Allogeneic Stem Cell Transplantation Using Myeloablative and Reduced-Intensity Conditioning in Patients with Major Histocompatibility Complex Class II Deficiency

Abstract

Major histocompatibility complex class II (MHC II) deficiency is a rare combined immunodeficiency disease. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Between June 1994 and February 2007, 30 children with MHC II deficiency underwent a total of 33 HSCT procedures. Median age at HSCT was 27 months. The stem cell source was unmanipulated bone marrow from HLA-identical related donors in 26 patients, one HLA antigen-mismatched bone marrow in 3 patients, and unrelated umbilical cord blood in 1 patient. Conditioning was with one of 3 myeloablative regimens—regimen A (18 patients): busulfan (Bu), cyclophosphamide (Cy), and etoposide; regimen B (2 patients): Bu, Cy, and antithymocyte globulin (ATG); or regimen C (1 patient): CY and total body irradiation (TBI)—or with a reduced-intensity regimen (12 patients): fludarabine, melphalan, and ATG. The median CD34 cell dose was 8.3 × 106/kg. Twenty patients experienced immune reconstitution and had sustained engraftment ranging from 9% to 100% for lymphoid lines and from 5% to 100% for myeloid lines that were significant to cure the disease. The overall disease-free survival rate was 66% and 76% after HLA-identical HSCT, with a median follow-up of 6.3 years, which is higher than previously reported. In HLA-identical transplant recipients, reliable donor stem cell engraftment and immune reconstitution were achieved through myeloablative or reduced-intensity conditioning. Further studies and long-term follow-up are needed to determine the appropriate conditioning regimen. Major histocompatibility complex class II (MHC II) deficiency is a rare combined immunodeficiency disease. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Between June 1994 and February 2007, 30 children with MHC II deficiency underwent a total of 33 HSCT procedures. Median age at HSCT was 27 months. The stem cell source was unmanipulated bone marrow from HLA-identical related donors in 26 patients, one HLA antigen-mismatched bone marrow in 3 patients, and unrelated umbilical cord blood in 1 patient. Conditioning was with one of 3 myeloablative regimens—regimen A (18 patients): busulfan (Bu), cyclophosphamide (Cy), and etoposide; regimen B (2 patients): Bu, Cy, and antithymocyte globulin (ATG); or regimen C (1 patient): CY and total body irradiation (TBI)—or with a reduced-intensity regimen (12 patients): fludarabine, melphalan, and ATG. The median CD34 cell dose was 8.3 × 106/kg. Twenty patients experienced immune reconstitution and had sustained engraftment ranging from 9% to 100% for lymphoid lines and from 5% to 100% for myeloid lines that were significant to cure the disease. The overall disease-free survival rate was 66% and 76% after HLA-identical HSCT, with a median follow-up of 6.3 years, which is higher than previously reported. In HLA-identical transplant recipients, reliable donor stem cell engraftment and immune reconstitution were achieved through myeloablative or reduced-intensity conditioning. Further studies and long-term follow-up are needed to determine the appropriate conditioning regimen. IntroductionMajor histocompatibility complex class II (MHC II) deficiency is a rare combined immunodeficiency disease characterized by profoundly deficient human leukocyte antigen (HLA) class II expression and lack of cellular and humoral immune responses to foreign antigens. The disease is also referred to as bare lymphocyte syndrome type II. Clinical manifestations include extreme susceptibility to viral, bacterial, fungal, and protozoal infections, primarily of the respiratory and gastrointestinal tract. Severe malabsorption with failure to thrive ensues, often leading to death in early childhood [1Griscelli C. Lisowska-Grospierre B. Mach B. Combined immunodeficiency with defective expression of MHC class П genes.Immunodef Rev. 1989; 1: 135-153PubMed Google Scholar, 2Klein C. Lisowska-Grospierre B. LeDeist F. et al.Major histocompatibility complex class П deficiency: clinical manifestations, immunological features and outcome.J Pediatr. 1993; 123: 921-928Abstract Full Text PDF PubMed Scopus (165) Google Scholar, 3Saleem M.A. Arkwright P.D. Davies E.G. et al.Clinical course of patients with major histocompatibility complex class П deficiency.Arch Dis Child. 2000; 83: 356-359Crossref PubMed Scopus (49) Google Scholar, 4Villard J. Masternak K. Lisowska-Grospierre B. et al.MHC class II deficiency: a disease of gene regulation.Medicine. 2001; 80: 405-418Crossref PubMed Scopus (50) Google Scholar].The disease is an autosomal recessive disease resulting from defects in several distinct transacting regulatory factors required for the expression of MHC II genes. This deficiency is classified into 4 complementation groups. Mutations in CIITA (complementation group A), RFXANK (complementation group B), RFX5 (complementation group C), and RFXAP (complementation group D) have been identified in individuals with MHC II deficiency [4Villard J. Masternak K. Lisowska-Grospierre B. et al.MHC class II deficiency: a disease of gene regulation.Medicine. 2001; 80: 405-418Crossref PubMed Scopus (50) Google Scholar].Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only available curative treatment for MHC II deficiency. HSCT can cure the disease, provided that it is performed before the development of complications leading to severe organ failure [5Klein C. Cavazzana-Calvo M. Le Deist F. et al.Bone marrow transplantation in major histocompatibility complex class II deficiency: a single-center study of 19 patients.Blood. 1995; 85: 580-587PubMed Google Scholar, 6Antoine C. Muller Cant A. Muller S. Cant A. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of European experience 1968–99.Lancet. 2003; 361: 553-560Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar]. In the European registry data, HSCT in patients with MHC class II deficiency was associated with a lower survival rate than HSCT performed for other primary immunodeficiencies [6Antoine C. Muller Cant A. Muller S. Cant A. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of European experience 1968–99.Lancet. 2003; 361: 553-560Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar, 7Buckley R.H. Fischer A. Bone marrow transplantation for primary immunodeficiency diseases.in: Ochs H.D. Smith C.E. Puck J.M. Primary Immunodeficiency Disease. Oxford University Press, Oxford, UK1999: 459-475Google Scholar]. These differences were observed for HSCT performed with matched and nonmatched donors alike, and MHC class II immunodeficiency seemed to carry a poor prognosis, especially after HLA nonidentical transplantation, with only 32% of patients surviving to 1 year [6Antoine C. Muller Cant A. Muller S. Cant A. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of European experience 1968–99.Lancet. 2003; 361: 553-560Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar]. The low survival after HLA-identical HSCT (53%) was likely related to the incidence of preexisting viral infections and was associated with a high incidence of acute graft-versus-host disease (aGVHD) [8Renella R. Picard C. Neven B. et al.Human leucocyte antigen–identical haematopoietic stem cell transplantation in major histocompatiblity complex class II immunodeficiency: reduced survival correlates with an increased incidence of acute graft-versus-host disease and preexisting viral infections.Br J Haematol. 2006; 134: 510-516Crossref PubMed Scopus (34) Google Scholar]. An interesting observation in long-term transplantation survivors is the persistence of a relative CD4 T cell lymphopenia, possibly because of a lack of HLA class II molecules on thymic epithelial cells [5Klein C. Cavazzana-Calvo M. Le Deist F. et al.Bone marrow transplantation in major histocompatibility complex class II deficiency: a single-center study of 19 patients.Blood. 1995; 85: 580-587PubMed Google Scholar].Given the available HSCT protocols for children with MHC II deficiency, intensive pretransplantation conditioning appears to be a prerequisite for reliable engraftment and complete immune reconstitution. But, this conditioning is associated with an increased risk of short-term and long-term toxicity, particularly infections and end-organ decompensation, leading to a high rate of treatment-related mortality, especially in older children who acquire organ dysfunction. Late adverse effects, including growth retardation, infertility, and secondary malignancies, also are of concern.Driven by concerns about myeloablative (MA) regimens, some groups have reported success using reduced-intensity conditioning (RIC) regimens in patients with hematologic malignancies [9Giralt S. Estey E. Albitar M. et al.Engraftment of allogeneic hematopoietic progenitor cells with purine analog–containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy.Blood. 1997; 89: 4531-4536PubMed Google Scholar, 10Slavin S. Nagler A. Naparstek E. et al.Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases.Blood. 1998; 91: 756-763PubMed Google Scholar, 11Childs R. Clave E. Contentin N. et al.Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses.Blood. 1999; 94: 3234-3241PubMed Google Scholar]. Recent reports of RIC regimen-based HSCT in patients with primary immunodeficiencies and significant organ dysfunction indicated good engraftment and immune reconstitution with minimal toxicity and GVHD [12Amrolia P. Gaspar H.B. Hassan A. et al.Nonmyeloablative stem cell transplantation for congenital immunodeficiencies.Blood. 2000; 96: 1239-1246PubMed Google Scholar]. In one series, high-risk patients treated with RIC-based HSCT had better survival than those treated with MA HSCT (94% vs 53%) [13Rao K. Amrolia P.J. Jones A. et al.Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen.Blood. 2005; 105: 879-885Crossref PubMed Scopus (192) Google Scholar]. Here we describe the outcomes of a large series of patients with MHC II deficiency who underwent HSCT at a single center using MA conditioning and RIC.Patients and MethodsPatient CharacteristicsBetween June 1994 and February 2007, 30 children with MHC II deficiency underwent 33 HSCT procedures at King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Saudia Arabia. Three patients required a second HSCT trial. A retrospective chart review was conducted with multivariate factors including pre-HSCT clinical and immunologic characteristics, HSCT characteristics (ie, age at HSCT; donor status including age, sex, and HLA match; serologic status; conditioning regimen; toxicity; stem cell origin; CD34+ cells dose infused; bone marrow manipulation; engraftment; GVHD; infections; and outcome), and immune reconstitution post-HSCT at last follow-up. The diagnosis was made through the analysis of MHC-II expression on peripheral blood monocytes, B cells, and activated T cells. Assessment of isolated pathogens was made through culture or polymerase chain reaction (PCR) of material obtained by specimen collection or biopsy. The study was approved by KFSHRC's Institutional Review Board.Preparative Regimen, Transplantation, and Supportive CareConditioning therapy consisted of one of 3 MA regimens—regimen A (18 patients): busulfan (Bu) 16 mg/kg (days -10 to -7), cyclophosphamide (Cy) 200 mg/kg (days -5 to -2), and etoposide (VP-16) 300 mg/m2/day (days -5 to -3), regimen B (2 patients): Bu, Cy, and antithymocyte globulin (ATG) 5 mg/kg/day (days -5 to -2), or regimen C (1 patient): Cy and total body irradiation (TBI)—or a RIC regimen (12 patients) comprising fludarabine 30 mg/m2 /day (days -7 to -3), melphalan 140 mg/m2 (day -2), and ATG 5 mg/kg/day (days -2 to +2). The stem cell sources were unmanipulated bone marrow from HLA-genoidentical siblings in 19 patients, HLA-phenotypically identical related donors in 7 patients, one antigen HLA-mismatched related donors in 3 patients, and unrelated umbilical cord blood in 1 patient. HLA-compatibility was assessed serologically at class 1 (A, B, and C loci) and molecularly at class 2 (DRB1 and DQB1 loci). The total number of CD34+ stem cells infused on the day of transplantation ranged from 3 to 20.7 × 106/kg (median, 8.7 × 106/kg). GVHD prophylaxis consisted of cyclosporine (CsA) and methotrexate (MTX) in 17 patients, CsA alone in 15 patients, and CsA and a steroid in 1 patient. All patients were placed in a positive-pressure isolation room. Febrile illnesses during periods of aplasia were treated with standard preemptive intravenous antibiotherapy. Hematologic support with matched erythrocytes and platelets was provided where indicated. All blood products were irradiated and were cytomegalovirus (CMV)-negative for CMV-negative patients. Detection of CMV in the donor or the recipient before transplantation led to preemptive treatment with intravenous acyclovir (1500 mg/m2/day) for 60 days. All patients received granulocyte colony-stimulating factor 5 μg/kg per day from day +8 until to × was 3 of and was by the of MHC-II expression on peripheral blood monocytes, B and activated T was by of peripheral blood cells was performed by with using for and T cell was in by to and was by diagnosis of GVHD was made to the for GVHD P. et on GVHD 1995; Google and by and All patients were treated with and received therapy as Clinical and clinical and immunologic characteristics are in The study group 19 and with a median age at diagnosis of 16 1 to infections, and failure to thrive were the clinical patients had of an or a including CMV and MHC II expression was on B cells and activated T cells in patients, and was Three patients were on because of a of MHC II deficiency. The median age at HSCT was 27 and (1 to infections, II expression II expression was on B cells and activated T cells to to hematopoietic stem cell major histocompatibility MHC II expression was on B cells and activated T cells in a at HSCT, × × cell 1 × disease, hematopoietic stem cell graft-versus-host reduced-intensity unrelated is on and in a and complications are in disease and significant were in the MA to infections, patients experienced than one of that was treated with standard preemptive intravenous and to culture CMV in patients with MA conditioning and 2 with and was treated with infections were observed in 5 patients. patients including 3 patients in the MA group (2 after second HSCT and 1 after unrelated umbilical cord blood secondary to toxicity, and failure and 1 in the RIC group secondary to overall disease-free survival was 66% and 76% after HLA-identical HSCT, with a median follow-up of 6.3 which is higher than previously reported [8Renella R. Picard C. Neven B. et al.Human leucocyte antigen–identical haematopoietic stem cell transplantation in major histocompatiblity complex class II immunodeficiency: reduced survival correlates with an increased incidence of acute graft-versus-host disease and preexisting viral infections.Br J Haematol. 2006; 134: 510-516Crossref PubMed Scopus (34) Google significant differences in disease after HLA-identical HSCT on conditioning regimen or or age at HSCT year or were All 3 patients who underwent HSCT from a one antigen-mismatched donor using an RIC regimen primary of the 3 patients who were early in because of of the disease and underwent preemptive HSCT before the development of infections and 1 of after a second median to to × was for the MA group and for the RIC The median to an of × was to for the MA group and for the RIC group chimerism that patients had sustained hematopoietic with donor lymphocyte cell chimerism ranging from 9% to 100% and donor myeloid cell chimerism ranging from 5% to The median lymphocyte cell and myeloid cell chimerism were and with a median follow-up of in the MA and and with a median of follow-up of in the RIC of were in the myeloablative group and Three patients 2 and 1 patients in the RIC group acute with other organ that to standard steroid patients HLA-identical sustained engraftment and immune reconstitution. reconstitution in the MA and RIC groups are in achieved lymphocyte by CD4 was with a median of T cell reconstitution was in patients through the of MHC II expression on activated T cells. to to in groups. donor B cell B cell to or months. in patients, and intravenous therapy was All patients a by to 3 of of and 1 dose of on MHC number of MHC including B cells and activated T to to hematopoietic stem cell major histocompatibility reduced-intensity number of MHC including B cells and activated T patients. in a Clinical and the of this patients were and All patients were to had a severe and those patients with preexisting and disease some clinical with treated with patients who underwent a second HSCT using MA conditioning Cy, and and Cy and secondary to toxicity, and who underwent 7 after the transplantation with a RIC regimen had sustained engraftment and immune high rate of in in an increased incidence of primary immunodeficiency including MHC II deficiency. is about the of this disease in Arabia. MHC deficiency is in 2 and it be of to study the defects in patients to for a in this and to the on the of study the series to of patients with MHC II deficiency who underwent allogeneic HSCT at a single who underwent HSCT with standard conditioning regimens had higher donor cell that this be a standard regimen for HSCT in patients with MHC II deficiency. An RIC regimen be particularly for patients with of are referred for allogeneic HSCT with a using an RIC regimen was and a lower incidence of complications and GVHD with HSCT with a standard conditioning regimen. this is it is by the studies are to and the long-term of the in a 76% disease-free survival rate in patients with MHC II deficiency who underwent HLA-identical related which is higher than reported previously [8Renella R. Picard C. Neven B. et al.Human leucocyte antigen–identical haematopoietic stem cell transplantation in major histocompatiblity complex class II immunodeficiency: reduced survival correlates with an increased incidence of acute graft-versus-host disease and preexisting viral infections.Br J Haematol. 2006; 134: 510-516Crossref PubMed Scopus (34) Google Scholar]. A significant incidence of chimerism was in the MA and RIC it is that chimerism is to cure the disease. CD4 T cell after HSCT and was by the type of conditioning possibly thymic of CD4 T cells because of MHC II expression in thymic The that patients were to viral infections and and to a significant of donor B cell patients were to and by The of in responses to the of B cell we have that reliable donor stem cell engraftment and immune reconstitution after HLA-identical HSCT can be achieved with an MA conditioning regimen or an RIC regimen. RIC is associated with a high rate of in A high rate was after second Further studies and long-term follow-up are needed to determine the appropriate conditioning the patients and for and and the and for the of the The have to provided the and data, and the provided and and Hassan provided IntroductionMajor histocompatibility complex class II (MHC II) deficiency is a rare combined immunodeficiency disease characterized by profoundly deficient human leukocyte antigen (HLA) class II expression and lack of cellular and humoral immune responses to foreign antigens. The disease is also referred to as bare lymphocyte syndrome type II. Clinical manifestations include extreme susceptibility to viral, bacterial, fungal, and protozoal infections, primarily of the respiratory and gastrointestinal tract. Severe malabsorption with failure to thrive ensues, often leading to death in early childhood [1Griscelli C. Lisowska-Grospierre B. Mach B. Combined immunodeficiency with defective expression of MHC class П genes.Immunodef Rev. 1989; 1: 135-153PubMed Google Scholar, 2Klein C. Lisowska-Grospierre B. LeDeist F. et al.Major histocompatibility complex class П deficiency: clinical manifestations, immunological features and outcome.J Pediatr. 1993; 123: 921-928Abstract Full Text PDF PubMed Scopus (165) Google Scholar, 3Saleem M.A. Arkwright P.D. Davies E.G. et al.Clinical course of patients with major histocompatibility complex class П deficiency.Arch Dis Child. 2000; 83: 356-359Crossref PubMed Scopus (49) Google Scholar, 4Villard J. Masternak K. Lisowska-Grospierre B. et al.MHC class II deficiency: a disease of gene regulation.Medicine. 2001; 80: 405-418Crossref PubMed Scopus (50) Google Scholar].The disease is an autosomal recessive disease resulting from defects in several distinct transacting regulatory factors required for the expression of MHC II genes. This deficiency is classified into 4 complementation groups. Mutations in CIITA (complementation group A), RFXANK (complementation group B), RFX5 (complementation group C), and RFXAP (complementation group D) have been identified in individuals with MHC II deficiency [4Villard J. Masternak K. Lisowska-Grospierre B. et al.MHC class II deficiency: a disease of gene regulation.Medicine. 2001; 80: 405-418Crossref PubMed Scopus (50) Google Scholar].Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only available curative treatment for MHC II deficiency. HSCT can cure the disease, provided that it is performed before the development of complications leading to severe organ failure [5Klein C. Cavazzana-Calvo M. Le Deist F. et al.Bone marrow transplantation in major histocompatibility complex class II deficiency: a single-center study of 19 patients.Blood. 1995; 85: 580-587PubMed Google Scholar, 6Antoine C. Muller Cant A. Muller S. Cant A. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of European experience 1968–99.Lancet. 2003; 361: 553-560Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar]. In the European registry data, HSCT in patients with MHC class II deficiency was associated with a lower survival rate than HSCT performed for other primary immunodeficiencies [6Antoine C. Muller Cant A. Muller S. Cant A. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of European experience 1968–99.Lancet. 2003; 361: 553-560Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar, 7Buckley R.H. Fischer A. Bone marrow transplantation for primary immunodeficiency diseases.in: Ochs H.D. Smith C.E. Puck J.M. Primary Immunodeficiency Disease. Oxford University Press, Oxford, UK1999: 459-475Google Scholar]. These differences were observed for HSCT performed with matched and nonmatched donors alike, and MHC class II immunodeficiency seemed to carry a poor prognosis, especially after HLA nonidentical transplantation, with only 32% of patients surviving to 1 year [6Antoine C. Muller Cant A. Muller S. Cant A. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of European experience 1968–99.Lancet. 2003; 361: 553-560Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar]. The low survival after HLA-identical HSCT (53%) was likely related to the incidence of preexisting viral infections and was associated with a high incidence of acute graft-versus-host disease (aGVHD) [8Renella R. Picard C. Neven B. et al.Human leucocyte antigen–identical haematopoietic stem cell transplantation in major histocompatiblity complex class II immunodeficiency: reduced survival correlates with an increased incidence of acute graft-versus-host disease and preexisting viral infections.Br J Haematol. 2006; 134: 510-516Crossref PubMed Scopus (34) Google Scholar]. An interesting observation in long-term transplantation survivors is the persistence of a relative CD4 T cell lymphopenia, possibly because of a lack of HLA class II molecules on thymic epithelial cells [5Klein C. Cavazzana-Calvo M. Le Deist F. et al.Bone marrow transplantation in major histocompatibility complex class II deficiency: a single-center study of 19 patients.Blood. 1995; 85: 580-587PubMed Google Scholar].Given the available HSCT protocols for children with MHC II deficiency, intensive pretransplantation conditioning appears to be a prerequisite for reliable engraftment and complete immune reconstitution. But, this conditioning is associated with an increased risk of short-term and long-term toxicity, particularly infections and end-organ decompensation, leading to a high rate of treatment-related mortality, especially in older children who acquire organ dysfunction. Late adverse effects, including growth retardation, infertility, and secondary malignancies, also are of concern.Driven by concerns about myeloablative (MA) regimens, some groups have reported success using reduced-intensity conditioning (RIC) regimens in patients with hematologic malignancies [9Giralt S. Estey E. Albitar M. et al.Engraftment of allogeneic hematopoietic progenitor cells with purine analog–containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy.Blood. 1997; 89: 4531-4536PubMed Google Scholar, 10Slavin S. Nagler A. Naparstek E. et al.Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases.Blood. 1998; 91: 756-763PubMed Google Scholar, 11Childs R. Clave E. Contentin N. et al.Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses.Blood. 1999; 94: 3234-3241PubMed Google Scholar]. Recent reports of RIC regimen-based HSCT in patients with primary immunodeficiencies and significant organ dysfunction indicated good engraftment and immune reconstitution with minimal toxicity and GVHD [12Amrolia P. Gaspar H.B. Hassan A. et al.Nonmyeloablative stem cell transplantation for congenital immunodeficiencies.Blood. 2000; 96: 1239-1246PubMed Google Scholar]. In one series, high-risk patients treated with RIC-based HSCT had better survival than those treated with MA HSCT (94% vs 53%) [13Rao K. Amrolia P.J. Jones A. et al.Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen.Blood. 2005; 105: 879-885Crossref PubMed Scopus (192) Google Scholar]. Here we describe the outcomes of a large series of patients with MHC II deficiency who underwent HSCT at a single center using MA conditioning and