Koen van Besien

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (287)

  • Hannah K. Choe · Usama Gergis · Sebastian A. Mayer · [...] · Koen van Besien
    [Show abstract] [Hide abstract] ABSTRACT: Background: Preliminary evidence indicates that the addition of low dose TBI (2-4 Gy) to reduced intensity conditioning may reduce the rate of relapse in allogeneic stem cell transplants. In very high risk patients receiving combination haploidentical-single unit cord blood transplants, we have added 4 Gy TBI to the widely used fludarabine, melphalan conditioning regimen, in hopes of reducing relapse and decreasing graft rejection. Methods: We retrospectively reviewed the posttransplant outcomes of patients who underwent haplo-cord SCT between May 2013 and March 2015 and who received fludarabine 30mg/m2 D-7 to -3, melphalan 140mg/m2 D-2, and 2 Gy TBI D-4 and -3. Results: All 25 patients achieved primary neutrophil engraftment after a median of 12 days. The median time to platelet engraftment was 27 days. The cumulative incidence of NRM was 16% by D+100 and 33% by 1-year. The cumulative incidence of Grade III-IV aGVHD was 36% by D+100. The CIR was 13% by D+100 and 29% by 1-year. The estimated 1-year OS and PFS were 40% and 37%, respectively. In a subgroup analysis, we compared the outcome of 13 AML patients receiving this conditioning regimen with age and DRI-matched AML patients receiving flu-mel without TBI. The TBI group had lower incidence of relapse at 1-year (15% versus 54%, p= 0.05). Conclusions: Overall, combination fludarabine-melphalan with low dose TBI after haplo-cord SCT assures good engraftment and leads to acceptable toxicity and disease control in the setting of high risk, heavily pretreated patients. These findings warrant further investigation at a larger-scale, prospective level.
    Article · Oct 2016 · Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: Analysis of the clinical characteristics of hematopoietic stem cell transplant (HSCT) donors has proven beneficial for identifying cases of heritable hematopoietic disorders. This study examines poor peripheral blood hematopoietic stem cell mobilization after G-CSF administration among 328 donors as a potential marker for suspected familial predisposition to myeloid malignancies. Here we present data comparing the clinical characteristics of poor versus non-poor mobilizing donors and the results of panel-based sequencing of hematopoietic genes in poor mobilizing donors. From this analysis, we identified a novel case of a donor-derived myelodysplastic syndrome in a HSCT recipient that is consistent with clonal evolution of TET2-mutated clonal hematopoiesis of indeterminate potential (CHIP) within the donor. This study demonstrates the potential risk of using hematopoietic stem cells from a donor with CHIP and raises the question of whether there should be increased screening measures to identify such donors.
    Article · Aug 2016 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • Daan Dierickx · Ben Sprangers · Koen Van Besien
    Article · Jul 2016 · Leukemia and Lymphoma
  • Koen van Besien · Richard Childs
    [Show abstract] [Hide abstract] ABSTRACT: Haplo-cord transplantation combines infusion of an umbilical cord blood unit with CD34 selected cells usually from HLA mismatched related donors. Initial rapid count recovery results from the haplo-identical hematopoietic progenitors, which in the majority of cases are gradually replaced by durable engraftment from umbilical cord blood progenitors. UCB grafts used for haplo-cord tend to be smaller, but better matched than those required for single or double UCB SCT. Over 200 patients with hematological malignancies have been transplanted at two institutions. Median age was 54 (17-74) and 77 patients were age 60 and older. One year survival was 64% for patients with intermediate and low risk disease, with no deaths occurring beyond two years. In patients with high risk disease, the one year survival was 44%. In a comparison with patients undergoing RIC transplant and double UCB SCT, haplo-cord transplant resulted in much faster hematopoietic recovery, lower rates of acute and chronic GVHD, lower rates of disease recurrence and improved GVHD- and Relapse-Free-Survival (GRFS). Excellent results were also reported for patients with aplastic anemia where 18 of 21 patients had sustained cord blood engraftment.
    Article · Jul 2016 · Seminars in Hematology
  • Koen van Besien · Nebu Koshy · Usama Gergis · [...] · Tsiporah Shore
    [Show abstract] [Hide abstract] ABSTRACT: Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood (UCB) graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic graft-versus-host disease (GVHD). But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), engrafted and in remission at 2 months. Median age was 66 (18-72) and all had intermediate, high, or very-high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% versus 11% p < 0.0001) and decrease in one year progression-free (20% versus 55%, p = 0.004) and overall survival (30% versus 62%, p = 0.02). Less than 100% UCB chimerism in the CD3 lineage was associated with increase rate of disease recurrence (46% versus 12%, p = 0.007). Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% versus 15%, p = 0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful graft-versus-leukemia (GVL) effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high.
    Article · Jun 2016 · Leukemia & lymphoma
  • Christan M Thomas · Cindy Ippoliti · Gail J Roboz · [...] · Koen van Besien
    Article · May 2016 · Leukemia & lymphoma
  • [Show abstract] [Hide abstract] ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) offers the potential to cure hematologic malignancies. In the absence of an HLA-matched donor, HLA mismatched unrelated donors may be used, although risks of GvHD and treatment-related mortality (TRM) are higher. Identification and avoidance of amino-acid substitution and position types (AASPT) conferring higher risks of TRM and GvHD would potentially improve the success of transplantation from single HLA mismatched unrelated donors. Using random forest and logistic regression analyses, we identified 19 AASPT associated with greater risks for at least one adverse transplant outcome: grade III-IV acute GvHD, TRM, lower disease-free survival or worse overall survival relative to HLA-matched unrelated donors and to other AASPT. When tested in an independent validation cohort of 3530 patients, none of the AASPT from the training set were validated as high risk, however. Review of the literature shows that failure to validate original observations is the rule and not the exception in immunobiology and emphasizes the importance of independent validation before clinical application. Our current data do not support avoiding any specific class I AASPT for unrelated donors. Additional studies should be performed to fully understand the role of AASPT in HCT outcomes.Bone Marrow Transplantation advance online publication, 23 May 2016; doi:10.1038/bmt.2016.142.
    Article · May 2016 · Bone Marrow Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: After a cluster of fatal toxoplasmosis among SCT recipients at two hospitals, surveillance with PCR (blood) was instituted. Rate of reactivation among seropositive recipients was 2.2 and 16 %. Parasitemia was successfully managed with preemptive treatment. For seropositive recipients unable to take prophylaxis, toxoplasma PCR surveillance should be routinely performed.
    Article · May 2016 · Clinical Infectious Diseases
  • [Show abstract] [Hide abstract] ABSTRACT: Advanced systemic mastocytosis (advanced SM), a rare disease closely associated with KIT mutations (most commonly KIT D816V), encompasses three variants: systemic mastocytosis (SM) with an associated hematologic clonal non-mast cell disorder, aggressive SM, and mast cell leukemia. All variants are associated with shortened survival. Although interferon-alpha or cladribine exhibit efficacy in selected patients, they do not result in cure. Imatinib is approved for the minority of aggressive SM patients with negative or unknown KIT D816V status. The multikinase/KIT inhibitor midostaurin is a promising agent for patients with advanced SM and is currently available on an investigational basis. We recently reported the largest retrospective study of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with advanced SM (n=57). The evidence from this study and a few case reports indicate that it can cure some patients and lead to long-term survival. However, there is still a significant gap of knowledge regarding the use of this high-intensity therapy in advanced SM. The present paper provides a consensus opinion on methods to optimize decision-making regarding the use of alloHCT in this patient population in light of currently available data. In addition, we outline strategies that combine midostaurin in the peritransplant setting. Such protocols should generate useful outcome data regarding the safety and efficacy of KIT inhibition in conjunction with high-intensity therapy in the treatment of advanced SM.
    Article · Apr 2016 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • Frank Cirrone · Cindy Ippoliti · Hanhan Wang · [...] · Koen van Besien
    [Show abstract] [Hide abstract] ABSTRACT: Human herpes virus type 6 can reactivate in patients after allogeneic stem cell transplantation and has been associated with serious sequelae such as delayed engraftment and an increased risk of developing acute graft-versus-host disease (GVHD). This study investigated human herpes virus type 6 (HHV-6) reactivation within 60 days of transplantation in stem cell transplants utilizing single umbilical cord blood, double umbilical cord blood, or umbilical cord blood plus haploidentical stem cells. Of 92 patients, 60 (65%) had HHV-6 reactivation. Reactivation was not significantly influenced by any patient characteristics, disease characteristics, or by stem cell source (umbilical cord blood only versus haploidentical plus umbilical cord blood). We did not observe any impact of HHV-6 reactivation on neutrophil or platelet count recovery or on relapse-free survival. HHV-6 reactivation was associated with subsequent development of prerelapse acute GVHD (HR = 3.00; 95% CI, 1.4 to 6.4; p = 0.004).
    Article · Mar 2016 · Leukemia & lymphoma
  • Article · Mar 2016
  • Hannah Choe · Koen van Besien
    Article · Mar 2016
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    Koen Van Besien · Parameswaran Hari · M.-J. Zhang · [...] · Andrew Artz
    [Show abstract] [Hide abstract] ABSTRACT: Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery we used co-infusion of progenitor cells from a partially matched related donor and an UCB (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord received fludarabine-melphalan-ATG. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low dose total body irradiation. In a multivariate analysis haplo-cord had faster neutrophil (HR = 1.42,P = 0.007) and platelet recovery (HR=2.54, P < 0.0001), lower risk of grade II-IV acute graft vs. host disease (GVHD) (HR = 0.26, P < 0.0001) and chronic GVHD (HR=0.06, P < 0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P = 0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival HR=0.97 ,P = 0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low dose total body irradiation conditioning. Graft-versus-host disease-free, relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA matched donors. Trials registered at ClinicalTrials.gov: NCT00943800 and NCT 01810588.
    Full-text available · Article · Feb 2016 · Haematologica
  • [Show abstract] [Hide abstract] ABSTRACT: Delayed engraftment and cord graft failure (CGF) are serious complications after unrelated cord blood (UCB) hematopoietic stem cell transplantation (HCT), particularly when using low cell dose UCB units. The haplo-cord HCT approach allows the use of a lower dose single UCB unit by co-infusion of a CD34+ selected haploidentical graft, which provides early transient engraftment while awaiting durable UCB engraftment. We describe the frequency, complications and risk factors of CGF following reduced-intensity conditioning (RIC) haplo-cord HCT. Among 107 patients who underwent haplo-cord HCT, 94 were evaluable for CGF, defined as <5% cord blood chimerism at Day 60 in the myeloid and CD3 compartments, irrespective of neutrophil and platelet counts. CGF occurred in 14 of 94 (15%) evaluable patients. Median survival after CGF was 12.7 months with haploidentical or mixed haploidentical-autologous hematopoiesis persisting in the seven surviving. Median progression free survival after CGF was 7.7 months, and was not statistically different from those without CGF (10.47 months; p=0.18). In univariate analyses, no UCB factors were associated with CGF, including cell dose, cell viability, recipient major ABO mismatch against the UCB unit, or degree of HLA-match. We also found no association of CGF with recipient CMV serostatus, haploidentical donor age, or Day 30 haploidentical chimerism. However, higher haploidentical total nucleated and CD34+ cell doses and Day 30 UCB chimerism <5% in either the myeloid or CD3 compartments were associated with greater risk of CGF. We conclude that assessing chimerism at Day 30 may foretell impending CGF and avoidance of high haploidentical cell doses may reduce risk of CGF after haplo-cord HCT. However, long-term survival is possible after CGF due to predominant haploidentical or mixed chimerism and hematopoietic function.
    Article · Feb 2016 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • Usama Gergis · Emil Kuriakose · Tsiporah Shore · [...] · Koen van Besien
    [Show abstract] [Hide abstract] ABSTRACT: Background: Thirty consecutive patients underwent hematopoietic stem cell transplantation for myelofibrosis (MF) at our institution. The median age at the time of transplant was 49 (range, 18-68) years, 74% of patients had advanced Dynamic International Prognostic Scoring System (DIPSS) scores, and 83% received reduced-intensity conditioning. Patients and methods: With a long follow-up of our patients, we analyzed disease and transplant variables that contributed to engraftment and outcomes. Results: Neutrophil engraftment was achieved in 27 patients (90%) at a median time of 15 (range, 10-44) days, and 19 patients (63%) achieved platelet recovery at a median time of 18 (range, 8-100) days. Splenomegaly was associated with poor neutrophil engraftment (subdistributional hazard ratio [SHR], 0.42; 95% confidence interval [CI], 0.21-0.83; P = .01) and platelet engraftment (SHR, 0.18; 95% CI, 0.07-0.48; P < .001). Increased levels of lactate dehydrogenase (LDH) was associated with poor platelet engraftment (SHR, 0.39; 95% CI, 0.16-0.94; P = .04). The median follow-up for surviving patients was 49 (range, 3-155) months. The 1-year cumulative incidence of nonrelapse mortality (NRM) and relapse were respectively, 57% (95% CI, 29%-76%) and 25% (95% CI, 7%-48%). Increased levels of LDH was associated with high NRM (SHR, 2.82; 95% CI, 1.08-7.35; P = .03). The 4-year overall survival (OS) and relapse-free survival (RFS) were 44% (95% CI, 29%-67%) and 37% (95% CI, 23%-61%), respectively. In the multivariable model, splenomegaly and Eastern Cooperative Oncology Group (ECOG) performance status (PS) > 1 were associated with worse OS (hazard ratio [HR], 5.40; 95% CI, 1.19-24.56); P = .03) and RFS (HR, 3.78; 95% CI, 1.01-14.06; P < .05), respectively. ECOG PS > 1 was also associated with worse RFS (HR, 5.00; 95% CI, 1.31-19.14; P = .02). In this patient group with advanced disease, DIPPS score, Lille score, Janus-Associated Kinase V617F (JAK2 V617F) mutation status, and donor type did not predict transplant outcome. Conclusion: We confirm curative potential, but high NRM of allogeneic transplant for advanced MF.
    Article · Feb 2016 · Clinical lymphoma, myeloma & leukemia
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Parainfluenza virus (PIV) causes severe respiratory infections in hematopoietic stem cell transplant (HSCT) recipients. Currently, no effective therapies are available. DAS181 is a novel antiviral agent that inhibits attachment of PIV to respiratory cells, but clinical data on the use of DAS181 for PIV infection are limited to case reports. Methods: We report the clinical manifestations and outcomes of 16 HSCT recipients who received DAS181 daily for the treatment of PIV infection through a compassionate-use protocol or single-arm clinical trial. Results: Of the 16 patients (clinical trial: 9; compassionate-use: 7), 13 were allogeneic HSCT recipients and 8 had graft-versus-host disease. PIV types were 3 (n=7), 4 (n=5), 1 (n=3) and a type 3 and 4 co-infection (n=1). Fourteen patients had pneumonia. All patients presented with cough, 14 had dyspnea, 11 had hypoxia and 8 had fever. Patients received 5-10 days of treatment. Nine patients (56%) had a complete clinical response after DAS181 therapy and four (25%) had a partial response. The three patients without a clinical response had co-infections with other pathogens. Of the 7 patients with virologic and spirometric data, five had a >1 log reduction in nasopharyngeal swab PIV viral load and four had improved forced expiratory volumes by end of treatment. Three (19%) patients died within 30 days and two of these deaths were related to PIV infection. Conclusions: Our data suggest that DAS181 may be an effective therapy for PIV pneumonia in HSCT recipients. Randomized, placebo-controlled trials are needed to better evaluate its efficacy.
    Article · Feb 2016 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • [Show abstract] [Hide abstract] 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.
    Article · Dec 2015 · Transfusion
  • Khilna Patel · Sapna Parmar · Shreya Shah · [...] · Koen van Besien
    [Show abstract] [Hide abstract] 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.
    Article · Nov 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • Koen van Besien
    Article · Oct 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    [Show abstract] [Hide abstract] 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 available · Article · Sep 2015 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology

Publication Stats

8k Citations


  • 2009
    • University of Texas MD Anderson Cancer Center
      • Department of Stem Cell Transplantation & Cellular Therapy
      Houston, Texas, United States
  • 2007
    • University of Chicago
      • Section of Hematology/Oncology
      Chicago, Illinois, United States
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2004
    • The University of Chicago Medical Center
      • Section of Hematology/Oncology
      Chicago, Illinois, United States
  • 1996
    • Houston Zoo
      Houston, Texas, United States