Use of chimerism analysis after allogeneic stem cell transplantation: Belgian guidelines and review of the current literature

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option in both adult and pediatric patients with malignant and non-malignant hematological diseases. Chimerism analysis, which determines the donor or recipient origin of hematopoietic cells in HSCT recipients, is an essential aspect of post-HSCT follow-up. Objectives: To review the current literature and develop Belgian consensus guidelines for the use of chimerism analysis in the standard of care after allogeneic HSCT. Methods: Non-systematic review of the literature in consultancy with the members of the BHS transplantation committee. Results: Clinical application with regards to prediction of graft failure or relapse as well as cell source are reviewed. A consensus guideline on the use of chimerism analysis after HSCT is presented. Conclusion: Monitoring of the dynamics or kinetics of a patient's chimerism status by serial analysis at fixed time points, as well as on suspicion of relapse or graft failure, is needed to monitor engraftment levels, as well as disease control and possible relapse.

Total Body Irradiation–Based Conditioning Regimen Improved the Survival of Adult Patients With T-Cell Lymphoblastic Lymphoma After Allogeneic Peripheral Blood Stem Cell Transplantation

“…Chimerism analysis was performed on bone marrow aspiration using short tandem repeat (STR)–PCR in patients with a sex-matched donor, and fluorescence in situ hybridization (FISH) analysis of X and Y chromosome in sex-mismatched patients. Complete chimerism was defined by the detection of ≥95% of donor cells using STR-PCR and FISH 16 – 18 . Acute GvHD (aGvHD) was graded according to the modified Glucksberg criteria 19 and chronic GvHD (cGvHD) according to the revised Seattle criteria 20 .…”

Immunophenotypic measurable residual disease monitoring in adult acute lymphoblastic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation

“…Therefore, any comparison between chimerism and post allo-HSCT MRD monitoring should consider the sensitivities and specificities of the techniques available in each center. As shown in Table 3, most of the techniques currently used for MRD evaluation (88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98) including MFC (88-90) display a higher sensitivity than the majority of chimerism detection methods.…”

“…We apologize to those authors whose work has not been cited. 95,97 x PB, BM, PB sorted lymphoid and myeloid cells 94,95,98 RFLP 96 x PB, BM, PB sorted lymphoid and myeloid cells 94,95,98 X/Y FISH 97 x x PB, BM, PB sorted lymphoid and myeloid cells 94,95,98 STR-PCR 94,95,96,97 x PB, BM, PB sorted lymphoid and myeloid cells 94,95,98 RQ-PCR 94,95,96,97 x x PB, BM, PB sorted lymphoid and myeloid cells 94,95,98 ddPCR 94,96 x x PB, BM, PB sorted lymphoid and myeloid cells 94,95,98 NGS 96,97 x x PB, BM, PB sorted lymphoid and myeloid cells 94,95,98…”

CAR-T after Stem Cell Transplantation in B-Cell Lymphoproliferative Disorders: Are They Really Autologous or Allogenic Cell Therapies?

“…For this reason, it is important to monitor donor-recipient chimerism and determine the origin of HSC in recipients to predict the outcome of the allo-HSCT [ 56 ]. Nonetheless, it has been reported that chimerism could be mixed (<95%) or persists even though the patient relapses (<95%) [ 57 ]. It has been demonstrated that chimerism is a dynamic process, as patients with complete chimerism post-transplant can later develop a “mixed chimerism” and conversely [ 54 ].…”