Bloodless Medicine Management of a Patient Receiving CAR T-Cell Therapy

A 70-year-old man who is a member of the Jehovah’s Witness congregation was diagnosed in 2002 with grade 2, stage IIIa follicular mixed lymphoma. His Follicular Lymphoma International Prognostic Index score was 3, indicating high-risk disease. He was initially treated with rituximab monotherapy and achieved complete remission.

The patient experienced relapses in 2006, 2008, 2009, and 2011. His treatment post relapse included iodine-131 tositumomab radioimmunotherapy, targeted radiation, and bendamustine/rituximab. In 2023, a left supraclavicular lymph node biopsy again confirmed relapse with no evidence of large-cell transformation. At this time, he was referred for possible CAR T-cell therapy.

During his initial consultation, he was enrolled in the institution’s bloodless medicine and transplant program. His advance directive healthcare power of attorney indicated that he declined major blood fractions such as white blood cells, plasma, platelets, and whole blood. However, the patient was agreeable to accepting minor fractions such as cryoprecipitate, albumin, and growth factors, as well as to the use of blood-conservation equipment.

His pre–CAR-T medical evaluation was negative for bone marrow or central nervous system involvement. Lab work showed white blood cell (WBC) count 5.9, hemoglobin (Hgb) 14.6, hematocrit (HCT) 43.6, and platelets (PLT) 136. The comprehensive metabolic panel was unremarkable, and iron studies were within normal limits. The decision was made to proceed with T-cell collection for tisagenlecleucel. The patient did not require bridging chemotherapy prior to proceeding with lymphodepletion. To mitigate the risk of prolonged cytopenias following CAR T-cell therapy, bendamustine 90 mg/m2 on Days -5 and -4 was used for the lymphodepleting regimen. On the day of admission for tisagenlecleucel infusion, his WBC was 6.8, Hgb 13.6, HCT 40.7, and PLT 115.

Management  

Upon admission, the bloodless medicine supportive care protocol was initiated, as detailed below. Lab draws were limited to every 3 days or as clinically needed. Pediatric vials were used when possible.

Bloodless Medicine Supportive Care Protocol 

Abbreviations: N/A, not applicable; plt, platelet; SC, subcutaneous; VTE, venous thromboembolism. 

Summary of Lab Values 

Abbreviations: CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome. 

During the course of his admission, his complete blood cell count remained stable, he did not require cryoprecipitate, and he had no evidence of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. He was discharged home on Day +12. A commercially available CAR T-cell persistence assay was sent on Day +60 that showed 2.072 CAR vector copies/μg to 1.392E+07 CAR vector copies/ug, indicating persistent circulating CAR T cells. Repeat CAR T-cell persistent assay sent 1 year post tisagenlecleucel infusion remains positive for circulating CAR T cells. The patient is now 2 years post tisagenlecleucel infusion, during which time his blood counts have remained stable, and he has not required IV immunoglobulin infusions.

Discussion 

There are more than 9 million people of the Jehovah’s Witness faith worldwide, with 1.2 million residing in the United States.¹ Members of the Jehovah’s Witness congregation do not accept blood products based on a scriptural command to abstain from blood, which is found in both the Old and New Testaments (Genesis 9:4; Leviticus 17:10; Acts 15:19-20).² As such, they cannot accept transfusions of major blood fractions: red blood cells, white blood cells, plasma, and platelets. The acceptance of minor blood fractions, such as albumin, clotting factors, cryoprecipitate, and stem cells, is a matter of individual choice.3 Healthcare providers should discuss with the patient in advance about which minor fractions, procedures, and blood-conservation measures are acceptable to that individual. These wishes should be documented on the advance directive healthcare power of attorney.

Blood and platelet transfusions are commonly given as a supportive care measure in patients with hematologic malignancies and those undergoing hematopoietic stem cell transplant and cellular therapies. The dependence on blood product transfusions during hematopoietic stem cell transplant and other cellular therapies such as CAR T-cell therapy can make treating patients of the Jehovah’s Witness faith a challenge. These patients are often not offered cellular therapies due to concern for toxicity. However, significant progress and understanding of bloodless medicine has led to improved outcomes, where risk–benefit analysis strongly favors treatment.⁴ The feasibility and safety of autologous stem cell transplantation are well documented in the literature, with overall survival rates and transplant-related mortality rates similar to those of patients who accept blood transfusion support.^4,5 Data for the management of patients of the Jehovah’s Witness faith undergoing CAR T-cell therapy are limited. A case study by Riedell et al. reported on two patients of the Jehovah’s Witness faith who underwent CAR T-cell therapy successfully by employing supportive care measures similar to those used for bloodless autologous stem cell transplant.⁶ 

A multidisciplinary approach that includes physicians, advanced practice providers, nurses, social workers, transplant coordinators, and the bloodless medicine team is integral in treating this patient population. As such, timely referral, careful patient selection, patient education, CAR-T product selection, selection and/or dose reduction of the lymphodepleting regimen, CAR T-cell infusion timing, and supportive care measures are paramount in ensuring positive outcomes.

References 

1. JW.org. How many of Jehovah’s Witnesses are there worldwide? Accessed April 4, 2025. https://www.jw.org/en/jehovahs-witnesses/faq/how-many-jw/. 
2. JW.org. Why don’t Jehovah’s Witnesses accept blood transfusion? Accessed April 4, 2025. https://www.jw.org/en/jehovahs-witnesses/faq/jehovahs-witnesses-why-no-blood-transfusions/. 
3. JW.org. Medical information for clinicians: religious and ethical position on medical therapy and related matters. Accessed April 4, 2025. https://www.jw.org/en/medical-library/medical-information/ret/religious-ethical-position.
4. Beck A, Lin R, Reza Rejali A, et al. Safety of bloodless autologous stem cell transplantation in Jehovah's Witness patients. Bone Marrow Transplant. 2020;55(6):1059–1067. doi:10.1038/s41409-019-0777-9. 
5.  Ford PA, Grant SJ, Mick R, Keck G. Autologous stem-cell transplantation without hematopoietic support for the treatment of hematologic malignancies in Jehovah's Witnesses. J Clin Oncol. 2015;33(15):1674–1679. doi:10.1200/JCO.2014.57.9912. 
6. Riedell PA, Wu M, Collins JM, et al. Bloodless chimeric antigen receptor (CAR) T-cell therapy in Jehovah's Witnesses. Leuk Lymphoma. 2021;62(6):1497–1501. doi:10.1080/10428194.2021.1876868.