The stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: results of the EORTC-GIMEMA AML-10 trial.
Variable numbers of CD34+ cells can be harvested from the blood of AML patients in CR after G-CSF supported mobilization following consolidation chemotherapy. We hypothesized that a decreased ability to mobilize stem cells reflects a chemotherapy-induced reduction in the number of normal and leukemic stem cells. We therefore analyzed whether the mobilizing capacity of these patients was of prognostic significance. 342 AML-patients in first CR received daily G-CSF from day 20 of the consolidation course and underwent 1-6 aphereses to obtain a minimum dose of 2 x 10(6) CD34+ cells/kg. Afterwards they were randomized for autologous bone marrow (BM) or blood SCT. As a surrogate marker for the mobilizing capacity, the highest yield of CD34+ cells of a single apheresis was adopted. Patients could be categorized into four groups: no harvest (n = 76), low yield (<1 x 10(6) CD34+/kg; n = 50), intermediate yield (1-6.9 x 10(6) CD34+ cells/kg; n = 128) and high yield (> or = 7 x 10(6) CD34+ cells/kg; n = 88). The median follow-up was 3.4 years; 163 relapses and 16 deaths in CR were reported. Autologous blood or BM SCT was performed in 36%, 64%, 81% and 88%, respectively, of the patients assigned to the no harvest, low, intermediate and high CD34+ yield group. The 3-year disease-free survival rate was 46.7%, 65.0%, 50.4% and 26.9% (P = 0.0002) and the relapse incidence was 47.5%, 30.1%, 43.1% and 71.9% (P < 0.0001). Multivariate Cox's proportional hazards model showed that the CD34+ yield was the most important independent prognostic variable (P = 0.005) after cytogenetics. Patients with the highest mobilizing capacity have a poor prognosis due to an increased relapse incidence.
Keating
S
S
Department of Hematology, St Radboud University Hospital, Nijmegen, The Netherlands.
Suciu
S
S
de Witte
T
T
Zittoun
R
R
Mandelli
F
F
Belhabri
A
A
Amadori
S
S
Fibbe
W
W
Gallo
E
E
Fillet
G
G
Varet
B
B
Meloni
G
G
Hagemeijer
A
A
Fazi
P
P
Solbu
G
G
Willemze
R
R
D000208:Acute Disease; D000328:Adult; D018952:Antigens, CD34 / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D003131:Combined Modality Therapy; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007958:Leukocyte Count; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D012074:Remission Induction; D013234:Stem Cells / Q000502:physiology*; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor