High-Dose Chemotherapy Intensification with Bone Marrow Support for Hormone Receptor Negative or Hormonal Refractory Relapsing Breast Cancer

Author(s):  
Frank R. Dunphy ◽  
Gary Spitzer ◽  
Aman U. Buzdar ◽  
Gabriel N. Hortobagyi ◽  
Frankie Holmes ◽  
...  
Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 2169-2174 ◽  
Author(s):  
Patrick Stiff ◽  
Bohao Chen ◽  
Wilbur Franklin ◽  
David Oldenberg ◽  
Eric Hsi ◽  
...  

Abstract The collection of small aliquots of bone marrow (BM), followed by ex vivo expansion for autologous transplantation may be less morbid, and more cost-effective, than typical BM or blood stem cell harvesting. Passive elimination of contaminating tumor cells during expansion could reduce reinoculation risks. Nineteen breast cancer patients underwent autotransplants exclusively using ex vivo expanded small aliquot BM cells (900-1200 × 106). BM was expanded in media containing recombinant flt3 ligand, erythropoietin, and PIXY321, using stromal-based perfusion bioreactors for 12 days, and infused after high-dose chemotherapy. Correlations between cell dose and engraftment times were determined, and immunocytochemical tumor cell assays were performed before and after expansion. The median volume of BM expanded was 36.7 mL (range 15.8-87.0). Engraftment of neutrophils greater than 500/μL and platelets greater than 20 000/μL were 16 (13-24) and 24 (19-45) days, respectively; 1 patient had delayed platelet engraftment, even after infusion of back-up BM. Hematopoiesis is maintained at 24 months, despite posttransplant radiotherapy in 18 of the 19 patients. Transplanted CD34+/Lin−(lineage negative) cell dose correlated with neutrophil and platelet engraftment, with patients receiving greater than 2.0 × 105 CD34+/Lin− cells per kilogram, engrafting by day 28. Tumor cells were observed in 1 of the 19 patients before expansion, and in none of the 19 patients after expansion. It is feasible to perform autotransplants solely with BM cells grown ex vivo in perfusion bioreactors from a small aliquot. Engraftment times are similar to those of a typical 1000 to 1500 mL BM autotransplant. If verified, this procedure could reduce the risk of tumor cell reinoculation with autotransplants and may be valuable in settings in which small stem cell doses are available, eg, cord blood transplants.


1999 ◽  
Vol 17 (3) ◽  
pp. 887-887 ◽  
Author(s):  
Dennis L. Carter ◽  
Lawrence B. Marks ◽  
Joseph M. Bean ◽  
Gloria Broadwater ◽  
Atif Hussein ◽  
...  

PURPOSE: To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer. PATIENTS AND METHODS: Between 1988 and 1994, 425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT−). The assignment of RT was not randomized. The RT+ and RT− groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated. RESULTS: Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT− patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT− groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT− groups, respectively (P = .20). CONCLUSION: Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.


Cancer ◽  
1994 ◽  
Vol 73 (8) ◽  
pp. 2157-2167 ◽  
Author(s):  
Frank R. Dunphy ◽  
Gary Spitzer ◽  
Jane E. Rossiter Fornoff ◽  
Jonathan C. Yau ◽  
Susan D. Huan ◽  
...  

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