RBC Exchange Transfusion As an Adjunct Therapy to Control Iron Overload in Patients with Transfusion-Dependent Thalassemia

Background

Patients with transfusion-dependent thalassemia (TDT) require red blood cell (RBC) transfusions as frequently as every 2-4 weeks to maintain a pre-transfusion hemoglobin of 9.0-10.5 g/dL for patients without cardiac complications. Chronic RBC transfusions increase body iron stores leading to iron deposition in liver, pancreatic, and cardiac tissues. Deferoxamine, deferiprone, and deferasirox are the iron chelators currently licensed for clinical use to manage iron overload in TDT patients with side effects ranging from nausea to nephrotoxicity and hearing loss.

RBC exchange transfusion (RBCX), particularly in conjunction with isovolumic hemodilution, has been utilized for patients with sickle cell disease as a means of stabilizing iron overload. The 2015 ASFA Red Blood Cell Exchange consensus supports RBCX to reduce or prevent iron overload in sickle cell disease. Review of literature shows that RBCX can be beneficial as an acute intervention for patients with TDT and pulmonary hypertension however there is a paucity of literature documenting chronic RBCX use in TDT patients with iron overload.

Case series

This series presents five patients with TDT who were transitioned from chronic simple RBC transfusions to chronic RBCX after developing treatment-refractory iron overload as evidenced by serum ferritin elevation. Patients were treated on a transfusion schedule with a pre-transfusion goal hemoglobin of 9.5g/dL or higher and interval 4-6 weeks. Patient A is a 14 year-old male who developed significant iron overload (peak ferritin of 7077) on deferasirox 20 mg/kg/day and MRI T2 imaging suggestive of iron deposition. After transition to RBCX, ferritin decreased significantly with a post-RBCX mean of 1382. Blood utilization was 4200 ml three months pre-RBCX and 5625 ml three months post-RBCX. Patient B is a 23 year-old male with a peak ferritin of 1310 prior to RBCX on 23 mg/kg/day of deferasirox complicated by mild hearing loss. Serum ferritin has shown stabilization, with a mean post-RBCX ferritin of 880. Blood utilization was 2400 ml three months pre-RBCX and 8100 ml three months post-RBCX. Patient C is a 17 year-old male with a peak ferritin of 1400 with deferasirox management complicated by acute renal injury. Mean serum ferritin of 633 post-RBCX. Blood utilization was 1200 ml three months pre-RBCX and 5200 ml three months post-RBCX. Patient D is a 17 year-old male managed on 23 mg/kg/day of deferasirox with a peak ferritin of 3060 on pre-RBCX. The patient transitioned to chronic RBCX with mean serum ferritin of 1073. Blood utilization was 1800 ml three months pre-RBCX and 7700 ml three months post-RBCX. Patient E is a 17 year-old male with peak ferritin of 3404 despite 20 mg/kg/day of deferasirox prior to chronic RBCX. Mean serum ferritin after transition to RBCX was found to be 1282. Blood utilization was 1500 ml three months pre-RBCX and 4900 ml three months post-RBCX. All 5 patients have tolerated RBC exchange procedures without complications.

Serum ferritin levels pre- and post-RBC exchange were trended pre- and post- RBCX (Figure 1). Serum ferritins were averaged together for each patient to obtain an equal number of time points considered prior to and after starting RBCX therapy. Descriptive statistics (Table 1) were used to summarize average ferritin levels for the patient group. A Wilcoxon signed-rank test was performed to assess the median difference in ferritin level from pre-RBCX to post-RBCX. All analyses were conducted in SAS version 9.4. P <0.05 is considered statistically significant. Median pre-RBCX ferritin level for the study group is 2489.3 (Inter-quartile range (IQR): 1190.0, 2659.0). The median post-RBCX ferritin level for the series is 1329.3 (IQR: 941.0, 1711.0). After subtracting the post-RBCX ferritin level from the pre-RBCX ferritin level, the median change for the group is 457 (IQR: 249.0, 1160.0) (p=0.06).

Conclusion

This case series documents the successful clinical application of chronic RBCX in TDT patients as a means of stabilizing serum ferritin levels over time. Mean ferritin levels were significantly lower, clinically, after transitioning from chronic simple RBC transfusion to RBCX (Table 1), though analysis is limited due to cohort size. Blood utilization increased after transitioning to RBCX. Next steps in evaluating our practice for the patient group will be to evaluate iron deposition status with MRI T2* imaging.