Foodborne agents associated with the consumption of aquaculture catfish.

In the Food, Conservation, and Energy Act (Farm Bill) of 2008, Congress amended the Federal Meat Inspection Act to provide that catfish be inspected by the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS). As part of the development of its inspection program, the FSIS conducted an assessment of the food safety risk associated with consuming farm-raised catfish. To thoroughly identify hazards for consideration in the risk assessment, the scientific literature was surveyed for all potential agents that have been linked to illness associated with farm-raised catfish consumption. A review of microbial hazards suggested that Salmonella is the foodborne pathogen most likely to be associated with catfish, but the impact of other pathogens remains unclear. This review also summarizes the current data available on chemical residues in catfish, including pesticides and heavy metals, and any regulatory levels that have been established for these compounds. The current usage of veterinary drugs in aquaculture also is outlined, including information on unapproved usage of drugs in catfish.

Application of Bayesian techniques to model the burden of human salmonellosis attributable to U.S. food commodities at the point of processing: adaptation of a Danish model.

Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country.

Radiosensitization of head/neck squamous cell carcinoma by adenovirus-mediated expression of the Nbs1 protein.

PURPOSE: Local failure and toxicity to adjacent critical structures is a significant problem in radiation therapy of cancers of the head and neck. We are developing a gene therapy based method of sensitizing head/neck squamous cell carcinoma (HNSCC) to radiation treatment. As patients with the rare hereditary disorder, Nijmegen breakage syndrome, show radiation sensitivity we hypothesized that tumor-specific disruption of the function of the Nbs1 protein would lead to enhanced cellular sensitivity to ionizing radiation. EXPERIMENTAL PROCEDURES: We constructed two recombinant adenoviruses by cloning the full-length Nbs1 cDNA as well as the C-terminal 300 amino acids of Nbs1 into an adenovirus backbone under the control of a CMV promoter. The resulting adenoviruses were used to infect HNSCC cell line JHU011. These cells were evaluated for expression of the viral based constructs and assayed for clonogenic survival following radiation exposure. RESULTS: Exposure of cells expressing Nbs1-300 to ionizing radiation resulted in a small reduction in survival relative to cells infected with control virus. Surprisingly, expression of full-length Nbs1 protein resulted in markedly enhanced sensitivity to ionizing radiation. Furthermore, the use of a fractionated radiation scheme following virus infection demonstrates that expression of full-length Nbs1 protein results in significant reduction in cell survival. CONCLUSIONS: These results provide a proof of principle that disruption of Nbs1 function may provide a means of enhancing the radiosensitivity of head and neck tumors. Additionally, this work highlights the Mre11 complex as an attractive target for development of radiation sensitizers.

Risk factors for primary hepatocellular carcinoma in black and white Americans in 2000.

BACKGROUND & AIMS: The incidence of primary hepatocellular carcinoma (HCC) is greater in black Americans compared with white Americans. The aim of this study was to better define racial disparity in HCC patients in the United States. METHODS: We compared HCC risk factors in 158 black and 701 white HCC patients > or = 11 years of age in the Nationwide Inpatient Sample for 2000. RESULTS: Black HCC patients were younger than white patients (mean age, 54.1 +/- 17.1 vs. 65.1 +/- 13.7 y; P < .002). Sixty-two percent of black HCC patients were age 60 or younger, whereas 68% of white HCC patients were age 61 or older. Hepatitis C virus (HCV) (25.4%), diabetes (22.1%), alcohol (15.1%), cryptogenic cirrhosis (8.6%), and hepatitis B virus (HBV) (7.3%) were the most prevalent risk factors for HCC overall. HBV (22.8% vs 3.9%, P < .0001; adjusted odds ratio [OR], 5.3; 95% confidence interval [CI], 3.0-9.2), HCV (34.8% vs 23.3%, P = .0003; OR, 1.3; 95% CI .9-1.9), concurrent HBV and HCV (8.2% vs 1.7%, P < .0001; OR, 4.5; 95% CI, 1.9-10.4), HBV plus diabetes (2.5% vs .3%, P = .002; OR, 14.1; 95% CI, 2.2-88.2), and HCV plus diabetes (8.9% vs 4.4%, P < .02; OR, 2.3; 95% CI, 1.2-4.6) were more common in black HCC patients. There was no racial difference in the frequency of alcoholic and cryptogenic liver diseases and diabetes. CONCLUSIONS: Higher rates of HBV, HCV, concurrent HBV and HCV, and viral hepatitis associated with diabetes might explain the greater burden of HCC in black Americans.

Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer.

Immunodeficiency is a barrier to successful vaccination in individuals with cancer and chronic infection. We performed a randomized phase 1/2 study in lymphopenic individuals after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for myeloma. Combination immunotherapy consisting of a single early post-transplant infusion of in vivo vaccine-primed and ex vivo costimulated autologous T cells followed by post-transplant booster immunizations improved the severe immunodeficiency associated with high-dose chemotherapy and led to the induction of clinically relevant immunity in adults within a month after transplantation. Immune assays showed accelerated restoration of CD4 T-cell numbers and function. Early T-cell infusions also resulted in significantly improved T-cell proliferation in response to antigens that were not contained in the vaccine, as assessed by responses to staphylococcal enterotoxin B and cytomegalovirus antigens (P < 0.05). In the setting of lymphopenia, combined vaccine therapy and adoptive T-cell transfer fosters the development of enhanced memory T-cell responses.

Docetaxel followed by hormone therapy in men experiencing increasing prostate-specific antigen after primary local treatments for prostate cancer.

PURPOSE: Prostatectomy or radiation for localized prostate cancer (PC) can fail in up to 15% to 30% of patients. The purpose of this study was to determine feasibility, tolerability, and outcome of docetaxel followed by hormone therapy in men experiencing an increasing prostate-specific antigen (PSA) after their primary local treatments for PC. PATIENTS AND METHODS: Men with increasing serum PSA after prostatectomy or/and radiation were eligible. Serum PSA had to be > or = 4 ng/mL and serum testosterone had to be in the noncastrate range. Treatment included docetaxel 70 mg/m2 every 3 weeks for up to six cycles, followed by total androgen suppression (luteinizing hormone-releasing hormone agonist plus bicalutamide) and peripheral androgen blockade (finasteride plus bicalutamide) for 12 to 20 months. RESULTS: Thirty-nine men were enrolled; 32 had PSA-only failure, seven also had clinical metastasis. Baseline median PSA was 13.7 ng/mL. Serum PSA decreased > or = 50% in 17 of 35 patients (48.5%) and > or = 75% in seven of 35 patients (20%) with docetaxel. The PSA decreased to a median of 0.1 ng/mL with subsequent hormone therapy. In 28 of 33 patients the PSA increased (median, 0.41 ng/mL) at a median follow-up of 2.3 months after treatment. In contrast, in five of 33 men the PSA remains at 0.1 ng/mL at a median of 18.9 months after therapy; three of these five men had soft tissue metastasis at entry but remain in complete remission. The most common grade 3 to 4 toxicity was neutropenia (61.5%). CONCLUSION: Docetaxel followed by hormone therapy of limited duration may provide disease control in subgroups of men experiencing failure after local treatments for PC.

Factors predicting local tumor control after gamma knife stereotactic radiosurgery for benign intracranial meningiomas.

PURPOSE: To determine the long-term outcomes and prognostic factors in benign intracranial meningiomas treated with gamma knife stereotactic radiosurgery (GK-SRS). METHODS AND MATERIALS: Between 1992 and 2000, 162 patients with benign meningiomas were treated with GK-SRS at the University of Maryland Medical Center. Complete follow-up was available in 137 patients. All patients underwent magnetic resonance imaging (MRI)-based treatment planning. Serial MRIs and clinical exams were performed to assess tumor response. GK-SRS was the primary treatment in 85 patients (62%), whereas 52 patients (48%) had prior surgical resections. The median prescribed dose was 14 Gy (range, 4-25 Gy) to the 50% isodose line. The median tumor volume, treatment volume, and conformity index were 4.5 cc (range, 0.32-80.0 cc), 6.3 cc (range, 1.0-75.2 cc), and 1.34 (range, 0.65-3.16), respectively. The median follow-up for the entire cohort was 4.5 years (range, 0.33-10.5 years). The following factors were included in the statistical analysis for disease-free survival (DFS) and overall survival (OS): sex, age, dose, gross tumor volume (GTV), conformity index (CI), and dural tail coverage. RESULTS: Serial MRI analysis was available in 121 patients (88.3%). Decrease in tumor size was observed in 34 patients (28.1%), whereas there was no change in 77 patients (63.6%), for a crude radiographic control rate of 91.7%. Increase in tumor size was seen in 10 patients (8.3%). New neurologic deficits attributed to the treatment developed in 10 patients (8.3%). The mean DFS and OS for the entire cohort are 4.6 years and 5.0 years, respectively. The 5-year actuarial DFS and OS were 86.2% and 91.0%, respectively. Univariate analysis revealed GTV, sex, CI, and dural tail treatment to be significant prognostic factors. Patients with GTV < or =10 cc also had longer survivals, with the 5-years DFS and OS of 91.9% vs. 68.0% (p = 0.038) and 100% vs. 59.7% (p = 0.0001), respectively. The 5-years actuarial DFS and OS for females vs. males were 90.2% vs. 74.2% (p = 0.0094) and 91.6% vs. 89.1% (p = 0.016), respectively. Patients with CI > or =1.4 achieved a longer DFS, with a 5-year DFS of 95.2% vs. 77.3% (p = 0.01). Patients who had the dural tail treated also had higher 5-year DFS (96.0% vs. 77.9%, p = 0.038). Patients with lower conformity (i.e., CI > or =1.4) tended to have the dural tail covered in the prescription isodose line (p = 0.04). The only factor significant in the multivariate analysis was for patients with GTV >10 cc, who had a worse DFS (hazard ratio 4.58, p = 0.05). CONCLUSIONS: This report adds to the literature that supports the efficacy and safety of GK-SRS in the management of patients with benign intracranial meningiomas. Our report identified male patients, patients with a CI <1.4, and tumor size greater than 10 cc to have a worse prognosis. Patients who were treated with less conformal plans to cover the dural tail had better outcomes. Our data clearly demonstrate the need to adequately cover the dural tail in patients treated with GK-SRS for benign intracranial meningiomas.

Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-d-arabinofuranosylcytosine, mitoxantrone, and bevacizumab.

PURPOSE: Vascular endothelial growth factor (VEGF) promotes acute myelogenous leukemia (AML) cell growth and survival and may contribute to drug resistance. bevacizumab, an anti-VEGF monoclonal antibody, exhibits clinical activity against diverse malignancies when administered with cytotoxic chemotherapy. We conducted a Phase II clinical trial of bevacizumab administered after chemotherapy to adults with refractory or relapsed AML, using a timed sequential therapy (TST) approach. EXPERIMENTAL DESIGN: bevacizumab 10 mg/kg was administered on day 8 after 1-beta-d-arabinofuranosylcytosine 2 g/m(2)/72 h beginning day 1 and mitoxantrone 40 mg/m(2) beginning day 4. In vivo laboratory correlates included AML cell VEGF receptor-1 (FLT-1) expression, marrow microvessel density, and free serum VEGF before and during TST with bevacizumab. RESULTS: Forty-eight adults received induction therapy. Myelosuppression occurred in all of the patients similar to other TST regimens. Toxicities were decreased ejection fraction (6%), cerebrovascular bleed (4%), and mortality of 15%. Overall response was 23 of 48 (48%), with complete response (CR) in 16 (33%). Eighteen (14 CR and 4 partial response) underwent one consolidation cycle and 5 (3 CR and 2 partial response) underwent allogeneic transplant. Median overall and disease-free survivals for CR patients were 16.2 months (64%, 1 year) and 7 months (35%, 1 year). Marrow blasts demonstrated FLT-1 staining before bevacizumab and marked decrease in microvessel density after bevacizumab. VEGF was detected in pretreatment serum in 67% of patients tested, increased by day 8 in 52%, and decreased in 93% (67% undetectable) 2 h after bevacizumab. CONCLUSIONS: In this single arm study, cytotoxic chemotherapy followed by bevacizumab yields a favorable CR rate and duration in adults with AML that is resistant to traditional treatment approaches. The clearance of marrow blasts in some patients after bevacizumab suggests that VEGF neutralization might result directly in leukemic cell death. The potential biological and clinical activity of bevacizumab in AML warrants additional clinical and laboratory study.

A phase II study of timed sequential therapy of acute myelogenous leukemia (AML) for patients over the age of 60: two cycle timed sequential therapy with topotecan, ara-C and mitoxantrone in adults with poor-risk AML.

Acute myeloid leukemia (AML) in the elderly is a serious problem characterized by poor response to therapy and short survival. To improve response to therapy, a timed sequential therapy (TST) approach was designed utilizing topotecan, cytosine arabinoside (ara-C) and mitoxantrone based on multiple studies suggesting that topotecan and mitoxantrone are effective in older patients. Thirty-two adults, >or=60-year-old (median age 69) were included. None had favorable cytogenetics and 44% had and antecedent myelodysplastic syndrome (MDS) or 2 degrees AML. Fifty-nine percent achieved a complete response (CR). Median overall survival (OS) was 6.5 months (95% confidence interval (CI): 3.1-12.0 months; range, 15 days to 25.3 months). Disease-free survival (DFS) for the 19 patients achieving a CR was 7.7 months (95% CI: 6.1-13.7 months; range, 2.9-25.3 months). There were no differences in OS or DFS between cytogenetic or disease etiology groups. Although TST was well tolerated, long-term results in this group of patients are not satisfactory and new approaches are needed.

Outcome analysis for stage IE and IIE thyroid lymphoma.

Previous reports have revealed modest results in the management of thyroid lymphoma with radiotherapy alone. This retrospective report evaluates the outcome of patients treated for thyroid lymphoma with radiotherapy alone and with combined modality therapy (chemotherapy and radiotherapy) at a single institution. Twenty-seven patients with stages IE and IIE non-Hodgkin's lymphoma of the thyroid gland were treated between 1960 and 1998 at Barnes-Jewish Hospital, of which 14 patients were stage IE and 13 patients were stage IIE. The median age at diagnosis was 67 years, and there were 21 females and 6 males evaluated. The median follow-up time was 38 months (range: 3-279 months). All patients had histologically proven non-Hodgkin's lymphoma, of which 22 patients (81%) were intermediate grade. Treatment consisted of radiotherapy alone in 19 patients and a combined modality therapy in 8 patients. The median radiation dose to the thyroid bed was 44 Gy, and most patients received a doxorubicin-containing regimen administered prior to radiotherapy. Patient, tumor, and treatment-related characteristics were evaluated using Cox regression analysis. Local-regional tumor control, disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Four patients had local relapse in this series, with a crude local tumor control rate of 85%. No factor was determined to be significant for local tumor control. The actuarial 5-year DFS and OS for the entire cohort were 57%, and 56%, respectively. In terms of DFS, both age and stage were statistically significant. The 5-year actuarial DFS for patients less than age 65 years was 83% versus 37% for those more than this age (p = 0.024). Furthermore, the 5-year actuarial DFS for patients with stage I and II disease was 69% and 45%, respectively (p = 0.022). In multivariate analysis, age continued to be significant for DFS (p = 0.049). Overall survival analysis revealed age, local tumor control, and stage to be significant in univariate analysis. Multivariate analysis was further carried out using Cox proportional hazard model, and it revealed age (p = 0.006) and local tumor control (p = 0.007) to be significant. Primary thyroid gland lymphomas have a favorable outcome with appropriate therapy, but prognosis depends on both clinical stage and age at presentation. Because of the risk of both local-regional and distant failure, combined modality approaches that use chemotherapy with radiotherapy are warranted for intermediate- and high grade thyroid lymphoma.

Allergic rhinitis: a potential cause of increased asthma medication use, costs, and morbidity.

Allergic rhinitis and asthma each require costly medical resource utilization, and the impact of both conditions is believed to be even greater. This retrospective cost of illness study evaluated the impact of allergic rhinitis on asthma medical care resource utilization rates and costs for patients with asthma plus allergic rhinitis vs. patients with asthma alone. Patients with one or more claims for asthma (n=27,398) were identified from a medical claims database from a large, northeastern U.S. health insurance plan (1992-1994). A subset of 9226 patients also had at least one visit for allergic rhinitis. Inpatient, professional service, major medical, and pharmaceutical (prescription medications) claims were examined. Patients with asthma and allergic rhinitis had greater medical utilization and costs than individuals with asthma only. The presence of allergic rhinitis was associated with greater frequencies and costs of prescriptions for all asthma-related medications evaluated in the study. Patients with both conditions were also more likely to receive care from medical specialists and less likely to be in managed care. Controlling for these factors, allergic rhinitis was still associated with an increase (P<0.0001) in annual costs of more than dollars 350. Allergic rhinitis in patients with asthma nearly doubles annual medical resource utilization and costs and is associated with increased utilization of asthma-related medications. Based on use of asthma medications, patients with concomitant allergic rhinitis can be regarded as having more severe asthma than do those without allergic rhinitis. Physicians should assess asthma patients for symptoms of allergic rhinitis to improve asthma treatment.

Hepatic vascular tumors, angiectasis in multiple organs, and impaired spermatogenesis in mice with conditional inactivation of the VHL gene.

von Hippel-Lindau (VHL) disease is a multisystem inherited cancer syndrome characterized by the development of highly vascular tumors including hemangioblastomas of the retina and central nervous system, pheochromocytomas, and clear cell renal carcinoma, which result from somatic inactivation of the wild-type VHL allele in cells harboring a germ-line VHL mutation. Homozygous inactivation of the VHL gene in mice resulted in embryonic lethality. To produce a mouse model that closely mimics human VHL disease and avoids embryonic lethality, we used Cre/lox site-specific recombination technology. We generated mice carrying conditional VHL alleles and a cre transgene under the control of the human beta-actin promoter, which directs cre expression in a mosaic pattern in multiple organs. VHL(f/d)/Cre mice developed multiple, hepatic hemangiomas that led to premature death, as well as angiectasis and angiogenesis in multiple organs. Interestingly, testes of male VHL(f/d)/Cre mice were unusually small with severely reduced sperm count resulting in infertility. Loss of pVHL function in this VHL conditional knockout mouse model results in an extensive abnormal vascular phenotype in multiple mouse organs, which will provide a useful animal model for testing potential antiangiogenic therapies for VHL disease treatment. Importantly, the phenotypic defects in sperm development observed in these mice support a novel role for VHL in spermatogenesis. This VHL conditional knockout mouse model will provide an in vivo system for studying the functional requirement of the VHL gene in reproductive biology.

Pooled analysis of the CYP1A1 exon 7 polymorphism and lung cancer (United States).

OBJECTIVE: Cytochrome P450 1A1 plays a major role in the bioactivation of a number of tobacco procarcinogens. Much interest has focused on a polymorphism in exon 7 of the CYP1A1 gene which has been associated with a more inducible form of the enzyme. However, past results of its association with lung cancer have been inconsistent, especially in Caucasians. We carried out a pooled analysis of the data submitted to the Genetic Susceptibility to Environmental Carcinogens (GSEC) database to further investigate this association and, especially, to examine the modifying effects of smoking status and race. METHODS: The data set used in this analysis included 11 studies and a total of 1950 cases and 2617 controls. Both fixed- and random-effects, meta-analysis models were used to investigate heterogeneity among studies. Because no clear heterogeneity was found, a pooled analysis was conducted using unconditional logistic regression. RESULTS: The pooled odds ratio for subjects heterozygous and homozygous for the exon 7 polymorphism was 1.15 (95% confidence interval: 0.95-1.39) and 1.54 (95% CI: 0.97-1.46), respectively (p for gene-dosage effect: 0.03). This association was stronger for squamous cell carcinoma (SCC) than adenocarcinoma, and appeared to be stronger in Caucasians than Asians (p for interaction: 0.03). Statistically significant interactions were also detected for smoking status and sex, with the effect of the polymorphism being stronger in never-smokers and in females. CONCLUSIONS: The present data suggest that the CYP1A1 exon 7 polymorphism may confer an increased risk of lung cancer, particularly of SCC, and especially in never-smokers and in women. These interactions need to be confirmed when additional studies are available for pooling.

Timed sequential therapy of acute myelogenous leukemia in adults: a phase II study of retinoids in combination with the sequential administration of cytosine arabinoside, idarubicin and etoposide.

Clinical outcome in acute myeloid leukemia (AML) is unsatisfactory. One strategy to augment cytotoxicity is TST. All-trans retinoic acid (ATRA) down-regulates bcl-2 expression and heightens AML sensitivity to cytosine arabinoside (ara-C)-induced apoptosis in vitro. We designed a trial of ATRA plus ara-C-based TST in an attempt to enhance drug-induced apoptosis and clinical outcome. Between January 1998 and February 2000, 63 patients received induction TST (oral ATRA days 1-6, ara-C and idarubicin days 2-4, VP-16 days 9-11) followed by consolidation TST (ATRA, ara-C and idarubicin followed by a second ara-C infusion days 11-13). Complete remission (CR) was 60%, with higher rates for patients of <60 years (79%), de novo AML (70%), and non-adverse cytogenetics (81%). Median disease-free survival (DFS) for CR patients was 11.2 months (32% at 3+ years). For patients <60 years with de novo AML and non-adverse cytogenetics who underwent two-cycle TST, DFS was 67% at 3+ years. However, patients of age equal to 60 years and those with poor-risk disease features still have poor CR and DFS, despite the addition of ATRA.

Resource utilization for patients undergoing hysterectomy with or without lymph node dissection for endometrial cancer.

OBJECTIVE: The objective was to study the association of age, comorbid illness, race, and type of hospital with resource use in patients undergoing hysterectomy and lymph node dissection for endometrial cancer. METHODS: The study was a population-based analysis of patients undergoing hysterectomy with a diagnosis of endometrial cancer in Maryland 1994-1996. Chi-square and t tests determined differences in means or proportions. Multivariate logistic regression methods were used to build predictive models. RESULTS: The 1281 women underwent total abdominal hysterectomy, 91%; total vaginal hysterectomy, 6%; radical hysterectomy, 2.5%, laparoscopically assisted total vaginal hysterectomy, 0.3%; 32% also underwent lymph node dissection. Neither age, nor race, nor comorbid illness influenced admission to teaching hospitals. Co-morbidity was documented in 56% of cases. African Americans were more likely to have one (P = 0.002) or >1 co-morbid illness (P = 0.045) than Caucasians. The most common complications were anemia (13.6%), infection/fever (12%), cardiac (9.4%), pneumonia (8%), ileus (5%), and bowel obstruction (5%). These complications occurred with higher frequency in teaching hospitals (P = 0.0001), In large hospitals (P = 0.0001), and in African American patients compared to Caucasians (P = 0.028). Multivariate regression analysis revealed that older age, admission to teaching or large hospitals, lymph node dissection, heart disease, and African American race were associated with significantly higher resource use. CONCLUSION: We documented age and racial/ethnic differences in comorbid illness, complications, and resource utilization for patients undergoing hysterectomy for endometrial cancer. The differences in resource use for teaching hospitals may be reflective of the severity of complications, which are indirectly determined by length of stay. Given the higher costs and skills required to care for elderly women with comorbid disease and complications, quantification of the complexity of care is of utmost importance for allocation of sufficient resources for the care of women with endometrial cancer.

ABO mismatch may affect engraftment in multiple myeloma patients receiving nonmyeloablative conditioning.

BACKGROUND: Blood group incompatibility does not appear to affect the overall outcome in patients undergoing myeloablative conditioning before allogeneic BMT. Data on ABO-mismatched transplantation in the nonmyeloablative setting are limited. STUDY DESIGN AND METHODS: A retrospective analysis of the effects of ABO mismatches in multiple myeloma patients who received a nonmyeloablative conditioning regimen was conducted. RESULTS: Three of 27 patients received a minor ABO-mismatched graft, all with evidence of hemolysis before converting to donor ABO group on Days 10, 15, and 6. Six patients received a major ABO-mismatched graft; of these, three developed GVHD of more than grade 2 and subsequently converted to the ABO blood group of the donor on Days 38, 33, and 43. Of the three patients without GVHD, one rejected the allograft and had autologous reconstitution. One remained a mixed chimera to Day 100 despite three donor lymphocyte infusions, and one developed pure RBC aplasia. None of the ABO-matched patients rejected the graft, whether they developed GVHD or not. RBC transfusions were significantly higher in the major and minor ABO-mismatched patients than in the ABO-matched patients, with medians of 12 units (range, 2-35), 13 units (range, 5-18), and 4 units (range, 2-15), respectively (p = 0.02). ABO-matched patients had a similar incidence of GVHD, with 5 of 9 ABO-mismatched patients (56%) having more than grade 2 versus 10 of 18 (56%). Four of 9 ABO-mismatched patients (44%) were mixed chimeras up to Day 100 versus 2 of 18 ABO-matched patients (11%), and the difference was significant (p = 0.01). CONCLUSION: Patients with ABO mismatch had problems with engraftment, including graft rejection, pure RBC aplasia, and mixed-lineage chimerism. RBC transfusions were significantly higher in the ABO-mismatched recipients. GVHD may play a role in engraftment, possibly by facilitating the disappearance of native ABO antibodies via graft-versus-plasma cell effect. A prospective study to evaluate the effects of ABO mismatch on engraftment in the nonmyeloablative setting is needed.