b. Newly appointed chair: Yago Nieto, MD; The University of Texas MD Anderson Cancer Center;

Transcription

1 Not for publication or presentation A G E N D A CIBMTR WORKING COMMITTEE FOR SOLID TUMORS Salt Lake City, Utah Friday, February 15, 2013, 2:45 4:45 PM Co-Chair: Co-Chair: Statisticians: Scientific Director: Michael R. Bishop, MD, University of Chicago Section of Hematology/Oncology, Chicago, IL Phone: ; Fax: ; mbishop.uchicagobmt@gmail.com Edward Stadtmauer, MD, Hospital of the University of Pennsylvania, Philadelphia, PA Phone: ; Fax: ; stadtmauer@uphs.upenn.edu Michael Hemmer, MS, CIBMTR, Milwaukee, WI Phone : , Fax : , mhemmer@mcw.edu Kwang Woo Ahn, PhD, CIBMTR Statistical Center, Milwaukee WI Phone: ; Fax: ; kwooahn@mcw.edu Mukta Arora, MD, MS University of Minnesota, Minneapolis, MN Phone: ; Fax: ; arora005@umn.edu 1. Introduction a Tandem Minutes for approval (Attachment 1) b. Newly appointed chair: Yago Nieto, MD; The University of Texas MD Anderson Cancer Center; ynieto@mdanderson.org. 2. Accrual summary (Attachment 2) 3. Presentation, published or submitted papers a. ST07-01 Hale GA, Arora M, Ahn KW, He W, Camitta B, Bishop MR, Bitan M, Cairo MS, Chan K, Childs RW, Copelan E, Davies SM, Diaz Perez MA, Doyle JJ, Gale RP, Vicent MG, Horn BN, Hussein AA, Jodele S, Kamani NR, Kasow KA, Kletzel M, Lazarus HM, Lewis VA, Myers KC, Olsson R, Pulsipher M, Qayed M, Sanders JE, Shaw PJ, Soni S, Stiff PJ, Stadtmauer EA, Ueno NT, Wall DA, Grupp SA. Allogeneic Hematopoietic Cell Transplantation for Neuroblastoma: The CIBMTR Experience. (In press) 4. Studies in progress (Attachment 3) a. ST00-02 Allogeneic stem cell transplant for renal cell cancer (J Barrett) (Attachment 4) b. ST09-01 Transplant trends for metastatic solid tumors in North America and Europe (R Childs/D Blaise) (Attachment 5) c. ST10-01 The value of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with high risk or metastatic inflammatory breast cancer (YC Cheng/NT Ueno) (Attachment 6) Data Collection Protocol Development Protocol Development 1

2 Not for publication or presentation 5. Deferred studies ST02-02 Allogeneic stem cell transplantation in colorectal cancer (L Barkholt/O Ringden/ M Aglietta) 6. Proposed studies PROP High dose chemotherapy and autologous stem cell transplantation for germ cell tumors. (M Qayed/T Olson/K Chiang) (Attachment 7) 7. Other business a. Brain-storming session 2

3 Not for publication or presentation Attachment 1 M I N U T E S CIBMTR WORKING COMMITTEE FOR SOLID TUMORS San Diego, California Wednesday, February 1, 2012, 12:15 pm 2:15 pm Co-Chair: Co-Chair: Statisticians: Michael R. Bishop, MD, Medical College of Wisconsin, Clinical Cancer Center, Milwaukee, WI Phone: Fax: ; mbishop@mcw.edu Edward Stadtmauer, MD, Hospital of the University of Pennsylvania, Philadelphia, PA Phone: ; Fax: ; stadtmauer@uphs.upenn.edu John Bosco Umejiego, MPH, CIBMTR, Minneapolis, MN Phone: ; Fax: ; jumejieg@nmdp.org Kwang Woo Ahn, PhD, CIBMTR Statistical Center, Milwaukee WI Phone: ; Fax: ; kwooahn@mcw.edu Scientific Director: Mukta Arora, MD, MS University of Minnesota, Minneapolis, MN Phone: ; Fax: ; arora005@umn.edu 1. Introduction The meeting was called to order at 12:15pm by Dr. Edward Stadtmauer. Co-chairs, scientific director and statisticians were introduced to the audience. Dr. Stadtmauer announced the new CIBMTR effort, the Forms Revision Process. All data collection forms are undergoing revision over the next two years, starting with the following: CRID (2804), Pre- TED (2400), Baseline (2000), Infectious Disease Markers (2004), HLA (2005), Infusion (2006), AML (2010/2110), ALL (2011/2111), MDS (2014/2114), JMML (2015/2115), Plasma Cell Disorders (2016/2116), Amyloidosis (2017/2117), Lymphoma (2018/2118) and Waldenstrom's Macroglobulinemia (2019/2119). The revised forms will coincide with the development of the new FormsNet application. Members are encouraged to become a member of the Forms Revision Review Committee in order to capture all the relevant information needed to produce high-quality studies. Suggestions for forms can be forwarded to the working committee leadership or Emilie Meissner at emeissne@nmdp.org Minutes of February, 2011 meeting (Attachment 1) The meeting minutes from the 2011 meeting were approved by the committee without any modification. 2. Accrual summary (Attachment 2) The accrual summary tables were briefly reviewed. Dr. Bishop led the discussion on the accrual summary and encouraged investigators with interest to participate in the STWC studies. He highlighted two areas that can be potentially focused on for studies. One area is the germ cell tumors. The committee had previously published manuscript on germ cell tumors a few years back, and it would be a great opportunity to keep investigating in this area. Interesting topics included effects of high dose therapy on germ cell tumor HCT survivors, effects of single vs. tandem HCTs and late 3

4 Not for publication or presentation Attachment 1 relapse after HCTs. Another area is the neuroblastoma and other related sarcomas. Current study ST07-01 looking at the allogeneic transplantation for neuroblastoma is an example of study in this area. 3. Published or submitted papers ST06-01 E Stadtmauer. AutoHCT for desmoplastic tumor. Submitted to Bone Marrow Transplantation. Dr. Stadtmauer presented this study. This study has been submitted to BMT and is currently under revision for re-submission. The objective of the study is to describe clinical outcomes of autologous transplant for desmoplastic small round cell tumors. There are 36 patients from 29 centers; 18 patients had additional comprehensive research data. This is the largest series study for desmoplastic small round cell tumors. Males were dominant. Majority patients received transplant between 2002 and Most of patients did not receive radiation therapy. About two third of patients never achieved complete response with therapy. About 71% of patients had relapsed after transplant and one patient died within 100 days of HCT. The study showed that an important predictor of long time survival was complete remission after HCT, with 57% of these patients alive at 3 years post-transplant. 4. Studies in progress (Attachment 3) a. ST00-02 Allotx for renal cell cancer (J Barrett) (Attachment 4) Supplemental Form/ Data Collection Dr. Barret presented this study. The specific aims of the study are to describe the worldwide experience of patients undergoing allogeneic peripheral blood stem cell transplants for renal cell cancer; to evaluate the results of allogeneic peripheral blood stem cell transplantation in renal cell cancer patients; and to identify patient, disease, and transplant-related prognostic factors for outcome after transplantation for renal cell cancer. Two hundred and four patients from 61 centers were identified. The study is at the data collection stage. Sixty two forms have been received from the centers. The meeting agreed to send out reminders to the transplant centers to complete the supplementary forms especially centers with high patient numbers. b. ST02-02 Allotx for colorectal cancer (O Ringdén) (Attachment 5) Supplemental Form / Data Collection Dr. Ringdén presented this study. The specific objectives of the study are to study the overall patient survival at 18 months and assessment of survival as compared to the population of untreated patients; to study the allogeneic tumoral response; to study the treatment related toxicity and infectious complications; study post-transplant immunological reactions; and to study the antitumoral activity against cell lines based on the primary tumor or corresponding tumor cell lines from the voluntary centers. This is a descriptive study and under form development. Up to 2005, only 40 patients registered and 19 patients reported to CIBMTR. Forms will be deployed to FormsNet2 this year. The leadership encouraged the audience to send in the forms. 4

5 Not for publication or presentation Attachment 1 c. ST07-01 Allogeneic HCT for Neuroblastoma (S Grupp) Manuscript preparation Dr. Grupp presented this study. This study is at manuscript preparation stage and was presented in the ASH 2011 poster presentation session. The objectives of this study were to describe outcomes after allogeneic HSCT in a modern treatment era in patients with neuroblastoma and to identify variables associated with improved disease-free survival (DFS). Outcomes to be evaluated include time to neutrophil and platelet engraftment, graft failure, acute and chronic graft-versus-host disease (GVHD), DFS, overall survival (OS), disease relapse, and treatment related mortality. The study period is and 143 patients were registered with CIBMTR with 66 patients having report forms. The patients were put in two categories; those who received only allogeneic HCT and those with allogeneic salvage therapy after autologous HCT. Dr Grupp observed that the practice in management of these patients is evolving as shown by the data. Patients with no prior autologous transplant had lower relapse rates and improved overall survival rates. Future studies comparing OS after autohct and allohct for patients in CR1 should be considered. d. ST09-01 HCT trends for metastatic solid tumors in NA (D Blaise / R Childs) (Attachment 6) Protocol Development Dr. Bishop presented this study. The main objective the study is to study trends in both autologous and allogeneic transplants for solid tumors in Europe and in North America reported through the CIBMTR and EBMT transplant registries between 1980 and The specific goals of the study are to characterize the overall number of allogeneic transplants performed for solid tumors, the annual number of autologous transplants for solid tumors and specific histology, types of allogeneic transplantation performed for solid tumors in terms of conditioning regimens and types of GVHD prophylaxis. There are 751 patients who have undergone allogeneic transplantation for solid tumors between 1981 and There are 32,410 patients who have undergone autologous transplants for solid tumors between 1982 and Discussion on this study centered on cooperation by EBMT and committee members agreed on a time line for the dataset for Europe to be obtained. This study was voted to move forward this year. e. ST10-01 High-dose chemo and autotx as adjuvant Rx in BC (N Ueno / Y Cheng) (Attachment 7) Protocol Development Dr. Arora presented this proposal. The objectives of this study are to determine the overall outcome of patients with IBC who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with high risk or metastatic disease; to determine the prognostic factors for survival in patients with IBC who benefit from high-dose chemotherapy and autologous hematopoietic stem cell transplantation; to compare outcomes of patients with IBC who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation to patients with non-ibc who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation high risk setting or 5

6 Not for publication or presentation Attachment 1 metastatic disease. One thousand one hundred and forty five patients with inflammatory breast cancer and 2152 patients with non-inflammatory breast cancer were identified. This study is under protocol development. The protocol will be circulated to the working committee later this year. This study was voted to move forward this year. 5. Other business The committee chairs reiterated their strong support for the members to submit new study ideas/proposals to the solid tumor working committee. Junior investigators are particularly welcomed to participate. The meeting adjourned at 2:00 pm. 6

7 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of autologous BMT for sarcoma and other sarcoma cancer reported to the CIBMTR between 1990 and 2012 Bone Sarcoma Other Sarcoma Characteristics TED Research TED Research Number of patients Number of centers Disease Bone sarcoma (exc. Ewing) 356 (26) 115 (27) 0 0 Ewing sarcoma 1003 (74) 304 (73) 0 0 Soft tissue sarcoma (82) 192 (85) Sarcoma unspecified (18) 35 (15) Year of transplant ( 6) 23 ( 5) 61 ( 9) 12 ( 5) ( 5) 24 ( 6) 49 ( 7) 11 ( 5) ( 7) 36 ( 9) 56 ( 8) 22 (10) (12) 86 (21) 126 (18) 71 (31) (18) 108 (26) 143 (21) 61 (27) (15) 54 (13) 68 (10) 24 (11) ( 9 20 ( 5) 60 ( 9) 7 ( 3) ( 9) 21 ( 5) 41 ( 6) 9 ( 4) ( 6) 18 ( 4) 38 ( 6) 5 ( 2) ( 7) 27 ( 6) 15 ( 2) 5 ( 2) ( 5) 2 (<1) 20 ( 3) ( 1) 0 5 (<1) 0 Age at transplant, median (range), years 17 (1-59) 17 (1-59) 16 (1-64) 15 (1-61) Gender Male 829 (61) 264 (63) 376 (55) 127 (56) Female 522 (38) 155 (37) 306 (45) 100 (44) Missing 8 (<1) Graft source Bone marrow 159 (12) 65 (16) 105 (15) 34 (15) PBSC 1072 (79) 326 (78) 500 (73) 174 (77) Bone marrow + PBSC 77 ( 6) 26 ( 6) 56 ( 8) 19 ( 8) Other/missing 51 ( 4) 2 (<1) 21 ( 3) 0 Median follow-up time, median (range), months 32 (<1-264) 72 (1-244) 33 (<1-216) 70 (2-216) 7

8 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of autologous BMT for Neuroblastoma and Breast Cancer reported to the CIBMTR between 1990 and 2012 Neuroblastoma Breast Cancer Characteristics TED Research TED Research Number of patients Number of centers Disease Neuroblastoma Breast cancer, NOS (87) 7281 (88) BC, inflammatory ( 2) 117 ( 1) BC, non-inflammatory (11) 844 (10) Year of transplant ( 5) 79 ( 6) 1539 ( 6) 737 ( 9) ( 5) 77 ( 6) 3067 (13) 1332 (16) ( 6) 127 (10) 5104 (21) 1994 (24) ( 7) 148 (12) 7118 (30) 2425 (29) (10) 193 (16) 6036 (25) 1520 (18) ( 9) 115 ( 9) 923 ( 4 ) 201 ( 2) (11) 67 ( 5) 160 (<1) 25 (<1) (12) 158 (13) 86 (<1) 6 (<1) ( 9) 94 (8) 17 (<1) (11) 133 (11) 22 (<1) 2 (<1) (13) 22 ( 2) 8 (<1) ( 2) 10 (<1) 0 0 Age at transplant, median (range), years 4 (<1-62) 4 (1-39) 46 (<1-73) 46 (1-72) Gender Male 2609 (58) 708 (58) 175 (<1) 44 (<1) Female 1838 (41) 513 (42) (99) 8197 (99) Missing 29 (<1) 2 (<1) 137 (<1) 1 (<1) Graft source Bone marrow 857 (19) 323 (26) 2824 (12) 1300 (16) PBSC 3405 (76) 852 (70) (72) 5803 (70) Bone marrow + PBSC 80 (2) 43 ( 4) 2576 (11) 1135 (14) Other/missing 134 (3) 5 (<1) 1307 ( 5) 4 (<1) Median follow-up time, median (range), months 31 (<1-263) 55 (<1-259) 48 (<1-270) 75 (<1-266) 8

9 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of autologous BMT for ovarian, testicular and germ cell tumors reported to the CIBMTR between 1990 and 2012 Ovarian and testicular tumor Germ Cell, Extragonadal Characteristics TED Research TED Research Number of patients Number of centers Disease Ovarian (epithelial) 2032 (46) 815 (50) 0 0 Testicular 2349 (54) 819 (50) 0 0 Germ Cell, extragonadal Year of transplant ( 9) 171 (10) 30 ( 3) 11 ( 6) ( 7) 176 (11) 35 ( 3) 11 ( 6) (11) 293 (18) 54 ( 5) 6 ( 3) (17) 362 (22) 24 ( 2) 8 ( 4) (16) 221 (14) 170 (15) 16 ( 9) ( 6) 95 ( 6) 170 (15) 19 (11) ( 6) 57 ( 3) 125 (11) 12 ( 7) ( 7) 51 ( 3) 138 (12) 20 (11) ( 5) 49 ( 3) 167 (15) 18 (10) ( 6) 139 ( 9) 99 ( 9) 52 (29) ( 8) 15 (<1) 98 ( 9) 5 ( 3) ( 2) 5 (<1) 21 ( 2) 0 Age at transplant, median (range), years 40 (2-76) 41 (2-76) 29 (1-69) 29 (2-58) Gender Male 2348 (54) 813 (50) 905 (80) 141 (79) Female 2029 (46) 821 (50) 225 (20) 37 (21) Missing 4 (<1) 0 1 (<1) 0 Graft source Bone marrow 501 (11) 289 (18) 62 ( 5) 18 (10) PBSC 3359 (77) 1176 (72) 1004 (89) 152 (85) Bone marrow + PBSC 281 ( 6) 147 ( 9) 46 ( 4) 7 ( 4) Other/missing 240 ( 5) 22 ( 1) 19 ( 2) 1 (<1) Median follow-up time, median (range), months 27 (<1-268) 48 (<1-241) 24 (<1-193) 42 (<1-193) 9

10 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of autologous BMT for Medulloblastoma and Wilm s Tumor reported to the CIBMTR between 1990 and 2012 Medulloblastoma Wilm s Tumor Characteristics TED Research TED Research Number of patients Number of centers Disease Medulloblastoma Wilm s Tumor Year of transplant (<1) 6 ( 1) 10 ( 3) (<1) 11 ( 2) 18 ( 5) 3 ( 5) (<1) 8 ( 2) 31 ( 9) 10 (16) ( 1) 9 ( 2) 34 (10) 6 (10) ( 9) 64 (14) 39 (11) 12 (19) ( 9) 60 (13) 36 (11) 8 (13) ( 9) 33 ( 7) 34 (10) 2 ( 3) (11) 39 ( 8) 44 (13) 9 (14) (21) 73 (16) 31 ( 9) 4 ( 6) (19) 160 (34) 33 (10) 9 (14) (16) 1 (<1) 29 ( 9) ( 4) 0 1 (<1) 0 Age at transplant, median (range), years 7 (1-56) 8 (1-49) 7 (1-49) 6 (1-49) Gender Male 1109 (63) 307 (66) 163 (48) 25 (40) Female 645 (37) 157 (34) 174 (51) 38 (60) Missing 1 (<1) 0 3 (<1) 0 Graft source Bone marrow 196 (11) 52 (11) 58 (17) 9 (14) PBSC 1505 (86) 397 (86) 262 (77) 50 (79) Bone marrow + PBSC 29 ( 2) 13 ( 3) 15 ( 4) 4 ( 6) Other/missing 25 ( 1) 2 (<1) 5 ( 1) 0 Median follow-up time, median (range), months 25 (<1-179) 50 (1-179) 49 (1-239) 51 (1-183) 10

11 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of autologous BMT for Lung Cancer and CNS Tumor reported to the CIBMTR between 1990 and 2012 Lung Cancer CNS Tumor Characteristics TED Research TED Research Number of patients Number of centers Disease Lung, small cell 202 (78) 125 (93) 0 0 Lung, non-small cell 39 (15) 10 ( 7) 0 0 Lung, not specified 19 ( 7) CNS tumor, including CNS PNET Year of transplant (27) 21 (16) 175 ( 5) 31 ( 3) (15) 30 (22) 124 ( 3) 46 ( 5) (20) 34 (25) 112 ( 3) 49 ( 5) (20) 37 (27) 167 ( 5) 52 ( 5) (11) 11 ( 8) 372 (10) 116 (12) ( 5) 2 ( 1) 322 ( 9) 131 (14) (<1) ( 9) 51 ( 5) (<1) ( 9) 70 ( 7) (15) 127 (13) (<1) (15) 280 (29) (13) 3 (<1) ( 4) 0 Age at transplant, median (range), years 49 (1-74) 50 (1-67) 7 (<1-69) 8 (<1-62) Gender Male 152 (58) 76 (56) 2135 (60) 565 (59) Female 108 (42) 59 (44) 1416 (40) 391 (41) Missing (<1) 0 Graft source Bone marrow 43 (17) 20 (15) 452 (13) 145 (15) PBSC 137 (53) 69 (51) 2852 (80) 764 (80) Bone marrow + PBSC 53 (20) 46 (34) 131 ( 4) 44 ( 5) Other/missing 27 (10) ( 3) 3 (<1) Median follow-up time, median (range), months 37 (<1-195) 43 (4-138) 25 (<1-236) 50 (1-218) Abbreviations: PBSC=peripheral blood stem cells 11

12 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of autologous BMT for Neuroblastoma and Breast Cancer reported to the CIBMTR between 1990 and 2012 Neuroblastoma Breast Cancer Characteristics TED Research TED Research Number of patients Number of centers Disease Neuroblastoma Breast cancer, NOS (87) 7281 (88) BC, inflammatory ( 2) 117 ( 1) BC, non-inflammatory (11) 844 (10) Year of transplant ( 5) 79 ( 6) 1539 ( 6) 737 ( 9) ( 5) 77 ( 6) 3067 (13) 1332 (16) ( 6) 127 (10) 5104 (21) 1994 (24) ( 7) 148 (12) 7118 (30) 2425 (29) (10) 193 (16) 6036 (25) 1520 (18) ( 9) 115 ( 9) 923 ( 4 ) 201 ( 2) (11) 67 ( 5) 160 (<1) 25 (<1) (12) 158 (13) 86 (<1) 6 (<1) ( 9) 94 (8) 17 (<1) (11) 133 (11) 22 (<1) 2 (<1) (13) 22 ( 2) 8 (<1) ( 2) 10 (<1) 0 0 Age at transplant, median (range), years 4 (<1-62) 4 (1-39) 46 (<1-73) 46 (1-72) Gender Male 2609 (58) 708 (58) 175 (<1) 44 (<1) Female 1838 (41) 513 (42) (99) 8197 (99) Missing 29 (<1) 2 (<1) 137 (<1) 1 (<1) Graft source Bone marrow 857 (19) 323 (26) 2824 (12) 1300 (16) PBSC 3405 (76) 852 (70) (72) 5803 (70) Bone marrow + PBSC 80 (2) 43 ( 4) 2576 (11) 1135 (14) Other/missing 134 (3) 5 (<1) 1307 ( 5) 4 (<1) Median follow-up time, median (range), months 31 (<1-263) 55 (<1-259) 48 (<1-270) 75 (<1-266) 12

13 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of autologous BMT for ovarian, testicular and germ cell tumors reported to the CIBMTR between 1990 and 2012 Ovarian and testicular tumor Germ Cell, Extragonadal Characteristics TED Research TED Research Number of patients Number of centers Disease Ovarian (epithelial) 2032 (46) 815 (50) 0 0 Testicular 2349 (54) 819 (50) 0 0 Germ Cell, extragonadal Year of transplant ( 9) 171 (10) 30 ( 3) 11 ( 6) ( 7) 176 (11) 35 ( 3) 11 ( 6) (11) 293 (18) 54 ( 5) 6 ( 3) (17) 362 (22) 24 ( 2) 8 ( 4) (16) 221 (14) 170 (15) 16 ( 9) ( 6) 95 ( 6) 170 (15) 19 (11) ( 6) 57 ( 3) 125 (11) 12 ( 7) ( 7) 51 ( 3) 138 (12) 20 (11) ( 5) 49 ( 3) 167 (15) 18 (10) ( 6) 139 ( 9) 99 ( 9) 52 (29) ( 8) 15 (<1) 98 ( 9) 5 ( 3) ( 2) 5 (<1) 21 ( 2) 0 Age at transplant, median (range), years 40 (2-76) 41 (2-76) 29 (1-69) 29 (2-58) Gender Male 2348 (54) 813 (50) 905 (80) 141 (79) Female 2029 (46) 821 (50) 225 (20) 37 (21) Missing 4 (<1) 0 1 (<1) 0 Graft source Bone marrow 501 (11) 289 (18) 62 ( 5) 18 (10) PBSC 3359 (77) 1176 (72) 1004 (89) 152 (85) Bone marrow + PBSC 281 ( 6) 147 ( 9) 46 ( 4) 7 ( 4) Other/missing 240 ( 5) 22 ( 1) 19 ( 2) 1 (<1) Median follow-up time, median (range), months 27 (<1-268) 48 (<1-241) 24 (<1-193) 42 (<1-193) 13

14 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of autologous BMT for Medulloblastoma and Wilm s Tumor reported to the CIBMTR between 1990 and 2012 Medulloblastoma Wilm s Tumor Characteristics TED Research TED Research Number of patients Number of centers Disease Medulloblastoma Wilm s Tumor Year of transplant (<1) 6 ( 1) 10 ( 3) (<1) 11 ( 2) 18 ( 5) 3 ( 5) (<1) 8 ( 2) 31 ( 9) 10 (16) ( 1) 9 ( 2) 34 (10) 6 (10) ( 9) 64 (14) 39 (11) 12 (19) ( 9) 60 (13) 36 (11) 8 (13) ( 9) 33 ( 7) 34 (10) 2 ( 3) (11) 39 ( 8) 44 (13) 9 (14) (21) 73 (16) 31 ( 9) 4 ( 6) (19) 160 (34) 33 (10) 9 (14) (16) 1 (<1) 29 ( 9) ( 4) 0 1 (<1) 0 Age at transplant, median (range), years 7 (1-56) 8 (1-49) 7 (1-49) 6 (1-49) Gender Male 1109 (63) 307 (66) 163 (48) 25 (40) Female 645 (37) 157 (34) 174 (51) 38 (60) Missing 1 (<1) 0 3 (<1) 0 Graft source Bone marrow 196 (11) 52 (11) 58 (17) 9 (14) PBSC 1505 (86) 397 (86) 262 (77) 50 (79) Bone marrow + PBSC 29 ( 2) 13 ( 3) 15 ( 4) 4 ( 6) Other/missing 25 ( 1) 2 (<1) 5 ( 1) 0 Median follow-up time, median (range), months 25 (<1-179) 50 (1-179) 49 (1-239) 51 (1-183) 14

15 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of autologous BMT for Lung Cancer and CNS Tumor reported to the CIBMTR between 1990 and 2012 Lung Cancer CNS Tumor Characteristics TED Research TED Research Number of patients Number of centers Disease Lung, small cell 202 (78) 125 (93) 0 0 Lung, non-small cell 39 (15) 10 ( 7) 0 0 Lung, not specified 19 ( 7) CNS tumor, including CNS PNET Year of transplant (27) 21 (16) 175 ( 5) 31 ( 3) (15) 30 (22) 124 ( 3) 46 ( 5) (20) 34 (25) 112 ( 3) 49 ( 5) (20) 37 (27) 167 ( 5) 52 ( 5) (11) 11 ( 8) 372 (10) 116 (12) ( 5) 2 ( 1) 322 ( 9) 131 (14) (<1) ( 9) 51 ( 5) (<1) ( 9) 70 ( 7) (15) 127 (13) (<1) (15) 280 (29) (13) 3 (<1) ( 4) 0 Age at transplant, median (range), years 49 (1-74) 50 (1-67) 7 (<1-69) 8 (<1-62) Gender Male 152 (58) 76 (56) 2135 (60) 565 (59) Female 108 (42) 59 (44) 1416 (40) 391 (41) Missing (<1) 0 Graft source Bone marrow 43 (17) 20 (15) 452 (13) 145 (15) PBSC 137 (53) 69 (51) 2852 (80) 764 (80) Bone marrow + PBSC 53 (20) 46 (34) 131 ( 4) 44 ( 5) Other/missing 27 (10) ( 3) 3 (<1) Median follow-up time, median (range), months 37 (<1-195) 43 (4-138) 25 (<1-236) 50 (1-218) 15

16 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of allogeneic BMT reported to the CIBMTR between 1990 and 2012 Characteristics TED Research Hepatobiliary Year of transplant ( 7) 2 (13) (10) 3 (19) (20) 5 (31) (33) 3 (19) (17) 2 (13) (10) ( 3) 1 ( 6) Renal carcinoma/kidney Year of transplant (<1) ( 4) 3 ( 1) (45) 127 (55) (37) 66 (28) ( 9) 22 ( 9) ( 2) 6 ( 3) ( 2) 8 ( 3) ( 1) Ovarian cancer Year of transplant ( 2) ( 2) 1 ( 6) ( 2) (10) 2 (12) (10) 1 ( 6) (20) 2 (12) (49) 11 (65)

17 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of allogeneic BMT reported to the CIBMTR between 1990 and 2012 TED Research Characteristics Year of transplant (continued) ( 3) Breast Cancer Year of transplant ( 2) 3 ( 2) ( 3) 5 ( 4) ( 7) 15 (11) (15) 32 (24) (20) 32 (24) (21) 23 (17) (16) 10 ( 7) (10) 11 ( 8) ( 5) 3 ( 2) ( 1) (<1) Other disease Other malignant, unknown 144 (34) 56 (37) Head and neck 2 (<1) 1 (<1) Lung cancer, small cell 4 (<1) 2 ( 1) Lung cancer, non-small cell 6 ( 1) 0 Pancreas 13 ( 3) 6 ( 4) Prostate 7 ( 2) 1 (<1) Testis 15 ( 4) 5 ( 3) Cervical 1 (<1) 1 (<1) Sarcoma unspecified 19 ( 5) 7 ( 5) Bone sarcoma (exc. Ewing) 29 ( 7) 10 ( 7) CNS tumors 8 ( 2) 5 ( 3) Wilm s tumor 8 ( 2) 2 ( 1) Retinoblastoma 3 (<1) 1 (<1) 17

18 Not for publication or presentation Attachment 2 Accrual Summary for Solid Tumor Working Committee Characteristic of recipients of allogeneic BMT reported to the CIBMTR between 1990 and 2012 TED Research Characteristics Other disease (continued) Ewing sarcoma 92 (22) 40 (26) Germ cell tumor 19 ( 5) 4 ( 3) Medulloblastoma 10 ( 2) 4 ( 3) PNET 3 (<1) 1 (<1) Gastric malig 1 (<1) 0 Thymoma 2 (<1) 1 (<1) Rhabdomyasarcoma 27 ( 6) 4 ( 3) Leiomyosarcoma 1 (<1) 0 Fibrosarcoma 3 (<1) 0 Synovial sarcoma 1 (<1) 0 18

19 Not for publication or presentation Attachment 3 TO: FROM: RE: Solid Tumors Working Committee Members Mukta Arora, MD, MS Scientific Director Solid Tumors Committee Studies in Progress Summery Studies in progress ST10-01: The value of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with high risk or metastatic inflammatory breast cancer (YC Cheng/NT Ueno) The objectives of this study are to determine the overall outcomes (overall survival, treatment-related mortality, disease-free survival, relapse and progression of disease) of patients with IBC who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with high risk or metastatic disease and to determine the prognostic factors in patients who benefit from such a treatment. A final objective is to compare outcomes of patients who underwent high-dose chemotherapy and autologous transplantation in a high-risk or metastatic setting with IBC to those with non-ibc. The revised protocol is available for review. Studies previously proposed, but not initiated ST00-02: Allogeneic stem cell transplants for renal cell cancer (J Barrett): The objectives of this study are to describe the worldwide experience of patients undergoing allogeneic peripheral blood stem cell transplants for renal cell cancer, to evaluate the results of these transplants and to identify patient-, disease- and transplant-related prognostic factors for the transplant s outcome. An updated protocol is available for review. ST09-01: Transplant trends for metastatic solid tumors in North America (R Childs): The main objective of this study is to evaluate trends in autologous and allogeneic hematopoietic stem cell transplantation in North America over the past 20 years. After initially limiting the scope of the study to North America transplants only, the Solid Tumor WC chairs decided it would be best to open the study to European transplants as well. An updated protocol is available for review. 19

20 Not for publication or presentation Attachment 4 CIBMTR ST00-02 ALLOGENEIC STEM CELL TRANSPLANTS FOR RENAL CELL CANCER Study Chair: Study Co-Chair: Study Statistician: A. John Barrett, MD Hematology Branch National Heart, Lung and Blood Institute National Institutes of Health, Bldg. 10, Room 7C Rockville Pike Bethesda, MD USA Telephone: Fax: barrettj@nhlbi.nih.gov Olle Ringdén, MD, PhD Professor of Transplantation Immunology Director, Bone Marrow Transplantation Huddinge University Hospital S Huddinge, Sweden Telephone: Fax: Olle.Ringden@impi.ki.se Kwang Woo Ahn, PhD, CIBMTR Statistical Center 8701 Watertown Plank Rd Milwaukee WI USA Phone: Fax: kwooahn@mcw.edu Michael Hemmer, MS CIBMTR Milwaukee 9200 W Wisconsin Ave. Milwaukee, WI USA Telephone: Fax: mhemmer@mcw.edu 20

21 Not for publication or presentation Attachment 4 Scientific Director: Working Committee Chairs: Mukta Aurora, MD University of Minnesota Division of Hematology/Oncology & Transplant Box 480 Mayo Building 420 Delaware Street Minneapolis, MN Telephone: Fax: arora005@umn.edu Michael R. Bishop, MD University of Chicago Section of Hematology/Oncology 5841 S Maryland Ave. MC2115 Chicago, IL USA Phone: Fax: mbishop.uchicagobmt@gmail.com Edward A. Stadtmauer, MD Abramson Cancer Center University of Pennsylvania 3400 Spruce St. 16 Penn Tower Philadelphia, PA USA Telephone: Fax: stadtmau@mail.med.upenn.edu 21

22 Not for publication or presentation Attachment HYPOTHESIS: Allogeneic stem cell transplantation (SCT) has a therapeutic role in the treatment of metastatic renal cell cancer (RCC). 2.0 OBJECTIVES: 2.1 To describe the worldwide experience of patients undergoing allogeneic peripheral blood stem cell transplants for renal cell cancer. 2.2 To evaluate the results of allogeneic peripheral blood stem cell transplantation in renal cell cancer patients. Outcomes to be assessed from the date of transplant include the following: Response rates; Acute and chronic GVHD; Treatment-related mortality; Progression/ Relapse; Renal cell cancer-free survival; Overall survival; Causes of death. 2.3 To identify patient-, disease-, and transplant-related prognostic factors for outcome after transplantation for renal cell cancer. 3.0 BACKGROUND: Allogeneic SCT can cure hematological malignancies by two mechanisms - (i) cytoreduction from dose-intensive chemoradiotherapy, (ii) a lymphocyte-mediated graft-versus-malignancy effect. It is possible that either or both these mechanisms may be effective in the treatment of RCC and other non-hematological malignancies. Recently there have been reports of tumor response in breast cancer, ovarian cancer and RCC recipients of allogeneic -SCT (1-4). In particular, the promising tumor responses and complete remissions seen in metastatic RCC following nonmyeloablative stem cell transplants (NST) have created wide interest in further exploring allogeneic SCT in this condition. Renal cell carcinoma is considered relatively insensitive to chemotherapy. Current conventional treatment focuses on enhancement of immunologic control using IFN and/or IL-2. The use of low intensity conditioning regimens to treat metastatic RCC is logical because dose intensification of chemotherapy does not have any advantage in the treatment of this malignancy. NST spares unnecessary toxicity while permitting the establishment of a donor hematopoietic and immune system to exert a graft-versus-tumor (GVT) effect (5). Currently the only published reports of NST in RCC are limited to a single series and several case reports (6-10). Many questions are posed by these initial findings concerning the reproducibility and characteristics of the GVT effect, the impact of different transplant techniques on the GVT effect and the overall probability of success in treating RCC by this technique. With its worldwide access to stem cell transplantation data IBMTR provides a unique opportunity to answer these questions. It is therefore proposed to use the CIBMTR reporting system to collect data on allogeneic SCT for RCC. We will attempt to identify response rates in RCC, and determine the role of specific transplant approaches and the impact of GVHD on disease response and survival. 22

23 Not for publication or presentation Attachment STUDY POPULATION: Patient eligibility/selection criteria include: 4.1 Patients undergoing allogeneic peripheral blood stem cell transplants for renal cell cancer between 1998 and 2002, reported to the CIBMTR. 5.0 OUTCOMES: Potential numbers of subjects are given in Tables 1 and Acute graft-versus-host disease: maximum overall grade, and occurrence of grade II, III and/or IV skin, gastrointestinal or liver abnormalities fulfilling the Glucksberg criteria of acute GVHD. 4.2 Chronic graft-versus-host disease: occurrence of symptoms in any organ system fulfilling the criteria of chronic GVHD. 4.3 Response rate: complete or partial response measured at 100 days and 1 year as described in Table Transplant-related mortality: patients who die in the first 28 days after transplant or deaths in continuous remission are considered events. Those who survive without relapse or progressive disease are censored at the date of last contact. This event is summarized by the cumulative incidence estimate with progression as the competing risk. 4.5 Progression/ Relapse: progressive disease as described in Table 3 or recurrence of disease for those in complete remission are events. Those who survive without recurrence or progressive disease are censored at the date of last contact. This event is summarized by the cumulative incidence estimate with death without progression as the competing risk. 4.6 Progression-free survival: survival without recurrence or tumor progression. Recurrence or progression of disease, as described in Table 3, and death from any cause are considered events. Those who survive without recurrence or progression are censored at the date of last contact. 4.7 Overall survival: time to death. Patients are censored at time of last contact. 6.0 VARIABLES TO BE ANALYZED: Patient-related: - Age: continuous - Gender: male vs female - Karnofsky performance status: 80 vs >80 Disease-related: - Histology: clear cell vs others - Sites of metastasis: bone vs CNS vs others 23

24 Not for publication or presentation Attachment 4 - Extent of disease: residual vs bulky - Surgery: yes/no - Interferon: yes/no - Chemotherapy: yes/no - Radiation: yes/no - Disease status at transplant: to be determined Transplant-related: - Time from diagnosis to transplant: continuous - Gender match: to be determined (based on feasibility) - Conditioning regimen: to be determined based on protocol regimens - Donor: HLA-identical sibling vs others - GVHD prophylaxis: to be determined Post-transplant immune therapy - Planned DLI (intention to treat): yes/no - DLI for progression: yes/no - Cytokines: yes/no - IL-2 Interferon: yes/no - GM-CSF: yes/no 7.0 DATA COLLECTION: The first step in this study is to prepare a data collection form capturing the disease-specific variables noted in section 6.0. Patient- and transplant-related variables will be captured using the standard CIBMTR Core Report Form and Graft Inserts. Centers registering eligible patients will be contacted requesting that the comprehensive Report Forms be completed (see Table 1). Centers wishing to participate in this study must report all consecutive transplants for renal cell cancer fulfilling the eligibility criteria noted in section STUDY DESIGN: Descriptive tables of patient-, disease-, and transplant-related factors will be prepared. These tables will list median and range for continuous variables and percent of total for categorical variables. The product-limit estimator proposed by Kaplan-Meier will be used to estimate the median and range of the follow-up time. Probability of progression-free survival and overall survival will be calculated using the Kaplan- Meier estimator, with the variance estimated by Greenwood s formula. Values for other endpoints will be generated using cumulative incidence estimates (11). Comparison of survival curves will be done using the log-rank test. Multivariate analyses will be performed using proportional hazards models. These analyses will fit models to determine which risk factors (Sec 6.0) may be related to a given outcome. All variables will first be examined to assure that they comply with the proportional hazards assumption. Factors found to have non-proportional hazards will be adjusted for in subsequent analyses. A stepwise model building approach will then be used to develop models for relapse, treatment-related mortality, progression-free survival and overall survival. 24

25 Not for publication or presentation Attachment 4 Multivariate analyses for response rate will be performed using binary logistic regression model. The response is partial or complete response. A forward stepwise model building approach will be used to model response. 9.0 REFERENCES: 1. Ueno NT, Rondon G, Mirza NQ, et al. Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer. J Clin Oncol 16:986, Eibl B, Schwaighofer H, Nachbaur D, et al. Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. Blood 88:1501, Childs R, Clave E, Plante M, et al. Successful treatment of metastatic renal-cell carcinoma with a non-myeloablative allogeneic peripheral blood progenitor cell transplant: evidence for a graft-versus-tumor effect. J Clin Oncol Bay JO, Choufi B, Pomel C, et al. Potential allogeneic graft-versus-tumor effect in a patient with ovarian cancer. Bone Marrow Transplant Mar;25(6): Barrett AJ, Childs RC. The benefits of an alloresponse - graft-versus-tumor. J Hematotherapy & Stem Cell Res., 2000, 9: Childs R, Chernoff A, Contentin N, et al. Regression of metastatic renal- cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem- cell transplantation. N Engl J Med Sep 14; 343(11): Rini B, Zimmerman TM, Gajewski TF, et al. Allogeneic peripheral blood stem cell transplantation for metastatic renal cell carcinoma. J Urol 2001 Apr; 165(3): Bregni M., Dodero A., Peccatori J. et al. Graft-vs-tumor effect in advanced solid tumors following reduced intensity stem cell allografting. Proceedings of The American Society of Clinical Oncology 2001:20; Makimoto A., Mineishi S., Tanosaki R. et al. Nonmyeloablative stem cell transplantation (NST) for refractory solid tumors. Proceedings of The American Society of Clinical Oncology 2001:20; Rini B., Zimmerman T.M., Gajewski T.F., et al. Allogeneic stem cell transplantation for metastatic renal cell cancer after nonmyeloablative chemotherapy: Engraftment rates, toxicity and initial clinical results. Proceedings of The American Society of Clinical Oncology 2001:20; Cox RD. Regression analysis and life tables. J of Royal Statist Soc 1972; B 34:

26 Not for publication or presentation Attachment 4 Table 2. Characteristics of patients who underwent allogeneic bone marrow or peripheral blood stem cell transplants for Renal Cell Cancer registered to the CIBMTR between Characteristics of patients: Number of patients 466 Number of centers 117 Age at transplant, median (range), years 52 (7-75) Age at transplant, years ( 3) ( 9) (28) (43) (17) Gender Male 356 (76) Female 110 (24) Graft type BM 21 ( 5) PBSC 444 (95) BM + PBSC 1 (<1) Donor HLA-identical sibling 382 (82) Other relative 25 ( 5) Unrelated 57 (12) TBD 2 (<1) Year of transplant (<1) ( 4) (15) (33) (20) (15) ( 6) ( 3) (<1) ( 1) ( 1) ( 1) ( 1) (<1) 26

27 Not for publication or presentation Attachment 4 Table 2. Continued. Characteristics of patients: GVHD Prophylaxis None 14 ( 3) T-Cell depletion 18 ( 4) CsA + MTX ± others 37 ( 8) CsA + MMF ± others 89 (19) CsA ± others 75 (16) FK506 + MTX ± others 41 ( 9) FK506 + MMF ± others 28 ( 6) FK506 ± others 13 ( 3) Other 17 ( 4) Missing 134 (29) a The CIBMTR collects data on two levels. All centers provide Registration data (age, sex, disease, disease stage and duration, graft type, donor type, conditioning regimen, graft treatment, GVHD prophylaxis and posttransplant disease status, survival, second cancers and primary cause of death) for all consecutive transplants. Registration data allow analysis of trends in transplant use and outcome and identification of patients for specific studies. Research data are collected on a subset of registered patients. Research data are collected on Report Forms which capture comprehensive clinical and demographic information. *Supplemental forms were sent out on to transplant centers to gather sufficient data on 84 Research patients to proceed with the study. As of , transplant centers for 72 patients have responded. Of the 12 remaining, it seems realistically impossible to retrieve data for 9 of them. 27

28 Not for publication or presentation Attachment 4 Table 3.CIBMTR criteria for definition of complete remission, partial response, stable disease, mixed response and progressive disease in patients with renal carcinoma. CR = Complete Remission Response - Disappearance of all target lesions for a period of at least one month CRU = Complete Response with persistent bone scan/x-ray abnormalities of unknown significance PR = Partial Response - At least 30% decrease in the sum of the longest diameter of measured lesions (target lesions) taking as reference the baseline sum of longest diameters SD = Stable Disease - Neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameters since the treatment started PD = Progressive Disease - At least a 20% increase in the sum of the longest diameter of measured lesions (target lesions), taking as reference the smallest sum of the longest diameters recorded since the treatment started or the appearance on one or more new lesions NETD = Not Evaluable, Toxic Death NE = Not Evaluable, specify reason 28

29 Not for publication or presentation Attachment 5 CIBMTR ST09-01 TRANSPLANT TRENDS FOR METASTATIC SOLID TUMORS IN NORTH AMERICA AND EUROPE DRAFT PROTOCOL Study Chair: Study Co-chair: Statistician: Richard Childs, MD National Heart, Lung and Blood Institute 10 Center Drive, Building 10, CRC Rm Bethesda, MD Telephone: Fax: childsr@nhlbi.nih.gov Didier Blaise, MD Institut Paoli Calmettes Marseille, France Telephone: Fax: blaised@marseille.fnclcc.fr Michael Hemmer, MS CIBMTR Milwaukee 9200 W Wisconsin Ave. Milwaukee, WI USA Telephone: Fax: mhemmer@mcw.edu Kwang Woo Ahn, PhD, CIBMTR Statistical Center 8701 Watertown Plank Rd Milwaukee WI USA Phone: Fax: kwooahn@mcw.edu 29

30 Not for publication or presentation Attachment 5 Scientific Director: Mukta Arora, MD Assistant Professor University of Minnesota Division of Hematology/Oncology & Transplant Box 480 Mayo Building 420 Delaware Street SE Minneapolis, MN USA Office: Fax: arora005@umn.edu Working Committee Chairs: Michael R. Bishop, MD University of Chicago Section of Hematology/Oncology 5841 S Maryland Ave. MC2115 Chicago, IL USA Phone: Fax: mbishop.uchicagobmt@gmail.com Edward A. Stadtmauer, MD Abramson Cancer Center University of Pennsylvania 3400 Spruce St. 16 Penn Tower Philadelphia, PA USA Telephone: Fax: stadtmau@mail.med.upenn.edu 30

31 Not for publication or presentation Attachment SPECIFIC AIMS: The main objective is to study trends in both auto and allo HCT for solid tumors in North America and Europe reported through the CIBMTR transplant registries over the past 20 years. Specific aims of the study are listed below: 1.1 To correlate the impact of published clinical trials on transplant trends and annual transplant numbers 1.2 To evaluate the impact of negative data on autohct for breast cancer on autohct numbers for other types of solid tumors 1.3 To evaluate the impact of recent advances in the treatment of metastaic RCC with agents such as sorafenib, sunitinib, and temsirolimus, on the number of transplants being performed for RCC over the past 3 years 1.4 Annual numbers of allohct performed for all solid tumors as well as tumor-specific transplant numbers 1.5 Annual numbers of autohct performed for all solid tumors as well as tumor-specific transplant numbers 1.6 The types of allohct being performed for solid tumors in terms of conditioning regimens (reduced intensity vs myeloablative, auto followed by reduced intensity allo, etc), and types of GVHD prophylaxis 1.7 To evaluate the trends comparatively in the US 1.8 Transplant related outcomes including Overall survival of autologous and allogeneic transplant for solid tumors Trends over time 2.0 SCIENTIFIC JUSTIFICATION: The number of autologous hematopoietic stem cell transplants (HCT) for metastatic breast cancer declined dramatically in the late 1990s following reports of randomized trials showing no benefit over conventional chemotherapy. European Bone Marrow Transplant (EBMT) data have shown that these negative trials have led to a reduction in autologous HCT being investigated for other solid tumors. Around this time, case reports of metastatic solid tumors regressing following reduced intensity allogeneic HCT as a consequence of a graft vs tumor (GVT) effect sparked global interest in the initiation of clinical trials exploring the potential of allogeneic immunotherapy to treat tumors of epithelial origin. Several small case series published in the early 2000s provided strong evidence for the existence of a GVT effect against metastatic renal cell carcinoma (RCC), ovarian cancer, breast cancer, and colon cancer. Importantly, some patients achieved durable complete responses raising the possibility that the GVT could in some cases be curative for treatment refractory solid tumors. It is unclear how many transplants for metastatic solid tumors and the type of metastatic solid tumors that allogeneic HCT has been explored. Hundreds of patients with metastatic solid tumors undergoing allogeneic HCT have been reported to both the CIBMTR through registration forms. It appears that allogeneic HCT for solid tumors has been pursued most commonly in patients with metastatic RCC, breast cancer, colon cancer, ovarian cancer, neuroblastoma, and sarcomas. However, data regarding transplant trends specific for different solid tumors over time has not been reported. Furthermore, considerable recent advances in the treatment of metastatic RCC with agents such as sorafenib, sunitinib, and temsirolimus have reduced the number of transplants being performed for RCC over the past 3 years. 31

32 Not for publication or presentation Attachment PATIENT ELIGIBILITY CRITERIA: All patients transplanted for solid tumors between 1985 and 2012 in North America and Europe and reported to the CIBMTR. 4.0 OUTCOMES: 4.1 Treatment-related mortality: Any death within the first 28 days of transplant or any death occurring after day 28 in the absence of overt disease progression. 4.2 Relapse/Progression: Progressive disease or recurrence of disease is considered an event. Those who survive without recurrence or progressive disease are censored at the date of last contact. 4.3 Progression-free survival (PFS): Survival without recurrence or tumor progression. Recurrence or progression of disease and death are events. Those who survive without recurrence or progression are censored at last contact survival without recurrence or tumor. 4.4 Overall survival: Time to death. Death from any cause will be considered an event. Surviving patients will be censored at time of last follow-up. Overall survival will be described as a time trend separately for auto or allo HCT for solid tumors. 5.0 VARIABLES TO BE ANALYZED: Patient-related variables: - Age: continuous - Gender: male vs. female - Karnofsky performance status: < 90% vs. > 90% Disease-related variables: - Disease type Transplant-related variables: - Time from diagnosis to transplant - Year of transplant - Conditioning regimen - Myeloablative regimen and reduced intensity regimen for allogeneic transplants - Allograft source (PBSC vs. BM vs. Cord Blood) - HLA match (matched vs. mismatched) and related vs. unrelated transplant 6.0 STUDY DESIGN: This will be a descriptive study of patients with auto or allo HCT for solid tumors. Descriptive tables of patients-, disease-, and transplant-related factors will be prepared. These tables will list median and range for continuous variables and percent of total for categorical variables. The product-limit estimator proposed by Kaplan-Meier will be used to estimate the median and range of the follow-up time. Probabilities of overall survival will be calculated using the Kaplan-Meier estimator, with the variance estimated by Greenwood s formula. 32