Fludarabine–Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia
Abstract
:1. Introduction
2. Materials and Methods
Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A. Prophylaxis and Treatment of Infections
References
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Category | Value | |
---|---|---|
Number of Patients | 56 | |
Sex | male | 33 |
female | 23 | |
Age at HCT in years | median | 9.4 |
range | 0.8–17.8 | |
Time from diagnosis to HCT in months | median | 4.57 |
range | 1.23–66.6 | |
Previous IS protocol | yes | 14 |
no | 32 | |
PNH clone | detectable | 8 |
undetectable | 48 | |
Donor | matched sibling donor | 18 |
matched unrelated donor | 38 | |
Degree of HLA match | matched sibling donor, 6/6 | 15 |
matched sibling donor, 10/10 | 2 | |
matched unrelated donor, 10/10 | 33 | |
matched sibling/unrelated donor, 9/10 | 6 | |
Stem cell source | bone marrow | 17 |
peripheral blood stem cells | 39 | |
Bone marrow CD34 + cells/kg in millions | median (range) | 3.54 (0.34–12.14) |
Peripheral blood CD34 + cells/kg in millions | median (range) | 9.31 (2.42–29.78) |
Antithymocyte globulin | Grafalon | 15 |
Thymoglobulin | 41 | |
Posttransplantation methotrexate | yes | 54 |
no | 2 | |
Posttransplantation follow-up in months | median | 44 |
range | 0–144 | |
Time to neutrophil count > 500/µL in days | median | 14 |
range | 10–22 | |
Time to platelet count > 20,000/µL in days | median | 16 |
range | 5–212 | |
Acute graft versus host disease | any grade | 22 |
grade III-IV | 6 | |
Chronic graft versus host disease | any grade | 7 |
moderate–severe grade | 5 |
Category | Number of Patients | 5-Year OS | Log-Rank p | 2-Year GFS | Log-Rank p | |
---|---|---|---|---|---|---|
Sex | male | 33 | 93.9 | ns | 84.5 | ns |
female | 23 | 91.3 | 63.4 | |||
Previous IS protocol | yes | 14 | 83.3 | p = 0.017 | 66.4 | ns |
no | 32 | 100 | 83.5 | |||
Time from diagnosis to HCT | <3 months | 14 | 100 | ns | 91.7 | ns |
>3 months | 41 | 90.2 | 70.4 | |||
PNH clone | detectable | 8 | 100 | ns | 100 | ns |
undetectable | 48 | 91.7 | 72 | |||
Donor | matched sibling donor | 18 | 94.1 | ns | 87.8 | ns |
matched unrelated donor | 38 | 92.3 | 71 | |||
Recipient–donor gender | Male donor–male recipient | 24 | 100 | p = 0.04 | 86.8 | ns |
Female donor–female recipient | 11 | 81.8 | 53 | |||
Male donor–female recipient | 9 | 77.8 | 77.8 | |||
Female donor–male recipient | 12 | 100 | 72.9 | |||
Donor gender | Male donor | 36 | 100 | p = 0.005 | 82.5 | ns |
Female donor | 20 | 80 | 64.6 | |||
CMV IgG status | Donor positive–recipient positive | 28 | 90.3 | ns | 73.1 | ns |
Donor positive–recipient negative | 4 | 100 | 100 | |||
Donor negative–recipient positive | 15 | 93.8 | 75 | |||
Donor negative–recipient negative | 4 | 100 | 75 | |||
Stem cell source | bone marrow | 17 | 88.2 | ns | 69.7 | ns |
peripheral blood stem cells | 39 | 94.9 | 79 | |||
Conditioning | Flu 160 mg/m2 + Cy 200 mg/kg BW | 12 | 85 | p = 0.0063 | 58.3 | ns |
Flu 120 mg/m2 + Cy 100 mg/kg BW | 44 | 97.7 | 81 | |||
Antithymocyte globulin | Grafalon | 15 | 100 | ns | 100 | ns |
Thymoglobulin | 41 | 90.2 | 70.7 | |||
Acute graft versus host disease | no | 34 | 91.2 | ns | n/a | |
grade I-II | 16 | 100 | ||||
grade III-IV | 6 | 83.3 | ||||
Chronic graft versus host disease | no | 49 | 97.8 | ns | n/a | |
any grade | 7 | 100 | ||||
Posttransplantation ADV replication | yes | 7 | 100 | ns | 76.9 | ns |
no | 49 | 91.8 | 71.4 | |||
Posttransplantation BKV replication | yes | 16 | 100 | ns | 87.5 | ns |
no | 40 | 90 | 71.9 | |||
Posttransplantation CMV replication | yes | 16 | 100 | ns | 93.8 | ns |
no | 40 | 90 | 69.1 | |||
Posttransplantation EBV replication | yes | 12 | 91.7 | ns | 74.1 | ns |
no | 44 | 93.2 | 76.7 |
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Salamonowicz-Bodzioch, M.; Rosa, M.; Frączkiewicz, J.; Gorczyńska, E.; Gul, K.; Janeczko-Czarnecka, M.; Jarmoliński, T.; Kałwak, K.; Mielcarek-Siedziuk, M.; Olejnik, I.; et al. Fludarabine–Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia. J. Clin. Med. 2021, 10, 4416. https://doi.org/10.3390/jcm10194416
Salamonowicz-Bodzioch M, Rosa M, Frączkiewicz J, Gorczyńska E, Gul K, Janeczko-Czarnecka M, Jarmoliński T, Kałwak K, Mielcarek-Siedziuk M, Olejnik I, et al. Fludarabine–Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia. Journal of Clinical Medicine. 2021; 10(19):4416. https://doi.org/10.3390/jcm10194416
Chicago/Turabian StyleSalamonowicz-Bodzioch, Małgorzata, Monika Rosa, Jowita Frączkiewicz, Ewa Gorczyńska, Katarzyna Gul, Małgorzata Janeczko-Czarnecka, Tomasz Jarmoliński, Krzysztof Kałwak, Monika Mielcarek-Siedziuk, Igor Olejnik, and et al. 2021. "Fludarabine–Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia" Journal of Clinical Medicine 10, no. 19: 4416. https://doi.org/10.3390/jcm10194416