Autologous Bone Marrow Transplant after Failed Peripheral Blood Stem Cell Mobilization Does Not Adversely Affect Engraftment or Transplant Related Toxicity.

Introduction: Chemotherapy and G-CSF are widely used to collect adequate numbers of peripheral blood stem cells (PBSC) prior to autologous transplant. However, 10–30% of patients (pts) will not mobilize adequately. Alternatives include use of stem cell factor (SCF) and bone marrow (BM) harvest. Limited information is available on the hematopoietic reconstitution and clinical outcome of intensively treated pts who fail to mobilize sufficient numbers of PBSC and receive BM grafts. We sought to determine whether BM is an acceptable source of stem cells in these pts.

Methods: We conducted a retrospective analysis of toxicity, engraftment parameters, transfusion requirements and outcome in pts who failed mobilization and underwent unprimed BM harvest at our institution.

Results: Between 02/97 and 07/05, 47 heavily pre-treated pts (male/female 22/27; median age 49, range 22–66) who failed mobilization underwent an autologous BM transplant. Diagnoses included non-Hodgkin’s lymphoma (n=37: 17 low grade and 20 intermediate grade), Hodgkin’s lymphoma (n=6), and multiple myeloma (n=4). Median number of chemotherapy cycles prior to harvest was 11 (range 5–20); 17 pts (36%) had previously received radiotherapy. 42 pts had 1 mobilization attempt and 5 pts had 2 attempts. Mobilization regimens included chemotherapy(C) + G-CSF (n=27), C + G-CSF + SCF (n=20), G-CSF + SCF (n=4) and C + GM-CSF (n=1). G-CSF was given at a minimum dose of 10μg/kg/day. Pts were defined as poor mobilizers if the peak value of CD34⁺ cells during mobilization was lower than 10 cells/μL (n=33) or in the case of stem cell collection, if less than 1 x 10⁶ CD34⁺ cells/kg were obtained (n=14). Conditioning regimens included: BEAC (n=38), Cy-TBI (n=5), high dose Melphalan (n=3), and BEAM (n=1). Infused median numbers of nucleated BM cells, CFU-GM and CD34⁺ cells per kilogram were 3.5×10⁸ (range 1.0–21.6), 7.33×10⁴ (range 0.3–52.7), and 1.1×10⁶ (range 0.3–2.3), respectively. 34 pts received G-CSF during their hospitalization (median 12 days; range 2–38). Following transplant, median times to achieve an ANC > 0.5×10⁹/L and platelet count >20×10⁹/L were 19 (range 10–42) and 24 days (range 9–233), respectively; median time to RBC transfusion independence was 33 days (range 1–425). Median time to hospital discharge was 25 days (range 14–64). With a median follow-up of 36 months (range 1–97), Kaplan-Meier estimates of overall and disease-free survival at 3 years are 67% and 44%, respectively. The Kaplan-Meier estimates of transfusion independence for platelets and RBC at 3 months are 86% and 84%, and at 1 year 97% and 95%, respectively. 2 pts (4.3%) experienced procedure related deaths prior to day +100, one of cardiac insufficiency on day +3 and one of septic shock on day +90. Cumulative incidences of non relapse mortality at 1, 3 and 5 years were 4.3%, 10.6% and 14.9%, respectively. The incidence of post transplant MDS/AML was 10.6%.

Conclusion: Autologous transplant with unprimed BM graft after failed PBSC mobilization does not adversely affect engraftment or transplant related toxicity significantly. Thus, hard to mobilize patients should not be excluded from a potentially curative treatment.