Hematopoietic stem cell transplantation (HSCT) from an HLA matched donor is the only curative therapy for sickle cell disease (SCD), with sibling donor survival rates approaching 95%. Referral from the primary hematologist for transplant evaluation is a key step in the process. Study aims were to assess pediatric SCD providers for: 1) Current perspectives and referral patterns; 2) Whether perspectives differ for those practicing at a transplant center.
All pediatric hematology providers at the designated newborn screening hemoglobinopathy centers within the seven state New York-Mid-Atlantic Consortium (NYMAC) were anonymously surveyed. Descriptive statistics and chi squared test or Fisher's exact test were used for analysis.
Of 197 pediatric SCD providers contacted through the NYMAC listserv, 104 (53%) responded, predominantly hematologists. Half (53%) of responders practice at sites performing HSCT for pediatric SCD. Overall, transplant centers had larger SCD patient populations (p<0.001).
Most providers (89%) had referred at least one child with SCD for transplant evaluation within the past two years. A higher proportion of practitioners at a transplant center had referred at least 3 patients for transplant evaluation, 84% vs. 53% (p=0.001).
Overall, 77% would limit HSCT to children with HbSS or HbS-β° thalassemia. Nearly half (44%) were less likely to refer a child for evaluation with SCD than with β-thalassemia major (no significant difference (NS) by practice setting). Those practicing at transplant centers were more certain of 6–16 years as an optimal transplant age (100% vs. 84%; p=0.004).
Single disease indications for transplant referral were stroke, acute chest syndrome or family request. Less commonly cited were abnormal TCD (31%) or clinically silent stroke (34%). Commonly listed treatment indications were a new stroke despite chronic transfusion (82%) or poor response to hydroxyurea (71%), not iron overload (22%) (NS by practice setting).
Most would offer HSCT to a child with multiple SCD complications with (95%) or without (66%) a sibling match; 37% would refer a child with limited disease despite a sibling donor (NS by practice setting).
The majority (78%) agreed that HSCT can improve health. Risk of mortality, lack of sibling match, and infertility were most commonly cited as barriers to referral. Most identified acceptable overall survival rates as 90–100% (divided between ≥90% or 95–100%). Providers at transplant centers were more likely to accept event-free survival rates of 75–90% (87% vs. 63%; p=0.002), rather than 95–100%.
While only one U.S. region was surveyed, NYMAC collectively diagnoses approximately 25% of all newborns with SCD (genes-r-us.uthscsa.edu). Actual referral patterns could not be verified. No adjustments were made for size of each practice site, nor were providers queried about perceived influence of payer mix or other patient demographics.
Most pediatric SCD providers accept HSCT as a treatment option, especially for children with severe disease complications or inadequate response to other therapies. Practitioners at transplant centers reported making more referrals for evaluation, having a stronger preferred age and accepting a broader range of event-free survival. Overall, only one third of providers deem eligible those patients with a sub-clinical stroke or stroke risk, or those with a sibling donor if without major disease complications. Most providers prefer transplant for children with a limited sickle hemoglobinopathy type, and almost half favor transplantation for β-thalassemia major. These findings suggest varying enthusiasm for HSCT for pediatric SCD beyond donor availability or current survival outcomes. The SCD provider is a critical conduit for ushering families towards transplantation and weighing difficult risk-benefit ratios. Informed decisions and referral may benefit from provider education, especially for those not practicing at transplant centers, as well as professional guidelines about current indications and research comparing outcomes of SCD versus HSCT.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.