Not for publication or presentation · AI06-03 Overview of Hematopoietic stem cell transplantation for autoimmune diseases ... Ahmed) Dr. Ibrahim Ahmed from University of New Mexico

Not for publication or presentation

A G E N D A CIBMTR AUTOIMMUNE DISEASES WORKING COMMITTEE Salt Lake City, Utah Saturday, February 13, 2013, 2:45 pm – 4:45 pm Co-Chair: Paulo Muraro, MD, PhD, Imperial College London, UK

Telephone: +44 (0) 207-594-6670; Fax: +44 (0) 207-594-6548 E-mail: [email protected] Co-Chair: Steven Pavletic, MD, National Cancer Institute, NIH, Bethesda, MD Telephone: 301-402-4899; Fax: 301-451-5578 E-mail: [email protected] Statisticians: Tony X. Zhong, MS, CIBMTR Statistical Center, Milwaukee, WI Telephone: 414-805-0567; Fax: 414-805-0714; E-mail: [email protected]

Kwang Woo Ahn, PhD, CIBMTR Statistical Center, Milwaukee, WI Telephone 414-456-7387; Fax: 414-456-6530; E-mail: [email protected] Scientific Director: Marcelo Pasquini, MD, MSc, CIBMTR Statistical Center, Milwaukee, WI Telephone: 414-805-0700; Fax: 414-805-0714; E-mail: [email protected] 1. Introduction

a. Minutes of Autoimmune Disease Tandem 2012 Meeting (Attachment 1)

2. Accrual summary (Attachment 2) 3. Presentations, published or submitted papers

a. AD06-03 Pasquini MC, Voltarelli J, Atkins HL, Hamerschlak N, Zhong X, Ahn KW,

Sullivan KM, Carrum G, Andrey J, Bredeson CN, Cairo M, Gale RP, Hahn T, Storek J,

Horowit MM, McSweeney PA, Griffith LM, Muraro PA, Pavletic SZ, Nash RA. Transplants for Autoimmune Diseases in North and South America: A Report of the Center for International Blood and Marrow Transplant Research (CIBMTR), BBMT, volume 18, issue 10, 1471-1478, Oct 2012

b. AI09-01 Muraro PA, Pasquini MC, Atkins H, Bowen J, Farge D, Fassas A, Freedman M,

Georges G, Hamerschlak N, Havdrova E, Kozak T, Mancardi GL, Morais D, Nash R, Pavletic S, Ouyang J, Saiz A, Badoglio M, Zhong X, Sormani MP, Saccardi R. Long-term follow-up for autologous transplant in multiple sclerosis. 2013 EBMT meeting

4. Studies in progress (Attachment 3)

a. AI06-01 HCT for autoimmune cytopenias (H Atkins/M Pasquini) Dropped b. AI06-02 Autoimmune outcomes in transplant for non-auto diagnosis

and co-existing autoimmune diagnosis (R Nash) Dropped

c.

AI09-01 Long-term follow-up for autologous transplant in multiple sclerosis (P Muraro) (Attachment 6)

Manuscript Preparation

d.

AI11-01 Identification of HLA functional motifs associated with severe systemic sclerosis and sclerotic-GVHD (Del Galdo)

Deferred

e. AI12-01 The Effect of Allogeneic Hematopoietic Cell Transplantation on the Activity and Progression of Multiple Sclerosis. (G Georges) (Attachment 4)

Protocol Development

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Not for publication or presentation

5. Proposals a. PROP 1212-07 Hematopoietic cell Transplantation for Systemic Lupus Erythematous

(Hasni/Pavletic) (Attachment 5) b. PROP 1212-08 Long term follow up for autologous hematopoietic cell transplantation for

systemic sclerosis (Farge) (Attachment 6)

6. EBMT Autoimmune Working Party – Saccardi

7. Workshop on Transplant and Cellular Therapy for Autoimmune Diseases

8. Other Business

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Not for publication or presentation Attachment 1

MINUTES CIBMTR WORKING COMMITTEE FOR AUTOIMMUNE DISEASES San Diego, CA Saturday, February 4, 2012, 12:15 pm – 2:15 pm Co-Chair: Paulo Muraro MD, PhD, Imperial College London, UK

Telephone: +44 (0) 207-594-6670; Fax: +44 (0) 207-594-6548 E-mail: [email protected]

Co-Chair: Steven Pavletic, MD, National Cancer Institute, NIH, Bethesda, MD Telephone: 301-402-4899; Fax: 301-451-5578 E-mail: [email protected] Statisticians: Tony X. Zhong, MS, CIBMTR Statistical Center, Milwaukee, WI Telephone: 414-805-0567; Fax: 414-805-0714; E-mail: [email protected] Kwang Woo Ahn, PhD, CIBMTR Statistical Center, Milwaukee, WI

Phone 414-456-7387; Fax: 414-456-6530; E-mail: [email protected] CIBMTR Sci. Dir: Marcelo Pasquini, MD, MSc, CIBMTR Statistical Center, Milwaukee, WI Telephone: 414-456-8325; Fax: 414-456-6530; E-mail: [email protected] 1. Introduction

The meeting started at 12:15pm. Committee chairs (Paulo Muraro, MD and Steve Pavletic, MD) and the scientific director (Marcelo Pasquini, MD) welcomed the committees and started the meeting. After the brief introduction, Dr. Muraro reminded the group to fill in evaluation sheets for the meeting and vote the impact scores on the two new proposals submitted in this year. Dr. Pasquini displayed a beautiful picture of Froedtert Cancer Center, reminding people that the information about the Autoimmune Diseases and Cellular Therapy Workshop in Milwaukee is coming in the meeting. The minutes from the 2011 meeting in Orlando were then approved by the committee.

2. Accrual Summary There was no formal presentation or review of the accrual summary.

However Dr. Muraro still went through 2 page slides of accrual summary in 2010. The CIBMTR have already started to collect data of autoimmune disease in 2010 and most of the information focusing on registration level data. About 490 cases have been reported to CIMBTR in this level since 1995, and most of these centers are in USA.

3. Studies in progress

AI06-01 Hematopoietic Cell Transplantation for Autoimmune Cytopenias (M. Pasquini and H. Atkins) Manuscripts. Dr. Pasquini presented the study to the committee. This is a descriptive study of patients who received transplantation for autoimmune cytopenias (ITP, haemolytic anaemia and Evan’s syndrome). He explained that all the information except the pre-transplant lab value for some patients has been collected via supplemental forms during the last year. CIBMTR is trying to collect rest of it and start the manuscript preparation. AI06-02 The Effect of Hematopoietic Cell Transplantation on Systemic Lupus Erythematous when Present as a Coexistent Disease at Time of Transplantation (R. Nash) Data File Preparation. Dr. Pasquini presented an update of the study to the group. The main focus of the study is to assess the effect of transplantation on SLE as co-existing autoimmune disease. Dr. Pasquini explained that when CIBMTR collected data from different centres. Some of them

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reported the cases of SLE as a history of SLE and the study cohorts will exclude these cases. By contacting the data managers in different centres during the last year, CIBMTR has cleaned the list of cases with active SLE (N=12 for active SLE in transplant and N=16 for history of SLE prior to transplant) and will collect information on these cases (N=12) this year. AI06-03 Overview of Hematopoietic stem cell transplantation for autoimmune diseases performed in North and South America and reported to CIBMTR Reject/Re-submission. No presentation for this study. Dr. Pasquini explained the situation of this study and the report will be resubmitted to BBMT early 2012.

AI09-01 Long Term Follow-up Analysis of Patients with MS after Auto Hematopoietic cell Transplantation (P. Muraro, M. Pasquini, and R. Saccardi) Data File Collection. Dr. Muraro updated committee on the status of the project. This is a collaborative study between the EBMT and CIBMTR which will use MS data from US, Canada, Brazil, Asia and Europe. The main aim of the study is to evaluate and describe then long term outcomes among MS patients who are alive beyond five years after auto transplant for MS. During the last year, both CIBMTR and EBMT have contact the reported centers and many of them shown interest in this study. The data file collection forms have been sent to centers and information is expected to be obtained in 2012.

AD11-01 Identification of HLA Functional Motifs Associated with Severe Systemic Sclerosis and Sclerotic-GVHD: the Shared Epitopes of Fibrosis (Del Galdo) Protocol Development. Dr. Pavletic presented study, which is to identify the HLA functional motifs associated with skin fibrosis by bio-informatics meta-analysis of the HLA typing data from sclerotic-chronic graft versus host disease patients and systemic sclerosis patients that required hematopoietic stem cell transplantation because of severe skin fibrosis. The key of moving this study is obtain the blood sample for study cohort. And the relative approval is needed before the execution.

New Proposals

a. PROP1111-05 Autoimmune Hemolytic Anemia Pre- and Post- subsequent allogeneic HSCT (I Ahmed) Dr. Ibrahim Ahmed from University of New Mexico presented the proposal. The study aims to analyze the incidences of pre-transplant and post-transplant autoimmune hemolytic anemia among patients who underwent allogeneic HSCT and determine the impact of transplantation to these cases. Some members asked why there were only 80 post-transplant cases out of 53992 transplants. Dr. Pasquini explained that based on the data form designed, the pre-transplant Hemolytic Anemia cases were well captured. However, there is no checking option for post-transplant Hemolytic Anemia cases. So the data quality of post-transplant cases is relative poor because of the subjective of data manager when they filled in the reported form. Committee members have different viewpoint on whether the study should focus on pre-transplant or report both pre-transplant and post-transplant cases but most members agreed that this is the key to move it forward.

b. PROP1111-37 Long Term Complication after Autologous Transplantation for Autoimmune

Disease (B Wirk) Dr. Baldeep Wirk from University of Florida presented this study, which try to analyze the long term complications that following the autologous transplantation for autoimmune diseases. There are current 425 cases reported to CIBMTR with autologous transplant for autoimmune diseases and most of them are registration level data. The questions from committee members focus on how to define the long-term complication in the study. Should it just check on the secondary malignancies, or include other possible incidence, for example VOD or other organ impairments. Since such information is only captured in research level data form, it needs to be figure out before contacting center for details information.

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4. Ongoing initiatives under then ADWC.

Dr. Pavletic appreciated all the committee members for their participation in the research of Autoimmune Disease Working Committee. Dr. Pavletic explained that the most difficulty in this working committee is collecting relative data from centers. In order to make it better, an Autoimmune Disorders and Cellular Therapy workshop for all the researchers in this field will be hold in fall 2012. This is a very good chance for all the researchers to communicate and improve this group.

5. The meeting completed in 2:45 PM.

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Accrual Summary for Autoimmune Diseases Working Committee

Characteristics of patients who underwent a first transplant for autoimmune diseases, registered to the CIBMTR between 1996 and 2012, by type of transplant

Characteristics of patients Allogeneic Autologous Number of patients 74 354Number of centers 44 92Region US 51 (69) 191 (54) Canada 3 ( 4) 34 (10) Europe 15 (20) 74 (21) Asia 0 ( 0) 12 ( 3) Australia/New Zealand 1 ( 1) 3 (<1) Mideast/Africa 4 ( 5) 8 ( 2) Central/South America 0 ( 0) 32 ( 9)Age, median (range), years 20 (<1 - 61) 37 (6 - 69) <18 36 (19) 28 ( 8) 18-39 18 (24) 172 (49) 40-59 18 (24) 148 (42) ≥ 60 2 ( 3) 6 ( 2)Gender Male 40 (54) 149 (42) Female 34 (46) 205 (58)Graft type Bone marrow 24 (32) 7 ( 2) Peripheral blood 40 (54) 346 (98) Umbilical Cord blood 10 (14) 1 (<1)Donor type HLA-identical sibling 34 (50) N/A Twin donor 6 ( 8) N/A Other related 5 ( 7) N/A Unrelated donor 29 (35) N/AYear of transplant 1996-1997 3 ( 4) 5 ( 2) 1998-1999 4 ( 5) 47 (13) 2000-2001 15 ( 20) 70 (20) 2002-2003 13 (18) 45 (13) 2004-2005 7 ( 9) 55 (16) 2006-2007 12 (16) 36 (10) 2008-2009 11 (15) 46 (13) 2010-2011 8 (11) 46 (13) 2012a 1 ( 1) 4( 1)

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Continued. Characteristics of patients Allogeneic Autologous Disease Autoimmune disease unclassified 2 ( 3) 37 (10) Multiple sclerosis 7 ( 9) 140 (40) System Scleroderma 19 (27) 88 (25) Systemic lupus erythematosis (SLE) 5 ( 7) 30 ( 8) Rheumatoid arthritis 603 1 ( 1) 11 ( 3) Juvenile idiopatic arthritis 1 ( 1) 4 ( 1) Wegener granulomatosis 610 1 ( 1) 0 ( 0) Aniphospholipid syndrome614 0 ( 0) 3 ( 1) Behcets Syndrome 638 0 ( 0) 1 (<1) Crohns disease 649 0 ( 0) 6 ( 2) Myasthenia gravis 601 1 ( 1) 3 ( 1) Other neurologic disorder, spec 644 4 ( 5) 11 ( 3) Idiopathic thrombocytopenic purpura 645 2 ( 3) 7 ( 2) Hemolytic anemia 646 7 ( 9) 0 ( 0) Evan syndrome 647 6 ( 8) 1 (<1) Autoimmune cytopenia 648 4 ( 5) 0 ( 0) Ulcerative colitis 2 ( 3) 0 ( 0) Other autoimmune disease 12 (16) 12 ( 3)Conditioning regimen TBI+FLUD ± others1 12 (16) 0 (23) TBI+CY ± others2 8 (11) 83 (23) TBI + ATG ± others3 0 ( 0) 1 (<1) BU + CY ± others4 8 (11) 8 ( 2) BU + LPAM ± other5 1 ( 1) 0 ( 0) BU+FLUD+others6 6 ( 8) 0 ( 0) CY+FLUD ± other7 10 (14) 31 ( 9) CY+ATG ± others8 3 ( 4) 84 (24) BEAM+ATG ± others9 0 ( 0) 21 ( 6) TLI ± others10 2 ( 3) 13 ( 3) CY ± others11 1 ( 1) 8 ( 4) BU ± others12 2 ( 3) 0 ( 0) LPAM ± others13 11 (14) 37 ( 8) FLUD ± others14 1 ( 1) 0 ( 0) TBI ± others15 2 ( 3) 4 ( 1) ATG ± others16 1 ( 1) 3 (<1) Others 7 ( 9) 61 (17)

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Continued. Characteristics of patients Allogeneic Autologous GVHD prophylaxis T-cell depletion+-others 3 ( 4) N/A CD34 select+-others 14 (13) N/A FK506+MMF+-others 7 ( 9) N/A FK506+MTX+-others 10 (13) N/A FK506+-others (Not MTX/MMF) 7 ( 9) N/A CSA+MMF+-others 4 ( 5) N/A CSA+MTX+-others 13 (17) N/A CSA+-others (Not MTX/MMF) 6 ( 8) N/A Others/unknown 14 (18) N/A

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TO: Autoimmune Diseases Working Committee Members FROM: Marcelo Pasquini, MD, MS, Scientific Director of Autoimmune Diseases Working Committee RE: Studies in Progress Summary

AD06-01: Hematopoietic Cell Transplantation for Autoimmune Cytopenias (H Atkins/ M Pasquini): This study proposes to describe outcomes of patients undergoing hematopoietic cell transplantation for treatment of autoimmune cytopenias, including immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), Evan’s Syndrome and other autoimmune cytopenias that were treated primarily with hematopoietic stem cell transplantation (HCT). The study is dropped temporarily. AD06-02: Effect of Allogeneic Hematopoietic Cell Transplantation on Systemic Lupus Erythematous When Present as Coexisting Disease at Time of Transplant (S Pavletic/R Nash): This study proposes to examine the impact of allogeneic hematopoietic cell transplantation (HCT) on systemic lupus erythematous (SLE) disease activity when it is present as a coexisting autoimmune disease at time of transplant. Centers were contacted and only a minority of patients had confirmed active SLE at time of transplant. Among them, 3 patients had survived longer than 6 months. The committee in 2010 requested attempt in collecting as much information on these patients as possible. Update file was created and additional patients were identified. The study is dropped temporarily. AD06-03: Overview of Hematopoietic Cell Transplant for Autoimmune Diseases Performed in North and South America and Reported to CIBMTR (M Pasquini/ P McSweeney): This study proposes to evaluate the activity of hematopoietic stem cell transplantation (HCT) for autoimmune diseases (AID) in North and South America. The finalized manuscripts have been published on BBMT. AD09-01: Long Term Outcome after Autologous Hematopoietic Cell Transplantation for Multiple Sclerosis (P Muraro/R Saccardi): This study is being done in collaboration with the Autoimmune Working Party from the EBMT. The objective is to analyze long term outcomes after autologous hematopoietic cell transplantation for multiple sclerosis (MS). Patients with a minimal follow up of 3 and 5 years will be selected for this study. The CIBMTR and EBMT database are identifying cases according to the eligibility. Transplant centers are being contacted to confirm whether the data required for this study is available. The abstract of this study has been submitted to EBMT and manuscript is on-going. AD11-01: Identification of HLA functional motifs associated with severe systemic sclerosis and sclerotic-GVHD: then shared epitopes of fibrosis (F Del Galdo/P Emery/E Cowen/ S Pavletic): The major goal of this study is to identify the HLA functional motifs associated with severe skin fibrosis in Systemic Sclerosis and SCL-CGVHD. The study is in protocol development step. This study has been deferred.

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AI1201

OUTCOME OF ALLOGENEIC TRANSPLANTS FOR PATIENTS WITH MS AS CO-MORBIDITY

Table1. Descriptive statistics Characteristics N (%)Number of patients 42Number of centers 33Age at transplant 55 (18-75) 18-50 17 (40) 50-60 11 (26) >60 14 (33)Sex Male 15 (26) Female 27 (64)KPR ≥90 26 (62) <90 16 (38)Main disease AML 24 (57) ALL 2 ( 5) CML 1 ( 2) MDS 8 (19) NHL 5 (12) Inherited abnormalities erythrocyte differential or function 2 ( 5)Graft type BM 3 ( 7) PB 35 (83) CB 4 (10)Donor type Sibling 20 (46) Identical twins 1 ( 2) Unrelated 21 (51)Conditioning regimens CY+TBI 10 (24) CY+BU 10 (24) BU+FLUD 8 (19) Melphalan+FLUD 5 (12) BCNU+FLUD 2 ( 5) BU+FLUD 2 ( 5) TBI+ETOP 1 ( 1) TBI+FLUD+Melphalan 1 ( 1) TBI+MAB 1 ( 1) TBI Pentostatin 1 (1) FLUD+MAB 1 ( 1)

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Table 1. Continued.

Characteristics N (%)Time from diagnosis to transplant, median (range), months <12 months 28 (67) 12-24 months 5 (12) 24-36 months 3 ( 7) >36 months 6 (14)Year of transplant 2008 6 (14) 2009 10 (24) 2010 11 (26) 2011 11 (26) 2012 4 (10)Median follow-up of survivors, median (range), months 22 (19-67)

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Study Proposal 1212-07 Study title: Hematopoietic Cell Transplantation for Systemic Lupus Erythematous (SLE) PI: Steven Pavletic, MD, National Cancer Institute, Washington DC Table1: descriptive statistics Characteristics Allogeneic AutologousNumber of patients 5 30Number of centers 3 15Age at transplant 18 (10-53) 30 (15-50) <18 3 (60) 5 (17) 18-50 1 (20) 25 (83) 50-60 1 (20) 0 ( 0)Sex Male 1 (20) 7 (23) Female 4 (80) 23 (77)KPR ≥90 0 ( 0) 15 (50) <90 1 (20) 6 (20) Missing 4 (80) 9 (30)Graft type BM 1 (20) 1 ( 3) PB 4 (80) 29 (97) CB Donor type Sibling 3 (60) -- Identical twin 1 (20) -- Related 1 (20) --Conditioning regimens Cyclophosphamide +ATG 1 (20) 18 (60) Cyclophosphamide +Fludarabine 0 ( 0) 8 (27) Cyclophosphamide +TBI 1 (20) 2 ( 7) TLI+ATG 2 ( 0) 0 ( 0) Melphalan+Etoposide 0 ( 0) 1 ( 3) Busulfan 1 (29) 0 ( 0) Cyclophosphamide 0 ( 0) 1 ( 3)Time from diagnosis to transplant, median (range), months <12 months 1 (20) 2 ( 7) 12-24 months 0 ( 0) 4 (13) 24-36 months 0 ( 0) 3 (10) >36 months 4 (80) 21 (70)Year of transplant 1996-2000 1 (20) 8 (12) 2001-2005 2 (40) 12 (40) 2006-2010 2 (40) 10 (33)Median follow-up of survivors, median (range), months 33 (16-53) 49 (16-50)

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Study Proposal: 1212-08 Study Title: Outcome of Autologous Transplants for Scleroderma Table1: Descriptive statistics Characteristics N (%)Number of patients 88Number of centers 35Age at transplant 42 (8-61) <18 4 ( 5) 18-50 63 (72) 50-60 19 (22) >60 2 ( 2)Sex Male 32 (36) Female 56 (64)KPR ≥90 27 (44) <90 35 (56)Graft type BM 1 ( 1) PB 86 (98) CB 1 ( 1)Conditioning regimens Cyclophosphamide+ATG 24 (27) Cyclophosphamide+ATG+TBI 44 (50) Cyclophosphamide+ATG+Fludarabine 6 ( 7) Cyclophosphamide+TBI 4 ( 5) ARAC+ETOP+Melphalan 2 ( 2) Cyclophosphamide+Fludarabine 2 ( 2) Cyclophosphamide+Buslfan+TBI+ARAC 1 ( 1) TBI+ATG 1 ( 1) Melpahlan+Fludarabine+ATG 1 ( 1) Cyclophosphamide 1 (1) Melphalan 2 ( 2)Time from diagnosis to transplant, median (range), months <12 months 24 (27) 12-24 months 29 (34) 24-36 months 12 (14) >36 months 23 (26)Year of transplant 1996-2000 11 (13) 2001-2005 29 (33) 2006-2010 40 (45) 2011-2012 8 ( 9)Median follow-up of survivors, median (range), months 46 (9-62)

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Documents

Not for publication or presentation · AI06-03 Overview of Hematopoietic stem cell transplantation for autoimmune diseases ... Ahmed) Dr. Ibrahim Ahmed from University of New Mexico