Impact Of ELN Risk Stratification, Induction Chemotherapy Regimens And Hematopoietic Stem Cell Transplantation On Outcomes In Hyperleukocytic Acute Myeloid Leukemia With Initial White Blood Cell Count More Than 100 × 10⁹/L

Figures & data

Table 1 Clinical Characteristics

Characteristics	n=52
Age (years), median (range)	46 (16–77)
Age group, n (%)
15–39	17 (32.7)
40–60	23 (44.2)
>60	12 (23.1)
Sex: M/F, n (%)	24/28 (46.2/53.8)
WBC at first diagnosis(×10^9/L), median (range)	172.3 (100.0–477.3)
PLT at first diagnosis(×10^9/L), median (range)	44.7 (5–125)
LDH level at first diagnosis, median (range)	934 (285–1802)
CD56 positive expression, n (%)	10/34 (29.4)
FAB-classification, n (%)
M5	28 (53.8)
M4	8 (15.4)
M2	12 (23.1)
M1	4 (7.7)
Molecular biology, n (%)
NPM1 mutation	4 (7.7)
FLT3-ITD mutation	6 (11.5)
FLT3 ^mutation MPM1 ^mutation	4 (7.7)
MLL arrangements	3 (5.8)
CEBPA mutation	4 (7.7)
Others	4 (7.7)
Negative detection	27 (51.9)
ELN risk assessment, n (%)
Favorable-risk	8 (15.4)
Intermediate-risk	25 (48.1)
High-risk	19 (36.5)
Tumor lysis syndrome (TLS), n (%)	7 (13.5)
Leukostasis, n (%)	26 (50.0)
DIC, n (%)	9 (17.3)
Severe infection at first diagnosis, n (%)	31 (59.6)
Pre-induction treatment before confirmed diagnosis, n (%)
Hydroxyurea	26 (50.0)
Hydroxyurea+ cytarabine+ etoposide	12 (23.1)
Hydroxyurea+ cytarabine	8 (15.4)
Cytarabine+ etoposide	3 (5.8)
Hydroxyurea+ daunorubicin	3 (5.8)
Intensive induction chemotherapy (n)	40
IDA 10~12mg/m2+ cytarabine 100mg/m2, n (%)	22 (55.0)
IDA 8mg/m2+ cytarabine 100mg/m2 or other regimens, n (%)	18 (45.0)
CNS events (infarction or bleeding) before or during induction, n (%)	11 (21.2)
Death before induction, n (%)	12 (23.1)
Death during induction, n (%)	16 (30.8)
First CR (CR1), n	24
One course induction to reach CR1, n (%)	15 (62.5)
More than one course induction to reach CR1, n (%)	9 (37.5)
Transplant, n	20 (38.5)
Time from diagnosis to transplant (months), median (range)	7 (5–12)

Abbreviations: WBC, white blood cell; PLT, platelet; LDH, lactate dehydrogenase; DIC, disseminated intravascular coagulation; IDA, idarubicin; CNS, central nervous system; CR, complete remission.

Figure 1 Flow diagram of the study.

Table 2 Transplant Characteristics

Characteristics	Transplantation
Total, n	20
Age at transplantation (years): median (range)	32 (16–53)
Sex: M/F, n (%)	11/9
ELN risk at first diagnosis, n (%)
High risk	7 (35.0)
Standard or intermediate risk	13 (65.0)
Disease stage in transplant, n (%)
CR1	15 (75.0)
≥CR2	3 (15.0)
No remission after relapse	2 (10.0)
Graft sources, n (%)
Cord blood	15 (75.0)
PBSC from matched sibling donor	4 (20.0)
Autologous PBSC	1 (5.0)
Myeloablative conditioning regimen, n (%)
BUCY2-based conditioning	12 (60.0)
TBICY-based conditioning	8 (40.0)
GVHD Prophylaxis, n (%)
CSA + MMF	17 (85.0)
CSA + MMF+ MTX	2 (10.0)
Total nucleated-cell dose, median (range) (×10^7/kg)
Cord blood	2.9 (2.1–3.7)
PBSC from matched sibling donor	68.2 (45.6–93.1)
Total CD34+ cell dose, median (range) (×10^5/kg)
Cord blood	2.2 (0.83–4.6)
PBSC from matched sibling donor	52.8 (22.6–88.5)
Neutrophil engraftment(days), median (range)
Cord blood	19.7 (16–25)
PBSC from matched sibling donor	11.8 (11–14)
Platelet engraftment(days), median (range)
Cord blood	40.7 (19–65)
PBSC from matched sibling donor	13.3 (12–15)
Grade Ⅱ-Ⅳacute GVHD, n
Cord blood	2
PBSC from matched sibling donor	0
Chronic GVHD, n
Cord blood	3
PBSC from matched sibling donor	1
Follow-up among survivors, (months), median (range)	38.7 (15–70)

Abbreviations: CR, complete remission; PBSC, peripheral blood stem cell; BUCY, busulfan and cyclophosphamide; TBICY, total body irradiation and cyclophosphamide GVHD, graft-versus-host disease CSA, cyclosporine; MMF, mycophenolate mofetil; MTX, methotrexate.

Figure 2 Overall survival. The 3-year overall survival (OS) rate in the 15–39 years old and 40–60 years old group was 58.8% (95% CI: 32.5–77.8%) and 25.4% (95% CI: 8.4–46.8%), respectively; and the longest survival time in patients aged >60 years was only 8 months, and the 8-month OS rate was 8.3% (p=0.002) (A).The 3-year OS rate of patients with and without leukostasis was 27.7% (95% CI: 11.2–47.1) and 33.0% (95% CI: 15.9–51.2%), respectively (p=0.31) (B). The 3-year OS rate of the patients in the favorable risk group, intermediate risk group and high risk group was 50% (95% CI: 15.2–77.5%), 28.0% (95% CI: 12.4–46.0%), and 29.5%(95% CI:10.8–51.2%), respectively (p=0.374) (C). The 3-year OS rate of patients carrying CEBPA or NPM1 mutation and those with FLT3-ITD or MLL mutation was 37.5% (95% CI: 8.7–67.4) and 30.0% (95% CI: 8.9–54.9%), respectively (p=0.63) (D). The 3-year OS rate of patients employing an induction regimen of a standard IA regimen was 58.4% (95% CI: 35.2–75.8%), and of those employing a non-standard IA regimen was 22.2% (95% CI: 6.9–42.9%) (p=0.065) (E). The 3-year OS rate of the transplantation patients reached 73.8% (95% CI: 47.8–88.3%), while the 9-month OS rate of patients without transplantation was 11.4% (95% CI: 1.97–30.2%) (p<0.001) (F).

Figure 3 TRM, relapse and survival of patients in transplant. The 3-year transplant-related mortality (TRM) rate was 15% (95% CI: 3.5–34.1%) in all transplant patients, and the 3-year TRM in UCBT patients was 20% (95% CI: 4.5–43.3%), and allo-PBSCT patients showed no transplant-related death (A). The 3-year relapse rate for transplant patients was 15.4% (95% CI: 3.6–34.8%), of whom the 3-year relapse rate for UCBT patients was 14.0% (95% CI: 2.0–37.2%), and the 3-year relapse rate for allo-PBSCT patients was 25% (95% CI: 0.3–71.4%) (B). The 3-year leukemia-free survival (LFS) rate for all transplant patients was 69.6% (95% CI: 44.5–85.1%), including 66% for UCBT patients (95% CI: 36.5–84.3%) and 75% for allo-PBSCT patients (95% CI: 21.7–96.1%) (C). The 3-year OS rate for UCBT patients was 71.1% (95% CI: 39.4–88.3%) and for allo-PBSCT patients was 75.0% (95% CI: 21.7–96.1%) (D).