Reduced-Intensity Regimens in Allogeneic Hematopoietic Stem Cell Transplantation for Hemoglobinopathies

Abstract

The only well-established curative therapy for patients with hemoglobinopathies is allogeneic hematopoietic stem cell transplantation (HSCT), which, in the last 20 years, has been mainly performed from an HLAmatched, related donor, using bone marrow as source of hematopoietic progenitors. More recent studies indicate that HSCT from unrelated donors may offer results comparable to those obtained with HLAidentical family donors, provided that stringent criteria of compatibility are employed for selecting the donor. Cord blood transplantation was also suggested to be an equally effective, but safer, procedure than bone marrow transplantation, due to the lower incidence and severity of both acute and chronic graft-versushost disease. In view of the early, as well as late, morbidity and mortality associated with conventional myeloablative transplantation in patients with hemo-

Donor/recipient mixed chimerism does not predict graft failure in children with -thalassemia given an allogeneic cord blood transplant from an HLA-identical sibling

“…However, the available evidence indicates that the barrier to stable partial donor engraftment after minimally toxic regimens employed for transplantation in patients with hemoglobinopathies seems to be much more difficult to overcome than in adults with hematologic malignancies. 46,47 In summary, this is the first study addressing the issue of donor/recipient chimerism in patients with β-thalassemia undergoing RD-CBT from an HLA-identical relative in a longitudinal study; it shows that mixed chimerism sustained over time in circulating mononuclear cells can be found in a large proportion of these patients, without predicting the occurrence of graft failure.…”

Mixed haematopoietic chimerism for sickle cell disease prevents intravascular haemolysis

“…Thus, the development of therapies that correct intravascular haemolysis and its complications are increasingly recognized as important for the long‐term prognosis of the SCD patient. Haematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for SCD, and recent improvements in supportive care and the development of reduced‐intensity conditioning regimens have substantially lessened the severity of the immediate toxicities of the transplant procedure (Locatelli, 2006). When lower intensity conditioning regimens are utilized, host haematopoiesis is incompletely eliminated, and mixed haematopoietic chimerism frequently results.…”

Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin

“…However, the ability of HSCT to cure a broad range of non-malignant diseases is severely underutilized. Hemoglobinopathies, such as sickle cell anemia and thalassemia, which affect millions of patients globally, are curable by HSCT when stable mixed chimerism (>25% donor-derived leukocytes in peripheral blood) restores hemoglobin and red blood cell parameters to >95% of normal 2 ; disease-free survival in such cases is >90% 3–6 . In addition to hemoglobinopathies, the hematologic manifestations of other non-malignant conditions, such as Fanconi anemia 7 and Wiskott-Aldrich syndrome 8 ; genetic conditions that cause neurologic decline, such as metachromatic leukodystrophy 9 ; and immunodeficiencies, such as adenosine deaminase severe combined immunodeficiency (SCID) 10 , can be cured by HSCT.…”