Clinical Outcomes Following Bone Marrow Transplant in Patients with Sickle Cell Disease: A Cohort Study of US Medicaid Enrollees
Authors: Mahesri Mufaddal , Schneeweiss Sebastian , Levin Raisa , Globe Denise , McKerracher Krista , Mutebi Alex , Bohn Rhonda , Achebe Maureen , Desai Rishi J 
Published: November 2019

Introduction: Sickle cell disease (SCD) is a hereditary condition characterized by severe complications and repeated episodes of acute illness throughout life, leading to premature death. Blood and Marrow Transplantation (BMT) is the only available cure for this debilitating disorder; however, it remains infrequently used because of challenges in finding matched donors and a high risk of post-transplant complications. Claims analyses of clinical outcomes among SCD patients undergoing BMT are limited. Using US Medicaid claims data, we sought to describe the rates of vaso-occlusive crises (VOCs), transplant complications, and mortality in a cohort of SCD patients after BMT.
Methods: We conducted a cohort study of SCD patients who underwent BMT during 2000-2013, using longitudinal claims data from the US Medicaid health insurance program. We identified all individuals who had ≥1 inpatient or ≥2 outpatient HbSS SCD diagnosis, (ICD-9 codes of 282.61 and 282.62) and a claim for BMT (ICD-9 code: 41.02. 41.03, 41.05, 41.06, 41.08; CPT code: 38240) after ≥12 months of continuous Medicaid enrollment (or since birth if age at diagnosis is <1 year) and excluded all patients diagnosed with any cancer prior to BMT. The follow-up period started on the BMT date and continued until death, loss of Medicaid eligibility or end of study period (December 31, 2013). Outcomes analyzed in the follow-up period included: VOCs requiring an emergency department visit or hospitalization, (ICD-9 codes: 282.62, 517.3, 729.5, 786.50, 786.59, 289.52, 607.3), all-cause mortality, post-transplant complications (ICD-9 code: 996.85), occurrence of graft-versus-host disease (GvHD ICD-9 codes of 279.50, 279.51, 279.52, 279.53), and various healthcare utilization outcomes (e.g., hospitalizations and blood transfusions). Incidence rates along with 95% confidence intervals were calculated.
Results: Among the SCD patients identified in our Medicaid cohort, only 0.5% received a transplant during this period. A total of 204 SCD patients were included in the analysis with a median follow-up time of 2.0 years (Interquartile range, IQR: 0.8 - 4.3 years), mean (SD) age of 10.6 (7.3) years, with 52.9% male and 67.6% African Americans. Pre-BMT median (IQR) VOCs was 1 (0-3). The overall average VOC rate throughout the available post-BMT follow up period was 0.98 per person-year (95% CI: 0.91 - 1.06). In the 1st year post-transplant, 164(80.4%) patients were free of VOCs post-BMT, while 138 (67.6%) remained free of VOCs throughout all available follow up. The median time to the first post-BMT VOC event (among those who had post-BMT VOCs) was 226.5 days (IQR: 45 - 632 days). There were 123 (60.3%) patients who did not require any blood transfusions while 48 (23.5%) patients required < 2 blood transfusions during the 1st year post-BMT, excluding the peri-transplant period. The mortality rate in this cohort was 0.62 (95% CI: 0.23 - 1.64) per 100 person-years. A total of 113 (55.4%) patients had a transplant-related complication with an incidence rate of 38.2 (95% CI: 31.7 - 45.9) per 100 person-years. Forty-seven (23%) patients developed GvHD with an incidence rate of 8.0 (95% CI: 6.0 - 10.6) per 100 person-years. In the post-BMT period, solid tumor malignancies were observed in 19 (9.3%) patients [incident rate: 3.3 (95%CI: 2.1-5.2) per 100 person-years], hematological malignancies were observed in 11 (5.4%) patients [incident rate: 1.8 (95% CI: 1.0 - 3.2) per 100 person-years]. Immunologic disorders were observed in 20 (9.8%) patients [incidence rate 3.3 (95%CI: 2.1-5.1) per 100 person years].
Conclusion: In a cohort of Medicaid beneficiaries with SCD, approximately 0.5% of the patients underwent BMT and two thirds of the transplant recipients remained VOC event-free over a median follow-up of almost 2.0 years. Transplant patients experience substantial transplant-related complications, including GvHD, malignancies, and mortality. The findings highlight continuing unmet need in the treatment of SCD as well as the need for alternative BMT procedures with fewer complications.

Disclosures
Schneeweiss: Genentech: Research Funding; Whiscon LLC: Consultancy; Aetion, Inc.: Consultancy, Equity Ownership; Boehringer Ingelheim: Research Funding. Globe:Vertex Pharmaceuticals Incorporated: Employment. McKerracher:CRISPR Therapeutics: Employment. Mutebi:Vertex Pharmaceuticals Incorporated: Employment. Bohn:Vertex Pharmaceuticals Inc: Consultancy; Bohn Epidemiology: Equity Ownership. Achebe:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Fulcrum Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees. Desai:Merck: Research Funding; Bayer: Research Funding.