The aml Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the aml Hub cannot guarantee the accuracy of translated content. The aml and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The AML Hub is an independent medical education platform, sponsored by Astellas, Daiichi Sankyo, Johnson & Johnson, Kura Oncology and Syndax, and has been supported through educational grants from Bristol Myers Squibb and the Hippocrate Conference Institute, an association of the Servier Group. The funders are allowed no direct influence on our content. The levels of sponsorship listed are reflective of the amount of funding given. View funders.
Now you can support HCPs in making informed decisions for their patients
Your contribution helps us continuously deliver expertly curated content to HCPs worldwide. You will also have the opportunity to make a content suggestion for consideration and receive updates on the impact contributions are making to our content.
Find out moreCreate an account and access these new features:
Bookmark content to read later
Select your specific areas of interest
View aml content recommended for you
In most patients with acute myeloid leukemia (AML), the only curative option is allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, patients with AML are frequently elderly with comorbidities which limits their eligibility for myeloablative conditioning (MAC) followed by allo-HSCT. The use of non-myeloablative (NMA) conditioning has enabled patients, who might otherwise have been deemed ineligible, to access allo-HSCT. NMA conditioning relies more on the graft-versus-leukemia response than on the anti-leukemic effect of the conditioning regimen. The two main NMA options are low dose chemotherapy (fludarabine/busulfan; FB2) or low dose radiotherapy (fludarabine/total-body-irradiation; FluTBI2Gy).
Thomas Heinicke of the Department of Hematology and Oncology, Otto-von-Guericke University, Magdeburg, DE, and colleagues recently published the results of their retrospective analysis of outcomes following the two NMA conditioning regimens prior to allo-HSCT for AML in Bone Marrow Transplantation. They performed a registry analysis using the European Society for Blood and Marrow Transplantation (EBMT) central database to compare outcomes in patients who had undergone allo-HSCT (from matched sibling donors [MSD] or matched unrelated donors [MUD]) for AML treatment during their first complete remission (CR1) using NMA conditioning with either FB2 or FluTBI2Gy.
IQR; interquartile range, secAML; secondary AML, MSD; matched sibling donor, FB2 fludarabine/busulfan; FluTBI2Gy fludarabine total-body-irradiation (2Gy), MUD; matched unrelated donor, GvHD; graft-versus-host-disease, CSA; cyclosporine, MTX; methotrexate, MMF; mycophenolate mofetil, TACRO; tacrolimus, TCD in vivo T-cell depletion. * p values from comparisons of missing/incomplete data
FB2
(n= 553)
FluTBI2Gy
(n= 535)
p value
Follow up (reverse Kaplan-Meier; months)
Median (IQR)
26.7 (12.3–51.1)
47.7 (20.2–74.5)
< 0.001
Age at HSCT (years)
Median (IQR)
64.8 (62.2–67.2)
65.3 (62.7–68.2)
0.0023
Time between diagnosis and HSCT (months)
Median (IQR)
5.4 (4.4–6.9)
4.6 (3.6–5.8)
< 0.0001
Year of treatment
Median (IQR)
2014 (2005–2017)
2012 (2003–2017)
< 0.0001
Donor age (years)
Median (IQR)
Missing
47.8 (30.7–59.3)
103 (18.62%)
49.4 (29.7–61.7)
206 (38.5%)
0.44
< 0.0001*
Diagnosis
De novo
secAML
408 (73.78%)
145 (26.22%)
417 (77.94%)
118 (22.06%)
0.11
Cytogenetics
Good
Intermediate
Poor
NA/failed
12 (2.17%)
291 (52.62%)
119 (21.52%)
131 (23.69%)
7 (1.31%)
223 (41.68%)
78 (14.58%)
227 (42.43%)
0.59
< 0.0001*
Karnofsky performance score
< 90
≥ 90
missing
130 (23.51%)
371 (67.09%)
52 (9.4%)
161 (30.09%)
318 (59.44%)
56 (10.47%)
0.01
0.56*
Donor type
MSD
MUD 10/10
270 (48.82%)
283 (51.18%)
240 (44.86%)
295 (55.14%)
0.19
GvHD prevention
CSA
CSA + MTX
CSA + MMF +/- MTX
TACRO +/- other
Other
161 (29.11%)
207 (37.43%)
155 (28.03%)
17 (3.07%)
13 (2.35%)
7 (1.31%)
6 (1.12%)
405 (75.7%)
112 (20.93%)
5 (0.93%)
< 0.0001
TCD
No
Yes
115 (20.8%)
438 (79.2%)
535 (100%)
0
< 0.0001
95% CI; 95% confidence interval, MSD; matched sibling donor, cGvHD; chronic graft-versus-host-disease, GRFS; refined graft-versus-host disease-free relapse-free survival, TCD in vivo T-cell depletion, FB2; fludarabine/busulfan, FluTBI2Gy; fludarabine total-body-irradiation (2Gy)
FluTBI2Gy, No TCD
FB2, TCD
FB2, No TCD
p value
cGvHD, incidence
43.6% (95% CI: 36.8−50.3)
30.5% (95% CI: 22.9−38.4)
43.4% (95% CI: 30.8−55.3)
0.01
Extensive cGvHD, incidence
25.1% (95% CI: 19.3−31.3)
13.7% (95% CI: 8.4−20.4)
24.6% (95% CI: 14.9−35.5)
0.007
GRFS
31.4% (95% CI: 25.2−37.6)
35.2% (95% CI: 27−43.4)
25.8% (95% CI: 15.6−36)
0.07
Table 3: Univariate analysis of incidence of GvHD and probability of GRFS in MUD transplanted patients95% CI; 95% confidence interval, MSD; matched sibling donor, cGvHD; chronic graft-versus-host-disease, GRFS; refined graft-versus-host disease-free relapse-free survival, TCD in vivo T-cell depletion, FB2; fludarabine/busulfan, FluTBI2Gy; fludarabine total-body-irradiation (2Gy)
FluTBI2Gy
FB2
p value
cGvHD, incidence
56.6% (95% CI: 49.8–62.9)
32.7% (95% CI: 26.6–38.9)
< 0.0001
Extensive cGvHD, incidence
34.2% (95% CI: 27.9−40.6)
11.9% (95% CI: 7.9–16.7)
< 0.0001
GRFS
26% (95% CI: 20.4−31.6)
42.4% (95% CI: 35.9−48.9)
< 0.001
Thomas Heinicke and colleagues discussed how results from this study differed from the phase II trial by Didier Blaise2 in terms of aGvHD and cGvHD incidence, relapse rates and NRM, but felt that it was due to differences in patient selection, busulfan formulation, post grafting immunosuppression, and donors. They argued that the lower incidence of cGvHD and extensive cGvHD seen in the FB2 treatment group may be effected by the difference in TCD between the two treatment groups (79% of the FB2 group received TCD, but none in the FluTBI2Gy had TCD), and that the use of TCD in the MSD group treated with FB2 decreased rates of cGvHD, which was in agreement with previous studies.2 The authors went on to discuss the protective effect that TCD seemed to offer against cGvHD, which had also been seen in other studies4-7 with comparable rates of aGvHD and cGvHD.8
The study, being retrospective, has limitations due to the unknown reason behind patients being given each treatment regimens, unknown type and dose of ATG (for TCD), and missing data on residual disease. Despite the limitations, Heinicke and colleagues feel the results were important to the allo-HSCT field due to the large homogenous study cohort. They concluded by highlighting that in this group of patients, those receiving transplants from MUDs with FB2 conditioning and TCD had a lower incidence of cGvHD, extensive cGvHD, and improved GRFS when compared to FluTBI2Gy without TCD.
References
Please indicate your level of agreement with the following statements:
The content was clear and easy to understand
The content addressed the learning objectives
The content was relevant to my practice
I will change my clinical practice as a result of this content