Koen van Besien

The University of Chicago Medical Center, Chicago, Illinois, United States

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Publications (133)768.79 Total impact

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    ABSTRACT: New York Presbyterian Hospital [NYPH]/Weill Cornell and Memorial-Sloan Kettering Cancer Center [MSKCC], New York, NY Background: Fulminant toxoplasmosis is a rare and difficult to diagnose complication after HSCT. Disseminated toxoplasmosis has a reported incidence of 0.1 to 6% in allogeneic transplants and is often fatal. Methods: We report a cluster of 6 cases of fulminant toxoplasmosis, diagnosed within a 1-year period, at 2 neighboring transplant centers in NYC. Toxoplasmosis was diagnosed by positive serum PCR or at autopsy. Results: Between December 2012 and September 2013, six patients were diagnosed with fulminant toxoplasmosis at MSKCC (4 cases) and NYPH/Weill Cornell (2 cases). The incidence of cases, preceding this study, was 1-2 cases per year at MSKCC and zero over the prior 5 years at NYP/Weill Cornell. Underlying diagnosis were acute lymphoblastic leukemia (2), acute myeloid leukemia, myeloma, lymphoma and myelodysplastic syndrome (1 each). Patients received ex-vivo T-cell depleted peripheral blood stem cell (TCD-PBSC) allograft (3) or umbilical cord + TCD-PBSC allografts (3). Five patients received anti-thymocyte globulin during their conditioning regimen. Five of 6 patients had positive Toxoplasma IgG prior to transplant. All patients presented with fevers prior to developing respiratory failure and death. Median days from transplant to death was 37 days (range 23-135 days). Diagnosis of toxoplasmosis was made by serum PCR (n=4 patients, range 45,100-4,900,000 copies/ml) or at autopsy (n=2 patients). None of the patients were taking prophylaxis with activity against toxoplasma prior to diagnosis. No epidemiologic risk factors to explain the increased incidence were identified. Conclusion: We report an unexplained cluster of 6 cases of fulminant and fatal toxoplasmosis, occurring within a 1 year period, in TCD and UCB recipients at 2 centers in NYC. No common epidemiologic link was identified. We urge a high index of suspicion for toxoplasmosis, and prompt investigation using toxoplasma serum PCR, for severely immunosuppressed HSCT recipients who are toxoplasma seropositive and present with unexplained fevers.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: The treatment of multiple myeloma (MM) has dramatically changed in the last decade due to the introduction of the immunomodulatory drugs (IMIDs) and proteasome inhibitors, otherwise known as the novel agents. Prior to the advent of the novel agents, the gold standard of treatment had been high-dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) for eligible candidates. Given the remarkable activity of the novel agents, and the significant morbidity of HDT/ASCT, the role of stem cell transplantation has now come into question. In this review, we explore the benefits and drawbacks to HDT/ASCT in the era of the novel therapies.
    Current Hematologic Malignancy Reports 08/2014;
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    ABSTRACT: Allogeneic hematopoietic cell transplantation is increasingly utilized in older adults. This study prospectively evaluated the prognostic utility of geriatric assessment domains prior to allogeneic transplantation in recipients 50 years and older. Geriatric assessment was performed prior to transplant, and included validated measures across domains of function and disability, comorbidity, frailty, mental health, nutritional status, and systemic inflammation. 203 patients completed geriatric assessment and underwent transplant. The median age was 58 years (range, 50-73). After adjusting for established prognostic factors, limitations in instrumental activities of daily living (HR 2.38, 95% CI 1.59-3.56; P < .001), slow walk speed (HR 1.80, 95% CI 1.14-2.83; P = .01), high comorbidity by hematopoietic cell transplantation-specific comorbidity index (HR 1.56, 95% CI 1.07-2.28; P = .02), low mental health by short-form-36 mental component summary (HR 1.67, 95% CI 1.13-2.48; P = .01), and elevated serum C-reactive protein (HR 2.51, 95% CI 1.54-4.09; P < .001) were significantly associated with inferior overall survival. These associations were more pronounced in the cohort 60 years and older. Geriatric assessment measures confer independent prognostic utility in older allogeneic transplant recipients. Implementation of geriatric assessment prior to allogeneic transplantation may aid in appropriate selection of older adults.
    Haematologica 05/2014; · 5.94 Impact Factor
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    ABSTRACT: Microchimerism represents a condition where one individual harbors genetically distinct cell populations, and the chimeric population constitutes<1% of the total number of cells. The most common natural source of microchimerism is pregnancy. The reciprocal cell exchange between a mother and her child often leads to the stable engraftment of hematopoietic and non-hematopoietic stem cells in both parties. Interaction between cells from the mother and those from the child may result in maternal immune cells becoming sensitized to inherited paternal alloantigens of the child, which are not expressed by the mother herself. Vice versa, immune cells of the child may become sensitized toward the non-inherited maternal alloantigens of the mother. The extent of microchimerism, its anatomical location, and the sensitivity of the techniques used for detecting its presence collectively determine whether microchimerism can be detected in an individual. In this review, we focus on the clinical consequences of microchimerism in solid organ and hematopoietic stem cell transplantation, and propose concepts derived from data of epidemiologic studies. Next, we elaborate on the latest molecular methodology, including digital PCR, for determining in a reliable and sensitive way the extent of microchimerism. For the first time, tools have become available to isolate viable chimeric cells from a host background, so that the challenges of establishing the biologic mechanisms and function of these cells may finally be tackled.
    Chimerism. 04/2014; 5(2).
  • Koen van Besien, Richard R Furman
    Leukemia & lymphoma 04/2014; · 2.61 Impact Factor
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    ABSTRACT: Non-Hodgkin lymphomas (NHL) disproportionately affect older patients who uncommonly receive allogeneic hematopoietic cell transplantation (HCT). We analyzed CIBMTR data on 1248 patients ≥40 years receiving reduced-intensity conditioning (RIC) or non-myeloablative (NMA) HCT for aggressive (n=668) and indolent (n=580) NHL. Aggressive lymphoma was more frequent in the oldest cohort [(age 40-54) 49% vs. (55-64) 57% vs. (≥65) 67% p=0.0008]; fewer patients ≥65 had prior autografting [26% vs. 24% vs. 9%; p=0.002)]. Rates of relapse, acute and chronic GVHD and non-relapse mortality (NRM) at one year were similar [22%, 95% confidence interval (CI) 19-26%; 27%, 95% CI 23-31%; 34%, 95% CI 24-44%]. Progression-free (PFS) and overall (OS) survival at 3 years was slightly lower in older cohorts [OS:54%, 95% CI 50-58%; 40%, 95% CI 36-44%; 39%, 95% CI 28-50%; p<0.0001]. Multivariate analysis revealed no significant effect of age on acute or chronic GVHD or relapse. Age ≥55 years, Karnofsky performance status <80, and HLA-mismatch adversely impacted NRM, PFS, and OS. Disease status at HCT, but not histologic subtype, worsened NRM, relapse, PFS and OS. Even for patients ≥55 years, OS still approached 40% at 3 years suggesting HCT effects long-term remissions and remains underutilized in qualified older patients with NHL.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2014; · 3.15 Impact Factor
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    ABSTRACT: ABSTRACT We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for hematopoietic stem cell transplantation (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration-time curve (AUC), maximum concentration and clearance, were measured and patients were monitored for renal injury. All patients had normal pre-treatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal.
    Leukemia & lymphoma 02/2014; · 2.61 Impact Factor
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    ABSTRACT: ABSTRACT As antimicrobial resistance increases, understanding the current epidemiology of bloodstream infections (BSIs) in hematopoietic stem cell transplant (HSCT) recipients is essential to guide empirical antimicrobial therapy. We therefore reviewed microbial etiologies, timing and outcomes of BSIs in patients who were transplanted from September 2007-December 2011. Vancomycin-resistant enterococci (VRE) were the most common pathogens in allogeneic HSCT recipients and 4(th) most common after autologous transplantation. VRE did not cause any of 101 BSIs in neutropenic patients who were not receiving antibacterials, but caused 32 (55%) of 58 BSIs in neutropenic patients receiving a broad-spectrum β-lactam agent (P<0.001). Rates of septic shock and seven-day mortality were 5% and 0% for streptococcal bacteremia, 12% and 18% for VRE bacteremia, and 20% and 14% for Gram-negative bacteremia. In conclusion, VRE bacteremia was the most common BSI in allogeneic HSCT recipients, occurred primarily in neutropenic patients receiving broad-spectrum β-lactams, and was associated with poor outcomes.
    Leukemia & lymphoma 02/2014; · 2.61 Impact Factor
  • Bone marrow transplantation 02/2014; · 3.00 Impact Factor
  • Source
    Satyajit Kosuri, Koen van Besien
    Leukemia & lymphoma 01/2014; · 2.61 Impact Factor
  • Koen van Besien
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    ABSTRACT: Abstract The 11th international Cord Blood Meeting was devoted to advances in umbilical cord blood research and transplantation. Results of cord blood transplant (UCB-SCT) for congenital storage disease and hemoglobinopathies are encouraging, but UCB-SCT may also be useful for older adults with hematologic malignancies and UCB have potential in regenerative medicine, particularly for neurological disorders and may serve as excellent targets for gene therapy. UCB donor selection should consider high resolution HLA typing, maternal HLA typing and detection of donor specific HLA-antibodies. The issue of delayed hematopoietic reconstitution has hamstrung UCB SCT but is addressed to a large extent by co-infusion of third party progenitor cells. A number of cell expansion technologies also have great potential. Novel data show more limited benefits of double vs single umbilical cord blood transplantation. Advances in QC of UCB products and other improvements in cord blood banking technology will further improve the quality of stored UCB products.
    Leukemia & lymphoma 11/2013; · 2.61 Impact Factor
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    ABSTRACT: Cyclophosphamide combined with total body irradiation (Cy/TBI) or busulfan (BuCy) are the most widely used myeloablative conditioning regimens for allotransplants. Recent data regarding their comparative effectiveness is lacking. We analyzed data from the Center for International Blood and Marrow Transplant Research for 1230 subjects receiving a first hematopoietic cell transplant from a human-leukocyte antigen matched sibling or unrelated donor during years 2000-2006 for acute myeloid leukemia (AML) in first complete remission (CR) after conditioning with Cy/TBI or oral or intravenous (IV) BuCy. Multivariate analysis showed significantly less non-relapse mortality (relative risk [RR]=0.58; 95% confidence interval [CI]:0.39 - 0.86; P=0.007), and relapse after, but not before, 1 year post-transplant (RR=0.23; 95% CI: 0.08 - 0.65; P=0.006), and better leukemia-free survival (RR=0.70; 95% CI: 0.55 - 0.88; P=0.003) and survival (RR=0.68; 95% CI: 0.52 - 0.88; P=0.003) in persons receiving IV, but not oral, Bu compared to TBI. In combination with Cy, IV Bu is associated with superior outcomes compared to TBI in patients with AML in first CR.
    Blood 09/2013; · 9.78 Impact Factor
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    ABSTRACT: PURPOSETo analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma. PATIENTS AND METHODS Outcomes of 241 patients (112 anaplastic large-cell lymphoma, 102 peripheral T-cell lymphoma not otherwise specified, 27 angioimmunoblastic T-cell lymphoma) undergoing autologous HCT (autoHCT; n = 115; median age, 43 years) or allogeneic HCT (alloHCT; n = 126; median age, 38 years) were analyzed. Primary outcomes were nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Patient, disease, and HCT-related variables were analyzed in multivariate Cox proportional hazard models to determine association with outcomes.ResultsAutoHCT recipients were more likely in first complete remission (CR1; 35% v 14%; P = .001) and with chemotherapy-sensitive disease (86% v 60%; P < .001), anaplastic large-cell histology (53% v 40%; P = .04), and two or fewer lines of prior therapy (65% v 44%; P < .001) compared with alloHCT recipients. Three-year PFS and OS of autoHCT recipients beyond CR1 were 42% and 53%, respectively. Among alloHCT recipients who received transplantations beyond CR1, 31% remained progression-free at 3 years, despite being more heavily pretreated and with more refractory disease. NRM was 3.5-fold higher (95% CI, 1.80 to 6.99; P < .001) for alloHCT. In multivariate analysis, chemotherapy sensitivity (hazard ratio [HR], 1.8; 95% CI, 1.16 to 2.87) and two or fewer lines of pretransplantation therapy (HR, 5.02; 95% CI, 2.15 to 11.72) were prognostic of survival. CONCLUSION These data describe the roles of autoHCT and alloHCT in T-cell non-Hodgkin lymphoma and suggest greater effectiveness earlier in the disease course, and limited utility in multiply relapsed disease. Notably, autoHCT at relapse may be a potential option for select patients, particularly those with anaplastic large-cell lymphoma histology.
    Journal of Clinical Oncology 07/2013; · 18.04 Impact Factor
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    ABSTRACT: This is a phase I study to determine the maximal tolerated dose (MTD) of CPX-351 when administered sequentially with allogeneic hematopoietic stem cell transplantation (HSCT) in patients with refractory acute leukemia. CPX-351 is a novel liposomal formulation, which combines cytosine arabinoside (ara-c) and daunorubicin in a fixed, molar ratio of 5:1. Patients in cohorts of 3 were treated with CPX-351 followed by fludarabine and busulfan (Bu/Flu) conditioning at 4 (schedule A) or 3 weeks (Schedule B) intervals. CPX-351 doses were escalated in 20 units/m(2) increments starting at 60 units/m(2) x 3 doses. Thirty-six patients were enrolled, 29 patients were able to undergo HSCT and 7 patients did not proceed to transplantation, primarily on schedule A, due to rapid disease progression. The MTD of CPX-351 was not reached at the 120 units/m(2) x 3 dose level. All 29 patients who proceeded to transplant had adequate neutrophil and platelet engraftment. The median follow-up time on the study for all 36 patients was 205 days (range: 20-996 days). The 1-year cumulative incidence of relapse and non-relapse mortality (NRM) for the 36 patients, were 60.1% (95% CI = 43.4%, 77.3%) and 23.8% (95% CI = 10.9%, 47.4%) respectively. The 1-year overall survival (OS) and leukemia free survival (LFS) were 37% (95% CI = 21%-53%) and 27% (95% CI = 13%-43%) respectively. A phase II trial should incorporate CPX-351 120 units/m(2) x 3 on schedule B. Patients with good performance status and those who achieve effective cytoreduction from CPX-351 derived the most benefit.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2013; · 3.15 Impact Factor
  • Koen van Besien, Hong-Tao Liu, A Artz
    Chimerism. 03/2013; 4(3).
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    ABSTRACT: Bendamustine has efficacy in multiple myeloma with a toxicity profile limited to myelosuppression. We hypothesized that adding bendamustine to autologous stem cell transplant conditioning in myeloma would enhance response without significant additional toxicity. We conducted a phase 1 trial adding escalating doses of bendamustine to the current standard conditioning of melphalan 200mg/m2. Twenty-five subjects were enrolled onto 6 cohorts. A maximum tolerated dose was not encountered and the highest dose level cohort of bendamustine 225mg/m2 + melphalan 200mg/m2 was expanded to further evaluate safety. Overall, there was no transplant related mortality and only 1 grade 4 dose-limiting toxicity was observed. Median number of days to neutrophil and platelet engraftment was 11 (9-14) and 13 (10-21), respectively. Disease responses at day +100 post-transplant were: progression in 5 (21%), partial response in 1 (4%), very good partial response in 7 (33%), complete response in 1 (4%), and stringent complete response in 9 (38%). Six patients (24%) with preexisting high-risk disease died from progressive myeloma during study follow-up, all at or beyond 100 days after ASCT. Bendamustine up to a dose of 225mg/m2 added to autologous stem cell transplant conditioning with high dose melphalan in multiple myeloma did not exacerbate expected toxicities.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2013; · 3.15 Impact Factor
  • Koen van Besien, Tsiporah Shore, Melissa Cushing
    New England Journal of Medicine 01/2013; 368(3):287-8. · 54.42 Impact Factor
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    ABSTRACT: BACKGROUND: The management of relapsed aggressive lymphomas remains problematic. Ixabepilone (BMS-247550, epothilone B analog), a potent inhibitor of tubulin disassembly, has promising preclinical and early-phase clinical activity in drug-resistant malignancies. METHODS: This multicenter phase 2 clinical trial tested the activity and safety of ixabepilone in relapsed/refractory aggressive lymphoma patients with either chemosensitive (at least a partial response [PR] to most recent chemotherapy) or chemoresistant (less than PR to most recent chemotherapy) disease at 20 mg/m(2) given intravenously weekly on days 1, 8, and 15 of a 28-day cycle. RESULTS: Fifty-one enrolled patients with a median age of 66 years received at least 1 dose of ixabepilone. Diffuse large B-cell lymphoma (n = 25; 49%), mantle cell lymphoma (n = 16; 31%), and transformed follicular lymphoma (n = 5; 10%) were the most frequent histologies. Patients were heavily pretreated, with more than one-quarter having received 4 or more prior therapies. The overall response rate was 27% (14 of 51 patients) with 12% (6 patients) experiencing complete responses and 16% (8 patients) with PRs. All responses were in patients with chemosensitive disease. The median time to response was 2 cycles with a median duration of response of 9.7 months. CONCLUSIONS: Ixabepilone was well-tolerated, with neutropenia, peripheral sensory neuropathy, fatigue, and nausea as the major toxicities. Ixabepilone has modest single-agent activity in patients with recurrent chemosensitive aggressive lymphomas. Cancer 2013;. © 2013 American Cancer Society.
    Cancer 01/2013; · 5.20 Impact Factor
  • Koen van Besien
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    ABSTRACT: Allogeneic transplantation constitutes curative treatment for acute myeloid leukemia and myelodysplastic syndrome. Its therapeutic effects are to a large extent mediated by GVL effects, but partially offset by treatment-related mortality and loss of quality of life caused by acute and chronic GVHD. Although severe acute and chronic GVHD are associated with a reduction in relapse risk, they are not associated with improved survival. Recent efforts to modulate the GVL-GVH balance include novel methods of in vitro or in vivo T-cell depletion that are associated with a minimal impact on rates of disease recurrence and a dramatically decreased risk for GVHD. Donor selection algorithms may also have a significant impact on transplantation outcomes. Low-expression HLA alleles, particularly HLA-DP, should be incorporated in selection of adult unrelated donors. Evolving data suggest that KIR typing may also be important. High-resolution HLA typing and the importance of fetal-maternal interactions in umbilical cord blood transplantation are also briefly discussed. A combination of donor selection strategies and GVHD prophylaxis methods will favorably affect long-term outcomes and create an environment suitable for effective posttransplantation interventions.
    Hematology 01/2013; 2013:56-62. · 1.49 Impact Factor
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    ABSTRACT: Therapy-related myeloid neoplasm (t-MN) is a subtype of acute myeloid leukemia with adverse cytogenetics and poor overall prognosis despite intensive induction chemotherapy and allogeneic hematopoietic cell transplantation (allo-HCT). It is increasingly recognized as a late complication of chronic immunosuppression in patients who have received solid organ transplantation. In this paper, we describe a case of t-MN following orthotopic cardiac transplantation and its treatment with allo-HCT. We discuss molecular and biological challenges and considerations in double solid organ and bone marrow transplantation and review similar cases at our institution. Our experience suggests general feasibility and safety of allo-HCT in patients who have received solid organ transplantation.
    Case reports in hematology. 01/2013; 2013:140138.

Publication Stats

2k Citations
768.79 Total Impact Points


  • 2009–2013
    • The University of Chicago Medical Center
      • • Section of Hematology/Oncology
      • • Department of Medicine
      Chicago, Illinois, United States
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 2002–2013
    • University of Chicago
      • • Section of Hematology/Oncology
      • • Department of Pathology
      • • Department of Medicine
      Chicago, Illinois, United States
  • 2012
    • Cornell University
      Ithaca, New York, United States
    • Universitair Ziekenhuis Leuven
      Louvain, Flanders, Belgium
  • 1997–2012
    • University of Texas MD Anderson Cancer Center
      • Department of Stem Cell Transplantation & Cellular Therapy
      Houston, TX, United States
  • 2011
    • Cliniques Universitaires Saint-Luc
      Bruxelles, Brussels Capital Region, Belgium
  • 2010–2011
    • National Institutes of Health
      • Branch of Experimental Transplantation and Immunology
      Bethesda, MD, United States
    • Hospital of the University of Pennsylvania
      Philadelphia, Pennsylvania, United States
  • 2005–2011
    • University of Texas Health Science Center at San Antonio
      San Antonio, Texas, United States
  • 2002–2011
    • University of Illinois at Chicago
      • Section of Hematology and Oncology
      Chicago, Illinois, United States
  • 2009–2010
    • Case Western Reserve University
      • • Department of Medicine (University Hospitals Case Medical Center)
      • • School of Medicine
      Cleveland, OH, United States
  • 2004–2010
    • Northwestern University
      • Division of Hematology/Oncology
      Evanston, IL, United States
  • 2003–2008
    • Medical College of Wisconsin
      • Center for International Blood & Marrow Transplant Research
      Milwaukee, WI, United States
    • MacNeal Hospital
      Berwyn, Illinois, United States
  • 2006
    • Genentech
      San Francisco, California, United States