Journal of Clinical Oncology, Vol 15, 1575-1582, Copyright © 1997 by American Society of Clinical Oncology
Mobilization and transplantation of Philadelphia-negative peripheral- blood progenitor cells early in chronic myelogenous leukemia
AM Carella, I Cunningham, E Lerma, A Dejana, F Benvenuto, M Podesta, L Celesti, F Chimirri, M Abote, F Vassallo, O Figari, C Parodi, M Sessarego, M Valbonesi, P Carlier, E Prencipe, AM Gatti, D van den Berg, R Hoffman and F Frassoni
Hematology and Autologous Bone Marrow Transplant Unit, Ospedale San Martino, Genova, Italy.
PURPOSE: Mobilization of Philadelphia (Ph) chromosome-negative progenitors
is now possible in many Ph1-positive chronic myelogenous leukemia (CML)
patients who had received interferon alfa (IFN-alpha) with no cytogenetic
response. In this pilot study, we used this approach in patients without
prior IFN-alpha therapy to determine if the number and quality of mobilized
progenitors would be increased and to evaluate the potential effect of
these cells as autografts. PATIENTS AND METHODS: Twenty-two untreated
patients were mobilized within 12 months of diagnosis. The treatment
regimen consisted of the mini-ICE protocol. Beginning on day +8,
granulocyte colony-stimulating factor (G- CSF) was used in all patients.
Leukophoresis was performed as the patients were recovering from aplasia,
when WBC count exceeded 0.8 x 10(9)/L. RESULTS: In 14 patients, (63%) the
leukophoresis product was entirely Ph1-negative and in four patients the
Ph1-positive cell rate was < or = 7%. Significant numbers of long-term
culture-initiating cells (LTC-IC) and CD34+ Thy1+Lin- cells were found in
most of the Ph1- negative collections that were tested. Twelve patients
underwent autografting with their mobilized peripheral-blood progenitor
cells (PBPC) (Ph1-negative collections, 10 patients; major cytogenetic
response, two patients). All patients engrafted and are alive; six have
Ph1-negative marrow 7 to 15 months after autografting. Posttransplant
treatment was IFN-alpha combined with interleukin (IL)-2 because of the
recent demonstration of synergistic activity in augmenting cytolytic
activity. CONCLUSION: Intensive chemotherapy given in early chronic phase
of CML is well tolerated and results in high numbers of circulating
Ph1-negative precursor cells.
