Reduced Intensity Conditioning (RIC) Regimen of Alemtuzmab (A), Fludarabine (F), and Melphalan (M) for Transplantation of Pediatric Non-Malignant Hematologic Disorders (NMHD): Outcome Affected by Stem Cell Source.

Abstract 3490

Hematopoietic stem cell transplantation (HSCT) can be curative for NMHD but is associated with acute toxicities and long-term squeale. Use of RIC regimen may minimize these complications but the risk of graft failure is high. The RIC regimen of A given three weeks and F + M one week prior to HSCT has been previously reported. We reviewed a series of 24 children, median age of 3 years (0.4 to 22 years), with sickle cell disease (SCD) (8), hemophagocytic lymphohistiocytosis (HLH) (7), thalassemia (2), congenital neutropenia (2), chronic granulomatous disease (2), leukocyte adhesion deficiency (1), Chediak Higashi disease (1), and Wiskott Aldrich syndrome (1) transplanted using this regimen. Stem cell sources were umbilical cord blood cells (UCB) (12), related donor (RD) marrow/blood stem cells (7/1), and matched unrelated donor (MUD) marrow /blood stem cells (3/1). UCB were 6/6 (3), 5/6 (8), and 4/6 (1) HLA-matched, with a median cell dose 12.6 (range 5.2–25.3) × 10⁷ TNC/kg. All MUD and 7/8 RD were 10/10 matched. The RIC regimen was well tolerated. With a median follow-up of 555 days (range 109-1, 128), all patients are alive. Nine patients had complete donor chimerism (DC), defined as > 95% donor cells, detected by PCR-based methodology. Three developed primary graft failure: SCD (1), HLH (1) and leukocyte adhesion deficiency (1), all after UCB transplants. Twelve developed mixed chimerism (MC) (3/8 MSD, 2/4 MUD, and 7/9 UCB) - 8 MC were detected before, and 4 detected after, 2 months post HSCT (latest at 15 months). Of these 12, eight either converted to DC or remained with stable MC. Four (2/4 MUD and 2/9 UCB recipients) have progressive declining chimerism: 2 received donor lymphocyte infusion (DLI) and 2 lost graft function. Lineage-specific chimerism studies were followed serially in 9 recipients with MC. Myeloid MC developed earlier, was more severe, and was the only lineage affected in 4 recipients. Lymphoid MC tended to be more stable. Viral reactivation was common in the first 3 months after HSCT and included cytomegalovirus (6), herpesvirus type 6 (5), adenovirus (3), and Epstein-Barr virus (1). There was no association between viral infection and graft failure. Grade II-IV acute graft-versus-host disease (GVHD) developed in 13 patients, and chronic GVHD was diagnosed in 12 patients (limited to skin 5, extensive 7). At the time of this report 7 of 21 patients remain on systemic immunosuppression. In summary the RIC regimen of A, F, and M was well tolerated with no mortality. Primary disease control was achieved in 11/12 peripheral blood or marrow recipients (2 after DLI); engraftment was less predictive with UCB grafts and 8/12 achieved disease control. Thus RIC can lead to successful outcomes in NMHD: UCB grafts may benefit from further intensification of immune suppression pre-HSCT.