Scoping review of factors associated with stem cell mobilization and collection in allogeneic stem cell donors

BACKGROUND: There is a large inter-individual variation in the efficacy of CD34+ cell mobilization and collection in healthy allogenic hematopoietic stem cell donors. Donor characteristics, blood cell counts, and factors related to mobilization and collection have previously been associated with blood CD34+ cell count or CD34+ cell yield after G-CSF mobilization and collection. Since the literature reporting associations is heterogeneous, we clarify the determinants of CD34+ count and yield in a scoping review.MATERIALS AND METHODS: Studies published between 2000 and 2023 were evaluated if they reported allogeneic donors undergoing G-CSF mobilization and peripheral blood stem cell collection (PBSC). Eligible studies assessed blood CD34+ cell count or CD34 + cell yield in the first PBSC collection after mobilization with 4 or 5 days of G-CSF treatment. Associations were recorded between these outcomes and donor factors (age, gender, weight, ethnicity), mobilization factors (G-CSF scheduling or dose), collection factors (venous access, processed blood volume) or laboratory factors (blood cell counts at baseline or after mobilization). RESULTS: The 52 studies each evaluated between 15 and 20,884 donors. 43 studies were retrospective, 33 assessed blood CD34+ cell counts and 39 assessed CD34+ cell yield from PBSC. Blood CD34+ cell counts consistently predicted CD34+ cell yield. Younger donors usually had higher blood CD34+ cell counts and CD34+ cell yield. Most studies that investigated the effect of donor ancestry found that non-European ancestry donors had higher blood CD34+ cell counts after mobilization and CD34+ cell yields from collection.CONCLUSIONS: There remains poor consensus about the best predictors of blood CD34+ cell counts and yield that requires further prospective study, particularly of the role of donor ancestry. The current focus on donor gender as a major predictor requires re-evaluation.</p

Scoping review of factors associated with stem cell mobilization and collection in allogeneic stem cell donors

BACKGROUND: There is a large inter-individual variation in the efficacy of CD34+ cell mobilization and collection in healthy allogenic hematopoietic stem cell donors. Donor characteristics, blood cell counts, and factors related to mobilization and collection have previously been associated with blood CD34+ cell count or CD34+ cell yield after G-CSF mobilization and collection. Since the literature reporting associations is heterogeneous, we clarify the determinants of CD34+ count and yield in a scoping review.MATERIALS AND METHODS: Studies published between 2000 and 2023 were evaluated if they reported allogeneic donors undergoing G-CSF mobilization and peripheral blood stem cell collection (PBSC). Eligible studies assessed blood CD34+ cell count or CD34 + cell yield in the first PBSC collection after mobilization with 4 or 5 days of G-CSF treatment. Associations were recorded between these outcomes and donor factors (age, gender, weight, ethnicity), mobilization factors (G-CSF scheduling or dose), collection factors (venous access, processed blood volume) or laboratory factors (blood cell counts at baseline or after mobilization). RESULTS: The 52 studies each evaluated between 15 and 20,884 donors. 43 studies were retrospective, 33 assessed blood CD34+ cell counts and 39 assessed CD34+ cell yield from PBSC. Blood CD34+ cell counts consistently predicted CD34+ cell yield. Younger donors usually had higher blood CD34+ cell counts and CD34+ cell yield. Most studies that investigated the effect of donor ancestry found that non-European ancestry donors had higher blood CD34+ cell counts after mobilization and CD34+ cell yields from collection.CONCLUSIONS: There remains poor consensus about the best predictors of blood CD34+ cell counts and yield that requires further prospective study, particularly of the role of donor ancestry. The current focus on donor gender as a major predictor requires re-evaluation.</p

Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia

Abstract Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level <1% to 2% with a <1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received ≥2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD−; 30%) or retaining a low-level NPM1mut transcript (12% for ≥12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction <4.4-log) at EOT

A national service for delivering CD19 CAR-Tin large B-cell lymphoma - The UK real-world experience

CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR-T in the UK. Consecutive patients with r/r LBCL approved for CAR-T by the National CAR-T Clinical Panel between December 2018 and November 2020 across all UK CAR-T centres were included. 404/432 patients were approved [292 axicabtagene ciloleucel (axi-cel), 112 tisagenlecleucel (tisa-cel)], 300 (74%) received the cells. 110/300 (38.3%) patients achieved complete remission (CR) at 6 months (m). The overall response rate was 77% (52% CR) for axi-cel, 57% (44% CR) for tisa-cel. The 12-month progression-free survival was 41.8% (axi-cel) and 27.4% (tisa-cel). Median overall survival for the intention-to-treat population was 10.5 m, 16.2 m for infused patients. The incidence of grade ≥3 cytokine release syndrome and neurotoxicity were 7.6%/19.6% for axi-cel and 7.9%/3.9% for tisa-cel. This prospective RW population of CAR-T eligible patients offers important insights into the clinical benefit of CD19 CAR-T in LBCL in daily practice. Our results confirm long-term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR-T failure

A national service for delivering CD19 CAR-Tin large B-cell lymphoma – The UK real-world experience

CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR-T in the UK. Consecutive patients with r/r LBCL approved for CAR-T by the National CAR-T Clinical Panel between December 2018 and November 2020 across all UK CAR-T centres were included. 404/432 patients were approved [292 axicabtagene ciloleucel (axi-cel), 112 tisagenlecleucel (tisa-cel)], 300 (74%) received the cells. 110/300 (38.3%) patients achieved complete remission (CR) at 6 months (m). The overall response rate was 77% (52% CR) for axi-cel, 57% (44% CR) for tisa-cel. The 12-month progression-free survival was 41.8% (axi-cel) and 27.4% (tisa-cel). Median overall survival for the intention-to-treat population was 10.5 m, 16.2 m for infused patients. The incidence of grade ≥3 cytokine release syndrome and neurotoxicity were 7.6%/19.6% for axi-cel and 7.9%/3.9% for tisa-cel. This prospective RW population of CAR-T eligible patients offers important insights into the clinical benefit of CD19 CAR-T in LBCL in daily practice. Our results confirm long-term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR-T failure