Indication for allogeneic stem cell transplantation in Glanzmann’s thrombasthenia

Abstract

SummaryGlanzmann’s thrombasthenia (GT) is an autosomal recessive disorder characterized by a lack of thrombocyte aggregation due to the absence of thrombocyte glycoproteins IIb and αIIbβ3. The role of haematopoietic stem cell transplantation (HSCT) in GT remains controversial. However, HSCT offers the only curative approach for patients with a severe clinical phenotype.In this review, we will discuss the limitation of current status evidence and the specific risk of GT, in particular the alloimmunization and refractoriness to thrombocyte infusions. 19 successful HSCT in 18 GT type I patients have been reported. Mean age at transplantation was 5 years. All patients are still alive. The majority received sibling bone marrow transplant with busulfan and cyclophosphamid conditioning. GvHD incidence was within the normal range, but 10 patients showed alloimmunization of thrombocytes. Median follow up is 25 months.

High-level transgene expression in induced pluripotent stem cell–derived megakaryocytes: correction of Glanzmann thrombasthenia

“…4 A few patients have undergone allogeneic bone marrow transplantation with its attendant complications. 5 Gene therapy holds promise for a cure for GT and other IPDs. A recent study in an aIIb-deficient canine model for GT showed improved hemostasis with modest restoration of platelet surface aIIbb3 by lentiviral transduction of mobilized hematopoietic stem cells.…”

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“…A literature search showed only 19 successful hematopoietic stem cell transplants in 18 previously reported patients. 12 The most recent cases were reported in 2011. 12 Our case was an 18-year-old woman and was older than previously reported cases except for 1 Reduced conditioning is less toxic and was used for stem cell transplant for children with peripheral blood cells from an unrelated donor.…”

“…12 The most recent cases were reported in 2011. 12 Our case was an 18-year-old woman and was older than previously reported cases except for 1 Reduced conditioning is less toxic and was used for stem cell transplant for children with peripheral blood cells from an unrelated donor. 7 The incidence of GVHD was within usual range in that report, and our patient developed mild acute and extensive chronic GVHD that responded and was controlled with our treatment.…”

“…[7][8][9][10][11] A literature search showed 18 cases of Glanzmann thrombasthenia treated with allogeneic hematopoietic stem cell transplant. 12 We report an 18-year-old woman who presented with severe, repeated bleeding. She was treated successfully with allogeneic hematopoietic stem cell transplant in our center from her HLA-matched sister.…”

Megakaryocyte- and megakaryocyte precursor–related gene therapies

“…38 Allogenic bone marrow transplant has been used successfully to correct dogs and humans with GT, 39,40 although transplant-related complications (eg, graft-versus-host disease, graft failure) has limited the use of this treatment. 41,42 Gene transfer into cytokine-mobilized CD34…”