Abstract
Unmanipulated haploidentical stem cell transplantation (haploSCT) with post-transplant cyclophosphamide is an option for patients with advanced hematologic malignancies. It offers a platform both for non-major histocompatibility complex-restricted alloimmunity due to killer-like immunoglobulin receptor (KIR)-mediated mechanisms of natural killer lymphocyte regulation and for classical T-cell mediated antileukemic effects. The devastating long-term sequelae after total body irradiation (TBI) in children are encouraging omission of irradiation techniques in pediatric stem cell transplantations (SCT). Five children, 4 with acute leukemia and 1 with hemophagocytic lymphohistiocytosis, aged from 1 to 10 years, underwent haploSCT with post-transplantation cyclophosphamide. In all children, the conditioning regimen consisted of chemotherapy without TBI. The graft material was bone marrow (BM) in 4 cases and peripheral blood stem cells in 1 case. Three out of 5 leukemic patients showed better KIR haplotype associated with augmented alloreactivity. Engraftment with complete donor chimerism was achieved in 4 patients, and 1 recipient died before leukocyte recovery. Three patients developed skin acute graft-versus-host-disease (aGvHD), 1 gut aGvHD and 1 liver aGvHD. In 2 recipients, chronic graft-versus-host-disease (cGvHD) was observed (1 limited and 1 extensive). The 4 engrafted patients were alive and in complete remission 3, 9, 32, and 36 months after transplantation. A T-cell count of 200 cells/uL was reached 90 days after haploSCT in all patients. HaploSCT with TBI-free protocols can be a viable option for heavily pretreated patients with advanced malignancies.
Highlights
The limited availability of matched stem cell donors was, in the past, a vital problem for patients requiring allogeneic stem cell transplantation (SCT) because partially matched donors could not have been accepted due to the high risk of a fatal graft-versus-host-disease (GvHD) and high risk of rejection
HaploSCT with total body irradiation (TBI)-free protocols can be a viable option for heavily pretreated patients with advanced malignancies
One patient died before leukocyte recovery on day +10 due to gut associated Achromobacter xylosoxidans sepsis
Summary
The limited availability of matched stem cell donors was, in the past, a vital problem for patients requiring allogeneic stem cell transplantation (SCT) because partially matched donors could not have been accepted due to the high risk of a fatal graft-versus-host-disease (GvHD) and high risk of rejection. The first successful attempt in SCT crossing the human leukocyte antigen barrier was achieved in 1983 with the development of T-lymphocyte depletion by differential agglutination with soybean agglutinin (SBA) and subsequent E-rosette depletion.[1] Haploidentical stem cell transplantation (haploSCT) had become a part of transplant methods in children since the introduction of immunomagnetic selection in 1996.2 Techniques enabling physical removal of donor T-lymphocytes from the graft material were highly effective, but high cost and the requirements for an established graft processing lab were limiting interest in haploSCT despite further refinements Another milestone in haploSCT was marked by successful application of post-transplantation GvHD prophylaxis with cyclophosphamide (PTCY),[3] which in turn started an avalanche of clinical trials with unmanipulated (T-cell replete) haploSCT. It offers a platform both for non-major histocompatibility complex-restricted alloimmunity due to killer-like immunoglobulin receptor (KIR)-mediated mechanisms of natural killer lymphocyte regulation and for classical T-cell mediated antileukemic effects
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