Lack of utility of chimerism studies obtained 2–3 months after myeloablative hematopoietic cell transplantation for ALL

Abstract

Lineage specific chimerism studies are commonly obtained at several time points after nonmyeloablative haematopoietic cell transplantation to assess the tempo and degree of engraftment, and to monitor graft rejection. For patients who receive myeloablative transplants, the value of frequent chimerism analyses using sensitive molecular techniques is less certain. In this study, a retrospective analysis was performed to assess the transplant outcome of 89 adult patients with acute lymphocytic leukaemia who had chimerism studies of unfractionated bone marrow cells or peripheral blood subsets performed approximately 80 days after transplantation. These patients received unmanipulated, myeloablative transplants using either HLA-identical or HLA-mismatched, related or unrelated donor stem cells. Incomplete donor engraftment was present only in the CD3 + peripheral blood T-cells in a small percentage of patients. There was no correlation of mixed chimerism with transplant outcome. Routine "Day 80" chimerism studies in this group of patients who receive intensive, myeloablative conditioning regimens are not recommended.

Comparison of donor chimerism following myeloablative and nonmyeloablative allogeneic hematopoietic SCT

“…The 2001 workshop of the American Society of Blood and Marrow Transplantation and the International Bone Marrow Transplant Registry recommended against the routine assessment of chimerism in this group of patients. 1 Some recent studies have confirmed these findings and recommendations; 4,5 however, a recent report found that 28% of patients showed mixed chimerism at day 90 following MA HSCT, and these patients had worse outcomes than those with complete chimerism. The authors concluded that the detection of mixed chimerism following MA HSCT should prompt clinical intervention.…”

“…The results reported here are similar to those reported by others. [2][3][4][5][6][7][12][13][14] These data undermine the use of the terms 'myeloablative' and 'nonmyeloablative'. As Deeg 15 has recently pointed out, all transplantations in patients with malignant hematological disorders are designed to be myeloablative in order to achieve disease eradication.…”

“…A limitation to our study and those of others, however, is that we did not analyze what interventions may have been prompted by the results of these chimerism studies, which may then have affected the patient's clinical outcome. As factors other than preparative regimen including primary diagnosis, previous treatment, stem cell source, cell dose, histocompatibility and GVHD prevention [1][2][3][4][5][6][7][8] are important determinants of the speed and extent of donor chimerism, the conventional reliance on type of preparative regimen alone to determine whether to perform chimerism surveillance may be oversimplified. This study suggests the need for a fresh look at present indications for surveillance of chimerism following transplantation.…”

Early recipient chimerism testing in the T- and NK-cell lineages for risk assessment of graft rejection in pediatric patients undergoing allogeneic stem cell transplantation

“…Despite its diagnostic potential, it is not established as a routine parameter after RIC. The relevance of subset-specific chimerism testing after MA conditioning regimens has been discussed controversially, 5,12,20,27 and studies in pediatric patients are scarce. 1,15,16,18 The ultimate objective of chimerism analysis in the context of graft rejection is to identify impending graft loss as soon as possible to permit timely onset of therapeutic interventions to stabilize the graft, such as reducing immunosuppressive drugs or applying targeted donor leukocyte infusions (DLI).…”

“…5,6,[15][16][17][18] The plethora of different schedules and technical approaches to the detection and monitoring of chimerism renders the comparison of published data on the utility of chimerism testing for the prediction of graft rejection difficult. 6,8,[15][16][17][19][20][21][22] Moreover, the significance of different leukocyte subsets for graft rejection does not necessarily correlate with their relative and absolute levels due to their distinct immunological properties. In a number of studies, analysis of chimerism in purified leukocyte fractions was shown to be more informative than testing total leukocytes.…”