Follow-up and outcome of the twelve-year experience in adult patients with acute promyelocytic leukemia

Steffenello-Durigon, Giovanna; Bigolin, Alisson; Moraes, Ana Carolina Rabello de; Rudolf-Oliveira, Renata Cristina; Moral, Joanita Angela Gonzaga Del; Santos-Silva, Maria Claudia

doi:10.1016/j.htct.2019.12.001

Acessibilidade / Reportar erro

Brasil

Hematology, Transfusion and Cell Therapy

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Original Articles • Hematol., Transfus. Cell Ther. 43 (1) • Jan-Mar 2021 • https://doi.org/10.1016/j.htct.2019.12.001 copy

Follow-up and outcome of the twelve-year experience in adult patients with acute promyelocytic leukemia

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Acute promyelocytic leukemia is a subtype of acute myeloid leukemia, characterized by the presence of neoplastic promyelocytes, due to the reciprocal balanced translocation between chromosomes 15 and 17. Currently, with the use of agents that act directly on this molecular change, such as all-trans retinoic acid and arsenic trioxide, APL has shifted from a highly mortal to a curable disease. However, some cases are still at high risk of death, especially early death, and acquiring a better understanding of the clinical and biological factors involving APL is needed to correctly identify and treat such cases. The early suspected diagnosis and prompt initiation of the target therapy are important for better response rates. The follow-up and outcomes, using real-life data from 44 consecutive APL patients, were studied between 2001 and 2013. The overall survival rate was 82.7% and early death was 16%. Almost all patient deaths were due to severe bleeding, which was confirmed by multivariate analysis, as the most important prognostic factor leading to death. A better understanding the pathogenesis of the hemorrhagic complications in APL is needed, as well as the risk factors associated with early death in APL patients, as this has become synonymous with overall mortality.

Keywords:
Acute promyelocytic leukemia; Early death; PML-RARα

Variables	n: 44 (1.0%)	Variables	n: 44 (1.0%)
Consumption of alcohol		Comorbidity
Yes	6 (13.6%)	Yes	14 (31.8%)
No	38 (86.4%)	No	30 (68.2%)
Use of illicit drugs		Neutropenia (≤500/mm³)
Yes	3 (6.8%)	Yes	20 (45.5%)
No	41 (93.2%)	No	24 (54.5%)
Performance status (0-5)		Hypogranular APL
0-1	12 (27.3%)	Yes	6 (13.6%)
2-3	32 (72.7%)	No	38 (86.4%)
Presence of coagulation disturbance	Presence of fever
Yes	26 (59.1%)	Yes	9 (20.5%)
No	18 (40.9%)	No	35 (79.5%)
LDH (≥1.5× normal)		T (15;17) by RT-PCR
Yes	20 (45.5%)	Yes	41 (93.2%)
No	24 (54.5%)	Not performed	3 (6.8%)
Risk stratification^a a Risk stratification by Sanz et al. (2000).		Presence of FLT3 mutations^b b n = 36.
Low	7 (15.9%)	Yes	2 (4.5%)
Intermediate	26 (59.1%)	No	15 (34.1%)
High	11 (25.0%)	Not performed	27 (61.4%)
CD34		Additional chromosome abnormalities (ACAs)^c c ACAs: der(7); +8; ring chromosome; der(5); +13q; hypoploid.
Positive	12 (27.3%)	Yes	7 (15.9%)
Negative	32 (72.7%)	No	37 (84.1%)
Presence of infection		Presence of ATRA syndrome
Yes	12 (27.3%)	Yes	10 (22.7%)
No	32 (72.7%)	No	34 (77.3%)
Presence of severe bleeding		Use of preemptive ATRA
Yes	8 (18.2%)	Yes	41 (93.2%)
No	36 (81.8%)	No	3 (6.8%)
Death		Presence of CNS infiltration
Yes	10 (22.7%)	Yes	1 (2.3%)
No	34 (77.3%)	No	43 (97.7%)
Relapse		Treatment dropout
Yes	8 (22%)	Yes	2 (4.5%)
No	28 (78%)	No	42 (95.5%)
Time to death since diagnosis	Toxicity
0-24 hours	1 (2.3%)	Congestive cardiac insufficiency	3 (6.8%)
2-30 days	6 (13.7%)	Hepatotoxicity	2 (4.5%)
31-60 days	1 (2.3%)	Bone marrow aplasia	37 (86%)
2.1-24 months	2 (4.5%)	Autologous HSCT in relapse
Use of ATO^d d In relapse.		Yes	3 (6.8%)
Yes	6 (13.6%)	No	41 (93.2%)
No	38 (86.4%)
Signs and symptoms
Asthenia	41 (93.2%)
Bleeding Disorders^e e Metrorrhagia, oral cavity bleeding, epistaxis, hematuria, and diarrhea with blood.	40 (90.9%)
Skin disorders^f f Ecchymosis and petechiae.	40 (90.9%)
Pain	2 (4.5%)
Weight loss	9 (20.5%)
Cough	1 (2.3%)

Variables	Median (range)
Hemoglobin (g/dl)	7.8 (4.8-12.6)
Leucocytes (×10⁹/l)	3.8 (0.3-89.4)
Neutrophils (/mm³)	500.0 (50.0-12,000.0)
Blasts (%)	29.5 (2.0-91.0)
Platelets (×10⁹/l)	22.0 (0.02-83.0)

Variables	Event type
Variables	Deathn (%)	p	Relapsen (%)	p
Age (years)
Median	37	0.64^a a Directly proportional association.	21.5	0.41^b b inversely proportional association.
Range	16 - 58		15 - 58
Gender
Male	5 (20.8%)	1.00	6 (25.0%)	0.25
Female	5 (25.0%)		2 (10.0%)
Comorbidity	4 (13.3%)	0.05	2 (14.3%)	0.70
Consumption of alcohol	1 (16.7%)	1.00	3 (50.0%)	0.06
Use of illicit drugs	1 (33.3%)	1.00	3 (100.0%)	0.004
Coagulation disturbance	10 (50.0%)	0.001	5 (25.0%)	0.43
Hypogranular APL	3 (50.0%)	0.12	1 (16.7%)	1.00
ACAs	3 (42.9%)	0.32	1 (14.3%)	1.00
CD34+	6 (50.0%)	0.01	4 (33.3%)	0.18
Severe bleeding	8 (100.0%)	0.001	2 (25.0%)	0.62
Infection	7 (58.3%)	0.001	4 (44.4%)	0.04
Performance status 2-3	8 (33.3%)	0.03 ^a a Directly proportional association.	5 (15.6%)	0.68
Platelets ≤40 × 10⁹/l	10 (22.7%)	1.00	8 (18.2%)	0.41
Hemoglobin (g/dl)
Median	7.2	0.10^b b inversely proportional association.	9.1	0.20^b b inversely proportional association.
Range	5.5 - 10.9		6.8 - 10.9
Blasts (%)
Median	24	0.87^a a Directly proportional association.	48	0.34^a a Directly proportional association.
Range	2 - 91		4 - 81
LDH (U/l)
Median	378	0.19^a a Directly proportional association.	299	0.71^a a Directly proportional association.
Range	125 - 2,734		125 - 741
Low risk	0 (0.0%)	0.17	0 (0.0%)	0.31
Intermediate risk	7 (26.9%)	0.48	5 (19.2%)	1.00
High risk	3 (27.3%)	1.00	3 (27.3%)	0.65
Preemptive ATRA	8 (19.5%)	0.12	8 (19.5%)	0.61
No chemotherapy	3 (100.0%)	0.001	0 (0.0%)	0.39
Ara-C included^d d In consolidation. Significant when p ≤ 0.05.	1 (12.5%)	0.65	3 (37.5%)	0.14
Treatment dropout	1 (50.0%)	0.43	2 (100.0%)	0.03
Relapse	2 (25.0%)	1.00	-	-
PML-RARα type bcr3	1 (8.3%)	0.96	1 (8.3%)	0.85
Neutropenia^c c Neutrophils ≤ 500/mm3. Mann-Whitney Tests.	6 (30.0%)	0.47	4 (20.0%)	1.00

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] *Corresponding author at: Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Departamento de Análises Clínicas, Campus Trindade, CEP: 88040-900, Florianópolis, SC, Brazil. E-mail address: maria.claudia.silva@ufsc.br (M.C. Santos-Silva).