Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with recurrent indolent non-Hodgkin's lymphoma.
OBJECTIVE
To evaluate the results of high-dose chemotherapy and transplantation of highly purified "mobilized" peripheral blood CD34+Thy-1+ hematopoietic stem cells (HSCs) in patients with recurrent indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL).


METHODS
Twenty-six patients with recurrent indolent NHL or MCL were mobilized witheither granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSF. Apheresis was performed, and the product was purified using the Isolex immunomagnetic positive CD34+ cell selection device initially and subsequent high-speed flow-cytometric cell sorting for the final purification of CD34+Thy-1+ HSCs. The patients received high-dose chemotherapy with BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide) followed by transplantation with the purified HSCs in 2 dose cohorts (cohort 1: > or =5 x 10(5) viable and pure HSC/kg; cohort 2: > or =3 x 10(5) HSC/kg).


RESULTS
We attempted to mobilize 26 patients with G-CSF alone. Six patients did not collect adequate cells with G-CSF alone; subsequent mobilization with cyclophosphamide plus G-CSF was attempted, but adequate CD34+Thy-1+ HSCs could not be collected on these 6 patients. Twenty patients underwent transplantation with the BEAC transplantation regimen followed by purified HSCs. Patients in cohort 1 engrafted at a median of day 12 to an absolute neutrophil count (ANC) >500/microL, a median of day 19 for platelet transfusion independence, and a median of day 20 for red blood cell transfusion independence. Patients in cohort 2 engrafted at a median of day 12 to an ANC >500/microL, a median of day 12 for platelet transfusion independence, and a median of day 12 for red blood cell transfusion independence. Fourteen of the 20 patients had significant infections reported at some point posttransplantation, including influenza, respiratory syncytial virus, pneumonitis, and Pneumocystis carinii pneumonia. With a median follow-up of 38 months, 8 of the 20 patients have had progressive lymphoma and 5 patients have died. The 3-year event-free survival is 55%, and overall survival is 78%.


CONCLUSIONS
CD34+Thy-1+ HSCs can be collected successfully from most lymphoma patients mobilized with G-CSF alone. The engraftment and disease outcomes in the patients in this small pilot study using these cells do not appear to be different from the outcomes of similar patients cited in the literature. However, the short- and long-term risks of infection were a concern in this patient population.
Vose
J M
JM
University of Nebraska Medical Center, Omaha 68198-7680, USA. jmvose@unmc.edu
Bierman
P J
PJ
Lynch
J C
JC
Atkinson
K
K
Juttner
C
C
Hanania
C E
CE
Bociek
G
G
Armitage
J O
JO
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D015415:Biomarkers; D002452:Cell Count; D002469:Cell Separation; D015331:Cohort Studies; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000254:growth & development; D020522:Lymphoma, Mantle-Cell / Q000150:complications / Q000175:diagnosis / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis; D016879:Salvage Therapy; D016019:Survival Analysis; D018800:Thy-1 Antigens / Q000032:analysis; D016896:Treatment Outcome
D018952:Antigens, CD34; D015415:Biomarkers; D018800:Thy-1 Antigens