Impact on outcomes of non-T-depleted haplo-SCT and PTCy in patients with sAML vs de novo AML

In comparison with de novo acute myeloid leukemia (AML), patients with secondary AML (sAML) typically present with poorer overall outcomes, including lower levels of complete remission (CR), relapse-free survival, and a reduced overall survival rate.¹ These inferior outcomes in patients with sAML are attributable to an increased likelihood of adverse molecular mutations and high-risk cytogenetic abnormalities in addition to being older and having prior hematologic disease.

The AML Hub is pleased to summarize a recent study by Nagler et al.¹ comparing the impact of non-T-depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in combination with posttransplant cyclophosphamide (PTCy) on clinical outcomes in patients with sAML versus de novo AML in first CR.

Study design¹

This was a retrospective analysis from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) in patients aged ≥18 years with de novo or sAML in first CR who underwent a first HSCT between 2010 and 2021 from a haploidentical donor and were treated with PTCy. To validate the general population data and limit the impact of individual variables, a matched-pair analysis in a ratio of 1:2 (sAML: de novo AML) was also conducted. Table 1 outlines the baseline characteristics of both cohorts.

Table 1. Baseline patient characteristics*

AML, acute myeloid leukemia; CMV, cytomegalovirus; HCT-CI, hematopoietic cell transplantation specific comorbidity index; MRD, measurable residual disease; sAML, secondary AML. *Adapted from Nagler, et al.1
Characteristic, % (unless otherwise stated)	de novo AML cohort (n = 1,480)	sAML cohort (n = 231)	p value
Median age (range), years	55.8 (18.1–82.5)	60.8 (20.8–75.7)	<0.0001
Sex
Male	57.5	61.9	0.21
Female	42.5	38.1	—
Adverse cytogenetics	29.9	32.9	—
Median time from diagnosis to HSCT (range), months	5.2 (1.0–23.9)	4.9 (1.3–20.5)	0.005
MRD pretransplant
Negative	63.5	59.4	0.51
Positive	36.5	40.6	—
HCT-CI
HCT-CI = 0	57.1	41.8	<0.0001
HCT-CI = 1 or 2	21.6	17.4	—
HCT-CI ≥3	21.3	40.8	—
Karnofsky score
<90	22.0	31.5	0.002
≥90	78.0	68.5	—
Patient CMV
Negative	21.3	23.8	0.4
Positive	78.7	76.2	—
Donor CMV
Negative	37.3	43.8	0.063
Positive	62.7	56.2	—

Results¹

Transplantation outcomes

Incidence of engraftment (95.1% vs 94.4%) and acute graft-versus-host disease (aGvHD) Grade 1–2 (27.2% vs 29.1%) and Grade 3–4 (9.2% vs 6.6%) did not differ significantly between sAML and de novo AML cohorts, respectively. The 2-year incidence of chronic GvHD was also similar between the sAML and de novo AML cohorts (32.2% vs 33.3%, respectively). The presence of prior hematologic disorders did not impact the transplant outcomes in either cohort; Table 2 shows sAML per antecedent hematologic disorder versus de novo AML for posttransplant outcomes.

Table 2. sAML per antecedent hematologic disorder versus de novo AML in posttransplant outcomes*

aGvHD, acute graft-versus-host disease; AML, acute myeloid leukemia; BMFS, bone marrow failure syndrome; cGvHD, chronic GvHD; GRFS, GvHD-free relapse-free survival; HR, hazard ratio; LFS, leukemia-free survival; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm; NRM, non-relapse mortality; OS, overall survival; OMHD/ST, other malignant hematologic disorders/solid tumors. *Adapted from Nagler, et al.1
Relative risk, HR (p value)	de novo AML	MDS/MPN/BMFS	OMHD/ST
Relapse	1	1.02 (0.91)	1.01 (0.96)
NRM	1	0.87 (0.5)	1.18 (0.52)
LFS	1	0.95 (0.73)	1.1 (0.62)
OS	1	0.88 (0.43)	1.1 (0.63)
GRFS	1	0.97 (0.8)	0.89 (0.52)
aGvHD II–IV	1	1.09 (0.65)	0.95 (0.84)
aGvHD III–IV	1	0.77 (0.47)	0.66 (0.42)
cGvHD	1	1.14 (0.42)	0.62 (0.099)
Extensive cGvHD	1	0.81 (0.46)	0.32 (0.055)

Leukemia-free survival, overall survival, non-relapse mortality, GvHD-free relapse-free survival, and relapse rates (Figure 1) were similar between patients with de novo and sAML.

AML, acute myeloid leukemia; GRFS, GvHD-free relapse-free survival; GvHD, graft-versus-host disease; LFS, leukemia-free survival; NRM, non-relapse mortality; OS, overall survival; sAML secondary AML.
*Data from Nagler, et al.¹ 

Matched-pair analysis

The findings from the matched-pair analysis were consistent with previously reported data, highlighting no significant difference in the outcomes of patients with de novo AML and sAML following haplo-HSCT and PTCy. Relapse rates were 21.4% in the de novo arm compared with 21% in the sAML arm. Figure 2 shows matched-pair data at 2 years posttransplant for corresponding clinical outcomes including relapse, non-relapse mortality, leukemia-free survival, overall survival, and GvHD-free relapse-free survival.

AML, acute myeloid leukemia; GRFS, GvHD-free relapse-free survival; GvHD, graft-versus-host disease; LFS, leukemia-free survival; NRM, non-relapse mortality; OS, overall survival; sAML secondary AML.
*Data from Nagler, et al.¹

Mortality rates

During the study period, a total of 564 patients died, with the most common cause of death being the original disease. Infection-related mortality was the second most frequent cause, accounting for 30.5% and 26.3% of deaths in the de novo AML and sAML cohorts, respectively (Figure 3).

AML, acute myeloid leukemia; GvHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplant; sAML, secondary AML.
*Data from Nagler, et al.¹

Conclusion

This retrospective analysis demonstrates that transplantation outcomes were similar between de novo AML and sAML cohorts. In addition, there were no differences observed in the transplantation outcomes irrespective of prior hematologic disease. The findings suggest that haplo-HSCT in combination with PTCy may present a strategy to overcome the typically poor prognosis of patients with sAML. However, the findings were limited by the study design being retrospective in nature and limited to patients in CR1; therefore only presenting favorable outcome data for comparison.