title: Minimal residual disease is common after allogeneic stem cell transplantation in patients with B cell chronic lymphocytic leukemia and may be controlled by graft-versus-host disease.
abstract: Following allogeneic stem cell transplantation (SCT), we studied the presence of donor and recipient derived cells within the CD19+ B cell fraction, in patients with B cell chronic lymphocytic leukemia (CLL). The chimeric status of the six patients studied was further investigated with minimal residual disease (MRD) detection, by sequencing and using patient-specific primers derived from junctional regions of clonally rearranged immunoglobulin heavy-chain (IgH) receptor genes. To date, five of six patients are alive with a median follow-up time of 24 months (range 15-60) post-SCT. All patients experienced acute and chronic graft-versus-host disease and responded clinically to SCT. All patients were MRD positive after SCT, which correlated to mixed chimerism within the CD19+ cell fraction in all samples except one (25/26). High levels of tumor necrosis factor-alpha (TNF-alpha) and soluble interleukin-2 receptor (sIL-2R) indicated advanced disease, and patients with increased levels pre- and post-SCT were also those with the most long-lasting PCR-detectable MRD post-SCT. Hence, a high tumor burden pre-SCT may reflect the long duration of detectable MRD in patients with B-CLL after SCT. A durable anti-leukemic effect was probably important in these patients.
authors.affiliation: Centre for Allogeneic Stemcell Transplantation, Karolinska Institute at Huddinge Hospital, Huddinge, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Mattsson
authors.forename: M
authors.initials: M
authors.lastname: Uzunel
authors.forename: M
authors.initials: M
authors.lastname: Remberger
authors.forename: P
authors.initials: P
authors.lastname: Ljungman
authors.forename: E
authors.initials: E
authors.lastname: Kimby
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
authors.forename: H
authors.initials: H
authors.lastname: Zetterquist
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000517:prevention & control; D016133:Polymerase Chain Reaction; D015375:Receptors, Interleukin-2 / Q000097:blood; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007136:Immunoglobulins; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha