Allogeneic hematopoietic stem cell transplantation for nonmalignant hematologic disorders using chemotherapy-only cytoreductive regimens and T-cell-depleted grafts from human leukocyte antigen–matched or –mismatched donors

Abstract

Non-malignant hematologic disorders (NMHD) of childhood comprise a variety of disorders including acquired severe aplastic anemia, and inherited marrow failure syndromes. Patients with high risk NMHD without matched related donors fare poorly with allogeneic hematopoietic alternative donor stem cell transplantation (allo-HSCT) and are at high risk for developing graft versus host disease following unmodified grafts. We retrospectively analyzed data on 18 patients affected by NMHD, lacking an HLA-identical sibling donor, who underwent an alternative donor allo-HSCT at our institution between April 2005 and May 2013. 50% had received prior immunosuppressive therapy, 72% had a history of infections, and 56% were transfusion-dependent at the time of transplant. Cytoreduction included a combination of three of five agents: fludarabine, melphalan, thiotepa, busulfan and cyclophosphamide. Grafts were T-cell depleted. All evaluable patients engrafted. Five died of transplant complications. The cumulative incidence of graft versus host disease was 6%. No patient had recurrence of disease. 5-year overall survival was 77%. Age at transplant <6 years was strongly associated with better survival. Based on these results, transplant with chemotherapy-only cytoreductive regimens and T-cell depleted stem cell transplants could be recommended for patients with high risk NMHD especially at a younger age.

Outcome Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia Treated with Total Body Irradiation–Free Allogeneic Hematopoietic Stem Cell Transplantation: Comparison of Patients with and Without Central Nervous System Involvement

“…In this context, investigators began to evaluate reduced-intensity and even TBI-free conditioning regimens, and so, the use of such regimens has shown an increasing trend [20,[44][45][46]. Initially, a consensus was reached that TBI-excluding preparative regiments might be effective for patients with nonmalignant hematologic disorders [20,43,47]. Subsequently, hematologists recognized the feasibility of excluding TBI for nonlymphoblastic leukemias, including AML and CML, [48].…”

Impact of Day 14 Peripheral Blood Chimerism after Allogeneic Hematopoietic Stem Cell Bone Transplantation on the Treatment Outcome of Non-Malignant Disease

“…Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been a curative modality for various non-malignant diseases, including bone marrow failure syndromes (BMFS), primary immunodeficiency diseases, hemophagocytic lymphohistiocytosis, inherited metabolic disorders, and many other hematologic disorders 1234. Analysis of the chimerism status has become an important diagnostic tool for post-transplant investigation of engraftment and prediction of disease recurrence.…”

CD3+/CD19+ Depleted Matched and Mismatched Unrelated Donor Hematopoietic Stem Cell Transplant with Targeted T Cell Addback Is Associated with Excellent Outcomes in Pediatric Patients with Nonmalignant Hematologic Disorders

“…We have used various methods of ex vivo partial T cell depletion (pTCD) in unrelated donor HSCT for nearly 2 decades [17À19]. pTCD enables reduction in rates of severe GVHD while avoiding the higher rates of graft rejection and infections seen with complete T cellÀdepletion strategies [20,21]. These pTCD strategies are particularly beneficial in reducing risk of GVHD in patients in whom a fully MUD cannot be identified and consequently a 7/8 or 9/10 match is the best available donor, a scenario common for patients of non-European ancestry who lack sibling donors [22].…”