Nonmyeloablative stem cell transplantation for congenital immunodeficiencies

Abstract

The optimal approach for stem cell transplantation in children with immunodeficiency has yet to be determined. Conditioning therapy is necessary for reliable engraftment and full immune reconstitution; however, the beneficial effect of cytoreductive conditioning is counterbalanced by increased short- and long-term treatment-related toxicity. Whether bone marrow transplantation with a nonmyeloablative preparative regimen was sufficient for the establishment of donor immune reconstitution, with the resultant correction of disease phenotype, was investigated. Eight patients with severe immunodeficiency states underwent T-cell replete bone marrow transplantation from a human leukocyte antigen-matched unrelated (n = 6) or sibling (n = 2) donor with nonmyeloablative conditioning using a fludarabine–melphalan–anti-lymphocyte globulin-based regimen. All patients had severe organ dysfunction that precluded transplantation with conventional conditioning. All patients were engrafted with predominantly donor hematopoiesis, and the duration of neutropenia was brief. Significant acute graft-versus-host disease (GVHD) did not develop, but one patient had limited chronic GVHD. One patient died of disease recurrence, and 3 have stable, mixed chimerism. At a median follow-up of 1 year, all patients have had good recovery of CD3+ T-cell numbers, and 6 of 7 evaluable patients have normal phytohemagglutinin stimulation indices. The rate of immune reconstitution is comparable with that of historical controls undergoing standard myeloablative protocols. Two patients with CD40 ligand deficiency now show significant expression, and a patient with adenosine deaminase deficiency has improved deoxy adenosine triphosphate metabolites. In summary, it has been demonstrated that nonmyeloablative stem cell transplantation permits rapid engraftment from both sibling and unrelated donors with minimal toxicity even in the presence of severe organ dysfunction. If long-term immune reconstitution of patients treated with this protocol is demonstrated, it is believed this approach might offer significant advantages compared with standard protocols by combining adequate immune reconstitution with reduced short- and long-term toxicity.

Unrelated cord blood transplantation can restore hematologic and immunologic functions in patients with Chediak–Higashi syndrome

“…Similar observations have also been made in patients with FHLH who have undergone HSCTs, in whom even low numbers of normal leukocytes were sufficient to control the abnormal activation of macrophages and lymphocytes (12,16). Hence, reports have suggested that full myeloablative conditioning might not be necessary (9,17), particularly in patients with preexisting comorbidities, as the use of reduced-intensity conditioning in CHS may be a potential way to reduce the high transplantation-related mortality (18). It also provides rapid engraftment and reduces shortand long-term toxicity, thus offering acute survival advantage.…”

Hematopoietic stem cell transplant for hyper‐IgM syndrome due to CD40L defects: A single‐center experience

“…A MEDLINE literature review from 1993 to 2013 was conducted. A total of 21 papers were identified (Table S1), with 20 written in English (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)36) and one written in Dutch (30). The majority of publications were case reports, along with a few single-center studies (16)(17)(18).…”

“…Stem cell transplant therapy was therefore recently tested as a potential to cure for this disease (14,15), but only a few single-center studies have been published (16)(17)(18). In addition, a European survey was published approximately a decade ago (19), but the available publications are otherwise limited to case reports (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). This report represent a single-center experience of HSCT in a cohort of five patients with HIGM I syndrome.…”

Successful unrelated cord blood transplantation for chronic granulomatous disease: A case report and review of the literature

“…RIC regimens are associated with less toxicity and may be an alternative option for nonmalignant disease, particularly for those who already have several complications (7,(17)(18)(19)(20). However, for CGD patients who have normal immunity except for oxidative killing and have never received myelosuppressive chemotherapy, the RIC regimen which we used at the first transplantation would not be sufficient to establish enough donor chimerism after haploidentical BMT.…”