Work

CD34+ Cell Dose and Full Donor Chimerism at Day +100 Is Associated with Survival in Patients Who Received Reduced-Intensity Conditioning (RIC) With Fludarabine/Melphalan Prior To Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Hematologic Malignancies

Year: 2009

Type: article

Abstract: Nonmyeloablative, reduced-intensity conditioning extends allogeneic HSCT as a therapeutic option for elderly or frail patients with relapsed, refractory, or other high-risk hematologic malignancies. We reviewed the medical records of the first 50 patients (34 M, 16 F) at our institution who underwent fludarabine/melphalan RIC from 9/00 to 9/07 to determine factors associated with survival. The median age at transplant was 53.5 years (range 20–67 years). Most patients received HSCT for myeloid malignancies (18 AML, 11 MDS, 8 NHL, 7 MM, 2 each CML and CLL, and 1 each AMM and HL), were in remission at transplant (16 in CR, 9 in PR, 13 relapsed/refractory, and 12 untreated), received stem cells from a matched related versus unrelated donor (37 vs. 13 pts), and were a full 6/6 for sibling donors or 10/10 antigen match for URD (46 versus 4 patients with a single antigen mismatch). Half (25 pts) had received prior HSCT, and 3 had prior chemotherapy for solid tumors. 28% of patients experienced grade 3–4 acute GVHD, and 46% experienced chronic GVHD (38% extensive). 26 of 50 pts have died, 5 from relapsed disease. Only one of the deaths before day +100 was due to relapsed disease, and treatment-related mortality (TRM) at day +100 was 26% (13 pts). 24 patients (48%) are alive after a median of 24 months of follow up. Factors associated with survival on univariate analysis included CD34+ cell dose greater than the median of 5.5 × 106/L (p = 0.0463), day +100 disease remission status, (p<0.0001), day +100 chimerism status (p<0.0001), any chronic GVHD (p = 0.0005), and favorable/standard versus poor risk karyotype for myeloid malignancies (p = 0.0149). On multivariate analysis, CD34 cell dose greater than 5.5 × 106/L (RR 0.19, 95% CI 0.0389 – 0.7222, p = 0.0136) and full donor chimerism at day +100 (RR 0.05, 95% CI 0.0099 – 0.2327, p = 0.0002) remained an independent prognostic factors. Achievement of full donor chimerism was not related to CD34 cell dose (p = 0.46). In our series, achievement of full donor chimerism at day +100 is associated with 70% 2 year survival, a favorable outcome in this high risk group of patients. While the infused CD34 cell dose can occasionally be a modifiable variable, whether any other host and/or graft factors could be modified to promote the establishment of full chimerism and improve survival remains largely unknown and merits confirmation in larger series.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2008.12.319