Molecular monitoring of minimal residual disease in two patients with MLL-rearranged acute myeloid leukemia and haploidentical transplantation after relapse

Experimental Hematology & Oncology

Lutz Uharek¹  Rolf Marschalek³  Carola Tietze-Bürger¹  Gunnar Lohm⁷  Igor Wolfgang Blau⁵  Jörg Beyer⁴  Birte Friedrichs⁵  Stefan Schwartz⁵  Nils Lachmann⁶  Claus Meyer²  Mara Molkentin⁵  Thomas Burmeister⁵ 

[1] Stem Cell Facility, Charité CBF, Hindenburgdamm 30, 12200, Berlin, Germany;Diagnostikzentrum für akute Leukämie (DCAL), Zentrum für Kinder- und Jugendmedizin, Goethe-Universität, Theodor Stern Kai 7, 60590, Frankfurt, Germany;Institut für Pharmazeutische Biologie, Biocenter, Goethe-Universität, Marie-Curie-Str. 9, 60439, Frankfurt, Germany;Vivantes Klinik Am Urban, Klinik für Hämatologie, Dieffenbachstraße 1, 10967, Berlin, Germany;Klinik für Hämatologie, Charité CBF, Hindenburgdamm 30, 12200, Berlin, Germany;Labor für Gewebetypisierung/HLA-Labor, Charité CVK, Augustenburger Platz 1, 13353, Berlin, Germany;Klinik für Radioonkologie und Strahlentherapie, Charité CBF, Hindenburgdamm 30, 12200, Berlin, Germany

关键词: Acute myeloid leukemia;    KIR;    MLL;    Haploidentical stem cell transplantation;    Minimal residual disease;   

Others  :  814860
DOI  :  10.1186/2162-3619-1-6

 received in 2012-03-16, accepted in 2012-04-18,  发布年份 2012

【 摘 要 】

This report describes the clinical courses of two acute myeloid leukemia patients. Both had MLL translocations, the first a t(10;11)(p11.2;q23) with MLL-AF10 and the second a t(11;19)(q23;p13.1) with MLL-ELL fusion. They achieved a clinical remission under conventional chemotherapy but relapsed shortly after end of therapy. Both had a history of invasive mycoses (one had possible pulmonary mycosis, one systemic candidiasis). Because no HLA-identical donor was available, a haploidentical transplantation was performed in both cases. Using a specially designed PCR method for the assessment of minimal residual disease (MRD), based on the quantitative detection of the individual chromosomal breakpoint in the MLL gene, both patients achieved complete and persistent molecular remission after transplantation. The immune reconstitution after transplantation is described in terms of total CD3⁺/CD4⁺, CD3⁺/CD8⁺, CD19⁺, and CD16⁺/CD56⁺ cell numbers over time. The KIR and HLA genotypes of donors and recipients are reported and the possibility of a KIR-mediated alloreactivity is discussed. This report illustrates that haploidentical transplantation may offer a chance of cure without chronic graft-versus-host disease in situations where no suitable HLA-identical donor is available even in a high-risk setting and shows the value of MRD monitoring in the pre- and posttransplant setting.

【 授权许可】

   
2012 Burmeister et al.; licensee BioMed Central Ltd.

【 图 表 】

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