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Unrelated cord blood transplantation and reduced-intensity conditioning regimen for graft failure in a child with Major Histocompatibility Complex class II deficiency

Bone Marrow Transplantation volume 43, pages 817–818 (2009)Cite this article

Allogeneic hematopoietic SCT is currently the only procedure capable of curing children with MHC class II deficiency.1, 2, 3, 4 However, the survival rate is much lower than in other primary immunodeficiency disorders (PID), with graft failure and GVHD being the major causes of treatment failure.2, 4 The optimal approach to hematopoietic SCT in children with PID who lack a matched sibling donor is controversial.5 Some centers continue to use myeloablative conditioning regimen in children with PID who undergo HLA-mismatched related T-cell-depleted BMT associated with high risk of graft failure.2, 5 However, recent success with reduced-intensity conditioning regimen before unrelated BMT shows that this may provide better engraftment, immune reconstitution and survival for patients with PID than the previous alternative.6, 7 Very few patients with this pediatric emergency have undergone transplantation choosing umbilical cord blood as a first choice of hematopoietic stem cell source, despite the significantly faster availability of banked cryopreserved umbilical cord blood units and the higher frequency of rare haplotypes compared with BM registries.8, 9, 10

In September 2004, a 1-month-old boy with the diagnosis of MHC class II deficiency was referred to our BMT Service. Previously, his two brothers and one sister had died of recurrent infections in their hometown before the age of 7 months. A fourth child was born, and she was diagnosed in our hospital with MHC class II deficiency. She underwent a T-cell-depleted haploidentical BMT in another institution, but died of a severe acute GVHD. This family belongs to Kolla Amerindians, an ethnic minority from the far northwest of Argentina. During the neonatal period, the boy had received BCG immunization without any complications. After his evaluation, a T-cell-depleted haploidentical BMT from his mother was performed. Conditioning consisted of BU (20 mg/kg), CY (200 mg/kg) and rabbit antithymocyte globulin (30 mg/kg). The graft was T-cell-depleted by means of soybean agglutination and E-rosetting. CsA was administered for GVHD prophylaxis. On day +7, he developed acute skin and intestinal GVHD, which resolved with methylprednisolone. On day +43, grade III acute intestinal and liver GVHD were confirmed by biopsies; tacrolimus was therefore initiated after CsA was discontinued. On day +56, the boy developed congestive heart failure, and an echocardiography showed hypertrophic cardiomyopathy. Thus, despite the improvement in clinical manifestations and laboratory findings, tacrolimus was stopped and methylprednisolone was continued at a dose of 2 mg/kg/day. On day +83, the GVHD resolved and the cardiomyopathy had regressed completely. DR expression on monocytes and B lymphocytes was only transitorily detected during the first 6 months post transplantation (Table 1).

Table 1 Immunological characteristics pre-BMT, post-BMT and post-CBT
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Authors and Affiliations

  1. Bone Marrow Transplantation Service, Hospital de Pediatría ‘Prof Dr Juan P Garrahan’, Buenos Aires, Argentina

    M Bonduel, R Staciuk & C Figueroa

  2. Immunology Service, Hospital de Pediatría ‘Prof Dr Juan P Garrahan’, Buenos Aires, Argentina

    M Oleastro & J Rossi

  3. Transfusion Medicine Service, Hospital de Pediatría ‘Prof Dr Juan P Garrahan’, Buenos Aires, Argentina

    C Gamba & A del Pozo

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  1. M Bonduel
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Correspondence to M Bonduel.

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Bonduel, M., Staciuk, R., Figueroa, C. et al. Unrelated cord blood transplantation and reduced-intensity conditioning regimen for graft failure in a child with Major Histocompatibility Complex class II deficiency. Bone Marrow Transplant 43, 817–818 (2009). https://doi.org/10.1038/bmt.2008.399

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