Successful haploidentical PBSCT with subsequent T‐cell addbacks in a boy with HyperIgM syndrome presenting as severe congenital neutropenia

Abstract

HIGM syndrome is a group of primary immunodeficiency disorders characterized by recurrent bacterial and opportunistic infections; it is also associated with normal to elevated serum IgM levels and a concomitant deficiency of IgG, IgA, and IgE. In this report, we give account of a boy with X-linked HIGM and a novel Y172C mutation within his CD40LG gene. He presented with severe neutropenia as the dominating symptom. His bone marrow showed maturation arrest at the promyelocyte/myelocyte stage, typical of congenital neutropenia. This boy suffered from life-threatening infections and required high doses of rhG-CSF, and a haploidentical PBSCT was also successfully performed, thus leading to reconstitution of CD40L expression on activated CD4+ T cells (as assessed with flow cytometry six months after the procedure). Two low-dose T-cell addbacks were required to re-establish full donor chimerism and clear CMV reactivation. The report demonstrates that in select cases, alternative donor allogeneic HSCT supported by DLI may be effective in correcting the defect in X-linked HIGM, and HSCT in HIGM children is not necessarily limited to matched sibling donor transplantation.

Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single Institution Experience

“…Conservative management consists of immunoglobulin replacement therapy, prophylaxis against PJP, granulocyte‐colony stimulating factor (GCSF) for severely neutropenic patients, rCD40L therapy, and measures to decrease the risk of cryptosporidium infections, such as avoiding swimming in ponds and lakes and drinking boiled water . However, the only curative therapy is allogeneic hematopoietic stem cell transplantation (HSCT), as suggested by limited published data . Also, advances in diagnosis, donor selection, preparative regimens, and supportive care have led to improved outcomes following transplantation for primary immunodeficiencies .…”

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

“…14,15 Since Kolb et al first reported sustained remission after DLI in patients with CML relapse after allogeneic BMT in 1990, 16 unmanipulated DLI has become the mainstay allogeneic cellular therapy. However, owing to high risk of GVHD, 17,18 broad use of this monotherapy had been limited until 1996 when an Israeli group described a new approach using lymphocytes treated in vivo or in vitro with recombinant IL-2, by which better therapeutic response was achieved even in those who were previously resistant to unmanipulated DLI. 19 The aim of using DLI in hematological malignancies is to enhance the responsiveness and, at the same time, to lessen the toxicity.…”

Combined umbilical cord blood and bone marrow transplantation from a sibling in a patient with Fanconi anemia

“…The availability of donor blood/bone marrow for posttransplant immunological manipulations played a crucial role in graft rejection prophylaxis and establishing sustained and stable donor chimerism. In the setting of non-malignant disease, GVHD confers no advantage and therefore donor lymphocyte infusion (DLI) with the associated high risk of GVHD, has been only used exceptionally [14,15]. Nevertheless, the presented case demonstrates efficacy of DLI in the induction of donor chimerism.…”