title: High-dose chemo-radiotherapy followed by autologous Philadelphia chromosome-negative blood progenitor cell transplantation in patients with chronic myelogenous leukemia.
abstract: Twenty-three patients with chronic myelogenous leukemia in early chronic phase (ECP) and not previously treated with alpha-interferon (IFN-alpha) (10 patients), in ECP but pretreated with IFN-alpha (<12 months) (seven patients) and in late chronic phase (LCP) pretreated with IFN-alpha (>12 months) (six patients) underwent autografting with Philadelphia (Ph) chromosome-negative blood progenitor cells (BPCs) (20 patients), or partially/totally Ph-positive BPCs (three patients), previously mobilized during the early phase of recovery after aplasia induced by intensive chemotherapy. The conditioning regimen consisted of high-dose chemotherapy alone or followed by total body irradiation (TBI). Recombinant G-CSF was given after BPCs infusion on day +8. All patients in ECP not pretreated with IFN-alpha are alive and five of them are Ph-negative in the marrow after autografting. Six of seven patients autografted with Ph-negative BPCs in the group of ECP pretreated with IFN-alpha (<12 months) are alive and two of them are still Ph-negative in the marrow. In the same group, the only patient transplanted with partially Ph-positive BPCs, died of blastic transformation 2 months after reinfusion. Three patients (two patients autografted with Ph-negative BPCs and one patient with Ph-positive BPC) in the group of LCP pretreated with IFN-alpha >12 months are alive but Ph-positive after autografting. The other three patients of the same group died of procedure-related toxicity (two patients) and blastic transformation (one patient). Seventeen patients (10/10 ECP not pretreated with IFN-alpha; 5/7 ECP pretreated with IFN-alpha and 2/6 LCP pretreated with IFN-alpha) of 23 autografted patients were treated with IFN-alpha +/- IL-2. Toxicities after autografting were mostly related to myelosuppression, particularly thrombocytopenia. All patients of the two groups pretreated with IFN-alpha developed febrile episodes during the aplastic phase following BPCs reinfusion. No patient autografted in ECP and those not pretreated with IFN-alpha developed febrile episodes. This is also probably due to the use of i.v. antibiotic and antimicotic prophylaxis when neutrophils were < or = 1 x 10(9)/l after autografting. Greater toxicity was observed in patients pretreated with IFN-alpha, being lethal in two cases in LCF. In conclusion, the "in vivo' manipulation approach employed in our institution is a safe procedure and it results in a high collection of Ph-negative cells in the blood if the cells are harvested: (1) in early chronic phase; (2) in early phase of recovery after chemotherapy-inducing aplasia; (3) in patients not extensively pretreated with IFN-alpha. The data presented here have shown encouraging trends in chronic phase of CML and offer new perspective for patients without an HLA-identical donor or for patients who do not respond to IFN-alpha.
authors.affiliation: Hematology and ABMT Unit, Ospedale S Martino, Genova, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Carella
authors.forename: F
authors.initials: F
authors.lastname: Chimirri
authors.forename: M
authors.initials: M
authors.lastname: Podestà
authors.forename: A
authors.initials: A
authors.lastname: Pitto
authors.forename: G
authors.initials: G
authors.lastname: Piaggio
authors.forename: A
authors.initials: A
authors.lastname: Dejana
authors.forename: E
authors.initials: E
authors.lastname: Lerma
authors.forename: N
authors.initials: N
authors.lastname: Pollicardo
authors.forename: F
authors.initials: F
authors.lastname: Vassallo
authors.forename: M
authors.initials: M
authors.lastname: Soracco
authors.forename: F
authors.initials: F
authors.lastname: Benvenuto
authors.forename: M
authors.initials: M
authors.lastname: Valbonesi
authors.forename: P
authors.initials: P
authors.lastname: Carlier
authors.forename: R
authors.initials: R
authors.lastname: Vimercati
authors.forename: E
authors.initials: E
authors.lastname: Prencipe
authors.forename: A M
authors.initials: AM
authors.lastname: Gatti
authors.forename: R A
authors.initials: RA
authors.lastname: Ferrara
authors.forename: M
authors.initials: M
authors.lastname: Incagliato
authors.forename: G
authors.initials: G
authors.lastname: Florio
authors.forename: F
authors.initials: F
authors.lastname: Frassoni
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000209:etiology / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001752:Blast Crisis / Q000401:mortality; D001853:Bone Marrow / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007155:Immunologic Factors / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D007937:Leukapheresis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D009360:Neoplastic Cells, Circulating; D010677:Philadelphia Chromosome; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000209:etiology / Q000628:therapy; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D007155:Immunologic Factors; D016898:Interferon-alpha; D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide