Corey Cutler

Publications (80)538.19 Total impact

• Article: Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease.

  Ken-Ichi Matsuoka, John Koreth, Haesook T Kim, Gregory Bascug, Sean McDonough, Yutaka Kawano, Kazuyuki Murase, Corey Cutler, Vincent T Ho, Edwin P Alyea, Philippe Armand, Bruce R Blazar, Joseph H Antin, Robert J Soiffer, Jerome Ritz
  [show abstract] [hide abstract]
  ABSTRACT: CD4(+)Foxp3(+) regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation. We recently reported that daily administration of low-dose interleukin-2 (IL-2) induces selective expansion of functional Tregs and clinical improvement of chronic graft-versus-host disease (GVHD). To define the mechanisms of action of IL-2 therapy, we examined the immunologic effects of this treatment on homeostasis of CD4(+) T cell subsets after transplant. We first demonstrated that chronic GVHD is characterized by constitutive phosphorylation of signal transducer and activator of transcription 5 (Stat5) in conventional CD4(+) T cells (Tcons) associated with elevated amounts of IL-7 and IL-15 and relative functional deficiency of IL-2. IL-2 therapy resulted in the selective increase of Stat5 phosphorylation in Tregs and a decrease of phosphorylated Stat5 in Tcons. Over an 8-week period, IL-2 therapy induced a series of changes in Treg homeostasis, including increased proliferation, increased thymic export, and enhanced resistance to apoptosis. Low-dose IL-2 had minimal effects on Tcons. These findings define the mechanisms whereby low-dose IL-2 therapy restores the homeostasis of CD4(+) T cell subsets and promotes the reestablishment of immune tolerance.
  Science translational medicine 04/2013; 5(179):179ra43. · 7.80 Impact Factor
• Article: Busulfan Dose Intensity and Outcomes in Reduced Intensity Allogeneic Peripheral Blood Stem Cell Transplantation for MDS/AML.

  Yi-Bin Chen, Erin Coughlin, Kevin F Kennedy, Edwin P Alyea, Philippe Armand, Eyal C Attar, Karen K Ballen, Corey Cutler, Bimalangshu R Dey, John Koreth, Steven L McAfee, Thomas R Spitzer, Joseph H Antin, Robert J Soiffer, Vincent T Ho
  [show abstract] [hide abstract]
  ABSTRACT: Comparisons of myeloablative conditioning versus reduced intensity conditioning (RIC) have demonstrated a tradeoff between relapse and toxicity. Dose intensity across RIC regimens vary and may affect treatment outcomes. In this retrospective analysis, we investigated if IV busulfan dosing (total dose 3.2 mg/kg vs. 6.4 mg/kg) in fludarabine/busulfan (Flu/Bu) RIC regimens would affect outcomes in patients undergoing HSCT for MDS or AML. A total of 217 consecutive patients with MDS or AML underwent first Bu/Flu RIC PBSCT from well matched related or unrelated donors at our institutions between 2004 and 2009. 135 patients received Bu1 (busulfan 3.2 mg/kg) and 82 patients received Bu2 (busulfan 6.4 mg/kg), both with daily fludarabine (30 mg/m2/d x 4 days). The choice of RIC regimens was based on temporal institutional standard, enrollment on protocols, and physician choice. Patients had similar characteristics with a few notable differences: patients receiving Bu1 were younger (median age 61 vs 64, p<0.001), received more single-antigen mismatched unrelated grafts (14.1% vs. 1.2%, p<0.001), received more sirolimus based GVHD prophylaxis regimens (63% vs 45%, p < .0001), received less ATG for GVHD prophylaxis (0% vs. 22%, p < 0.001) and had less enrollment on a clinical trial using prophylactic rituximab for the prevention of chronic GVHD (2.2% vs. 11.0%, p=0.011). Clinical disease status was similar between the two groups. Median follow-up for survivors was 4.4 years for Bu1 and 3.2 years for Bu2. Due to the differences in characteristics, the two groups were compared with the adjustment of a propensity score predicting Bu2 to account for measured differences. The day +200 cumulative incidence of grades II-IV acute GVHD (Bu1 17% vs Bu2 8.5%, HR 0.56 [0.22, 1.41], p=0.22) or grades III-IV acute GVHD (Bu1 6.7% vs. Bu2 4.9%) were not different. The 2-year cumulative incidence of chronic GVHD (Bu1 41.5% vs Bu2 28%, HR 0.70 [0.42, 1.17], p=0.09) was not significantly different. 2-year non-relapse mortality (NRM) was similar (Bu1 8.9% vs Bu2 9.8%, HR 0.80 [0.29, 2.21], p=0.67). 2-year progression-free survival (Bu1 40.6% vs Bu2 39.3%, HR 0.82 [0.57, 1.30], p=0.33) and overall survival (Bu1 47.4% vs Bu2 48.8%, HR 0.96 [0.64, 1.44], p=0.85) were also similar. Subset analysis defined by clinical disease and cytogenetic risk with the propensity risk score applied suggest that in patients with high clinical disease risk and non-adverse cytogenetics, the higher dose busulfan RIC regimen may be of marginal benefit (2-year PFS, HR 0.54 [0.29, 1.03], p=.062). For the majority of patients with MDS/AML undergoing Bu/Flu RIC PBSCT, however, the dose of busulfan (3.2 mg/kg vs 6.4 mg/kg) is not associated with significant differences in overall outcomes.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2013; · 3.15 Impact Factor
• Article: Hand grip strength and 2 minute walk test in chronic GVHD assessment: An analysis from the Chronic GVHD Consortium.

  Joseph Pidala, Xiaoyu Chai, Paul Martin, Yoshihiro Inamoto, Corey Cutler, Jeanne Palmer, Daniel Weisdorf, Steven Pavletic, Mukta Arora, Madan Jagasia, David Jacobsohn, Stephanie J Lee
  [show abstract] [hide abstract]
  ABSTRACT: Hand grip strength (HGS) and 2 minute walk test (2MWT) have been proposed as elements of chronic graft-vs-host disease (GVHD) assessment in clinical trials. Using all available data (n=584 enrollment visits, 1,689 follow-up visits, total of 2,273 visits) from a prospective observational cohort study, we explored the relationship between HGS and 2MWT and patient-reported measures (Lee symptom scale, SF-36 and FACT-BMT quality of life instruments, and Human Activity Profile, or HAP), chronic GVHD global severity (NIH global 0-3 score, clinician global 0-3 score, and patient-reported global 0-3 score), calculated and clinician-reported chronic GVHD response, and mortality (overall survival (OS), non-relapse mortality (NRM), and failure-free survival (FFS)) in multivariable analyses adjusted for significant covariates. 2MWT was significantly associated with intuitive domains of the Lee Symptom Scale (overall, skin, lung, energy), SF-36 domain and summary scores, FACT summary and domain scores, and HAP scores (all p < 0.001). Fewer associations were detected with the HGS. The 2MWT and HGS both had significant association with global chronic GVHD severity. In multivariable analysis, 2MWT was significantly associated with OS, NRM, and FFS, while no association was found for HGS. 2MWT and HGS were not sensitive to NIH or clinician-reported response. Based on independent association with mortality, these data support the importance of the 2MWT for identification of high-risk chronic GVHD patients. However, change in 2MWT is not sensitive to chronic GVHD response, limiting its usefulness in clinical trials.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2013; · 3.15 Impact Factor
• Article: Analysis of gastrointestinal and hepatic chronic GVHD manifestations on major outcomes: A Chronic GVHD Consortium study.

  Joseph Pidala, Xiaoyu Chai, Brenda F Kurland, Yoshihiro Inamoto, Mary E D Flowers, Jeanne Palmer, Nandita Khera, Madan Jagasia, Corey Cutler, Mukta Arora, Georgia Vogelsang, Stephanie J Lee
  [show abstract] [hide abstract]
  ABSTRACT: While data support adverse prognosis of overlap subtype of chronic GVHD, the importance of site of gastrointestinal (GI) and type of hepatic involvement is not known. Using data from the Chronic GVHD Consortium observational cohort study (n=567, total of 2115 visits), we examined whether the site of GI (esophageal, upper GI, lower GI) and type of hepatic (bilirubin, alkaline phosphatase (AP), alanine aminotransferase (ALT)) involvement are associated with overall survival (OS)and non-relapse mortality (NRM), symptoms, quality of life (QOL) and functional status measures. In multivariate analysis utilizing data from enrollment visits only, lower GI involvement (HR 1.67, p=0.05) and elevated bilirubin (HR 2.46, p=0.001) were associated with OS; both were also associated with NRM. In multivariable analysis using all visits (time-dependent covariates), GI score greater than zero (HR 1.69, p=0.02) and elevated bilirubin (HR 3.73, p<0.001) were associated with OS; results were similar for NRM. Any esophageal involvement and GI score greater than zero were associated with both symptoms and QOL while elevated bilirubin was associated with QOL. We found no consistent evidence that upper GI involvement, AP, ALT, or NIH liver score add prognostic value for survival, overall symptom burden, or quality of life. These data support important differences in patient-reported outcomes according to GI and hepatic involvement among chronic GVHD affected patients, and identify those with elevated bilirubin or higher GI score at any time, or lower GI involvement at cohort enrollment, as patients at greater risk for mortality under current treatment approaches.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2013; · 3.15 Impact Factor
• Article: Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia.

  Andromachi Scaradavou, Claudio G Brunstein, Mary Eapen, Jennifer Le-Rademacher, Juliet N Barker, Nelson Chao, Corey Cutler, Colleen Delaney, Fangyu Kan, Luis Isola, Chatchada Karanes, Mary J Laughlin, John E Wagner, Elizabeth J Shpall
  [show abstract] [hide abstract]
  ABSTRACT: Cell dose is a major limitation for umbilical cord blood (UCB) transplantation since units containing a minimum of 2.5 x 10(7) total nucleated cells (TNC)/ kilogram patient body weight are frequently not available. The transplantation of two partially HLA-matched UCB units has been adopted as a simple approach for increasing the TNC. We sought to determine whether the relative safety and efficacy of this approach was comparable to a single UCB transplant. Included are adults with acute leukemia transplanted with one (n=106) or two UCB units (n=303). All UCB units for single UCB transplants contained TNC ≥2.5 x 10(7)/kg. For double UCB transplants, the total TNC for units 1 and 2 were greater than 2.5 x 10(7)/kg but in about half of these transplants, one of the two units contained <2.5 x 10(7) TNC/kg. Adjusting for factors associated with outcomes, risks of neutrophil recovery (OR 0.83, p=0.59), transplant-related mortality (HR 0.91, p=0.63), relapse (HR 0.90, p=0.64) and overall mortality (HR 0.93, p=0.62) was similar after double UCB and adequate dose single UCB transplants. These data support double UCB unit transplantation for acute leukemia when an adequately dosed single UCB unit is not available thereby extending access to nearly all patients.
  Blood 12/2012; · 9.90 Impact Factor
• Article: Improving outcomes in umbilical cord blood transplantation: State of the art.

  Corey Cutler, Karen K Ballen
  [show abstract] [hide abstract]
  ABSTRACT: Only 30% of patients who require an allogeneic hematopoietic cell transplant will have a HLA matched sibling donor. Many patients, particularly those patients with diverse racial and ethnic backgrounds, may not be able to identify a suitably matched unrelated donor. Over 25,000 umbilical cord blood transplant procedures have been performed in the last 25years. Considerable challenges exist in defining the appropriate conditioning regimen and graft vs host disease prophylaxis, surmounting issues of cell dose and delayed engraftment, and improving immune recovery. In this review, we discuss strategies to improve umbilical cord blood transplant outcomes, focusing on cord blood unit selection, expansion, and homing efficiency.
  Blood reviews 09/2012; · 7.19 Impact Factor
• Article: How we treat oral chronic graft-versus-host disease.

  Nathaniel Treister, Christine Duncan, Corey Cutler, Leslie Lehmann
  [show abstract] [hide abstract]
  ABSTRACT: Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation that is associated with a diminished quality of life. The oral cavity is frequently affected, with a wide variety of signs and symptoms that can result in significant short- and long-term complications ranging from mucosal sensitivity and limited oral intake to secondary malignancy and early death. This article provides a comprehensive approach to the diagnosis and clinical management of patients with oral cGVHD, with particular attention to differential diagnosis, control of symptoms, and prevention of and screening for secondary complications. The clinical considerations and recommendations presented are intended to be practical and relevant for all clinicians involved in the care of patients with oral cGVHD, with the ultimate goal of improving care and outcomes.
  Blood 08/2012; 120(17):3407-18. · 9.90 Impact Factor
• Article: Bortezomib-Based Graft-Versus-Host Disease Prophylaxis in HLA-Mismatched Unrelated Donor Transplantation.

  John Koreth, Kristen E Stevenson, Haesook T Kim, Sean M McDonough, Bhavjot Bindra, Philippe Armand, Vincent T Ho, Corey Cutler, Bruce R Blazar, Joseph H Antin, Robert J Soiffer, Jerome Ritz, Edwin P Alyea
  [show abstract] [hide abstract]
  ABSTRACT: PURPOSE HLA-mismatched unrelated donor (MMUD) hematopoietic stem-cell transplantation (HSCT) is associated with increased graft-versus-host disease (GVHD) and impaired survival. In reduced-intensity conditioning (RIC), neither ex vivo nor in vivo T-cell depletion (eg, antithymocyte globulin) convincingly improved outcomes. The proteasome inhibitor bortezomib has immunomodulatory properties potentially beneficial for control of GVHD in T-cell-replete HLA-mismatched transplantation. PATIENTS AND METHODS We conducted a prospective phase I/II trial of a GVHD prophylaxis regimen of short-course bortezomib, administered once per day on days +1, +4, and +7 after peripheral blood stem-cell infusion plus standard tacrolimus and methotrexate in patients with hematologic malignancies undergoing MMUD RIC HSCT. We report outcomes for 45 study patients: 40 (89%) 1-locus and five (11%) 2-loci mismatches (HLA-A, -B, -C, -DRB1, or -DQB1), with a median of 36.5 months (range, 17.4 to 59.6 months) follow-up. Results The 180-day cumulative incidence of grade 2 to 4 acute GVHD was 22% (95% CI, 11% to 35%). One-year cumulative incidence of chronic GVHD was 29% (95% CI, 16% to 43%). Two-year cumulative incidences of nonrelapse mortality (NRM) and relapse were 11% (95% CI, 4% to 22%) and 38% (95% CI, 24% to 52%), respectively. Two-year progression-free survival and overall survival were 51% (95% CI, 36% to 64%) and 64% (95% CI, 49% to 76%), respectively. Bortezomib-treated HLA-mismatched patients experienced rates of NRM, acute and chronic GVHD, and survival similar to those of contemporaneous HLA-matched RIC HSCT at our institution. Immune recovery, including CD8(+) T-cell and natural killer cell reconstitution, was enhanced with bortezomib. CONCLUSION A novel short-course, bortezomib-based GVHD regimen can abrogate the survival impairment of MMUD RIC HSCT, can enhance early immune reconstitution, and appears to be suitable for prospective randomized evaluation.
  Journal of Clinical Oncology 08/2012; 30(26):3202-8. · 18.37 Impact Factor
• Article: Safety and efficacy of defibrotide for the treatment of severe hepatic veno-occlusive disease.

  Paul G Richardson, Vincent T Ho, Sergio Giralt, Sally Arai, Shin Mineishi, Corey Cutler, Joseph H Antin, Nicole Stavitzski, Dietger Niederwieser, Ernst Holler, Enric Carreras, Robert Soiffer
  [show abstract] [hide abstract]
  ABSTRACT: Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). VOD may occur in up to 62% of patients undergoing SCT, with onset generally within the first month after SCT. In severe cases, 100-day mortality is in excess of 80%. Current management consists of best supportive care, with no agents to date approved for treatment in the USA or the EU. Defibrotide, a polydisperse oligonucleotide, has been shown in phase II and III trials to improve complete response and survival in patients undergoing SCT with severe VOD. This article reviews our current understanding of VOD, and examines recent clinical findings on defibrotide for the treatment and prophylaxis of VOD.
  Therapeutic advances in hematology. 08/2012; 3(4):253-65.
• Article: Correlation between NIH composite skin score, patient-reported skin score, and outcome: results from the Chronic GVHD Consortium.

  David A Jacobsohn, Brenda F Kurland, Joseph Pidala, Yoshihiro Inamoto, Xiaoyu Chai, Jeanne M Palmer, Sally Arai, Mukta Arora, Madan Jagasia, Corey Cutler, Daniel Weisdorf, Paul J Martin, Steven Z Pavletic, Georgia Vogelsang, Stephanie J Lee, Mary E D Flowers
  [show abstract] [hide abstract]
  ABSTRACT: There are no validated criteria to measure skin response in chronic GVHD. In a prospectively assembled, multicenter cohort of patients with chronic GVHD (N = 458), we looked for correlation of change in several different scales recommended by the National Institutes of Health (NIH) Consensus with clinician and patient perception of change and overall survival. Of the clinician scales, the NIH composite 0-3 skin score was the only one that correlated with both clinician and patient perception of improvement or worsening. Of the patient-reported scales, the skin subscale of the Lee Symptom Scale was the only one that correlated with both clinician and patient perception of improvement or worsening. At study entry, NIH skin score 3 and Lee skin symptom score > 15 were both associated with worse overall survival. Worsening of NIH skin score at 6 months was associated with worse overall survival. Improvement in the Lee skin symptom score at 6 months was associated with improved overall survival. Our findings support the use of the NIH composite 0-3 skin score and the Lee skin symptom score as simple and sensitive measures to evaluate skin involvement in clinical trials as well as in the clinical monitoring of patients with cutaneous chronic GVHD.
  Blood 07/2012; 120(13):2545-52. · 9.90 Impact Factor
• Article: Phase II Trial of Parathyroid Hormone after Double Umbilical Cord Blood Transplantation.

  Karen Ballen, Adam M Mendizabal, Corey Cutler, Ioannis Politikos, Katarzyna Jamieson, Elizabeth J Shpall, Bimalangshu R Dey, Eyal Attar, Steven McAfee, Colleen Delaney, [......], David Avigan, Richard T Maziarz, Vincent T Ho, John Koreth, Edwin Alyea, Robert Soiffer, John R Wingard, Vicki Boussiotis, Thomas R Spitzer, Joseph H Antin
  [show abstract] [hide abstract]
  ABSTRACT: Transplantation of 1 or 2 umbilical cord blood products is a useful alternative stem cell source. However, the limited number of stem cells in each infusion results in slow engraftment. In mouse models, administration of parathyroid hormone (PTH) is an effective way to enhance the ability of limited numbers of hematopoietic stem cells to support hematopoiesis. In this study, patients received either a myeloablative or a reduced-intensity double umbilical cord blood transplantation, followed by PTH at 100 μg/day for 28 days. Thirteen patients (median age, 42 years) were enrolled. All patients engrafted; the median time to neutrophil and platelet engraftment of >20 × 10(9) cells/L was 30 days and 61 days, respectively. The incidence of grade II-IV acute GVHD was 38.5% at day 100. Four deaths occurred before day 100, prompting early study closure. No patient who received a myeloablative regimen relapsed. Overall survival at 6 months after transplantation was 62%, and disease-free survival at 2 years was 39%. At the dose and schedule studied, there was no evidence that PTH influenced blood count recovery.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2012; · 3.15 Impact Factor
• Article: A disease risk index for patients undergoing allogeneic stem cell transplantation.

  Philippe Armand, Christopher J Gibson, Corey Cutler, Vincent T Ho, John Koreth, Edwin P Alyea, Jerome Ritz, Mohamed L Sorror, Stephanie J Lee, H Joachim Deeg, Barry E Storer, Frederick R Appelbaum, Joseph H Antin, Robert J Soiffer, Haesook T Kim
  [show abstract] [hide abstract]
  ABSTRACT: The outcome of allogeneic HSCT varies considerably by the disease and remission status at the time of transplantation. Any retrospective or prospective HSCT study that enrolls patients across disease types must account for this heterogeneity; yet, current methods are neither standardized nor validated. We conducted a retrospective study of 1539 patients who underwent transplantation at Dana-Farber Cancer Institute/Brigham and Women's Hospital from 2000 to 2009. Using multivariable models for overall survival, we created a disease risk index. This tool uses readily available information about disease and disease status to categorize patients into 4 risk groups with significantly different overall survival and progression-free survival on the basis of primarily differences in the relapse risk. This scheme applies regardless of conditioning intensity, is independent of comorbidity index, and was validated in an independent cohort of 672 patients from the Fred Hutchinson Cancer Research Center. This simple and validated scheme could be used to risk-stratify patients in both retrospective and prospective HSCT studies, to calibrate HSCT outcomes across studies and centers, and to promote the design of HSCT clinical trials that enroll patients across diseases and disease states, increasing our ability to study nondisease-specific outcomes in HSCT.
  Blood 06/2012; 120(4):905-13. · 9.90 Impact Factor
• Article: Poor Agreement between Clinician Response Ratings and Calculated Response Measures in Patients with Chronic Graft-versus-Host Disease.

  Jeanne M Palmer, Stephanie J Lee, Xiaoyu Chai, Barry E Storer, Mary E D Flowers, Kirk R Schultz, Yoshihiro Inamoto, Corey Cutler, Joseph Pidala, Mukta Arora, David A Jacobsohn, Paul A Carpenter, Steven Z Pavletic, Paul J Martin
  [show abstract] [hide abstract]
  ABSTRACT: In 2005, a National Institutes of Health consensus conference was held to refine methods for research in patients with chronic graft-versus-host disease, including proposed objective response measures and a provisional algorithm for calculating organ-specific and overall response. In this study, we used weighted kappa statistics to evaluate the level of agreement between clinician response ratings and calculated response categories in patients with chronic graft-versus-host disease. The study included 290 patients who had paired enrollment and follow-up visits. Based on a set of objective measures, 37% of the patients had an overall complete or partial response, whereas clinicians reported an overall complete or partial response rate of 71% (slight to fair agreement, weighted kappa 0.20). Agreement rates between calculated organ-specific responses and clinician-reported changes in skin, mouth, and eyes were fair to moderate (weighted kappa, 0.28-0.54). We conclude that for both overall and organ-specific comparisons, clinician response ratings did not agree well with calculated response categories. Possible reasons for this discrepancy include a high clinical sensitivity for detecting response, a clinical predisposition to recognize selective improvements as overall response, the large change in objective measures proposed to define response, and the high incidence of progressive disease based on new manifestations. Conclusions from prior literature reporting high overall response rates based on clinician judgment would not be supported if the provisional algorithm had been applied to calculate response. Our analysis also highlights the need to define an overall response measure that incorporates both patient-reported and objective measures and accurately reflects the outcome in patients with a mixed response in which one organ or site improves, whereas another shows new involvement.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2012; 18(11):1649-55. · 3.15 Impact Factor
• Article: Clinical Benefit of Response in Chronic Graft-versus-Host Disease.

  Yoshihiro Inamoto, Paul J Martin, Xiaoyu Chai, Madan Jagasia, Jeanne Palmer, Joseph Pidala, Corey Cutler, Steven Z Pavletic, Mukta Arora, David Jacobsohn, Paul A Carpenter, Mary E D Flowers, Nandita Khera, Georgia B Vogelsang, Daniel Weisdorf, Barry E Storer, Stephanie J Lee
  [show abstract] [hide abstract]
  ABSTRACT: To determine whether changes in objective response measures proposed by the National Institutes of Health correlate with clinical benefit, such as symptom burden, quality of life, and survival outcomes, we analyzed data from a multicenter prospective cohort of 283 patients with chronic graft-versus-host disease requiring systemic treatment. The median follow-up time of survivors was 25.1 months (range, 5.4-47.7 months) after enrollment. Symptom measures included the Lee symptom scale and 10-point patient-reported symptoms. Quality-of-life measures included the Short Form-36, Functional Assessment of Cancer Therapy-Bone Marrow Transplantation, and Human Activities Profile. Overall and organ-specific responses were calculated by comparing manifestations at the 6-month visit and those at the enrollment visit using a provisional algorithm. Complete or partial responses were considered "response," and stable or progressive disease was considered "no response." Overall response rate at 6 months was 32%. Organ-specific response rates were 45% for skin, 23% for eyes, 32% for mouth, and 51% for gastrointestinal tract. Response at 6 months, as calculated according to the provisional response algorithm, was correlated with changes in symptom burden in patients with newly diagnosed chronic graft-versus-host disease, but not with changes in quality of life or survival outcomes. Modification of the algorithm or validation of other more meaningful clinical endpoints is warranted for future clinical trials of treatment for chronic graft-versus-host disease.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2012; 18(10):1517-24. · 3.15 Impact Factor
• Article: Cord-blood hematopoietic stem cell transplant confers an increased risk for human herpesvirus-6-associated acute limbic encephalitis: a cohort analysis.

  Joshua A Hill, Sophia Koo, Belisa B Guzman Suarez, Vincent T Ho, Corey Cutler, John Koreth, Philippe Armand, Edwin P Alyea, Lindsey R Baden, Joseph H Antin, Robert J Soiffer, Francisco M Marty
  [show abstract] [hide abstract]
  ABSTRACT: Human herpesvirus-6 (HHV-6) frequently reactivates after allogeneic hematopoietic stem cell transplantation (HSCT); its most severe manifestation is the syndrome of posttransplantation acute limbic encephalitis (HHV-6-PALE). The epidemiology, risk factors, and characteristics of HHV-6-PALE after unrelated cord-blood transplantation (UCBT) are not well characterized. We analyzed 1344 patients undergoing allogeneic HSCT between March 2003 and March 2010 to identify risk factors and characteristics of HHV-6-PALE. The cohort included 1243 adult-donor HSCT and 101 UCBT recipients. All patients diagnosed with HHV-6-PALE had HHV-6 DNA in cerebrospinal fluid (CSF) specimens in addition to symptoms and studies indicating limbic encephalitis. Nineteen cases (1.4%) of HHV-6-PALE were identified during this study: 10 after UCBT (9.9%) and 9 after adult-donor HSCT (0.7%), for an incidence rate of 1.2 cases/1000 patient-days compared to 0.08 cases/1000 patient-days (P < .001), respectively. Risk factors for HHV-6-PALE on multivariable Cox modeling were UCBT (adjusted hazard ratio [aHR], 20.0; 95% confidence interval [CI], 7.3-55.0; P < .001), time-dependent acute graft-versus-host disease (aGVHD) grades II to IV (aHR, 7.5; 95% CI, 2.8-19.8; P < .001), and adult-mismatched donor (aHR, 4.3; 95% CI, 1.1-17.3; P = .04). Death from HHV-6-PALE occurred in 50% of affected patients undergoing UCBT and no recipients of adult-donor cells. Patients receiving UCBT have increased risk for HHV-6-PALE and greater morbidity from this disease.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2012; 18(11):1638-48. · 3.15 Impact Factor
• Article: First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation.

  Paul J Martin, J Douglas Rizzo, John R Wingard, Karen Ballen, Peter T Curtin, Corey Cutler, Mark R Litzow, Yago Nieto, Bipin N Savani, Jeffrey R Schriber, Paul J Shaughnessy, Donna A Wall, Paul A Carpenter
  [show abstract] [hide abstract]
  ABSTRACT: Despite prophylaxis with immunosuppressive agents or a variety of other approaches, many patients suffer from acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation. Although consensus has emerged supporting the use of high-dose methylprednisolone or prednisone for initial treatment of aGVHD, practices differ among centers with respect to the initial glucocorticoid dose, the use of additional immunosuppressive agents, and the approach to withdrawal of treatment after initial improvement. Despite many studies, practices vary considerably with respect to the selection of agents for treatment of glucocorticoid-resistant or refractory GVHD. Investigators and clinicians have recognized the lack of progress and lamented the absence of an accepted standard of care for secondary treatment of aGVHD. The American Society of Blood and Marrow Transplantation has developed recommendations for treatment of aGVHD to be considered by care providers, based on a comprehensive and critical review of published reports. Because the literature provides little basis for a definitive guideline, this review also provides a framework for the interpretation of previous results and the design of future studies.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2012; 18(8):1150-63. · 3.15 Impact Factor
• Article: Reduced-intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes.

  Claudio G Brunstein, Mary Eapen, Kwang Woo Ahn, Frederick R Appelbaum, Karen K Ballen, Richard E Champlin, Corey Cutler, Fangyu Kan, Mary J Laughlin, Robert J Soiffer, Daniel J Weisdorf, Anne Woolfrey, John E Wagner
  [show abstract] [hide abstract]
  ABSTRACT: We report the relative efficacy of co-infusing 2 umbilical cord blood units (dUCB) compared with peripheral blood progenitor cells (PBPCs) from 8 of 8 or 7 of 8 HLA-matched unrelated donors. All patients received reduced-intensity conditioning (RIC) regimens. Four treatment groups were evaluated: 4-6 of 6 matched dUCB-TCF (n = 120; TCF = total body irradiation [TBI] 200 cGy + cyclophosphamide + fludarabine), 4-6 of 6 matched dUCB-other (n = 40; alkylating agent + fludarabine ± TBI), and 8 of 8 (n = 313) and 7 of 8 HLA-matched PBPCs (n = 111). Compared with matched 8 of 8 PBPC transplantations, transplantation-related mortality (TRM), and overall mortality were similar after dUCB-TCF (relative risk [RR] 0.72, P = .72; RR 0.93, P = .60) but higher after dUCB-other RIC (hazard ratio [HR] 2.70, P = .0001; 1.79 P = .004). Compared with 7 of 8 PBPC transplantations, TRM (but not overall mortality) was lower after dUCB-TCF (RR 0.57, P = .04; RR 0.87 P = .41). The probabilities of survival after dUCB-TCF, dUCB-other RIC, and 8 of 8 PBPC and 7 of 8 PBPC transplantations were 38%, 19%, 44%, and 37%, respectively. With similar survival after 8 of 8, 7 of 8 matched PBPCs, and dUCB-TCF, these data support use of dUCB-TCF transplantation in adults with acute leukemia who may benefit from RIC transplantation urgently or lack a 7-8 of 8 unrelated donor.
  Blood 04/2012; 119(23):5591-8. · 9.90 Impact Factor
• Article: Does iron overload really matter in stem cell transplantation?

  Philippe Armand, Marie-Michele Sainvil, Haesook T Kim, Joanna Rhodes, Corey Cutler, Vincent T Ho, John Koreth, Edwin P Alyea, Ellis J Neufeld, Raymond Y Kwong, Robert J Soiffer, Joseph H Antin
  [show abstract] [hide abstract]
  ABSTRACT: A growing body of evidence suggests that iron overload is associated with inferior outcomes after myeloablative allogeneic hematopoietic stem cell transplantation (HSCT). However, all of those studies used surrogate markers of iron overload, especially serum ferritin, and most had a retrospective design. We conducted a prospective observational study in patients with myelodysplastic syndrome or acute leukemia undergoing myeloablative HSCT. Forty-five patients who were followed for over 1 year, with serial measurements of serum iron parameters, as well as liver and cardiac magnetic resonance imaging. There was no significant increase in ferritin, liver or cardiac iron content in the 12 months following HSCT. Although serum ferritin still appeared to have prognostic significance, as previously reported, pre-HSCT iron overload (as reflected in liver iron content) was not associated with increased mortality, relapse, or graft-versus-host disease. These results raise the possibility that the adverse prognostic impact of pre-HSCT hyperferritinemia may be related to factors independent of iron overload.
  American Journal of Hematology 03/2012; 87(6):569-72. · 4.67 Impact Factor
• Article: HLA DR15 antigen status does not impact graft-versus-host disease or survival in HLA-matched sibling transplantation for hematologic malignancies.

  Minoo Battiwalla, Kristin Ellis, Peigang Li, Steven Z Pavletic, Gorgun Akpek, Peiman Hematti, Thomas R Klumpp, Richard T Maziarz, Bipin N Savani, Mahmoud D Aljurf, [......], Theresa Hahn, Nandita Khera, Mark R Litzow, Alison W Loren, Wael Saber, Mukta Arora, Alvaro Urbano-Ispizua, Corey Cutler, Mary E D Flowers, Stephen R Spellman
  [show abstract] [hide abstract]
  ABSTRACT: The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2012; 18(8):1302-8. · 3.15 Impact Factor
• Article: GVHD prevention: an ounce is better than a pound.

  Pavan Reddy, Gérard Socié, Corey Cutler, Daniel Weisdorf
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2012; 18(1 Suppl):S17-26. · 3.15 Impact Factor