Background
Indication and timing of allo-HSCT
Author [ref.] | Patients | No | Diagnosis | CIR | OS | LFS |
---|---|---|---|---|---|---|
Wang et al. [27], 2013 | HID-HSCT, retrospective | 756 | Leukemia | 15% (SR), 26% (HR) at 2 years | 68% (SR) at 3 years 49% (HR) at 3 years | |
Huang et al. [15], 2012 | HID-HSCT vs CT prospective | 58 vs 74 | AML-CR1 adults IR or HR | 12 vs 57%* | 7.5 vs 54.7%* at 4 years | 73.1 vs 44.2%* at 4 years |
Zhu et al. [35], 2013 | HSCT vs CT | 58 vs 58 | ETO(+) adults AML-CR1 | 22.1 vs 78.9% (HR)* 14.7 vs 5.3% (LR) | 71.6 vs 26.7% (HR)* 75.7 vs 100% (LR) | 61.7 vs 19.6% (HR)* 70.3 vs 94.7% (LR) |
Qin et al. [36], 2015 | HSCT vs CT | 57 vs 29 | In(16) adults AML-CR1 | 7.1 vs. 87.7% (poor MR)*; 0 vs. 26.9% (good MR); | 93.3 vs. 40.0%, (poor MR)*; 72.9 vs. 77.1% (good MR) | 86.7 vs. 12.3% (poor MR)* 72.9 vs. 73.1% (good MR) |
Yan et al. [82], 2014 | HID-HSCT vs CT | 79 vs 59 | SR-ALL-CR1 adults | 29.9 vs 66.3%* at 5 years | 70.4 vs 28%* at 5 years | 54.4 vs 23.9%* at 5 years |
Sun et al. [83], 2014 | HID-HSCT vs CT | 79 vs 104 | HR-ALL-CR1 adults | 18.7 vs 60.5%* at 3 years | 72.5 vs 26.6%*; at 3 years | 63.9 vs 21.1%* at 3 years |
Wang et al. [84], 2012 | HID-HSCT, T-ALL | 72 | T-ALL | 18.8% (CR1) 37.5% (non-CR1) | 54.8% (CR1) 12.5% (non-CR1) | |
Xu et al. [46], 2016 | HSCT | 52 | Pediatric T-ALL(HR) | 32.7% at 3 years | 55.5% at 3 years | 54.1% at 3 years |
Jiang et al. [85], 2011 | HSCT vs IM | 87 vs 45 | CML-AP adults | 81.2 vs 100% (LR) at 6 years 81.3 vs 61.3% (IR)* at 6 years 100 vs 17.7% (HR)* at 5years | 80.7 vs 80.9% (LR) at 6 years, 61.9 vs 47.1% (IR)* at 6 years 66.7 vs 9.3% (HR)* at 5 years | |
Xu et al. [52], 2016 | HSCT vs TKI2 | 60 vs 33 | CML-AP adults | 86.4 vs. 42.9%* at 5 years | 76.1 vs. 14.3%* at 5 years |
Acute myeloid leukemia
Author | HSCT type | Case number | Diagnosis | TRM | CIR | aGVHD | OS | LFS |
---|---|---|---|---|---|---|---|---|
Wang et al. [18], 2015 | HID vs MSD multicenter, prospective | 231 vs219 | Adults IR/HR AML-CR1 | 3 years, 13 vs 8% | 3 years, 15 vs 15% | 3 years, 79 vs 82% | 3 years, 74 vs 78% | |
Liu et al. [61], 2013 | HID vs MSD | 212 vs 46 | Pediatric AL | II–IV* 40.8 vs 20%; III–IV 14.3 vs 16.9% | 77.8 vs 65.5% | 68.9 vs 52.5% (ALL-CR1); 82.5% vs 71.7% (AML-CR1) | ||
Wang et al. [17], 2016 | HID ns MSD Adults Phase II randomizes | 121 vs 89 | (Ph-)ALL-CR1(HR) | 3 years, 18 vs 24% | 3 years, 61 vs 60% | |||
Chen et al. [43], 2015 | HID vs MSD | 101 vs 38 | Ph + ALL | 15.6% at 5 years | 20.3% at 5 years | 74.0 vs 68% at 5 years | 65.8 vs 61% at 5 years | |
Gao et al. [44], 2015 | HID vs MSD | 47 vs 35 | Ph + ALL | 21.3 vs 17.1% | 19.1* vs 44.8%. | III–IV 17.0 vs 11.4% | 2 years, 63.8 vs 62.6% | 2 years, 59.5 vs 45.7% |
Wang et al. [19], 2016 CBMTR data based | HIDs vs MRD | 136 (3/6) vs 90(4/6) vs 228 | MDS | 58 vs 63 vs 73% | 58%*, 63 vs 71% | |||
Ma et al. [64], 2016 | HID vs MSD | 67 vs 23 | CML-BC | 3 years, 60.0 vs 55.3% | 3 years, 51.1 vs 47.8% | |||
Xu et al. [33], 2016 | HID vs MSD\prospective | 101 vs 48 | SAA failure to previous IST | II–IV* 33.7 vs 4.2%; III–IV, 7.9 vs 2.1% | 3 years, 89.0 vs. 91.0% | 3-year FFS 86.8 vs. 80.3% | ||
Xu et al. [34], 2017 | HID vs MSD Data based | 89 vs 69 | SAA, upfront | 97.8 vs 97.1% | II–IV* 30.3 vs. 1.5%, III–IV* 10.1 vs. 1.5% | 3 years, 86.1 vs 91.3% | 3-year FFS 85.0 vs 89.8% | |
Sun [79], 2016 | HID vs URD, Pair-match | 87 vs 87 | AML-CR1 | 13.8 vs 15.7% | 12.7 vs 24% | III–IV 9.2 vs 9.4% | 5 years, 78.2 vs 63.6% | 5 years, 73.5 vs 60.3% |
Huang et al. [13], 2009 | HID vs URD | 219 vs 78 | Malignant | 2 years, 20 vs 18% | 2 years, 12 vs 18% | II–IV 47 vs 31% | 4 years, 74 vs 74% | 4 years, 67 vs 61% |
Han et al. [39], 2017 | HID, vs MSD vs MUD | 127 vs 144 vs 77 | Adult patients | 16.4 vs 11.6 vs 19.6% | 14.8 vs 21.1 vs 16.7% | III–IV 11.4 vs 7.7 vs 13.5% | 70.1 vs, 73.7 vs 69.8% | 5-years DFS 68.7 vs 67.3 vs 63.7% |
Luo et al. [23], 2014 | HRD vs URD vs MSD prospective ChiCTR-OCH-12002490 | 99 vs 116 vs 90 | Hematologic malignancies | 30.5 vs 22 vs 4.7%* | 14.2* vs 21.2 vs 34%; 15.4* vs 28.2 vs 49.9% (in HR pts) | II–IV 42.4 vs 39.7 vs 15.6% | 60.8 vs 63.5 vs 77.2%, | 58.3 vs 58.4, vs 63.6% |
Mo et al. [81], 2016 | HID vs CBT multiple centers | 65 vs 64 | ALL (HR) pediatric | 2 years, 12.8 vs 18.8% | 2 years, 16.1 vs 24.1% | 2 years, 82 vs 69.6% | 2 years, 71 vs 57.2%* |
Acute lymphoblastic leukemia
Myelodysplastic syndromes (MDS)
Chronic myelogenous leukemia
Severe aplastic anemia
Recommendation: indications and timing for allo-HSCT
Patients with non-malignant hematological diseases
Patients with non-malignant hematological diseases
Donor selection and graft source
HID-HSCT
MUD-HSCT
CB-HSCT
Recommendations: donor selection and mobilization
General principle of donor selection
Algorithm for HID
Algorithm for MUD
Algorithm for CB
General principle of mobilization
Conditioning regimens
MAC | Drug | Dose(total) | Schedule(d) | Donor type |
---|---|---|---|---|
Traditional | ||||
Cy/TBI | Cy | 120 mg/kg | − 6, − 5 | Allo-HSCT |
f-TBI | 12 ~ 14 Gy | − 3 ~ − 1 | ||
Bu/Cy | Bu | 16 mg/kg(po)or 12.8/kg(iv) | −7 ~ − 4 | Allo-HSCT |
Cy | 120 mg/kg | − 3, − 2 | ||
Modified (PUPH) | ||||
mBuCy | Hu | 80 mg/kg, divided in twice | − 10 | HLA-matched sibling HSCT |
Ara-C | 2 g/m2 | − 9 | ||
Bu | 9.6 mg/kg(iv) | − 8 ~ − 6 | ||
Cy | 3.6 g/m2 | − 5, − 4 | ||
MeCCNU | 250 mg/m2(po) | − 3 | ||
mCy/TBI | Single TBI | 770 cGy | − 6 | HLA-matched sibling HSCT |
Cy | 3.6 g/m2 | − 5, -4 | ||
MeCCNU | 250 mg/m2 | − 3 | ||
mBuCy+ATG | Ara-C | 4~ 8 g/m2 | − 10, − 9 | URD, CBT, HID-HSCT |
Bu | 9.6 mg/kg(iv) | − 8 ~ − 6 | ||
Cy | 3.6 g/m2 | − 5, − 4 | ||
ATG | 10 mg/kg | −5 ~ − 2 | ||
Or ATG-F | 40 mg/kg | −5 ~ − 2 | ||
mCy/TBI + ATG | TBI | 770 cGy | − 6 | URD-HSCT, HID-HSCT |
Cy | 3.6 g/m2 | − 5, − 4 | ||
MeCCNU | 250 mg/m2 | −3 | ||
ATG | 10 mg/kg | −5 ~ − 2 | ||
Or ATG-F | 40 mg/kg | −5 ~ − 2 |
Conditioning regimen | Drug | Dose (total) | Schedule(d) | Donor type |
---|---|---|---|---|
International regimen | ||||
Flu/Mel | Flu | 150 mg/m2 | − 7 ~ − 3 | Allo-HSCT |
Mel | 140 mg/m2 | − 2, − 1 | ||
Flu/Bu | Flu | 150 mg/m2 | − 9 ~ − 5 | Allo-HSCT |
Bu | 8~ 10 mg/kg (po) | − 6 ~ − 4 | ||
Flu/Cy | Flu | 150 mg/m2 | − 7 ~ − 3 | Allo-HSCT |
Cy | 140 mg/m2 | − 2, − 1 | ||
Flu/Bu/TT | Flu | 150 mg/m2 | − 7 ~ − 5 | Allo-HSCT |
Bu | 8 mg/kg (po) | − 6 ~ − 4 | ||
Thiotepa | 5 mg/kg | − 3 | ||
TBI/Cy/ATG | TBI | 4 Gy | − 5 | Flu+Ara-C+AMSA, followed by allo-HSCT |
Cy | 120 mg/kg | − 4, − 3 | ||
ATG | ||||
Modified regimen(PUPH) | ||||
RIC-mBuCy | Hu | 80 mg/kg (divided in two) | − 10 | HLA-matched sibling HSCT |
Ara-C | 2 g/m2 (CI) | − 9 | ||
Bu | 4.8 mg/kg (iv) | − 10, − 9 | ||
Cy | 2.0 g/m2 | − 5, − 4 | ||
MeCCNU | 250 mg/m2 (po) | − 3 | ||
ATG | 10 mg/m2 | − 5 ~ − 2 | ||
or ATG-F | 40 mg/kg | − 5 ~ − 2 | ||
RIC-BuFlu | Hu | 80 mg/kg (divided in two) | − 10 | HLA-matched sibling HSCT |
Ara-C | 2 g/m2 (CI) | − 9 | ||
Bu | 9.6 mg/kg (iv) | − 8 ~ − 6 | ||
Flu | 150 mg/m2 | − 6 ~ − 2 | ||
MeCCNU | 250 mg/m2 | − 3 | ||
RIC-mBuFluATG | Ara-C | 8 g/m2 (CI) | − 10/− 9 | HID-HSCT |
Bu | 9.6 mg/kg (iv) | − 8 ~ − 6 | ||
Flu | 150 mg/m2 | − 6 ~ − 2 | ||
MeCCNU | 250 mg/m2 | − 3 | ||
ATG | 10 mg/kg | − 5 ~ − 2 | ||
or ATG-F | 40 mg/kg | − 5 ~ − 2 | ||
RIC-mBuCyFlu+ATG | Ara-C | 8 g/m2 (CI) | − 10/− 9 | HID-HSCT |
Bu | 9.6 mg/kg (iv) | − 8 ~ − 6 | ||
Flu | 150 mg/m2 | − 6 ~ − 2 | ||
Cy | 2.0 g/m2 | − 5, − 4 | ||
MeCCNU | 250 mg/m2 | − 3 | ||
ATG | 10 mg/kg | − 5 ~ − 2 | ||
or ATG-F | 40 mg/kg | − 5 ~ − 2 |
Conditioning regimen | Drugs | Dose(total) | Scheduled(d) | Donor type |
---|---|---|---|---|
International regimen | ||||
Cy/VP/TBI | Cy | 120 mg/kg | − 6, − 5 | Allo-HSCT |
Vp16 | 30 ~ 60 mg/m2 | − 4 | ||
FTBI | 12.0 ~ 13.8Gy | − 3 ~ − 1 | ||
TBI/TT/Cy | FTBI | 13. 8 Gy | − 9 ~ − 6 | Allo-HSCT |
TT | 10 mg/kg (po) | − 5, − 4 | ||
Cy | 120 mg/kg | − 6, − 5 | ||
Bu/Cy/MEL | Bu | 16 mg/kg (po) | − 7 ~ − 4 | Allo-HSCT |
Cy | 120 mg/kg | − 3, − 2 | ||
Mel | 140 mg/m2 | − 1 | ||
Regimens in China | ||||
Liu QF et al. | Flu | 150 mg/m2 | − 10 ~ − 6 | Allo-HSCT |
Ara-C | 5 ~ 10 g/m2 | − 10 ~ − 6 | ||
TBI | 9 Gy | − 5, − 4 | ||
Cy | 120 mg/kg | − 3, − 2 | ||
Vp16 | 30 mg/kg | − 3, − 2 |
Recommendation: conditioning regimen
For patients with malignant hematological diseases
Conditioning regimen | Drug | Dose (total) | Time(d) | Transplantation type |
---|---|---|---|---|
BEAM | BCNU | 300 mg/m2 | −6 | Allo-HSCT of lymphoma |
Vp16 | 800 mg/m2 | −5 ~ − 2 | ||
Ara-C | 800 mg/kg | −5 ~ − 2 | ||
Mel | 140 mg/m2 | −1 | ||
Flu/MEL | Flu | 150 mg/m2 | −7 ~ − 3 | Allo-HSCT of multiple myeloma |
Mel | 140 mg/m2 | −2, − 1 | ||
Bortizomib | ||||
Flu/Bu | Flu | 150 mg/m2 | −10 ~ 6 | Allo-HSCT of multiple myeloma |
Bu | 6.4~ 9.6 mg/kg (iv) | − 7 ~ − 4 |
For patients with non-malignant hematological diseases
Conditioning regimen | Drug | Dose (total) | Time(d) | Transplantation type |
---|---|---|---|---|
International regimen | ||||
Cy-ATG | Cy | 200 mg/kg | −5 ~ − 22 | HLA-matched sibling HSCT |
ATG | 11.25 ~ 15.00 mg/kg | −5 ~ − 3, − 2 | ||
FluCy-ATG | Flu | 120 mg/m2 | −5 ~ − 2 | HLA-matched unrelated HSCT |
Cy | 120 mg/kg | −5, − 2 | ||
ATG | 11.25 ~ 15.00 mg/kg | −5 ~ − 3, − 2 | ||
Regimens in China | ||||
mBuCyATG-SAA | Bu | 6.4 mg/kg(ivgtt) | −7, − 6 | Haploidentical-HSCT |
Cy | 200 mg/kg | −5, − 2 | ||
ATG | 10 mg/kg | −5 ~ − 2 | ||
or ATG-F | 40 mg/kg | −5 ~ − 2 | ||
mBuCyFluATG | Bu | 6,4mg/kg(ivgtt) | −7 ~ − 6 | Haploidentical-HSCT |
Flu | 120 mg/m2 | −10 ~ − 7 | ||
Cy | 200 mg/kg | −6 ~ − 3 | ||
ATG-F | 20 mg/kg | −4 ~ − 1 | ||
or ATG | 10 mg/kg | −4 ~ − 1 | ||
FluCy-ATG | Flu | 120 mg/m2 | −5 ~ − 2 | Haploidentical-HSCT |
Cy | 90 mg/kg | −3, − 2 | ||
ATG | 10 mg/kg | −5 ~ − 2 |
Conditioning regimen | Drug | Dose | Time(d) | Transplantation |
---|---|---|---|---|
General intensity | ||||
Regimens for leukemia | The same as leukemia | Same as leukemia | Allo-HSCT | |
BuCy | Bu | 14 mg/kg(po) | Allo-HSCT | |
Cy | 200 mg/kg | |||
Intensified regimen | ||||
NF0-8-TM | Cy | 110 mg/kg | −10, −9 | HLA-matched sibling transplantation |
Flu | 200 mg/m2 | −8 ~ − 4 | Unrelated HLA-matched transplantation | |
TT | 10 mg/kg | −5 | ||
Bu | ivgtt,QD(−8d) Css 300 ~ 600 ng/L | −8 ~ − 6 | Haploidentical-HSCT | |
Azathioprine | 3 mg/kg,QD | From D−45 | ||
Hu | 30 mg/kg,QD | From D−45 | ||
FluBuCyATG | Flu | 150mg/m2 | −12 ~ − 10 | Allo-HSCT |
Bu | 12.8 mg/kg(ivgtt) | −9 ~ − 6 | ||
Cy | 200 mg/kg | −5 ~ − 2 | ||
ATG | 10 mg/kg | −5 ~ − 2 | ||
Hu | 20 mg/kg,QD | 3 months before |