Prompt initiation of immunotherapy in children with an increasing number of autologous cells after allogeneic HCT can induce complete donor-type chimerism: a report of 14 children

How and when should we monitor chimerism after allogeneic stem cell transplantation?

“…Using STR-PCR-based serial analysis of microsatellite regions in short time intervals, it could be shown that patients with rapidly increasing mixed chimerism have the highest risk of relapse. [13][14][15] These reports could be confirmed by others, [96][97][98][99] whereas some studies did not find a correlation between chimerism and relapse. 22,38,100,101 These discrepancies may partly be explained with sampling protocols used in the studies.…”

“…Based on these studies, several consecutive trials were initiated, evaluating the possibility to prevent relapse by pre-emptive immunotherapy on the basis of chimerism analysis in patients with acute leukemias. 96,99,[105][106][107][108] Most recently, our group could show in 163 children with ALL that STR-based chimerism analysis in short time interval is able to define a great cohort of children with impending relapse and also that overt relapse, in principle, could be prevented by preemptive immunotherapy on the basis of increasing mixed chimerism. 109 However, these analysis showed also that (i) it was not possible to realize impending relapse in all patients and (ii) the time interval between the conversion of chimerism and relapse can be very short.…”

Monitoring of post-transplant remission of childhood malignancies: is there a standard?

“…By using short tandem repeat (STR)-PCR-based serial analysis of microsatellite regions at short time intervals, it could be shown that patients with rapidly increasing mixed chimerism have the highest risk of relapse. 3,9 These reports could be confirmed by others, [10][11][12] whereas some studies did not find a correlation between chimerism and relapse. 13 These discrepancies may partly be explained with sampling protocols used in the studies.…”

“…On the basis of these studies, several consecutive trials were initiated, evaluating the possibility of preventing relapse by pre-emptive immunotherapy on the basis of chimerism analysis in patients with acute leukemias. 10,12 Most recently, our group showed in 163 children with ALL that STR-based chimerism analysis at short time interval is able to define a large cohort of children with impending relapse and also that overt relapse, in principle, could be prevented by preemptive immunotherapy on the basis of increasing mixed chimerism. 16 However, these analyses also showed, that (i) it was not possible to identify impending relapse in all patients and (ii) the time interval between the identification of chimerism and relapse can be very short.…”

Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies

“…Coexistence of donor and host hematopoietic cells, called mixed chimerism (MC), and particularly an increasing proportion of host cells following allogeneic transplant for acute leukemia has been linked to the increased risk of relapse. [1][2][3][4][5] Although MC may predict relapse, detecting residual host cells after transplant, is not equivalent to detecting minimal residual disease. In the early post-transplant period, MC is caused predominantly by normal recipient hematopoietic cells.…”