A National Consensus on Hematopoietic Stem Cell Transplantation for Patients with Inborn Errors of Immunity
-
Reza Yazdani
,
Samaneh Abdolahzadeh
,
Marjan Aghajani
,
Mina Ahmadi
,
Mostafa Alavi-Moghaddam
,
Saba Arshi
,
Maryam Asarehzadegan Dezfouli
,
Marzieh Asgharyan
,
Parisa Ashournia
,
Ayda Askarisarvestani
,
Raheleh Assari
,
Hadi Badiee
,
Sima Bahrami
,
Maryam Behfar
,
Nasrin Behniafard
,
Mahsa Choroom Kheirabadi
,
Zahra Daneshmandi
,
Mohammad Hassan Bemanian
,
Taher Cheraghi
,
Kian Darabi
,
Sepideh Darougar
,
Sarehsadat Ebrahimi
,
Golnaz Eslamian
,
Maryam Esmaeilbeig
,
Morteza Fallahpour
,
Nader Faraji
,
Shahin Farzadmanesh
,
Kimia HajiAbbasi Someesaraie
,
Arash Kalantari
,
Mahdieh Karimizadeh
,
Elham Kaviani
,
Mehrnaz Mesdaghi
,
Majid Marjani
,
Mohammadreza Modaresi
,
Iraj Mohammadzadeh
,
Mahshid Movahedi
,
Masoud Movahedi
,
Mostafa Moosavian
,
Mohammamd Nabavi
,
Leyla Norouzi-Barough
,
Anahita Razaghian
,
Mansoureh Shariat
,
Sahar Seraj
,
Soodeh Seyedi
,
Seyedehshabnam Seyedsalehi
,
Alireza Shafiei
,
Zahra Shahraki Ghadimi
,
Behzad Shakerian
,
Samin Sharafian
,
Sima Shokri
,
Marziyeh Tavakol
,
Ahmad Vosughi Motlagh
,
Nima Rezaei
Abstract
At present, a national consensus on hematopoietic stem cell transplantation (HSCT) for patients with inborn errors of immunity (IEI) is lacking. This consensus is written based on a combination of scientific literature and comments from the expert panel of Iranian immunologists. We formed a panel of clinical immunologists at a meeting titled “Second Meeting on the Diagnosis of IEI by IEI Experts” to receive their comments in this field. All authors reviewed and agreed on the current consensus. This consensus guideline provides recommendations on donor selection, stem cell source, conditioning regimen, mobilization and collection, stem cell infusion, engraftment and chimerism assessment, and post-transplant care for patients with IEI. The current recommendations reflect Iranian practice and do not necessarily represent global preferences.
1. Bousfiha AA, Jeddane L, Moundir A, Poli MC, Aksentijevich I, Cunningham-Rundles C, et al. The 2024 update of IUIS phenotypic classification of human inborn errors of immunity. J Hum Immun. 2024;1(1):e20250002.
2. Fekrvand S, Esfahani ZH, Yarahmadi M, Saeedi-Boroujeni A, Salehi H, Hakimelahi A, et al. Mortality rate and causes of death in inborn errors of immunity: A systematic review and meta-analysis. Mutat Res Rev Mutat Res. 2025;796:108564.
3. Albert MH, Sirait T, Eikema DJ, Bakunina K, Wehr C, Suarez F, et al. Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity: an EBMT IEWP study. Blood. 2022;140(14):1635-49.
4. Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014;371(5):434-46.
5. Ferrua F, Galimberti S, Courteille V, Slatter MA, Booth C, Moshous D, et al. Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study. J Allergy Clin Immunol. 2019;143(6):2238-53.
6. Wadbudhe AM, Meshram RJ, Tidke SC. Severe Combined Immunodeficiency (SCID) and Its New Treatment Modalities. Cureus. 2023;15(10):e47759.
7. Majhail NS. Long-term complications after hematopoietic cell transplantation. Hematol Oncol Stem Cell Ther. 2017;10(4):220-7.
8. Lankester AC, Albert MH, Booth C, Gennery AR, Güngör T, Hönig M, et al. EBMT/ESID inborn errors working party guidelines for hematopoietic stem cell transplantation for inborn errors of immunity. Bone Marrow Transplant. 2021;56(9):2052-62.
9. Alsaati N, Grier A, Ochfeld E, McClory S, Heimall J. Hematopoietic stem cell transplantation for primary immunodeficiency. Allergy Asthma Proc. 2024;45(5):371-83.
10. Slatter MA, Gennery AR. Haematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease. J Clin Med. 2023;12(18).
11. Slatter MA, Gennery AR. Hematopoietic cell transplantation in primary immunodeficiency - conventional and emerging indications. Expert Rev Clin Immunol. 2018;14(2):103-14.
12. Castagnoli R, Delmonte OM, Calzoni E, Notarangelo LD. Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Diseases: Current Status and Future Perspectives. Front Pediatr. 2019;7:295.
13. Notarangelo LD. Genetically-determined defects of T cell development. Allergy Asthma Proc. 2024;45(5):326-31.
14. Cordero E, Goycochea-Valdivia W, Mendez-Echevarria A, Allende LM, Alsina L, Bravo García-Morato M, et al. Executive Summary of the Consensus Document on the Diagnosis and Management of Patients with Primary Immunodeficiencies. J Allergy Clin Immunol Pract. 2020;8(10):3342-7.
15. Albert MH, Slatter MA, Gennery AR, Güngör T, Bakunina K, Markovitch B, et al. Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis. Blood. 2022;139(13):2066-79.
16. Jimenez Jimenez AM, Spellman SR, Politikos I, McCurdy SR, Devine SM, Malki MMA, et al. Allogeneic Hematopoietic Cell Donor Selection: Contemporary Guidelines from the NMDP/CIBMTR. Transplant Cell Ther. 2025.
17. Howard CA, Fernandez-Vina MA, Appelbaum FR, Confer DL, Devine SM, Horowitz MM, et al. Recommendations for donor human leukocyte antigen assessment and matching for allogeneic stem cell transplantation: consensus opinion of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Biol Blood Marrow Transplant. 2015;21(1):4-7.
18. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110(13):4576-83.
19. Woolfrey A, Klein JP, Haagenson M, Spellman S, Petersdorf E, Oudshoorn M, et al. HLA-C antigen mismatch is associated with worse outcome in unrelated donor peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2011;17(6):885-92.
20. Spellman SR, Eapen M, Logan BR, Mueller C, Rubinstein P, Setterholm MI, et al. A perspective on the selection of unrelated donors and cord blood units for transplantation. Blood. 2012;120(2):259-65.
21. Spellman S, Bray R, Rosen-Bronson S, Haagenson M, Klein J, Flesch S, et al. The detection of donor-directed, HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure. Blood. 2010;115(13):2704-8.
22. Ciurea SO, Thall PF, Wang X, Wang SA, Hu Y, Cano P, et al. Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation. Blood. 2011;118(22):5957-64.
23. Marciano BE, Zerbe CS, Falcone EL, Ding L, DeRavin SS, Daub J, et al. X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability. J Allergy Clin Immunol. 2018;141(1):365-71.
24. Hamidieh AA, Behfar M, Pourpak Z, Faghihi-Kashani S, Fazlollahi MR, Hosseini AS, et al. Long-term outcomes of fludarabine, melphalan and antithymocyte globulin as reduced-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiency disorders: a prospective single center study. Bone Marrow Transplant. 2016;51(2):219-26.
25. Cheuk DK. Optimal stem cell source for allogeneic stem cell transplantation for hematological malignancies. World J Transplant. 2013;3(4):99-112.
26. Czerw T, Labopin M, Schmid C, Cornelissen JJ, Chevallier P, Blaise D, et al. High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia - an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Oncotarget. 2016;7(19):27255-66.
27. Sandmaier BM, Mackinnon S, Childs RW. Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: current perspectives. Biol Blood Marrow Transplant. 2007;13(1 Suppl 1):87-97.
28. Shaw P, Shizuru J, Hoenig M, Veys P. Conditioning Perspectives for Primary Immunodeficiency Stem Cell Transplants. Front Pediatr. 2019;7:434.
29. Mackall C, Fry T, Gress R, Peggs K, Storek J, Toubert A. Background to hematopoietic cell transplantation, including post transplant immune recovery. Bone Marrow Transplant. 2009;44(8):457-62.
30. Blouin AG, Ye F, Williams J, Askar M. A practical guide to chimerism analysis: Review of the literature and testing practices worldwide. Hum Immunol. 2021;82(11):838-49.
31. Ogonek J, Kralj Juric M, Ghimire S, Varanasi PR, Holler E, Greinix H, et al. Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2016;7:507.
32. Albert MH, Freeman AF. Wiskott-Aldrich Syndrome (WAS) and Dedicator of Cytokinesis 8- (DOCK8) Deficiency. Front Pediatr. 2019;7:451.
33. Burroughs LM, Petrovic A, Brazauskas R, Liu X, Griffith LM, Ochs HD, et al. Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report. Blood. 2020;135(23):2094-105.
34. Eissa H, Thakar MS, Shah AJ, Logan BR, Griffith LM, Dong H, et al. Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study. J Allergy Clin Immunol. 2024;153(1):287-96.
35. Neven B, Leroy S, Decaluwe H, Le Deist F, Picard C, Moshous D, et al. Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency. Blood. 2009;113(17):4114-24.
36. Griffith LM, Cowan MJ, Notarangelo LD, Puck JM, Buckley RH, Candotti F, et al. Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management. J Allergy Clin Immunol. 2009;124(6):1152-60.e12.
37. Heimall J, Buckley RH, Puck J, Fleisher TA, Gennery AR, Haddad E, et al. Recommendations for Screening and Management of Late Effects in Patients with Severe Combined Immunodeficiency after Allogenic Hematopoietic Cell Transplantation: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT. Biol Blood Marrow Transplant. 2017;23(8):1229-40.
38. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143-238.
39. Penack O, Marchetti M, Aljurf M, Arat M, Bonifazi F, Duarte RF, et al. Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol. 2024;11(2):e147-e59.
40. Lum SH, Hoenig M, Gennery AR, Slatter MA. Conditioning Regimens for Hematopoietic Cell Transplantation in Primary Immunodeficiency. Curr Allergy Asthma Rep. 2019;19(11):52.
2. Fekrvand S, Esfahani ZH, Yarahmadi M, Saeedi-Boroujeni A, Salehi H, Hakimelahi A, et al. Mortality rate and causes of death in inborn errors of immunity: A systematic review and meta-analysis. Mutat Res Rev Mutat Res. 2025;796:108564.
3. Albert MH, Sirait T, Eikema DJ, Bakunina K, Wehr C, Suarez F, et al. Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity: an EBMT IEWP study. Blood. 2022;140(14):1635-49.
4. Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014;371(5):434-46.
5. Ferrua F, Galimberti S, Courteille V, Slatter MA, Booth C, Moshous D, et al. Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study. J Allergy Clin Immunol. 2019;143(6):2238-53.
6. Wadbudhe AM, Meshram RJ, Tidke SC. Severe Combined Immunodeficiency (SCID) and Its New Treatment Modalities. Cureus. 2023;15(10):e47759.
7. Majhail NS. Long-term complications after hematopoietic cell transplantation. Hematol Oncol Stem Cell Ther. 2017;10(4):220-7.
8. Lankester AC, Albert MH, Booth C, Gennery AR, Güngör T, Hönig M, et al. EBMT/ESID inborn errors working party guidelines for hematopoietic stem cell transplantation for inborn errors of immunity. Bone Marrow Transplant. 2021;56(9):2052-62.
9. Alsaati N, Grier A, Ochfeld E, McClory S, Heimall J. Hematopoietic stem cell transplantation for primary immunodeficiency. Allergy Asthma Proc. 2024;45(5):371-83.
10. Slatter MA, Gennery AR. Haematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease. J Clin Med. 2023;12(18).
11. Slatter MA, Gennery AR. Hematopoietic cell transplantation in primary immunodeficiency - conventional and emerging indications. Expert Rev Clin Immunol. 2018;14(2):103-14.
12. Castagnoli R, Delmonte OM, Calzoni E, Notarangelo LD. Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Diseases: Current Status and Future Perspectives. Front Pediatr. 2019;7:295.
13. Notarangelo LD. Genetically-determined defects of T cell development. Allergy Asthma Proc. 2024;45(5):326-31.
14. Cordero E, Goycochea-Valdivia W, Mendez-Echevarria A, Allende LM, Alsina L, Bravo García-Morato M, et al. Executive Summary of the Consensus Document on the Diagnosis and Management of Patients with Primary Immunodeficiencies. J Allergy Clin Immunol Pract. 2020;8(10):3342-7.
15. Albert MH, Slatter MA, Gennery AR, Güngör T, Bakunina K, Markovitch B, et al. Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis. Blood. 2022;139(13):2066-79.
16. Jimenez Jimenez AM, Spellman SR, Politikos I, McCurdy SR, Devine SM, Malki MMA, et al. Allogeneic Hematopoietic Cell Donor Selection: Contemporary Guidelines from the NMDP/CIBMTR. Transplant Cell Ther. 2025.
17. Howard CA, Fernandez-Vina MA, Appelbaum FR, Confer DL, Devine SM, Horowitz MM, et al. Recommendations for donor human leukocyte antigen assessment and matching for allogeneic stem cell transplantation: consensus opinion of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Biol Blood Marrow Transplant. 2015;21(1):4-7.
18. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110(13):4576-83.
19. Woolfrey A, Klein JP, Haagenson M, Spellman S, Petersdorf E, Oudshoorn M, et al. HLA-C antigen mismatch is associated with worse outcome in unrelated donor peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2011;17(6):885-92.
20. Spellman SR, Eapen M, Logan BR, Mueller C, Rubinstein P, Setterholm MI, et al. A perspective on the selection of unrelated donors and cord blood units for transplantation. Blood. 2012;120(2):259-65.
21. Spellman S, Bray R, Rosen-Bronson S, Haagenson M, Klein J, Flesch S, et al. The detection of donor-directed, HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure. Blood. 2010;115(13):2704-8.
22. Ciurea SO, Thall PF, Wang X, Wang SA, Hu Y, Cano P, et al. Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation. Blood. 2011;118(22):5957-64.
23. Marciano BE, Zerbe CS, Falcone EL, Ding L, DeRavin SS, Daub J, et al. X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability. J Allergy Clin Immunol. 2018;141(1):365-71.
24. Hamidieh AA, Behfar M, Pourpak Z, Faghihi-Kashani S, Fazlollahi MR, Hosseini AS, et al. Long-term outcomes of fludarabine, melphalan and antithymocyte globulin as reduced-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiency disorders: a prospective single center study. Bone Marrow Transplant. 2016;51(2):219-26.
25. Cheuk DK. Optimal stem cell source for allogeneic stem cell transplantation for hematological malignancies. World J Transplant. 2013;3(4):99-112.
26. Czerw T, Labopin M, Schmid C, Cornelissen JJ, Chevallier P, Blaise D, et al. High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia - an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Oncotarget. 2016;7(19):27255-66.
27. Sandmaier BM, Mackinnon S, Childs RW. Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: current perspectives. Biol Blood Marrow Transplant. 2007;13(1 Suppl 1):87-97.
28. Shaw P, Shizuru J, Hoenig M, Veys P. Conditioning Perspectives for Primary Immunodeficiency Stem Cell Transplants. Front Pediatr. 2019;7:434.
29. Mackall C, Fry T, Gress R, Peggs K, Storek J, Toubert A. Background to hematopoietic cell transplantation, including post transplant immune recovery. Bone Marrow Transplant. 2009;44(8):457-62.
30. Blouin AG, Ye F, Williams J, Askar M. A practical guide to chimerism analysis: Review of the literature and testing practices worldwide. Hum Immunol. 2021;82(11):838-49.
31. Ogonek J, Kralj Juric M, Ghimire S, Varanasi PR, Holler E, Greinix H, et al. Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2016;7:507.
32. Albert MH, Freeman AF. Wiskott-Aldrich Syndrome (WAS) and Dedicator of Cytokinesis 8- (DOCK8) Deficiency. Front Pediatr. 2019;7:451.
33. Burroughs LM, Petrovic A, Brazauskas R, Liu X, Griffith LM, Ochs HD, et al. Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report. Blood. 2020;135(23):2094-105.
34. Eissa H, Thakar MS, Shah AJ, Logan BR, Griffith LM, Dong H, et al. Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study. J Allergy Clin Immunol. 2024;153(1):287-96.
35. Neven B, Leroy S, Decaluwe H, Le Deist F, Picard C, Moshous D, et al. Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency. Blood. 2009;113(17):4114-24.
36. Griffith LM, Cowan MJ, Notarangelo LD, Puck JM, Buckley RH, Candotti F, et al. Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management. J Allergy Clin Immunol. 2009;124(6):1152-60.e12.
37. Heimall J, Buckley RH, Puck J, Fleisher TA, Gennery AR, Haddad E, et al. Recommendations for Screening and Management of Late Effects in Patients with Severe Combined Immunodeficiency after Allogenic Hematopoietic Cell Transplantation: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT. Biol Blood Marrow Transplant. 2017;23(8):1229-40.
38. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143-238.
39. Penack O, Marchetti M, Aljurf M, Arat M, Bonifazi F, Duarte RF, et al. Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol. 2024;11(2):e147-e59.
40. Lum SH, Hoenig M, Gennery AR, Slatter MA. Conditioning Regimens for Hematopoietic Cell Transplantation in Primary Immunodeficiency. Curr Allergy Asthma Rep. 2019;19(11):52.
| Files | ||
| Issue | Vol 9, No 1 (2026) | |
| Section | Review Article | |
| DOI | https://doi.org/10.18502/igj.v9i1.21880 | |
| Keywords | ||
| Consensus Hematopoietic Stem Cell Transplantation HSCT Inborn Errors of Immunity IEI | ||
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How to Cite
1.
Yazdani R, Abdolahzadeh S, Aghajani M, Ahmadi M, Alavi-Moghaddam M, Arshi S, Asarehzadegan Dezfouli M, Asgharyan M, Ashournia P, Askarisarvestani A, Assari R, Badiee H, Bahrami S, Behfar M, Behniafard N, Choroom Kheirabadi M, Daneshmandi Z, Bemanian MH, Cheraghi T, Darabi K, Darougar S, Ebrahimi S, Eslamian G, Esmaeilbeig M, Fallahpour M, Faraji N, Farzadmanesh S, HajiAbbasi Someesaraie K, Kalantari A, Karimizadeh M, Kaviani E, Mesdaghi M, Marjani M, Modaresi M, Mohammadzadeh I, Movahedi M, Movahedi M, Moosavian M, Nabavi M, Norouzi-Barough L, Razaghian A, Shariat M, Seraj S, Seyedi S, Seyedsalehi S, Shafiei A, Shahraki Ghadimi Z, Shakerian B, Sharafian S, Shokri S, Tavakol M, Vosughi Motlagh A, Rezaei N. A National Consensus on Hematopoietic Stem Cell Transplantation for Patients with Inborn Errors of Immunity. Immunol Genet J. 2026;9(1):1-10.
