Myeloablative Allogeneic Stem Cell Transplantation after Cytoreductive Therapies for Adult Patients with RAEB-2
Authors: Wang Ying , Chen Jia , Wu Depei 
Published: November 2019

Abstract
Background:
The prognosis of refractory anemia with excess blasts (RAEB)-2 is poor and allogeneic hematopoietic stem cell transplantation (HSCT) is believed to be the only curative treatment. New strategies are under active investigation to further advance the efficacy after HSCT. Here, we report on the outcome of 35 adults with RAEB-2 using cytoreductive therapies as a bridge to subsequent myeloablative allogeneic HSCT.
Patients and Methods:
A total of 35 adult patients (19 males and 16 females) with RAEB-2 who received cytoreductive therapies before allogeneic HSCT at our institution between January 2011 and April 2016 were analyzed. The median age was 41 years (range, 12 - 54 years). The IPSS scores at diagnosis were INT-1 in 3 (8%), INT-2 in 24 (69%) and high risk in 8 (23%). Prior to transplantation, 8 patients had been treated with only hypomethylating agents (HMAs), 4 with only chemotherapy, and 23 with HMAs in combination with chemotherapy. The median time from diagnosis to transplantation is 3 months (range, 2 - 9 months). Graft source was HLA-identical sibling in 8 (23%), unrelated donor in 10 (29%), and haploidentical related donor in 17 (48%). 7 (20%) recipients received bone marrow (BM), 14 (40%) received peripheral blood stem cells (PBSCs), and 14 (40%) received BM plus PBSCs. The median number of CD34-positive cells was 3.97 × 106 cells per kg (range, 1.69 - 12.17 × 106 cells per kg). All patients received a myeloablative conditioning regimen consisting of busulfan and cyclophosphamide, while rabbit antithymocyte globulin was given as an additional immunosuppressive measure in patients transplanted from non-HLA-identical sibling donors. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Recipients of non-HLA-identical sibling transplants also received mycophenolate mofetil.
Results:
22 patients received 1course, 9 received 2 courses and 4 received more cycles of cytoreductive treatment. In general, treatment was well tolerated and infection (63%) was the most frequent adverse events. Transplantation was postponed for about two months in 2 patients due to pneumonia. At time of transplantation, 11 (31%) achieved marrow complete remission (CR) and hematologic improvement, 11 (31%) had marrow blasts decreased more than 50% (including 1 patient showed CR response after induction, but relapsed prior to HSCT), and 13 (37%) had persistent or progressive disease before HSCT. All patients showed primary eneutrophil engraftment after a median of 12 days (range, 10 - 20 days). For patients achieving platelet engraftment (34/35), the median time to platelet recovery was 14 days (range 11-193 days). Acute graft-versus-host disease (GVHD) grade II-IV developed in 30%, and extensive chronic GVHD in 18% of the patients. After a median follow-up of 25 months, the 2-year overall and disease-free survival estimates were 61% and 57%, respectively. The 2-year cumulative incidences of relapse and non-relapse mortality were 3% and 32%, respectively. Refractory to cytoreductive therapies was the only prognostic factor for poor overall survival after HSCT.
Conclusion:
This study indicates that the safety and high response rate of 1-2 courses of HMA-containing cytoreductive therapies before HSCT and a high probability of survival for adult patients with RAEB-2 after a myeloablative allogeneic HSCT.

Disclosures
No relevant conflicts of interest to declare.