Original Article

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Blood Res 2022; 57(4):

Published online December 31, 2022

https://doi.org/10.5045/br.2022.2022194

© The Korean Society of Hematology

Reduced-intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for patients with myelofibrosis

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).

Received: September 27, 2022; Revised: November 21, 2022; Accepted: November 24, 2022

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

Article

Original Article

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.

Reduced-intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for patients with myelofibrosis

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).

Received: September 27, 2022; Revised: November 21, 2022; Accepted: November 24, 2022

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.

Abstract

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

Fig 1.

Figure 1.Patient flow chart diagram.Abbreviations: MAC, myeloablative conditioning; MF, myelofibrosis; RIC, reduced intensity conditioning.
Blood Research 2022; 57: 264-271https://doi.org/10.5045/br.2022.2022194

Fig 2.

Figure 2.Survival outcomes. (A) Kaplan–Meier curves of progression-free survival for all patients (left) according to conditioning intensity (right). (B) Kaplan–Meier curves of overall survival for all patients (left) according to conditioning intensity (right). (C) Cumulative incidence of non-relapse mortality in all patients (left) according to conditioning intensity (right).
Blood Research 2022; 57: 264-271https://doi.org/10.5045/br.2022.2022194

Fig 3.

Figure 3.Cumulative incidence of acute graft-versus-host disease (GVHD). (A) Cumulative incidence of acute GVHD in all patients (left) according to conditioning intensity (right). (B) Cumulative incidence of grade Ⅲ–Ⅳ acute GVHD in all patients (left) according to conditioning intensity (right).
Blood Research 2022; 57: 264-271https://doi.org/10.5045/br.2022.2022194

Fig 4.

Figure 4.Cumulative incidence of chronic graft-versus-host disease (GVHD). (A) Cumulative incidence of chronic GVHD in all patients (left) according to conditioning intensity (right). (B) Cumulative incidence of moderate to severe chronic GVHD in all patients (left) according to conditioning intensity (right).
Blood Research 2022; 57: 264-271https://doi.org/10.5045/br.2022.2022194

Table 1 . Baseline characteristics..

All patients (N=25)MAC group (N=13)RIC group (N=12)P
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 MF6 (24)3 (23.1)3 (25)1.000
Splenomegaly at diagnosis21 (84)11 (84.6)10 (83.3)1.000
Spleen status at HSCT
Splenomegaly17 (68)7 (53.8)10 (83.3)0.250
Splenectomy prior to HSCT4 (16)3 (23.1)1 (8.3)0.647
RT to spleen prior to HSCT1 (4)0 (0)1 (8.3)0.967
Ruxolitinib before HSCT10 (40)0 (0)10 (83.3)0.000
Mutation status (positive/tested)
Not assessed660
JAK2 V617F10/192/78/120.259
JAK2 exon 120/20/10/1
CALR0/40/20/2
MPL0/40/20/2
Triple negative
Cytogenetics0.360
Normal15 (68.2)6 (54.5)9 (81.8)
Abnormal7 (31.8)5 (45.5)2 (18.2)
D-IPSS at diagnosis
Low5 (20)2 (15.4)3 (25)0.920
Intermediate-19 (36)5 (38.5)4 (33.3)1.000
Intermediate-29 (36)5 (38.5)4 (33.3)1.000
High2 (8)1 (7.7)1 (8.3)1.000
D-IPSS at HSCT
Low000
Intermediate-1000
Intermediate-218 (72)12 (92.3)6 (50)0.056
High7 (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 related16 (64)8 (61.5)8 (66.7)1.000
Matched unrelated3 (12)2 (15.4)1 (8.3)1.000
Mismatched unrelated3 (12)2 (15.4)1 (8.3)1.000
Haplo-identical3 (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 (%)
Cyclosporine25 (100)13 (100)12 (100)
Tacrolimus000
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; CALR, calreticulin; CBC, complete blood count; D-IPSS, Dynamic International Prognostic Scoring System; HSCT, hematopoietic stem cell transplantation; JAK2, janus kinase 2; MAC, myeloablative conditioning; MF, myelofibrosis; MPL, myeloproliferative leukemia virus; RIC, reduced intensity conditioning; RT, radiotherapy; WBC, white blood cell..


Table 2 . Transplantation outcomes..

MAC groupRIC groupP
Neutrophil engraftment11 (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 GVHD7 (53.8)2 (16.7)0.096
Chronic GVHD, any, N (%)5 (38.5)4 (33.3)1.000
Moderate to severe chronic GVHD4 (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 progression2 (20.0)3 (50.0)0.486
Graft failure2 (20.0)0 (0.0)0.696
GVHD1 (10.0)1 (16.7)1.000
Infection3 (30.0)0 (0.0)0.408
Others2 (20.0)2 (33.3)1.000
Complete chimerism achievement, N (%)
At initial post-transplantation evaluation1 (7.7)4 (33.3)0.271
During follow-up5 (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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