Analysis of early death in critically ill patients with acute promyelocytic leukaemia in HICU

doi:10.21203/rs.3.rs-4072940/v1

This study was conducted to identify the characteristics and risk factors for early death of the critically ill acute promyelocytic leukaemia (APL) patients in Hemato-oncologyical ICU (HICU). A total of 44 APL patients from 2017 to 2023 were recruited. The mortality of APL patients in HICU was high (27/44, 61.36%). In comparison to patients who survived, nonsurvivors had longer PT (P = 0.02), lower FIB (P = 0.004), and higher WBC (P = 0.004) at hosipital admission. Severe bleeding was the most frequent complication (34 cases, 77.27%), which occurred either pre-induction or on day 5 (IQR, 3-7.5 days) of induction therapy. The leading cause of death was fatal hemorrhage (18 cases, 40.90%), which occurred either pre-induction or on day 4 (IQR, 3–7 days) of induction therapy. In conclusion, the primary cause of mortality for APL patients in the HICU was fatal bleeding, whereas patients who experienced severe bleeding were more likely to die from secondary infection.

Health sciences/Diseases

Health sciences/Medical research

Health sciences/Oncology

Health sciences/Risk factors

Health sciences/Signs and symptoms

Acute promyelocytic leukaemia

Early death

Fatal bleeding

APL is a special subtype of acute myeloid leukemia (AML) that is identified by the presence of the chromosomal translocation (t15;17) (q24; q21) resulting in the production of PML-RARAα fusion protein, in 95% of cases, which prevents both apoptosis and differentiation at the promyelocyte stage ^[1].

The present remarkable complete remission (CR) rates in over 90% of APL patients, and improved long-term survival of APL patients are largely attributable to the introduction of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in the induced differentiation therapy ^{[2, 3]}. However, in APL cohorts, early death (ED) defined as death between 0 to 30 days after diagnosis continues to be significant, accounting for 8.2–32.6% of total mortality ^[4–6].

APL frequently involves severe complications such as differentiation syndrome (DS), bleeding, and infection, etc, pre, during or post induction treatment. ED due to serious complications of initial APL continues to be a major contributor to treatment failure ^[7–9]. The presenting coagulopathy is often linked to ED for APL, Most typically, complications associated to the condition, like bleeding, cause deaths within the first week of hospital admission. In contrast, severe infection might also be the cause of fatalities that happen later than that of bleeding ^[10]. In addition, venous and arterial thrombosis occurs in up to 20% of APL patients, the frequent thrombotic events include deep vein thrombosis (DVT), pulmonary embolism, myocardial infarction and ischaemic cerebrovascular events. However, thrombotic complications rarely result in mortality ^[11–13].

Frequently, these severe complications result in admission to the HICU, and aggressive supportive measures of severe complications is essential for improving the CR and long-term survival. Induction differentiation treatment was frequently administered concurrently to APL patients in HICU. The induction treatment-related DS, leukocytosis, respiratory failure, aggravated hemorrhage and secondary infection worsen the patient's state. Therefore, the severe complications and causes of death of APL patients in HICU show certain characteristics ^[14].

Consequently, It is crucial for clinicians, especially those working in the ICU, to be knowledgeable about the special complications and management concerns that critically ill APL patients face. Furthermore, understanding of the factors affecting mortality during induction therapy is essential to critical care providers.

In this study, 52 APL patients in the HICU were included. 8 cases, however, were excluded because one case receive intermittent dialysis due to chronic renal failure; and 4 cases declined therapy, and 3 cases who did not receive ATO as part of their induction regimen. 44 APL patients were ultimately included in this study (Figure 1).

27 (61.36%) of the 44 patients in total passed away. Of the 44 patients, 28 (63.63%) males, and 67.85% of them died (19/28); 16 females (36.36%), and 50% of them passed away (8/16). There was no statistical difference in the mortality rates for males and females (Table 1).

Table 1 displays the clinical data of patients including age, underlying disease, Cr, PT, FIB, DD, WBC, HGB, and PLT, as well as information on APL induction therapy and a comparison of CRRT and mechanical ventilation during HICU treatment. Compared to patients who survived, nonsurvivors had a longer PT (P=0.02), a lower FIB (P=0.004), and a higher WBC (P=0.004) upon hospital admission. Three patients passed away pre-induction, and the remaining 41 patients received ATO-based induction treatment, 24 (24/41, 58.53%) of them died during induction therapy. ATO plus chemotherapy resulted in a higher mortality rates (14/17, 82.35%) compared to ATO alone (10/28, 41.66%) (P=0.012). The median time of induction treatment for nonsurvivors was 7 days (IQR 4-32 days), which was notably lower than that of survivors (31 days, IQR 28-32 days) (P<0.001).

The median HICU treatment duration of all APL patients was 2.5 days (IQR 1-7 days), and neither the underlying diseases nor the HICU treatment duration differed statistically between the nonsurvivors and survivors. Compared with survivors, most nonsurvivors received mechanical ventilation treatment due to respiratory failure （20/27, 74% vs 0/17, 0%，P<0.001）(Table1).

Time distribution of severe complications in APL patients

In this study, the most prevalent severe complication in this study was severe bleeding, which occurred in 34 (77.27%) of the APL patients during their hospital stay. The median time of severe bleeding during induction therapy was day 5 (IQR 3-7.5 days). Cerebral bleeding was the most common (20 cases, 45.45%), it occurred pre-induction (13 cases, 29.45%) and at the first week of induction therapy (7 cases, 15.9%), respectively. The median time of cerebral bleeding during induction therapy was day 4 (IQR 3-5 days). The second was gastrointestinal bleeding (17 cases, 38.63%), it occurred pre-induction (9 cases, 20.45%), and at the first week (6 cases, 13.63%), the second week (1 case, 2.27%) and the third week (1 case, 2.27%) of induction therapy , respectively. The median time of gastrointestinal bleeding during induction therapy was day 4 (IQR 3-7.75 days). The third was pulmonary bleeding (12 cases, 27.27%), it occurred pre-induction (6 cases, 13.63%), at the first week (3 cases, 6.81%) and the second week of induction therapy (3 cases, 6.81%), respectively. The median time of pulmonary bleeding during induction therapy was day 7 (IQR 5-11.5 days), there were no additional cases of severe bleeding post-induction therapy. In this study, 5 cases continued anti-infection therapy, and the remaining 12 cases were discharged after induction therapy.

Sepsis was another prevalent severe complication of APL patients in HICU. 18 (40.90%) cases developed sepsis during hospitalization, which occurred pre-induction (2 cases, 4.54%), week one (4 cases, 9.09%) , week two (9 cases, 20.45%), week third (2 cases, 4.54%), and week four (1 cases, 2.27%) of induction therapy. Sepsis developed later than severe bleeding (P=0.011), the median time of sepsis during induction therapy was day 8 (IQR 7.25-11.75 days). There were no additional cases of sepsis post-induction.

It is common for severe DS to develop during induction therapy (8 cases, 18.18%), it occurred in the first week (2 cases, 4.54%), the second week (4 cases, 9.09%) and the third week (2 cases, 4.54%), respectively. The median time of severe DS during induction therapy was day 12 (IQR 7.25-17 days).

There were few cases of severe thrombotic complications, one case each of pulmonary embolism, multiple cerebral infarction, and lower extremity deep venous thrombosis pre-induction. an additional 2 (4.54%) cases experienced acute renal insufficiency pre-induction, and 1 (2.27%) case experienced ventricular tachycardia on the 22nd day of induction therapy. as shown in Fig. 2 and Table 2.

In summary, severe bleeding were the most common complication in the early stages of APL. After two weeks of induction therapy, the incidence of severe bleeding decreased gradually, while the incidence of sepsis and severe DS rose to a high value. Severe complications became much less common after the third week of induction therapy.

Reasons for HICU admission

In this study, for APL patients, cerebral bleeding complicated with consciousness disturbance was the most common reason of HICU admission (18 cases, 40.9%). of these, 11 (25%) cases were admitted to the HICU before induction therapy, and the remaining 7 (15.9%) cases were admitted at the first week of induction therapy. For cerebral bleeding with consciousness disturbance during induction therapy, the median time of HICU admission was day 3 (IQR 3-5 days). 2 (4.54%) cases entered HICU due to subarachnoid bleeding complicated with serious headache pre-induction.

For respiratory failure, 13 (29.54%) cases were admitted to HICU. of these, 4 (9.09%) cases complicated by respiratory failure pre-induction due to pulmonary bleeding (3 cases) and pulmonary embolism (1 case); Another 9 (20.45%) cases experienced respiratory failure during induction therapy due to pulmonary bleeding (5 cases), serious DS (1 case) and pulmonary infection (3 cases). The median time of HICU admission for respiratory failure during induction therapy was day 8 (IQR 7-12 days).

For sepsis or septic shock, 7 (15.9%) cases were admitted to HICU. Of these, 2 (4.54%) individuals experienced septic shock pre-induction, while 5 (11.36%) cases experienced sepsis or septic shock during induction therapy. During induction, the median time of HICU admission for sepsis or septic shock was day 8 (IQR 7-11 days). There were no cases of sepsis post-induction.

Furthermore, on day 23 of induction therapy, 1 case experienced ventricular tachycardia admitted to the HICU. Due to acute renal insufficiency, one case developed anuria pre-induction and one case developed oliguria on the eighth day of induction therapy, they were sent to the HICU for CRRT. On the seventh day of induction therapy, one case experienced gastrointestinal bleeding accompanied by hypovolemic shock and was admitted to HICU (Table 3).

Reasons of death

A total of 27 (61.36%) cases passed away, of those, 3 (6.81%) cases died before induction therapy and 24 (54.54%) died during induction therapy. During induction therapy, the median time of death was day 7 (IQR 3-11 days). Sepsis, fatal bleeding and pulmonary embolism were the causes of death. After induction treatment, no one passed away.

Fatal bleeding was the leading cause of death, with the highest mortality (18 cases, 40.90%), the median time of death during induction therapy was day 4 (IQR 3-7 days). There were 3 (6.81%) cases of pulmonary bleeding and 15 (34.09%) cases of cerebral bleeding. Of the cases that died of cerebral bleeding, 3 (6.81%) cases died prior to induction therapy, while 12 (27.27%) cases died during the first week of induction treatment. During induction therapy, the median time of death for cerebral bleeding was day 2 (IQR 1-3.75 days). Pulmonary bleeding patients died during induction therapy, with a median death time of day 9 (IQR 3-12 days), and a marginally lower mortality rates (6.81%) than cerebral bleeding. Following the third week of induction therapy and until the end of the treatment, no fatal bleeding deaths were reported.

Sepsis is another important cause of death in APL patients in HICU. Mortality from sepsis (8 cases, 18.18%) was slightly lower than that from fatal bleeding. It was more common in the second week of induction therapy, and death cases of sepsis were still occasionally seen in the later period of induction therapy. During induction therapy, the median time of mortality from sepsis was day 12 (IQR 9.5-24.75 days).

Death due to thrombotic complications was rare, only 1 (2.27%) case experienced pulmonary embolism pre-induction therapy and passed away on the seventh day of induction therapy. There were no deaths due to DS in our study (Table 4) (Figure 3).

Only 5 of the 12 (45.45%) cases who suffered from cerebral bleeding survived, and 15 (15/20, 75%) cases perished. The basal ganglia region was the most frequently occurring (11/20, 55%) and most fatal (all died) site of cerebral bleeding. In addition, subarachnoid bleeding was also the frequent site of cerebral bleeding (7/20, 35%), with 3 cases (3/20, 15%) dying and 4 cases (4/20, 20%) surviving. One case (1/20, 5%) experienced a small amount of thalamic hemorrhage and recovered completely. One (1/20, 5%) case died of multiple-site cerebral bleeding. There was a significant difference (P=0.013) in the cerebral bleeding site between the surviving and dying patients. (Table 5).

The most frequent infection site among the 18 APL patients with sepsis were pulmonary infection (12/18, 66.66%), bloodstream infection (4/18, 22.22%) and skin and soft tissue infection (2/18, 11.11%).

Among 18 patients with sepsis, bacteria were the most common pathogenic bacteria (6/18, 33.33%), followed by fungi (1/18, 5.55%) and viruses (1/18, 5.55%). The infection site or etiology of sepsis showed no statistically significant between survivors and nonsurvivors (Table 5).

Serious complications in the early stages of APL are frequently fatal and account for the majority of deaths, making APL a particularly concerning condition. APL patients who survive the early stages of the illness have high rate of both CR and long-term survival. In the HICU, there is a special group of critically ill APL patients. The clinical features and causes of death were analyzed. The results suggest that fatal bleeding is the most prevalent severe complication and the main cause of death in the early stage of APL.

there was only one study published in 2018 that detailed the clinical characteristics of initial APL patients in ICU ^[17]. The study comprised 18 APL patients discovered that the most common reason for ICU admission was respiratory failure (39%, n = 7), which was followed by septic shock (22%, n = 4). multiple organ failure and cerebral bleeding are the most common causes of death among APL patients.

Our study indicates that cerebral bleeding is the most significant consequence, accounting for the majority of HICU admissions due to its frequent presentation of consciousness alteration, coma, or severe headache. There was a high incidence of cerebral bleeding in the early stage of APL, as evidenced by the majority of cases occurring before and within the first week of induction therapy. However, there were no incidences of cerebral bleeding occurred from the second week of induction therapy, indicating that the risk of cerebral bleeding in APL patients decreased significantly after aggressive treatment, including PLT infusion, anticoagulation and other symptomatic supportive treatment, for one week. Pulmonary bleeding was comparatively uncommon as opposed to cerebral bleeding. When it develops, patients typically require HICU treatment because of respiratory failure brought on by significant pulmonary bleeding.

Sepsis-related HICU admissions of patients in this study were also frequent, they often present with shock or respiratory failure. Sepsis frequently occurs during the second week of induction therapy. This is related to APL patients' compromised immune systems, the use of glucocorticoids in DS, and the subtle infection signs that might easily be missed by doctors and can lead to sepsis or septic shock.

APL patients were admitted to HICU due to thrombotic complications are rare in this investigation. and the majority of thrombotic complications' clinical signs are modest, or if more significant accompanying complications mask the symptoms, doctors might neglect it.

Some APL patients were treated with CRRT after admission to the HICU due to acute renal failure, which was associated with microvascular thrombosis and leukemic cell infiltration. Only one case was brought to the HICU because of severe DS complicated with respiratory failure and the remaining cases of severe DS occurred during induction therapy in HICU.

In this study, the mortality of APL patients was as high as 61.36%, fatal bleeding, sepsis and pulmonary embolism were the causes of death. Fatal bleeding was the leading cause of death, accounting for 40.90% of deaths pre-induction and within two weeks of induction therapy.

Intracranial bleeding, particularly in the subarachnoid region and basal ganglia, are the most frequent sources of death. Basal ganglia bleeding was the most common and fatal, and all cases with basal ganglia bleeding died as their condition deteriorated rapidly. This is the primary reason for the high mortality rates. In addition, multiple cerebral bleeding and subarachnoid major bleeding deaths were also observed. A tiny quantity of subarachnoid or thalamic hemorrhage is characteristic of survivors. suggesting that the location and volume of intracranial bleeding are closely related to the prognosis. Pulmonary bleeding is a comparatively uncommon cause of death in APL patients in HICU.

Sepsis associated with weakened immune system of APL patients is also a common cause of death in HICU. Additionally, a few cases who had pulmonary or cerebral bleeding also passed away from a subsequent serious pulmonary infection or sepsis brought on by lack of autonomous expectoration capacity, aspiration, ventilator-associated pneumonia and other factors. According to our data, sepsis primarily occurred in the first two weeks of induction therapy, particularly in the second week. Sepsis-related deaths were also frequent during the second week of induction treatment. It is evident that in HICUs, patients with severe bleeding complications, even if they manage to survive after aggressive therapy, are more likely to die from secondary sepsis.

APL patients treated with ATO and chemotherapy had a higher mortality rates than those treated with ATO alone. The reasons are as follows: Chemotherapy were given for leukocytosis APL which is frequently linked to more severe illness. Stated differently, the patients in the ATO and chemotherapy group were more sicker than the ones in the ATO alone group. Furthermore, cytotoxic chemotherapies tend to aggravate coagulopathy, so the mortality rates was higher in the ATO + chemotherapy group.

There are limitations to the study. Due to the limited sample size, further researches ought to conduct from multicentered researches. It remains to identify if there are any particular subgroups of APL patients who would benefit from early intensive care management before severe bleeding or sepsis develops.

In summary, the mortality of APL patients in the HICU is significant high. Fatal bleeding was the leading cause of death in APL patients in the HICU. Patients who have survived from severe bleeding were at a higher risk of succumbing to subsequent sepsis.

Patients

A retrospective study with medical chart review was performed. Data was collected between October 2017 and May 2023. 52 patients with positive t (15;17) and/or positive PML-RARα APL diagnose admitted to the HICU were identified, in the first affiliated hospital of Harbin Medical University, China. The Harbin Medical University Ethics Committee gave its approval to this study. Written Informed consent was obtained from all subjects. All study procedures were performed in accordance with the relevant guidelines and regulations.

HICU admission and discharge criteria

Criteria for HICU admission: patient developed serious complications, such as significant bleeding, including gastrointestinal, pulmonary, and cerebral bleeding; Sepsis or septic shock; Serious thrombotic complications, such as pulmonary embolism; And serious DS. When the aforementioned problems resulted in life-threatening symptoms such as shock, respiratory failure, disturbance of consciousness, multiple organ failure, malignant arrhythmia, etc.

Criteria for HICU discharge: The patient's vital signs remained consistent. Additionally, the patient's condition gradually got better and required no critical care; Conscious and capable of communicate clearly; Infection under control; No continuous bleeding.

Inclusion and exclusion criteria

Inclusion criteria: Newly diagnosed critically ill APL patients admitted to HICU for aggressive supportive measures; Age ≥ 10 years.

Exclusion criteria: For a variety of reasons, the patient's intense therapy was discontinued upon transfer to the HICU; Chronic renal failure patients receiving regular dialysis in the HICU.

Treatment strategies for critically ill APL patients in HICU

Once a morphological diagnosis of APL is made, the patients received an arsenic trioxide (ATO) induction regimen immediately (generally no later than 48 hours after hosipital admission), that is, ATO 0.16mg×kg^− 1×d^− 1 for 18 hours, with a daily maximum dose of 10 mg, and engaging in induction therapy for a minimum of 28 days until CR.

For cases whose white blood cell (WBC) count was more than 20×10⁹/L, hydroxyurea (2-4g/d) was given. When a patient's WBC was more than 50×10⁹/L, 100 mg of cytarabine was given daily until the WBC fell to 20×10⁹/L. Platelet (PLT) infusion was administered when PLT less than 30×10⁹/L; Fibrinogen (FIB) therapy was administered when FIB less than 2g/L;

At least 400ml of fresh frozen plasma were administered every day in cases of abnormal coagulation index, such as prothrombintime (PT) extended greater than 3s or activated partial thromboplastin time (APTT) extended greater than 10s; At least 200ml of fresh frozen plasma were administered every day when the coagulation index was near to normal; In the case of DS, dexamethasone (10–20 mg/d) was given.

Intense care and treatment protocols are provided to critically ill APL patients. Patients with respiratory failure were managed with either mechanical ventilation or high-flow oxygen therapy. The International Guidelines for the Management of Sepsis and Septic Shock were followed while sepsis occurs [15].

Patients with acute renal failur and volume overload were treated with continuous renal replacement therapy (CRRT).

Clinical data collection

Obtain the general clinical information about APL patients, including gender, age, and underlying diseases; Obtain the laboratory results at the time of hospital admission, such as WBC, hemoglobin (HGB), PLT, PT, FIB, D dimer (DD), and creatinine (Cr).

Information was gathered about APL patients' induction treatment schedules. assemble data regarding the incidence and temporal distribution of sereve complications during three time periods: Pre-induction, During induction, and Post-induction till hosipital discharge; The reasons and timing of the HICU admission; And the causes and temporal distribution of death during hospitalization, as well as the CRRT and mechanical ventilation treatment during HICU therapy.

Definitions and Criteria

Sepsis-3.0 was used to confirm the diagnosis of sepsis or sepsis shock [16]; A severe complication is defined as a life-threatening complication requiring ICU care and treatment.

Statistical Analysis

The measurement data were represented by median (interquartile range (IQR)); The categorical variables were represented as frequency (percentage) and compared using the Chi-square test; Variables with non-normal distribution were compared by Mann-Whitney U non-parametric test. In all statistical analyses, a p < 0.05 was considered statistically significant. IBM SPSS Statistics Version 25.0 was used to analyze the data.

APL, acute Promyelocytic Leukaemia; APTT, activated partial thromboplastin time; ATO, arsenic trioxide; ATRA, all-trans retinoic acid; BSI, bloodstream infection; CR, complete remission; CRRT,continuous renal replacement therapy; DD, D dimer; DIC, disseminated intravascular coagulation; DS, Differentiation syndrome; DVT, deep vein thrombosis; FIB, fibrinogen; HGB, haemoglobin; IMV, invasive mechanical ventilation; PT, prothrombintime; PLT, platelet; SSTIS, skin and soft tissue infection; WBC, white blood cell count.

Author Contributions

Haitao Li and Yingmei Zhang conceived and designed the study. Haitao Li collected the data. Haitao Li and Yingmei Zhang analyzed the data, prepared tables and figures, and wrote the manuscript. All authors reviewed the manuscript.

Funding

None

Ethics declarations

Ethics approval was obtained from the ethics committee of the participant hospital, and the study was conducted in adherence to the Declaration of Helsinki. Signed permission was waived because this was a retrospective study and did not involve patients' private information or commercial interests

Conflict of interest

The authors declare no competing interests.

Data availability statement

All relevant data are within the paper.

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Table 1. General information of APL patients.

Variable	Survivor (n=17)	Nonsurvivor (n=27)	P
Gender, No. (%)
Female	9 (32.14)	19 (67.85)	0.242
Male	8 (50)	8 (50)
Age, years, median (IQR)	49 (27, 58.5)	46 (36, 55)	0.893
Comorbidity, No. (%)
Diabetes	4 (9.09)	1 (2.27)	0.065
CHD	3 (6.81)	1 (2.27)	0.282
Hypertension	2 (9.09)	1 (2.27)	0.549
Peripheral blood count, median (IQR)
WBC, ×10⁹ /L	2.35 (0.99, 16.32)	36.95 (7.11, 92.38)	0.004
HGB, g/L	72.52 (62, 82.9)	77 (60.87, 92.5)	0.913
PLT, ×10⁹ /L	9 (6, 49)	19 (9.5, 30)	0.228
Coagulation indexes, median (IQR)
PT, s	13.2 (12.27, 14.9)	16.5 (14.2, 19.3)	0.02
FIB, g/L	2.3 (1.24, 4.1)	1.03 (0.65, 1.63)	0.004
DD, mg/L	20.15 (4.38, 37.58)	27.26 (8.38, 37.2)	0.314
Creatinine, μmol/L, median (IQR)	53 (41.35, 67.1)	69.5 (48.6, 133)	0.858
Induction therapy, No. (%)	17 (41.46)	24 (58.53)
ATO+chemotherapy, No. (%)	3 (17.64)	14 (82.35)	0.012
ATO, No. (%)	14 (58.33)	10 (41.66)
Induction therapy time, median (IQR)	31 (28, 32)	7 (4, 32)	<0.001
HICU treatment, No. (%)
IMV	0	20 (100)	<0.001
CRRT	2 (100)	0	0.144
Length of stay in HICU，median (IQR)	4 (2, 10.5)	2 (1, 6)	0.096

Abbreviations: ATO, arsenic trioxide; CRRT,continuous renal replacement therapy; CHD,Coronary heart disease; DD, D dimer; FIB, Fibrinogen; HGB, Haemoglobin; PT, Prothrombintime; PLT, Platelet; WBC, White blood cell count; IMV, Invasive mechanical ventilation. The Boldface indicated that p values < 0.05 are considered statistically significant.

Table 2. Occurrence and time of serious complications in APL patients after hospital admission.

Complication	All	Pre-induction	During Induction		Post-induction
	No. (%)	No. (%)	No. (%)	Time, median (IQR)	No.
Serious bleeding	34 (77.27)	20 (45.45)	14 (31.81)	5 (3, 7.5)	0
Cerebral bleeding	20 (45.45)	13 (29.54)	7 (15.9)	4 (3, 5)	0
Gastrointestinal bleeding	17 (38.63)	9 (20.45)	8 (18.18)	4 (3, 7.75)	0
Pneumorrhagia	12 (27.27)	6 (13.63)	6 (13.63)	7 (5, 11.5)	0
Thromboembolic complication	3 (6.81)	3 (6.81)	0	/	0
MCI	1 (2.27)	1 (2.27)	0	/	0
Pulmonary embolism	1 (2.27)	1 (2.27)	0	/	0
DVT	1 (2.27)	1 (2.27)	0	/	0
Sepsis, No. (%)	18 (40.90)	2 (4.54)	16 (36.36)	8 (7.25, 11.75)	0
DS, No. (%)	8 (18.18)	0	8 (18.18)	12.5 (7.25, 17)	0
Acute renal failure, No. (%)	2 (4.54)	1 (2.27)	0	/	0
Malignant arrhythmia, No. (%)	1 (2.27)	0	1 (2.27)	23	0

Abbreviations: DS, Differentiation syndrome; DVT, Deep venous thrombosis; MCI, Multi-Cerebral Infarction.

Table 3. Reasons and time for HICU admission in APL patients after hospital admission.

Indication of HICU admission	All	Pre-induction	During induction		Post-induction
	No. (%)	No. (%)	No. (%)	Time, median (IQR)	No.
Consciousness disorder	18 (40.90)	11 (25)	7 (15.90)	3 (3, 5)	0
Respiratory failure	13 (29.54)	4 (9.09)	9 (20.45)	8 (7, 12)	0
Sepsis/sepsis shock	7 (15.90)	2 (4.54)	5 (11.36)	8 (7, 11)	0
Headache	2 (4.54)	2 (4.54)	0	0	0
Oliguria or anuria	2 (4.54)	1 (2.27)	1 (2.27)	8	0
VT	1 (2.27)	0	1 (2.27)	23	0
Hypovolemic shock	1 (2.27)	0	1 (2.27)	7	0

Abbreviations: VT, Ventricular tachycardia.

Table 4. Cause and time distribution of death in APL patients in HICU

Causes of death	All	Pre-induction	During induction		Post-induction
	No. (%)	No. (%)	No. (%)	Time, median (IQR)	No.
Fatal bleeding	18 (40.90)	3 (6.81)	15 (34.09)	4 (3, 7)	0
Cerebral bleeding	15 (34.09)	3 (6.81)	12 (27.27)	2 (1, 3.75)	0
Pneumorrhagia	3 (6.81)	0	3 (6.81)	9 (3, 12)	0
Sepsis	8 (18.18)	0	8 (18.18)	12 (9.5, 24.75)	0
Pulmonary embolism	1 (2.27)	0	1 (2.27)	7	0
mortality	27 (61.36)	3 (6.81)	24 (54.54)	7 (3, 11)	0

Table 5. Characteristics of causes of death in APL patients.

Complication		All (%)	Survivors (%)	Nonsurvivors (%)	P *
Cerebral bleeding		20 (45.45)	5 (25)	15 (75)
	Site of bleeding
	Subarachnoid space	7 (35)	4 (20)	3 (15)	0.013
	Basal ganglion	11 (55)	0	11 (55)
	Thalamus	1 (5)	1 (5)	0
	Multiple Site	1 (5)	0	1 (5)
Sepsis		18 (40.90)	7 (38.88)	11 (61.11)
	Site of infection
	Pulmonary infection	12 (66.66)	5 (27.77)	7 (38.88)	0.792
	BSI	4 (22.22)	1 (5.55)	3 (16.66)
	SSTIS	2 (11.11)	1 (5.55)	1 (5.55)
	Pathogen
	Bacterial infection	6 (33.33)	2 (11.11)	4 (22.22)	0.315
	Fungal infection	1 (5.55)	1 (5.55)	0
	Virus infection	1 (5.55)	0	1 (5.55)

Abbreviations: BSI, Bloodstream infection; SSTIS, Skin and soft tissue infection. The Boldface indicated that p values < 0.05 are considered statistically significant. *: Pearson’s or Fisher’schi-square test.

No competing interests reported.

supplementaryfile.xlsx

Analysis of early death in critically ill patients with acute promyelocytic leukaemia in HICU

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Abstract

Figures

Introduction

Results

Discussion

Conclusions

Methods

Patients

HICU admission and discharge criteria

Inclusion and exclusion criteria

Treatment strategies for critically ill APL patients in HICU

Clinical data collection

Definitions and Criteria

Statistical Analysis

Abbreviations

Declarations

Ethics declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1