Abstract
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.
Highlights
Acute myeloid leukemia (AML) is a molecularly heterogeneous disease
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 minimal residual disease (MRD) monitoring in the pre- and posttransplant setting
Haploidentical transplantation and the possible role of killer cell immunoglobulin-like (KIR) mismatches The difficulties in finding a suitable HLA-identical donor for every patient in need for it led to the idea of considering the “always present but overlooked” [6] haploidentical relatives as potential donors
Summary
Acute myeloid leukemia (AML) is a molecularly heterogeneous disease. Around 5–10% of affected patients show MLL translocations and an additional 8% have a MLL partial internal duplication. Reproducible sensitivity was 10-4 in each case (terminology according to van der Velden [14]) This PCR showed continuously decreasing MRD which was below the detection limit after the second and third consolidation cycle (Figure 1). Case 2 Features at presentation (relapse) A 28-year-old female patient was admitted to our hospital after diagnosis of relapsed acute myeloid leukemia She had been diagnosed with AML FAB M2 16 months earlier and had been treated elsewhere according to the AML2003 protocol (see above) arm B with two cycles of DA induction therapy and 3 cycles of high-dose. A bone marrow investigation shortly before start of conditioning revealed an MRD level of 10-2, which was only slightly higher compared to that achieved one month ago after FlAmsa therapy (Figure 1). A peak in CD8+ cells was observed on day +49 followed by a peak in CD8+ cells on day +58
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