Systematic analysis of interference due to stutter in estimating chimerism following hematopoietic cell transplantation

Thyagarajan, Bharat; Young, S. L.; Floodman, Stacy; Peterson, Randolph; Wang, Xinjing

doi:10.1002/jcla.20336

Cited by 5 publications

(2 citation statements)

References 8 publications

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“…This has proved to be a reliable assay in the setting of AML, where NK donor expansion is seen with 90–100% donor chimerism (29). The test was performed by the University of Minnesota clinical molecular diagnostics laboratory (30). The primary endpoint of the study was to evaluate the successful in vivo expansion of the infused allogeneic donor NK cell product.…”

Section: Methodsmentioning

confidence: 99%

A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer

et al. 2011

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Background Natural killer (NK) cells derived from patients with cancer exhibit diminished cytotoxicity compared with NK cells from healthy individuals. We evaluated the tumor response and in vivo expansion of allogeneic NK cells in recurrent ovarian and breast cancer. Methods Patients underwent a lymphodepleting preparative regimen: fludarabine 25 mg/m2 × 5 doses, cyclophosphamide 60 mg/kg × 2 doses, and, in seven patients, 200 cGy total body irradiation (TBI) to increase host immune suppression. An NK cell product, from a haplo-identical related donor, was incubated overnight in 1000 U/mL interleukin (IL)-2 prior to infusion. Subcutaneous IL-2 (10 MU) was given three times/week × 6 doses after NK cell infusion to promote expansion, defi ned as detection of ≥ 100 donor-derived NK cells/µL blood 14 days after infusion, based on molecular chimerism and flow cytometry. Results Twenty (14 ovarian, 6 breast) patients were enrolled. The median age was 52 (range 30–65) years. Mean NK cell dose was 2.16 × 107 cells/kg. Donor DNA was detected 7 days after NK cell infusion in 9/13 (69%) patients without TBI and 6/7 (85%) with TBI. T-regulatory cells (Treg) were elevated at day +14 compared with pre-chemotherapy (P = 0.03). Serum IL-15 levels increased after the preparative regimen (P = <0.001). Patients receiving TBI had delayed hematologic recovery (P = 0.014). One patient who was not evaluable had successful in vivo NK cell expansion. Conclusions Adoptive transfer of haplo-identical NK cells after lymphodepleting chemotherapy is associated with transient donor chimerism and may be limited by reconstituting recipient Treg cells. Strategies to augment in vivo NK cell persistence and expansion are needed.

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Section: Methodsmentioning

confidence: 99%

A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer

et al. 2011

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“…Antigens evaluated included CD3, CD7, CD10, CD13, CD14, CD15, CD19, CD33, CD34, CD45, CD56, CD117, and HLA-DR. Myeloid maturation patterns by flow cytometry were not evaluated. Engraftment/chimerism analysis was performed as previously described [ 10 ], with interpretive reports reviewed for this study.…”

Section: Methodsmentioning

confidence: 99%

Impending relapse of myelodysplastic syndrome after allogeneic transplant is difficult to diagnose and requires a multi-modal approach

et al. 2017

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BackgroundThe only potentially curative therapy for myelodysplastic syndrome is allogeneic hematopoietic cell transplant; unfortunately, there is a high relapse rate. The objective of this study was to perform a detailed clinicopathologic study of patients with relapsed myeloid neoplasm following allogeneic hematopoietic cell transplant for myelodysplastic syndrome.MethodsPre-transplant, post-transplant, and relapse bone marrow and peripheral blood morphologic features (including dysplasia) were retrospectively evaluated by study authors. Clinical features and results of cytogenetic analysis and engraftment/chimerism studies were obtained from the medical record.ResultsOur study describes 21 patients with a median time to relapse of 6 months (range 2–82). Ten of the patients relapsed with higher grade disease, including six with overt acute myeloid leukemia. Pre-transplant megakaryocyte dysplasia was associated with dysplastic megakaryocytes in the relapse specimen; however, neither erythroid dysplasia nor granulocytic dysplasia were associated with their counterpart in the relapse specimen. Relapse specimens had a lower marrow cellularity and higher blast percentage than pre-transplant disease. Cytogenetic comparisons before and after transplant showed variety, including clonal evolution (22%), the same abnormal clone (33%), or a different abnormal clone (22%).ConclusionsOur detailed review of post-transplant marrow biopsies prior to relapse highlights the difficulty in diagnosing relapse and particularly impending relapse.

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Engraftment Analysis Using Short Tandem Repeats Following Allogeneic Hematopoietic Cell Transplantation

Warshawsky¹,

Chi²

2012

Laboratory Hematology Practice

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Systematic analysis of interference due to stutter in estimating chimerism following hematopoietic cell transplantation

Cited by 5 publications

References 8 publications

A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer

A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer

Impending relapse of myelodysplastic syndrome after allogeneic transplant is difficult to diagnose and requires a multi-modal approach

Engraftment Analysis Using Short Tandem Repeats Following Allogeneic Hematopoietic Cell Transplantation

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