5.2 EL CUERPO DEL DELIRIO Y LA DESAPARICIÓN FORZADA 164
5.2.1 Desaparición y perplejidad en dos textos de Evelio Rosero 165
8.6 GRAFT-VS-HOST DISEASE WORKING COMMITTEE
Co-Chair: Corey Cutler, MD, MPH, Dana Farber Cancer Institute
Email: [email protected]
Co-Chair: Daniel Couriel, MD, University of Michigan
Email: [email protected]
Co-Chair: Amin Alousi, MD, MD Anderson Cancer Center
Email: [email protected]
Scientific Director: Mukta Arora, MD, MS, CIBMTR Minneapolis
Email: [email protected]
Scientific Director: Steve Spellman, MBS, CIBMTR Minneapolis
Email: [email protected]
PhD Statistician: Tao Wang, PhD, CIBMTR Milwaukee
Email: [email protected]
MS Statistician: Michael Hemmer, MS, CIBMTR Milwaukee
Email: [email protected]
RECENTLY COMPLETED STUDIES
Study # GV04-02 / GV05-03c
Journal Citation: Boyiadzis M, Arora M, Klein J, Hassebroek A, Hemmer M, Urbano-Ispizua A,
Antin JH, Bolwell B, Cahn J-Y, Cairo MS, Cutler C, Flowers M, Gale R, Herzig R, Isola L, Jacobsohn D, Jagasia M, Klumpp T, Lee SJ, Petersdorf E, Santarone S, Spellman S, Schouten HC, Verdonck L, Wingard J, Weisdorf D, Horowitz M, Pavletic S. Impact of chronic graft-versus-host disease on late relapse and
survival on 7489 patients after myeloablative allogeneic hematopoietic cell transplantation for leukemia. Clinical Cancer Research. doi:10.1158/1078-
0432.CCR-14-0586. Epub 2014 Oct 27.
Abstract: Purpose: Malignancy relapse remains a major obstacle for successful alloHCT. Chronic GVHD is associated with fewer relapses. However, when studying effects of chornic GVHD on relapse, it is difficult to separate from acute GVHD effects as most cases of chronic GVHD occur within the first year post-transplant at the time when acute GVHD is still active. Experimental design: The current study based on CIBMTR registry data investigated chronic GVHD and its association with the incidence of late relapse and survival in 7,489 patients with AML, ALL, CML, and MDS who were leukemia-free at 12 months after MAC alloHCT. Results: Forty-seven percent of the study population was diagnosed with chronic GVHD at 12 months after transplant. The protective effect of chronic GVHD on relapse was present only in patients with CML (RR 0.47, 95% CI 0.37- 0.59, P<0.0001). Chronic GVHD was significantly associated with higher risk of TRM (RR 2.43, 95% CI 2.09-2.82, P<0.0001) and inferior OS (RR 1.56, 95% CI 1.41- 1.73, P<0.0001) for all diseases. In patients with CML, all organ sites and
presentation types of chronic GVHD were equally associated with lower risk of late relapse. Conclusions: These results indicate that clinically relevant anti-
8.6 GRAFT-VS-HOST DISEASE WORKING COMMITTEE CIBMTR Progress Report 2014
leukemia effects of chronic GVHD on late relapses are present only in CML but not in AML, ALL, or MDS. Chronic GVHD in patients who are one-year
survivors after MAC alloHCT is primarily associated with higher TRM and inferior survival.
Study # GV06-04
Journal Citation: Arai S, Arora M, Wang T, Spellman SR, He W, Couriel DR, Urbano-Ispizua A,
Cutler CS, Bacigalupo AA, Battiwalla M, Flowers ME, Juckett MB, Lee SJ, Loren AW, Klumpp TR, Prockup SE, Ringdén OT, Savani BN, Socié G, Schultz KR, Spitzer T, Teshima T, Bredeson CN, Jacobsohn DA, Hayashi RJ, Drobyski WR, Frangoul HA, Akpek G, Ho VT, Lewis VA, Gale RP, Koreth J, Chao NJ, Aljurf MD, Cooper BW, Laughlin MJ, Hsu JW, Hematti P, Verdonck LF, Solh MM, Norkin M, Reddy V, Martino R, Gadalla S, Goldberg JD, McCarthy PL, Pérez- Simón JA, Khera N, Lewis ID, Atsuta Y, Olsson RF, Saber W, Waller, Blaise D, Pidala JA, Martin PJ, Satwani P, Bornhäuser M, Inamoto Y, Weisdorf DJ, Horowitz MM, Pavletic SZ. Increasing incidence of chronic graft-versus-host
disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research. Biology of Blood and Marrow
Transplantation: Journal of the American Society for Blood and Marrow Transplantation. doi:10.1016/j.bbmt.2014.10.021. Epub 2014 Oct 30.
Abstract: Although transplant practices have changed over the last decades, there is no information on trends in incidence and outcome of chronic GVHD over time. This study utilized the central database of the CIBMTR to describe the time trends for chronic GVHD incidence, NRM, and the risk factors for chronic GVHD. The 12-year period was divided into three intervals: 1995-1999, 2000- 2003, 2004-2007, and included 26,563 patients with acute leukemia, CML, and MDS. In the multivariate analysis, the incidence of chronic GVHD was shown to be increased in more recent years (OR 1.19, p<0.0001) and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with chronic GVHD, NRM has decreased over time, but at five-years post- transplant there were no significant differences among different time periods. Risk factors for chronic GVHD were in line with previous studies. This is the first comprehensive characterization of the trends in chronic GVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.
Study # GV11-04
Journal Citation: Arora M, Hemmer MT, Ahn KW, Klein JP, Cutler CS, Urbano-Ispizua A, Couriel
DR, Alousi AM, Gale RP, Inamoto Y, Weisdorf DJ, Li P, Antin JH, Bolwell BJ, Boyiadzis M, Cahn J-Y, Cairo MS, Isola LM, Jacobsohn DA, Jagasia M, Klumpp TR, Petersdorf EW, Santarone S, Schouten HC, Wingard JR, Spellman SR, Pavletic SZ, Lee SJ, Horowitz MM, Flowers ME. CIBMTR chronic GVHD risk score
predicts mortality in an independent validation cohort. Biology of Blood and
Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation. doi:10.1016/j.bbmt.2014.10.022. Epub 2014 Dec 18.
CIBMTR Progress Report 2014 8.6 GRAFT-VS-HOST DISEASE WORKING COMMITTEE Abstract: We previously reported a risk score that predicted mortality in patients with
chronic GVHD after HCT between 1995-2004 and reported to the CIBMTR. We sought to validate this risk score in an independent CIBMTR cohort of 1,128 patients with chronic GVHD transplanted between 2005-2007 using the same inclusion criteria and risk-score calculations. According to the sum of the overall risk score (range 1 to 12), patients were assigned to 4 risk groups (RGs): RG1 (0- 2), RG2 (3-6), RG3 (7-8), and RG4 (9-10). RG3 and 4 were combined as RG4 comprised only 1% of the total cohort. Cumulative incidences of NRM and probability of OS were significantly different between each RG (all p<0.01). NRM and OS at 5 years after chronic GVHD for each RG were 17% and 72% in RG1, 26% and 53% in RG2, and 44% and 25% in RG 3, respectively (all p<0.01). Our study validates the prognostic value of the CIBMTR chronic GVHD RGs for OS and NRM in a contemporary transplant population. The CIBMTR chronic GVHD RGs can be used to predict major outcomes, tailor treatment planning, and enrollment in clinical trials.
PRELIMINARY RESULTS
Study # GV11-03
Title: A retrospective comparison of tacrolimus versus cyclosporine with methotrexate for immunosuppression after allogeneic hematopoietic cell transplantation according to graft and donor type
Study Chairs: Yoshihiro Inamoto (National Cancer Center Hospital) Paul Martin (Fred Hutchinson Cancer Research Center)
Alvaro Urbano-Ispizua (University of Barcelona, IDIBAPS, and Institute of Research Josep Carreras)
Mary Flowers (Fred Hutchinson Cancer Research Center)
MS Statistician: Michael Hemmer ([email protected])
PhD Statistician: Tao Wang ([email protected]) Study Status: Manuscript preparation
Abstract: Combinations of CSP with MTX have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with TAC+MTX vs CSP+MTX after transplantation from HLA-identical siblings (SIB) or URD in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute GVHD, chronic GVHD, and overall mortality. TAC+MTX was used more frequently in older patients and in recent years in both groups. In multivariate analysis, TAC+MTX was associated with a lower risk of overall mortality in URD recipients and with slightly earlier neutrophil recovery in SIB recipients. Other outcomes and causes of death did not differ statistically between the two regimens. Although no firm conclusions were reached regarding which GVHD prophylaxis is better, the use of TAC+MTX might decrease overall mortality in URD recipients with acquired aplastic anemia.
8.6 GRAFT-VS-HOST DISEASE WORKING COMMITTEE CIBMTR Progress Report 2014
STUDIES IN PROGRESS
Study # SC10-02
Title: Chronic graft-versus-host disease and relapse in cord blood transplants in children with leukemia
Study Chair: Mary Eapen (Froedtert & Medical College of Wisconsin)
MS Statistician: Mary Eapen ([email protected])
PhD Statistician: Tao Wang ([email protected]) Study Status: Analysis in progress
Study # GV11-02
Title: Acute and chronic graft-versus-host disease after unrelated umbilical cord blood transplantation: analysis of risk factors and outcomes
Study Chairs: Yi-Bin Chen (Dana Farber Cancer Institute) Corey Cutler (Dana Farber Cancer Institute)
MS Statistician: Michael Hemmer ([email protected])
PhD Statistician: Tao Wang ([email protected]) Study Status: Analysis in progress
Study # GV12-01
Title: Outcomes of grades 3-4 acute graft-versus-host disease post-allogeneic hematopoietic cell transplantation: how much progress was achieved?
Study Chair: H. Jean Khoury (Emory University Hospital)
MS Statistician: Michael Hemmer ([email protected])
PhD Statistician: TBD
Study Status: Data file preparation
Study # GV12-02
Title: Prognostic implications of acute upper gastrointestinal graft-versus-host disease in patients undergoing myeloablative hematopoietic cell transplantation
Study Chairs: Sarah Nikiforow (Dana Farber Cancer Institute) Corey Cutler (Dana Farber Cancer Institute)
MS Statistician: Michael Hemmer ([email protected])
PhD Statistician: TBD
CIBMTR Progress Report 2014 8.6 GRAFT-VS-HOST DISEASE WORKING COMMITTEE Study # GV13-01
Title: Impact of donor sex, parity, and sibling / unrelated status on outcomes of allogeneic hematopoietic cell transplantation
Study Chairs: Anita Kumar (Abramson Cancer Center University of Pennsylvania Medical Center)
Alison Loren (Perelman School of Medicine at the University of Pennsylvania)
MS Statistician: Michael Hemmer ([email protected])
PhD Statistician: TBD
Study Status: Data file preparation
Study # GV13-02
Title: The impact of the combination and sequence of immunosuppressive treatments on outcomes of acute graft-versus-host disease: a methodological exercise in modeling adaptive treatment strategies
Study Chairs: Elizabeth Krakow (Maisonneuve-Rosemont Hospital)
Erica Moodie (Gill University Health Centre - Royal Victoria Hospital)
MS Statistician: Michael Hemmer ([email protected])
PhD Statisticians: Tao Wang ([email protected])
Elizabeth Krakow ([email protected])
Study Status: Analysis in progress
Study # GV14-01
Title: Comparison of mycophenolate versus methotrexate in combination with a calcineurin inhibitor for graft-versus-host disease prophylaxis in allogeneic HCT
Study Chairs: Betty Hamilton (Cleveland Clinic)
Saurabh Chhabra (Medical University of South Carolina) Navneet Majhail (Cleveland Clinic)
Luciano Costa (University of Alabama at Birmingham) Robert Stuart (Medical University of South Carolina) Dennis Kim (Princess Margaret Hospital)
Olle Ringdén (Karolinska University Hospital, Centre for Allogeneic Stem Cell Transplantation)
MS Statistician: Michael Hemmer ([email protected])
PhD Statistician: TBD
8.6 GRAFT-VS-HOST DISEASE WORKING COMMITTEE CIBMTR Progress Report 2014 Study # GV14-02
Title: Influence of donor and recipient age on risk for acute and chronic graft versus host disease in children receiving bone marrow transplantation
Study Chairs: Muna Qayed (Emory University Hospital)
John Horan (Columbia University Medical Center)
MS Statistician: Michael Hemmer ([email protected])
PhD Statistician: TBD
Study Status: Protocol development
Study # SC14-03
Title: Comparison of survival and clinical endpoints for pediatric patients with acute graft versus host disease from the CIBMTR registry with those for patients from the OSIRIS Protocol 275 Study
Study Chair: Donna Skerrett (Mesoblast, Inc.)
MS Statistician: Michael Hemmer ([email protected])
PhD Statistician: TBD