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

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. T...

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Vydáno v:American journal of hematology Ročník 95; číslo 6; s. 662 - 671
Hlavní autoři: Sung, Anthony D., Jauhari, Shekeab, Siamakpour‐Reihani, Sharareh, Rao, Arati V., Staats, Janet, Chan, Cliburn, Meyer, Everett, Gadi, Vijayakrishna K., Nixon, Andrew B., Lyu, Jing, Xie, Jichun, Bohannon, Lauren, Li, Zhiguo, Hourigan, Christopher S., Dillon, Laura W., Wong, Hong Yuen, Shelby, Rebecca, Diehl, Louis, Castro, Carlos, LeBlanc, Thomas, Brander, Danielle, Erba, Harry, Galal, Ahmed, Stefanovic, Alexandra, Chao, Nelson, Rizzieri, David A.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Hoboken, USA John Wiley & Sons, Inc 01.06.2020
Wiley Subscription Services, Inc
Témata:
Chemotherapy
Chimerism
Cytarabine
Cytogenetics
Cytokines
Geriatrics
Graft-versus-host reaction
Hematology
Hematopoietic stem cells
Inflammation
Lymphocytes T
Patients
Remission
Stem cells
T cell receptors
ISSN:0361-8609, 1096-8652, 1096-8652
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Shrnutí: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.
Bibliografie:Abbreviations
AML, acute myeloid leukemia; ANC, absolute neutrophil count; CRS, the cytokine release syndrome; EFS, event‐free survival; HR, hazard ratios; HiDAC, high dose cytarabine; GVHD, graft vs host disease; MST, microtransplantation; OS, overall survival; PBMC, peripheral blood mononuclear cell; TCR, T cell receptor.
Anthony D. Sung and Shekeab Jauhari contributed equally to this paper.
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Current Affiliation: Florida Cancer Specialists / Sarah Cannon Research Institute, Lake Mary, FL
Anthony Sung, MD and Shekeab Jauhari, MD contributed equally to this paper
ISSN:0361-8609
1096-8652
1096-8652
DOI:10.1002/ajh.25781