Chimerism and transplant-related diagnostics

Müller‐Bérat, Nicole; Lion, Thomas

doi:10.1038/sj.leu.2404268

Cited by 9 publications

(5 citation statements)

References 36 publications

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“…The chimerism assay system is robust and reliable, has now been standardized to a fluorescent based assay (Lion, 2003;McCann et al , 2005) and is used by many laboratories worldwide. As discussed in the “Chimerism Debate” in the Leukemia journal, (Dubovsky et al , 1999;Klingebiel et al , 2001; Lawler, 2001; Lion, 2001, 2003; Lion et al , 2001; Lion & Muller‐Berat, 2003; Baron & Sandmaier, 2006; Muller‐Berat & Lion, 2006), it is now apparent that chimerism information can be considered in combination with other criteria as an indicator for clinical intervention in a selected number of diseases. This study indicates that SAA is one of the diseases where we should consider routine testing for chimerism analysis post‐SCT.…”

Section: Discussionmentioning

confidence: 99%

Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA

et al. 2009

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Summary Ninety‐one patients were studied serially for chimeric status following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA) or Fanconi Anaemia (FA). Short tandem repeat polymerase chain reaction (STR‐PCR) was used to stratify patients into five groups: (A) complete donor chimeras (n = 39), (B) transient mixed chimeras (n = 15) (C) stable mixed chimeras (n = 18), (D) progressive mixed chimeras (n = 14) (E) recipient chimeras with early graft rejection (n = 5). As serial sampling was not possible in Group E, serial chimerism results for 86 patients were available for analysis. The following factors were analysed for association with chimeric status: age, sex match, donor type, aetiology of aplasia, source of stem cells, number of cells engrafted, conditioning regimen, graft‐versus‐host disease (GvHD) prophylaxis, occurrence of acute and chronic GvHD and survival. Progressive mixed chimeras (PMCs) were at high risk of late graft rejection (n = 10, P < 0·0001). Seven of these patients lost their graft during withdrawal of immunosuppressive therapy. STR‐PCR indicated an inverse correlation between detection of recipient cells post‐SCT and occurrence of acute GvHD (P = 0·008). PMC was a bad prognostic indicator of survival (P = 0·003). Monitoring of chimeric status during cyclosporin withdrawal may facilitate therapeutic intervention to prevent late graft rejection in patients transplanted for SAA.

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Section: Discussionmentioning

confidence: 99%

Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA

et al. 2009

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“…11 The ability to monitor and modulate donor chimerism by changes in immunosuppression and donor lymphocyte infusions forms integral part of the procedure. 27 These techniques require laboratory infrastructure, repetitive monitoring and might be more costly long term. With limited resources, standard conditioning might be the preferred choice.…”

Section: Discussionmentioning

confidence: 99%

Results of the EBMT activity survey 2005 on haematopoietic stem cell transplantation: focus on increasing use of unrelated donors

Gratwohl

Baldomero

Frauendorfer

et al. 2007

Bone Marrow Transplant

100

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This EBMT activity report documents the haematopoietic stem cell transplantation (HSCT) activity in Europe in 2005. It provides numbers of HSCT by indication, donor type and stem cell source, lists the new practice of planned double transplants with allogeneic after autologous HSCT and concentrates on the increasing role of unrelated transplants over the last years. In 2005, there were 24 168 first HSCT, 8890 allogeneic (37%), 15 278 autologous (63%) and 3773 additional re-or multiple transplants reported from 597 centres in 43 participating countries. Main indications were leukaemias (7404 (31%; 82% allogeneic)); lymphomas (13 825 (57%; 89% autologous)); solid tumours (1655 (7%; 92% autologous)) and non-malignant disorders (1131 (5%; 93% allogeneic)). A total of 671 planned allogeneic after autologous HSCT were reported; the majority for myeloma (52%), lymphoma (28%) and acute myeloid leukaemia (11%). Compared to 2004, there was a 20% increase in allogeneic HSCT; numbers of autologous HSCT remained constant. The most noticeable increase was in unrelated HSCT, which comprise 41% of all allogeneic HSCT. Unrelated HSCT were preferentially performed for leukaemias and in countries with high income according to World Bank criteria. These data illustrate the current experience in Europe and form the basis for patient counselling and decisions making at health care institutions.

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“…57,58 The clinical value of regular monitoring of chimerism in myeloid malignancies after SCT is demonstrated by reports on the successful withdrawal of immunosuppression and adoptive immunotherapeutic intervention by DLI in case of decreasing chimerism as reported by Bader et al 59 in five pediatric patients with AML and MDS. The introduction of RIC has further increased the clinical importance of chimerism as patients show more frequently mixed chimerism (MC) when compared to standard conditioning regimens.…”

Section: Chimerismmentioning

confidence: 99%

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

Bacher

Zander

Haferlach

et al. 2008

Bone Marrow Transplant

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Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloproliferative diseases (CMPDs) and in poor-risk AML. Techniques to monitor the minimal residual disease, for example, by PCR or immunophenotyping gain increasing importance in the post transplantation period as basis for improved and earlier therapeutic interventions in impending relapse. Recent markers such as the NPM1 mutations in AML or the JAK2V617F mutation in the CMPD can be exactly quantified by real-time PCR and were evaluated for their prognostic value in the post transplantation phase and for their utility to plan adoptive immunotherapy in case of molecular relapse. With respect to chimerism, new and very sensitive methods were introduced, for example, quantitative assessment of genetic polymorphisms by realtime PCR, but also methods here are still highly individualized. Only in CML, where SCT focuses now on poor-risk cases or cases of tyrosine kinase inhibitor failure, follow-up schedules are standardized. Standardization of the different diagnostic techniques and of the intervals in the post transplantation period is urgently needed also in other myeloid malignancies and should be focus of future studies.

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Chimerism and transplant-related diagnostics

Abstract: The editors of Leukemia encourage the submission of highly selective quality articles fitting within the scope of the new Section.

Cited by 9 publications

References 36 publications

Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA

Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA

Results of the EBMT activity survey 2005 on haematopoietic stem cell transplantation: focus on increasing use of unrelated donors

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

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