Towards the Development of a Closed, Nanofiber-Based Culture System for Clinical Expansion of Cord Blood CD34+ Cells

Stephen E. Fischer, Yukang Zhao, Anirudhasingh Sodha, Caitlin Smith, Yiwei Ma
2013 Biology of Blood and Marrow Transplantation  
We conducted an eleven-year retrospective review (2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012) of 65 HSCT patients with myeloid malignancies (n¼ 32), lymphoid malignancies (n¼27) or CML (n¼6) who received DLI post-transplant to treat mixed chimerism (MC, n¼15), minimal residual disease (MRD, n¼15) or relapsed disease (RD, n¼35). Patients had received transplants from related (n¼20) including haploidentical (n¼26), unrelated (n¼35) or cord blood (n¼1) donors. Forty-two
more » ... patients received total body irradiation (TBI) and cyclophosphamide-based conditioning while 16 received busulfan and cyclophosphamide-based regimens. Twentyseven patients received conditioning with other chemotherapies AE TBI. MC was defined as evidence of recipient cells on whole blood or bone marrow analysis using fluorescence in-situ hybridization (FISH) or short tandem repeats. Nine of the 15 MC patients who received DLI did so after the discontinuation (median of 35 days, range 1-217) of graft versus host disease (GvHD) prophylaxis, while the 6 remaining DLI recipients had not been on prophylactic therapy. MRD was defined as the detection of a clone ! 0.01% using polymerase chain reaction or FISH. Relapse was defined as any patient with a ! 5% blast population detected in peripheral blood and confirmed by microscopic or flow cytometric analysis. As a group, 26/65 patients are alive after receiving DLI with a median follow-up of 24 months (range 3-102). Of patients with MC, 9/15 remained in remission for a median of 22 months (range 3-85) with 7/15 experiencing Grade II-IV aGvHD. Of patients with MRD, 12/15 remained in remission for a median of 77 months (range 5-102) with 5/15 experiencing grade II-IV aGvHD. Eight of these 12 surviving patients were Philadelphia chromosome-positive. Of patients with RD, 5/36 remain alive with 3/5 in remission for a median of 43 months (range 4-63). 11/31 patients who expired experienced Grade II-IV aGvHD. Hence, DLI may benefit pediatric myeloid and lymphoid malignancy patients post-HSCT with MC and MRD (especially those with Philadelphia chromosome-positive leukemia). However, DLIs produced remission in only 3/36 patients with RD and the associated risk of significant GvHD likely worsens quality of remaining life in the non-responders.
doi:10.1016/j.bbmt.2012.11.208 fatcat:uddka47uxngijfm3radvf4itye