Durable remission following a third allogeneic stem cell transplantation in a patient with repeatedly relapsing SAA. The importance of stroma cells for sustained engraftment?

Abstract

Diagnosis of acquired AATP which finally progressed to SAA was established in an eight-yr-old boy. PBSCT from an HLA-identical unrelated donor using high numbers of CD34+ selected stem cells was performed and resulted in complete remission for almost two yr. However, SAA reoccurred with 100% donor hematopoiesis and was reversed by a second CD 34+ selected PBSCT from the same donor. Declining blood cell counts after an interval of two yr indicated second relapse. Chimerism analysis in PB and BM aspirates revealed a small autologous cell population of 4-12% and 2-11%, respectively. Finally, a third transplantation with unmanipulated BM from the same donor resulted in sustained remission with 100% donor hematopoiesis. The patient is in complete remission for more than five yr following the third SCT. Late graft failure or late graft rejection known to occur after transplantation of highly purified CD34+ cells, or even graft exhaustion caused by stromal dysfunction due to the underlying disease necessitated a third transplantation. Regardless of the cause of relapse, transplantation of unmanipulated BM instead of highly purified PBSCTs led to a permanent and stable engraftment in a third attempt after two previous PBSCTs.

Congenital amegakaryocytic thrombocytopenia: The diagnostic importance of combining pathology with molecular genetics

“…The prolonged thrombocytopenia following SCT is of interest, especially as no recipient cells were documented. Abnormal mesenchymal stem cell–stromal interactions, in patients with amegakaryocytic thrombocytopenia and aplastic anemia, may result in a defective bone marrow environment, making graft rejection and/or graft failure more likely 13.…”

Time to engraftment following allogeneic stem cell transplantation is significantly longer in patients with myelodysplastic syndrome than with acute myeloid leukemia

“…Since the stromal microenvironment following SCT remains of host origin, 14 we hypothesized that engraftment of normal donor stem cells post-SCT might be impaired. This assumption was also raised in a report by Weber-Mzell et al, 15 where the authors speculated that support by stroma-derived cells was the reason for durable engraftment in a patient with severe aplastic anemia and two failures of previous allogeneic peripheral blood SCT. The time required to achieve engraftment of donor stem cells, as well as patient-donor chimerism status post transplantation, is included in the majority of reports dealing with transplantation of AML and MDS patients as one group.…”

Homing of chloromethylbenzoyl ammonia-labeled bone marrow mesenchymal stem cells in an immune-mediated bone marrow failure mouse model in vivo

“…BMSCs also have immunoregulatory activity, which can reversibly inhibit the proliferation of T cells in mixed lymphocyte reactions. BMSCs inherently have low immunogenicity portability, which could be exploited for transplantations and play an important role in AA cell therapy (Ball et al, 2007;Weber-Mzell et al, 2007).…”