Comparison of Melphalan Combined with Treosulfan or Busulfan as High-Dose Chemotherapy before Autologous Stem Cell Transplantation in AML
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Treatment
2.3. Supportive Therapy
2.4. Assessment of Adverse Events and Survival Rates
2.5. Plasma Concentration Measurement
2.6. Statistical Analysis
3. Results
3.1. Patient Characteristics and Treatment
3.2. Hematologic Recovery
3.3. Infections during Hospitalization
3.4. Other Non-Hematologic Toxicities during Hospitalization
3.5. Treosulfan Plasma Concentration and Correlation with Non-Hematologic Toxicities
3.6. Progression-Free Survival and Overall Survival
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | BuMel (n = 16) | TreoMel (n = 20) | All Patients (n = 36) | p-Value |
---|---|---|---|---|
Mean age at diagnosis, years (range) | 57 (38–73) | 51 (33–72) | 54 (34) | 0.120 |
Males/females (ratio) | 8/8 (1.0) | 14/6 (2.3) | 22/14 (1.6) | 0.667 |
ELN risk categories, favorable | 8 | 9 | 17 | 0.999 |
intermediate | 5 | 10 | 15 | 0.492 |
adverse | 3 | 1 | 4 | 0.292 |
FAB classification, M0 | 2 (13%) | 1 (5%) | 3 (8%) | 0.574 |
M1 | 6 (38%) | 4 (20%) | 10 (28%) | 0.285 |
M2 | 2 (13%) | 9 (45%) | 11 (31%) | 0.067 |
M4 | 3 (19%) | 4 (20%) | 7 (19%) | 0.999 |
M5 | 2 (13%) | 2 (10%) | 4 (11%) | 0.999 |
Secondary AML | 1 (6%) | 1 (5%) | 2 (6%) | 0.999 |
Peripheral Blood Parameters | ||||
WBC, G/L | 18 (±24) | 41 (±78) | 30 (±61) | 0.264 |
Platelets, G/L | 89 (±79) | 77 (±57) | 82 (±67) | 0.603 |
Hemoglobin, g/dL | 92 (±28) | 89 (±23) | 90 (±24) | 0.735 |
Peripheral blasts, % | 37 (±30) | 43 (±26) | 43 (±27) | 0.285 |
BM blasts, % | 72 (±24) | 76 (±20) | 75 (±22) | 0.621 |
LDH, U/L | 956 (±834) | 889 (±531) | 938 (±705) | 0.065 |
Parameter | BuMel (n = 16) | TreoMel (n = 20) | All Patients (n = 36) | p-Value |
---|---|---|---|---|
Median follow up, months (range) | 36.5 (6–48) | 23 (3–28) | 23.5 (3–48) | 0.0089 |
Median time from diagnosis to ASCT, months (range) | 4 (2–13) | 3 (2–6) | 3 (2–13) | 0.164 |
Median CD34+ cells at ASCT, n × 106 /kg b.w. (range) | 4.12 (2.46–8.12) | 3.86 (2.85–5.94) | 4.03 (2.46–8.12) | 0.788 |
Median time to neutrophil recovery, days (range) | 12 (11–33) | 12 (11–21) | 12 (11–33) | 0.417 (ns) |
Median time to neutropenia, days (range) | 5 (2–7) | 5 (2–8) | 5 (2–8) | 0.567 (ns) |
Median time in neutropenia, days (range) | 7 (5–28) | 8 (5–11) | 7.5 (5–28) | 0.507 (ns) |
Median time to platelet recovery, days (range) | 23 (13–137) | 23 (11–89) | 36 (11–137) | 0.221 (ns) |
Median hospitalization duration, days (range) | 25 (21–39) | 20 (18–101) | 24 (18–101) | 0.574 (ns) |
Relapse, n (%) | 7 (44%) | 11 (55%) | 18 (50%) | 0.738 (ns) |
Median interval to relapse, months (range) | 6 (2–8) | 6 (2–23) | 6 (1–23) | 0.547 (ns) |
Deaths, number (%) | 6 (38%) | 6 (30%) | 12 (33%) | 0.730 (ns) |
Median time to death, months (range) | 9 (6–21) | 8 (3–25) | 9 (3–25) | 0.766 (ns) |
Parameter | BuMel (n = 16) | TreoMel (n = 20) | p-Value |
---|---|---|---|
Febrile episode | 16 (100%) | 20 (100%) | 0.999 |
Causative agent identified | 12 (75%) | 14 (70%) | 0.999 |
Bacterial agent identified | 12 (75%) | 13 (65%) | 0.718 |
Viral agent identified | 3 (19%) | 2 (10%) | 0.632 |
Fungal agent identified | 1 (7%) | 1 (5%) | 0.999 |
Multiple infectious foci identified | 4 (25%) | 1 (5%) | 0.141 |
Parameter | Grade I | Grade II | Grade III | Grade IV | p-Value | ||||
---|---|---|---|---|---|---|---|---|---|
Toxicity, n (%) | Bu Mel n = 16 | Treo Mel n = 20 | Bu Mel n = 16 | Treo Mel n = 20 | Bu Mel n = 16 | Treo Mel n = 20 | Bu Mel n = 16 | Treo Mel n = 20 | |
Diarrhea | 8 (50) | 6 (30) | 0 (0) | 4 (20) | 4 (25) | 8 (40) | 0 (0) | 0 (0) | 0.374 |
Mucositis | 5 (31) | 7 (35) | 1 (6) | 2 (10) | 3 (19) | 3 (15) | 0 (0) | 0 (0) | 0.999 |
Irreversible alopecia | 3 (19) | 0 (0) | 4 (25) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0.0014 |
Partial | 3 (19) | 0 (0) | - | - | - | - | - | - | 0.078 |
Complete | - | - | 4 (25) | 0 (0) | - | - | - | - | 0.031 |
Increase of liver enzymes | 7 (44) | 37 (5) | 4 (25) | 7 (35) | 4 (25) | 4 (20) | 1 (6) | 0 (0) | 0.492 |
Veno-occlusive disease | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0.999 |
Epileptic seizure | 0 (0) | 0 (0) | 1 (6) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0.444 |
Encephalopathy | 1 (6) | 0 (0) | 1 (6) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0.191 |
Thrush | 2 (13) | 8 (40) | 1 (6) | 0 (0) | 2 (13) | 0 (0) | 0 (0) | 0 (0) | 0.731 |
Engraftment syndrome | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 5 (31) | 4 (20) | 0 (0) | 0 (0) | 0.470 |
Reference | Number of Patients | Median Age (Years) | AUC, μg/mL*h (Mean ± SD) |
---|---|---|---|
Mohanan et al. [30] | 87 | 9 | 1396 ± 715 |
Sender et al. [31] | 10 | 51 | 1104 ± 173 |
Nemecek et al. [16] | 12 | 34 | 1309 ± 262 |
Baronciani et al. [32] | 7 | 7.5 | 2400 ± 1267 |
Present study | 20 | 50.9 | 836.79 ± 117.27 |
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Gurevich, E.; Hayoz, M.; Aebi, Y.; Largiadèr, C.R.; Mansouri Taleghani, B.; Bacher, U.; Pabst, T. Comparison of Melphalan Combined with Treosulfan or Busulfan as High-Dose Chemotherapy before Autologous Stem Cell Transplantation in AML. Cancers 2022, 14, 1024. https://doi.org/10.3390/cancers14041024
Gurevich E, Hayoz M, Aebi Y, Largiadèr CR, Mansouri Taleghani B, Bacher U, Pabst T. Comparison of Melphalan Combined with Treosulfan or Busulfan as High-Dose Chemotherapy before Autologous Stem Cell Transplantation in AML. Cancers. 2022; 14(4):1024. https://doi.org/10.3390/cancers14041024
Chicago/Turabian StyleGurevich, Ekaterina, Michael Hayoz, Yolanda Aebi, Carlo R. Largiadèr, Behrouz Mansouri Taleghani, Ulrike Bacher, and Thomas Pabst. 2022. "Comparison of Melphalan Combined with Treosulfan or Busulfan as High-Dose Chemotherapy before Autologous Stem Cell Transplantation in AML" Cancers 14, no. 4: 1024. https://doi.org/10.3390/cancers14041024