Allogeneic CD34⁺ selected hematopoietic stem cell boost following CAR T‐cell therapy in a patient with prolonged cytopenia and active infection

Abstract

Hematological toxicity (hematotoxicity) leading to peripheral cytopenias is a common long‐term adverse effect following the use of CD19‐chimeric antigen receptor (CD19‐CAR) T‐cell therapies. However, management remains unclear for patients whose cytopenias persist beyond 1 month after CAR T‐cell infusion. We present the case of a 21‐year old who received CD19‐CAR T‐cell therapy for relapse following a haploidentical transplant. He developed hematotoxicity and consequently multiple life‐threatening infections. We administered a CD34+ hematopoietic stem cell boost (HSCB) from his transplant donor, which led to hematopoietic recovery and resolution of his infections without any effect on the activity of CD19‐CAR T cells. CD34+ HSCB can be a safe and effective option to treat hematotoxicity following CD19‐CAR T‐cell therapy.

Hematopoiesis and immune reconstitution after CD19 directed chimeric antigen receptor T‐cells (CAR‐T): A comprehensive review on incidence, risk factors and current management

“…CD8+ T‐cells and CD56+ natural killer (NK) cells fully recovered in all patients by 1 year, while reconstitution of CD4+ T cells was delayed, with normalization in only 67% of patients at 1 year. Similarly, in 39 CAR‐T recipients with R/R, the absolute counts of CD4+, CD8+, and CD16/56+ lymphocytes decreased significantly after lymphodepleting chemotherapy: while CD8+ and CD16/CD56+ cell counts rapidly recovered in all patients at a median time of 21 days, 7–10,12–15,17,21,22,24–64,66–92 a slower recovery was observed for CD4+, which recovered within 60 days in only 5 (23.81%) of patients 71 …”

“…If CAR-T cells were administered after a previous allogeneic HSCT, donor-derived CD34+ boost in patients experiencing persistent grade ≥ 3 cytopenias has also been reported, with no GVHD occurrence. 21,91,92 When sequential treatment with tandem infusion of CAR-T and autologous or allogeneic HSCT was performed inside clinical trials, it was observed that CAR-T did not impact hematopoietic recovery or GVHD after transplants. 93,94 In a real-life survey, autologous stem cell boosts, when available, were the preferred option for the rescue of persistent neutropenia in 63% of centers, while it was considered a therapeutic option for persisting thrombocytopenia refractory to TPO-RA by 43% of experts.…”

“…In the cohort of pediatric pts with B‐ALL, Deyà‐Martinez et al, observed that 71% of patients developed undetectable IgM levels at a median of 71 days after infusion 9,11,14,16–22,36,50–64,66–98 ; IgA levels decreased in 13% of patients to undetectable levels at 185 days after infusion (11–308). Patients with undetectable IgM, showed a longer CAR‐T persistence (373.5 vs. 60 days; p : <.001).…”

Prolonged haematologic toxicity in CAR‐T‐cell therapy: A review

“…In two case reports, auto‐HSCB reversed CAR‐T‐cell‐mediated prolonged pancytopenia in lymphoma and multiple myeloma patients 81,82 . Similarly, allo‐HSCB improved the prognosis of two B‐ALL patients with prolonged cytopenia and infection following CAR‐T‐cell therapy 83,84 . In addition to case reports, a multicentre study reported results for 31 patients receiving HSCB (auto, n = 30; allo, n = 1) for sustained severe and moderate neutropenia.…”

“… 81 , 82 Similarly, allo‐HSCB improved the prognosis of two B‐ALL patients with prolonged cytopenia and infection following CAR‐T‐cell therapy. 83 , 84 In addition to case reports, a multicentre study reported results for 31 patients receiving HSCB (auto, n = 30; allo, n = 1) for sustained severe and moderate neutropenia. A total of 84% (26/31) of patients achieved neutrophil recovery or improvement.…”