Blood Res 2022; 57(2): 152-157
Published online June 30, 2022
https://doi.org/10.5045/br.2022.2022047
© The Korean Society of Hematology
Correspondence to : Kyung-Nam Koh, M.D., Ph.D.
Ho Joon Im, M.D., Ph.D.
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, 88, Olympic-ro, 43-gil, Songpa-gu, Seoul 05505, Korea
E-mail: K.N.K., pedkkn@amc.seoul.kr
H.J.I., hojim@amc.seoul.kr
*This study was supported by a grant from the Korea Disease Control and Prevention Agency (2019ER690301, 2022ER050200).
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
The incorporation of a reduced-intensity conditioning (RIC) regimen in hematopoietic cell transplantation (HCT) for patients with hemophagocytic lymphohistiocytosis (HLH) has decreased early mortality but is associated with a high rate of mixed chimerism and graft failure. Here, we present a successful single-center experience using busulfan and a fludarabine-based RIC regimen for the treatment of HLH.
Methods
The medical records of pediatric patients with HLH who underwent HCT using a busulfan/ fludarabine-based RIC regimen between January 2008 and December 2017 were reviewed retrospectively.
Results
Nine patients received HCT with a busulfan/fludarabine-based RIC regimen. Three patients had primary HLH, and the other six patients had secondary HLH with multiple reactivations. All three patients with primary HLH had UNC13D mutations. All patients achieved neutrophil and platelet engraftment at a median of 11 days (range, 10‒21) and 19 days (range, 13‒32), and all eight evaluable patients had sustained complete donor chimerism at the last follow-up. Two patients (22%) experienced grade 2 acute graft-versus- host disease (GVHD). Two patients (22%) developed chronic GVHD, and one died from chronic GVHD. One patient (11%) experienced reactivation 4 months after HCT from a syngeneic donor and died of the disease. The 8-year overall survival and event-free survival rates were 78%. No early treatment-related mortality within 100 days after HCT was observed.
Conclusion
Our experience suggests that a busulfan/fludarabine-based RIC regimen is a viable option for pediatric patients with HLH who require HCT.
Keywords Hematopoietic stem cell transplantation, Pediatric, Hemophagocytic lymphohistiocytosis
Blood Res 2022; 57(2): 152-157
Published online June 30, 2022 https://doi.org/10.5045/br.2022.2022047
Copyright © The Korean Society of Hematology.
Jin Kyung Suh1, Young Kwon Koh2, Sung Han Kang2, Hyery Kim2, Eun Seok Choi2, Kyung-Nam Koh2, Ho Joon Im2
1Department of Pediatrics, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, 2Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea
Correspondence to:Kyung-Nam Koh, M.D., Ph.D.
Ho Joon Im, M.D., Ph.D.
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, 88, Olympic-ro, 43-gil, Songpa-gu, Seoul 05505, Korea
E-mail: K.N.K., pedkkn@amc.seoul.kr
H.J.I., hojim@amc.seoul.kr
*This study was supported by a grant from the Korea Disease Control and Prevention Agency (2019ER690301, 2022ER050200).
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
The incorporation of a reduced-intensity conditioning (RIC) regimen in hematopoietic cell transplantation (HCT) for patients with hemophagocytic lymphohistiocytosis (HLH) has decreased early mortality but is associated with a high rate of mixed chimerism and graft failure. Here, we present a successful single-center experience using busulfan and a fludarabine-based RIC regimen for the treatment of HLH.
Methods
The medical records of pediatric patients with HLH who underwent HCT using a busulfan/ fludarabine-based RIC regimen between January 2008 and December 2017 were reviewed retrospectively.
Results
Nine patients received HCT with a busulfan/fludarabine-based RIC regimen. Three patients had primary HLH, and the other six patients had secondary HLH with multiple reactivations. All three patients with primary HLH had UNC13D mutations. All patients achieved neutrophil and platelet engraftment at a median of 11 days (range, 10‒21) and 19 days (range, 13‒32), and all eight evaluable patients had sustained complete donor chimerism at the last follow-up. Two patients (22%) experienced grade 2 acute graft-versus- host disease (GVHD). Two patients (22%) developed chronic GVHD, and one died from chronic GVHD. One patient (11%) experienced reactivation 4 months after HCT from a syngeneic donor and died of the disease. The 8-year overall survival and event-free survival rates were 78%. No early treatment-related mortality within 100 days after HCT was observed.
Conclusion
Our experience suggests that a busulfan/fludarabine-based RIC regimen is a viable option for pediatric patients with HLH who require HCT.
Keywords: Hematopoietic stem cell transplantation, Pediatric, Hemophagocytic lymphohistiocytosis
Table 1 . Patient characteristics before HSCT..
Patient no. | Sex | Age at diagnosis, years | Diagnosis | Genetic mutation or underlying cause | No. of reactivation before HSCT | Duration of chemoimmunotherpy, months | Status at HSCT |
---|---|---|---|---|---|---|---|
1 | M | 0.3 | Primary HLH | 2 | 10.3 | PR | |
2 | M | 7.6 | Secondary HLH | Not identified | 1 | 2.1 | CR |
3 | F | 0.6 | Primary HLH | 2 | 4.6 | CR | |
4 | M | 9.9 | Secondary HLH | Not identified | 3 | 2.5 | NR |
5 | M | 8.5 | Secondary HLH | EBV associated | 1 | 2.3 | CR |
6 | F | 0.2 | Primary HLH | 0 | 5.3 | CR | |
7 | M | 13.2 | Secondary HLH | CAEBV | 2 | 4.3 | PR |
8 | F | 1.9 | Secondary HLH | EBV associated | 2 | 4.6 | CR |
9 | F | 11.5 | Secondary HLH | SLE | 2 | 4.0 | PR |
Abbreviations: CAEBV, chronic active EBV infection; CR, complete response; HLH, hemophagocytic lymphohistiocytosis; HSCT, hematopoietic stem cell transplantation; NR, non-response; PR, partial response; SLE, systemic lupus erythematosus..
Table 2 . Count of infused CD34+ cells and donor chimerism of each patient..
Patient no. | CD34+ cells, 106/kg | Donor chimerism, % | |||||
---|---|---|---|---|---|---|---|
1 mo | 2 mo | 3 mo | 6 mo | 1 yr | 2 yr | ||
1 | 8.77 | 100 | 100 | 100 | 100 | 100 | 100 |
2 | 6.54 | 90 | 74 | 74 | 100 | 100 | 100 |
3 | 8.35 | 100 | 100 | 98 | 100 | 100 | 100 |
4 | 11.91 | Syngeneic | |||||
5 | 9.17 | 100 | 100 | 96 | 100 | 100 | 100 |
6 | 6.17 | 99 | NA | 95 | 100 | 100 | 100 |
7 | 2.84 | 95 | 100 | 100 | 100 | 100 | Dead |
8 | 10.05 | 98 | 100 | 100 | 100 | 100 | 100 |
9 | 7.46 | 99 | NA | 98 | 100 | 100 | 100 |
Abbreviation: NA, not available..
Table 3 . Transplant characteristics and outcomes..
Patient no. | Time from diagnosis to HSCT, mo | Type of donor | Conditioning regimen | Acute GVHD | Chronic GVHD | a)Performance score before HSCT, % | a)Performance score after HSCT, % | Disease status | Survival |
---|---|---|---|---|---|---|---|---|---|
1 | 12.2 | URD | FluBuCy | No | No | 50 | 90 | CR | Alive |
2 | 28.7 | MSD | FluBuCy | No | Yes, limited | 70 | 100 | CR | Alive |
3 | 4.8 | MSD | FluBuCy | No | No | 90 | 100 | CR | Alive |
4 | 7.4 | MSD (syngeneic) | FluBuCyATG | No | No | 70 | - | NR | Dead (DOD) |
5 | 5.4 | URD | FluBuCyATG | Yes (Gr 2, skin) | No | 90 | 100 | CR | Alive |
6 | 6.1 | URD | FluBuCyATG | No | No | 90 | 100 | CR | Alive |
7 | 3.1 | MSD | FluBuCy b)VpATG | No | Yes, extensive | 70 | - | CR | Dead (TRM) |
8 | 5.0 | MSD | FluBuCy b)VpATG | No | No | 90 | 100 | CR | Alive |
9 | 28.2 | URD | FluBuCyATG | Yes (Gr 2, skin and gut) | No | 70 | 80 | CR | Alive |
a)Performance score was evaluated using the Lansky score, which was not provided to patients who died. b)Patients who developed HLH flare during conditioning received additional doses of VP-16 and dexamethasone..
Abbreviations: CR, complete response; DOD, death from disease; GVHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplantation; MSD, matched sibling donor; NA, not available; NR, nonresponse; PR, partial response; TRM, treatment-related mortality; URD, unrelated donor..
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