Mobilization of cytogenetically 'normal' blood progenitors cells by intensive conventional chemotherapy for chronic myeloid and acute lymphoblastic leukemia.
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)
Carella
A M
AM
Division of Hematology I, Ospedale S. Martino, Genova, Italy.
Pollicardo
N
N
Pungolino
E
E
Raffo
M R
MR
Podesta
M
M
Ferrero
R
R
Pierluigi
D
D
Nati
S
S
Naibo
K
K
Congiu
A
A
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
D000970:Antineoplastic Agents