Koen van Besien

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

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Publications (242)1372.36 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Transfusion 03/2015; DOI:10.1111/trf.13076 · 3.57 Impact Factor
  • 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.
    Cytotherapy 03/2015; 17(6). DOI:10.1016/j.jcyt.2015.02.005 · 3.10 Impact Factor
  • 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.
    Current Hematologic Malignancy Reports 02/2015; 10(1). DOI:10.1007/s11899-014-0245-y · 2.29 Impact Factor
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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.
    Transfusion 02/2015; DOI:10.1111/trf.13015 · 3.57 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2015; 21(2):S383-S384. DOI:10.1016/j.bbmt.2014.11.631 · 3.35 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2015; 21(2):S285. DOI:10.1016/j.bbmt.2014.11.452 · 3.35 Impact Factor
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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: 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.
    Clinical advances in hematology & oncology: H&O 09/2014; 12(9):565-73.
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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; 9(4). DOI:10.1007/s11899-014-0230-5 · 2.29 Impact Factor
  • 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.
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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; DOI:10.3324/haematol.2014.103655 · 5.87 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.
    04/2014; 5(2). DOI:10.4161/chim.28908
  • Koen van Besien, Richard R Furman
    Leukemia & lymphoma 04/2014; 55(6). DOI:10.3109/10428194.2014.903394 · 2.61 Impact Factor
  • Cytotherapy 04/2014; 16(4):S54-S55. DOI:10.1016/j.jcyt.2014.01.198 · 3.10 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; 55(12). DOI:10.3109/10428194.2014.897701 · 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; DOI:10.3109/10428194.2014.896007 · 2.61 Impact Factor
  • Bone marrow transplantation 02/2014; 49(5). DOI:10.1038/bmt.2014.11 · 3.47 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2014; 20(2):S225-S226. DOI:10.1016/j.bbmt.2013.12.381 · 3.35 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2014; 20(2):S295. DOI:10.1016/j.bbmt.2013.12.499 · 3.35 Impact Factor
  • Source
    Satyajit Kosuri, Koen van Besien
    Leukemia & lymphoma 01/2014; DOI:10.3109/10428194.2014.887715 · 2.61 Impact Factor

Publication Stats

6k Citations
1,372.36 Total Impact Points


  • 2012–2015
    • Weill Cornell Medical College
      • Department of Medicine
      New York, New York, United States
    • Cornell University
      Ithaca, New York, United States
  • 2014
    • New York Presbyterian Hospital
      New York, New York, United States
  • 2002–2012
    • University of Chicago
      • • Department of Medicine
      • • Section of Hematology/Oncology
      Chicago, Illinois, United States
  • 1998–2012
    • University of Texas MD Anderson Cancer Center
      • • Department of Stem Cell Transplantation & Cellular Therapy
      • • Division of Pathology and Laboratory Medicine
      Houston, TX, United States
  • 2004–2011
    • The University of Chicago Medical Center
      • Section of Hematology/Oncology
      Chicago, Illinois, United States
  • 1998–2011
    • University of Illinois at Chicago
      • Section of Hematology and Oncology
      Chicago, Illinois, United States
  • 2009
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 2007
    • Cancer Research Center of Lyon
      Lyons, Rhône-Alpes, France
  • 2005
    • University of Texas Health Science Center at San Antonio
      San Antonio, Texas, United States
  • 1998–2003
    • Medical College of Wisconsin
      • Center for International Blood & Marrow Transplant Research
      Milwaukee, WI, United States
  • 2001
    • Case Western Reserve University
      • School of Medicine
      Cleveland, Ohio, United States
    • Baylor College of Medicine
      • Center for Cell and Gene Therapy
      Houston, Texas, United States
  • 1999
    • Indiana Blood and Marrow Transplantation
      Indianapolis, Indiana, United States
  • 1996
    • Houston Zoo
      Houston, Texas, United States