y), live closer to their FUP (median 60 mi vs 150 mi), less likely to have prescription drug insurance (85% vs 94%), and were less likely to have undergone stem-cell transplantation. Patients seen by single FUP chose their physician more because of preference and quality of care than because of proximity, and were seen less frequently by their FUP as compared to the multiple FUPs. In addition, patients of single providers were seen shorter on their follow-up visits and were less likely to call their FUP with health-related questions. Five patterns of follow-up care were associated with HCU within 6 mos: 1) consult made for cancer-related problems, 2) consult made for other medical problems, 3) referral to another specialist, 4) call made to FUP for medical questions, and 5) ancillary procedures performed (ct, x-ray, ultrasound). In the multivariate analysis, patients seen by single or multiple FUP did not differ in HCU, quality of life and patient satisfaction. However, patients who were seen either by a single or multiple FUP and with low FUIS had significantly lower odds of HCU compared with single FUP with high FUIS [OR 0.11 (95%CI 0.05-0.25), p<0.001; OR 0.26 (95% CI 0.09-0.71), p<0.001) respectively. Patients seen by multiple FUP and have low FUIS also had lower odds of HCU compared with patients with multiple FUP and have high FUIS (OR 0.30, 95% CI 0.10-0.85, p<0.001). We failed to detect differences between patients seen by single or multiple FUPs with low FUIS. No differences in quality of life or patient satisfaction were noted.In summary, patients with hematologic malignancies do not differ between patients who sought follow-up care from single or multiple FUP on HCU, quality of life or patient satisfaction. However, the FUIS shows potential to identify patients who may benefit from an intensive follow-up care plan geared towards preventing hospitalization because it demonstrated that high FUIS scores were associated with increased HCU within a 6 mo. period. The utility of the FUIS in predicting HCU between 6 and 12 months and in different types of malignancies should also be evaluated.No relevant conflicts of interest to declare.

Objectives: We evaluated the association of the primary area of residence (urban vs. rural) and treatment (trt) provider (university-based vs. community-based) with overall survival in patients with lymphoma, and determined if there are patient subgroups that could benefit from better coordination of care. Methods: We performed a population-based study in 2,330 patients with centrally confirmed lymphoma from Nebraska and surrounding states reported to the Nebraska Lymphoma Study Group between 1982 and 2006. Patient residential ZIP codes at the time to trt were used to determine rural/urban designation, household income and distance to trt center; while trt providers were categorized into university-based or community based. Multivariate analyses were used to group patients into risk levels based on 8 factors found to be associated with survival at the time of trt (age, performance score, Ann Arbor stage, presence of B symptoms, LDH levels, tumor bulk, nodal and extranodal involvement). The following categories were identified: low-risk (1–3 factors), intermediate risk (4–5 factors), and high-risk (≥6 factors). Cox proportional regression analyses, stratified by type of lymphoma (low-grade NHL, high-grade NHL and Hodgkin) were used to evaluate the association between place of residence and trt provider with overall survival. Results: Among urban residents, 321 (14%) were treated by university-based providers (UUB) and 816 (35%) were treated by community-based providers (UCB). Among rural residents, 332 (14%) were treated by university-based providers (RUB) and 861 (37%) were treated by community-based providers (RCB). Patients from rural areas were more likely to be older and Caucasian, with a lower median household income, greater travel distance to seek trt, and more likely to have high-risk disease when compared to patients from urban areas. In multivariate analysis, using all patients regardless of risk level, the relative risk of death (RR) among UUB, UCB and RUB was not statistically different. However, RCB had a higher risk of death RR 1.37, 95% CI 1.14–1.65, p=0.01; RR 1.18, 95% CI 1.04–1.33, p<0.01; and RR 1.26, 95% CI 1.06–1.49, p=0.01 when compared with UUB, UCB and RUB, respectively. This association remained true in both low- and intermediate-risk patients. Among high-risk patients, both RUB and RCB were at higher risk of death when compared with UUB or UCB, while UCB were not different from UUB. We found no differences in progression-free survival according to place of residence and trt provider. The use of stem cell transplantation was significantly higher in patients coming from urban and rural areas treated by university-based providers (UUB 19%, RUB 16%) compared to urban and rural patients treated by community-based providers (UCB 11%, RCB 10%, p < 0.01). Patients from rural areas (RUB and RCB) were slightly less likely to die from lymphoma-related causes than patients from urban areas (75% versus 80%, p=0.04). Conclusion: Overall survival in patients with lymphoma is inferior in patients coming from rural areas. This relationship varies according to treatment provider and pretreatment risk levels. Further studies in patients from rural areas are needed to understand how coordination of care is carried to design appropriate interventions that may improve the disparity noted.

Mantle cell lymphoma (MCL) accounts for 7% of all non-Hodgkin’s lymphomas, with median overall survival in most series of 3–4 years. MCL has been classified into three histological subtypes which include diffuse MCL, nodular MCL, and blastic MCL. A relatively small number of studies have examined the prognostic importance of histology in MCL. The aim of this study was to determine if the progression free survival (PFS) and overall survival (OS) rates in mantle cell lymphoma differ among histological subtypes. A total of 102 patients with MCL, treated by the Nebraska Lymphoma Study Group between January 1986 and June 2006, with a median age of 60 years (range 32–89 years) were available for study. Patients were treated with HyperCVAD or a CHOP like regimen with or without rituximab and autologous hematopoetic stem cell transplant (ASCT). All cases were confirmed using cyclin D1 staining. Regardless of treatment, our study failed to show a significant difference in PFS (p=0.26) or OS (P=0.06) among histological subtypes. There was a trend for better survival in patients with nodular MCL. However, in patients receiving ASCT, there was a significantly higher PFS (P=0.0001) and OS (p=0.0005) compared to patients not receiving ASCT. The 3 year PFS for patients receiving HyperCVAD followed by ASCT was 64% compared to the 3 year PFS for HyperCVAD alone of 0 (p=0.008). In conclusion, we failed to show association between histological subtypes of MCL with outcomes regardless of treatment. However, the use of ASCT improved survival.

Background: The use of auto-HSCT has expanded to include older patients. Age is a risk factor for the development of AF in the general population. As more elderly patients undergo auto-HSCT, the risk of developing AF post-transplant may also increase. The development of AF may increase morbidity, may prolong hospitalization, and may increase the cost of hospitalization. However, few data exist evaluating the factors that contribute to the development of AF following auto-HSCT. At our institution, we have observed a large number of patients with this complication. Therefore, we performed a retrospective case-control study to determine the incidence of AF following auto-HSCT and to determine risk factors associated with the development of AF. Patients and Methods: We performed a chart review on all patients at our institution who received an auto-HSCT from November 1999 to May 2004. Cases were identified by reviewing EKGs performed post-transplant. Controls consisted of patients with similar age, year of transplant, and underlying hematologic malignancy. The following variables were examined for their association with AF: age, sex, diagnosis, disease stage at transplant, conditioning regimen, year of transplant, previous medical history including cardiac history, pre-transplant cardiology work-up, and electrolyte abnormalities immediately following auto-HSCT. Patients who developed AF were compared to controls. Multivariate logistic regression was done to evaluate the factors associated with the development of AF. Results: During the study period, 44 patients developed AF at a median of four days (range days 1–9) following auto-HSCT; incidence of 8.5%. We identified 516 patients who did not develop AF who had auto-HSCT in the same time period. Of these, 179 patients with similar characteristics were used as controls. The following variables were associated with developing AF in the multivariate model: age at transplant; median age 63 yrs (50–72) for cases vs 57 (49–72) for controls (p<0.001), abnormal renal function as determined by serum creatinine (p=0.008), history of previous arrhythmia (p<0.001), and a history of mediastinal irradiation (p=0.003). Although not significant in the multivariate model, we observed that 45% of the patients who developed AF had increased left atrial size on a pre-transplant echocardiogram as opposed to none in the controls (p<0.001). There was no difference in the length of hospital stay between the cases and controls (p=0.13). We did not detect a significant difference in the 100d survival between those who did and did not develop AF (90% vs 96%, p=0.25). However, patients who did not develop AF had a better overall survival (Log-rank p=0.04). Conclusions: Patients with older age, elevated serum creatinine level, history of previous arrhythmia, or history of previous mediastinal irradiation are more likely to develop AF following an auto-HSCT. Future studies should investigate whether interventions such as prophylactic beta-blockers can decrease the incidence of AF following auto-HSCT.

Background: There is limited information regarding the patterns of use of VAD in patients undergoing HSCT. With its frequent use in HSCT and its potential to cause morbidity, studying the patterns of VAD use have clinical and preventive implications. Methods: A World Wide Web based 19-item questionnaire was designed to determine the patterns of use of VAD in patients undergoing HSCT. The questionnaire was sent via electronic mail to the directors of HSCT programs throughout the world. Results: Of the 445 centers surveyed, 163 centers replied for a response rate of 37%. Fifty-seven percent of the respondents were from North America, 21% from Europe, 7% from Asia and 15% from other geographic areas. Sixty-two percent of the institutions were university-based or teaching institutions and 18% were primarily cancer center-based. In 26% of the institutions VAD are inserted by interventional radiologists and in 18% by general surgeons. The remaining institutions utilize several healthcare professionals for VAD insertion including physicians, physician assistants, and nurses. Sixty-two percent of centers use the subclavian vein as the preferred site of insertion while 31% prefer to use the internal jugular vein. VAD insertions are done in the operating room in 36% of centers, while 26% of the institutions prefer to use the radiology suite. The majority of the institutions (82%) did not give prophylactic antibiotics to patients before VAD insertion. The most commonly used method to determine catheter position was chest X-ray (62%) followed by fluoroscopy (36%). The most frequently utilized VAD for autologous peripheral blood stem cell (PBSC) harvest when peripheral vein access was not possible was the two-lumen silicone pheresis type catheter (62%). Fifty-eight percent of the institutions utilize the same catheter used for PBSC harvest to provide vascular access support during the transplant. The most frequently utilized VAD for allogeneic stem cell transplantation was the multilumen silicone pheresis type catheter (68%). Only 18% utilize low-dose warfarin routinely for prophylaxis of VAD-related thrombosis. When thrombosis of the catheter is suspected, 82% of the transplant centers routinely perform radiologic studies. The most common radiologic study performed to evaluate VAD thrombosis was sonography (63%) followed by venography (25%). Medications utilized by the institutions for initial therapy of VAD occlusion included recombinant tissue plasminogen activator (48%), urokinase (23%) and heparin (18%). Of interest, 64% of the institutions had established criteria for removal of VAD when infection was suspected or documented and only 48% had established criteria for removal of VAD when occlusion was suspected or established. Sixty-nine percent of the institutions had established criteria for removal of VAD after transplantation. Conclusions: The patterns of use of VAD during HSCT vary widely across institutions. Many centers do not have established criteria for VAD removal after HSCT or in response to VAD complications. Studies should be performed to determine the optimal use of VAD during HSCT.

In 2001, the Docket Report from the Food and Drug Administration expressed concerns regarding the potential of microbially contaminated hematopoietic stem cell products to produce morbidity and mortality in transplant recipients. This concern was the basis for development of regulatory standards for hematopoietic stem cell products. We surveyed a total of 2972 patients at 121 U.S. transplant centers that registered patients with the CIBMTR in the years 2000 and 2001. Information regarding microbial contamination of infused grafts was obtained from 94 transplant centers (80% response rate) for 2312 patients. 52 (2%) of 2286 infused grafts tested were culture positive for bacterial or fungal organisms. The microbial isolates included: coagulase negative staphylococcus (56%), gram negative organisms (15%), coagulase positive staphylococcus (10%), gram positive rods (10%), streptococcus (8%), and fungus (1%). Prophylactic antibiotics targeted at the contaminant were given to 17 of the 52 recipients of contaminated grafts. Antibiotic regimens included vancomycin alone (76%), aminoglycosides and vancomycin (12%), or cephalosporin and vancomycin (12%). 47 (50%) of the centers that participated have existing policies regarding contaminated products. Patients with non-malignant disorders or who received bone marrow were more likely to have a contaminated graft. No differences in age distribution, sex, race, type of transplant (allogeneic vs autologous) and year of transplant were noted between recipients of contaminated and non-contaminated grafts. The unadjusted 100-day survival of persons receiving contaminated grafts was 86% (95% Confidence Interval [CI] 72–93%) versus 81% (95% CI 80–83%) among those receiving non-contaminated grafts, p=0.35. In summary, about 2% of hematopoietic stem cell products infused for allogeneic or autologous transplantations in U.S. centers will test positive for microbial contamination, but such contamination does not increase posttransplant mortality. The absence of significant 100-day mortality among patients infused with contaminated grafts suggests that stringent regulatory policies regarding the use of contaminated hematopoietic cell products may not be indicated.