1. Retrospective analysis of conditioning regimen containing decitabine of allogeneic stem cell transplantation for myelodysplastic syndrome and myeloproliterative neoplasms
Erlie Jiang, Yigeng Cao, Qiaoling Ma, Weihua Zhai, Chen Liang, Gang Li, Xin Chen, Yuanyuan Shi, Jianli Sun, Jianfeng Yao, Yawei Zheng, Sizhou Feng, Mingzhe Han*
Institute of Hematology & Blood Diseases Hospital, CAMs & PUMC, TianJin , China
*Corresponding author: Mingzhe Han;
Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is an optimal therapy for patients with myelodysplastic syndromes (MDS) and myeloproliterative neoplasms (MPN). Decitabine, as a hypomethylating agent, has been proven to be a safe and effective bridging therapy followed by allogenic HSCT in the treatment of MDS and may contribute to disease control post- transplantation.
We assessed the efficacy of a new conditioning regimen consisted of Decitabine (Dec), Busulfan (Bu), Fludarabine (Flud), Ara-c, Cyclophosphamide (Cy) and/or antithymocyte globulin (ATG) for allo-HSCT in patients with MDS and MPN. The clinical characteristics and curative effect of MDS and MPN patients who received the new conditioning regimen before HSCT in our institution from 2015 April to 2017 February were retrospectively analyzed.
At a median follow-up of 253 (15-729) days, the overall survival (OS) was 86%, the disease free survival（DFS） was 76%. Three patients (11%) died and all of them died of nonrelapse mortality. One patient (4%) relapsed at day 412 after transplantation and got complete remission after chemotherapy and donor lymphocyte infusion. Successful repopulation was reached in 25 patients (93%), after a median of 13 days (range, 10 to 22 days) for neutrophil and 15 days (range, 11 to 227 days) for platelet. From the conditioning regimen to the hematopoietic reconstitution, the median of platelets and red cells transfusions was 7 (2-56) and 18 (2-176) U, respectively. Eleven patients developed acute graft versus host disease (GVHD), classified as grade I-II aGVHD in 5 patients (19%) and grade III-IV in 6 patients (22%). Five patients (19%) developed chronic GVHD (3 with limited cGVHD and 2 with extensive cGVHD).
Figure 1. The conditioning regimen.
Result
Figure 2. OS and DFS after Dec included conditioning at a median follow-up of 253 days post-allogeneic HSCT.
Table 1. Patient and Transplantation Characteristics.
Table 2. Results Post-Allogeneic HSCT
Characteristic
Value (n=27)
Age, yr, median (range)
41 (13-59)
Sex, n (%)
Male
17 (62)
Female
10 (37)
MDS, n (%)
24 (89)
MDS-RAEBI
9 (33)
MDS-RAEBII
11 (41)
MDS-RCMD
4 (15)
IPSS-R classification
Extremely low risk groups
1 (4)
Low risk group
Intermediate risk group
7 (26)
High risk group
8 (30)
Extremely high risk group
CMML, n (%)
3 (11)
CMML-1
2 (7)
CMML-2
3 (4)
WBC at diagnosis,109/L,median (range)
2.6(1-277)
Disease status at allogeneic HCT, n (%)
CR1
CR2
No CR
2(7)
Untreated
20 (74)
Decitabine dosage before HSCT, mg, median (range)
0 (0-838)
KPS before HSCT, median (range)
92(90-95)
Donor/HLA match, n (%)
Matched related
17(63)
Mismatched related
5 (19)
Matched unrelated
Mismatched unrelated
MNC,×108/L, median (range)
7.3 (3.3-15)
CD34+ cells,×106/L, median (range)
2.2 ( )
Result
Value
Repopulation, n (%)
25 (93)
neutrophil repopulation, d, median (range)
13 (10-22)
platelet repopulation, d, median (range)
15 (11-227)
Platelets transfusions, U, median (range)*
7 (2-56)
Red cells transfusions, U, median (range)*
18 (2-176)
aGVHD, n (%)
Grade III-IV
6 (22)
Grade I-II
5 (19)
Outcome of GVHD, n
Remission 9
No remission/dead 2
cGVHD, n (%)
limited
3 (11)
extensive
2 (7)
Relapse/progressive disease, n (%)
1 (4)
Death, n (%)
Relapse/progressive disease, n
GVHD, n
Other, n# 1
Infections <100 d, n (%)
15 (56)
Cytomegalovirus disease/reactivation, n 3
Bacterial, n 7
Fungus, n
Other, n&
* From the conditioning regimen to the hematopoietic reconstitution;
# Pulmonary embolism leading to respiratory failure;
& Other virus infection like herpes zoster virus.
Conclusion
MDS indicates Myelodysplastic syndrome; CMML, chronic myelomonocytic leukemia;
CR indicates complete response; HSCT, Hematopoietic Setm Cell Transplantation;
KPS, Karnofsky performance score.
The addition of decitabine to a traditional condition regimen is effective and feasible.
Further studies are needed to confirm our results.