title: Mobilization of cytogenetically 'normal' blood progenitors cells by intensive conventional chemotherapy for chronic myeloid and acute lymphoblastic leukemia.
abstract: Various lines of evidence suggest that substantial numbers of very primitive normal hematopoietic cells persist in the marrow of most patients with CML, despite the presence of an expanded Philadelphia-Chromosome (Ph) positive population, and that normal clones might, in certain circumstances, have a proliferative advantage over leukemic populations. We have recently demonstrated in 5/8 CML patients with blastic phase (BP) that the blood progenitor cells/(BPC) harvested during early recovery from marrow aplasia were Ph-negative on cytogenetic analysis, suggesting that leukapheresis may provide a useful source of 'normal' progenitors for subsequent reinfusions. We report here an update on 40 patients with Ph + CML and 9 patients with ALL in first or subsequent relapses with associated cytogenetic translocations including t(8;14) t(4;8) t(4;11) and t(9;22). All these patients received intensive conventional chemotherapy and during early recovery from marrow aplasia, when the WBC reached 0.5-2.0 x 10(9)/L, BPC were collected by 4-8 leukapheresis and tested for the persistence of the marker translocations and, when possible, for the presence of the hybrid bcr/abl transcripts by polymerase chain reaction (PCR). In seven out of 10 patients with chronic phase CML, BPC were Ph-negative and in 5 PCR negative. In both accelerated phase patients, BPC were Ph-negative but PCR-positive and in eight out of 28 blastic CML patients, BPC were Ph-negative and in two cases also PCR-negative. Six out of 9 ALL patients, lost the cytogenic translocations. After complete recovery, 16 patients were subsequently given high-dose therapy followed by reinfusion of 'normal' BPC.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Hematology I, Ospedale S. Martino, Genova, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Carella
authors.forename: N
authors.initials: N
authors.lastname: Pollicardo
authors.forename: E
authors.initials: E
authors.lastname: Pungolino
authors.forename: M R
authors.initials: MR
authors.lastname: Raffo
authors.forename: M
authors.initials: M
authors.lastname: Podesta
authors.forename: R
authors.initials: R
authors.lastname: Ferrero
authors.forename: D
authors.initials: D
authors.lastname: Pierluigi
authors.forename: S
authors.initials: S
authors.lastname: Nati
authors.forename: K
authors.initials: K
authors.lastname: Naibo
authors.forename: A
authors.initials: A
authors.lastname: Congiu
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007937:Leukapheresis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents