Mixed chimerism of bone marrow CD34+ progenitor cells (genotyping, bcr/abl analysis) after allogeneic transplantation for chronic myelogenous leukemia1

Abstract

The lineage-restricted MCh of progenitors after BMT is in keeping with the assumption that leukemic (bcr/abl ) precursors represent only a fraction of the total host-derived (chimeric) CD34 cells. These residual clonally transformed progenitors survive myeloablative treatment and thus may be the source for a later relapse.

Differences in proportion and dynamics of recipient hematopoiesis following hematopoietic cell transplantation in CML and IMF

“…However, it has to be considered that the number of host cells does not necessarily reflect the number of neoplastic hematopoiesis (17,18,20) and the relevance of host cell number on HCT outcome remains controversial (27)(28)(29)(30). Analyzing the same BM biopsies, we reported a BCR/ABL positive population within the CD34 + cell compartment ranging from 5 to 10% (18) indicating that 30-50% of the host CD34 + cells bear the translocation. These data indicate that an increase in mCh indeed is a powerful indicator of initial relapse and therefore an important tool to initialize accurate treatment as soon as possible (31).…”

“…In other words, the presented data indicate that the interplay between reduction of the host cell mass and efficiency of the unedited donor immune system in eradication of host and tumor cells has to be linked to each disease and disease stage. An excess of tumor mass over each individual threshold therefore leads to uncontrolled proliferation of the neoplastic progenitors, an observation that can be underlined by previously published FISH data on sequential trephine biopsies of relapsing CML patients (17,18). The finding that myeloablative regime may not be sufficient to cure CML at least in advanced disease, points to the same direction (3,37,38).…”

“…The immature, potentially dormant hematopoiesis was detected by CD34 IHC. Morphological control of the stained cells within the BM allowed a clear discrimination from CD34 endothelial cells because BM vessels were omitted in the evaluation (18).…”

“…Assuming that the majority of neoplastic cells are comprised in this compartment our data are in line with the findings that early leukemia relapse is indicated by sequential monitoring of mCh in PB CD34 + cells (36). Concerning CML, the prominent role of BM CD34 + cells is further highlighted by the finding of constant persistence of malignant hematopoietic progenitors in patients in complete PB cytogenetic remission (18). Although a direct comparison was not conducted it is likely that these findings affect CD34 + progenitors from both sources, PB and BM, respectively.…”

“…Patients had received BM grafts (median size 2.3x10 8 /kg nucleated cells) from sexmismatched HLA identical family donors at the University Hospital of Essen, Germany, following standard procedures that included conditioning regimens (Cy 60 mg/kg/day x 2; dose of total body irradiation (TBI) 4 x 2.5 Gy cobalt-60 and GvHD prophylaxis (MTX + Cyclosporin A). A successful engraftment according to standard criteria was established at day 24±5 in all patients (17,18). Acute GvHD grade II-III developed in five patients and limited chronic GvHD was diagnosed in three patients.…”