Transplante de células tronco hematopoiéticas e doença de Crohn: posição do Comitê de Transplantes do Grupo Brasileiro para estudo das doenças inflamatórias do intestino (GEDIIB)

RUIZ, Milton Artur; PARRA, Rogério Serafim; ZABOT, Gilmara Pandolfo; ANDRADE, Adriana Ribas; PIRON-RUIZ, Lilian; FONSECA-HIAL, Ana Marcela Rojas; MARTIN, Eloisa Moreira; PINHO, Tainara Souza; QUADROS, Luiz Gustavo de; KAISER JUNIOR, Roberto Luiz; PARENTE, José Miguel Luz

Milton Artur RUIZ

literature review

interpretation of the data

wrote and critically revised the manuscript

Associação Portuguesa Beneficência, São José do Rio Preto, SP, Brasil.

https://orcid.org/0003-0000-2212-4883

Rogério Serafim PARRA

literature review

interpretation of the data

wrote and critically revised the manuscript

Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Ribeirão Preto, SP, Brasil.

https://orcid.org/0000-0002-5566-9284

Gilmara Pandolfo ZABOT

literature review

interpretation of the data

wrote and critically revised the manuscript

Hospital Moinhos de Vento, Porto Alegre, RS, Brasil.

https://orcid.org/0000-0002-1253-4945

Adriana Ribas ANDRADE

literature review

interpretation of the data

wrote and critically revised the manuscript

Hospital São Rafael, Salvador, BA, Brasil.

https://orcid.org/0000-0001-6012-2155

Lilian PIRON-RUIZ

literature review

interpretation of the data

Associação Portuguesa Beneficência, São José do Rio Preto, SP, Brasil.

https://orcid.org/0000-0002-3602-5897

Ana Marcela Rojas FONSECA-HIAL

literature review

interpretation of the data

wrote and critically revised the manuscript

Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brasil.

https://orcid.org/0000-0002-6683-3836

Eloisa Moreira MARTIN

literature review

Hospital do Servidor Público Estadual de São Paulo, São Paulo, SP Brasil.

https://orcid.org/0000-0001-6104-9690

Tainara Souza PINHO

literature review

interpretation of the data

Associação Portuguesa Beneficência, São José do Rio Preto, SP, Brasil.

https://orcid.org/0000-0003-3531-079X

Luiz Gustavo de QUADROS

literature review

interpretation of the data

contributed to the critical revision of the manuscript

Associação Portuguesa Beneficência, São José do Rio Preto, SP, Brasil.

https://orcid.org/0000-0001-9586-8109

Roberto Luiz KAISER JUNIOR

literature review

interpretation of the data

contributed to the critical revision of the manuscript

Associação Portuguesa Beneficência, São José do Rio Preto, SP, Brasil.

https://orcid.org/0000-0003-1952-1255

José Miguel Luz PARENTE

literature review

interpretation of the data

contributed to the critical revision of the manuscript

Universidade Federal do Piauí, Departamento de Clínica Médica, Gastroenterologia, Teresina, PI, Brasil.

https://orcid.org/0000-0003-4563-2784

Corresponding author: Milton Artur Ruiz. E-mail: milruiz@yahoo.com.br

All authors granted final approval of the version to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved.

Declared conflict of interest of all authors: Parra RS has received fees for serving as a speaker and/or an advisory board member for AbbVie, Ferring Pharmaceuticals, Janssen, and Takeda. Zabot GP has received fees for serving as a speaker and/or an advisory board member for AbbVie, Takeda, and Janssen. Andrade AR has received fees for serving as a speaker and/or an advisory board member for AbbVie, Janssen, and Takeda.

Reference	HSCT type	#of pts	Indication	Outcome
Drakos 1993²⁹29. Drakos PE, Nagler A, Or R. Case of Crohn’s disease in bone marrow transplantation. Am J Hematol. 1993;43:157-8.	Autologous	1	NHL	Remission of both diseases at 6 months

Castro 1996³⁰30. Castro J, Bentch H SL. Prolonged clinical remission in patients with inflammatory bowel disease(IBD) after high dose chemotherapy(HDC)and autologous blood stem cell transplantation. Blood. 1996;88(Suppl):133A.	Autologous	1	Breast cancer	Remission of both diseases at 7 years

Talbot 1998³¹31. Talbot DC, Montes A, Teh WL, Nandi A PRL. Remission of Crohn’s disease following allogeneic bone marrow transplant for acute leukaemia. Hosp Med. 1998;59:580-1.	Allogeneic	1	AL	Remission of both diseases >8 years

Lopez-Cubero 1998³²32. Lopez-Cubero SO, Sullivan KM, McDonald GB. Course of Crohn’s disease after allogeneic marrow transplantation. Gastroenterology. 1998;114:433-40.	Allogeneic	1	AML	CD Remission between 4,5 to 15 years and one patient relapsed CD 1,5 years after HSCT
		5	CML

Kashyap 1998³³33. Kashyap, Forman SJ. Autologous bone marrow transplantation for non-Hodgkin’s lymphoma resulting in long-term remission of coincidental Crohn’s disease. Br J Haematol. 1998;103:651-2.	Autologous	1	LNH	Remission both disease >7 years

Musso 2000³⁴34. Musso M, Porretto F, Crescimanno a, Bondì F, Polizzi V, Scalone R. Crohn’s disease complicated by relapsed extranodal Hodgkin’s lymphoma: prolonged complete remission after unmanipulated PBPC autotransplantation. Bone Marrow Transplant. 2000;26:921-3.	Autologous	1	HL	Remission of both diseases for >3years

Soderhölm 2002³⁵35. Soderholm JD, Malm C, Juliusson G, Sjodahl R. Long-term endoscopic remission of crohn disease after autologous stem cell transplantation for acute myeloid leukaemia. Scand J Gastroenterol. 2002;37:613-6.	Autologous	1	AML	Remission of both diseases for >5 years

Ditschowski 2003³⁶36. Ditschkowski M, Einsele H, Schwerdtfeger R, Bunjes D, Trenschel R, Beelen DW, et al. Improvement of inflammatory bowel disease after allogeneic stem-cell transplantation. Transplantation. 2003;75:1745-7.	Allogeneic	1	AML	10 pts alive without IBD symptoms after 34 months.
	7 CD pts	9	CML	One patient with mild persistent symptoms of
	4 UC pts	1	Secondary MDS	Crohn’s disease early after transplant

Anumakonda³⁷37. Anumakonda V, Hayee C-FG. Remission and relapse of Crohn’s disease following autologous haematopoietic stem cell transplantation for non-Hodgkin’s lymphoma. Gut. 2007;56:1323-4.	Autologous	1	NHL	Relapsed CD after 8 years HSCT

Nishimoto 2013³⁸38. Nishimoto M, Nakamae H, Watanabe K, Koh H, Nakane T, Ohsawa M, et al. Successful treatment of both acute leukemia and active crohn’s disease after allogeneic hematopoietic stem cell transplantation using reduced-intensity conditioning with fludarabine and busulfan: A case report. Transplant Proc. 2013;45:2854-7.	Allogeneic	1	AML	Remission of both diseases for 20 months

Hu 2014³⁹39. Hu C, Lv L, Liu D, Huo J. Treatment of Crohn’s disease complicated with myelodysplastic syndrome via allogeneic hematopoietic stem cell transplantation: Case report and literature review. Clin J Gastroenterol. 2014;7:299-304.	Allogeneic	1	MDS	Remission of both diseases for 25 months

Rabian 2016⁴⁰40. Rabian F, Porcher R, Sicre de Fontbrune F, Lioure B, Laplace A, Nguyen S, et al. Influence of Previous Inflammatory Bowel Disease on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation: A Matched-Pair Analysis. Bone Marrow Transplant . 2016;22:1721-4.	Allogeneic	9	AL	59% Overall survival for 48 months. Status: ND
		7	MDS/MPL
		1	NHL
		1	MM

Zhang 2020⁴¹41. Zhang Y, Lou L, Shi X, Lu S, Zhang L, Huang X, et al. Allogeneic hematopoietic stem cell transplantation for Crohn disease complicated with myelodysplastic syndrome. MEDICINE. 2020;10:6-9.	Allogeneic	1	MDS	Death, 125 d. after HSCT with pulmonary mucormycosis

Reference	#pts	Mobilization	Conditioning	Outcome
Burt 2003⁴⁵45. Burt RK, Traynor A, Oyama Y, Craig R. High-dose immune suppression and autologous hematopoietic stem cell transplantation in refractory Crohn disease. Blood. 20031;101:2064-6.*	2	CY 2g/m²	CY 200 mg/kg hATG 90 mg/kg	Remission for 1 year - no histologic remission

Kreisel 2003⁴³43. Kreisel W, Potthoff K, Bertz H, Schmitt-Graeff A, Ruf G, Rasenack J, et al. Complete remission of Crohn’s disease after high-dose cyclophosphamide and autologous stem cell transplantation. Bone Marrow Transplant . 2003;32:337-40.	1	CY 4g/m²	CY 200 mg/kg	Relapsed 9 m after mobilization. Clinical remission for 9 months - no histologic remission

Craig 2003⁴⁴44. Craig RM, Traynor A, Oyama Y, Burt RK. Hematopoietic stem cell transplantation for severe Crohn’s disease. Bone Marrow Transplant . 2003;32 (Suppl 1):S57-59.*	4	CY 2g/m²	CY 200 mg/kg hATG 90 mg/kg	CDAI remission at 11 months - no endoscopic remission

Scimè 2004⁵¹51. Scimé R, Cavallaro AM, Tringali S, Santoro A. Complete Clinical Remission after High- Dose Immune Suppression and Autologous Hematopoietic Stem Cell Transplantation in Severe Crohn ’ s Disease Refractory to Immuno- suppressive and Immu- nomodulator Therapy. Inflamm Bowel Dis. 2004;10:892-4.	1	CY 2g/m²	CY 200 mg/kg	ND

Oyama 2005⁵²52. Oyama Y, Craig RM, Traynor AE, Quigley K, Statkute L, Halverson A, et al. Autologous Hematopoietic Stem Cell Transplantation for Crohn’s Disease : High Risk for a High Reward. Gastroenterology. 2005;11:778-9.**	12	CY 2g/m²	CY 200 mg/kg hATG 90 mg/kg	11/12 CDAI <150 clinical remission for mean of 18.5 months - endoscopic remission rare

Cassinotti 2008⁵³53. Cassinotti A, Annaloro C, Ardizzone S, Onida F, Della Volpe A, Clerici M, et al. Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn’s disease. Gut. 2008;57:211-7.*	4	CY 1.5/m²	CY 200 mg/kg rATG 7.5 mg/kg	3/4 (75%) clinical (CDAI <150) and endoscopic remission at mean of 16.5 months

Burt 2010⁴⁶46. Burt RK, Craig RM, Milanetti F, Quigley K, Gozdziak P, Bucha J, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up. Blood. 2010;116:6123-32.*	24	CY 2 g/m²	CY 200 mg/kg hATG 90 mg/kg or rATG 6.0 mg/kg	CDAI <150 in 91%, 63%, 57%, 39% and 19% at 1, 2, 3, 4, and 5 years, respectively - no histologic remission

Clerici 2011⁵⁴5 4. Clerici M, Cassinotti A, Onida F, Trabattoni D, Annaloro C, Della Volpe A, et al. Immunomodulatory effects of unselected haematopoietic stem cells autotransplantation in refractory Crohn’s disease. Dig Liver Dis. 2011;43:946-52.*	6	CY 1.5/m²	CY 200 mg/kg rATG 7.5 mg/kg	CDAI and endoscopic remission in 5/6 at 1 year. TNFα, IL-10 decreased at 1 year

Hommes 2011⁵⁵55. Hommes DW, Duijvestein M, Zelinkova Z, Stokkers PCF, Ley MH, Stoker J, et al. Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn’s disease. J Crohns Colitis . 2011;5:543-9.**	3	CY 4g/m²	CY 200 mg/kg hATG 90 mg/kg	1 patient mobilized only - relapsed after 2 years 2 of 3 underwent HSCT - relapsed at 6 and 12 months

Kountouras 2011⁵⁶56. Kountouras J, Sakellari I, Tsarouchas G, Tsiaousi E, Michael S, Zavos C, et al. Autologous haematopoietic stem cell transplantation in a patient with refractory Crohn’s disease. J Crohns Colitis . 2011;5:275-6.*	1	CY 4g/m²	CY 200 mg/kg rATG 10 mg/kg	Clinical, endoscopic, histologic remission for 31 months

Hasselblatt 2012⁵⁷57. Hasselblatt P, Drognitz K, Potthoff K, Bertz H, Kruis W, Schmidt C, et al. Remission of refractory Crohn’s disease by high-dose cyclophosphamide and autologous peripheral blood stem cell transplantation. Aliment Pharmacol Ther. 2012;36:725-35.**	12	CY 4g/m²	CY 200 mg/kg	12 mobilized, 9 underwent HSCT - 5/9 clinical end endoscopic remission at 6 months, 7/9 relapsed by 12 months
Kriván 2014⁵⁸58. Krivan G, Doloresz S, Krisztian K, Gabor B CK. Successful autologous hematopoietic stem cell transplantation in severe, therapy-resistant childhood-onset Crohn’s disease. Report on the first case in Hungary. Orvosi Hetilap. 2014;155:789-92.*	1	CY 2 g/m²	CY 200 mg/kg hATG 30 mg/kg	Relapsed at 1 year

Snowden 2014⁵⁹59. Snowden J a, Ansari A, Sachchithanantham S, Jackson G, Thompson N, Lobo A, et al. Autologous stem cell transplantation (asct) in severe, resistant crohn’s disease: long-term follow-up of UK patients treated on compassionate basis. QJM. 2014;107:871-7.*	6	CY 4g/m²	CY 200 mg/kg rATG 7.5 mg/kg	Median time to relapse: 10 months

Hawkey 2015⁴⁷47. Hawkey CJ, Allez M, Clark MM, Labopin M, Lindsay JO, Ricart E, et al. Autologous Hematopoietic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial. JAMA. 2015;314:2524-34.***	45	CY 4g/m²	CY 200 mg/kg rATG 6.5 mg/kg	Complex end point CDAI <150, no immune drugs, no endoscopic or radiologic disease - not significant compared to control

Ruiz 2015⁶⁰60. Ruiz MA, Kaiser Junior RL, Gouvêa Faria MA, de Quadros LG. Remission of refractory Crohn ‘s disease after autologous hematopoietic stem cell transplantation. Rev Bras Hematol Hemoter. 2015;37:136-9.	1	CY 2g/m²	CY 200 mg/kg rATG 6.5 mg/kg	Clinical, endoscopic, histologic remission for 7 years

Lopez-Garcia 2017⁶¹61. López-García A, Rovira M, Jauregui-Amezaga A, Marín P, Barastegui R, Salas A, et al. Hematopoietic, Autologous Cell, Stem For, Transplantation Crohn, Refractory Cohort, Single-centre Cohort. J Crohns Colitis . 2017;11:116:116.**	35	CY 4g/m²	CY 200 mg/kg rATG 6.5 mg/kg	CDAI <150 and SES <7 in 61%, 52%, 47%, 39%, 15% at 1, 2, 3, 4, and 5 years, respectively

Lindsay 2017²⁵25. Lindsay JO, Allez M, Clark M, Labopin M, Ricart E, Rogler G, et al. Autologous stem-cell transplantation in treatment-refractory Crohn’s disease: an analysis of pooled data from the ASTIC trial. Lancet Gastroenterol Hepatol. 2017;2:399-406.**	40	CY 4g/m²	CY 200 mg/kg rATG 6.5 mg/kg	CDAI <150 (steroid free) at 1 year in 38%

Ruiz 20107²⁸2 8. Ruiz MA, Kaiser RL, de Quadros LG, Piron-Ruiz L, Peña-Arciniegas T, Faria MAG, et al. Low toxicity and favorable clinical and quality of life impact after non-myeloablative autologous hematopoietic stem cell transplant in Crohn’s disease. BMC Res Notes. 2017;10:495.**	14	CY 2g/m²	CY 200 mg/kg rATG 6.5 mg/kg	13/14 in remission CDAI <150 at 30 days

Ruiz 2017⁶²62. Ruiz MA, Kaiser Junior RL, De Quadros LG, Caseiro GHX, Oliveira AF, Peña-Arciniegas T, Piron-Ruiz L. Hematopoietic stem cell transplantation in a severe refractory Crohn’s disease patient with intestinal stoma : a case report. Int Med Case Rep J. 2017;10:353-9.*	1	CY 2g/m²	CY 200 mg/kg rATG 6.5 mg/kg	Clinical remission at 1 year, no endoscopic remission

Hernanz 2019⁴⁹49. Hernanz N, Sierra M, Volpato N, Núñez-Gómez L, Mesonero F, Herrera-Puente P, et al. Autologous haematopoietic stem cell transplantation in refractory Crohn’s disease: Experience in our centre. Gastroenterol Hepatol. 2019;42:16-22.*	7	CY 4g/m²	CY 200 mg/kg rATG (ND)	5/7 (71%) relapsed after mean of 13.8 months

Ruiz 2020⁶³63. Ruiz MA, Junior RLK, Piron-Ruiz L, Saran PS, Castiglioni L, de Quadros LG, et al. Medical, ethical, and legal aspects of hematopoietic stem cell transplantation for Crohn’s disease in Brazil. World J Stem Cells . 2020;12:1113-23.**	50	CY 2g/m²	Cy200 mg/kg rATG 6.5 mg/kg	CDAI <150 in 97%, 80%, 65%, 38% and 20% at 1, 2, 3, 4, and 5 years, respectively

Drug	Criteria
Corticosteroids	Inability to withdraw from methylprednisolone (1 mg/kg) after 4-6 weeks without relapse or having relapse within 1 year of completing course of corticosteroids.
Methylprednisolone 1 mg/kg
Immunosuppressors	Failure to achieve steroid-free remission after 16 weeks of therapy.
Azathioprine (2.0-2.5 mg/kg/day) or 6-mercaptopurine (0.75-1.5 mg/kg/day)
Biologic Therapy
TNF inhibitors	at week 12 to 14.
Ustekinumab	at week 8.
Vedolizumab	at week 14, after additional administration of 300 mg of vedolizumab from week 10 in non-responders.

Comorbidities	Renal: creatinine clearance <40 mL/min (measured or estimated).
	Cardiac: clinical evidence of refractory congestive heart failure, left ventricular ejection fraction <45% by multigated radionuclide angiography or cardiac echo; uncontrolled ventricular arrhythmia; pericardial effusion with hemodynamic consequences evaluated by experienced echocardiographer.
	Hepatic: AST >2 times upper limit of normal.
	Concurrent neoplasms.
	Bone marrow insufficiency defined as neutropenia with absolute neutrophil count <1 × 10⁹/L or thrombocytopenia with a platelet count <50 × 10⁹/L or anemia with hemoglobin <80 g/L.
	Uncontrolled hypertension, defined as resting systolic blood pressure ≥140 mmHg and/or resting diastolic pressure ≥90 mmHg despite at least 2 anti-hypertensive agents.
	Uncontrolled acute or chronic infection with HCV, HBV, HIV, HTLV - 1 or 2, hepatitis viruses, Chagas Disease, SARS-CoV-2 or any other infection.
	Other chronic diseases causing significant organ failure, including established cirrhosis with evidence of impaired synthetic function in biochemical testing and known respiratory disease causing resting arterial oxygen tension < 8 kPa or CO₂ tension >6.7 kPa. FEV₁/FVC <50%.
Past history	Active or latent mycobacterial infection.
	Prior exposure to HBV, HCV or HIV 1+2.
Increased risk of infection	Positive or indeterminate serology: CMV, toxoplasmosis, HSV, SARS-COV2.
	Evidence of enteric or systemic infection.
Disease profile	No evidence of active CD in CDAI, HBI or CCSI or endoscopic screening.
	Inability to assess endoscopic active disease due to strictures.
	Evidence of intra-abdominal sepsis on abdominal MRI.
	Undrained perianal fistulae (patients with previous perianal disease or perianal disease adequately drained with seton in situ are eligible).
	Presence of undrained perianal sepsis on screening pelvic MRI.
Others	Participants currently pregnant, breastfeeding or planning pregnancy within duration of study. Current pregnancy confirmed with pregnancy test at screening assessment.
	Unwilling to use adequate contraception (if appropriate) for at least 12 months after last dose of study drug.
	Contraindication to use of CY, fludarabine, G-CSF or rATG.
	Psychiatric comorbidity.

Scenario	Low-disease risk	High-disease risk	Notes
Confirmed diagnosis	Deferred for 3 months	Deferred, until asymptomatic and 3 negative PCRs at least one week apart
Symptoms of URTI	Testing with multiplex respiratory viral PCR, consider deferral	Testing with multiplex respiratory viral PCR, consider deferral	COVID-19 testing on case-by-case basis per local guidelines
Close contact with case of COVID-19	PCR test for COVID-19, deferred for 14-21 days	PCR test for COVID-19, deferral based on clinical judgment	Follow local guidelines for isolation and testing for COVID-19
Travel to high-risk areas or close contact with person travelling from high-risk areas	Deferred for 14-21 days	Deferral based on clinical judgment	Follow local guidelines for isolation and testing for COVID-19

Clinical response	Decrease of at least 50% in PRO2 (abdominal pain and stool frequency)¹²⁴124. Signorelli J, Zimmer A, Liewer S, Shostrom VK, Freifeld A. Incidence of Febrile Neutropenia in Autologous Hematopoietic Stem Cell Transplant (HSCT) Recipients on levofloxacin prophylaxis. Transpl Infect Dis. 2020;22:e13225. doi: 10.1111/tid.13225. https://doi.org/10.1111/tid.13225... ^,¹²⁵125. Balassa K, Danby R, Rocha V. Haematopoietic stem cell transplants: principles and indications. Br J Hosp Med (Lond). 2019;80:33-9. doi: 10.12968/hmed.2019.80.1.33. https://doi.org/10.12968/hmed.2019.80.1.... .

Clinical remission	CDAI <150¹²⁶126. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JA, Boeckh MJ; Center for International Blood and Marrow Research; National Marrow Donor program; European Blood and MarrowTransplant Group; American Society of Blood and Marrow Transplantation; Canadian Blood and Marrow Transplant Group; Infectious Diseases Society of America; Society for Healthcare Epidemiology of America; Association of Medical Microbiology and Infectious Disease Canada; Centers for Disease Control and Prevention. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant . 2009;15:1143-238. doi: 10.1016/j.bbmt.2009.06.019. https://doi.org/10.1016/j.bbmt.2009.06.0... .
	HBI <5¹²⁷127. Majhail NS. Long-term complications after hematopoietic cell transplantation. Hematol Oncol Stem Cell Ther. 2017;10:220-7. doi: 10.1016/j.hemonc.2017.05.009. https://doi.org/10.1016/j.hemonc.2017.05... .
	PRO2 (abdominal pain ≤1 and stool frequency ≤3)⁷³73. Turner D, Ricciuto A, Lewis A, D’Amico F, Dhaliwal J, Griffiths AM, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160:1570-83..

Endoscopic remission	Endoscopic remission (SES-CD ≤2 points or CDEIS <3) and lack of ulcerations (i.e., any ulcerations, including aphthous ulcers)⁷³73. Turner D, Ricciuto A, Lewis A, D’Amico F, Dhaliwal J, Griffiths AM, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160:1570-83.^,¹²⁸128. Burns LJ. Late effects after autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant . 2009;15(Suppl 1):21-4. doi: 10.1016/j.bbmt.2008.10.009. https://doi.org/10.1016/j.bbmt.2008.10.0... .

Disease Free Remission 1 (DFR1)	Disease Free Remission, Type 1: CDAI <150, without CD-related medications, without endoscopic evidence of disease and MRI or CT without evidence of disease.

Disease Free Remission 2 (DFR2)	Disease Free Remission type 2: CDAI <150, without CD-related medications, without endoscopic evidence of disease, without MRI or CT evidence of disease and without histological evidence of disease.

Transmural healing	Magnetic Resonance Index of Activity score below 7¹²⁹129. Pegoraro F, Favre C. Post-transplantation lymphoproliferative disorder after haematopoietic stem cell transplantation. Ann Hematol. 2021;100:865-78. doi: 10.1007/s00277-021-04433-y. https://doi.org/10.1007/s00277-021-04433... ^,¹³⁵135. Buisson A, Pereira B, Goutte M, Reymond M, Allimant C, Obritin-Guilhen H, et al. Magnetic resonance index of activity (MaRIA) and Clermont score are highly and equally effective MRI indices in detecting mucosal healing in Crohn’s disease. Dig Liver Dis. 2017;49:1211-7..

Health-related quality of life	IBDQ¹³⁰130. Bojic D, Bodger K, Travis S. Patient Reported Outcome Measures (PROMs) in Inflammatory Bowel Disease: New Data. J Crohns Colitis . 2017;11(Suppl 2):S576-S585.^,¹³⁶136. Guyatt G, Mitchell A, Irvine EJ, Singer J, Williams N, Goodacre R, et al. A new measure of health status for clinical trials in inflammatory bowel disease. Gastroenterology. 1989;96:804-10.: bowel-related symptoms, systemic function, social function, emotional status.
	Response: increase ≥16 points.
	Remission ≥210 points.
	SF 36: vitality, mental health, emotional aspects, general health, social aspects, physical limitations, pain, functional capacity.

Disability	IBD Disability Index¹³¹131. Feagan B, Sandborn WJ, Rutgeerts P, Levesque BG, Khanna R, Huang B, et al. Performance of Crohn’s disease Clinical Trial Endpoints based upon Different Cutoffs for Patient Reported Outcomes or Endoscopic Activity: Analysis of EXTEND Data. Inflamm Bowel Dis . 2018;24:932-42.^,¹³⁷137. Gower-Rousseau C, Sarter H, Savoye G, Tavernier N, Fumery M, Sandborn WJ, et al. Validation of the Inflammatory Bowel Disease Disability Index in a population-based cohort. Gut. 2017;66:588-96..
	Comprises following domains: mobility, self-care, major daily life activities, gastrointestinal-related problems, mental health and interaction with environment.
	No disability: 0-20.

Overall survival	Percentage of HSCT survival in patients with CD.

Clinical relapse-free survival after HSCT	Time between HSCT and disease flareup.

Transplant-related mortality	Mortality directly related to HSCT.

[1] Corresponding author: Milton Artur Ruiz. E-mail: milruiz@yahoo.com.br

CD confirmed diagnosis	By clinical, endoscopic methods (endoscopy/colonoscopy/enteroscopy), histology, laboratorial (inflammatory markers) and cross-sectional imaging (CT or MRI enterography, bowel ultrasound).
Clinically active disease	CDAI >150.
	HBI >8.
	CCSI >15.
Endoscopic active disease	Ileal or ileocolonic disease: SES-CD ≥7 or CDEIS ≥9.
	For jejunoileal disease: Lewis ≥790.
	CECDAI >9.2.
	Esophageal, gastroduodenal disease: visual aspect of ulcers.
Refractory disease (at least 1 relapse/year)	Refractory or intolerant to immunosuppressors: azathioprine, 6-mercaptopurine and/or methotrexate or cyclosporine.
	Refractory or intolerant to at least two biologic therapies (anti-TNF therapy, anti-integrin or anti-IL12/IL23), one of which is TNF blocker (infliximab or adalimumab); all with optimized dose.
Surgery criteria	Candidate for whom surgery is considered not appropriate or has been declined.
	Refusal to accept proposed mutilating surgery.

Brasil

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Transplante de células tronco hematopoiéticas e doença de Crohn: posição do Comitê de Transplantes do Grupo Brasileiro para estudo das doenças inflamatórias do intestino (GEDIIB)

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