Microtransplantation in older patients with AML: A pilot study of safety, efficacy and immunologic effects

Abstract

Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical outcomes compared with chemotherapy alone. This is the first trial reporting on broad correlative studies to define immunologic mechanisms of action of MST in older AML patients. Older patients with newly diagnosed AML were eligible for enrollment, receiving induction chemotherapy with cytarabine (100 mg/m2) on days 1‐7 and idarubicin (12 mg/m2) on days 1‐3 (7 + 3). MST was administered 24 hours later. Patients with complete response (CR) were eligible for consolidation with high dose cytarabine (HiDAC) and a second cycle of MST. Responses were evaluated according to standard criteria per NCCN. Immune correlative studies were performed. Sixteen patients were enrolled and received 7 + 3 and MST (median age 73 years). Nine (56%) had high‐risk and seven (44%) had standard‐risk cytogenetics. Ten episodes of CRS were observed. No cases of GVHD or treatment‐related mortality were reported. Event‐free survival (EFS) was 50% at 6 months and 19% at 1 year. Overall survival (OS) was 63% at 6 months and 44% at 1 year. Donor microchimerism was not detected. Longitudinal changes were noted in NGS, TCR sequencing, and cytokine assays. Addition of MST to induction and consolidation chemotherapy was well tolerated in older AML patients. Inferior survival outcomes in our study may be attributed to a higher proportion of very elderly patients with high‐risk features. Potential immunologic mechanisms of activity of MST include attenuation of inflammatory cytokines and emergence of tumor‐specific T cell clones.

Non-Ablative Chemotherapy Followed by HLA-Mismatched Allogeneic CD3+ T-Cells Infusion Causes An Augment of T-Cells With Mild CRS: A Multi-Centers Single-Arm Prospective Study on Elderly Acute Myeloid Leukemia and int-2/High Risk Myelodysplastic Syndrome Patients

“…Sung et al. also reported an incidence of HLA-mismatched stem cell transplantation-related CRS of 40%, of which most cases were mild ( 62 ). There is currently no recognized term for this CRS, and we therefore referred to it as “post-TLI CRS”.…”

“…Indeed, HLAmismatched HSCT-related CRS was proposed as early as 2009 in a study of non-engraftment haploidentical cellular immunotherapy, termed "haplo immunostorm", which presents with a series of clinical symptoms accompanied by cytokine flux, and has been shown to be sensitive to steroids (67). Sung et al also reported an incidence of HLA-mismatched stem cell transplantation-related CRS of 40%, of which most cases were mild (62). There is currently no recognized term for this CRS, and we therefore referred to it as "post-TLI CRS".…”

“…Some cytokines are involved in the anti-tumor immunity of T-cells, while others contribute to the proliferation of hematopoietic cells. Previous studies showed changes in serum concentrations of several cytokines, such as IL-6, IL-8, and TNF-β, after HLA-mismatched allo-TLI ( 62 ). In the present study, IL-2, IL-10, IL-6, and IFN-γ levels increased significantly after HLA-mismatched allo-TLI, but IL-4, IL-17A, and TNF-α were unchanged.…”

Microtransplantation for myeloid sarcoma: Two case reports

“…Microtransplantation is an HLA-mismatched granulocyte colony-stimulating factor-mobilized donor peripheral blood stem-cell infusion, without HLA-restriction. At present, it has been reported that microtransplantation can improve the overall survival of elderly AML patients who cannot undergo HSCT, and shows high tolerance and low severe toxicity ( 10 , [12] , [13] , [14] , [15] ). A multicenter clinical study found a high CR rate (74.6%) in AML patients aged 60 to 85 years after microtransplantation, with 1.1% underwent GVHD ( 10 ).…”

Microtransplantation improves the outcome of older patients with newly diagnosed acute myeloid leukaemia: a single-centre study with long-term follow-up

“…Some centres have reported that MST could improve the outcomes of AML patients [15][16][17][18][19][20] . However, other institutions did not nd similar e cacy of MST in treating AML patients [21,22] . Brie y, more studies need to be conducted to validate the e cacy and safety of MST in treating older AML patients.…”