A G E N D A CIBMTR WORKING COMMITTEE FOR ACUTE LEUKEMIA Honolulu, HI Saturday, February 20, 2016, 12:15 2:15 pm

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1 Not for publication or presentation A G E N D A CIBMTR WORKING COMMITTEE FOR ACUTE LEUKEMIA Honolulu, HI Saturday, February 20, 2016, 12:15 2:15 pm Co-Chair: Co-Chair: Co-Chair: Scientific Director: Assistant Scientific Director: Statistical Director: Statistician: Marcos de Lima, MD, University Hospitals Case Medical Center, Cleveland, OH; Telephone: ; marcos.delima@uhhospitals.org H Jean Khoury, MD, Winship Cancer Institute of Emory University, Atlanta, GA; Telephone: ; hkhoury@emory.edu Brenda Sandmaier, MD, Fred Hutchinson Cancer Research Center, Seattle, WA; Telephone: ; bsandmai@fredhutch.org Daniel J. Weisdorf, MD, University of Minnesota Medical Center, Minneapolis, MN; Telephone: ; weisd001@umn.edu Wael Saber, MD, MS, CIBMTR Statistical Center, Milwaukee, WI; Telephone: ; wsaber@mcw.edu Mei-Jie Zhang, PhD, CIBMTR Statistical Center, Milwaukee, WI; Telephone: ; meijie@mcw.edu Hai-Lin Wang, MPH, CIBMTR Statistical Center, Milwaukee, WI; Telephone: ; hwang@mcw.edu 1. Introduction a. Minutes and Overview Plan from February 2015 meeting (Attachment 1) 2. Accrual summary (Attachment 2) 3. Presentations, published or submitted papers a. LK09-02 Pasquini MC, Zhang MJ, Medeiros BC, Armand P, Hu ZH, Nishihori T, Aljurf MD, Akpek G, Cahn JY, Cairo MS, Cerny J, Copelan EA, Deol A, Freytes CO, Gale RP, Ganguly S, George B, Gupta V, Hale GA, Kamble RT, Klumpp TR, Lazarus HM, Luger SM, Liesveld JL, Litzow MR, Marks DI, Martino R, Norkin M, Olsson RF, Oran B, Pawarode A, Pulsipher MA, Ramanathan M, Reshef R, Saad AA, Saber W, Savani BN, Schouten HC, Ringdén O, Tallman MS, Uy GL, Wood WA Jr, Wirk B, Pérez WS, Batiwalla M, Weisdorf DJ. Hematopoietic cell transplantation outcomes in monosomal karyotype myeloid malignancies. Biol blood Marrow Transplant, [Epub ahead of print] b. LK11-01 Goyal SD, Zhang MJ, Wang HL, Akpek G, Copelan EA, Freytes C, Gale RP, Hamadani M, Inamoto Y, Kamble RT, Lazarus HM, Marks DI, Nishihori T, Olsson RF, Reshef R, Ritchie DS, Saber W, Savani BN, Seber A, Shea TC, Tallman MS, Wirk B, Bunjes DW, Devine SM, de Lima M, Weisdorf DJ, Uy GL. Allogeneic hematopoietic cell transplant for acute myeloid leukemia: no impact of pretransplant extramedullary disease on outcome. Bone Marrow Transplantation, 2015 Aug; 50(8):

2 Not for publication or presentation c. LK12-01 Seftel MD, Neuberg D, Zhang MJ, Wang HL, Ballen KK, Bergeron J, Couban S, Freytes CO, Hamadani M, Kharfan-Dabaja MA, Lazarus HM, Nishihori T, Paulson K, Saber W, Sallan SE, Soiffer R, Tallman MS, Woolfrey AE, DeAngelo DJ, Weisdorf DJ. Pediatric-inspired Therapy compared to Allografting for Philadelphia Chromosome Negative Adult ALL in First complete Remission. American Journal of Heamatology, [Epub ahead of print] d. LK12-02 Deol A, Sengsayadeth S, Ahn HW, Wang HL, Aljurf M, Antin JH, Bornhauser M, Cahn JY, Camitta B, Chen YB, Cutler CS, Gale RP, Ganguly S, Hamadani M, Inamoto Y, Jagasia M, Kamble R, Koreth J, Lazarus HM, Liesveld J, Litzow MR, Marks DI, Nishihori T, Olsson RF, Reshef R, Rowe JM, Saad AA, Sabloff M, Schouten HC, Shea TC, Soiffer RJ, Uy GL, Waller EK, Wiernik PH, Wirk B, Woolfrey AE, Bunjes D, Devine S, de Lima M, Sandmaier BM, Weisdorf DJ, Khoury HJ, Saber W. FLT3 Mutation Does Not Significantly Impact Overall Survival after Allogeneic Hematopoietic Cell Transplant for AML: A CIBMTR Analysis. Submitted. e. LK13-03 Munker R, Brazauskas R, Wang HL, de Lima M, Khoury HJ, Gale RP, Maziarz RT, Sandmaier BM, Weisdorf DJ, Saber W. Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia. Submitted. f. LK14-03 Ganzel C, Mathews V, Alimoghaddam K, Ghavamzadeh A, Kuk D, Devlin S, Wang HL, Zhang M- J,Weisdorf D, Douer D, Rowe JM, Estev J, Nagler A, Mohty M, Tallman MS. Autologous Transplant remains the Preferred Therapy for Relapsed APL in CR2. Submitted. 4. Studies in progress (Attachment 3) a. LK13-01 Evaluating outcomes of reduced intensity conditioning allogeneic SCT in older adult lymphoblastic leukemia patients reported to the CIBMTR: impact of age on transplant outcomes (A Rosko/M de Lima/M Mohty/V Bachanova) Manuscript preparation b. LK13-02 Prognostic significance of cytogenetic abnormalities in patients with Philadelphia - negative acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission (A Lazaryan/V Bachanova/D Weisdorf) Protocol development c. LK14-01 Effect of post-remission consolidation chemotherapy prior to allogeneic transplantation for acute lymphocytic leukemia in first complete remission (N Bejanyan/A Lazaryan/D Weisdorf) Protocol development d. LK14-02 Prognostic factors in patients 60 years undergoing allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first and second complete remission (F Michelis/V Gupta) Manuscript preparation e. LK15-01 AlloHCT vs. other consolidation therapies per Alliance protocols in older AML in CR1 (A Artz / C Ustun) Analysis f. LK15-02 Impact of GVHD on outcome after allogeneic hematopoietic cell transplantation for acute lymphocytic leukemia (M Yeshurun/J Rowe/M Tallman/V Bachanova) Protocol development g. LK15-03 Comparison of outcomes of older adolescents and young adults with Philadelphiachromosome/BCR-ABL1-negative acute lymphoblastic leukemia receiving post-remission consolidation chemotherapy with pediatric-inspired chemotherapy on CALGB or myeloablative allogeneic hematopoietic cell transplantation (M Wieduwilt/W Stock) Protocol development h. LK15-04 Outcome of hematopoietic stem cell transplantation using total body irradiation-based versus chemotherapy-based full intensity conditioning regimens for adults with acute lymphoblastic leukemia (P Kebriaei/I Aldoss/V Pullarkat/C Anasetti/D Marks) Protocol development 2

3 Not for publication or presentation i. LK15-05 Umbilical cord blood transplants for FLT3 positive acute myeloid leukemia (C Ustun/M Eapen/ D Weisdorf) Manuscript preparation 5. Introduction to TED (Transplant Essential Data) vs. CRF (Case Report Form) level database (W Saber) 6. Future/proposed studies a. PROP Evaluation of Allogeneic Stem Cell Transplantation Outcomes and Prognostic Factors in T-Cell Acute Lymphoblastic Leukemia (J Brammer /P Kebriaei /C Hosing) (Attachment 4) b. PROP Prognostic Impact of a modified European LeukemiaNet (ELN) classification for predicting outcomes in adults with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation (A Jimenez / K Komanduri /M de Lima) (Attachment 5) c. PROP Comparison of Outcomes between Reduced Intensity and Myeloablative Conditioning for AML and MDS Patients with Complex Cytogenetics (S Ciurea / Kongtim /A Nagler /B Savani /M de Lima / Labopin / Champlin) (Attachment 6) d. PROP DRI-guided Choice of Conditioning Intensity for Allogeneic Hematopoietic Cell Transplantation in Adults with Acute Myeloid Leukemia and Myelodysplastic Syndromes (N Bejanyan / E Warlick /C Brunstein /D Weisdorf) (Attachment 7) e. PROP Outcomes and Prognostic Factors after Allogeneic Transplant for Relapsed or Refractory AML in Patients 60 years and Older (A Artz /C Ustun) (Attachment 8) f. PROP Evaluating Primary Refractory Acute Myeloid Leukemia; the effects of Disease Characteristics and Outcomes of Allogeneic Stem Cell Transplantation (K Adekola /J Mehta /N Majhail) (Attachment 9) g. PROP / Blastic Plasmacytoid Dendritic Cell Neoplasm undergoing Allogeneic stem cell transplantation: A CIBMTR analysis (UR Deotare / FV Michelis / JH Lipton / S Ganguly) (Attachment 10) h. PROP / Allogeneic Transplantation To Treat Therapy Related AML and MDS (NS Callander / L Metheny / M de Lima / AC Hall) (Attachment 11) i. PROP / / Reduced Intensity Conditining (RIC) regimens for Acute Myeloid Leukemia (AML): A comparison of Busulfan (B) and Melphlan (M) based regimens from the CIBMTR database (R Nath / Z Zhou / J Cerny / Z Gul / G Ahmed / MW Khan / GC Hilderbrandt / HB Alkhateeb / MB Damlaj / MM Patnaik) (Attachment 12) j. PROP / Comparing Outcomes between HLA-Haploidentical and Matched Sibling Allogeneic Transplants in Patients with AML (A Rashidi/R Romee/W Saber/ M Hamadani) (Attachment 13) k. PROP Haplo-Identical vs Matched Unrelated Donor Transplantation For Acute Lymphocytic Leukemia (L Metheny / M de Lima) (Attachment 14) Dropped proposed studies a. PROP Assessing the significance of conditioning regimen intensity (myeloablative vs. reduced intensity/non-myeloablative) in non-t-cell depleted haploidentical donor transplantation for acute leukemias (ALL/AML/MDS) when using post-transplant cyclophosphamide. Dropped due to feasibility b. PROP Reduced Intensity Conditioning Compared With Myeloablative Conditioning Using Haploidentical Donor Transplants in Patients with Myeloid Malignancies. Dropped due to feasibility c. PROP Evaluate the outcomes of patients with AML undergoing Allogeneic Stem Cell Transplantation after receiving Non-intensive therapies for remission induction. Dropped due to feasibility- insufficient follow up d. PROP Can RIC HCT control disease relapse after lower intensity pre-hct therapy (hypomethylating agents or low dose cytarabine) for elderly AML? Dropped due to feasibilityinsufficient follow up 3

4 Not for publication or presentation e. PROP Outcomes following maintenance azacitidine therapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic cell transplantation. Dropped due to feasibility- insufficient follow up f. PROP Do hypo-methylating agents following HLA/KIR mismatched transplantation improve clinical outcome in acute myeloid leukemia? Dropped due to feasibility- insufficient follow up g. PROP Impact of maintenance therapy post allogeneic hematopoietic stem cell transplant on outcomes in acute myeloid leukemia and myelodysplastic syndromes. Dropped due to feasibilityinsufficient follow up h. PROP Outcomes in high risk AML patients utilizing maintenance with hypomethylating agents after allogeneic stem cell transplantation. Dropped due to feasibility- insufficient follow up i. PROP A study of clinical outcomes among patients receiving calcineurin inhibitors vs. calcineurin inhibitors +methotrexate for acute graft versus host disease prophylaxis following matched sibling allogeneic bone marrow transplantation for acute lymphoblastic leukemia. Dropped due to feasibility - low numbers in subgroup j. PROP The clinical outcome of rare cytogenetic abnormalities on post-transplant outcomes in patients with acute myeloid leukemia in complete remission. Dropped due to feasibility k. PROP Does prophylactic cranial radiation improve relapse rate in patients with acute leukemias who have allogeneic transplantation? Dropped due to feasibility l. PROP Impact of pre-transplant chemotherapeutic regimen on outcome after allogeneic hematopoietic stem cell transplant (hsct) in adult Ph+ ALL. Dropped due to feasibility 7. Other business 4

5 Not for publication or presentation Attachment 1 MINUTES AND OVERVIEW PLAN CIBMTR WORKING COMMITTEE FOR ACUTE LEUKEMIA San Diego, CA Friday, February 13, 2015, 12:15 2:15 pm Co-Chair: Co-Chair: Co-Chair: Statisticians: Scientific Director: Assistant Scientific Director: Steven Devine, MD, The Ohio State University, Columbus, OH; Telephone: ; Fax: ; steven.devine@osumc.edu Marcos de Lima, MD, University Hospitals Case Medical Center, Cleveland, OH; Telephone: ; Fax: ; marcos.delima@uhhospitals.org Brenda M. Sandmaier, MD, Fred Hutchinson Cancer Research Center, Seattle, WA; Telephone: ; Fax: ; bsandmai@fredhutch.org Mei-Jie Zhang, PhD, CIBMTR Statistical Center, Milwaukee, WI; Telephone: ; Fax: ; meijie@mcw.edu Hai-Lin Wang, MPH, CIBMTR Statistical Center, Milwaukee, WI; Telephone: ; Fax: ; hwang@mcw.edu Daniel J. Weisdorf, MD, University of Minnesota Medical Center, Minneapolis, MN; Telephone: ; Fax: ; weisd001@umn.edu Wael Saber, MD, MS, CIBMTR Statistical Center, Milwaukee, WI; Telephone: ; Fax: ; wsaber@mcw.edu 1. Introduction The CIBMTR Acute Leukemia Working Committee was called to order at 12:15 pm on Friday, February 13th, 2015, by Dr. Steven Devine. The chairs, scientific director and statisticians were presented. Attendees were asked to have their name badges scanned for attendance purposes and to maintain committee membership, and to fill out the Working Committee evaluations and voting sheets for proposals. The meeting was limited to presentation and discussion of proposals. Dr. Devine briefly introduced committee s accomplishments for the past year and progress of ongoing studies. Each proposal presentation was limited to 5 minutes (maximum 6 slides) to allow for adequate time for discussion (5 minutes). The minutes of the February 2014 meeting were approved without modifications. Dr. H Jean Khoury, MD was introduced and welcomed as newly appointed LKWC chair starting March Accrual Summary Due to the full agenda, the accrual summary of registration and research cases between 1995 and 2014 were not presented to the committee but were available as part of the Working Committee attachments 3. Presentations, published or submitted papers Due to the full agenda, the 2014 presentations and published papers were mentioned, but not presented. Three papers were published, one submitted, two ASH and one ASBMT tandem presentations were given during the past year. a. LK04-01 Holter Chakrabarty JL, Rubinger M, Le-Rademacher J, Wang HL, Grigg A, Selby GB, Szer J, Rowe JM, Weisdorf DJ, Tallman MS. Autologous is superior to allogeneic hematopoietic cell 5

6 Not for publication or presentation Attachment 1 transplantation for Acute Promyelocytic Leukemia in second complete remission. Biol Blood Marrow Transplant, 2014 Jul;20(7): b. LK07-03c McClune BL, Ahn KW, Wang HL, Antin JH, Artz AS, Cahn JY, Deol A, Freytes CO, Hamadani M, Holmberg LA, Jagasia MH, Jakubowski AA,Kharfan-Dabaja MA, Lazarus HM, Miller AM, Olsson R, Pedersen TL, Pidala J, Pulsipher MA, Rowe JM, Saber W, van Besien KW, Waller EK, Aljurf MD, Akpek G, Bacher U, Chao NJ, Chen YB, Cooper BW, Dehn J, de Lima MJ, Hsu JW, Lewis ID, Marks DI, McGuirk J,Cairo MS, Schouten HC, Szer J, Ramanathan M, Savani BN, Seftel M, Socie G, Vij R, Warlick ED, Weisdorf DJ. Allotransplantation for patients age 40 years with non-hodgkin Lymphoma: Encouraging progression-free survival. Biol Blood Marrow Transplant, 2014 Jul;20(7): c. LK12-03 Bejanyan N, Weisdorf DJ, Logan BR, Wang HL, Devine SM, de Lima M, Bunjes DW, Zhang MJ. Survival of AML patients relapsing after allogeneic hematopoietic cell transplantation: a CIBMTR study. Biol Blood Marrow Transplant [Epub ahead of print]. d. LK11-01 Goyal SD, Zhang MJ, Wang HL, Akpek G, Copelan EA, Freytes C, Gale RP, Hamadani M, Inamoto Y, Kamble RT, Lazarus HM, Marks DI, Nishihori T, Olsson RF, Reshef R, Ritchie DS, Saber W, Savani BN, Seber A, Shea TC, Tallman MS, Wirk B, Bunjes DW, Devine SM, de Lima M, Weisdorf DJ, Uy GL. Allogeneic hematopoietic cell transplant for acute myeloid leukemia: no impact of pretransplant extramedullary disease on outcome. Submitted. e. LK12-01 Seftel MD, Neuberg D, Zhang MJ, Wang HL, Bergeron J, Couban S, DeAngelo DJ, de Lima M, Devine SM, Eapen M, Horowitz M, Pasquini M, Rizzo D, Saber W, Sallan S, Sandmaier BM, Weisdorf DJ. Superiority Of Pediatric Chemotherapy Over Allogeneic Hematopoietic Cell Transplantation for Philadelphia Chromosome Negative Adult ALL in First Complete Remission: A Combined Analysis of Dana-Farber ALL Consortium And CIBMTR Cohorts. Presentation at annual ASH meeting in San Francisco, CA, December Submitted. f. LK12-02 Deol A, Sengsayadeth S, Jagasia M, Ahn KW, Wang HL, Sandmaier BM, Devine SM, de Lima M, Weisdorf DJ, Saber W. FLT3 Mutation Increases Relapse Risk After Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia in First or Second Complete Remission: A CIBMTR Analysis. Presentation at annual ASH meeting in San Francisco, CA, December Manuscript in preparation. g. LK13-03 Munker R, Wang HL, Brazauskas R, Saber W, Weisdorf DJ. Allogeneic transplant for acute biphenotypic leukemia: characteristics and outcome in the CIBMTR database. Presentation at annual ASBMT meeting in San Diego, CA, February Studies in progress (Attachment 3) The progress of the ongoing studies during the past year was not presented in order to provide reasonable time to the new proposals for presentation and discussion. A summary of the progress was provided as an attachment to the committee members. LK09-02: Impact of monosomal karyotype in the outcome of hematopoietic cell transplantation for Acute Myeloid Leukemia and Myelodysplasia (M Pasquini/ M Battiwalla) The purpose of this study is to identify the impact of high risk cytogenetic subsets: specifically chromosome 7 abnormalities (either monosomy7 or del(7q)) and monosomal karyotype in outcomes for AML and MDS after allogeneic HCT and to evaluate the impact of conditioning intensity in the outcome of patients with AML and monosomal karyotype. 6

7 Not for publication or presentation Attachment 1 Analysis is completed and draft manuscript is being prepared by PI. LK12-02: FLT3/ITD mutation in acute myeloid leukemia remains a poor prognostic factor compared to conventional cytogenetics with increased risk of relapse and decreased overall survival after allogeneic stem cell transplantation in first complete remission (S Sengsayadeth) The purpose of this study is to (1) To study the prognostic significance of FLT3/ITD mutation in AML in patients receiving allo-hsct in CR1 and (2) To study the impact of FLT3/ITD mutation on incidence of relapse, disease-free survival (DFS), overall survival (OS) after allo-sct in CR1. Analysis is completed and 1 st draft manuscript is available. LK13-01: Allogeneic Transplantation for older patients with Acute Lymphoblastic Leukemia reported to the CIBMTR and EBMT: Impact of age on transplant outcomes (A Rosko/ M de Lima/ M Mohty/ V Bachanova) The purpose of this study is to (1) To analyze outcomes of allogeneic donor transplantation for older patients with acute lymphoblastic leukemia ages 55 years and older who underwent reduced intensity conditioning (2) To define the prognostic factors (patient, disease and transplant related) that impact mortality, relapse and survival. Analysis is underway. LK13-02: Prognostic significance of cytogenetic abnormalities in patients with Philadelphia-negative ALL undergoing allogeneic Hematopoietic Stem Cell Transplantation in complete remission (A Lazaryan/ V Bachanova) The purpose of this study is to (1) To develop allo-hct specific cytogenetic classification of Phnegative ALL for prognostication of relapse and survival outcomes following allo-hct (2) To validate within the CIBMTR database the prognostic significance of existing cytogenetic classifications of Ph-negative ALL in the context of the allo-hct (3) To compare the performance of both CIBMTR-based and existing classifications of Ph-negative ALL treated with allo-hct. Protocol development and cytogenetic data review is underway. LK13-03: Allogeneic transplantation for Acute Biphenotypic Leukemia (ABiL): Disease characteristics, complications and outcomes (R Munker) The purpose of this study is to (1) Describe frequency of allogeneic transplant for ABiL, demographics and disease characteristics before transplant (2) Assess patient-, disease- and transplant- related factors which influence the outcome of allogeneic transplant for ABiL. Analysis nearly complete. LK14-01: Effect of post-remission consolidation chemotherapy prior to allogeneic transplantation for acute lymphocytic leukemia in first complete remission (N Bejanyan/ A Lazaryan/ D Weisdorf) The purpose of this study is to (1) To study relapse, TRM and survival outcomes of ALL patients in CR1 receiving 0 vs. 1 vs. 2 post-remission consolidation cycles prior to allo-hct. (2) To study relapse, TRM and survival outcomes in subgroup of ALL patients with MRD positivity who receive 0 vs. 1 vs. 2 post-remission consolidation cycles prior to allo-hct. Protocol development is underway. LK14-02: P ro gno stic facto rs in patients 60 years undergoing allogeneic hem ato po ietic cell transplantatio n for acute myeloid leukemia in first and second complete remission (F Michelis/ V Gupta) The purpose of this study is to (1)To identify patient, disease, and transplant related characteristics associated with outcomes for older patients in particular ( 60 years) with AML undergoing allo-hct in CR1 and CR2. (2) To compare outcomes between patients within different age (<60 yrs vs. 60 yrs) or remission status (CR1 vs. CR2) group. (3) To assess the impact of HCT-CI (0-2 vs. 3) on outcomes in all patients with HCT-CI available and a subgroup of CR2 patients only. Protocol development is underway. 7

8 Not for publication or presentation Attachment 1 LK14-03: Autologous transplant vs. arsenic trioxide in relapsed Acute Promyelocytic Leukemia (C Ganzel / M Tallman) The purpose of this study is to compare between the 2 treatment groups for demographics, details of disease presentation, frontline treatment and outcomes including disease free survival and overall survival. Analysis is under way. LK15-01: Comparison of Allogeneic Hematopoietic Cell Transplantation (AlloHCT) with Other Consolidation Therapies P er Alliance P ro to co ls in Older ( 60 years) AML P atients in First Co m plete Rem ission (CR1 ) (A Artz / C Ustun) The purpose of this study is to (1) To compare DFS and TRM between allohct and nonallohct consolidations (2) To find the frequency of acute and chronic graft-versus-host disease (GVHD) in the allohct cohort (3) To identify patient or disease characteristics (age, cytogenetic risk group, etc.) which preferentially benefit patients receiving allohct vs. non-allohct consolidation therapy. Data preparation and protocol review is underway. 5. Future/proposed studies Drs. Devine, de Lima and Sandmaier led this session. a. PROP / Comparison of Outcomes between Conditioning Regimens using Reduced Intensity conditioning of Fludarabine plus Melphalan and Myeloablative Regimens Using IV Busulfan plus Fludarabine or IV Busulfan plus Cyclophosphamide in AML and MDS. (DA Hutcherson / HT Liu/ A Nooka / A Langston / M Bishop) Dr. Hutcherson presented this proposal. There are 1569, 1466 and 885 cases who received 1 st allo-hct for AML/MDS between 2002 and 2012 and had conditioning regimens of MAC IV Bu + Cy, MAC IV Bu + Flu and RIC Flu + Mel respectively. There were comments about the intensity and dosing of regimen. b. PROP Outcomes of allogeneic transplant for core binding factor leukemia in second or subsequent complete remission. (L Costa / A Saad / S Mineishi) Dr. Saad presented this proposal. There are 449 cases who received 1 st allo-hct in 2 nd or subsequent remission for core-binding factor AML between 2000 and There were comments about the unavailability of c-kit mutation and details of salvage therapy after relapse as surrogate for MRD evidence. c. PROP Effect of in vivo T cell depletion on transplant outcomes in CMV seropositive and seronegative recipients with acute myeloid leukemia. (M Shanavas / D Kim) Dr. Shanavas presented this proposal. There are 946 cases who received 1 st allo-hct for AML in CR1/CR2 with in-vivo T-cell depletion between 2000 and Dr. Weisdorf commented on data collection of CMV reactivation post-hct. Also suggestion was made to look at association between chimerism and CMV reactivation. d. PROP / Impact of GVHD on outcome after allogeneic hematopoietic cell transplantation for acute lymphocytic leukemia: a retrospective registry study (M Yeshurun / JM Rowe / MS Tallman / V Bachanova) Dr. Yeshurun presented this proposal. There are 3334 cases who received 1 st allo-hct for ALL between 2000 and 2012, among whom 1983 had agvhd and/or cgvhd before post-hct relapse. Questions were raised about the bias of patients who relapsed/died early before getting GVHD and possibility of including haplo-identical donor cases. e. PROP Comparison of outcomes of older adolescents and young adults with Philadelphiachromosome/BCR-ABL1-negative acute lymphoblastic leukemia receiving post-remission consolidation chemotherapy with pediatric-inspired chemotherapy on CALGB or myeloablative allogeneic hematopoietic cell transplantation. (M Wieduwilt / W Stock) Dr. Wieduwilt presented this proposal. There are 470 cases aged between years old who received 1 st allo-hct for Ph- ALL in CR1 between 2003 and There were comments about the 8

9 Not for publication or presentation Attachment 1 follow-up time of CALGB cohort and possibility of cases receiving HCT after pediatric style chemotherapy. Also question was asked about the difference between CALGB cohort and DFCI cohort from LK f. PROP Prognostic risk factors of patients undergoing allogeneic stem cell transplantation for acute erythroleukemia. (J Cerny / R Nath / Z Zhou) Dr. Cerny presented this proposal. There are 379 cases who received 1 st allo-hct for AEL between 2000 and There were comments about the completeness of cytogenetics and post-hct treatment data. g. PROP Comparison of outcomes post allogeneic hematopoietic cell transplant between patients with de novo and secondary acute myeloid leukemia in first complete remission. (F Michelis / H Messner) Dr. Michelis presented this proposal. There are 2880 and 1050 cases who received 1 st HLA-identical sibling or well/partially matched unrelated donor allo-hct for de-novo and secondary AML separately in CR1 between 2000 and Comment was made regarding the importance and potential difficulty in discriminating post MDS from post MPN AML. h. PROP / Comparison of total body irradiation (TBI)-based with intravenous (i.v.) busulfan (Bu) containing chemotherapy-only myeloablative transplant conditioning regimens in adult patients with acute lymphoblastic leukemia (ALL) (P Kebriaei / I Aldoss / V Pullarkat / C Anasetti / D Marks) Dr. Kebriaei presented this proposal. There are 1183, 151 and 103 cases from CIBMTR, MD Anderson Cancer Center and Moffitt Cancer Center separately who received 1 st allo-hct for ALL in CR1/CR2 with specified conditioning regimen. There were comments about possible center effects and selection bias of TBI treatment based on patient condition. i. PROP Allogeneic (allo) stem cell transplant (SCT) for AML: A comparison of three different reduced intensity conditioning (RIC) regimens in the CIBMTR data base. (R Nath / Z Zhou / J Cerny) Dr. Nath presented this proposal. There are 1921 cases who received 1 st allo-hct for AML with reduced intensity conditioning containing TBI/Bu/Mel between 2001 and There were comments about the strong correlation between TBI based regimen and cord blood donor source, and concern about insufficient cases if the population need to be narrowed down for homogeneity. 6. Other Business Dr. Weisdorf made closing remarks and presented a souvenir to departing chair Dr. Devine. Without additional comments, the meeting was adjourned at 1:50 pm. After the new proposals were presented, each participant in the meeting had the opportunity to rate each proposal using paper ballots. Based on the voting results, current scientific merit and the impact of the study on the field, the following studies will move forward as the committee s research portfolio for the upcoming year: PROP / Comparison of total body irradiation (TBI)-based with intravenous (i.v.) busulfan (Bu) containing chemotherapy-only myeloablative transplant conditioning regimens in adult patients with acute lymphoblastic leukemia (ALL) (P Kebriaei / I Aldoss / V Pullarkat / C Anasetti / D Marks) PROP Comparison of outcomes of older adolescents and young adults with Philadelphiachromosome/BCR-ABL1-negative acute lymphoblastic leukemia receiving post-remission consolidation chemotherapy with pediatric-inspired chemotherapy on CALGB or myeloablative allogeneic hematopoietic cell transplantation. (M Wieduwilt / W Stock) 9

10 Not for publication or presentation Attachment 1 PROP / Impact of GVHD on outcome after allogeneic hematopoietic cell transplantation for acute lymphocytic leukemia: a retrospective registry study (M Yeshurun / JM Rowe / MS Tallman / V Bachanova) 10

11 Not for publication or presentation Attachment 1 Working Committee Overview Plan for a. LK09-02: Impact of monosomal karyotype in the outcome of hematopoietic cell transplantation for Acute Myeloid Leukemia and Myelodysplasia. Analyses completed and manuscript is under preparation. Submission is anticipated by June b. LK11-01: Impact of extramedullary disease on the outcome of allogeneic HCT in AML. Manuscript preparation is complete and submitted. Publication of paper is expected by June c. LK12-01: Chemotherapy versus Allogeneic Hematopoietic Cell Transplantation in Philadelphia negative chromosome negative adult ALL. Manuscript preparation is complete and submitted. Publication of paper is expected by June d. LK12-02: FLT3/ITD mutation in acute myeloid leukemia remains a poor prognostic factor compared to conventional cytogenetics with increased risk of relapse and decreased overall survival after allogeneic stem cell transplantation in first complete remission. Manuscript preparation is underway and we plan to submit paper by June e. LK13-01: Evaluating outcomes of reduced intensity conditioning allogeneic SCT in older adult lymphoblastic leukemia patients reported to the CIBMTR and EBMT. Analysis is underway and we plan to move to manuscript preparation by June f. LK13-02: Prognostic significance of cytogenetic abnormalities in patients with Philadelphia negative acutelymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission. Protocol development and request of cytogenetics information is underway and we plan to move to data file preparation by June 2015 and submit paper by June g. LK13-03: Allogeneic transplantation for Acute Biphenotypic Leukemia: Disease characteristics, complications and outcomes. Analysis underway and we plan to move to manuscript preparation by June 2015 and submit paper by June h. LK14-01: Effect of post-remission consolidation chemotherapy prior to allogeneic transplantation for acute lymphocytic leukemia in first complete remission: A Center for International Blood and Marrow Transplant Research Study. Protocol development is underway and we plan to move to data file preparation by June 2015 and finish analysis by June i. LK14-02: Prognostic factors in patients 60 years undergoing allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first and second complete remission. Protocol development is underway and we plan to move to data file preparation by June 2015 and finish analysis by June j. LK15-01: Comparison of Allogeneic Hematopoietic Cell Transplantation with Other Consolidation Therapies Per Alliance Protocols in Older ( 60 years) AML Patients in First Complete Remission. Protocol development is underway and we plan to move to analysis by June 2015 and move to manuscript preparation by June k. LK15-02: Impact of GVHD on outcome after allogeneic hematopoietic cell transplantation for acute lymphocytic leukemia. We anticipate developing the study protocol after July 2015 and move to data file preparation and analysis by June

12 Not for publication or presentation Attachment 1 l. LK15-03: Comparison of outcomes of older adolescents and young adults with Philadelphiachromosome/BCR-ABL1-negative acute lymphoblastic leukemia receiving post-remission consolidation chemotherapy with pediatric-inspired chemotherapy on CALGB or myeloablative allogeneic hematopoietic cell transplantation. We anticipate developing the study protocol after July 2015 and move to data file preparation and analysis by June m. LK15-04: Comparison of total body irradiation (TBI)-based with intravenous (i.v.) busulfan (Bu) containing chemotherapy-only myeloablative transplant conditioning regimens in adult patients with acute lymphoblastic leukemia. We anticipate developing the study protocol after July 2015 and move to data file preparation and analysis by June n. LK15-05: Umbilical cord blood transplantation outcomes in FLT3 mutation positive patients with Acute Myelogenous Leukemia. We anticipate developing the study protocol after July 2015 and move to analysis by June

13 Not for publication or presentation Attachment 1 Oversight Assignments for Working Committee Leadership (March 2015) Daniel Weisdorf Wael Saber Marcos de Lima Brenda Sandmaier H Jean Khoury LK12-01: Chemotherapy versus Allogeneic Hematopoietic Cell Transplantation in Philadelphia negative chromosome negative adult ALL LK13-02: Prognostic significance of cytogenetic abnormalities in patients with Philadelphia negative acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission LK15-01: Comparison of Allogeneic Hematopoietic Cell Transplantation with Other Consolidation Therapies Per Alliance Protocols in Older ( 60 years) AML Patients in First Complete Remission. LK15-03: Comparison of outcomes of older adolescents and young adults with Philadelphia-chromosome/BCR-ABL1-negative acute lymphoblastic leukemia receiving post-remission consolidation chemotherapy with pediatric-inspired chemotherapy on CALGB or myeloablative allogeneic hematopoietic cell transplantation. LK15-05: Umbilical cord blood transplantation outcomes in FLT3 mutation positive patients with Acute Myelogenous Leukemia. LK12-02: FLT3/ITD mutation in acute myeloid leukemia remains a poor prognostic factor compared to conventional cytogenetics with increased risk of relapse and decreased overall survival after allogeneic stem cell transplantation in first complete remission LK13-01: Evaluating outcomes of reduced intensity conditioning allogeneic SCT in older adult lymphoblastic leukemia patients reported to the CIBMTR and EBMT LK15-04: Comparison of total body irradiation (TBI)-based with intravenous (i.v.) busulfan (Bu) containing chemotherapy-only myeloablative transplant conditioning regimens in adult patients with acute lymphoblastic leukemia. LK09-02: Impact of monosomal karyotype in the outcome of hematopoietic cell transplantation for Acute Myeloid Leukemia and Myelodysplasia LK11-01: Impact of extramedullary disease on the outcome of allogeneic HCT in AML. LK13-03: Allogeneic transplantation for Acute Biphenotypic Leukemia: Disease characteristics, complications and outcomes. LK15-02: Impact of GVHD on outcome after allogeneic hematopoietic cell transplantation for acute lymphocytic leukemia. LK14-01: Effect of post-remission consolidation chemotherapy prior to allogeneic transplantation for acute lymphocytic leukemia in first complete remission. LK14-02: Prognostic factors in patients 60 years undergoing allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first and second complete remission. 13

14 Not for publication or presentation Attachment 2 Accrual Summary for the Acute Leukemia Working Committee Characteristics of recipients of first allogeneic transplants for AML and ALL reported a to the CIBMTR between 1995 and 2015 Variable AML ALL Number of patients Number of centers Age in decades Median (range) 43 (<1-83) 21 (<1-75) < (9) 2444 (24) (10) 2428 (24) (12) 1791 (18) (14) 1318 (13) (19) 1125 (11) (21) 695 (7) (13) 221 (2) (2) 4 (<1) Gender Male (53) 6149 (61) Female 9074 (47) 3876 (39) Missing 1 (<1) 1 (<1) HCT-CI (16) 1449 (14) (5) 314 (3) (4) 219 (2) (11) 489 (5) N/A, earlier than (65) 7533 (75) Missing 99 (<1) 22 (<1) Disease status prior to HCT Primary induction failure 2539 (13) 343 (3) CR (47) 4055 (40) CR (21) 3449 (34) CR3 382 (2) 891 (9) Relapse 3123 (16) 1279 (13) Missing 62 (<1) 9 (<1) Time from diagnosis to HCT Median (range) 6 (<1-607) 12 (<1-499) <6 months 9099 (47) 2795 (28) 6-12 months 4665 (24) 2297 (23) >12 months 5476 (28) 4929 (49) Missing 20 (<1) 5 (<1) 14

15 Not for publication or presentation Attachment 2 Variable AML ALL Conditioning regimen intensity Myeloablative (74) 9165 (91) RIC 3009 (16) 407 (4) NMA 1269 (7) 218 (2) TBD 470 (2) 154 (2) Missing 167 (<1) 82 (<1) Graft type Bone marrow 6610 (34) 4745 (47) Peripheral blood (54) 3534 (35) Umbilical cord blood 2277 (12) 1743 (17) Missing 10 (<1) 4 (<1) Type of donor HLA-identical sibling 6371 (33) 2931 (29) Identical twin 83 (<1) 55 (<1) Other relative 1116 (6) 600 (6) Unrelated 9365 (49) 4677 (47) Cord blood 2277 (12) 1743 (17) Missing 48 (<1) 20 (<1) Year of HCT (9) 1306 (13) (8) 1135 (11) (8) 1068 (11) (9) 1101 (11) (11) 1116 (11) (14) 1249 (12) (13) 1068 (11) (11) 636 (6) b 898 (5) 424 (4) b 2478 (13) 923 (9) Median follow-up of survivors (range), months 72 (1-244) 74 (1-244) a Patients have available comprehensive research form and consented for research b Cases continue to be reported in this interval 15

16 Not for publication or presentation Attachment 2 Accrual Summary for Acute Leukemia Working Committee Characteristics of recipients of first autologous transplants for AML and ALL reported a to the CIBMTR between 1995 and 2015 Variable AML ALL Number of patients Number of centers Age in decades Median (range) 44 (<1-78) 30 (1-66) <10 61 (6) 16 (10) (7) 25 (16) (12) 38 (24) (17) 19 (12) (19) 28 (18) (22) 23 (15) (16) 7 (4) 70 8 (<1) 0 Gender Male 496 (51) 98 (63) Female 481 (49) 58 (37) Disease status prior to HCT Primary induction failure 10 (1) 2 (1) CR1 634 (65) 99 (63) CR2 250 (26) 44 (28) CR3 14 (1) 6 (4) Relapse 66 (7) 5 (3) Missing 3 (<1) 0 Time from diagnosis to HCT Median (range) 7 (<1-182) 9 (2-153) <6 months 410 (42) 22 (14) 6-12 months 263 (27) 73 (47) >12 months 304 (31) 61 (39) Conditioning regimen intensity Myeloablative 788 (81) 148 (95) NMA 8 (<1) 2 (1) TBD 180 (18) 6 (4) Missing 1 (<1) 0 Graft type Bone marrow 170 (17) 25 (16) Peripheral blood 804 (82) 130 (83) Missing 3 (<1) 1 (<1) 16

17 Not for publication or presentation Attachment 2 Variable AML ALL Year of HCT (27) 55 (35) (23) 45 (29) (11) 16 (10) (9) 12 (8) (7) 5 (3) (9) 9 (6) (10) 10 (6) (2) 1 (<1) b 6 (<1) b 16 (2) 3 (2) Median follow-up of survivors (range), months 95 (1-247) 123 (2-241) a Patients have available comprehensive research form and consented for research b Cases continue to be reported in this interval 17

18 Not for publication or presentation Attachment 3 TO: FROM: RE: Acute Leukemia Working Committee Members Daniel J. Weisdorf, MD; Scientific Director and Wael Saber, MD, MS; Assistant Scientific Director for the Acute Leukemia Working Committee Studies in Progress Summary LK13-01: Evaluating outcomes of reduced intensity conditioning allogeneic SCT in older adult lymphoblastic leukemia patients reported to the CIBMTR: impact of age on transplant outcomes (A Rosko/ M de Lima/ M Mohty/ V Bachanova) The purpose of this study is (1) To analyze outcomes of allogeneic donor transplantation for older patients with acute lymphoblastic leukemia ages 55 years and older who underwent reduced intensity conditioning (2) To define the prognostic factors (patient, disease and transplant related) that impact mortality, relapse and survival. Manuscript is being finalized. LK13-02: Prognostic significance of cytogenetic abnormalities in patients with Philadelphia-negative ALL undergoing allogeneic Hematopoietic Stem Cell Transplantation in complete remission (A Lazaryan/ V Bachanova) The purpose of this study is (1) To develop allo-hct specific cytogenetic classification of Ph-negative ALL for prognostication of relapse and survival outcomes following allo-hct (2) To validate within the CIBMTR database the prognostic significance of existing cytogenetic classifications of Ph-negative ALL in the context of the allo-hct (3) To compare the performance of both CIBMTR-based and existing classifications of Ph-negative ALL treated with allo-hct. Data file preparation is underway. LK14-01: Effect of post-remission consolidation chemotherapy prior to allogeneic transplantation for acute lymphocytic leukemia in first complete remission (N Bejanyan/ A Lazaryan/ D Weisdorf) The purpose of this study is (1) To study relapse, TRM and survival outcomes of ALL patients in CR1 receiving 0 vs. 1 vs. 2 postremission consolidation cycles prior to allo-hct (2) To study relapse, TRM and survival outcomes in subgroup of ALL patients with MRD positivity who receive 0 vs. 1 vs. 2 post-remission consolidation cycles prior to allo-hct Data file preparation is underway. LK14-02: Prognostic factors in patients 60 years undergoing allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first and second complete remission (F Michelis/ V Gupta) The purpose of this study is (1)To identify patient, disease, and transplant related characteristics associated with outcomes for older patients in particular ( 60 years) with AML undergoing allo-hct in CR1 and CR2 18

19 Not for publication or presentation Attachment 3 (2) To compare outcomes between patients within different age (<60 yrs vs. 60 yrs) or remission status (CR1 vs. CR2) group (3) To assess the impact of HCT-CI (0-2 vs. 3) on outcomes in all patients with HCT-CI available and a subgroup of CR2 patients only Manuscript preparation is underway. LK15-01: Comparison of Allogeneic Hematopoietic Cell Transplantation (AlloHCT) with Other Consolidation Therapies Per Alliance Protocols in Older ( 60 years) AML Patients in First Complete Remission (CR1) (A Artz / C Ustun) The purpose of this study is (1) To compare DFS and TRM between allohct and non-allohct consolidations (2) To find the frequency of acute and chronic graft-versus-host disease (GVHD) in the allohct cohort (3) To identify patient or disease characteristics (age, cytogenetic risk group, etc.) which preferentially benefit patients receiving allohct vs. non-allohct consolidation therapy. Analysis is underway. LK15-02: Impact of GVHD on outcome after allogeneic hematopoietic cell transplantation for acute lymphocytic leukemia (M Yeshurun/ J Rowe/ M Tallman/ V Bachanova) The purpose of this study is (1) Identify any differential GVHD-associated GVL influences after allohct for ALL, using either myeloablative or reduced intensity conditioning regimens (2) Study the impact of acute and chronic GVHD and its extent on relapse, NRM, DFS and OS rates after allohct for ALL. Protocol development is underway. LK15-03: Comparison of outcomes of older adolescents and young adults with Philadelphiachromosome/BCR-ABL1-negative acute lymphoblastic leukemia receiving post-remission consolidation chemotherapy with pediatric-inspired chemotherapy on CALGB or myeloablative allogeneic hematopoietic cell transplantation (M Wieduwilt/ W Stock) The purpose of this study is (1) To compare overall survival, relapse-free survival, relapse, and non-relapse mortality between older adolescent and young adults aged years with Ph/BCR-ABL1-negative acute lymphoblastic leukemia in first complete remission receiving consolidation therapy with pediatric-inspired chemotherapy on CALGB to myeloablative allogeneic hematopoietic cell transplantation (2) To compare outcomes of CALGB to allogeneic HCT using fully matched related or unrelated donors in patients who attained CR1 in <8 weeks (3) To compare outcomes of obese and non-obese ALL patients between cohorts (4) To compare CNS relapse rates in the two cohorts (5) To determine patient and disease factors influencing outcomes of consolidation with pediatricinspired chemotherapy versus allogeneic hematopoietic cell transplantation. Protocol development is underway. LK15-04: Outcome of hematopoietic stem cell transplantation using total body irradiation-based versus chemotherapy-based full intensity conditioning regimens for adults with acute lymphoblastic leukemia (P Kebriaei/ I Aldoss/ V Pullarkat/ C Anasetti/ D Marks) The purpose of this study is (1) To compare HCT outcomes [overall survival (OS), leukemia-free survival (LFS), relapse rate (RR) and non-relapse mortality (NRM)] between TBI- and non-tbi-, i.v. Bu-based myeloablative conditioning regimens in adults with ALL undergoing allogeneic HCT (2) To evaluate the influence of the conditioning regimen (TBI versus i.v. Bu) on post HCT outcomes among ALL risk subgroups (standard versus high) classified based on age, initial WBC and cytogenetics at 19

20 Not for publication or presentation Attachment 3 diagnosis in adults with ALL undergoing allogeneic HCT. This aim will also address the effect of remission status (CR1 versus CR2) on the outcomes after TBI based versus Bu-based conditioning (3) To evaluate the impact on extramedullary relapse patterns, specifically central nervous system relapse, with the two different conditioning approaches (4) To evaluate the regimen related toxicity profile, and to compare graft versus host disease, of the two different conditioning approaches. Protocol development is underway. LK15-05: Umbilical cord blood transplants for FLT3 positive acute myeloid leukemia (C Ustun / M Eapen / D Weisdorf) The purpose of this study is to compare HCT outcomes (overall survival, relapse, leukemia free survival, transplant related mortality) between umbilical cord blood, HLA-identical sibling and unrelated donor for AML FLT3 mutated patients. Manuscript preparation is underway. 20

21 Not for publication or presentation Attachment 4 Proposal Title: Evaluation of Allogeneic Stem Cell Transplantation Outcomes and Prognostic Factors in T-Cell Acute Lymphoblastic Leukemia Jonathan, Edward, Brammer, MD, University of Texas MD Anderson Cancer Center, jebrammer@mdanderson.org Partow Kebriaei, MD, University of Texas MD Anderson Cancer Center, pkebriae@mdanderson.org Chitra Hosing, MD, University of Texas MD Anderson Cancer Center, cmhosing@mdanderson.org Hypothesis: Allogeneic Stem Cell Transplantation provides curative therapy for patients with T-Cell Acute Lymphoblastic Leukemia, with improved outcomes in those transplanted in first complete remission. The use of both alternative donors (haploidentical and cord blood), and chemotherapy-based conditioning regimens is a viable alternative to standard matched-donor transplants utilizing TBI-based conditioning. Specific aims: To determine the outcomes (OS, PFS, NRM, Relapse) of allogeneic stem cell transplantation (allo-sct) in T-Acute Lymphoblastic Leukemia (T-ALL) and identify prognostic factors associated with improved outcomes To determine the effect of remission status (first remission, second remission, progressive/refractory disease) on outcomes (OS, PFS, NRM, Relapse) in patients receiving allo-sct for T-ALL To determine whether chemotherapy-based conditioning regimens are comparable to total body irradiation (TBI)-based conditioning regimens with regards to OS, PFS, NRM, and relapse in T-ALL To determine the outcomes in T-ALL utilizing alternative donor sources and reduced-intensity conditioning regimens and compare them to traditional matched-donor transplants Scientific justification: T-cell acute lymphoblastic leukemia (T-ALL) represents approximately 20-25% of all cases of acute lymphoblastic leukemia (ALL) diagnoses per year. 1 Given the rarity of T-ALL, patients are typically treated in a similar fashion to B-cell acute lymphoblastic leukemia (B-ALL) with dose-intense, multi-agent chemotherapy regimens. 2-4 The largest cohort of T-ALL patients studied was in the MRC UKALL XII/ECOG E2993 international ALL trial. 5 In this cohort of patients, 356 adult patients younger than 60 years of age were treated with intensive chemotherapy. Patients with a sibling donor in complete remission (CR) proceeded to allogeneic stem cell transplantation (allo-sct) and had improved 5-year overall survival (OS) versus those without a donor (61% vs 46%, p=0.02). 6 The largest published report on transplantspecific outcomes in T-ALL is from Saudi Arabia, in which 53 patients received allo-sct. OS was 43.5%, and patients in CR1 had improved OS versus those in CR2 (53.5% vs 31.9%). 7 A large study from the EBMT in abstract form suggested patients transplanted in CR1 with TBI-based conditioning had improved outcomes, though data from this study are limited and it has not been published. 8 These data suggest that at least a proportion of patients with T-ALL would benefit from transplantation in CR1. Identification of this high-risk group of patients who might benefit from early allo-sct is crucial in T-ALL because effective salvage therapies are limited, and thus patients have a low likelihood of achieving remission to then procced to transplant. 21

22 Not for publication or presentation Attachment 4 A recent multi-center analysis initiated at our institution of 102 patients submitted for publication demonstrated a trend toward improved outcomes after allo-sct in T-ALL for patients transplanted in CR1 (62% vs 24%), though due to low numbers, the p-value was not significant (p=0.2). 9 Furthermore, in the same analysis, TBI-based conditioning therapy was not superior to chemotherapy-based conditioning (HR 1.02, p=0.9), and there was no difference between outcomes of reduced intensity (RIC) and non-myeloablative (NMA) conditioning when compared to myeloablative conditioning (MAC). Likewise, stem cell source, including cord-blood transplants were not inferior to standard peripheral blood or bone marrow. However, these analyses are limited by relatively low patient numbers. Given T-ALL is a rare disease, there is limited data on transplant outcomes in this population, and the CIBMTR has not analyzed this specific disease in the adult population. A large analysis utilizing the CIBMTR database will allow the transplant community to clearly define the outcomes of allo-sct in patients with T-ALL, identify prognostic markers for improved outcomes, and help to elucidate the utility of both alternative (haploidentical and cord blood), and chemotherapy-based regimens against the standard matched-donor transplants utilizing TBI-based conditioning. Patient Eligibility Population: Patients 18 years of age or older who received an allo-sct for T-ALL between Data requirements: This proposed study will require no supplemental data to be collected. The current data is included in the CIBMTR collection forms for Pre-HSCT and Post-HSCT Acute Lymphocytic Leukemia Study design: This study is a retrospective registry analysis of all patients who received allo-sct for T-ALL between Baseline characteristics and known prognostic variables will be collected from CIBMTR database forms. These characteristics will include: median age, sex, Karnofsky performance status, presence of extranodal disease at diagnosis (including CNS), WBC at diagnosis, immune-phenotype at diagnosis (in particular CD1a negative vs CD1a+, and ETP vs non-etp as defined by Coustan-Smith et al 10 ), number of prior chemotherapy regimens, time from diagnosis to transplant, remission status at transplant (first remission, second remission, progressive/refractory disease), conditioning therapy (chemotherapybased or total body irradiation based, including chemotherapy type and TBI dose), conditioning intensity (MAC, RIC, NMA), use of anti-thymocyte globulin, presence of minimal residual disease prior to transplant (molecular data or flow cytometry data), donor source (peripheral blood, cord, bone marrow), transplant type (haploidentical, 1 or 2 HLA-antigen mismatch, MUD, sibling donor, cord blood), hematopoietic cell transplantation-co-morbidity index (HCT-CI), and cytogenetics at diagnosis. Transplant outcomes (OS, PFS, cumulative incidence (CI) NRM, and CI Relapse) will be evaluated for all patients, patients in CR1, second remission and greater (CR2+), and those with progressive/refractory disease. Additionally, transplant outcomes will be evaluated for patients receiving TBI-based conditioning (defined as >2 Gy of TBI) and non-tbi (<2 Gy) based conditioning, as well as MAC versus RIC/NMA conditioning as defined by Giralt et al. 11 Finally, outcomes will be evaluated for Haploidentical and Cord-Blood Transplantation. Median overall survival, and progression-free survival will be calculated utilizing Kaplan-Meier analysis and compared utilizing the log-rank test. Cumulative incidences of NRM, Relapse, and GVHD (chronic and acute) will be performed utilizing the cumulative incidence procedure to account for competing risks, and comparison will be performed utilizing the Fine-Gray test. 22