Chimerism does not predict for outcome after alemtuzumab-based conditioning: lineage-specific analysis of chimerism of specific diseases may be more informative

Lim, Zi Yi; Pearce, Laurence; Ingram, Wendy; Ho, A Y L; Mufti, Ghulam J.; Pagliuca, Antonio

doi:10.1038/sj.bmt.1705937

Cited by 18 publications

(11 citation statements)

References 11 publications

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“…This is likely related to a number of factors, including difficulties in interpreting changes in WB chimerism and their relationship to relapse, 20 the cost of frequent chimerism tests, particularly when subsets are obtained, availability of flow cytometry for minimal residual disease detection, 21 lack of options for post-transplant interventions and toxicities of available therapies, such as donor lymphocyte infusions. There have been significant changes in techniques for chimerism testing over time, from the variable number of tandem repeats to short tandem repeats and currently the single nucleotide polymorphism.…”

Section: Discussionmentioning

confidence: 99%

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

Horn

Soni

Khan

et al. 2008

Bone Marrow Transplant

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An increasing percentage of autologous cells (increasing chimerism) in the whole blood (WB) chimerism test following allogeneic transplant is related to a very high risk of relapse. Preemptive immunotherapy may decrease the risk of relapse in some patients. Our prospective multiinstitutional study evaluated the feasibility of longitudinal chimerism testing in a central laboratory, compared WB, CD3 þ and leukemia-specific lineage chimerism in patients with a variety of hematologic malignancies, and evaluated the feasibility of fast withdrawal of immunosuppression based on WB chimerism results. Centralized chimerism testing was feasible and showed low interassay variability. Increasing mixed chimerism (MC) in WB was not useful as a predictor of relapse in our study. The presence of full donor chimerism in WB, CD3 þ and leukemia-specific lineages on all measurements was related to a significantly lower risk of relapse than the presence of MC in either subset (11 vs 71%, respectively; P ¼ 0.03). Increasing host chimerism in leukemia-specific lineage heralds relapse, but it was not detected early enough to allow immunotherapy. Further studies correlating lineage-specific chimerism and minimal residual disease are required. The goal of preemptive immunotherapy should be to achieve full donor chimerism in WB in CD3 þ and leukemia-specific lineages.

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Section: Discussionmentioning

confidence: 99%

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

Horn

Soni

Khan

et al. 2008

Bone Marrow Transplant

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“…6 Although the methods of chimerism testing are well established and its importance for graft monitoring is widely accepted, there is still considerable controversy regarding the actual relevance of distinct levels of recipient chimerism (RC) and its dynamics for graft outcome. [7][8][9][10][11][12] It is conceivable that the predictive value of chimerism levels might vary significantly depending on the underlying disease, the preparative regimen, the donor/recipient constellation and post-transplant immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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Timely diagnosis of impending graft rejection is crucial for effective therapeutic intervention after allogeneic hematopoietic stem cell transplantation (SCT). We have investigated the predictive potential of early leukocyte subset-specific chimerism for graft loss in children undergoing SCT. In total, 192 pediatric patients transplanted for the treatment of malignant and non-malignant diseases after reduced-intensity or myeloablative conditioning were investigated. Surveillance of lineage-specific chimerism was initiated upon first appearance of leukocyte counts amenable to cell sorting. Graft rejection occurred in 23 patients between 24 and 492 days post-transplant (median 63 days). The first chimerism analysis of T and NK cells performed at a median of 20 days after SCT identified three different risk groups that were independent from the conditioning regimen: recipient chimerism (RC) levels in T cells below 50% indicated a very low risk of rejection (1.4%), whereas high levels of RC (490%) both in T and NK cells heralded graft loss in the majority of patients (90%) despite therapeutic interventions. RC 450% in T cells and p90% in NK cells defined an intermediate-risk group in which timely immunotherapy frequently prevented rejection. Early assessment of T-and NK-cell chimerism can therefore be instrumental in the risk assessment and therapeutic management of imminent graft rejection.

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“…Moreover chimerism analysis in subpopulations could provide indications for early graft rejection, GVHD and relapse. 4,[8][9][10][11][12][13][14][15] Therefore, enrichment of cell subpopulations is essential to enable lineage-specific chimerism analyses. Most prevalent are two different enrichment technologies: Fluorescence-Activated Cell Sorting (FACS) and Magnetic Cell Sorting (MACS, Miltenyi Biotec, Bergisch Gladbach, Germany).…”

Section: Introductionmentioning

confidence: 99%

Enrichment of cell subpopulations applying automated MACS technique: purity, recovery and applicability for PCR-based chimerism analysis

Willasch

Eing

Kuçi

et al. 2009

Bone Marrow Transplant

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Enrichment of cell subpopulations is a prerequisite for lineage-specific chimerism analysis (LCA), a frequent approach in follow-up after allo-SCT. An efficient enrichment technique is Magnetic Cell Sorting (MACS) using the AutoMACS separator. However, evaluation of purity, recovery and applicability for PCR-based chimerism analysis of MACS-enriched subpopulations from post-transplant peripheral blood, providing reduced cell numbers and/or unbalanced proportions of subpopulations, is currently unavailable. We performed enrichment of CD3-, CD14-, CD15-, CD19-and CD56-positive subpopulations using 'Whole Blood MicroBeads' and AutoMACS separator in 137 prospectively collected peripheral blood samples from 15 paediatric patients after allo-CD3-/CD19-depleted SCT. Purity was assessed by immune phenotyping. Recovery and applicability for chimerism analysis was evaluated. Excellent purity 490% was achieved in CD14-, CD15-positive cells in 81%, 95% of the isolates and in 86% of CD3 and CD19 isolates, if ACC was 4400 cells per ll. Median purity of CD56-positive isolates was 78.9%. Recovery 490% was between 93 (CD56) and 37% (CD15). Conventional and real-time PCR-based chimerism analysis was feasible in virtually all samples. Isolation of cell subpopulations by automated cell enrichment in post-transplant peripheral blood is feasible and fast providing excellent purity and recovery for routine lineage-specific chimerism analysis.

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Chimerism does not predict for outcome after alemtuzumab-based conditioning: lineage-specific analysis of chimerism of specific diseases may be more informative

Cited by 18 publications

References 11 publications

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

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

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

Enrichment of cell subpopulations applying automated MACS technique: purity, recovery and applicability for PCR-based chimerism analysis

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