Response: young adults with sickle cell disease have more transplant options

We appreciate the comments by Kuentz et al and are encouraged by their experience using myeloablative HSCT in young adults with SCD.¹  Although 8 of their 15 patients were 16 or 17 years old and another 5 patients were 20 and 22 years old, 2 were 26 and 27 years old extending this approach well into the next decade of life. The acute GVHD rate in this group was predictably higher (grade 2 and 3, 7 of 15 = 47%) than their pediatric experience (20%)² ; however, the GVHD appeared easily treated by single agent prednisone. With the extensive transplant experience that this group and others have reported,^3-7  there is certainly a place for full ablative HSCT in pediatric patients with SCD, and this new experience now suggests that the same is true for young adults eligible for this approach. These accumulating reports continue to confirm a very favorable benefit to risk ratio making this a truly exciting time for patients and physicians contemplating HSCT for SCD.

Myeloablative conditioning and the ensuing risk of GVHD, however, require robust organ function. We now have transplanted 23 patients with severe disease at our center with nonmyeloablative conditioning, their ages ranging from 17 to 65 years. All patients are alive, and engraftment was achieved in 20 (87%). Importantly, 5 of the first 10 patients reported⁸  are now off immunosuppression with continued stable mixed chimerism. Equally important, none of the engrafted patients has experienced any GVHD. In addition, 3 patients have produced offspring naturally (1 male and 2 female). This larger experience suggests that with this nonmyeloablative approach, the risk of rejection is similar, the risk of GVHD is lower, long-term immunosuppression is not absolutely required, and stable mixed chimerism is achievable. It is important to note that nearly half (10 of 23) of our patients would be ineligible for myeloablative transplantation because of comorbidities including cirrhosis and poor lung function.

Thus for patients in their second and third decade of life, options include both full and nonmyeloablative transplant conditioning, with the choice depending on organ involvement, potential transplant-related complications, and the desire for future fertility. It is our opinion that patients in this age group should be transplanted as a part of an ongoing clinical trial. HSCT for SCD remains under-utilized and the time to seriously consider this therapeutic option is now.