Effective Tacrolimus Treatment for Patients with Non-Severe Aplastic Anemia That is Refractory/Intolerant to Cyclosporine A: A Retrospective Study

Abstract

Background

For symptomatic non-severe aplastic anemia (NSAA) patients who cannot afford anti-thymocyte globulin (ATG) or allogeneic hematopoietic stem cell transplantation (HSCT), tacrolimus (FK) may be an option if these patients do not respond or become tolerant to cyclosporine A (CsA).

Methods

We enrolled 101 NSAA patients who were refractory or intolerant to CsA with no chance of HSCT or ATG treatment and treated these patients with tacrolimus for at least 6 months, with follow-up for at least one year.

Results

The overall response rate (ORR) was 38.6% (complete response: 9.9%; partial response: 28.7%), and the median time to optimal response was 6 (3～10) months. Thirty-two (31.7%) cases had elevated creatinine levels. Eight (7.9%) cases had elevations in AST/ALT. A total of 25.6% (10/39) of patients relapsed at the end of follow-up. Age (P=0.0005), FK concentration (4.0~12 ng/mL, P=0.0005) and intolerance to CsA (P=0.012) were the independent risk factors for ORR. Treg cell levels pre-FK treatment were much lower than those of healthy controls (3.7±0.6% vs 6.8±0.7%, P=0.0004) but increased significantly after FK treatment (3.7±0.6% vs 7.1±0.8%, P=0.0039).

Conclusion

Our data suggest that tacrolimus is a salvage treatment for patients with NSAA that is refractory or intolerant to CsA.

Keywords:

• non-severe aplastic anemia
• tacrolimus
• cyclosporine A

Abbreviations

NSAA, non-severe aplastic anemia; SAA, severe aplastic anemia; AA, aplastic anemia; ATG, anti-thymocyte globulin; HSCT, hematopoietic stem cell transplantation; FK, tacrolimus; CsA, cyclosporine A; ORR, overall response rate; CR, complete response; PR, partial response; NR, no response; OR, odds ratio; IST, immunosuppression therapy; GVHD, graft-versus-host disease; PUMCH, Peking Union Medical College Hospital; AE, adverse events; CTCAE, common toxicity criteria for adverse events; Treg cells, regulatory T cells; CI, confidence interval; AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; PNH, paroxysmal nocturnal hemoglobinuria.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

Written informed consent was obtained from all patients over 18 years old and patients or legal guardian for patients under the age of 18 years old. Before data collected, and all clinical procedures were performed in accordance with the Declaration of Helsinki.

Consent for Publication

Consent for publication was obtained from all patients and accompanied by informed consent at the beginning of the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflicts of interest for this work.