Allogeneic Stem Cell Transplantation with Sequential Melphalan-Based Conditioning in AML: Residual Morphological Blast Count Determines the Risk of Relapse

Figures & data

Table 1 Patient Characteristics

Characteristics	N = 173 (%)
Age
Median [Range], years	56 [17–75]
≤65 years	138 (80%)
>65 years	35 (20%)
Patient gender
Male	92 (53%)
Female	81 (47%)
Karnofsky Score
90–100	85 (49%)
<90	56 (32%)
<80	25 (14%)
Missing	7 (4%)
Sorror Score
0	29 (17%)
1–2	78 (45%)
>2	64 (37%)
Missing	2 (1%)
AML type
De novo	106 (61%)
Secondary	52 (30%)
Therapy-related	15 (9%)
Treatment status prior HCT conditioning
1st line	110 (64%)
1x Induction therapy	35 (20%)
2x Induction therapy	22 (13%)
1x IT and 1x consolidation	53 (31%)
Relapse	63 (36%)
Bone marrow blast count prior HCT conditioning
Median [Range], %	10 [0–96]
Bone marrow cellularity (cytomorphology)
Aplastic/Hypocellular	112 (65%)
Normocellular	20 (12%)
Hypercellular	11 (6%)
Unknown/not done	30 (17%)
ELN
Low	15 (9%)
Intermediate I	47 (27%)
Intermediate II	63 (36%)
High	48 (28%)
FLT3 mutation (N=156)
Positive	30 (19%)
Negativ	126 (81%)
NPM1 mutation (N=152)
Positiv	23 (15%)
Negativ	129 (85%)

Abbreviations: AML, acute myeloid leukemia; HCT, allogeneic hematopoietic cell transplantation; IT, induction chemotherapy; ELN, European Leukemia Net.

Figure 1 OS, EFS, CIR and NRM for the entire cohort.

Abbreviations: OS, overall survival; EFS, event-free survival; CIR, cumulative incidence of relapse; NRM, non-relapse mortality; Prob., probability; HCT, allogeneic hematopoietic cell transplantation.

Table 2 Multivariate Analysis for Overall Survival, Event-Free Survival, Relapse Incidence and Non-Relapse Mortality

Characteristics	N	Overall Survival			Event-Free Survival			Relapse Incidence			Non-Relapse Mortality
		HR	(95%-CI)	p	HR	(95%-CI)	p	HR	(95%-CI)	p	HR	(95%-CI)	p
Bone marrow blasts prior to HCT
<5%	57	1			1			1			1
5–20%	58	1.40	(0.82–2.38)	0.22	1.62	(0.99–2.64)	0.056	2.44	(1.09–5.46)	0.030	1.18	(0.62–2.22)	0.61
>20%	58	1.80	(1.07–3.02)	0.026	1.93	(1.18–3.14)	0.009	3.43	(1.56–7.54)	0.002	1.24	(0.66–2.36)	0.50
Age at HCT (cont. in decades from 18years)	173	1.26	(1.05–1.50)	0.012	1.19	(1.01–1.40)	0.040	1.10	(0.87–1.40)	0.42	1.26	(1.00–1.58)	0.047
Karnofsky
90–100	85	1			1			1			1
≤80 or missing information	88	1.44	(0.94–2.20)	0.09	1.33	(0.89–1.97)	0.16	1.26	(0.68–2.34)	0.47	1.39	(0.82–2.35)	0.23
AML type
De novo	106	1			1			1			1
Secondary	52	0.76	(0.46–1.26)	0.29	0.74	(0.46–1.17)	0.20	0.65	(0.32–1.31)	0.23	0.84	(0.45–1.58)	0.59
Therapy-related	15	2.10	(1.04–4.24)	0.039	1.64	(0.83–3.26)	0.16	0.00	-	-	3.39	(1.59–7.22)	0.002
ELN 2010 risk
Low/intermediate	125	1			1			1			1
High	48	1.18	(0.72–1.93)	0.51	1.23	(0.77–1.94)	0.39	1.62	(0.80–3.30)	0.18	1.01	(0.53–1.89)	0.99
Treatment status at HCT
1^st line	110	1			1			1			1
Relapse	63	1.66	(0.99–2.78)	0.053	1.56	(0.97–2.52)	0.07	1.47	(0.72–3.04)	0.29	1.61	(0.84–3.07)	0.15
Conditioning regimen
Flu/Mel	140	1			1			1			1
Clo/Mel	33	0.57	(0.31–1.05)	0.07	0.85	(0.50–1.45)	0.56	1.55	(0.73–3.28)	0.26	0.53	(0.24–1.14)	0.10
Donor type
HLA-identical Sibling	40	1			1			1			1
8/8 HLA-matched unrelated donor	82	1.60	(0.89–2.85)	0.12	1.25	(0.74–2.10)	0.40	0.64	(0.32–1.30)	0.22	2.46	(1.07–5.65)	0.033
Partially matched unrelated or haploidentical	51	1.78	(0.96–3.29)	0.07	1.35	(0.77–2.38)	0.30	0.85	(0.37–1.96)	0.71	2.34	(0.98–5.55)	0.054

Notes: P-values are italicized. Bold p-values indicate a statistically significant difference with a p-value <0.05.

Abbreviations: OS, overall survival; EFS, event-free survival; RI, incidence of relapse; NRM, non-relapse mortality; HCT, allogeneic hematopoietic cell transplantation; cont., continously; AML, acute myeloid leukemia; ELN, European leukemia net; Flu/Mel, fludarabin/melphalan; Clo/Mel, clofarabine/melphalan.

Figure 2 Four year point estimator of treatment outcome by pretransplant bone marrow blast count. The dots display the point estimates, whereas the bars display the corresponding 95% confidence intervals. The p values represent the Log rank test for OS and EFS and the score test of univariate cause-specific Cox models for CIR and NRM.

Abbreviations: OS, overall Survival; EFS, event-free survival; CIR, cumulative incidence of relapse; NRM, non-relapse mortality.

Figure 3 Effect of bone marrow blast count prior to HCT on event-free survival and on incidence of relapse. The red curve displays the smoothed spline-based hazard ratio of the dependence of the bone marrow blast count prior to HCT on the all-time risk of relapse or death (left panel) and the all-time risk of relapse (right panel). The hazard ratio is adjusted for age, Karnofsky performance status, AML type, ELN risk, treatment status at HCT, conditioning and donor type. The ribbon represent the pointwise 90% confidence intervals of the hazard ratios. The small lines on x-axis display the individual blast counts of patients having blast counts of 50% at most.

Abbreviation: EFS, event-free survival; CIR, cumulative incidence of relapse; HCT, allogeneic hematopoietic cell transplantation.

Figure 4 OS, EFS, CIR and NRM for relapsed patients (left side) and first-line patients (right side).

Abbreviations: OS, overall survival; EFS, event-free survival; CIR, cumulative incidence of relapse; NRM, non-relapse mortality; Prob., probability; HCT, allogeneic hematopoietic cell transplantation.