Pulmonary, Gonadal, and Central Nervous System Status after Bone Marrow Transplantation for Sickle Cell Disease

Abstract

We conducted a prospective, multicenter investigation of human-leukocyte antigen (HLA) identical sibling bone marrow transplantation (BMT) in children with severe sickle cell disease (SCD) between 1991 and 2000. To determine if children were protected from complications of SCD after successful BMT, we extended our initial study of BMT for SCD to conduct assessments of the central nervous system (CNS) and of pulmonary function 2 or more years after transplantation. In addition, the impact on gonadal function was studied. After BMT, patients with stroke who had stable engraftment of donor cells experienced no subsequent stroke events after BMT, and brain magnetic resonance imaging (MRI) exams demonstrated stable or improved appearance. However, 2 patients with graft rejection had a second stroke after BMT. After transplantation, most patients also had unchanged or improved pulmonary function. Among the 11 patients who had restrictive lung changes at baseline, 5 were improved and 6 had persistent restrictive disease after BMT. Of the 2 patients who had obstructive changes at baseline, 1 improved and 1 had worsened obstructive disease after BMT. There was, however, significant gonadal toxicity after BMT, particularly among female recipients. In summary, individuals who had stable donor engraftment did not experience sickle-related complications after BMT, and were protected from progressive CNS and pulmonary disease.

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

“…3,33 In a series studying 137 patients on chronic transfusion therapy for secondary stroke prevention, 31 patients had a second stroke while receiving chronic transfusion therapy. 33 Similar to the results described by Walters et al, 11 our series also showed a stabilizing effect on central nervous system function and prevention of future stroke. However, neurological toxicities due to calcineurin inhibitors can occur following allo-SCT 34,35 as noted in one patient.…”

“…With respect to pulmonary function, stability and improvement were observed at 2 years post allo-SCT, similar to the results that have been reported by Walters et al 11 following BU/CY conditioning and sibling BMT in pediatric recipients with SCD. Furthermore, stability in the pulmonary function tests post allo-SCT also suggests that our conditioning regimen did not induce significant long-term pulmonary toxicity post allo-SCT.…”

“…A major limitation to MAC conditioning followed by allo-SCT is long-term organ dysfunction. [10][11][12] An alternative is to utilize reduced-toxicity conditioning (RTC) regimens to decrease the risk of TRM. 13,14 This is defined as a regimen associated with myeloablation but associated with reduced toxicity secondary to conditioning.…”

Targeted Busulfan therapy with a steady-state concentration of 600–700 ng/mL in patients with sickle cell disease receiving HLA-identical sibling bone marrow transplant

“…Among evaluable male patients, four out of 13 patients tested had abnormal luteinizing hormone and folliclestimulating hormone levels and 10 out of 13 had abnormal testosterone levels; whereas eight of 14 females tested had either abnormal luteinizing hormone, follicle-stimulating hormone or estradiol levels and 75% had amenorrhea. 19 As gonadal toxicity may be correlated with the pubertal stage at the time of transplant, long-term follow-up of our young patients will be necessary to assess the ultimate gonadal function post transplant. Of interest, infertility was not a major concern for the eligible families we encountered.…”

Secondary Prevention of Overt Strokes in Sickle Cell Disease: Therapeutic Strategies and Efficacy

“…Nevertheless, recent evidence from Walters et al strongly suggests that, when available, matched-sibling donor HSCT should be the first option for the secondary prevention of strokes. 28 In the most comprehensive study to date, which was performed from 1991-2000, none of the 28 patients with engraftment experienced recurrent strokes or had evidence of silent cerebral infarct events after HSCT, with a mean follow-up of 3.6 years (range 0.6-7.3 years).…”