Unmanipulated peripheral blood stem cell autograft in chronic lymphocytic leukemia: clinical findings and biological monitoring.
OBJECTIVE
To investigate the feasibility of peripheral blood stem cell (PBSC) transplantion in patients with high-risk chronic lymphocytic leukemia (CLL) in remission after fludarabine therapy, the clinical impact of minimal residual disease (MRD) monitoring and the immunologic reconstitution after transplantation.


METHODS
Twenty CLL patients, in clinical complete remission (CR) after fludarabine, were offered an unmanipulated PBSC transplant and were longitudinally monitored for MRD and immunologic reconstitution.


RESULTS
Due to unsatisfactory PBSC collection, 4 patients received bone marrow cells. All patients engrafted. Two patients died, one due to infection and one because of another neoplasia. Thirteen patients are at present in clinical CR after a median follow-up of 17 months and 18 patients are alive with a survival probability of 0.87 (+/-0.04) at 52 months after transplant. Fifteen patients had a molecular remission. Three of them showed a molecular relapse 16-28 months after autograft, followed by a clinical relapse 10-16 months later. Three of the four patients who remained persistently rearranged could be revaluated over time and showed an immunologic relapse 11-26 months after transplant; two of these had a clinical relapse 12 and 7 months later. A marked and persistent impairment of both the B- and T-immunologic compartments was recorded in the horizontal follow-up.


CONCLUSIONS
Unmanipulated PBSC autograft is a feasible procedure that produces prolonged molecular remissions in high-risk CLL patients. Persistence or reappearance of a molecular signal after engraftment is predictive of subsequent immunologic and clinical CLL recurrence. The long -lasting impairment of the host immune repertoire after fludarabine followed by autograft has to be taken into account in the patients' management.
Meloni
G
G
Dipartimento di Biotecnologie Cellulari ed Ematologia, University "La Sapienza", Roma, Italy. meloni@bce.med.uniroma1.it
Proia
A
A
Mauro
F
F
Amaranto
P
P
Capria
S
S
Cimino
G
G
Cordone
I
I
de Fabritiis
P
P
Rapanotti
C
C
Reato
G
G
Vignetti
M
M
Foa
R
R
Mandelli
F
F
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000276:immunology / Q000628:therapy*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000276:immunology; D010865:Pilot Projects; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use / Q000633:toxicity
D014740:Vidarabine; C024352:fludarabine