Hillard M Lazarus

Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada, United States

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Publications (548)3412.28 Total impact

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    ABSTRACT: Anthracyclines are the cornerstone of therapy for a wide spectrum of malignancies and have improved patient survival. Concern for anthracycline-related cardiotoxicity often leads to dose reductions or use of second-line regimens, which may adversely impact survival. Development of cardiotoxicity depends on a combination of cumulative dose modulated by individual patient characteristics, which we have termed individual cardiotoxic threshold (ICT). Patients with cancer often have characteristics such as age, gender, genetic predisposition and preexisting cardiovascular disease that can potentiate cardiotoxicity. Specialty cardiovascular assessment, more sensitive monitoring technology, and timely interventions in selected patients can decrease cardiotoxicity and improve patient outcomes. Prophylaxis with cardioprotective agents and other strategies have shown promising results in randomized trials and may improve tolerance to anthracyclines. In this review we introduce the concept of ICT and critically analyze the evidence supporting existing strategies to modulate it and increase cardiovascular tolerability of anthracyclines.
    Blood Reviews 11/2015; DOI:10.1016/j.blre.2015.11.001 · 5.57 Impact Factor
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    ABSTRACT: Risk factors for non-Aspergillus mold infection (NAMI) and the impact on transplant outcome are poorly assessed in the current era of antifungal agents. Outcomes of 124 patients receiving allogeneic hematopoietic cell transplantation (HCT) diagnosed with either mucormycosis (n=72) or fusariosis (n=52) between days 0 and 365 after HCT are described and compared with a control cohort (n=11 856). Patients with NAMI had more advanced disease (mucormycois: 25%, fusariosis: 23% and controls: 18%; P=0.004) and were more likely to have a Karnofsky performance status (KPS) <90% at HCT (mucormycosis: 42%, fusariosis: 38% and controls: 28%; P=0.048). The 1-year survival after HCT was 22% (15-29%) for cases and was significantly inferior compared with controls (65% (64-65%); P<0.001). Survival from infection was similarly dismal regardless of mucormycosis: 15% (8-25%) and fusariosis: 21% (11-33%). In multivariable analysis, NAMI was associated with a sixfold higher risk of death (P<0.0001) regardless of the site or timing of infection. Risk factors for mucormycosis include preceding acute GvHD, prior Aspergillus infection and older age. For fusariosis, increased risks including receipt of cord blood, prior CMV infection and transplant before May 2002. In conclusion, NAMI occurs infrequently, is associated with high mortality and appears with similar frequency in the current antifungal era.Bone Marrow Transplantation advance online publication, 2 November 2015; doi:10.1038/bmt.2015.263.
    Bone marrow transplantation 11/2015; DOI:10.1038/bmt.2015.263 · 3.57 Impact Factor

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    ABSTRACT: Grade 3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade 3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs autologous hematopoietic cell transplantation (auto-HCT) in the rituximab era. A total of 197 patients undergoing first reduced-intensity conditioning (RIC) allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naive patients were excluded. Allo-HCT recipients were younger, more heavily pretreated and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, PFS and overall survival (OS) for auto-HCT vs allo-HCT groups were 4% vs 27% (P<0.001), 61% vs 20% (P<0.001), 36% vs 51% (P=0.07) and 59% vs 54% (P=0.7), respectively. On multivariate analysis, auto-HCT was associated with reduced risk of NRM (relative risk (RR)=0.20; P=0.001). Within the first 11 months post HCT, auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11 months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; P=0.003) and inferior PFS (RR=3.2; P=0.005). In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.42; P=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; P=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors.Bone Marrow Transplantation advance online publication, 5 October 2015; doi:10.1038/bmt.2015.223.
    Bone marrow transplantation 10/2015; DOI:10.1038/bmt.2015.223 · 3.57 Impact Factor
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    ABSTRACT: Purpose: Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and methods: Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results: Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m(2) or greater were associated with worsened OS. Conclusion: Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.
    Journal of Clinical Oncology 09/2015; DOI:10.1200/JCO.2015.62.4015 · 18.43 Impact Factor
  • Michael R. Jacobs · Hillard M. Lazarus · Robert W. Maitta ·
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    ABSTRACT: To the Editor: In their Perspective article on pathogen-reduction technology (PRT) (May 14 issue),(1) Snyder et al. praise the value of this technology. However, they omit a discussion of concerns about the safety and efficacy of PRT, stating that "Numerous studies demonstrate little substantive negative effect from pathogen reduction on plasma proteins or platelets." A study in the Netherlands was terminated because of increased bleeding complications in the PRT group,(2) and a U.S. study documented five fatal cases of the acute respiratory distress syndrome in the PRT group (1.6%) versus none in the control group.(3) Furthermore, PRT fails to inactivate . . .
    New England Journal of Medicine 08/2015; 373(9):882. DOI:10.1056/NEJMc1507761#SA1 · 55.87 Impact Factor
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    ABSTRACT: In patients with multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (auto-HCT), peripheral blood progenitor cells may be collected following mobilization with growth factor alone (GF) or cytotoxic chemotherapy plus GF (CC+GF). It is uncertain whether the method of mobilization affects post-transplant outcomes. We compared these mobilization strategies in a retrospective analysis of 968 patients with MM from the Center for International Blood and Marrow Transplant Research database who received an auto-HCT in the US and Canada between 2007 and 2012. The kinetics of neutrophil engraftment (⩾0.5 × 10(9)/L) was similar between groups (13 vs 13 days, P=0.69) while platelet engraftment (⩾20 × 10(9)/L) was slightly faster with CC+GF (19 vs 18 days, P=0.006). Adjusted 3-year PFS was 43% (95% confidence interval (CI) 38-48) in GF and 40% (95% CI 35-45) in CC+GF, P=0.33. Adjusted 3-year OS was 82% (95% CI 78-86) vs 80% (95% CI 75-84), P=0.43 and adjusted 5-year OS was 62% (95% CI 54-68) vs 60% (95% CI 52-67), P=0.76, for GF and CC+GF, respectively. We conclude that MM patients undergoing auto-HCT have similar outcomes irrespective of the method of mobilization and found no evidence that the addition of chemotherapy to mobilization contributes to disease control.Bone Marrow Transplantation advance online publication, 24 August 2015; doi:10.1038/bmt.2015.190.
    Bone marrow transplantation 08/2015; DOI:10.1038/bmt.2015.190 · 3.57 Impact Factor
  • N Epperla · T S Fenske · H M Lazarus · M Hamadani ·
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    ABSTRACT: Disease relapse after autologous hematopoietic transplant (auto-HCT) remains the number one cause of post-transplant therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at the prevention of post-auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. Although high dose therapy (HDT) provides durable responses in chemosensitive relapsed diffuse large B-cell lymphoma (DLBCL), a sizable subset experiences disease relapse. Unfortunately, the addition of rituximab as a post-auto-HCT maintenance strategy did not improve survival outcomes. The preliminary results with programmed death -1 (PD-1) Ab as post-auto maintenance in DLBCL is promising but requires randomized validation. In follicular lymphoma, the 5- and 10-year PFS rates are ~60% and 31%, respectively. Although the addition of rituximab improved PFS, there is no survival benefit, to date. Disease relapse after auto-HCT in mantle cell lymphoma (MCL) is not uncommon. Rituximab maintenance in this setting provides a PFS benefit. Given the poor prognosis of post-auto-HCT failures in MCL, maintenance can be considered on a case-by-case basis. In chemosensitive relapsed Hodgkin lymphoma, addition of brentuximab vedotin after auto-HCT improved 2-year PFS (65 vs 45%) and can be considered as an option for maintenance therapy post auto-HCT, in select higher risk patients. Ongoing trials evaluating the efficacy of post-auto-HCT maintenance with novel agents (for example, immunomodulators, proteasome inhibitors, PD-1 inhibitors, Bruton's tyrosine kinase inhibitors and so on) will likely change the practice landscape for lymphoma patients following HDT and auto-HCT.Bone Marrow Transplantation advance online publication, 17 August 2015; doi:10.1038/bmt.2015.184.
    Bone marrow transplantation 08/2015; DOI:10.1038/bmt.2015.184 · 3.57 Impact Factor
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    ABSTRACT: Comparison of long-term outcomes in patients with refractory/relapsed grade 1-2 follicular lymphoma (FL) after allogeneic (allo-HCT) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. Adult patients with relapsed/refractory grade 1-2 FL undergoing 1(st) reduced-intensity allo-HCT or 1(st) autograft during 2000-2012 were evaluated. A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger; more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto- vs. allo-HCT groups for non-relapse mortality (NRM) were 5% vs. 26% (p<0.0001); relapse/progression: 54% vs. 20% (p<0.0001); progression-free survival (PFS): 41% vs. 58% (p<0.001) and overall survival (OS): 74% vs. 66% (p=0.05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months post-HCT (RR=4.4; p<0.0001), and worse PFS (RR=2.9; p<0.0001) beyond 11 months post HCT. In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.41; p<0.0001), but beyond 24 months with inferior OS (RR=2.2; p=0.006). A landmark analysis of patients alive and progression-free at 2-years post-HCT confirmed these observations, showing no difference in further NRM between both groups, but significantly higher risk of relapse/progression (RR=7.3; p<0.0001) and inferior PFS (RR=3.2; p<0.0001) and OS (RR=2.1; p=0.04) following auto-HCT. The 10-year cumulative incidence of second hematological malignancies following allo- and auto-HCT was 0% and 7%, respectively. Auto- and RIC-allo-HCT as 1(st) transplantation approach can provide durable disease control in grade 1-2 FL patients. Continued disease relapse-risk following auto-HCT translates into improved PFS and OS following allo-HCT, in long-term survivors. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 08/2015; DOI:10.1016/j.bbmt.2015.07.028 · 3.40 Impact Factor
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    ABSTRACT: Autologous hematopoietic cell transplantation (AutoHCT) is a potentially curative treatment modality for relapsed/refractory Hodgkin lymphoma (HL). However, no large studies have evaluated pretransplant factors predictive of outcomes of AutoHCT in children, adolescents and young adults (CAYA, age <30 years). In a retrospective study, we analyzed 606 CAYA patients (median age 23 years) with relapsed/refractory HL who underwent AutoHCT between 1995 and 2010. The probabilities of PFS at 1, 5 and 10 years were 66% (95% confidence interval (CI): 62-70), 52% (95% CI: 48-57) and 47% (95% CI: 42-51), respectively. Multivariate analysis for PFS demonstrated that at the time of AutoHCT patients with Karnofsky/Lansky score ⩾90, no extranodal involvement and chemosensitive disease had significantly improved PFS. Patients with time from diagnosis to first relapse of <1 year had a significantly inferior PFS. A prognostic model for PFS was developed that stratified patients into low-, intermediate- and high-risk groups, predicting for 5-year PFS probabilities of 72% (95% CI: 64-80), 53% (95% CI: 47-59) and 23% (95% CI: 9-36), respectively. This large study identifies a group of CAYA patients with relapsed/refractory HL who are at high risk of progression after AutoHCT. Such patients should be targeted for novel therapeutic and/or maintenance approaches post-AutoHCT.Bone Marrow Transplantation advance online publication, 3 August 2015; doi:10.1038/bmt.2015.177.
    Bone marrow transplantation 08/2015; DOI:10.1038/bmt.2015.177 · 3.57 Impact Factor
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    ABSTRACT: The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, N=240) and in myelodysplastic syndrome (MK+MDS, N=221) on hematopoietic cell transplantation (HCT) outcomes compared to other cytogenetically defined groups (AML, N=3,360; MDS, N=1,373) as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1998 to 2011. MK+AML was associated with higher disease relapse (hazard ratio [HR] 1.98, p<0.01), similar transplant related mortality (TRM, HR 1.01, p=0.9) and worse survival (HR 1.67, p<0.01) compared to other cytogenetically defined AML. Among patients with MDS, MK+MDS was associated with higher disease relapse (HR 2.39, p<0.01), higher TRM (HR 1.80, p<0.01) and worse survival (HR 2.02, p<0.01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (HR 1.72, p<0.01) and MDS (HR1.79, p<0.01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 08/2015; DOI:10.1016/j.bbmt.2015.08.024 · 3.40 Impact Factor
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    ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) occurs in 3-7% of the elderly population, with higher prevalence in renal failure patients, and is associated with a 25-fold increased lifetime risk for plasma cell myeloma (PCM), also known as multiple myeloma. Using the California State Inpatient, Emergency Department, and Ambulatory Surgery Databases components of the Healthcare Cost and Utilization Project (HCUP), we sought to determine if patients with MGUS who undergo solid organ allograft (n=22,062) are at increased adjusted relative risk (aRR) for hematological malignancy and other complications. Among solid organ transplant patients, patients with preexisting MGUS had higher aRR of PCM (aRR 19.46; 95%CI 7.05, 53.73; p<0.001), venous thromboembolic events (aRR 1.66; 95%CI 1.15, 2.41; p=0.007), and infection (aRR 1.24; 95%CI 1.06, 1.45; p=0.007). However, when comparing MGUS patients with and without solid organ transplant, there was decreased aRR for PCM with transplant (aRR 0.34; 95%CI 0.13, 0.88; p=0.027), and increased venous thromboembolic events (aRR 2.33; 95%CI 1.58, 3.44; p<0.001) and infectious risks, (aRR 1.44; 95%CI 1.23, 1.70; p<0.001). While MGUS increased the risk of PCM overall following solid organ transplantation, there was lower risk of PCM development compared to MGUS patients who did not receive a transplant. MGUS should not preclude solid organ transplant. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Transplantation 07/2015; 29(9). DOI:10.1111/ctr.12595 · 1.52 Impact Factor
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    ABSTRACT: Previous studies have shown that risks of collection-related pain and symptoms are associated with sex, body mass index (BMI), and age in unrelated donors undergoing collection at National Marrow Donor Program (NMDP) centers. We hypothesized that other important factors (race, socioeconomic status (SES), and number of procedures at the collection center) might affect symptoms in donors. We assessed outcomes in 2,726 bone marrow (BM) and 6,768 peripheral blood stem cell (PBSC) donors collected between 2004 and 2009. Pain/symptoms are reported as maximum levels over mobilization and collection (PBSC) or within 2 days of collection (BM) and at 1 week after collection. For PBSC donors, race and center volumes were not associated with differences in pain/symptoms at any time. PBSC donors with high SES levels reported higher maximum symptom levels 1 week post donation (p=0.017). For BM donors, black males reported significantly higher levels of pain (OR=1.90, CI=1.14-3.19, p=0.015). No differences were noted by SES groups. BM donors from low volume centers reported more toxicity (OR=2.09, CI=1.26-3.46, p=0.006). In conclusion, race and SES have a minimal effect on donation associated symptoms. However, donors from centers performing ≤1 BM collection every 2 months have more symptoms following BM donation. Approaches should be developed by registries and low volume centers to address this issue. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2015; 21(10). DOI:10.1016/j.bbmt.2015.06.013 · 3.40 Impact Factor
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    ABSTRACT: High-dose chemotherapy followed by autologous hematopoietic cell transplantation (HCT) improves outcomes in relapsed lymphoma, but the relative efficacy of different preparative regimens is not well defined. We included patients undergoing autologous HCT using BEAM (carmustine, 300 mg/m2, etoposide, cytarabine, and melphalan) or BEP (carmustine 600 mg/m2, etoposide, and cisplatin) between January 2004 and December 2013; 65 patients received BEP and 64 patients BEAM. Both cohorts were similar for advanced-stage disease, extranodal and bulky disease, and prior therapies. Median neutrophil and platelet engraftment was 10 and 20 days for both regimens, respectively. Febrile neutropenia, serum creatinine concentration increase, and electrolyte abnormalities were more frequent with BEP. Incidence of carmustine pneumonitis was not higher with BEP, likely the result of corticosteroid prophylaxis, although 2 cases of fatal pneumonitis were observed after BEP. One-year nonrelapse mortality was 6.8% after BEP and 0% after BEAM (P = .379). After a median follow-up of 39.4 months (range, 1 to 128), 4-year rates of overall survival (OS) after BEP and BEAM were 80.4% and 72.3%, respectively (P = .611). Diffuse large B cell lymphoma patients transplanted after early relapse post–rituximab-based first-line therapy presented 3-year rates of OS and progression-free survival (PFS) of 73.8% and 65%, respectively. There were no statistically significant differences in the OS and PFS of follicular lymphoma, mantle cell lymphoma, or Hodgkin lymphoma. BEP is a valid alternative to BEAM in autologous HCT. Although associated with more renal and electrolytic toxicities, BEP results in similar disease control and long-term survival as BEAM. Prospective studies are needed to confirm whether intensification of conditioning regimens for autologous HCT can improve disease control in high-risk relapsed lymphoma patients.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2015; 21(11). DOI:10.1016/j.bbmt.2015.06.007 · 3.40 Impact Factor
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    ABSTRACT: Controversy surrounds the question of whether clinical trial participants have better outcomes than comparable patients who are not treated on a trial. We explored this question using a recent large, randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) transplantation from unrelated donors (URD), conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). We compared characteristics and outcomes of study participants (n=494) and non-participants (n=1384) who appeared eligible and received similar treatment without enrolling on the BMT CTN trial at participating centers during the study time-period. Data were obtained from the Center for International Blood and Marrow Transplant Research. Outcomes were compared between the two groups using Cox proportional hazards regression models. No significant differences in age, sex and disease distribution, race/ ethnicity, HLA matching, comorbidities and interval from diagnosis to HCT were seen between the participants and non-participants. Non-participants were more likely to have lower performance status, lower-risk disease, and older donors, and to receive myeloablative conditioning and anti-thymocyte globulin. Non-participants were also more likely to receive PB grafts, the intervention tested in the trial (66% vs. 50% p<0.001). Overall survival, transplant-related mortality, and incidences of acute or chronic GVHD were comparable between the two groups though relapse was higher (HR 1.22, 95% CI 1.02-1.46, p=0.028) in non-participants. Despite differences in certain baseline characteristics, survival was comparable between study participants and non-participants. The results of the BMT CTN trial appear generalizable to the population of trial-eligible patients. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2015; 21(10). DOI:10.1016/j.bbmt.2015.06.004 · 3.40 Impact Factor
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    ABSTRACT: Prior studies report that 9-27% of persons receiving a hematopoietic cell transplant develop arrhythmias, but the effect on outcomes is largely unknown. We reviewed data from 1177 consecutive patients ⩾40 years old receiving a hematopoietic cell transplant at one center during 1999-2009. Transplant indication was predominately leukemia, lymphoma and multiple myeloma. Overall, 104 patients were found to have clinically significant arrhythmia: 43 before and 61 after transplant. Post-transplant arrhythmias were most frequently atrial fibrillation (N=30), atrial flutter (N=7) and supraventricular tachycardia (N=11). Subjects with an arrhythmia post transplant were more likely to have longer median hospital stays (32 days vs 23, P=<0.001), a greater probability of an intensive care unit admission (52% vs 7%; P<0.001), greater probability of in-hospital deaths (28% vs 3%, P<0.001), and greater probability of death within 1 year of transplant (41% vs 15%; P<0.001) compared with patients without arrhythmia at any time. In a multivariate model including age at transplant, diagnosis, history of pretransplant arrhythmia, and transplant-related variables, post-transplant arrhythmia was associated with a greater risk for death within a year of transplant (odds ratio 3.5, 95% confidence interval: 2.1, 5.9; P<0.001). Our data suggest that arrhythmias after transplants are associated with significant morbidity and mortality. A prospective study of arrhythmia in the transplant setting is warranted.Bone Marrow Transplantation advance online publication, 1 June 2015; doi:10.1038/bmt.2015.127.
    Bone marrow transplantation 06/2015; 50(9). DOI:10.1038/bmt.2015.127 · 3.57 Impact Factor

  • Erica L Campagnaro · Teresa E Goebel · Hillard M Lazarus ·
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    ABSTRACT: Plasma cell myeloma (PCM) is a hematologic malignancy that primarily affects the elderly. Approximately two-thirds of patients are aged 65 years or older at diagnosis. Major advances in testing, treatment, and supportive care have resulted in substantial improvement in overall survival in younger, standard-risk, PCM patients over the past 3 decades. However, this positive impact progressively diminishes with advancing age, with some studies showing no improvement in survival outcomes in the elderly. Slow improvement in survival for elderly PCM patients is likely multifactorial, influenced by factors such as age-related physiologic changes, increased comorbidities, decreased treatment tolerance, socioeconomic barriers, and possible differences in disease biology. The standard approach of basing treatment decisions on age and performance status does not account for this complexity, and can be insufficient to determine the risks and benefits of treatment. Comprehensive geriatric assessment (CGA) produces a more thorough iteration of the factors influencing an individual's treatment risk, and can potentially identify targets for intervention to lower risk. Ongoing studies are looking at developing and refining the tools available for risk screening and assessment. Treating elderly PCM patients with novel agent-based regimens with or without autologous stem cell transplantation has improved response rates and survival in some studies, but elderly PCM patients have benefitted less than their younger counterparts from recent advances in PCM treatment. Personalizing treatment decisions, based on predictions of risk, determined by geriatric assessment, and response, determined by precision medicine (our understanding of the genetic, molecular, and cellular pathways that drive an individual's cancer) will help maximize the benefit and minimize the risk of PCM treatment for each patient. Continued evaluation of new strategies and treatments for PCM in clinical trials specifically designed for elderly patients is needed to continue to improve outcomes for elderly PCM patients in the future.
    05/2015; 32(6). DOI:10.1007/s40266-015-0265-x
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    ABSTRACT: To analyze the impact of graft versus host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), peripheral T-cell lymphoma (PTCL), or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor HCT between 1997 and 2009 were included. Two thousand six hundred and eleven cases were included. Reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplants. In a multivariate analysis of myeloablative cases (n=970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n=1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (RR 0.51, p=0.049) and in MCL (RR 0.41, p=0.019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR 0.14, p=0.007; and RR 0.15, p=0.0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment related mortality (TRM) and overall survival (OS) in FL cases, and did not impact TRM, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in follicular and mantle cell lymphoma patients. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2015; 21(10). DOI:10.1016/j.bbmt.2015.05.010 · 3.40 Impact Factor
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    ABSTRACT: Assessment with (18)F-fluorodeoxy glucose-positron emission tomography (FDG-PET) prior to hematopoietic cell transplantation (HCT) for lymphoma may be prognostic for outcomes. Patients with chemotherapy-sensitive non-Hodgkin lymphoma (NHL) undergoing allogeneic HCT reported to the Center of International Blood and Marrow Transplantation Registry between 2007-2012 were included. Pre-HCT PET status (positive vs. negative) was determined by the reporting transplant centers. We analyzed 336 patients; median age was 55 years and 60% were males. Follicular lymphoma (n=104) was more common than large cell (n=85), mantle cell (n=69), and mature NK or T cell lymphoma (n=78); two-thirds of the cohort received reduced intensity conditioning; half had unrelated donor grafts. Patients underwent PET scanning a median of 1 month (range 0.07-2.83 months) before HCT; 159 were PET positive and 177 PET negative. At 3-years, relapse/progression, progression-free survival (PFS), and overall survival (OS) in PET-positive vs. PET-negative groups were 40% vs. 26%; p=0.007; 43% vs. 47%; p=0.47 and 58% vs. 60%; p=0.73, respectively. On multivariate analysis, a positive pre-transplant PET was associated with an increased risk of relapse/progression (risk ratio [RR] 1.86; p=0.001), but was not associated with worse OS (RR 1.29, 95% CI 0.96-1.7,p=0.08), PFS (RR 1.32, 95% CI 0.95-1.84,p=0.10) or NRM (RR 0.75 (0.48-1.18, p=0.22). PET status conferred no influence on graft-versus-host disease. A positive PET scan prior to HCT is associated with increased relapse risk but should not be interpreted as a barrier to a successful allograft. PET status does not appear to predict survival after allogeneic HCT for NHL. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2015; 21(9). DOI:10.1016/j.bbmt.2015.05.007 · 3.40 Impact Factor

Publication Stats

21k Citations
3,412.28 Total Impact Points


  • 2013-2015
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States
  • 1982-2015
    • Case Western Reserve University
      • • Division of Hematology and Oncology
      • • Case Comprehensive Cancer Center
      • • School of Medicine
      • • Department of Medicine (University Hospitals Case Medical Center)
      • • Institute of Pathology
      Cleveland, Ohio, United States
  • 1981-2015
    • Case Western Reserve University School of Medicine
      • • Department of Medicine
      • • Department of Physiology and Biophysics
      Cleveland, Ohio, United States
  • 1980-2015
    • Cleveland State University
      Cleveland, Ohio, United States
  • 2011
    • Roswell Park Cancer Institute
      Buffalo, New York, United States
    • Moffitt Cancer Center
      Tampa, Florida, United States
    • Fox Chase Cancer Center
      Philadelphia, Pennsylvania, United States
    • Mayo Clinic - Rochester
      • Department of Hematology
      Rochester, Minnesota, United States
  • 2010
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
  • 2009-2010
    • University Hospitals Bristol NHS Foundation Trust
      Bristol, England, United Kingdom
  • 2002-2010
    • University of Toronto
      Toronto, Ontario, Canada
  • 2008
    • British Society of Blood and Marrow Transplantation
      Bristol, England, United Kingdom
  • 2003-2007
    • Northwestern University
      • Division of Hematology/Oncology
      Evanston, Illinois, United States
  • 2006
    • Cardiff University
      Cardiff, Wales, United Kingdom
  • 2001-2006
    • Technion - Israel Institute of Technology
      H̱efa, Haifa, Israel
  • 2005
    • University of Chicago
      • Section of Hematology/Oncology
      Chicago, Illinois, United States
  • 2004
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1996-2004
    • Medical College of Wisconsin
      • Center for International Blood & Marrow Transplant Research
      Milwaukee, WI, United States
  • 1999
    • Hôpital Maisonneuve-Rosemont
      Montréal, Quebec, Canada
  • 1995
    • University of South Florida
      • Department of Internal Medicine
      Tampa, Florida, United States
  • 1994
    • Centers for Disease Control and Prevention
      Atlanta, Michigan, United States
  • 1993
    • University Of Miami Hospital
      Miami, Florida, United States
  • 1989
    • Vancouver General Hospital
      Vancouver, British Columbia, Canada
  • 1988
    • University of Florida
      Gainesville, Florida, United States
  • 1987
    • Vanderbilt University
      • Department of Preventive Medicine
      Нашвилл, Michigan, United States
  • 1986
    • University of British Columbia - Vancouver
      • Faculty of Medicine
      Vancouver, British Columbia, Canada
  • 1983-1986
    • Washington University in St. Louis
      • Division of Hematology and oncology
      San Luis, Missouri, United States