Split chimerism between nucleated and red blood cells after bone marrow transplantation for haemoglobinopathies

Andreani, Marco; Testi, Manuela; Battarra, Mariarosa; Lucarelli, G

doi:10.4161/chim.15057

Cited by 25 publications

(24 citation statements)

References 18 publications

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“…23 Moreover, the proportion of donor-derived erythroid precursors is equivalent to that observed in the mature NC, rather than that of the RBC. These results suggest that for patients with MC, a selective advantage of maturation of donor erythroid precursors might successfully offset the problems associated with the recipient’s ineffective erythropoiesis and that evaluation of RBC chimerism might provide relevant clinical information in the routine monitoring of engraftment.…”

Section: Thalassemiamentioning

confidence: 99%

“…22 Emerging evidence supports the importance of looking at lineage-specific chimerism, for example, erythroid chimerism to help guide clinical decision making. 23 Evidence looking at MC in other inherited BMFs has not been studied; however, it is likely that anything less than complete engraftment increases the risk of leukemia from the remaining recipient hematopoiesis.…”

Section: Engraftmentmentioning

confidence: 99%

See 1 more Smart Citation

Alternative donor transplant of benign primary hematologic disorders

Tolar

Sodani²,

Symons

2015

Bone Marrow Transplant

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Hematopoietic SCT is currently the only curative therapy for a range of benign inherited and acquired primary hematologic disorders in children, including BM failure syndromes and hemoglobinopathies. The preferred HLA-matched sibling donor is available for only about 25% of such children. However, there has been substantial progress over the last four decades in the use of alternative donors for those without a matched sibling—including HLA-matched unrelated donors, HLA-haploidentical related donors and unrelated-donor umbilical cord blood—so that it is now possible to find a donor for almost every child requiring an allograft. Below, we summarize the relative merits and limitations of the different alternative donors for benign hematologic conditions, first generally, and then in relation to specific disorders, and suggest recommendations for selecting such an alternative donor.

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Section: Thalassemiamentioning

confidence: 99%

Section: Engraftmentmentioning

confidence: 99%

Alternative donor transplant of benign primary hematologic disorders

Tolar

Sodani²,

Symons

2015

Bone Marrow Transplant

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“…Mixed chimerism after nonmyeloablative HSCT has been found beneficial for both thalassemia and SCA patients, [76][77][78][79] where a limited percentage of engrafted donor cells may be sufficient to overcome disease phenotype. Thus, the rationale for lowerintensity conditioning is relevant, because of its ability to promote mixed tolerance and the decreased risk for transplant-related toxicity and mortality, which will open HSCT-curative treatment to more patients.…”

Section: Potential Application Of Megadose Hsct With Tcm Veto Cells Fmentioning

confidence: 99%

The role of donor-derived veto cells in nonmyeloablative haploidentical HSCT

Or-Geva

Reisner

2015

Bone Marrow Transplant

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Allogeneic HSCT offers a route for achieving immune tolerance via mixed chimerism and remains the sole curative option for many nonmalignant, autoimmune and metabolic diseases. Present-day improvements of nonmyeloablative protocols are increasing the safety of HSCT, thereby widening the target population and resurrecting the interest of HSCT application as a platform for tolerance induction in organ transplantation. Using high cell doses of T-cell-depleted (TCD) grafts has been shown to circumvent graft-vs-host disease, leaving graft rejection as the main hindrance due to the robust host immunity that remains after mild conditioning. In this review we highlight the advantages of utilizing unique non-alloreactive 'veto' cells, such as anti-third party central memory CD8 T cells (Tcm), to enable induction of mixed chimerism after megadose HSCT under nonmyeloablative conditioning. Co-administration of HSCT with veto Tcm allows for induction of mixed chimerism that was successfully translated into immune tolerance, as demonstrated by engraftment of donor-type skin grafts. These veto Tcm cells have been shown to specifically eradicate anti-donor host T cells, through lymph-node sequestration and deletion, thus sparing host immunity and circumventing the need for life-long immunosuppression. Hence, data indicate that this treatment modality of combined TCD HSCT and adoptive transfer of Tcm veto cells under nonmyeloablative conditions may serve as a valuable tool for treatment of patients with a wide array of disorders such as hemoglobinopathies, autoimmune diseases and as a prelude for organ tolerance.

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“…We recently published a paper describing four long-term transplanted patients affected by hemoglobinopathies (Andreani et al 2011a). These patients are characterized by the presence of few donor-engrafted nucleated cells, both in the peripheral blood and in the bone marrow; the majority of the erythrocytes were of donor origin.…”

Section: Mixed Chimerism Following Hsct For Thalassemiamentioning

confidence: 99%

“…All patients had sustained engraftment with donor chimerism of 100%, except for one patient, who showed a persistent MC with 25% of donor cells. Starting 2 mo after transplantation, this patient showed a progressive decrease in donor chimerism until 25%; she had stable mixed chimerism for more than 4 yr without SCD-related events and was transfusion independent (Andreani et al 2011a). All of the remaining patients had full donor chimerism in lymphoid and myeloid lineages.…”

Section: Hematopoietic Stem Cell Transplantation For Sickle Cell Diseasementioning

confidence: 99%

Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Anemia

Lucarelli

Isgrò²,

Sodani³

et al. 2012

Cold Spring Harbor Perspectives in Medicine

141

106

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The globally widespread single-gene disorders b-thalassemia and sickle cell anemia (SCA) can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT treatment of thalassemia has substantially improved over the last two decades, with advancements in preventive strategies, control of transplant-related complications, and preparative regimens. A risk class-based transplantation approach results in disease-free survival probabilities of 90%, 84%, and 78% for class 1, 2, and 3 thalassemia patients, respectively. Because of disease advancement, adult thalassemia patients have a higher risk for transplant-related toxicity and a 65% cure rate. Patients without matched donors could benefit from haploidentical mother-to-child transplantation. There is a high cure rate for children with SCA who receive HSCT following myeloablative conditioning protocols. Novel nonmyeloablative transplantation protocols could make HSCT available to adult SCA patients who were previously excluded from allogeneic stem cell transplantation.

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Split chimerism between nucleated and red blood cells after bone marrow transplantation for haemoglobinopathies

Cited by 25 publications

References 18 publications

Alternative donor transplant of benign primary hematologic disorders

Alternative donor transplant of benign primary hematologic disorders

The role of donor-derived veto cells in nonmyeloablative haploidentical HSCT

Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Anemia

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