Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia

Abstract

A multicenter investigation of allogeneic bone marrow transplantation for children with sickle cell disease was conducted that included 27 European and North American transplant centers. Fifty-nine patients who ranged in age from 3.3 to 15.9 years (median, 10.1 years) received HLA-identical sibling marrow allografts between September 1991 and April 2000. Fifty-five patients survive, and 50 survive free from sickle cell disease, with a median follow-up of 42.2 months (range, 11.8 to 115 months) after transplantation. Of the 50 patients with successful allografts, 13 developed stable mixed donor-host hematopoietic chimerism. The level of donor chimerism, measured > or =6 months after transplantation in peripheral blood, varied between 90% and 99% in 8 patients. Five additional patients had a lower proportion of donor cells (range, 11% to 74%). Among these 5 patients, hemoglobin levels varied between 11.2 and 14.2 g/dL (median, 11.3 g/dL; mean, 12.0 g/dL). In patients who had donors with a normal hemoglobin genotype (Hb), the Hb S fractions were 0%, 0%, and 7%, corresponding to donor chimerism levels of 67%, 74%, and 11%, respectively. Among patients who had donors with sickle trait, the Hb S fractions were 36% and 37%, corresponding to donor chimerism levels of 25% and 60%, respectively. Thus, allograft recipients with stable mixed chimerism had Rb S levels similar to donor levels, and only 1 patient required a red blood cell transfusion beyond 90 days posttransplantation. None of the patients have experienced painful events or other clinical complications related to sickle cell disease after transplantation. These observations strongly suggest that patients with sickle cell disease who develop persistent mixed hematopoietic chimerism after transplantation experience a significant ameliorative effect.

Increasing mixed chimerism and the risk of graft loss in children undergoing allogeneic hematopoietic stem cell transplantation for non-malignant disorders

“…The study included 24 children (median age 7.6 years, range (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)) undergoing first unmodified allogeneic HSCT for a non-malignant disorder at University of California, San Francisco, (UCSF) Children's Hospital, Pediatric Blood and Marrow Transplant Unit (PBMTU) between January 2001 and March 2007. Only patients who received fludarabine-or cyclophosphamide-based conditioning regimen and had chimerism testing done by the STR technique were included.…”

“…4,11 However, experience in patients with hemoglobinopathies indicates that chimerism can fluctuate for years following transplant and, once tolerance of donor cells is achieved, rejection does not occur even with a very low percentage of donor WB engraftment. [12][13][14][15][16][17] Our institution has been using fludarabine-based conditioning regimens for children with non-malignant disorders since the year 2000. 8 We introduced routine post transplant short-tandem repeats (STR) subset chimerism testing in January 2001.…”

Outcome of hematopoietic cell transplantation in children with sickle cell disease, a single center's experience

“…10 An early age at transplant before the onset of severe chronic organ damage is likely to provide the best outcomes. Thus, it is important to identify SCD patients early as serious candidates for HCT.…”

Reconsideration of Age as a Contraindication for Curative Therapy of Sickle Cell Disease

“…The event-free survival and overall survival reported in this updated study of adults, aged 16 through 65 years, are comparable with those of matched sibling transplants in children with sickle cell disease, aged 2 through 22 years, receiving myeloablative conditioning regimens. [13][14][15] Importantly, both acute (0%) and chronic graft-vs-host disease (0%) were significantly lower than the rates reported for children (12.5%-40% and 40%, respectively). In addition, both morbidity and treatment-related mortality appear significantly less than those previously reported about children receiving matched-sibling transplants despite significantly greater fixed organ dysfunction and alloimmunization in these adult transplant recipients.…”

“…However, this cohort does represent an older group of patients with sickle cell disease who have significant premorbid conditions, and the patients tolerated the preparative regimen with engraftment rates similar to myeloablative regimens, even among children with sickle cell disease. [13][14][15] A subset of patients had donor CD3 chimerism of less than 50%, and these adults continued to take immunosuppression medications. When comparing the pretransplant medical regimen with posttransplant, these patients should still be experiencing a more positive experience.…”