A G E N D A CIBMTR WORKING COMMITTEE FOR GRAFT-VERSUS-HOST DISEASE San Diego, CA Wednesday, February 11, 2015, 2:45 4:45 pm

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1 Not for publication or presentation A G E N D A CIBMTR WORKING COMMITTEE FOR GRAFT-VERSUS-HOST DISEASE San Diego, CA Wednesday, February 11, 2015, 2:45 4:45 pm Co-Chair: Co-Chair: Co-Chair: Statisticians: Scientific Directors: Corey Cutler, MD, MPH, Dana-Farber Cancer Institute, Boston, MA; Telephone: ; Fax: ; corey_cutler@dfci.harvard.edu Daniel Couriel, MD, The University of Michigan, Ann Arbor, MI; Telephone: ; Fax: ; dcouriel@med.umich.edu Amin Alsousi, MD, MD Anderson Cancer Center, Houston, TX; Telephone: ; Fax: ; aalousi@mdanderson.org Tao Wang, PhD, CIBMTR Statistical Center, Milwaukee, WI; Telephone: ; Fax: ; taowang@mcw.edu Michael Hemmer, MS, CIBMTR Statistical Center, Milwaukee, WI; Telephone: ; Fax: ; mhemmer@mcw.edu Mukta Arora, MD, MS, University of Minnesota Medical Center, Minneapolis, MN; Telephone: ; Fax: ; arora005@umn.edu Stephen Spellman, MBS, CIBMTR Statistical Center, Minneapolis, MN; Telephone: ; Fax: ; sspellma@nmdp.org 1. Introduction a. Minutes and Overview Plan from February 2014 meeting (Attachment 1) b. Introduction of incoming Co-Chair: Joseph Pidala, MD; H. Lee Moffitt Cancer Center and Research Institute; Telephone: ; joseph.pidala@moffitt.org; Areas of focus: GVHD prevention and treatment. 2. Accrual Summary (Attachment 2) 3. Presentations, published or submitted papers a. GV04-02/05-03c Boyiadzis M, Arora M, Klein JP, Hassebroek A, Hemmer M, Urbano-Ispizua A, Antin JH, Bolwell BJ, Cahn JY, Cairo MS, Cutler CS, Flowers ME, Gale RP, Herzig R, Isola LM, Jacobsohn DA, Jagasia MH, Klumpp TR, Lee SJ, Petersdorf EW, Santarone S, Spellman SR, Schouten HC, Verdonck LF, Wingard JR, Weisdorf DJ, Horowitz MM, Pavletic SZ. Impact of chronic graft-versus-host disease on late relapse and survival after myeloablative allogeneic hematopoietic cell transplantation for leukemia. Clinical Cancer Research Oct; [Epub ahead of print]. b. GV11-04 Flowers M, Ahn K, Hemmer MT, Li P, Cutler CS, Urbano-Ispizua A, Couriel DR, Gale RP, Inamoto Y, Antin JH, Bolwell BJ, Boyiadzis M, Cahn J, Cairo MS, Isola LM, Jacobsohn DA, Jagasia M, Klumpp TR, Peterdorf EW, Schouten HC, Wingard JR, Spellman S, Weisdorf DJ, Pavletic SZ, Lee SJ, Horowitz MM and Arora M. The CIBMTR Chronic GVHD Risk Group Predicts Major Outcomes in an Independent Validation Cohort. Biology Blood Marrow Transplant Dec; [Epub ahead of print]. 1

2 Not for publication or presentation c. GV06-04 Arai S, Arora M, Wang T, He W, Couriel DR, Urbano-Ispizua A, Cutler CS, Spellman S and Pavletic SZ. Current trends in chronic GVHD updated report from the CIBMTR/NMDP. Biology Blood Marrow Transplant Oct; [Epub ahead of print]. d. GV11-03 Inamoto Y, Martin PJ, Flowers ME, Urbano-Ispizua A, Wang T, Hemmer MT, Cutler CS, Couriel DR, Alousi AM, Arora M, Spellman SR. Comparison of tacrolimus versus cyclosporine with methotrexate for immunosuppression after allogeneic hematopoietic cell transplantation for severe aplastic anemia: A CIBMTR analysis. Presentation at ASH meeting in San Francisco, CA, December Manuscript in preparation. 4. Future/proposed studies a. PROP Development of a chronic GVHD-related co-morbidity measure using CIBMTR data (SW Choi / D Couriel / N Majhail) (Attachment 3) b. PROP Risks and outcomes of orthotopic liver transplantation for hepatic GVHD in HCT patients (S Hashmi / M Jagasia / J Palmer / J Koreth / M Litzow) (Attachment 4) c. PROP The role of TBI in sclerotic-type cgvhd of the skin (EW Cowen / S Pavletic / KJ Martires) (Attachment 5) d. PROP Impact of donor obesity and inflammation on acute and chronic GVHD among HCT recipients (L Turcotte / M Verneris) (Attachment 6) Dropped proposals e. PROP Comparison of post-transplant Cy to CNI-based GVHD prophylaxis regimen (AS Al- Homsi / S Williams / T Roy / U Duffner) Dropped due to insufficient numbers of post-tx Cy alone cohort and overlap with ongoing clinical trial. f. PROP Comparison of CNI + MTX with post-transplant Cy alone as GVHD prophylaxis in patients undergoing allogeneic HCT (UR Deotare / MD Seftel) Dropped due to insufficient numbers of post-tx Cy alone cohort and overlap with ongoing clinical trial. g. PROP Comparison of cyclosporine versus tacrolimus with MMF for GVHD prophylaxis after umbilical cord blood transplant (R Hanna / B Hamilton / M Jagasia / N Majhail) Dropped due to overlap with current GVWC study (GV11-02). 5. Studies in progress (Attachment 7) a. GV11-03 Comparison of tacrolimus versus cyclosporine with methotrexate Manuscript Preparation for immunosuppression after allogeneic HCT for severe aplastic anemia (Y Inamoto / P Martin / M Flowers / A Urbano-Ispizua) b. GV11-02 Acute and chronic GVHD after unrelated umbilical cord blood Analysis transplantation: Analysis of risk factors and outcomes (Y-B Chen / C Cutler) Presentation: Yi-Bin Chen, MD e. GV13-02 The impact of the combination and sequence of Analysis immunosuppressive treatments on outcomes of acute GVHD: A methodological exercise in modeling adaptive treatment strategies (E Krakow / E Moodie) f. GV12-02 Prognostic implications of acute upper gastrointestinal GVHD in Analysis patients undergoing myeloablative HCT (S Nikiforow / C Cutler) g. GV12-01 Outcomes of grades 3-4 acute GVHD post-allogeneic HCT: How Data File Preparation 2

3 Not for publication or presentation much progress was achieved? (HJ Khoury) h. GV13-01 Impact of donor parity and donor type on outcomes of allogeneic HCT (A Kumar / A Loren) i. GV14-01 Comparison of MMF vs. MTX in combination with a CNI for GVHD prophylaxis in allogeneic HCT (B Hamilton / S Chhabra / N Majhail / L Costa / R Stuart / D Kim / O Ringden) j. GV14-02 Influence of donor and recipient age on risk for GVHD in children receiving HLA-identical bone marrow transplantation (M Qayed / J Horan) Data File Preparation Protocol Development Protocol Development 6. Other Business 3

4 Not for publication or presentation Attachment 1 MINUTES AND OVERVIEW PLAN CIBMTR WORKING COMMITTEE FOR GRAFT-VERSUS-HOST DISEASE Grapevine, Texas Thursday, February 27, 2014, 2:45 4:45 PM Co-Chair: Co-Chair: Co-Chair: Statisticians: Scientific Directors: Alvaro Urbano-Ispizua, MD; Hospital Clinic of Barcelona, SPAIN Telephone: ; Fax: ; aurbano@clinic.ub.es Corey Cutler, MD, MPH, Dana Farber Cancer Institute, Boston, MA Telephone: ; Fax: ; cscutler@partners.org Mary Flowers, MD, Fred Hutchinson Cancer Research Center, Seattle, WA Telephone: ; Fax: ; mflowers@fhcrc.org Michael Hemmer, MS, CIBMTR Statistical Center, Milwaukee, WI Telephone: ; Fax : ; mhemmer@mcw.edu Tao Wang, PhD, CIBMTR, Medical College of Wisconsin, Milwaukee, WI Telephone : ; Fax : ; taowang@hpi.mcw.edu Mukta Arora, MD, MS, CIBMTR, Minneapolis, MN Telephone: ; Fax: ; arora005@umn.edu Stephen Spellman, MS, CIBMTR, Minneapolis, MN Telephone: ; Fax: ; sspellma@nmdp.org 1. Introduction a Tandem Minutes & Overview Plan for approval b. Newly appointed chair: Amin Alousi, MD; MD Anderson Cancer Center, Houston, TX; Telephone: ; aalousi@mdanderson.org; Focus on prevention and treatment of acute and chronic GVHD. Dr. Dan Couriel began introductions by introducing himself and the incoming chair, Dr. Amin Alousi. The rest of the GVWC leadership introduced themselves to the committee with their names and affiliations. 2. Accrual summary Dr. Alvaro Urbano-Ispizua explained the Accrual summary tables could be found with the rest of the meeting s materials online, and had been available for the past few weeks. 3. Presentations, published or submitted papers Dr. Urbano-Ispizua presented brief updates on these presentations made from the GVWC in the past year. One paper has been submitted and three have been presented as 2013 ASH oral abstracts. a. GV04-02/05-03c Boyiadzis M, Arora M, Klein JP, Hassebroek A, Hemmer MT, Urbano-Ispizua A, Antin JH, Bolwell BJ, Cahn JY, Cairo MS, Cutler CS, Flowers ME, Gale RP, Herzig R, Isola LM, Jacobsohn DA, Jagasia MH, Klumpp TR, Lee SJ, Petersdorf EW, Santarone S, Spellman SR, Schouten HC, Verdonck LF, Wingard JR, Weisdorf DJ, Horowitz MM, Pavletic SZ. Impact of chronic graft- 4

5 Not for publication or presentation Attachment 1 versus-host disease on late relapse and survival after myeloablative allogeneic hematopoietic cell transplantation for leukemia. Submitting to Clinical Cancer Research. The main take-away from GV04-02/05-03c was that GVHD had a protective effect on CML patients in terms of overall survival, but still led to higher rates of non-relapse mortality. b. GV11-04 Flowers M, Ahn K, Hemmer MT, Li P, Cutler CS, Urbano-Ispizua A, Couriel DR, Gale RP, Inamoto Y, Antin JH, Bolwell BJ, Boyiadzis M, Cahn J, Cairo MS, Isola LM, Jacobsohn DA, Jagasia M, Klumpp TR, Peterdorf EW, Schouten HC, Wingard JR, Spellman S, Weisdorf DJ, Pavletic SZ, Lee SJ, Horowitz MM and Arora M. The CIBMTR Chronic GVHD Risk Group Predicts Major Outcomes in an Independent Validation Cohort. Presentation at the ASH Meetings in New Orleans, LA, December GV11-04 is a study to validate a risk score initially proposed by the CIBMTR several years ago. There were patients fulfilling 4 of the 6 risk groups defined in the initial study, but due to small sample sizes, risk group 3 and 4 were combined. c. GV06-04 Arai S, Arora M, Wang T, He W, Couriel DR, Urbano-Ispizua A, Cutler CS, Spellman S and Pavletic SZ. Current trends in chronic GVHD updated report from the CIBMTR/NMDP. Presentation at the ASH Meetings in New Orleans, LA, December GV06-04 studied the change in cgvhd incidence over time. Year of transplant proved to be an important factor in determining cgvhd incidence, and it was observed that unrelated donors and peripheral blood stem cell grafts were used increasingly over time. d. LYWC Urbano-Ispizua A, Pavletic SZ, Flowers M, Zhang M, Carreras J, Maloney D, Montoto S, Cutler CS, Walters M, Smith S, Saber W. Association of GVHD with a lower relapse/progression rate after allohsct with reduced intensity conditioning in patients with follicular and mantle cell lymphoma. Presentation at the ASH Meetings in New Orleans, LA, December The main conclusion from the study was that there was a significant association of GVHD with a lower rate of relapse/progression post-transplant in patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) and this relationship also appeared to be more prominent in reduced intensity transplants. However, GVHD did not lead to improved rates of overall or progressionfree survival in FL or MCL due to excess non-relapse mortality. 4. Future/proposed studies Dr. Corey Cutler first thanked Dr. Urbano-Ispizua, who will be leaving the leadership as an outgoing chair, for his contributions towards the GVWC over the past 5 years. Dr. Cutler then reminded the committee that everyone is encouraged to vote on the scientific impact each proposal would have on the field, with a score of 1 being most impactful and 9 being least impactful. a. PROP Influence of donor and recipient age on risk for acute and chronic graft versus host disease in children receiving HLA identical BMT (M Qayed/J Horan) Dr. Muna Qayed presented this proposal, which wanted to explore influences that the age of the donor and recipient had on a protective effect against GVHD in pediatric patients that has been seen in previous literature, but there is room for a more detailed investigation in recipients younger than 10. Dr. Qayed s proposal further wants to address the question if reducing the intensity of GVHD prophylaxis on these pediatric patients could be a solution to reducing posttransplant relapse. While the initial population looked into recipients 10 years old or younger and 5

6 Not for publication or presentation Attachment 1 HLA-identical sibling donors, the GVWC leadership recommended expanding the cohort to include recipients younger than 18 years old and from unrelated donors in an effort to increase sample size. There are 953 patients who are under 18 years old receiving their first myeloablative allogeneic transplant from an unrelated or HLA-identical sibling donor from a non T-cell depleted bone marrow graft source with calcineurin inhibitor-based GVHD prophylaxis from for AML or ALL in 1 st or 2 nd complete remission (of the 953 total patients, 601 had an unrelated donor and 352 had an HLA-identical sibling donor). The outcomes on interest are acute and chronic GVHD. There was concern expressed by members of the GVWC about the potential for low numbers of patients, specifically when dividing the patients into categories to analyze the effect of donor and recipient age (i.e. donor age < 5 & recipient age < 5 vs. donor age 5-10 & recipient < 5 vs. ). Dr. Qayed acknowledged the numbers could become an issue, and the age categories described in her presentation (< 5, 5-9, 10-14, 15-18) were arbitrary and could be changed. There was an expressed interest in evaluating patients younger than 5 years old, as recipients this young typically do not experience GVHD, but have high rates of relapse. Another comment was whether it would be possible to seek collaboration with the EBMT in an effort to gather more patients. Dr. Cutler responded that that could be something we propose to the EBMT if the sample sizes prove to be prohibitive to an analysis with the CIBMTR s data. b. PROP The impact of season on the incidence and severity of acute GVHD (A El-Jawahri/Y Chen) Dr. Areej El-Jawahri presented the proposal. Dr. El-Jawahri began by stating that viral infection at time of transplant could play a pivotal role in the outcomes of a transplant and hypothesized that there were specific times of the year when a transplant would be favorable compared to other times. Dr. El-Jawahri first addressed this question within the Dana Farber database by evaluating the incidence of grade III-IV acute GVHD for each month of transplant. Dr. El-Jawahri found that there was a statistically significant difference in the rates of grade III-IV acute GVHD between her defined flu season (of October May) and non-flu season (June September). Dr. El-Jawahri specified the aims of the proposal are to determine the impact of whether a transplant occurred within this flu season or not on the incidence and grade of acute GVHD, in addition to relapse, NRM, DFS and OS. There were patients 18 years old or older from who had received their first allogeneic transplant from an HLA-identical sibling or unrelated donor for a hematologic malignancy (the table presented in the proposal was restricted to the patients from North America). Comments from the GVWC were that the PIs were boxing themselves in by already defining a flu and non-flu season, and that line of thinking also assumes that the time points within flu season are equal (beginning or end of flu season could make a difference). It would be more beneficial to evaluate as narrow a period time as you can (months would probably be most practical). When asked if the CIBMTR could address the issue of pneumonitis, Dr. Mukta Arora said the only way the CIBMTR forms capture this information is on an Other, specify field for cause of death. Similarly, the CIBMTR forms do not capture whether a recipient had received a flu shot prior to transplant. When asked, Dr. El-Jawahri explained the clinical impact of this study would be to educate patients about the impact of viral infections, patients who are scheduling non-urgent transplants far ahead in advance could plan to avoid a time when they re more likely to get the flu and could start asking the question if patients in flu season should be managed differently (Dr. El- 6

7 Not for publication or presentation Attachment 1 Jawahri acknowledged that this study alone won t be able to answer that question, but could lead to a clinical trial). c. PROP / / / Comparison of mycophenolate versus methotrexate in combination with a calcineurin inhibitor for GVHD prophylaxis in allogeneic HCT (B Hamilton/S Chhabra) Dr. Betty Hamilton presented this proposal, which will compare outcomes of grade II-IV and grade III-IV acute GVHD, incidence and severity of chronic GVHD, hematopoietic recovery, graft failure, CMV viremia, infection, organ toxicities, relapse, TRM, LFS and OS between patients that receive mycophenolate mofetil (MMF) versus those who receive methotrexate (MTX) in a calcineurin inhibitor-based GVHD prophylaxis setting. Since the CIBMTR recently presented the results finding worse outcomes of acute and chronic GVHD in patients receiving MMF compared to MTX from unrelated donors in reduced intensity conditioning setting, this study will analyze conditioning intensities separately. Within the myeloablative setting, the analysis will evaluate potential interactions between donor type (unrelated vs. sibling), graft source (BM vs. PBSC) and type of calcineurin inhibitor (tacrolimus vs. cyclosporine). In the reduced intensity setting, the effects of graft source and calcineurin inhibitor will be assessed. In order to meet either population, the patient had to be 20 years old or older receiving their first allogeneic transplant from with a calcineurin inhibitor plus either MMF or MTX for GVHD prophylaxis. There were 5660 patients receiving their first myeloablative transplant for AML, ALL, CML or MDS from an HLA-identical sibling or unrelated donor with a BM or PBSC graft source. There were 965 patients receiving their first reduced-intensity or non-myeloablative allogeneic transplant for AML, ALL, CML, MDS or NHL from an HLA-identical sibling donor with a PBSC graft source. Comments from Dr. Alousi were that if the proposal wanted to evaluate agvhd treatment, it would be very dependent on transplant center and the grade of acute GVHD (and grading can vary by center as well). Dr. Arora confirmed that dosing for GVHD prophylaxis is not collected on the CIBMTR forms. Tao Wang explained that there are 2 ways the analysis for this study could be implemented; (1) using Cox model to analyze the crude hazard of agvhd or (2) using the pseudovalue approach to look at the cumulative agvhd rate at certain fixed time points by treating death without agvhd as a competing risk. The effect of transplant center could be adjusted by random effect models. DROPPED Dr. Arora presented several slides on each of the dropped proposals, detailing the intended aims, population and study design, as well as the reasons why the proposals weren t feasible within the GVWC. d. PROP Refinement of risk factors for the development of sclerotic chronic GVHD and immunosuppressant cessation (D Kim/J Uhm) Dropped due to insufficient data collection on immunosuppressant duration, and sclerotic chronic GVHD on older forms. The CIBMTR forms aren t designed to collect cgvhd information according to the NIH consensus criteria. While there were a sufficient number of patients who identified as experiencing sclerotic 7

8 Not for publication or presentation Attachment 1 cgvhd, there were an equivalent number of patients who could not be identified as having sclerotic cgvhd or not because this information was not collected by the CIBMTR for unrelated donors prior to e. PROP Survival after severe agvhd: Are we making progress? (K Jamani/J Storek) Dropped due to overlap with current study GV f. PROP A CIBMTR retrospective study of incidence of sclerodermous cgvhd in patients with BCR-ABL-positive CML/ALL receiving tyrosine kinase inhibitors post allohct (A Salhotra/R Nakamura) Dropped due to insufficient data collection on tyrosine kinase inhibitors post-transplant, and on sclerotic chronic GVHD on older forms. The concerns about sclerotic cgvhd mentioned above in PROP apply to this proposal as well. Additionally, post-transplant TKI usage and dosage were not collected on the CIBMTR forms prior to Studies in progress In the interest of time, Dr. Couriel gave brief updates on the first 5 studies below. a. GV06-04 Current trends in chronic GVHD updated report from the Manuscript Preparation CIBMTR/NMDP (S Arai) b. GV11-04 Validation of cgvhd CIBMTR risk score associated with Manuscript Preparation major outcomes (M Flowers) c. GV11-02 Acute and chronic GVHD after unrelated umbilical cord Data File Preparation blood transplantation: Analysis of risk factors and outcomes (Y-B Chen/C Cutler) d. GV11-03 Comparison of tacrolimus versus cyclosporine with Analysis methotrexate for immunosuppression after allogeneic HCT for severe aplastic anemia (Y Inamoto/P Martin/M Flowers/A Urbano-Ispizua) e. GV13-02 The impact of the combination and sequence of Analysis immunosuppressive treatments on outcomes of acute GVHD: A methodological exercise in modeling adaptive treatment strategies (E Krakow/E Moodie) f. GV12-01 Outcomes of grades 3-4 acute GVHD post-allogeneic HCT: How much progress was achieved? (HJ Khoury) Protocol Development Dr. Khoury presented the update. The objectives of the study are to determine the change and prognostic factors in determining OS, DFS, TRM and relapse of adult allogeneic transplant recipients for AML, ALL, CML and MDS who developed severe (grade III-IV) agvhd from Comments from the GVWC were to consider adding children to the study population. g. GV12-02 Prognostic implications of acute upper gastrointestinal GVHD in patients undergoing myeloablative HCT (S Nikiforow/C Cutler) Protocol Development Dr. Cutler presented the update. The study s first objective is to determine the impact on prognosis and outcomes of OS, TRM, DFS and incidence of cgvhd between those patients who had isolated upper gastrointestinal (UGI) agvhd vs those with no agvhd vs those with agvhd without UGI involvement. The second objective is to determine within each individual grade of 8

9 Not for publication or presentation Attachment 1 agvhd, the impact on prognosis and outcomes that UGI involvement has. The study population consists of 7889 adult patients undergoing first non T-cell depleted myeloablative allogeneic transplant with an HLA-identical sibling donor or 8/8, 7/8, 6/8 unrelated donor with BM or PBSC graft sources and calcineurin inhibitor-based GVHD prophylaxis. This total number of patients will change to address each of the two objectives specified above. Comments from the GVWC were clarifying that the Glucksberg agvhd scale (I-IV) would be used to grade agvhd. When asked if the IBMTR scale (A-D) should be used instead, Dr. Cutler said that that would be considered. h. GV13-01 Impact of donor parity and donor type on outcomes of Protocol Development allogeneic HCT (A Kumar/A Loren) Dr. Couriel presented this update on behalf of the PIs. The primary objective of the study is to compare acute and chronic GVHD and OS between transplant recipients with HLA-identical female parous donors versus 8/8-matched unrelated male donors, as well as to determine whether the relationship between donor type, parity, gender and GVHD is impacted by other transplant variables. The secondary objective is to compare these 2 cohorts in terms of LFS and TRM. The study population consists of 1869 adult patients receiving their first non T-cell depleted, myeloablative allogeneic HCT for AML or ALL from an HLA-identical sibling female parous donor or 8/8-matched unrelated male donor between Dr. Couriel confirmed that specific organ involvement of acute and chronic GVHD can be investigated via the CIBMTR forms. 6. Other Business Hearing no items for other business, Dr. Couriel adjourned the meeting at 4:30 pm and reminded people to turn in their voting sheets and working committee evaluations. 9

10 Not for publication or presentation Attachment 1 Working Committee Overview Plan for a. GV04-02/05-03c Impact of cgvhd on late relapse, TRM and survival after allogeneic HCT for hematological malignancies. The manuscript is being revised to be submitted to Clinical Cancer Research. We anticipate the manuscript will be submitted by March b. GV06-04 Current trends in chronic GVHD - updated report from the CIBMTR/NMDP. The manuscript is undergoing revisions to be submitted to Blood. We anticipate the manuscript will be submitted by March c. GV11-04 Validation of cgvhd CIBMTR risk score associated with major outcomes. The initial draft of the manuscript is being prepared by Dr. Mukta Arora. We anticipate the manuscript will be submitted by July d. GV11-03 Comparison of tacrolimus versus cyclosporine with methotrexate for immunosuppression after allogeneic HCT for severe aplastic anemia. Analysis will begin shortly after Tandem and expected to be finished by April We plan on submitting the study as an abstract for ASH 2014 and submitting the manuscript by March e. GV11-02 Acute and chronic GVHD after unrelated umbilical cord blood transplantation: Analysis of risk factors and outcomes. We anticipate the protocol will be brought to the Stats Meeting for a second time by May 2014 and since a large portion of the data file has already been prepared, we plan to finish the analysis by July We plan on submitting the study as an abstract for ASH 2014 and submitting the manuscript by March f. GV12-01 Outcomes of grades 3-4 acute graft-versus-host disease post-allogeneic hematopoietic stem cell transplantation: how much progress was achieved? We anticipate the study will be in data file preparation by July After July, we anticipate preparing the data file and finishing the analysis by September 2014 so that the abstract may be submitted for Tandem We further anticipate submitting the manuscript by July g. GV12-02 Prognostic implications of acute upper gastrointestinal GVHD in patients undergoing myeloablative HCT. We anticipate the study will be in data file preparation by July After July, we anticipate preparing the data file, finalizing the analysis and having the manuscript in preparation by July h. GV13-01 Impact of donor parity and donor type on outcomes of allogeneic HCT. We anticipate the study to be in data file preparation by July i. GV13-02 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. The data file preparation and analysis is being completed by the PI as a part of her Master s thesis project. We anticipate the analysis will be completed and the manuscript will be in preparation by December j. GV14-01 (PROP ) Influence of donor and recipient age on risk for acute and chronic graft versus host disease in children receiving HLA identical BMT. We anticipate finalizing the protocol after July 2014 and that the study will be in data file preparation by July

11 Not for publication or presentation Attachment 1 k. GV14-02 (PROP / / / ) Comparison of mycophenolate versus methotrexate in combination with a calcineurin inhibitor for GVHD prophylaxis in allogeneic HCT. We anticipate finalizing the protocol after July 2014 and that the study will be in data file preparation by July

12 Not for publication or presentation Attachment 1 Oversight Work Assignments for Working Committee Leadership (February 2014) Corey Cutler Daniel Couriel Amin Alousi GV11-02: Acute and chronic GVHD after unrelated umbilical cord blood transplantation: Analysis of risk factors and outcomes GV11-04: Validation of cgvhd CIBMTR risk score associated with major outcomes GV12-01: Outcomes of grades 3-4 acute graft-versus-host disease post-allogeneic hematopoietic stem cell transplantation: how much progress was achieved? GV12-02: Prognostic implications of acute upper gastrointestinal GVHD in patients undergoing myeloablative HCT GV04-02/05-03c: Impact of cgvhd on late relapse, TRM and survival after allogeneic HCT for hematological malignancies GV06-04: Current trends in chronic GVHD - updated report from the CIBMTR/NMDP GV11-03: A retrospective comparison of tacrolimus versus cyclosporine with methotrexate for immunosuppression after allogeneic HCT according to graft and donor type GV14-02 Comparison of mycophenolate versus methotrexate in combination with a calcineurin inhibitor for GVHD prophylaxis in allogeneic HCT GV13-01: Impact of donor parity and donor type on outcomes of allogeneic HCT GV13-02: The impact of the combination and sequence of immunosuppressive treatments on outcomes of acute graftversus-host disease: A methodological exercise in modeling adaptive treatment strategies GV14-01 Influence of donor and recipient age on risk for acute and chronic graft versus host disease in children receiving HLA identical BMT 12

13 Not for publication or presentation Attachment 2 Accrual Summary for the Graft-vs-Host Disease Working Committee Characteristics of leukemia patients receiving allogeneic HCT between Other Characteristics of patients: HLA-identical sibling related donor Unrelated donor Identical twin Cord blood Number of patients Number of centers Age at transplant, years, median (range) 37 (<1-78) 30 (<1-83) 39 (<1-83) 38 (1-77) 16 (<1-81) Disease AML 8420 (37) 1240 (38) 9428 (35) 131 (38) 2039 (41) ALL 4532 (20) 823 (25) 5363 (20) 71 (21) 1711 (34) Other leukemia 1058 (5 ) 127 (4 ) 1340 (5 ) 30 (9 ) 230 (5 ) MDS 3324 (15) 463 (14) 5254 (20) 52 (15) 755 (15) CML 5433 (24) 599 (18) 5338 (20) 61 (18) 236 (5 ) Gender Male (58) 1950 (60) (58) 202 (59) 2757 (55) Female 9572 (42) 1301 (40) (42) 143 (41) 2214 (45) Missing 2 (<1) 1 (<1) 7 (<1) 0 0 Graft source Bone marrow (58) 1983 (61) (57) 177 (51) - Peripheral blood 9444 (41) 1261 (39) (43) 165 (48) - Missing 30 (<1) 8 (<1) 39 (<1) 3 (<1) - Conditioning regimen Myeloablative (87) 2671 (82) (79) 318 (92) 3977 (80) Reduced intensity 1529 (7 ) 218 (7 ) 3627 (14) 10 (3 ) 276 (6 ) Non-myeloablative 983 (4 ) 281 (9 ) 1520 (6 ) 4 (1 ) 665 (13) Missing 375 (2 ) 82 (3 ) 568 (2 ) 13 (4 ) 53 (1 ) GVHD prophylaxis None 910 (4 ) 289 (9 ) 984 (4 ) 266 (77) 312 (6 ) FK506 + MTX 2153 (9 ) 153 (5 ) 5226 (20) 5 (1 ) 155 (3 ) FK506 + MTX + other 554 (2 ) 80 (2 ) 2635 (10) 0 77 (2 ) FK506 + MMF 369 (2 ) 95 (3 ) 987 (4 ) (12) FK506 + MMF + other 130 (<1) 184 (6 ) 573 (2 ) (4 ) FK (<1) 24 (<1) 404 (2 ) 1 (<1) 81 (2 ) FK506 + other 387 (2 ) 32 (<1) 748 (3 ) 2 (<1) 247 (5 ) CsA + MTX (46) 944 (29) 6181 (23) 27 (8 ) 165 (3 ) CsA + MTX + other 2130 (9 ) 288 (9 ) 3686 (14) 3 (<1) 140 (3 ) CsA + MMF 1646 (7 ) 686 (21) 3629 (14) 3 (<1) 1320 (27) CsA + MMF + other 49 (<1) 19 (<1) 304 (1 ) (6 ) CsA 1725 (8 ) 175 (5 ) 438 (2 ) 23 (7 ) 158 (3 ) CsA + other 1461 (6 ) 243 (7 ) 634 (2 ) 8 (2 ) 1145 (23) Other 472 (2 ) 40 (1 ) 294 (1 ) 7 (2 ) 54 (1 ) 13

14 Not for publication or presentation Attachment 2 Characteristics of patients: HLA-identical sibling Other related donor Unrelated donor Identical twin Cord blood Number of patients Grade of Acute GVHD None (50) 1503 (46) 9403 (35) 291 (84) 2236 (45) Grade I 4155 (18) 552 (17) 4873 (18) 29 (8 ) 821 (17) Grade II 3280 (14) 521 (16) 5742 (21) 11 (3 ) 988 (20) Grade III 2951 (13) 482 (15) 4438 (17) 14 (4 ) 654 (13) Grade IV 1043 (5 ) 194 (6 ) 2267 (8 ) (5 ) Organ involvement of agvhd Skin 4935 (43) 739 (42) 7083 (41) 31 (57) 1200 (44) Skin + Liver 1155 (10) 153 (9 ) 1448 (8 ) 0 97 (4 ) Skin + Liver + UGI 1621 (14) 316 (18) 2765 (16) 2 (4 ) 217 (8 ) Skin + Liver + LGI 62 (<1) 9 (<1) 129 (<1) 0 22 (<1) Skin + Liver + UGI + LGI 197 (2 ) 46 (3 ) 228 (1 ) 0 75 (3 ) Skin + UGI 486 (4 ) 64 (4 ) 1016 (6 ) 1 (2 ) 259 (9 ) Skin + LGI 1410 (12) 258 (15) 2599 (15) 10 (19) 402 (15) Liver 220 (2 ) 19 (1 ) 209 (1 ) 1 (2 ) 38 (1 ) Liver + UGI 28 (<1) 4 (<1) 27 (<1) 0 10 (<1) Liver + LGI 272 (2 ) 26 (1 ) 324 (2 ) 0 48 (2 ) Liver + UGI + LGI 55 (<1) 7 (<1) 45 (<1) 1 (2 ) 29 (1 ) UGI 207 (2 ) 25 (1 ) 405 (2 ) 1 (2 ) 101 (4 ) LGI 602 (5 ) 69 (4 ) 841 (5 ) 6 (11) 150 (5 ) UGI + LGI 179 (2 ) 14 (<1) 201 (1 ) 1 (2 ) 87 (3 ) Incidence of cgvhd No (63) 2353 (72) (57) 312 (90) 3548 (71) Yes 8238 (36) 860 (26) (40) 23 (7 ) 1295 (26) Missing 286 (1 ) 39 (1 ) 812 (3 ) 10 (3 ) 128 (3 ) Maximum grade of cgvhd Limited 2822 (34) 325 (38) 2551 (24) 10 (43) 504 (39) Extensive 5342 (65) 525 (61) 8229 (76) 13 (57) 784 (61) Missing 74 (<1) 10 (1 ) 25 (<1) 0 7 (<1) Overall severity of cgvhd Mild 3521 (43) 380 (44) 3764 (35) 13 (57) 741 (57) Moderate 2965 (36) 296 (34) 3127 (29) 7 (30) 332 (26) Severe 1626 (20) 164 (19) 2030 (19) 3 (13) 202 (16) Missing 126 (2 ) 20 (2 ) 1884 (17) 0 20 (2 ) 14

15 Not for publication or presentation Attachment 2 Characteristics of patients: HLA-identical sibling Other related donor Unrelated donor Identical twin Cord blood Number of patients Year of transplant (38) 1151 (35) 4051 (15) 142 (41) 83 (2 ) (23) 753 (23) 6132 (23) 77 (22) 452 (9 ) (19) 532 (16) 7318 (27) 56 (16) 955 (19) (14) 397 (12) 6696 (25) 44 (13) 2226 (45) (6 ) 419 (13) 2526 (9 ) 26 (8 ) 1255 (25) Follow-up of survivors, months, median (range) 93 (0-294) 72 (0-290) 88 (0-294) 82 (2-289) 50 (0-227) Abbreviations: AML=Acute myelogenous leukemia, ALL=Acute lymphoblastic leukemia, CML=Chronic myelogenous leukemia, MDS=Myelodysplastic-myeloproliferative diseases, FK506=Tacrolimus, MTX=Methotrexate, CsA=Cyclosporine. 15

16 Not for publication or presentation Attachment 2 Characteristics of non-leukemia patients receiving allogeneic HCT between Characteristics of patients: HLA-identical sibling Other related donor Unrelated donor Identical twin Cord blood Number of patients Number of centers Age at transplant, years, median (range) 27 (<1-82) 10 (<1-76) 29 (<1-75) 43 (3-77) 4 (<1-73) Disease NHL 2782 (26) 311 (21) 2487 (36) 141 (35) 382 (16) HD 335 (3 ) 57 (4 ) 557 (8 ) 31 (8 ) 115 (5 ) SAA 2736 (26) 192 (13) 1251 (18) 63 (15) 150 (6 ) MM 1413 (13) 74 (5 ) 546 (8 ) 112 (27) 39 (2 ) Inherited abnormalities of erythrocyte 2213 (21) 242 (17) 561 (8 ) 12 (3 ) 359 (15) diff-or function SCID & other immune system disorders 462 (4 ) 424 (29) 590 (9 ) 3 (<1) 546 (23) Inherited abnormality of platelets 21 (<1) 7 (<1) 33 (<1) 0 29 (1 ) Histiocytic disorders 99 (<1) 40 (3 ) 270 (4 ) 1 (<1) 199 (8 ) Other 613 (6 ) 115 (8 ) 561 (8 ) 45 (11) 595 (25) Gender Male 6352 (60) 910 (62) 4298 (63) 204 (50) 1465 (61) Female 4322 (40) 552 (38) 2558 (37) 204 (50) 949 (39) Graft source Bone marrow 6737 (63) 929 (64) 3997 (58) 156 (38) - Peripheral blood 3920 (37) 524 (36) 2844 (41) 250 (61) - Missing 17 (<1) 9 (<1) 15 (<1) 2 (<1) - Conditioning regimen Myeloablative 7268 (68) 945 (65) 3511 (51) 298 (73) 1579 (65) Reduced intensity 1609 (15) 145 (10) 1757 (26) 59 (14) 322 (13) Non-myeloablative 1436 (13) 276 (19) 1386 (20) 20 (5 ) 459 (19) Missing 361 (3 ) 96 (7 ) 202 (3 ) 31 (8 ) 54 (2 ) GVHD prophylaxis None 642 (6 ) 283 (19) 327 (5 ) 341 (84) 220 (9 ) FK506 + MTX 677 (6 ) 35 (2 ) 1042 (15) 5 (1 ) 58 (2 ) FK506 + MTX + other 187 (2 ) 34 (2 ) 616 (9 ) 1 (<1) 40 (2 ) FK506 + MMF 187 (2 ) 35 (2 ) 354 (5 ) 1 (<1) 190 (8 ) FK506 + MMF + other 76 (<1) 75 (5 ) 177 (3 ) 0 86 (4 ) FK (<1) 18 (1 ) 143 (2 ) 1 (<1) 36 (1 ) FK506 + other 137 (1 ) 7 (<1) 193 (3 ) (5 ) CsA + MTX 4388 (41) 317 (22) 1188 (17) 12 (3 ) 85 (4 ) CsA + MTX + other 989 (9 ) 109 (7 ) 707 (10) 0 62 (3 ) CsA + MMF 1012 (9 ) 260 (18) 1329 (19) 2 (<1) 539 (22) 16

17 Not for publication or presentation Attachment 2 Characteristics of patients: HLA-identical sibling Other related donor Unrelated donor Identical twin Cord blood Number of patients GVHD prophylaxis (continued) CsA + MMF + other 43 (<1) 13 (<1) 119 (2 ) (5 ) CsA 1033 (10) 113 (8 ) 171 (2 ) 35 (9 ) 95 (4 ) CsA + other 1065 (10) 122 (8 ) 394 (6 ) 4 (<1) 733 (30) Other 149 (1 ) 41 (3 ) 96 (1 ) 6 (1 ) 29 (1 ) Grade of Acute GVHD None 6411 (60) 816 (56) 3099 (45) 370 (91) 1271 (53) Grade I 1590 (15) 221 (15) 1077 (16) 17 (4 ) 396 (16) Grade II 1232 (12) 202 (14) 1183 (17) 12 (3 ) 401 (17) Grade III 1089 (10) 155 (11) 966 (14) 8 (2 ) 235 (10) Grade IV 352 (3 ) 68 (5 ) 531 (8 ) 1 (<1) 111 (5 ) Organ involvement of agvhd Skin 2006 (47) 306 (47) 1603 (43) 22 (58) 590 (52) Skin + Liver 398 (9 ) 45 (7 ) 243 (6 ) 0 43 (4 ) Skin + Liver + UGI 500 (12) 92 (14) 531 (14) 1 (3 ) 75 (7 ) Skin + Liver + LGI 24 (<1) 0 20 (<1) 0 5 (<1) Skin + Liver + UGI + LGI 65 (2 ) 10 (2 ) 37 (<1) 0 28 (2 ) Skin + UGI 135 (3 ) 22 (3 ) 172 (5 ) 0 93 (8 ) Skin + LGI 613 (14) 101 (16) 631 (17) 10 (26) 172 (15) Liver 80 (2 ) 12 (2 ) 43 (1 ) 0 6 (<1) Liver + UGI 8 (<1) 0 6 (<1) 0 1 (<1) Liver + LGI 98 (2 ) 6 (<1) 99 (3 ) 0 25 (2 ) Liver + UGI + LGI 9 (<1) 6 (<1) 14 (<1) 0 3 (<1) UGI 58 (1 ) 6 (<1) 82 (2 ) 2 (5 ) 26 (2 ) LGI 229 (5 ) 31 (5 ) 238 (6 ) 2 (5 ) 54 (5 ) UGI + LGI 40 (<1) 9 (1 ) 38 (1 ) 1 (3 ) 22 (2 ) Incidence of cgvhd No 7794 (73) 1121 (77) 4174 (61) 378 (93) 1770 (73) Yes 2624 (25) 286 (20) 2460 (36) 10 (2 ) 572 (24) Missing 256 (2 ) 55 (4 ) 222 (3 ) 20 (5 ) 72 (3 ) Maximum grade of cgvhd Limited 1013 (39) 125 (44) 634 (26) 4 (40) 286 (50) Extensive 1584 (60) 161 (56) 1819 (74) 6 (60) 285 (50) Missing 27 (1 ) 0 7 (<1) 0 1 (<1) 17

18 Not for publication or presentation Attachment 2 Characteristics of patients: HLA-identical sibling Other related donor Unrelated donor Identical twin Cord blood Number of patients Overall severity of cgvhd Mild 1230 (47) 142 (50) 932 (38) 4 (40) 335 (59) Moderate 891 (34) 83 (29) 730 (30) 6 (60) 142 (25) Severe 465 (18) 58 (20) 513 (21) 0 86 (15) Missing 38 (1 ) 3 (1 ) 285 (12) 0 9 (2 ) Year of transplant (30) 375 (26) 723 (11) 108 (26) 39 (2 ) (26) 335 (23) 1271 (19) 111 (27) 210 (9 ) (27) 326 (22) 2377 (35) 59 (14) 592 (25) (14) 257 (18) 1940 (28) 66 (16) 1015 (42) (3 ) 169 (12) 545 (8 ) 64 (16) 558 (23) Follow-up of survivors, months, median (range) 86 (0-294) 64 (0-287) 74 (0-269) (0-245) (2-268) Abbreviations: NHL=Non-Hodgkin lymphoma, HD=Hodgkin disease, SAA=Severa aplastic anemia, FK506=Tacrolimus, MTX=Methotrexate, CsA=Cyclosporine. 18

19 Not for publication or presentation Attachment 3 Study Title: Development of a chronic GVHD-related disability measure using CIBMTR data Sung Won Choi, MD, MS, University of Michigan, sungchoi@med.umich.edu Daniel Couriel, MD, MS, University of Michigan, dcouriel@med.umich.edu Navneet Majhail, MD, MS, Cleveland Clinic, majhain@ccf.org Hypothesis: Chronic graft-versus-host disease (GVHD) increases the risk of physical disability after allogeneic hematopoietic stem cell transplantation (HSCT). Using existing CIBMTR data, we can develop a composite measure of physical disability to assess the impact of comorbidity associated with chronic GVHD, and also as a clinically meaningful outcome in hematopoietic stem cell transplant (HSCT) studies. Specific Aims: 1. To develop a composite disability measure for patients with chronic GVHD 2. To evaluate the composite disability measure as a predictor for non-relapse mortality after allogeneic HSCT Scientific Justification: Chronic GVHD is a major complication of allogeneic HSCT. Endpoints for GVHD-related clinical trials typically include incidence of GVHD, steroid-free survival, or non-relapse mortality. However, very little is known about the role of disability measures as an endpoint in GVHD studies. Designing the appropriate endpoints for clinical trials is imperative. Moreover, accurate knowledge about clinical benefits that are applicable in real-life settings and generalizable beyond the study population is necessary. Improvements in allogeneic HCT have led to an increased number of procedures being performed annually. In this study, we will develop a composite disability measure. This study will serve as a: 1) potential endpoint in future GVHD-related clinical trials, and 2) framework to evaluate cost analyses of allogeneic HSCT survivors. Outcomes that would be included as potential markers of disability include day 100, 365, and 730 Karnofsky Performance Score, non-infectious pulmonary abnormalities (BOS, pulmonary hemorrhage, COP), mechanical ventilation, cirrhosis, avascular necrosis, cataracts, congestive heart failure, hemorrhagic cystits/hematuria, myocardial infarction, pancreatitis, hypothyroidism, renal failure, stroke/seizure, infections, and new malignancy/second cancer. While the incidence of these disability outcomes individually may be low (i.e., rare events), collectively, a composite measure may provide a prognostic and predictive model for survivors of allogeneic HSCT. Patient Eligibility Population: The study population will include patients of any age (pediatric and adults) undergoing allogeneic HSCT after myeloablative or reduced intensity/nonmyeloablative conditioning reported to the CIBMTR between We have chosen this time period as CIBMTR data collection forms starting in 2007 captured more detailed data on GVHD as well as organ dysfunction. Malignant and non-malignant hematologic disorders will be included. All donor sources such as bone marrow, peripheral blood, umbilical cord, haploidentical will be included. Our study will focus on patients who have survived through day 100 in remission. Data Requirements: Variables Associated with Disability occurring between day years post transplantation: 19

20 Not for publication or presentation Attachment 3 KPS Non-infectious pulmonary abnormalities (BOS, pulmonary hemorrhage, COP) Mechanical ventilation Cirrhosis Avascular necrosis Cataracts Congestive heart failure Hemorrhagic cystitis/hematuria requiring medical intervention Myocardial infarction Pancreatitis Hypothyroidism Renal failure requiring dialysis Stroke/seizure Infections New malignancy/second cancer Chronic GVHD related variables: Date of onset of chronic GVHD Chronic GVHD grade Overall severity of chronic GVHD Organ involvement Other variables: Patient-related: Age Gender Race KPS at transplant Smoke (tobacco) use: Y or N FEV1 or DLCO: >80% vs % vs. <65% Disease-related: Malignant vs non-malignant CIMBTR Disease risk: early vs. intermediate vs. advanced Prior chest XRT: Y or N Transplant-related: Cell source: BM, PB, umbilical cord Donor HLA status: matched related, mismatched related, matched unrelated, mismatched unrelated, haploidentical CMV status Conditioning: myeloablative vs reduced intensity/nonmyeloablative Conditioning: TBI vs none ABO incompatibility GVHD prophylaxis: CSA vs Tacrolimus-based Year of allogeneic HSCT Study Design: The proposed study will develop a composite chronic GVHD related disability measure. We will look forward to obtaining CIBMTR statistical input on the study design. An example to approach this may be 20

21 Not for publication or presentation Attachment 3 to have cohorts development and validation cohorts. The development cohort can be used to come up with a scoring system while evaluating nonrelapse mortality as an endpoint among patients with no, mild, moderate and severe chronic GVHD. The score that has been developed can be validated through a second cohort from the study population. Sample Requirements: N/A References: 1. Chronic GVHD Consortium. Rationale and design of the chronic GVHD cohort study. Biol Blood Marrow Transplant 2011; 8: Inamoto Y, Martin PJ, Chai X, Jagasia M, Palmer J, Pdala J, Cutler C, Pavletic SZ, Arora M, Jacobsohn D, Carpenter PA, Flowers ME, Khera N, Vogelsang GV, Weisdorf D, Storer BE, Lee SJ. Chronic GVHD Consortium. Clinical benefits of response in chronic GVHD. Biol Blood Marrow Transplant 2012; 10: Khera, N., Zeliadt, S.B., Lee, S.j. Economics of hematopoietic cell transplantation. Blood 2012; 120(8): Majhail, N., Giralt, S, LeMaistre, C.F., Pasquini, M., Saber W., Farnia S., Bonagura A., Crawford S., Omel J. Guidelines for defining standard episode for hematopoietic stem cell transplantation patient care within the context of clinical trials. CIMBTR Martin PJ. Study design and endpoints in graft-versus-host disease. Best Pract Res Clin Haematol 2008; 21(2): Martin PJ, Bachier CR, Klingemann HG, McCarthy PL, Szabolcs P, Uberti JP, Shuster MW, Weisdorf D, Chao NJ, Kebriaei P, Shpall EJ, Macmillan ML, Soiffer RJ. Endpoints for clinical trials testing treatment of acute GVHD: a joint statement. Biol Blood Marrow Transplant 2009; 15(7): Pasquini M, Wang Z, Horowtiz MM, Gale RP report from the Center for International Blood and Marrow Transplant Research (CIBMTR): current uses and outcomes of hematopoietic cell transplants for blood and marrow disorders. Clin Transpl 2013: Pavletic SZ. Response as an end point in treatment trials for acute GVHD. Bone Marrow Transplant 2012; 47(2):

22 Not for publication or presentation Attachment 3 Table 1. Characteristics of patients who survived at least 100 days post-transplant from , as reported to the CIBMTR Characteristics of patients: HLA-id sibs Other related URD Number of patients Number of centers Patient-related Age at transplant, years, median (range) 48 (<1-78) 43 (<1-77) 41 (<1-81) Age at transplant, years (11) 168 (17) 1976 (20) (9 ) 106 (11) 1092 (11) (8 ) 93 (10) 920 (9 ) (9 ) 88 (9 ) 930 (9 ) (18) 123 (13) 1297 (13) (28) 183 (19) 1870 (19) (18) 215 (22) 1900 (19) Gender Male 2206 (57) 603 (62) 5827 (58) Female 1674 (43) 373 (38) 4156 (42) Missing (<1) Race Caucasian 3217 (83) 681 (70) 8353 (84) African-American 265 (7 ) 150 (15) 674 (7 ) Asian/Pacific Islander 249 (6 ) 97 (10) 523 (5 ) Others 76 (2 ) 33 (3 ) 209 (2 ) Missing 73 (2 ) 15 (2 ) 226 (2 ) Karnofsky score prior to transplant < (30) 254 (26) 2722 (27) > (67) 682 (70) 6947 (70) Missing 124 (3 ) 40 (4 ) 316 (3 ) Recipient cigarette smoking history No 2327 (60) 579 (59) 5340 (53) Yes 1165 (30) 255 (26) 2345 (23) Missing 388 (10) 142 (15) 2300 (23) 22

23 Not for publication or presentation Attachment 3 Table 1 (continued): HLA-id sibs Other related URD Number of patients Disease-related Malignant disease Non-malignant 515 (13) 180 (18) 1281 (13) Malignant 3199 (82) 770 (79) 8120 (81) Missing 166 (4 ) 26 (3 ) 584 (6 ) Disease AML 1434 (37) 280 (29) 3662 (37) ALL 475 (12) 124 (13) 1533 (15) CML 179 (5 ) 35 (4 ) 384 (4 ) MDS 583 (15) 95 (10) 1372 (14) Other leukemia 178 (5 ) 37 (4 ) 525 (5 ) NHL 311 (8 ) 129 (13) 578 (6 ) HD 7 (<1) 19 (2 ) 36 (<1) MM 27 (<1) 47 (5 ) 23 (<1) Other malignancies 5 (<1) 4 (<1) 7 (<1) SAA 223 (6 ) 56 (6 ) 307 (3 ) Inherited abnormalities erythrocyte diff-funct. 176 (5 ) 47 (5 ) 250 (3 ) SCID & other immune system disorders 84 (2 ) 69 (7 ) 419 (4 ) Inherited abnormalities of platelets 3 (<1) 0 23 (<1) Inherited disorders of metabolism 19 (<1) 6 (<1) 256 (3 ) Autoimmune diseases 5 (<1) 1 (<1) 6 (<1) Other 5 (<1) 1 (<1) 20 (<1) Missing 166 (4 ) 26 (3 ) 584 (6 ) Transplant-related D-R URD HLA match 8/8 N/A N/A 4442 (44) 7/8 N/A N/A 1398 (14) < 6/8 N/A N/A 1711 (17) Well-matched N/A N/A 270 (3 ) Partially-matched N/A N/A 185 (2 ) Mismatched N/A N/A 296 (3 ) Missing N/A N/A 1683 (17) D-R CMV match -/ (38) 346 (35) 2283 (23) -/+ 461 (12) 111 (11) 1114 (11) +/- 856 (22) 170 (17) 2715 (27) +/+ 963 (25) 221 (23) 2464 (25) Missing 126 (3 ) 128 (13) 1409 (14) 23

24 Not for publication or presentation Attachment 3 Table 1 (continued): HLA-id sibs Other related URD Number of patients D-R ABO match Matched 2244 (58) 501 (51) 1576 (16) Minor mismatch 525 (14) 108 (11) 934 (9 ) Major mismatch 511 (13) 91 (9 ) 900 (9 ) Bidirectional mismatch 122 (3 ) 14 (1 ) 329 (3 ) Missing 478 (12) 262 (27) 6246 (63) Graft type BM 869 (22) 369 (38) 1787 (18) PBSC 2936 (76) 549 (56) 4899 (49) UCB 38 (<1) 26 (3 ) 3256 (33) BM+UCB 35 (<1) 5 (<1) 6 (<1) PB+UCB 2 (<1) 27 (3 ) 37 (<1) Conditioning intensity MA 2449 (63) 440 (45) 6128 (61) RIC 1057 (27) 381 (39) 3123 (31) NMA 289 (7 ) 109 (11) 589 (6 ) Missing 85 (2 ) 46 (5 ) 145 (1 ) TBI used in conditioning regimen No 2400 (62) 470 (48) 5390 (54) TBI 1226 (32) 387 (40) 4108 (41) Missing 254 (7 ) 119 (12) 487 (5 ) Year of transplant (40) 369 (38) 3954 (40) (33) 205 (21) 2973 (30) (28) 402 (41) 3058 (31) Follow-up of survivors, months, median (range) 48 (3-83) 37 (3-81) 47 (3-84) 24

25 Not for publication or presentation Attachment 3 Table 2. Post-Transplant Disability / Comorbidity Characteristics Characteristics of patients: HLA-id sibs Other related URD Number of patients Number of centers Post transplant-related cgvhd comorbidity variables All entries are 'no' 784 (20) 230 (22) 1498 (15) At least one 'yes' 3103 (78) 769 (75) 8557 (83) All missing 77 (2 ) 25 (2 ) 193 (2 ) Number of comorbidity variables missing (95) 984 (96) 9741 (95) 1 36 (<1) 7 (<1) 27 (<1) 2 61 (2 ) 3 (<1) 84 (<1) 3 20 (<1) 3 (<1) 19 (<1) 4 3 (<1) 0 48 (<1) (<1) (<1) (<1) 8 1 (<1) 0 43 (<1) 9 1 (<1) 1 (<1) 1 (<1) (<1) 11 4 (<1) 1 (<1) (2 ) 25 (2 ) 193 (2 ) Number of comorbidities (22) 255 (25) 1691 (17) (54) 541 (53) 5213 (51) (18) 150 (15) 2173 (21) (5 ) 57 (6 ) 817 (8 ) 4 44 (1 ) 15 (1 ) 271 (3 ) 5 8 (<1) 5 (<1) 68 (<1) 6 3 (<1) 1 (<1) 15 (<1) KPS on Day-100 form < (40) 267 (35) 3705 (43) > (49) 379 (49) 3687 (43) Missing 351 (11) 123 (16) 1165 (14) 25