Koen van Besien

Weill Cornell Medical College, New York, New York, United States

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Publications (257)1474.06 Total impact

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    ABSTRACT: Background: The coinfusion of haploidentical CD34+ selected peripheral blood stem cell products with umbilical cord blood (UCB) provides early neutrophil recovery, long-term UCB engraftment, and a lower incidence of graft-versus-host disease; however, this complex transplant presents a scheduling challenge for both the cellular therapy laboratory and the clinical team. Cryopreservation of the haploidentical product can facilitate scheduling, but has been previously shown to be associated with infusion reactions and delayed platelet (PLT) engraftment in allogeneic hematopoietic progenitor cell transplant. Study design and methods: To test whether cryopreservation of the CD34+ selected product compromises the graft, we compared neutrophil and PLT engraftment kinetics for patients receiving freshly infused or cryopreserved products. Seventy-two products collected from haploidentical related donors were CD34+ selected and infused in a combined transplant with UCB: 32 were cryopreserved before infusion and 40 were infused fresh. Results: No adverse infusion events were reported in either group and there was no difference in neutrophil and PLT engraftment time between fresh and cryopreserved products. Conclusion: Cryopreservation of a CD34+-selected product can be safely used in a combined transplant with UCB and does not affect engraftment time.
    No preview · Article · Dec 2015 · Transfusion
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    ABSTRACT: Objective: To compare infusion-related reactions and outcomes of using subcutaneous (subQ) alemtuzumab versus intravenous (IV) alemtuzumab as graft-versus-host disease (GVHD) prophylaxis for matched unrelated donor (MUD) stem cell transplants. Outcomes include incidence of cytomegalovirus (CMV)/Epstein-Barr virus (EBV) viremia, development of CMV disease or post-transplant lymphoproliferative disorder, fatal infections, acute and chronic GVHD, time to engraftment, relapse rate and survival. Methods: Retrospective study of all adult MUD SCT patients who received fludarabine/melphalan with subQ or IV alemtuzumab in combination with tacrolimus as part of their conditioning for unrelated donor transplantation at NewYork-Presbyterian/Weill Cornell Medical Center (NYP/WC) from January 1, 2012 to March 21, 2014. Alemtuzumab was administered at a total cumulative dose of 100 mg (divided over days -7 to -3). Results: Forty-six patients received an unrelated donor stem cell transplant with fludarabine/melphalan and either subQ (N=26) or IV (N=20) alemtuzumab in combination with tacrolimus. Within the evaluable population, 130 subQ and 100 IV alemtuzumab doses were administered. For the primary outcome, ≥ grade 2 infusion-related reactions occurred in 11 (8%) vs. 25 (25%) infusions in the subQ and IV cohorts, respectively (p=0.001). Overall, 12 twelve injections (9%) in the subQ arm versus 26 infusions (26%) in the IV arm experienced an infusion-related reaction of any grade (p=0.001). There were no significant differences between the subQ and IV arms in rates of reactivation of CMV/EBV, development of CMV disease or post-transplant lymphoproliferative disorder, fatal infections, acute and chronic GVHD, relapse or survival. Conclusion: Subcutaneous administration of alemtuzumab for GVHD prophylaxis was associated with fewer infusion- related reactions compared to IV administration in the stem cell transplant setting. Incidence of acute and chronic GVHD was similar between both arms. There was also no difference in reactivation of CMV/ EBV viremia, development of CMV disease or post-transplant lymphoproliferative disorder, fatal infections, relapse or survival.
    No preview · Article · Nov 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • Koen van Besien

    No preview · Article · Oct 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    ABSTRACT: Background: Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. Objectives: This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. Study design: From April 2012-March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. Results: One hundred and ten HM patients presented with HRV URTI (n=78) and HRV LRTI (n=32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0-9.2; p=0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. Conclusions: HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses.
    Full-text · Article · Sep 2015 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology

  • No preview · Article · Sep 2015
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    ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) is one of curative treatment options for patients with hematologic malignancies. Although GVHD mediated by the donor's T lymphocytes remains the most challenging toxicity of allo-HSCT, graft-versus-leukemia (GVL) effect targeting leukemic cells, has an important role in affecting the overall outcome of patients with AML. Here we comprehensively characterized the TCR repertoire in patients who underwent matched donor or haplo-cord HSCT using next-generation sequencing approach. Our study defines the functional kinetics of each TCRA and TCRB clone, and changes in T-cell diversity (with identification of CDR3 sequences) and the extent of clonal expansion of certain T-cells. Using this approach, our study demonstrates that higher percentage of cord-blood cells at 30 days after transplant was correlated with higher diversity of TCR repertoire, implicating the role of cord-chimerism in enhancing immune recovery. Importantly, we found that GVHD and relapse, exclusive of each other, were correlated with lower TCR repertoire diversity and expansion of certain T-cell clones. Our results highlight novel insights into the balance between GVHD and GVL effect, suggesting that higher diversity early after transplant possibly implies lower risks of both GVHD and relapse following the HSCT transplantation.Bone Marrow Transplantation advance online publication, 8 June 2015; doi:10.1038/bmt.2015.133.
    Full-text · Article · Jun 2015 · Bone marrow transplantation
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    ABSTRACT: The collection of autologous peripheral blood (PB) stem cells can be challenging in the subgroup of patients deemed "poor mobilizers" with granulocyte-colony-stimulating factor. Plerixafor, a CXCR-4 antagonist, is an alternative mobilizing agent, but is costly, and the optimal mobilization algorithm has yet to be determined. To address the question we developed a protocol measuring PB CD34 on Day 4 of mobilization. We examined 26 patients before initiating the protocol versus 24 patients after initiation. Significant differences (p ≤ 0.05) included fewer days of collection (1.25 days vs. 2.42 days), lower total blood volume processed (25.9 L vs. 57.2 L), lower total product volume (324 mL vs. 691 mL), lower RBC content (9 mL vs. 18 mL), and lower granulocyte percentage per collection (35% vs. 11%). There were no significant differences between the two groups in demographics, baseline platelet count, total CD34, or CD34/kg harvested. Use of a protocol to assess PB CD34 1 day before collection allows for preemptive administration of plerixafor to augment mobilization. Subsequently, days of collection and processed blood volume are reduced while there is less RBC and granulocyte contamination in the collected stem cell product. © 2015 AABB.
    No preview · Article · Mar 2015 · Transfusion
  • Caroline A. Lindemans · Koen Van Besien
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    ABSTRACT: Cord blood is increasingly recognized for its excellent stem cell potential, lenient matching criteria, instant availability and clinical behavior in transplants when cell dose criteria can be met. However with 1-2 log fewer total (stem cell) numbers in the graft compared with other cell sources, the infused cell dose per kilogram is critical for engraftment and outcome, creating the need for development of stem cell support platforms. The co-transplant platforms of haplo cord and double unit cord blood (DUCB) transplantation are aimed toward increasing stem cell dose. Together with the optimization of reduced-intensity protocols, long-term sustained engraftment using cord blood has become available to most patients, including elderly patients. Haplo cord has a low incidence of both acute and chronic graft-versus-host disease but may require anti-thymocyte globulin ATG for effective neutrophil recovery. DUCB can be performed without anti-thymocyte globulin with excellent immune reconstitution and disease-free survival, but engraftment is considerably slower, and graft-versus-host disease incidence significant. Both haplo-cord and DUCB transplantation appear to both be valid alternatives to matched unrelated donors in adults. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · Cytotherapy
  • Hongtao Liu · Koen van Besien
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    ABSTRACT: In the past decade, haplo-cord stem cell transplantation (SCT) using myeloablative or reduced intensive conditioning regimens has been shown to result in reliable and fast engraftment of neutrophils and platelets comparable to HLA-matched donors and much faster than after cord stem cell transplant. Haplo-cord SCT also has a low incidence of early non-relapse mortality, low incidences of acute and chronic graft-vs-host disease (GVHD), and excellent graft-vs-leukemia (GVL) effects. Favorable long-term outcomes for high-risk patients with hematologic malignancies have been reported, including older patients. Haplo-cord SCT will likely overcome the limitations of cell dose during cord stem cell selection and might significantly expand the use of cord stem cell transplant in the adult population. The comparable survival outcomes of matched related donor (MRD), matched unrelated donor (MUD), and haplo-cord stem cell transplant strongly argue that haplo-cord SCT should be considered as effective alternative stem cell transplant for high-risk patients lacking standard donors. Further improvement in supportive care and incorporation of a better understanding of the human fetal immune development into the haplo-cord SCT are required to further improve this strategy.
    No preview · Article · Feb 2015 · Current Hematologic Malignancy Reports
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    ABSTRACT: Dextran 40 is the main component of the solution used to wash or dilute thawed cord blood unit (CBU) products for stem cell transplant. Dextran 40 became unavailable in the United States as of April 2014. Like many other cellular therapy laboratories in the United States, we found ourselves with limited dextran 40 inventory, a growing CBU transplant requirement, and no alternative solution. Since there are no published alternative washing solutions for cryopreserved CBU we had to develop and validate a new solution rapidly. We chose to validate hydroxyethyl starch (HES) due to its similar ability to stabilize red blood cells and reduce sudden changes in osmolality that occur during thawing. For the validation we used 3 CBUs and thawed and washed each unit with both dextran 40- and HES-based solutions; thus, each CBU served as its own control. We observed no significant differences between the two wash solutions for all the monitored variables including cell viability, cell recovery, or potency measured by colony-forming cell assay. Based on this initial validation we began using HES-albumin for CBU washing after our supply was exhausted. Our initial experience with the first 16 CBU transplants after validation indicates safe infusion and preliminary cord engraftment. © 2015 AABB.
    No preview · Article · Feb 2015 · Transfusion
  • Adrienne A Phillips · Koen van Besien

    No preview · Article · Feb 2015 · Leukemia and Lymphoma

  • No preview · Article · Feb 2015 · Biology of Blood and Marrow Transplantation

  • No preview · Article · Feb 2015 · Biology of Blood and Marrow Transplantation
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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.
    No preview · Conference Paper · Oct 2014

  • No preview · Article · Sep 2014 · Clinical Lymphoma, Myeloma and Leukemia
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    ABSTRACT: Transplant-associated thrombotic microangiopathy (TA-TMA) refers to inflammatory and thrombotic diseases of the microvasculature characterized by hemolytic anemia, thrombocytopenia, and evidence of organ damage, particularly acute renal failure. This syndrome occurs in 10% to 20% of patients with allogeneic hematopoietic stem cell transplants (HSCTs). It is much less frequent in the autologous setting. TA-TMAs present diagnostic challenges because they may not clearly fall into one of the categories of the 2 major TMAs: atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). In addition, complications of the transplant itself, including infection, graft-versus-host disease, and disseminated intravascular coagulation, as well as the side effects of immunosuppressive drugs, can mimic a TMA. Because the pathophysiology of TA-TMA is poorly understood, current treatment options are suboptimal, and the condition carries a very high mortality rate. In 3 recent case summaries, the median acute response rate to plasma exchange was as high as 55%, but this therapy failed to alter underlying disease pathology and had little impact on overall mortality, which was approximately 80%. Indeed, the vast majority of TA-TMA patients lack suppression of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity to less than 5% to 10% of normal and do not have a complete response to plasma exchange, characteristics indicating that a TTP-like disorder is not involved. Recent advances in the treatment of aHUS may offer a therapeutic option in the aHUS-like TMAs associated with HSCTs. These issues are discussed in the context of a patient recently evaluated and treated at our institution; the case serves to illustrate the difficulties associated with the diagnosis and treatment of TA-TMA.
    No preview · Article · Sep 2014 · Clinical advances in hematology & oncology: H&O
  • Isabel Ruth Preeshagul · Koen Van Besien · Tomer M Mark
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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.
    No preview · Article · Aug 2014 · Current Hematologic Malignancy Reports
  • Koen van Besien
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    ABSTRACT: Abstract From June 5(th) to 7(th) the 12(th) Annual International Cord Blood Symposium was held in San Francisco. The meeting was devoted to advances in umbilical cord blood research with a major focus on translational and clinical results in cord blood transplantation and in regenerative medicine. Over three days, a comprehensive summary of the state of the art was provided. We have summarized the most important data, organized around the following themes: use of umbilical cord blood for tissue repair - new indications for CBU SCT - enhancing count recovery after CBU SCT - improving outcomes - product quality - financial and cost considerations.
    No preview · Article · Jul 2014 · Leukemia and Lymphoma
  • Tsiporah Shore · Koen van Besien
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    ABSTRACT: This chapter addresses some management questions that remain or that have arisen as a consequence of novel developments in the field. It presents a series of questions and answers on hematopoietic cell transplantation in Hodgkin lymphoma (HL). The chapter commences with a discourse on whether residual marrow involvement affect the results of autologous transplantation, and ends with the changes related to brentuximab and its role in maintenance. It also discusses on role of autologous transplantation in the era of escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) BEACOPP and role for allogeneic transplantation.
    No preview · Article · Jun 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.
    Full-text · Article · May 2014 · Haematologica

Publication Stats

8k Citations
1,474.06 Total Impact Points


  • 2012-2015
    • Weill Cornell Medical College
      • • Department of Medicine
      • • Division of Hematology/Medical Oncology
      New York, New York, United States
    • New York Presbyterian Hospital
      New York, New York, United States
  • 2001-2015
    • University of Chicago
      • • Section of Hematology/Oncology
      • • Department of Medicine
      Chicago, Illinois, United States
  • 1994-2012
    • University of Texas MD Anderson Cancer Center
      • Department of Stem Cell Transplantation & Cellular Therapy
      Houston, TX, United States
  • 1997-2011
    • University of Illinois at Chicago
      • Section of Hematology and Oncology
      Chicago, Illinois, United States
  • 2010
    • Rush University Medical Center
      Chicago, Illinois, United States
  • 2004-2009
    • The University of Chicago Medical Center
      • Section of Hematology/Oncology
      Chicago, Illinois, United States
  • 2005
    • University of Texas Health Science Center at San Antonio
      San Antonio, Texas, United States
  • 2003
    • University of Nebraska Medical Center
      Omaha, Nebraska, United States
  • 1999
    • Cleveland State University
      Cleveland, Ohio, United States
  • 1998
    • Medical College of Wisconsin
      • Center for International Blood & Marrow Transplant Research
      Milwaukee, Wisconsin, United States
  • 1994-1997
    • University of Houston
      Houston, Texas, United States
  • 1996
    • Houston Zoo
      Houston, Texas, United States