Blood Res 2022; 57(4):
Published online December 31, 2022
https://doi.org/10.5045/br.2022.2022194
© The Korean Society of Hematology
Correspondence to : Ja Min Byun, M.D., Ph.D.
Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongro-gu, Seoul 03080, Korea
E-mail: jaminbyun@snu.ac.kr
*This study was partially supported by the National Research Foundation of Korea (NRF-2020R1F1A1076106).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
Allogeneic hematopoietic stem cell transplantation (alloSCT) is the sole curative option for myelofibrosis (MF). However, it is unknown as to which of the two, myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC), is a better preconditioning regimen.
Methods
Twenty-five patients with MF were treated with alloSCT, 12 of whom underwent RIC. Baseline characteristics, response to alloSCT, adverse events, including graft-versus-host disease (GVHD), and survival outcomes were reviewed.
Results
There was no difference in the neutrophil engraftment rate and time to engraftment between MAC vs. RIC. The time to platelet engraftment was significantly longer in the MAC group (median, 112.8 vs. 28.8 days for MAC vs. RIC, respectively, P=0.049). RIC was more advantageous in terms of achieving complete chimerism (38.5% vs. 83.3%, P=0.041). The incidence of acute GVHD was 84.6% (11 of 13) and 58.3% (7 of 12) in the MAC and RIC groups, respectively. The cumulative incidence of grade III‒IV acute GVHD was significantly higher in the MAC group than in the RIC group (P=0.03). No significant differences were observed in progression-free and overall survival. The 17-month probability of progression-free survival was 38.4% [95% confidence interval (CI), 19.3‒76.5] vs. 47.6% (95% CI, 25.7‒88.2) (P=0.21), and that of overall survival was 53.8% (95% CI, 32.5‒89.1) vs. 48.6% (95% CI, 26.8‒88.3) (P=0.85) for MAC vs. RIC, respectively.
Conclusion
RIC offers a significant advantage over MAC, even in younger patients with MF undergoing alloSCT, in terms of cell engraftment, rate of complete chimerism achievement, and incidence of acute GVHD.
Keywords: Myelofibrosis, Hematopoietic stem cell transplantation, Reduced intensity, Myeloablative
Blood Res 2022; 57(4): 264-271
Published online December 31, 2022 https://doi.org/10.5045/br.2022.2022194
Copyright © The Korean Society of Hematology.
Dong Hyun Kim, Jeongmin Seo, Dong-Yeop Shin, Youngil Koh, Junshik Hong, Inho Kim, Sung-Soo Yoon, Ja Min Byun
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
Correspondence to:Ja Min Byun, M.D., Ph.D.
Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongro-gu, Seoul 03080, Korea
E-mail: jaminbyun@snu.ac.kr
*This study was partially supported by the National Research Foundation of Korea (NRF-2020R1F1A1076106).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
Allogeneic hematopoietic stem cell transplantation (alloSCT) is the sole curative option for myelofibrosis (MF). However, it is unknown as to which of the two, myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC), is a better preconditioning regimen.
Methods
Twenty-five patients with MF were treated with alloSCT, 12 of whom underwent RIC. Baseline characteristics, response to alloSCT, adverse events, including graft-versus-host disease (GVHD), and survival outcomes were reviewed.
Results
There was no difference in the neutrophil engraftment rate and time to engraftment between MAC vs. RIC. The time to platelet engraftment was significantly longer in the MAC group (median, 112.8 vs. 28.8 days for MAC vs. RIC, respectively, P=0.049). RIC was more advantageous in terms of achieving complete chimerism (38.5% vs. 83.3%, P=0.041). The incidence of acute GVHD was 84.6% (11 of 13) and 58.3% (7 of 12) in the MAC and RIC groups, respectively. The cumulative incidence of grade III‒IV acute GVHD was significantly higher in the MAC group than in the RIC group (P=0.03). No significant differences were observed in progression-free and overall survival. The 17-month probability of progression-free survival was 38.4% [95% confidence interval (CI), 19.3‒76.5] vs. 47.6% (95% CI, 25.7‒88.2) (P=0.21), and that of overall survival was 53.8% (95% CI, 32.5‒89.1) vs. 48.6% (95% CI, 26.8‒88.3) (P=0.85) for MAC vs. RIC, respectively.
Conclusion
RIC offers a significant advantage over MAC, even in younger patients with MF undergoing alloSCT, in terms of cell engraftment, rate of complete chimerism achievement, and incidence of acute GVHD.
Keywords: Myelofibrosis, Hematopoietic stem cell transplantation, Reduced intensity, Myeloablative
Table 1 . Baseline characteristics..
All patients (N=25) | MAC group (N=13) | RIC group (N=12) | ||
---|---|---|---|---|
Age, years, median (range) | 49.9 (27–64) | 45.0 (27–64) | 55.2 (48–63) | 0.028 |
Sex, male, N (%) | 14 (56) | 5 (38.5) | 9 (75) | 0.151 |
Secondary MF | 6 (24) | 3 (23.1) | 3 (25) | 1.000 |
Splenomegaly at diagnosis | 21 (84) | 11 (84.6) | 10 (83.3) | 1.000 |
Spleen status at HSCT | ||||
Splenomegaly | 17 (68) | 7 (53.8) | 10 (83.3) | 0.250 |
Splenectomy prior to HSCT | 4 (16) | 3 (23.1) | 1 (8.3) | 0.647 |
RT to spleen prior to HSCT | 1 (4) | 0 (0) | 1 (8.3) | 0.967 |
Ruxolitinib before HSCT | 10 (40) | 0 (0) | 10 (83.3) | 0.000 |
Mutation status (positive/tested) | ||||
Not assessed | 6 | 6 | 0 | |
10/19 | 2/7 | 8/12 | 0.259 | |
0/2 | 0/1 | 0/1 | ||
0/4 | 0/2 | 0/2 | ||
0/4 | 0/2 | 0/2 | ||
Triple negative | ||||
Cytogenetics | 0.360 | |||
Normal | 15 (68.2) | 6 (54.5) | 9 (81.8) | |
Abnormal | 7 (31.8) | 5 (45.5) | 2 (18.2) | |
D-IPSS at diagnosis | ||||
Low | 5 (20) | 2 (15.4) | 3 (25) | 0.920 |
Intermediate-1 | 9 (36) | 5 (38.5) | 4 (33.3) | 1.000 |
Intermediate-2 | 9 (36) | 5 (38.5) | 4 (33.3) | 1.000 |
High | 2 (8) | 1 (7.7) | 1 (8.3) | 1.000 |
D-IPSS at HSCT | ||||
Low | 0 | 0 | 0 | |
Intermediate-1 | 0 | 0 | 0 | |
Intermediate-2 | 18 (72) | 12 (92.3) | 6 (50) | 0.056 |
High | 7 (28) | 1 (7.7) | 6 (50) | 0.056 |
Time to HSCT from diagnosis, months (range) | 30.9 (2.9–118.3) | 18.7 (2.9–114.5) | 44.1 (8.8–118.3) | 0.087 |
Donor type | ||||
Matched related | 16 (64) | 8 (61.5) | 8 (66.7) | 1.000 |
Matched unrelated | 3 (12) | 2 (15.4) | 1 (8.3) | 1.000 |
Mismatched unrelated | 3 (12) | 2 (15.4) | 1 (8.3) | 1.000 |
Haplo-identical | 3 (12) | 1 (7.7) | 2 (16.7) | 0.941 |
CD34+, ×106/kg, median (range) | 5.7 (2.12–12.23) | 6.2 (2.12–10.34) | 5.1 (3.39–12.23) | 0.426 |
Calcineurin inhibitor, N (%) | ||||
Cyclosporine | 25 (100) | 13 (100) | 12 (100) | |
Tacrolimus | 0 | 0 | 0 | |
Methotrexate, N (%) | 12 (48) | 6 (46.2) | 6 (50) | 1.000 |
ATG, N (%) | 21 (84) | 9 (69.2) | 12 (100) | 0.121 |
pre-HSCT CBC, median (range) | ||||
WBC count (103mL) | 10.7 (0.52–38.9) | 8.81 (1.08–34.4) | 12.75 (0.52–38.9) | 0.414 |
Hemoglobin (g/dL) | 7.9 (5–14.6) | 7.5 (5.5–14) | 8.4 (5–14.6) | 0.453 |
Platelet count (103/mL) | 137.4 (14–543) | 114.8 (14–543) | 161.9 (17–384) | 0.408 |
Blast (%) | 0.6 (0–6) | 0.07 (0–1) | 1.2 (0–6) | 0.201 |
Abbreviations: ATG, antithymocyte globulin;
Table 2 . Transplantation outcomes..
MAC group | RIC group | ||
---|---|---|---|
Neutrophil engraftment | 11 (84.6) | 12 (100) | 0.497 |
Time to engraftment, days (median, range) | 15.9 (8–23) | 15.8 (11–22) | 0.964 |
Platelet engraftment, N (%) | 9 (69.2) | 9 (75) | 1.000 |
Time to engraftment, days (median, range) | 112.8 (22–317) | 28.7 (16–74) | 0.049 |
Acute GVHD, any, N (%) | 11 (84.6) | 7 (58.3) | 0.201 |
Grade III–IV acute GVHD | 7 (53.8) | 2 (16.7) | 0.096 |
Chronic GVHD, any, N (%) | 5 (38.5) | 4 (33.3) | 1.000 |
Moderate to severe chronic GVHD | 4 (30.8) | 2 (16.7) | 0.644 |
Death, N (%) | 10 (76.9) | 6 (50) | 0.325 |
NRM, N (%) | 8 (61.5) | 3 (25.0) | 0.151 |
Causes of death, N (%) | 0.345 | ||
Disease recurrence or progression | 2 (20.0) | 3 (50.0) | 0.486 |
Graft failure | 2 (20.0) | 0 (0.0) | 0.696 |
GVHD | 1 (10.0) | 1 (16.7) | 1.000 |
Infection | 3 (30.0) | 0 (0.0) | 0.408 |
Others | 2 (20.0) | 2 (33.3) | 1.000 |
Complete chimerism achievement, N (%) | |||
At initial post-transplantation evaluation | 1 (7.7) | 4 (33.3) | 0.271 |
During follow-up | 5 (38.5) | 10 (83.3) | 0.041 |
Abbreviations: GVHD, graft-versus-host disease; MAC, myeloablative conditioning; NRM, non-relapse mortality; RIC, reduced intensity conditioning..
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