Hillard M Lazarus

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

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Publications (533)3230.28 Total impact

  • 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 · 3.47 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 · 3.35 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 · 3.47 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; DOI:10.1111/ctr.12595 · 1.49 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; DOI:10.1016/j.bbmt.2015.06.013 · 3.35 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; DOI:10.1016/j.bbmt.2015.06.007 · 3.35 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; DOI:10.1016/j.bbmt.2015.06.004 · 3.35 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; DOI:10.1038/bmt.2015.127 · 3.47 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; DOI:10.1016/j.bbmt.2015.05.010 · 3.35 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; DOI:10.1016/j.bbmt.2015.05.007 · 3.35 Impact Factor
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    ABSTRACT: Brentuximab vedotin (BV), an antibody-drug conjugate that targets CD30, induces high response rates in CD30+ lymphoid malignancies. It is unknown if BV use affects procurement of autologous CD34+ stem cells and hematopoietic engraftment after ASCT. We examined 42 patients treated with BV before mobilization. Median times from diagnosis to transplant, from initial BV treatment to transplant and from last BV treatment to stem cell collection were: 21 months (range, 10-210), 5 months (range, 1.5-16.8), and 30 days (range, 2-280), respectively. Mobilization was successful on first attempt in 38 patients (90.4%). The median number of infused CD34+ cells was 5.46x10(6)/kg (range, 1.65-54.78x10(6)/kg). The median times to neutrophil and platelet engraftment were 10 (range, 9-13), and 10.5 days (range, 7-35), respectively. BV before HDC-ASCT did not adversely affect peripheral blood stem cell mobilization and subsequent engraftment in a cohort of heavily pre-treated patients with CD30+ lymphomas. 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 04/2015; DOI:10.1016/j.bbmt.2015.04.022 · 3.35 Impact Factor
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    ABSTRACT: The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.Bone Marrow Transplantation advance online publication, 27 April 2015; doi:10.1038/bmt.2015.82.
    Bone marrow transplantation 04/2015; DOI:10.1038/bmt.2015.82 · 3.47 Impact Factor
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    ABSTRACT: Hematopoietic cell transplantation has increased the survival of patients with several types of malignant hematologic disease and hematologic disorders; however, these patients have an increased risk of posttransplant cutaneous malignant neoplasms. Physicians should be aware of associated risk factors to provide appropriate patient screening and long-term care. To identify the incidence and risk factors for cutaneous malignant neoplasms following hematopoietic cell transplantation. A systematic review was conducted using Medline and Cochrane databases from January 1995 to December 2013. Retrospective and prospective reviews containing at least 100 patients who underwent hematopoietic cell transplantation reporting skin cancer as a primary outcome were included. Information regarding the entire cohort, data for the subset who developed cutaneous malignant neoplasms, and cutaneous malignant neoplasm risk factors were extracted from included articles. The level of evidence for each study was assessed using the Strength of Recommendation Taxonomy scale. Patients who underwent hematopoietic cell transplantation had an increased risk of squamous cell carcinoma, basal cell carcinoma, and melanoma. Factors such as primary disease, chronic graft-vs-host disease, prolonged immunosuppression, radiation exposure, light skin color, sex, and T-cell depletion are risk factors for cutaneous malignant neoplasms. Given the increased risk of cutaneous malignant neoplasms in hematopoietic cell transplant recipients, this population should be educated on skin self-examination and pursue regular follow-up with dermatologists.
    04/2015; 151(7). DOI:10.1001/jamadermatol.2015.121
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    ABSTRACT: Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI N=948, TBICy N=821) recipients of related or unrelated hematopoietic cell transplantation (HCT) who received TBI (1200-1500cGY) for acute leukemia from 2003 to 2010. The two cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Ph+ ALL, HLA matched siblings, stem cell source, anti-thymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect TRM (24% vs. 23% at 3y, p=0.67; relative risk [RR] 1.01, p=0.91), leukemia relapse (27% vs. 29% at 3y, p=0.34; RR 0.89, p=0.18), leukemia-free survival (49% vs. 48% at3y, p=0.27; RR 0.93, p=0.29), chronic GVHD (45% vs. 47% at 1y, p=0.39; RR 0.9, p= 0.11) or overall survival (53% vs. 52% at 3y, p=0.62; RR 0.96, p=0.57) for CyTBI and TBICy respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (p=0.08). This study demonstrates that the sequence of Cy and TBI does not impact transplant outcomes and complications in patients with acute leukemia undergoing HCT with myeloablative conditioning. 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 03/2015; DOI:10.1016/j.bbmt.2015.03.017 · 3.35 Impact Factor
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    ABSTRACT: Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.
    Bone Marrow Transplantation 03/2015; · 3.47 Impact Factor
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    ABSTRACT: Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.Bone Marrow Transplantation advance online publication, 30 March 2015; doi:10.1038/bmt.2015.63.
    Bone marrow transplantation 03/2015; DOI:10.1038/bmt.2015.63 · 3.47 Impact Factor
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    ABSTRACT: Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23 272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs 7.3%; P<0.001). A 4-fold increase of PGF was observed in myeloproliferative disorders compared to acute leukemia (P<0.001). Other risk factors for PGF included recipient age below 30, HLA-mismatch, male recipients of female donor grafts, ABO-incompatibility, busulfan/cyclophosphamide conditioning, and cryopreservation. In bone marrow transplants, total nucleated cell doses ⩽2.4 × 10(8)/kg were associated with PGF (OR 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post-transplant may provide the rationale for an early request for additional hematopoietic stem cells.Leukemia accepted article preview online, 16 March 2015. doi:10.1038/leu.2015.75.
    Leukemia 03/2015; DOI:10.1038/leu.2015.75 · 9.38 Impact Factor
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    ABSTRACT: Therapeutic strategies for multiple myeloma (MM) have changed dramatically over the past decade. Thus the role of hematopoietic stem cell transplantation (HCT) must be considered in the context of this evolution. In this evidence-based review we have critically analyzed the data from the most recent clinical trials to better understand how to incorporate HCT and when HCT is indicated. We have provided our recommendations based on strength of evidence with the knowledge that ongoing clinical trials make this a dynamic field. Within this document we discuss the decision to proceed with autologous HCT, factors to consider before proceeding to HCT, the role of tandem auto-HCT, post-HCT maintenance therapy and the role of allogeneic HCT for patients with MM. 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 03/2015; 21(7). DOI:10.1016/j.bbmt.2015.03.002 · 3.35 Impact Factor
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    ABSTRACT: Midostaurin is a novel, orally available Fms-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitor that induces cell cycle arrest and apoptosis of leukemic cells expressing mutant and wild type FLT3 receptors, and has shown potential synergism with cytotoxic chemotherapy. We conducted a phase I study of azacitidine (intravenous 75 mg/m(2) daily for 7 days) with escalating doses of oral midostaurin (25 mg twice per day [b.i.d.], 50 mg b.i.d., and 75 mg b.i.d.) on days 8 to 21 of a 28-day cycle in untreated acute myeloid leukemia (AML) in older patients and/or relapsed AML. Patients were eligible regardless of FLT3 mutation status. Trough blood samples for pharmacokinetics were obtained on days 8, 15, and 21 before midostaurin dosing. Seventeen patients with a median age of 73 (range, 57-83) years were enrolled; 5 patients had previous conventional treatment and none of the patients had FLT3 mutations. Dose-limiting toxicities were not observed. Hospitalizations, primarily for infections, occurred in one-third of treatment cycles. Fourteen patients were evaluable for response: 3 attained complete remission and 2 had hematologic improvement. Median (range) survival from enrollment was 6 (1 to ≥ 19) months. Three patients died within 60 days of enrollment (2 progressive disease, 1 non-dose-limiting toxicity, treatment-related). Pharmacokinetic data at 75 mg orally b.i.d. showed increased trough levels of midostaurin during cycle 2 compared with cycle 1 and persistent and increasing levels of its active metabolite, CGP52421. The combination of sequential azacitidine and midostaurin is safe and tolerable with response rates comparable with azacitidine alone and should be studied further in FLT3 mutation-positive AML. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Lymphoma, Myeloma and Leukemia 02/2015; 15(7). DOI:10.1016/j.clml.2015.02.017 · 2.02 Impact Factor

Publication Stats

19k Citations
3,230.28 Total Impact Points

Institutions

  • 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
      Cleveland, Ohio, United States
  • 1980–2015
    • Cleveland State University
      Cleveland, Ohio, United States
  • 2002–2012
    • University of Toronto
      Toronto, Ontario, Canada
    • Columbia University
      New York, New York, United States
  • 2011
    • Roswell Park Cancer Institute
      Buffalo, New York, United States
    • Imperial College London
      • Division of Experimental Medicine
      London, ENG, United Kingdom
    • Moffitt Cancer Center
      Tampa, Florida, United States
    • Mayo Clinic - Rochester
      • Department of Hematology
      Rochester, Minnesota, United States
    • Fox Chase Cancer Center
      Philadelphia, Pennsylvania, United States
  • 2010
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
  • 2009–2010
    • University Hospitals Bristol NHS Foundation Trust
      Bristol, England, United Kingdom
  • 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
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, 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
    • Emory University
      Atlanta, Georgia, United States
  • 2000
    • Tufts University
      Georgia, United States
    • Loyola University Medical Center
      • Division of Hematology/Oncology
      Maywood, Illinois, United States
  • 1999
    • Treatment Research Institute, Philadelphia PA
      Philadelphia, Pennsylvania, United States
    • Hôpital Maisonneuve-Rosemont
      Montréal, Quebec, Canada
  • 1997
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 1995
    • University of South Florida
      • Department of Internal Medicine
      Tampa, Florida, United States
  • 1993
    • University Of Miami Hospital
      Miami, Florida, United States
  • 1991
    • Group Health Cooperative
      Seattle, Washington, United States
  • 1989
    • Vancouver General Hospital
      Vancouver, British Columbia, Canada
  • 1987–1989
    • Vanderbilt University
      • Department of Preventive Medicine
      Nashville, Michigan, United States
  • 1988
    • University of Florida
      Gainesville, Florida, 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